An amber prescription bottle tipped over on a pale wooden table with pink and white antibiotic capsules spilling out, beside a folded paper card, in bright window light

You Probably Are Not Allergic to Penicillin

On August 31, 2026 By Dr. Scott RennieIn Infectious DiseaseLeave a comment

About one in ten Americans carries a penicillin allergy in their chart (1). When those people are actually tested, the large majority are not allergic.

That gap is one of the most consequential unforced errors in medicine, and almost nobody goes back and checks.

Where the label usually comes from

Most penicillin allergy labels were applied in childhood, by someone who is no longer involved, based on something that happened once.

The classic story is a rash during a course of amoxicillin at age four. Here is the problem with that story. Viral illnesses cause rashes. Children with viral illnesses get prescribed antibiotics. When a rash appears on day three, the antibiotic is the thing everyone is looking at, so the antibiotic gets the blame and the label goes in the chart. It never comes out.

The other common origins are a family member’s allergy transferred onto the patient, and side effects filed as allergy. Nausea is not an allergy. Diarrhea is not an allergy. A yeast infection is not an allergy. They are all reasons to dislike a drug and none of them are reasons to avoid it for life.

Even genuine allergy fades. IgE-mediated penicillin sensitivity wanes over time, and a substantial proportion of people who really were allergic at twenty are not allergic at fifty.

The label is not free

This is the part I want to land, because people assume that avoiding penicillin is the cautious choice and therefore the safe one.

It is not. Blumenthal and colleagues followed 64,141 adults carrying a penicillin allergy label against 237,258 matched comparators for a mean of six years (2). The people with the label had an adjusted hazard ratio of 1.69 for MRSA and 1.26 for Clostridioides difficile.

The mechanism is not mysterious, and the authors show it. Those patients received far more of the alternatives: macrolides at over four times the rate, clindamycin at nearly four times, fluoroquinolones at twice (2). Those drugs do more collateral damage to the gut and select harder for resistance. The excess MRSA and C. difficile were mediated by that substitution.

So the label does not sit there harmlessly. It quietly buys worse antibiotics for the rest of a person’s life.

There is a score for this, and it runs on history alone

The thing that changed my thinking here is that you do not need a skin test to identify most of the people who are low risk. You need four questions.

PEN-FAST was derived and validated by Trubiano and colleagues (3). It scores like this:

Five years or fewer since the reaction: 2 points. Anaphylaxis or angioedema, or a severe cutaneous adverse reaction: 2 points. Treatment required for the episode: 1 point.

A score under 3 means low risk. In the derivation cohort, only 17 of 460 low-risk patients tested positive, giving a negative predictive value of 96.3 percent (3).

Read the criteria again and notice what is not in them. No skin prick. No specific IgE. No blood work at all. Every input is something the patient tells you.

That is why this belongs in a conversation rather than a laboratory, and it is why I think most clinicians could be doing more of this than they are.

What I actually do with this on a video visit

I ask everyone about allergies before I prescribe anything. That part is unremarkable. What is worth describing is what happens next, because it is where most of these labels give themselves away.

When somebody tells me they are allergic to amoxicillin, I ask what the reaction was.

Two answers come back more than any others. The first is that they do not really remember, because they were a baby and their parents told them. The second is some version of “I think I am allergic because my mom is.”

Neither of those is an allergy history. The second one is not even about the patient.

Here is where I part company with the enthusiastic version of this argument. A person who is sick today and needs an antibiotic today is not in a good position to test a theory about their own immune system. If there is any real concern about anaphylaxis in what I am hearing, I do not push it. I pick something else and move on, and I am comfortable with that.

I also do not send people off for an oral challenge as a matter of course. That is a real procedure with a real indication, and routing every vague childhood label into an allergy clinic is not a good use of anyone’s afternoon.

What I do instead is tell them the label is worth reopening properly, and that the time to do it is when they are well rather than in the middle of an infection. It belongs with whoever manages their ongoing care, in a visit where nobody is waiting on a prescription.

The distinction matters. The label deserves to be examined. The examination should not happen while someone is sick and I am trying to treat them.

What a real reaction looks like, and what has changed about treating it

None of the above applies to someone who has had a genuine severe reaction. Anaphylaxis, angioedema, or a severe cutaneous adverse reaction such as Stevens-Johnson syndrome or DRESS means the label stays. Those people are not candidates for de-labeling and should not be challenged.

Worth knowing what has changed on the treatment side. For decades the only option for anaphylaxis outside hospital was an intramuscular auto-injector. There is now an FDA-approved epinephrine nasal spray, neffy, the first intranasal adrenaline product to reach the market (4). Pharmacokinetic studies show plasma concentrations comparable to or exceeding intramuscular injection, and, counterintuitively, nasal congestion does not appear to impair absorption (5).

I mention it because needle avoidance is a real reason people leave their epinephrine at home, and a device you will actually carry beats a better device you will not. If someone genuinely needs to carry epinephrine and the needle is the barrier, that conversation is now worth having.

It does not change the rule that epinephrine is the treatment and antihistamines are not.

For patients

If your penicillin allergy dates from childhood and you cannot remember what happened, it is worth reopening. Ask specifically to be assessed rather than mentioning it in passing, because in passing it stays in the chart.

Before that conversation, work out three things: roughly when it happened, what you or your parents remember seeing, and whether anyone treated it. That is most of the assessment.

Raise it when you are well. A visit for an infection is the wrong moment, because whoever is treating you needs to choose an antibiotic today and will reasonably play it safe. Bring it to a routine appointment instead, when nobody is waiting on a prescription.

If you have taken amoxicillin, Augmentin or any similar antibiotic since the original reaction and were fine, say so early. It is the single most useful thing you can tell your clinician.

And if your reaction involved breathing trouble, swelling of the face or throat, or a blistering rash, the label is real and it stays.

For colleagues

PEN-FAST costs four questions and identifies low-risk labels at the point of care with a negative predictive value of 96.3 percent (3). We are not short of the tool. We are short of anyone taking ownership of the conversation.

Frame it as a safety intervention rather than a convenience one, because it is. The hazard ratios in the Blumenthal cohort are for MRSA and C. difficile, not for inconvenience (2).

And ask the question that costs nothing: has this person taken a penicillin since. A meaningful share of these labels fall over on that answer alone.

The Bottom Line

Roughly ten percent of people carry a penicillin allergy label and most of them are not allergic, usually because a childhood viral rash got blamed on an antibiotic. The label is not harmless. Carrying it is associated with a 69 percent higher risk of MRSA and a 26 percent higher risk of C. difficile, driven by the broader antibiotics used instead. Four questions, scored as PEN-FAST, identify most low-risk labels without any testing at all, which makes this one of the few things in medicine that is fixed by a conversation. If your reaction was anaphylaxis, angioedema or a blistering rash, the label stays and you keep your epinephrine, which now comes as a nasal spray as well as an injector.

Sources

1. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and management of penicillin allergy: a review. JAMA. 2019;321(2):188-199. PMID 30644987. https://pubmed.ncbi.nlm.nih.gov/30644987/

2. Blumenthal KG, Lu N, Zhang Y, Li Y, Walensky RP, Choi HK. Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ. 2018;361:k2400. PMID 29950489. https://pubmed.ncbi.nlm.nih.gov/29950489/

3. Trubiano JA, Vogrin S, Chua KYL, et al. Development and validation of a penicillin allergy clinical decision rule. JAMA Intern Med. 2020;180(5):745-752. PMID 32176248. https://pubmed.ncbi.nlm.nih.gov/32176248/

4. Hernandez-Trujillo V, Tachdjian R, et al. Successful administration of neffy (epinephrine nasal spray) by patients and caregivers. Ann Allergy Asthma Immunol. 2026. PMID 42476303. https://pubmed.ncbi.nlm.nih.gov/42476303/

5. Takahashi K, Yanagida N. Intranasal adrenaline: a new treatment for anaphylaxis. Pediatr Allergy Immunol. 2026;37(3):e70316. PMID 41796069. https://pubmed.ncbi.nlm.nih.gov/41796069/

Two empty medical vials and syringe beside an illustrated human brain

Does the Shingles Vaccine Lower Dementia Risk? What the Evidence Shows

On August 30, 2026August 31, 2026 By Dr. Scott RennieIn Infectious DiseaseLeave a comment

I wrote about shingles here in 2012. Back then the vaccine question was simple and slightly boring: there was one shot, it worked reasonably well, and most people over 60 were told to consider it.

The question I get now is different. People do not ask me whether the shingles vaccine prevents shingles. They ask whether it protects the brain.

That is a fair question, the evidence behind it is more interesting than most vaccine headlines, and it has a catch in it that almost nobody reporting on it mentions.

Start with the boring part, because it is the part that matters

Shingles is the chickenpox virus waking up. It sat in a nerve root for decades and then came back out along that nerve, which is why the rash arrives in a band on one side and stops at the midline.

The rash heals. The nerve pain is the problem. Postherpetic neuralgia is burning, electric pain in the same distribution that can outlast the rash by months, occasionally years, and it is genuinely difficult to treat once it settles in. That, not the rash, is the reason to care about this.

The current vaccine is Shingrix, given as two doses. In the ZOE-50 trial across more than 15,000 adults aged 50 and over, efficacy against shingles was 97.2 percent (1). In ZOE-70, in adults 70 and older, it was 89.8 percent, and in the pooled analysis of everyone over 70 across both trials, efficacy against postherpetic neuralgia specifically was 88.8 percent (2).

Those are very good numbers. Vaccines rarely perform like that in the age group where you most want them to work.

It is a reactogenic shot. Roughly one in six people feels properly unwell for a day or two after a dose, sore arm, tired, achy, sometimes feverish. I tell people that in advance, because a person who was warned takes the second dose and a person who was ambushed does not.

The dementia finding, and the catch

Here is where it gets interesting.

In 2025, a group at Stanford published a study in Nature that used an accident of Welsh policy (3). When Wales rolled out the shingles vaccine, eligibility was set by exact date of birth. Anyone born before 2 September 1933 was ineligible, permanently. Anyone born on or after that date was eligible.

Think about what that creates. A person born on 1 September 1933 and a person born on 3 September 1933 are, on average, identical in every way that matters. Same generation, same health, same everything. The only systematic difference between them is that one could get the vaccine and one could not. Uptake went from 0.01 percent in the group one week too old to 47.2 percent in the group one week younger.

That is as close to a randomized trial as you will ever get out of routine health records without running one.

Over seven years, the vaccinated group had a 3.5 percentage point lower probability of a new dementia diagnosis, which works out to a 20 percent relative reduction (3). The effect was stronger in women. The authors then reproduced it in a separate population using death certificates rather than diagnoses, which guards against the finding being an artifact of who happens to get diagnosed.

Now the catch.

Wales was using Zostavax, the old live-attenuated vaccine. That product was withdrawn from the US market in November 2020. It is not what you would be offered today, and the study does not tell you what Shingrix does.

A separate group looked at exactly that, using the rapid switchover from live to recombinant vaccine as its own natural experiment, and found the recombinant vaccine associated with a 17 percent increase in dementia-free time, about 164 extra days without a diagnosis among those who went on to be diagnosed, over six years (4). Again larger in women. I will note, because they note it, that the senior author consults for the manufacturer, and that GSK had no involvement in the study and did not know about it until after acceptance.

What I actually think about it

I think the signal is real and I do not think it should be the reason you get the shot.

Those are compatible positions. The dementia work is observational in design even when it is cleverly built, the mechanism is unproven, and no randomized trial has tested it. Something could still be wrong with it. Meanwhile the case for Shingrix rests on two large randomized controlled trials showing it prevents a disease that causes months of nerve pain, and that case was already sufficient on its own.

So my framing is this. Get it because postherpetic neuralgia is miserable and largely preventable. If the dementia finding holds up, you will have gotten that for free.

What the finding does change is urgency. I used to be relaxed when someone in their early fifties wanted to put it off a few years. I am less relaxed now, because if there is a neurological benefit it presumably accrues with time, and there is no advantage to waiting.

The part that belongs to my day job

Most of my practice is metabolic, and shingles turns out to sit closer to that than it looks.

A meta-analysis of sixteen studies put the risk of shingles in people with diabetes at a pooled relative risk of 1.38 compared with the general population (5). A separate population cohort found that people with diabetes had roughly 1.45 times the risk of postherpetic neuralgia, and that when they got it, it tended to be more severe and more persistent (6).

So the group most likely to get shingles, and most likely to be left with lasting nerve pain afterward, overlaps heavily with the group I see for weight and glucose.

There is a second reason this matters in diabetes that has nothing to do with the vaccine. Postherpetic neuralgia and diabetic peripheral neuropathy feel similar, they get treated with the same drugs, and I have seen the second diagnosis absorb the first. If burning pain shows up in a band, on one side, in a person who also has stocking-glove neuropathy, that is shingles until proven otherwise, whatever the chart already says.

Age 50 is also, not coincidentally, right in the middle of the menopause transition, which is the other half of what I do. If a woman is already in front of me talking about hormone therapy and bone density, the shingles vaccine is a reasonable thing to raise in the same visit, and often nobody has.

If you already have it, the clock is the thing

Antivirals for shingles work best started within 72 hours of the rash appearing. After that the benefit falls off steeply.

That single fact is the strongest argument I know for handling suspected shingles by video. A one-sided painful band of blistering rash with a burning prodrome is one of the more recognizable things in medicine, and a decent photograph plus a history usually settles it. The bottleneck has never been diagnostic difficulty. It has been how long it takes to be seen, and a visit you can get this afternoon beats a better visit on Thursday.

Two exceptions I do not manage remotely. A rash near or in the eye, particularly on the tip of the nose, needs same-day ophthalmology because of the risk to the cornea. Shingles in someone significantly immunocompromised, or a disseminated rash crossing the midline, goes in person.

For patients

If you are 50 or over, you are eligible for Shingrix regardless of whether you remember having chickenpox, and regardless of whether you had the old vaccine years ago.

If you are immunocompromised, the recommendation starts at 19 (7).

Expect to feel rough for a day after each dose, and get the second one anyway. One dose is not the regimen.

If a painful one-sided rash appears, get seen inside three days. Do not wait to see whether it spreads.

For colleagues

The dementia data is worth knowing and worth describing accurately. The strongest causal design was done on a product no longer sold in the United States, and patients who have read a headline usually have not been told that.

Diabetes belongs on the list of reasons to push the vaccine actively rather than mention it in passing.

And check the vaccine history of the metabolic patients. Nobody owns this conversation, so it tends not to happen. I have started treating it as part of the same visit rather than something to refer out, and it costs about ninety seconds.

The Bottom Line

Shingrix prevents shingles about 97 percent of the time in adults over 50, and it prevents postherpetic neuralgia, which is the thing actually worth avoiding. A natural experiment in Wales found 20 percent less dementia over seven years in vaccinated adults, and a second study suggests the current recombinant vaccine carries a similar signal, but the strongest of that evidence came from a live vaccine the United States no longer uses. Get the vaccine for the nerve pain it reliably prevents rather than the dementia it might. If you have diabetes, your risk of both shingles and lasting nerve pain afterward is meaningfully higher, which moves this up the list. And if a one-sided painful rash turns up, the antiviral window is 72 hours.

Sources

1. Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087-2096. PMID 25916341. https://pubmed.ncbi.nlm.nih.gov/25916341/

2. Cunningham AL, Lal H, Kovac M, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375(11):1019-1032. PMID 27626517. https://pubmed.ncbi.nlm.nih.gov/27626517/

3. Eyting M, Xie M, Michalik F, et al. A natural experiment on the effect of herpes zoster vaccination on dementia. Nature. 2025;641(8062):438-446. PMID 40175543. https://pubmed.ncbi.nlm.nih.gov/40175543/

4. Taquet M, Dercon Q, Todd JA, Harrison PJ. The recombinant shingles vaccine is associated with lower risk of dementia. Nat Med. 2024;30(10):2777-2781. PMID 39053634. https://pubmed.ncbi.nlm.nih.gov/39053634/

5. Huang CT, Lee CY, Sung HY, et al. Association between diabetes mellitus and the risk of herpes zoster: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2022;107(2):586-597. PMID 34536279. https://pubmed.ncbi.nlm.nih.gov/34536279/

6. Wen SY, Ou-Yang C, Hsu CY, et al. Impact of type 1 versus type 2 diabetes on developing herpes zoster and post-herpetic neuralgia: a population-based cohort study. Acta Derm Venereol. 2023;103:adv9400. PMID 37787418. https://pubmed.ncbi.nlm.nih.gov/37787418/

7. Anderson TC, Masters NB, Guo A, et al. Use of recombinant zoster vaccine in immunocompromised adults aged 19 years and older: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2022;71(3):80-84. PMID 35051134. https://pubmed.ncbi.nlm.nih.gov/35051134/

A folded white towel beside a plain bar of soap in a ceramic dish and a safety razor on a sunlit wooden bathroom shelf

Why Do I Keep Getting Boils?

On August 29, 2026August 30, 2026 By Dr. Scott RennieIn Skin & Wound CareLeave a comment

“Boil” is not a diagnosis. It is a word patients use for a painful lump that came up, hurt, and either drained or had to be opened. Underneath that one word sit at least four different problems with four different answers, and the reason people keep getting them is usually that nobody has said which one they have.

So the useful question is not what to put on it. It is where they keep happening.

Location does most of the diagnostic work

A furuncle is an infected hair follicle. It can turn up anywhere hair grows, it is usually staph, and a person who gets one is not necessarily a person who will get another.

Hidradenitis suppurativa lives in specific places. Armpits, groin, under the breasts, inner thighs, buttocks, around the anus. The same sites, over and over, often on both sides.

A pilonidal sinus sits in the cleft at the top of the buttocks and essentially nowhere else.

An inflamed epidermoid cyst comes back in exactly the same spot every time, because the sac is still there.

Four sites, four answers. If your lumps keep appearing in your armpits and groin, the working diagnosis is not recurrent boils.

The one that gets missed for years

Hidradenitis suppurativa is the diagnosis I most want people to know the name of, because the delay in getting it is measured in years rather than visits, and misdiagnosis is one of the biggest drivers of that delay (1).

What separates it from recurrent furuncles:

The same locations, repeatedly. Tunnels under the skin connecting one lesion to the next, which patients often describe as the drainage coming out somewhere other than where it went in. Rope-like scarring that builds up over years. Blackheads appearing in pairs, which is a small finding and quite specific. A family history, which is present often enough to be worth asking about.

Cultures from HS lesions frequently grow something, which is how it keeps getting called an infection. It is an inflammatory disease of the follicle, and antibiotics in it are working as anti-inflammatories more than as antimicrobials.

If you have been given six courses of antibiotics for boils in the same two places, you probably have HS and nobody has said so.

What actually treats an abscess

Drainage. Not antibiotics.

The IDSA guideline on skin and soft tissue infection puts incision and drainage as the treatment for a drainable abscess, with antibiotics as an adjunct in defined situations rather than a substitute (2). An abscess that is not opened does not resolve because someone took cephalexin.

This is why, practising by video, my rule is that a suspected abscess goes out to be drained rather than getting a prescription from me. I am firmer about that than some colleagues are, and I have not regretted it. A camera cannot tell me whether something is fluctuant, and a prescription that delays drainage by four days makes the eventual procedure bigger.

Why they keep coming back

For genuine recurrent furunculosis, the usual driver is staph colonization. The organism lives in the nose, the axillae, the groin, and it seeds new follicles.

Decolonization is the standard answer: intranasal mupirocin, chlorhexidine washes, attention to towels and razors. What is worth knowing is that treating the whole household beats treating the individual. Fritz and colleagues randomized exactly that comparison in children with community-associated staph infection and found household-wide decolonization more effective at eradication than treating the index patient alone (3).

That matters practically, because the patient who keeps recurring is often the one person in a house of four getting treated.

The part that belongs to my day job

Obesity, smoking and diabetes all sit behind recurrent skin infection, and they sit behind HS particularly hard.

Friction and skin folds are part of it, and plenty else is going on besides. Higher glucose impairs neutrophil function. Adipose tissue is metabolically active and inflammatory. Skin folds hold moisture and macerate. And the inflammatory biology of HS overlaps with metabolic disease in a way that is more than coincidence of body habitus.

What has changed recently is that we have a drug class that moves several of those levers at once. Multiple cohorts and case series now report reduced HS disease activity, fewer flares and less pain in patients treated with GLP-1 receptor agonists (4), and a cross-sectional survey found roughly two thirds of respondents reporting improvement in HS-specific measures (5).

I want to be careful here, because the enthusiasm is ahead of the evidence. These are retrospective cohorts and patient-reported surveys, not randomized trials with standardized background therapy. I take the signal seriously in a patient who has both conditions and would be a candidate for the drug anyway. I would not start an incretin in someone whose only indication is their skin.

Smoking is the other lever, and in HS it is a big one. If someone with HS smokes, that is the highest-yield conversation available, and it is not close.

For patients

Notice where they happen. If it is armpits, groin, under the breasts or the buttocks, and it is the same places repeatedly, ask your clinician about hidradenitis suppurativa by name. Naming it is often what gets the diagnosis moving.

If you have a painful lump with a pocket of pus in it, it needs draining. An antibiotic on its own will not finish the job.

If you get recurrent boils and there are other people in your house, ask whether the whole household should be treated rather than just you.

For colleagues

Ask where, not what. Location sorts furuncle from HS from pilonidal faster than any other question, and it is the question that shortens the diagnostic delay.

Household decolonization outperforms individual decolonization, and we mostly still prescribe the individual version.

The GLP-1 and HS literature is worth knowing and worth being careful with. When a patient with both asks whether the drug will help their skin, name the study designs and stop short of promising.

The Bottom Line

Recurrent boils in the armpits, groin, under the breasts or the buttocks are usually hidradenitis suppurativa, and the average person with it waits years for someone to say the word. A true abscess is treated by drainage, with antibiotics as an adjunct rather than a substitute. Recurrent furunculosis is usually a colonization problem, and treating the whole household beats treating the patient. And if the same person has recurrent skin infection, obesity and smoking, the skin is the symptom being presented and the other two are what is driving it.

Sources

1. Murray N, et al. Equity and Outcome Events in Hidradenitis Suppurativa: Exploring Effect Modifiers Associated with Diagnostic Delay in the Real World. Dermatol Ther (Heidelb). 2024;14(12):3211-3227. PMID 39487935. https://pubmed.ncbi.nlm.nih.gov/39487935/

2. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-52. PMID 24973422. https://pubmed.ncbi.nlm.nih.gov/24973422/

3. Fritz SA, Hogan PG, Hayek G, et al. Household versus individual approaches to eradication of community-associated Staphylococcus aureus in children: a randomized trial. Clin Infect Dis. 2012;54(6):743-751. PMID 22198793. https://pubmed.ncbi.nlm.nih.gov/22198793/

4. Rao S, et al. Skin Impacts and Tradeoffs of GLP-1 Therapy: Improved Patient-Reported Outcomes of Inflammatory Skin Disease. Dermatol Ther (Heidelb). 2026. PMID 42579223. https://pubmed.ncbi.nlm.nih.gov/42579223/

5. Javaheri ED, et al. Impact of GLP-1 Receptor Agonists on Hidradenitis Suppurativa: A Cross-Sectional Survey. Int J Dermatol. 2026 Jul 16. PMID 42461155. https://pubmed.ncbi.nlm.nih.gov/42461155/

6. DermNet. Hidradenitis suppurativa. https://dermnetnz.org/topics/hidradenitis-suppurativa

A stack of folded white cotton bed linens beside a plain tube of cream and a glass of water on a sunlit wooden nightstand

Why Am I Still Itching After Scabies Treatment?

On August 29, 2026August 30, 2026 By Dr. Scott RennieIn Infectious DiseaseLeave a comment

The scabies post I wrote in 2012 gets read more than anything else on this site, which still surprises me. And the question that comes back from it is almost always the same one. I did the treatment. Why am I still itching?

There are two very different answers, and telling them apart is the whole job.

Itching is not the same as infestation

Scabies itch is an allergic response. The mite burrows, and your immune system reacts to the mite, its eggs and its waste. Kill every mite tonight and all of that material is still sitting in your skin tomorrow, and your immune system is still reacting to it.

So the itch outlasts the infestation. Reliably. Two to four weeks is ordinary and six is not rare, and during that time you can be completely mite-free and completely miserable.

This is the single most useful thing to know about scabies, and almost nobody is told it at the pharmacy counter. People finish the cream, itch for another two weeks, conclude it failed, and go looking for a second prescription they may not need.

How to tell persistent itch from actual failure

The direction of travel matters more than the intensity.

Post-treatment itch gets slowly better. Some days are worse, but the trend over a fortnight runs downward, no new spots appear, and the places that itched worst at the start are the places that quiet down first, which is what you would expect if what is happening is an immune reaction winding itself down rather than an infestation carrying on.

Failure looks different. New burrows, fresh papules in places that were clear, itch that is escalating rather than settling, and household contacts starting to scratch two weeks after you did.

Burrows settle it. Thin, slightly raised, greyish lines a few millimetres long, most often in the finger webs, the wrists, the belt line, around the nipples, and on the genitals. New burrows mean live mites.

Timing helps too. An itch that was improving and then turned around at week three is reinfestation or failure. The tail of the original reaction does not do that.

Failure is more common than people think

A systematic review and meta-analysis in the British Journal of Dermatology pooled 147 studies and put the overall treatment failure rate at 15.2 percent (1). Not a rounding error. Roughly one in seven.

By drug, permethrin failed 10.8 percent of the time, oral ivermectin 11.8 percent and topical ivermectin 9.3 percent (1).

Two numbers from that paper changed how I think about this. The first is dosing: a single dose of oral ivermectin failed 15.2 percent of the time against 7.1 percent for two doses (1). Ivermectin does not kill eggs. One dose leaves the next generation to hatch, which is why the second dose at day eight to fourteen is not optional.

The second is the trend. Across studies from 1983 to 2021, overall failure rose by 0.27 percent per year, and permethrin failure by 0.58 percent per year (1). The authors are careful to say that no study in the review actually assessed resistance, so this is a signal and not a finding. But permethrin is working less well than it used to, and if your treatment failed, that is a real possibility rather than a personal failing.

The boring reasons treatment fails

Usually the reason is application.

Neck down, every square inch. People miss the same places every time: between the toes, under the fingernails and toenails, the navel, the buttock crease, behind the ears. In infants, the elderly and anyone immunosuppressed, the scalp and face need treating too, which contradicts the neck-down instruction most people are given.

Leave it on eight to fourteen hours. Wash hands after applying and it comes straight back off, so reapply to the hands after any handwashing.

Treat everyone in the household on the same day, symptoms or not. Someone incubating quietly will hand it back to you in three weeks.

Repeat at day seven. The cream does not reliably kill eggs either, which is the same problem ivermectin has and the same reason the second application exists.

On the laundry, I am less strict than most instructions you will read. Classic scabies transmits by prolonged skin-to-skin contact, and fomite transmission is minor outside crusted scabies. Bedding, towels and clothing from the last three days, hot wash or bagged for three days, is enough. Nobody needs to shampoo a mattress.

The lumps that stay for months

Nodular scabies is worth naming because it frightens people. Firm, itchy, reddish-brown nodules on the scrotum, groin or armpits. They can persist for weeks to months after successful treatment. They are a granulomatous immune response, not live infestation, and treating them again with a scabicide does nothing. They respond to a topical steroid and to time.

When the itch is not scabies at all

Here is where I want to be direct, because this is the failure mode I care most about.

If you were treated for scabies, you never had burrows, no household contact ever itched, and you are still itching at eight weeks, the working diagnosis was probably wrong.

Generalized itch with no primary rash is its own clinical problem, and the list behind it is largely internal. Dry skin and eczema account for most of it. But persistent itch without a rash is also how uncontrolled diabetes, chronic kidney disease, cholestatic liver disease, thyroid disease, iron deficiency and some blood disorders present. In a patient with unexplained itch and no burrows, I would rather check an A1c, a metabolic panel, liver function, thyroid and a CBC than write a third prescription for permethrin.

That scenario is not rare. It is the one that gets missed while everyone concentrates on the mite.

What I ask for on a video visit

Two photographs. One from a distance showing the distribution, which is diagnostic in itself, and one macro shot as close as the phone will focus, aimed at a finger web or a wrist. Back up six inches if it will not focus, which fixes it nearly every time.

I ask when the itch is worst, because scabies is classically worse at night, and I ask who else in the house is scratching. The household answer is often better evidence than the photographs.

For patients

Itching for two to four weeks after correct treatment is expected and does not mean it failed. Watch the direction, not the intensity.

If you were given a single dose of oral ivermectin and nothing else, ask about the second dose. If new spots or new burrows appear, go back. And if you have been itching for two months with nothing to see on the skin, ask for blood work rather than another cream.

For colleagues

The two-dose ivermectin regimen has the evidence behind it and single-dose prescriptions are still going out. That is the cheapest fix available in this whole area.

Tell people at the point of prescribing that the itch will outlast the mite. It prevents a second visit, a second prescription and a great deal of anxiety, and it takes about ten seconds.

And keep systemic pruritus on the list. A patient on their third scabicide with no burrows and no contacts deserves labs, not a refill.

The Bottom Line

Itch that is slowly improving two to four weeks after treatment is the immune system finishing its argument with a mite that is already dead. Itch that is escalating, or that comes with new burrows or newly scratching housemates, is failure or reinfestation, and failure runs around one in seven. If you got one dose of ivermectin, you got half a treatment. And if the itch has gone on for months with nothing visible on the skin, the problem may never have been on your skin at all.

Sources

1. Mbuagbaw L, Sadeghirad B, Morgan RL, et al. Failure of scabies treatment: a systematic review and meta-analysis. Br J Dermatol. 2024;190(2):163-173. PMID 37625798. https://pubmed.ncbi.nlm.nih.gov/37625798/

2. DermNet. Scabies. https://dermnetnz.org/topics/scabies

A plate of boiled eggs and cottage cheese beside a rolled gauze bandage and a glass of water on a sunlit wooden table

Why Won’t My Wound Heal?

On August 29, 2026August 30, 2026 By Dr. Scott RennieIn Skin & Wound CareLeave a comment

The question comes up on almost every wound follow-up, and it is nearly always phrased the same way. What should I be eating to make this heal faster?

It is a good question. The answer patients get is usually a list of vitamins, which is mostly wrong, or a shrug, which is worse. There is real evidence here. It just does not point where the supplement aisle points.

A healing wound is a construction project

Closing a wound means building tissue. Collagen synthesis, angiogenesis, epithelial migration, immune cell proliferation. All of that runs on amino acids and calories, and the demand is above baseline for as long as the wound is open. A large or chronic wound raises resting energy expenditure meaningfully.

Which means the first question is not which supplement. It is whether the person is eating enough of anything at all. In older adults with a chronic wound, the answer is frequently no, and no capsule fixes an 1,100 calorie a day intake.

What glucose does to the machinery

Hyperglycemia interferes with wound healing at several points at once. Glycosylation impairs neutrophil and macrophage function, which stretches out the inflammatory phase instead of letting the wound progress to proliferation. Fibroblast activity falls. VEGF expression falls, so new vessels are slower to arrive. Matrix metalloproteinase activity rises, which means the collagen that does get laid down is broken down faster than it should be. Collagen density ends up lower.

Put underlying peripheral arterial disease on top and the wound has a supply problem as well as a manufacturing problem.

This is why I care about the A1c on a wound visit and not only on a diabetes visit. The same laceration on a person running an A1c of 11 and a person running a 6 is two different clinical situations, and only one of them is going to close on schedule.

An aside that patients find more persuasive than any of the biochemistry: the glucose control that matters for a wound is the control over the next several weeks, not the number on the day of the injury. That is actionable. It gives someone something to do about a wound that is already there.

The protein number

For adults with a pressure injury who are malnourished or at risk of it, the 2019 international guideline from EPUAP, NPIAP and the Pan Pacific alliance recommends 1.25 to 1.5 grams of protein per kilogram of body weight per day, with 30 to 35 kilocalories per kilogram per day for energy (1).

Those are the best-supported numbers in wound nutrition, and I use them as the floor for any significant open wound, not only pressure injuries. Most people are nowhere near them. A 70 kilogram adult needs roughly 88 to 105 grams of protein a day on that recommendation, and the typical intake I hear described on a video visit is half that.

Worth noting the overlap with the rest of my practice. When I start a patient on an incretin I ask for 1.6 grams per kilogram per day and strength training two to three times a week, because the risk on those drugs is lean mass loss. A patient on an incretin who also has a wound is being asked for the same thing for two different reasons, which makes the conversation easier rather than harder.

Arginine, and how good the evidence actually is

Arginine gets singled out because it is a substrate for nitric oxide and for proline, and proline goes into collagen. The 2019 guideline recommends a high-calorie, high-protein oral nutrition supplement fortified with arginine, zinc and antioxidants for adults with a stage 2 or greater pressure injury who are malnourished or at risk of malnutrition (1).

Read that recommendation carefully, because it is narrower than how it gets quoted. It is for a specific wound severity, in a specific nutritional context, and the arginine comes inside a fortified supplement rather than as arginine on its own (2). The trials behind it tested the whole formulation. Nobody has shown that arginine by itself, added to an adequate diet in a well-nourished person, does anything for a wound.

I have no objection to those supplements in the patients the guideline describes. I do object to a well-fed person with a healing surgical incision spending money on arginine capsules.

Vitamin C and zinc

Both are genuinely required for wound healing. Vitamin C is a cofactor for the hydroxylation steps in collagen synthesis, and frank scurvy produces wounds that will not close. Zinc deficiency impairs epithelialization.

None of that means supplementing someone who is not deficient helps. Reviews of vitamin and mineral supplementation in wound care keep landing in the same place: unclear benefit unless there is a confirmed or suspected deficiency, and no well-powered randomized trial showing that routine vitamin C or zinc speeds healing in replete patients (3).

So I correct documented deficiencies and I do not supplement reflexively. High-dose zinc in particular is not harmless; it interferes with copper absorption over time.

This is the part of the conversation patients like least, and I say it anyway.

What matters more than any of it

Smoking. Sørensen’s meta-analysis of surgical patients found substantially higher rates of wound complications and infection in smokers, and improvement with cessation before surgery (4). If a patient with a slow wound smokes, that is the highest-yield thing on the list, and it is not close.

Then perfusion. A wound on a limb without a decent pulse is a vascular problem wearing a dressing, and no amount of protein fixes it.

Then offloading and moisture balance, which are mechanical rather than nutritional and are where most home wound care goes wrong.

Nutrition belongs on the list. It belongs below those.

For patients

Eat more protein than you think you need while a wound is open. Aim for something in the range of 1.25 to 1.5 grams per kilogram of your body weight per day, which for most adults means adding a protein source to every meal rather than eating one large dinner. If you are diabetic, the wound is a reason to tighten control now, not later.

Skip the wound-healing supplement stack unless your clinician has found an actual deficiency. If you smoke, stopping will do more for that wound than everything else on this page combined.

For colleagues

Ask what people are eating before you reach for a supplement, and ask in grams rather than in general terms. The 1.25 to 1.5 g/kg recommendation is easy to quote and rarely translated into food for the patient, which is where it fails.

Check a zinc or vitamin C level if the history suggests deficiency, then treat what you find. Do not treat the wound with a multivitamin on principle.

And put smoking cessation at the top of the plan for any wound that is behind schedule, ahead of the dressing change conversation.

The Bottom Line

Wounds heal on protein, calories and blood flow, in something like that order, and they stall on high glucose and tobacco. The guideline numbers worth remembering are 1.25 to 1.5 grams of protein per kilogram per day and 30 to 35 kilocalories per kilogram per day. Arginine and antioxidant supplements have a real place, in malnourished patients with stage 2 or worse pressure injuries, and almost nowhere else. Vitamin C and zinc are worth correcting when they are low and worth skipping when they are not. If you fix only one thing on this list, fix the smoking.

Sources

1. European Pressure Ulcer Advisory Panel, National Pressure Injury Advisory Panel and Pan Pacific Pressure Injury Alliance. The Role of Nutrition for Pressure Injury Prevention and Healing: 2019 International Clinical Practice Guideline recommendations. https://cdn.ymaws.com/npiap.com/resource/resmgr/The_Role_of_Nutrition_for_Pr.pdf

2. Chu AS, Delmore B. Arginine: What You Need to Know for Pressure Injury Healing. Adv Skin Wound Care. 2021;34(12):630-636. PMID 34807894. https://pubmed.ncbi.nlm.nih.gov/34807894/

3. Indian Health Service National Pharmacy and Therapeutics Committee. Formulary Brief: Nutritional Supplements in Wound Healing. https://www.ihs.gov/sites/nptc/themes/responsive2017/display_objects/documents/guidance/NPTC-Formulary-Brief-NutritionalSupplementsinWoundHealing.pdf

4. Sørensen LT. Wound healing and infection in surgery. The clinical impact of smoking and smoking cessation: a systematic review and meta-analysis. Arch Surg. 2012;147(4):373-383. PMID 22508785. https://pubmed.ncbi.nlm.nih.gov/22508785/

5. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017;376(24):2367-2375. PMID 28614678. https://www.nejm.org/doi/10.1056/NEJMra1615439

A hand mirror, a pair of folded cotton socks and a home glucose meter with a lancet on a sunlit wooden table

What Does Diabetes Do to Your Skin?

On August 29, 2026August 30, 2026 By Dr. Scott RennieIn Skin & Wound CareLeave a comment

Skin is the one organ I can actually see on a video visit. No stethoscope, no palpation, no reaching across the desk. Just a camera, whatever light the patient happens to have, and a screen. That limitation has made me pay closer attention to skin than I did when I worked in urgent care, because on video it is often the first physical evidence that something metabolic is going on.

Between 30 and 70 percent of people with diabetes develop a skin problem attributable to the disease at some point (1). That is an enormous range, which tells you the studies are measuring different populations and different definitions rather than anything precise. Take the range as what it is, a signal that this is common, not a statistic to quote back to anyone.

What follows is what I look for, why it matters, and where I think the usual advice is weaker than it sounds.

The velvet patch on the back of the neck

Acanthosis nigricans is the one I care about most, because it is visible, it is early, and patients almost never bring it up. Dark, thickened, velvety skin in the folds. Back of the neck, armpits, groin, under the breasts. Patients describe it as dirt that will not wash off, and some have been scrubbing at it for years.

The mechanism is insulin. Hyperinsulinemia drives IGF-1 receptor activation on keratinocytes and fibroblasts, which proliferate (2). So the plaque is a rough readout of how much insulin the pancreas has been pushing out to keep glucose in range. It shows up before the fasting glucose does. Sometimes years before.

Skin tags travel with it and share the same driver (2). A patient with acanthosis nigricans and a crop of acrochordons on the neck and axillae is telling you about their insulin resistance without a single lab drawn.

Here is where I differ from what patients are usually told. Dermatology handles acanthosis nigricans as a cosmetic complaint and offers topical retinoids, urea, sometimes laser. Those do something to the appearance. None of them touch the reason it is there. I follow the ADA rule and screen every adult from 35 regardless of BMI, and when I see that patch I do not wait for the birthday. I check an A1c.

It also improves. Not overnight, and not completely in everyone, but weight loss and improved insulin sensitivity soften the plaques over months. That is worth telling someone who has been scrubbing their neck since high school.

Skin tags carry information

I have a whole post on what skin tags are and what they look like, and it gets steady traffic from people worried about a lesion. What that post does not do is explain why someone in their thirties suddenly has fifteen of them.

Friction is part of it. Insulin is the rest.

What high glucose actually does to a wound

This one deserves its own post and is getting one. The short version: glycosylation impairs neutrophil and macrophage function, which prolongs the inflammatory phase instead of letting the wound move on to proliferation. Fibroblast activity drops, VEGF expression drops, matrix metalloproteinases go up, collagen density falls. Layer underlying vascular disease on top of that and you have a wound that stalls.

The practical consequence is that a cut on someone with an A1c of 11 is a different clinical problem than the same cut on someone with an A1c of 6, even though it looks identical on camera.

The infections that come with the territory

Candidal intertrigo lives in the skin folds, and the bigger the fold the more reliably it shows up. Beefy red, satellite lesions at the edge, itching or burning rather than pain. Patients treat it with hydrocortisone from the drugstore, which makes it worse, and then arrive convinced they have an allergy.

Tinea in all its addresses, feet, groin, nails. Onychomycosis in particular is stubborn and, in a diabetic foot, is not merely a nuisance: a thickened dystrophic nail is a pressure point and a portal.

Then cellulitis. Elevated glucose, impaired barrier, and a break in the skin from a fissure or a fungal infection between the toes. My rule for an abscess is that it goes out for drainage rather than getting empiric antibiotics from me over video, and I am firmer about that than some colleagues are.

Hidradenitis suppurativa, and what changed

HS has been badly served for a long time. Painful nodules and sinus tracts in the axillae, groin and under the breasts, frequently mistaken for recurrent boils for years before anyone names it. The association with obesity is strong and it is not a coincidence of body habitus alone; the inflammatory biology overlaps.

What has changed recently is incretin therapy. Multiple cohorts and case series now report reduced disease activity, fewer flares and less pain in HS patients treated with GLP-1 receptor agonists, alongside the expected BMI reduction (3). A cross-sectional survey found roughly two thirds of respondents reporting improvement in HS-specific measures (4).

I want to be honest about the strength of that evidence, because the enthusiasm is running ahead of it. These are retrospective cohorts, case series and patient-reported surveys. There is no adequately powered randomized trial with standardized background therapy. The signal is consistent enough that I take it seriously in a patient who has both conditions and would be a candidate for the drug anyway. It is not a reason to start an incretin in someone whose only indication is HS.

The foot

Somewhere between 19 and 34 percent of people with diabetes will develop a foot ulcer in their lifetime (5). The number that changed how I talk to patients is not that one, though. It is what happens after the ulcer closes: roughly 40 percent recur within one year, close to 60 percent within three years, and 65 percent within five (5).

Armstrong and colleagues argued from that data that a patient whose wound has closed should be thought of as in remission rather than healed (5). I use that word deliberately with patients now, because a person who believes they are healed puts the mirror away and stops looking at the bottom of their feet, while a person who believes they are in remission keeps checking, keeps wearing the shoes that were fitted for them, and calls about a blister on the day it appears rather than three weeks later when it has become something else. Remission gets you daily foot checks. Healed gets you a pair of sandals and a summer of walking on hot pavement with neuropathy.

That framing does more work in a fifteen-minute visit than any amount of education about glycemic targets.

What I ask for on video

Skin over a camera is genuinely hard. Autofocus hunts, phone processing smooths texture, and the color balance depends on whether someone is under a kitchen light or a window.

So I ask for two photographs of anything I need to actually assess. One from a distance, far enough back to show where the lesion sits and what the surrounding skin looks like, and one macro, as close as the phone will focus without blurring. Multiple angles if there is any elevation to it. The blur problem is the single most common reason I have to ask twice, and it is almost always because the patient is closer than the lens can handle. Backing up six inches fixes it.

For anything in a fold, I want the fold held open in the shot. For feet, I want the sole and between the toes, which usually means someone else holds the camera.

For patients

If the skin on the back of your neck or in your armpits has gone dark and thick and will not scrub off, that is not hygiene, and it is worth an A1c. If you are getting skin tags in bunches, same. If you have painful recurring lumps in your armpits or groin that have been called boils for years, ask specifically about hidradenitis suppurativa by name, because that is often what gets the diagnosis moving.

And if you have diabetes, look at your feet every day. Every day, including between the toes, including the bottom, using a mirror or a family member if you cannot see them.

For colleagues

Acanthosis nigricans in an adult is a screening prompt, not a dermatology referral. Check the A1c and the lipids before you send them for cosmetic treatment of the plaque.

The GLP-1 and HS literature is worth knowing about and worth being careful with. When a patient with both conditions asks whether the drug will help their skin, the honest answer names the cohorts, names their design, and stops short of promising anything.

On the foot, adopt the remission language. It changes adherence in a way that repeating ulcer statistics does not.

The Bottom Line

Skin is where metabolic disease announces itself, often years before a lab does. A velvety patch behind the neck, a crop of skin tags, a yeast infection in a fold that keeps coming back, a nail that will not clear. None of those are dermatologic curiosities to be treated in isolation. They are all the same disease showing up at the surface, and treating the surface without asking why it is there wastes the information. Check the A1c. Look at the feet. And when a wound closes on a diabetic foot, say remission, not healed.

Sources

1. Vâță D, et al. Cutaneous Manifestations Associated with Diabetes Mellitus: A Retrospective Study. Diseases. 2023;11(3). PMID 37606477. https://pubmed.ncbi.nlm.nih.gov/37606477/

2. Marchand L, et al. All about skin manifestations of insulin resistance and type 2 diabetes: acanthosis nigricans and acrochordons. Postgrad Med J. 2020;96(1134):237. PMID 31611265. https://pubmed.ncbi.nlm.nih.gov/31611265/

3. Rao S, et al. Skin Impacts and Tradeoffs of GLP-1 Therapy: Improved Patient-Reported Outcomes of Inflammatory Skin Disease. Dermatol Ther (Heidelb). 2026. PMID 42579223. https://pubmed.ncbi.nlm.nih.gov/42579223/

4. Javaheri ED, et al. Impact of GLP-1 Receptor Agonists on Hidradenitis Suppurativa: A Cross-Sectional Survey. Int J Dermatol. 2026 Jul 16. PMID 42461155. https://pubmed.ncbi.nlm.nih.gov/42461155/

5. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017;376(24):2367-2375. PMID 28614678. https://www.nejm.org/doi/10.1056/NEJMra1615439

6. International Working Group on the Diabetic Foot. IWGDF Guidelines on the prevention and management of diabetes-related foot disease, 2023. https://iwgdfguidelines.org/guidelines-2023/

A bedside table in soft morning light with a folded linen cloth, a glass of water and two books

Vaginal Dryness After Menopause: Why It Doesn’t Go Away

On August 29, 2026August 30, 2026 By Dr. Scott RennieIn Menopause & Women's HealthLeave a comment

Half the women who have it have never used a single treatment. Among the never-treated, close to three quarters have never mentioned it to a clinician. Both come from EMPOWER, a survey of 1,858 postmenopausal American women with genitourinary symptoms; most who stayed quiet assumed it was aging they had to live with (1).

That assumption is wrong in one specific way. Hot flashes usually fade. This does not.

Why the name changed in 2014

Genitourinary syndrome of menopause was coined at a 2013 ISSWSH and NAMS conference and endorsed by both boards in 2014 (2). It replaced vulvovaginal atrophy and atrophic vaginitis. Those terms implied an infection that is not there, and left out the urethra and bladder entirely (2).

Somewhere between 27% and 84%

That is the range cited by The Menopause Society and the 2025 AUA/SUFU/AUGS guideline (1)(3). A three-fold spread is less a number than a confession that case definitions vary wildly. One firmer figure: 84% of women six years past menopause had it (1).

Then the sentence that belongs on every package insert, verbatim from the 2020 position statement: “In contrast to vasomotor symptoms (VMS) that usually improve over time, GSM is generally progressive without effective therapy” (1). Generally, not always, but the direction is the point, and the 2025 guideline treats GSM as chronic (3). Untreated, it is also associated with women avoiding Pap smears (3). A complaint nobody raised becomes a screening gap.

What I can settle over video. What I can’t.

I practice entirely by telemedicine, so let me be direct about limits. The Menopause Society says diagnosis “requires the presence of both characteristic examination findings and bothersome symptoms” (1), and the 2025 guideline requires a genitourinary examination (3). No camera does that half.

Nearly everything else works remotely: the focused history, a medication review catching aromatase inhibitors and GnRH agonists, self-administered instruments like the Cervantes-GSM (3). And one free question: did the symptoms start before menopause? If so, another diagnosis is likelier (1). The mimics are the problem. Lichen sclerosus reads like GSM in a history and carries carcinoma risk. Postmenopausal bleeding I never close out on video. No guideline addresses telemedicine for GSM, so that division of labor is my own reasoning, not a society position.

So here is my position, and it diverges from the letter of the guideline. I recommend that a patient be examined in person for these symptoms. I also do not hesitate to treat her when what she describes is clearly GSM to me. The exam still needs to happen, and I say so. It does not have to happen first.

Red flags are where I hold the line. Bleeding after menopause, a visible lesion, or symptoms that predate menopause need eyes on them before anything else.

Start in the drugstore aisle

Lubricants and moisturizers get confused constantly. A lubricant goes on at the time of sex to cut friction. A moisturizer goes on a schedule, sex or no sex, to rehydrate tissue over time (1). Oil-based lubricants erode condoms. Hyaluronic acid sells at a premium with no evidence it beats products without it (1).

The humbling part. MsFLASH randomized 302 postmenopausal women to a 10-microgram vaginal estradiol tablet, a moisturizer, or dual placebo. At 12 weeks nothing beat placebo (P = .25 and .31) (4). The Menopause Society notes the placebo gel likely lubricated (1). The lesson survives: plenty improve on a drugstore moisturizer, which is why the guideline recommends them (3).

Low-dose vaginal estrogen

Most evidence, strongest recommendation (3). Vagifem (10 micrograms) and Imvexxy (4 or 10) run daily two weeks, then twice weekly; the Estring ring lasts 90 days; creams taper to two or three times weekly (1). After 14 days of daily use, serum estradiol on the inserts measured 3.6 and 4.6 pg/mL against 4.3 on placebo (1). Across 20 trials and 2,983 women exposed up to a year there was one endometrial cancer, and no progestogen is needed (1)(3).

The gap nobody advertises: the longest randomized trial of any vaginal estrogen ran 52 weeks (1), and this needs years of treatment. Reassurance past that is observational: 18 years of Nurses’ Health Study data found no excess chronic disease (5). Cochrane graded 30 trials low to moderate quality (6). Consistent direction, mediocre trials.

My own preference is the vaginal tablets. That is my preference and nothing stronger, and Cochrane found no efficacy difference between the preparations anyway (6). What decides it is what the patient prefers and what it costs her.

About that boxed warning, precisely

On November 10, 2025, FDA announced it was initiating removal of boxed warning language on menopausal hormone therapy, including low-dose vaginal estrogen, covering cardiovascular disease and breast cancer, plus probable dementia (7). The Menopause Society agreed, calling the warning a likely deterrent to a safe, effective therapy (8).

Implementation is running product by product. As of August 29, 2026, FDA’s updated-labeling list holds six drugs, and Estring is the only vaginal estrogen among them, its label updated April 27, 2026 (9)(10). Vagifem, Imvexxy and Premarin Vaginal Cream still carry the full boxed warning (11)(12)(13). Fill a prescription this week and you may find that warning in your own package. The paperwork has not caught up. Two things not to conflate: systemic estrogen-alone products keep a boxed warning for endometrial cancer, and ospemifene was never part of this action (7)(14).

DHEA, ospemifene, and the limits of systemic therapy

Vaginal DHEA (prasterone, Intrarosa) is a 6.5 mg insert used once daily, and endometrial sampling stayed inactive or atrophic in all 422 women studied for 52 weeks (1). It has never carried a boxed warning, and that predates the recent FDA action (15). Ospemifene (Osphena), the only oral option at 60 mg daily, holds the guideline’s weakest recommendation grade (3), causes hot flashes in 7.2% versus 2% on placebo (1), and its own boxed warning for endometrial cancer and cardiovascular disorders stands (14).

If you take systemic hormone therapy for hot flashes, do not assume it covers this. Some get inadequate GSM relief from it, and the guideline recommends adding local estrogen or DHEA (3). You will see percentages quoted for this. I could not trace one to a primary source, so I am not repeating one. The add-on rests on expert opinion, with no data on the combination’s risk (3).

Lasers

In a sham-controlled trial, 85 women were followed 12 months after three CO2 laser or sham treatments. Symptom severity fell 17.2 points with laser and 26.6 points with sham (16). Read that again. The point estimate favored sham, and the biopsy histology showed no difference either, so the collagen-remodeling mechanism they are sold on was never shown in tissue. The 2025 guideline calls them experimental outside trials (3), and no energy-based device is FDA-cleared for any gynecologic indication (17). Cash pay, expensive, and the widest gap between marketing and data here.

The best evidence here is about UTIs

Recurrent UTI means two culture-proven infections in six months, or three in a year (1). Vaginal estrogen for prevention is the only Grade B statement in the 2025 guideline; every other one is Grade C or expert opinion (3). Raz and Stamm, 1993: 93 postmenopausal women randomized to intravaginal estriol or placebo, infections falling to 0.5 episodes per patient-year against 5.9 (18). Estriol, oddly, is not sold as an FDA-approved product here (3), so the field’s cleanest result came from a drug Americans cannot prescribe. Pelvic floor physical therapy suits coexisting pelvic floor dysfunction, though its direct GSM evidence is one single-arm feasibility study (3).

After breast cancer, especially on an aromatase inhibitor

Aromatase inhibitors produce what the 2020 statement calls a profound estrogen-deficiency state, and severe GSM in most survivors (1). ACOG’s 2021 clinical consensus, which replaced its 2016 committee opinion: nonhormonal treatment first line; if that fails, low-dose vaginal estrogen may be used after breast cancer, including on tamoxifen, and in aromatase inhibitor users after shared decision-making between patient, gynecologist and oncologist (19). ACOG reviewed seven studies covering more than 4,000 survivors, median follow-up two to seven years, tamoxifen and aromatase inhibitor users alike, with no increased recurrence, and calls low-dose vaginal estrogen safe in women with hormone receptor-positive disease at low risk of recurrence (19).

The caution traces to one Danish cohort: 8,461 women with early ER-positive breast cancer, 1,957 of them vaginal estrogen users. Overall recurrence risk was not raised, relative risk 1.08 (95% CI 0.89 to 1.32); in the subgroup on adjuvant aromatase inhibitors it was 1.39 (95% CI 1.04 to 1.85), with no rise in mortality (20). The finding is contested; JNCI published four separate comments responding to it. It is an observational subgroup, and a 2024 meta-analysis of eight studies found no such increase (3). I will not tell you it is settled. Neither ACOG nor the urology panel did. Both put the oncologist in the room.

So who starts that conversation. She raises it with her oncologist, and I make sure that conversation starts from evidence rather than a package insert. ACOG puts that squarely on the prescriber: provide “data on the safety of low-dose vaginal estrogen to patients and their medical oncologists” (19). It matters because the warning FDA only began removing in November 2025 is still printed on three of the products named above, and an oncologist reading it has every reason to say no.

If you are the patient

Bring it up. That is the whole intervention, and most women never do. Say the words: dryness, burning, painful sex, urgency, recurring infections. Expect any prescription to work over weeks and to continue indefinitely.

Notes for clinicians

The screening question is the treatment. Asking costs thirty seconds. Two habits worth changing: stop ordering estradiol and FSH to diagnose this (3), and warn women about the boxed warning before the pharmacy does (1).

Here is mine, word for word.

“Do you experience vaginal dryness more now than you used to? Sometimes this can be a common side effect of menopause which can be related to painful intercourse.”

The Bottom Line

GSM reaches a quarter to four fifths of postmenopausal women and generally does not improve on its own. Half of affected women have never treated it, mostly because nobody asked. A drugstore moisturizer is a legitimate first step. Low-dose vaginal estrogen barely reaches the bloodstream and has 18 years of observational safety behind it, though most packages still carry a boxed warning FDA has already directed off. Lasers lost to sham. And a woman on an aromatase inhibitor deserves a real conversation with both her physicians, not a blanket no.

Sources

1. Menopause Society 2020 GSM position statement. https://menopause.org/wp-content/uploads/default-document-library/2020-gsm-ps.pdf

2. Portman DJ, Gass ML. Maturitas. 2014;79(3):349-354. https://pubmed.ncbi.nlm.nih.gov/25179577/

3. AUA/SUFU/AUGS GSM guideline, 2025. https://www.auanet.org/guidelines-and-quality/guidelines/genitourinary-syndrome-of-menopause

4. Mitchell CM, et al. MsFLASH. JAMA Intern Med. 2018;178(5):681-690. https://pubmed.ncbi.nlm.nih.gov/29554173/

5. Bhupathiraju SN, et al. Menopause. 2019;26(6):603-610. https://pubmed.ncbi.nlm.nih.gov/30562320/

6. Lethaby A, et al. Cochrane Database Syst Rev. 2016;(8):CD001500. https://pubmed.ncbi.nlm.nih.gov/27577677/

7. FDA labeling change request, 11/10/2025. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-requests-labeling-changes-related-safety-information-clarify-benefitrisk-considerations

8. Menopause Society comment on the FDA announcement. https://menopause.org/press-releases/the-menopause-society-comments-on-the-fda-announcement-on-hormone-therapy

9. FDA list of MHT products with updated prescribing information. https://www.fda.gov/drugs/drug-safety-and-availability/menopausal-hormone-therapies-updated-prescribing-information

10. DailyMed, ESTRING label, Apr 27, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=110b9865-5a07-4d45-b560-e89947f12600

11. DailyMed, VAGIFEM label, Feb 12, 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e5ad3cf6-dd96-4e64-af21-c1eee38d0b88

12. DailyMed, IMVEXXY label, Sep 18, 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=104be9f2-a8f6-430e-9e01-2ee7cc1861f1

13. DailyMed, PREMARIN VAGINAL CREAM label, Jun 02, 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=96609623-528e-4aba-cabe-7254aed816d5

14. DailyMed, OSPHENA label, Feb 17, 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9accbcc9-78ee-4f84-9b7e-704f2ab1c413

15. DailyMed, INTRAROSA label, Aug 03, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ada639d4-bac0-2ad0-e053-2a95a90afce7

16. Li FG, et al. JAMA. 2021;326(14):1381-1389. https://pmc.ncbi.nlm.nih.gov/articles/PMC8511979/

17. FDA CDRH letter to Inmode MD Ltd., July 24, 2018. https://www.fda.gov/files/medical%20devices/published/Inmode%20MD%20Lotd%20IHCTOA%20Letter.pdf

18. Raz R, Stamm WE. N Engl J Med. 1993;329(11):753-756. https://pubmed.ncbi.nlm.nih.gov/8350884/

19. ACOG Clinical Consensus Number 2, December 2021, “Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer” (replaces Committee Opinion 659, March 2016). https://www.acog.org/clinical/clinical-guidance/clinical-consensus/articles/2021/12/treatment-of-urogenital-symptoms-in-individuals-with-a-history-of-estrogen-dependent-breast-cancer

20. Cold S, et al. J Natl Cancer Inst. 2022;114(10):1347-1354. https://pubmed.ncbi.nlm.nih.gov/35854422/

A wooden table in warm morning light with a coiled cloth tape measure, a small hand weight and a folded linen cloth

Does Menopause Cause Weight Gain, or Is It Just Aging?

On August 29, 2026August 30, 2026 By Dr. Scott RennieIn Menopause & Women's Health, Weight Loss & Metabolic HealthLeave a comment

Your weight has been climbing about a pound a year since your early forties. Then something else changed. Same body, rearranged. The jeans that caught at the hip now catch at the waist.

Aging put the weight on. Menopause moved it.

The scale was never the menopause story

The Study of Women’s Health Across the Nation tracked women through the transition with repeated DXA scans. Weight and BMI gains that begin in premenopause “continue on an unaltered trajectory” through it, then flatten after the final period (1). Menopause does not bend the weight curve. The curve was already bending.

Two SWAN numbers circulate and both are real. In the full cohort of 3,064 women aged 42 to 52, weight rose 2.1 kg over three years, about 0.7 kg a year (2). In the smaller DXA sub-cohort, inside the 3.5-year window around the final period, 0.25 kg a year (1). Call it a pound to a pound and a half a year through midlife, none of it accelerated by menopause.

Where the fat goes

In 380 SWAN women with serial DXA, visceral fat drifted down before the transition at 1.85% a year, then climbed 6.24% a year inside the transition window (95% CI 4.31 to 8.17), settling at 1.47% after (3). Android fat went from 1.21% to 5.54%; the hip and thigh depot only to 2.03%. Lean mass flips sign in the same window, from gaining 0.2% a year to losing 0.2% (1), on top of the 3% to 8% per decade women lose after 30 (4).

Waist girth, meanwhile, rises 0.55% a year before the transition and 0.96% during it (3). Visceral fat moves six times faster than the tape can see, which is why a stable BMI and an unchanged waist are not reassurance.

Your metabolism did not crash at 50

Doubly labeled water, the reference method for what a human actually burns, was applied to 6,421 people across 29 countries. Total expenditure, basal expenditure and fat-free mass were “all stable from age 20 to 60” (5). The break point for adjusted total expenditure sits at 63.0 years, and the decline after it runs 0.7% a year (5).

The estradiol-specific effect is real and modest. Forty-five premenopausal women were randomized to ovarian suppression with placebo or transdermal estradiol add-back. Resting expenditure fell 54 kcal a day on placebo and did not fall at all with estradiol (6). Fifty-four calories. Measurable. Not a collapse.

Why it happens, and how much of that is known

Less than the confidence of the explanations would suggest. Estradiol loss lowers resting expenditure, since add-back prevented it in a randomized design (6), and the redistribution is time-locked to the final period rather than to birthdays (3). Past that it thins out fast. The one randomized ovarian-suppression trial measuring body composition and free-living expenditure together, 34 women over 24 weeks, found no endpoint that differed between groups (7). The Menopause Society says estrogen regulation of energy intake and expenditure “has not been well studied,” with “a paucity of studies” on estrogen and skeletal muscle (8). Falling estradiol, rising FSH, the androgen-to-estrogen shift: nobody has sorted out which drives it.

What shows up on your labs

SWAN modeled cardiovascular risk factors two ways in 1,054 women with a natural final period, once as chronological aging and once as ovarian aging. Only total cholesterol, LDL cholesterol and apolipoprotein B jumped inside the year before and after the final period (9). Glucose, insulin, blood pressure, fibrinogen and CRP fit the plain aging model (9), and the American Heart Association agrees (10).

So insulin resistance is not independently menopause-driven, whatever you have been told. The visceral fat is menopause-linked, and visceral fat drives insulin resistance on its own. A chain, not a shortcut, and it points at different treatment.

Here is where my own practice diverges from the cohort data. I screen lipids and apoB at intake, before starting any medication for weight loss, so my trigger is the visit rather than the menopausal stage. For hormone therapy I don’t routinely order them. I give the patient the options and tell her up front that insurance sometimes will not pay for apoB or apoA testing, which turns out to be a real constraint on what actually gets drawn.

Lift something heavy, then eat enough protein to use it

101 randomized trials, 5,697 postmenopausal women. Training raised fat-free mass 0.66 kg and cut fat mass 1.27 kg, and the modalities split: resistance work won for lean mass (+0.90 kg), aerobic for fat and waist (1.94 kg, 2.30 cm) (11).

Protein partners that work rather than replacing it. In 776 postmenopausal women aged 55 and older, whey improved lower-limb lean mass and strength when paired with resistance training, and had “no significant benefit on muscle strength or lean mass” without it (12). The powder is not the intervention.

Write down 1.2 g of protein per kilogram daily, 150 minutes of moderate activity weekly, strength training twice a week (4). On an incretin, higher: 1.2 to 1.6 g/kg/d, strength work three times weekly (13).

The strongest diet trial here is a prevention trial

The Women’s Healthy Lifestyle Project randomized 535 premenopausal women, mean age 47, and followed them 54 months through the transition. The intervention group finished 0.2 lb lighter. Controls gained 5.2 lb (14). Which diet matters less: 144 centrally obese postmenopausal women randomized to an energy-restricted Mediterranean or Central European diet both lost 7.6 kg and 24.6% of visceral fat in 16 weeks, with no difference between arms (15). Choose the one you will still be doing next year.

Hormone therapy, stated precisely in both directions

A Cochrane review of 28 randomized trials and 28,559 women found no evidence that estrogen alone or estrogen with progestogen affects body weight or prevents the BMI increase normally experienced at menopause (16). That review is old, last published in 2000, and still the largest pooled analysis of that endpoint. Hormone therapy does not cause weight loss, and it does not prevent menopausal weight gain.

What it does is narrower. The Menopause Society’s own key point: hormone therapy “may help attenuate abdominal adipose accumulation and weight gain associated with the menopause transition,” and “the effect is small” (8). In the WHI, no significant slowing of weight gain and a lesser waist increase over three years (8). On muscle, systematic reviews find neither benefit nor harm (8). A 2026 review is blunt: hormone therapy “should not be marketed or prescribed for weight loss or obesity treatment” (17).

Good drug. Vasomotor symptoms, genitourinary syndrome, bone. Abdominal fat is not on that list.

My own practice, stated plainly: I don’t prescribe MHT for patients who want to lose abdominal fat.

GLP-1s and the muscle question

Menopausal status does not blunt these drugs. A post hoc SURMOUNT analysis by reproductive stage found tirzepatide produced 23% weight reduction in postmenopausal women against 3% on placebo, matching premenopausal women at 26% versus 2% (18).

Now the counterintuitive part. In the SURMOUNT-1 DXA substudy, 160 participants scanned at baseline and week 72, tirzepatide produced 21.3% weight loss, 33.9% fat mass loss and 10.9% lean mass loss (19). Of the weight lost, roughly 75% was fat and 25% lean in both the tirzepatide and the placebo arms (19). The lean loss scales with the weight lost rather than with the drug.

DXA lean mass is also not muscle. It counts water, glycogen and organ mass, and modeling puts true muscle loss nearer 10% to 15% of weight reduction in women who are not strength training (13). In a 106-patient semaglutide cohort, grip strength rose 4.1 kg at a year and sarcopenic obesity fell from 49% to 33% (20). Function can improve while the DXA number falls.

Still, nobody has published incident sarcopenia or functional outcomes for postmenopausal women on these drugs. That gap is why protein and lifting belong in the prescription.

When I start a postmenopausal patient on an incretin, the instruction is 1.6 g of protein per kilogram of body weight a day, and strength training two to three times a week. That is the top of the range the evidence supports (13), and I put it there on purpose.

What is oversold

Supplements sold for menopausal weight loss. I looked for a randomized trial of any of them showing meaningful weight or visceral fat reduction and found none. Absence of evidence in one search is not proof of absence, so put it precisely: the marketing category exists; the trial literature does not. The Menopause Society does not recommend supplements or herbal remedies even for hot flashes (21).

Hormone therapy stacked on a GLP-1. Two retrospective cohorts, no randomized trial, and the 2026 review is unambiguous: do not start hormone therapy to boost an obesity medication (17).

And one asymmetry worth getting exactly right. Treating hot flashes or insomnia in order to lose weight has no trial behind it that I can find. The reverse direction is supported: the Menopause Society recommends weight loss for vasomotor symptoms, conceding those studies are small pilots and post hoc analyses (21).

If you are the patient reading this

Stop asking whether menopause made you gain weight. Ask where it went. Your BMI can sit still while visceral fat climbs 6% a year (3), so get lipids and apoB checked around your final period (9). Then put your effort where the randomized evidence is: resistance training, and a deficit you can hold for years.

Which raises the obvious question for a practice that runs entirely over video. So here is what I actually do. Patients get a Withings scale that syncs into the chart on its own and reports weight, BMI and body fat. A blood pressure cuff syncs the same way, automatically. The waist they measure themselves, with a tape, because the scale will not catch what the tape catches. Weight and blood pressure come in at least monthly and often more frequently than that, which means the trend is visible long before an annual visit would have found it.

For the clinicians

Screening beats explaining. The window runs roughly two years before to 18 months after the final period (1), and that is when lipids move and visceral fat accelerates (3)(9). Order the panel with apoB in it, and do not reassure a woman on a stable BMI or an unchanged waist; both understate a 6.24% per year visceral gain (3). When you start an incretin, write the protein target and the strength training into the plan (13). Hormone therapy earns its place on symptoms, bone and the diabetes signal (8), and no line at all on the weight plan.

The Bottom Line

Aging adds the weight, roughly a pound and a half a year through midlife, on a curve menopause does not bend (1)(2). Menopause moves the fat, visceral gain going from minus 1.85% to plus 6.24% a year inside a 3.5-year window (3). Metabolism holds steady to 60 (5). Hormone therapy treats symptoms and bone, not weight (8)(16). What changes the outcome is lifting, protein, a deficit you can sustain, and where indicated, a medication that works as well after menopause as before (11)(18).

Sources

1. Greendale GA, et al. Changes in body composition and weight during the menopause transition. JCI Insight 2019. https://pmc.ncbi.nlm.nih.gov/articles/PMC6483504/

2. Sternfeld B, et al. Physical activity and changes in weight and waist circumference in midlife women. Am J Epidemiol 2004. https://academic.oup.com/aje/article/160/9/912/86561

3. Greendale GA, et al. Changes in regional fat distribution and anthropometric measures. J Clin Endocrinol Metab 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8372653/

4. The Menopause Society. MenoNote: Midlife Weight Gain, 2025. https://menopause.org/wp-content/uploads/for-women/MenoNote-Weight-Gain.pdf

5. Pontzer H, et al. Daily energy expenditure through the human life course. Science 2021. https://doi.org/10.1126/science.abe5017

6. Melanson EL, et al. Regulation of energy expenditure by estradiol in premenopausal women. J Appl Physiol 2015. https://pmc.ncbi.nlm.nih.gov/articles/PMC4628992/

7. Gavin KM, et al. Ovarian suppression in premenopausal women: no change in free-living energy expenditure. Obesity 2020. https://pmc.ncbi.nlm.nih.gov/articles/PMC7653843/

8. North American Menopause Society. 2022 hormone therapy position statement. Menopause 2022. https://menopause.org/wp-content/uploads/professional/nams-2022-hormone-therapy-position-statement.pdf

9. Matthews KA, et al. Chronological aging or the menopausal transition? J Am Coll Cardiol 2009. https://doi.org/10.1016/j.jacc.2009.10.009

10. El Khoudary SR, et al. Menopause transition and cardiovascular disease risk. Circulation 2020. https://doi.org/10.1161/CIR.0000000000000912

11. Khalafi M, et al. Exercise training and body composition in postmenopausal women. Front Endocrinol 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10306117/

12. Kuo YY, et al. Whey protein supplementation in postmenopausal women. Nutrients 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC9572824/

13. Mozaffarian D, et al. Nutritional priorities to support GLP-1 therapy for obesity. Am J Clin Nutr 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC12612741/

14. Kuller LH, et al. Women’s Healthy Lifestyle Project: results at 54 months. Circulation 2001. https://doi.org/10.1161/01.cir.103.1.32

15. Bajerska J, et al. Energy-restricted Mediterranean and Central-European diets in postmenopausal women. Sci Rep 2018. https://pmc.ncbi.nlm.nih.gov/articles/PMC6057942/

16. Kongnyuy EJ, et al. Hormone replacement therapy: weight and body fat distribution. Cochrane Database Syst Rev CD001018. https://www.cochrane.org/evidence/CD001018_hormone-replacement-therapy-has-no-effect-body-weight-and-cannot-prevent-weight-gain-menopause

17. Younglove C. Menopause hormone therapy in weight management. Obesity Pillars 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC13010941/

18. Tchang BG, et al. Weight reduction with tirzepatide by reproductive stage: SURMOUNT post hoc analysis. Obesity 2025. https://doi.org/10.1002/oby.24254

19. Look M, et al. Body composition changes with tirzepatide in SURMOUNT-1. Diabetes Obes Metab 2025. https://doi.org/10.1111/dom.16275

20. Alissou M, et al. Semaglutide, fat mass, lean mass and muscle function: SEMALEAN. Diabetes Obes Metab 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC12673431/

21. North American Menopause Society. 2023 nonhormone therapy position statement. Menopause 2023. https://menopause.org/wp-content/uploads/professional/2023-nonhormone-therapy-position-statement.pdf

Round beige adhesive bandage on an adult's upper arm after a vaccination

2026-2027 COVID Vaccine: Who Qualifies, and Do You Need a Doctor’s Note?

On August 28, 2026August 30, 2026 By Dr. Scott RennieIn Infectious DiseaseLeave a comment

The updated COVID-19 shots were approved on August 27 and 28, 2026, and they started shipping the same week. If you went looking for one last fall and got turned around at the pharmacy counter, or told to come back with something in writing from your physician, this post is mostly for you.

Here is what is out, who can get it, what counts as high risk, and what the virus is doing right now.

What was approved, and when you can actually get it

FDA cleared XFG-adapted formulas from all three manufacturers. Pfizer-BioNTech’s Comirnaty was approved August 27 (1). Moderna’s Spikevax and mNexspike followed (2). Novavax announced its Nuvaxovid approval on August 28, alongside clearances in the EU and Japan (3). XFG is a recombinant in the JN.1 family, and it replaces last season’s LP.8.1 formula (4).

Now the part I get asked about most, and the part I cannot give you: there is no state-by-state rollout calendar. No health department publishes a date on which residents of that state become eligible, because distribution is commercial rather than federally allocated. Manufacturers ship to distributors, distributors ship to chains and clinics, and stock arrives store by store over days to a few weeks. Your pharmacy may have doses Tuesday while the one four miles down the road is waiting on Thursday’s truck.

So do not wait for an announcement. Set an alert on your pharmacy’s scheduling page, or call and ask when their first shipment lands.

Where the virus is right now

I want to be careful here, because the headlines and the data are telling slightly different stories.

CDC’s wastewater program is the most reliable read we have. For the week ending August 22, 2026, the national wastewater viral activity level for SARS-CoV-2 was 2.14, which CDC classifies as Very Low (5). That same number sat at 1.00 through most of July. It has roughly doubled in six weeks while staying inside the lowest category. So yes, transmission is climbing on the usual back-to-school schedule. No, we are not in a surge yet.

The regional picture is lopsided. The South is currently the highest region at 3.34. Texas is the real outlier at 11.76 across 40 reporting sites, the only state sitting in the Very High band. Mississippi reads 8.92 and South Carolina 7.47, but both are flagged for limited coverage, with two and three reporting sites respectively, so treat those as a signal rather than a measurement. Hawaii is at 7.26 across ten sites. Then Nevada 6.01, California 5.87 across 79 sites, West Virginia 5.61, Louisiana 5.31, and Florida 5.30 (6).

The variant names have shuffled again. Over the four weeks ending August 1, 2026, the two most common in CDC’s sequencing were SW.2 at about 21 percent and XFG.1.1 at about 16 percent (7). XFG.1.1 belongs to a family. Count its close relatives together and the XFG group accounts for roughly 35 percent of what is going around, which is why FDA picked XFG as this year’s vaccine target. NB.1.8.1, the one the press nicknamed Nimbus last summer, has faded to about 4 percent. BA.3.2 sits near 2 percent.

Here is the caveat, and most coverage skips it. Those percentages rest on a very small number of samples. CDC flags all eighteen of the lineages it reported for that period as based on fewer than ten sequenced specimens, or unreliable for other statistical reasons (7). In February the agency could name more than two hundred lineages circulating in the country. This month it could name eighteen. Genetic sequencing of the virus has dropped off sharply, so the variant list is a rough sketch rather than a headcount.

Which is why I put more weight on the wastewater curve than on the variant percentages right now. Genomics tells you the flavor. Wastewater tells you the size.

The page to bookmark

CDC posts wastewater viral activity by state here, and it is updated every Friday with the previous week’s numbers:

https://www.cdc.gov/wastewater/respiratory-viruses/state.html

It covers influenza A, SARS-CoV-2 b (Covid-19), and RSV on the same page, so you can see which of the three is actually moving in your area before you decide whether that sore throat needs a test. If you want the county-level view alongside emergency department visit data, CDC’s Respiratory Illnesses Data Channel has a search box for your state or county:

https://www.cdc.gov/respiratory-viruses/data/index.html

Bookmark the first one. It answers the question patients are really asking, which is not “how bad is COVID nationally” but “is there anything going around here.”

Who the FDA says can get it

The licensed indications are narrower than they were before 2025, and they differ slightly by product:

Comirnaty (Pfizer-BioNTech), mRNA: ages 65 and older, or ages 5 through 64 with at least one condition that raises the risk of severe COVID-19 (1)
Spikevax (Moderna), mRNA: ages 65 and older, or 6 months through 64 with at least one such condition (2)
mNexspike (Moderna), mRNA: ages 65 and older, or 12 through 64 with at least one such condition (2)
Nuvaxovid (Novavax), protein-based rather than mRNA: ages 65 and older, or 12 through 64 with at least one such condition (3)

CDC’s own recommendation, unchanged since the September 2025 ACIP vote, covers everyone 6 months and older under individual-based decision-making (8). So the federal recommendation is broader than the federal license. That gap is exactly where the confusion at the pharmacy counter lives, and nobody at either agency has resolved it for you.

The high-risk list is longer than you think

Most people badly underestimate how wide this list is. CDC’s conditions, in alphabetical order rather than order of risk: cancer, cerebrovascular disease, chronic kidney disease at any stage, chronic liver disease, chronic lung disease including asthma, cystic fibrosis, dementia and other neurologic conditions, type 1 or type 2 diabetes, disabilities, heart conditions, hemoglobin blood disorders, HIV, an immunocompromising condition, mental health conditions, overweight and obesity, physical inactivity, pregnancy, current or former smoking, solid organ or stem cell transplant, substance use disorders, and tuberculosis (9).

Read the back half of that again. Overweight is defined as a BMI of 25 or higher (9). About 72 percent of American adults age 20 and over fall at or above that line, combining the 31.7 percent who are overweight with the 40.3 percent who have obesity (10). Current smoking counts, and so does former smoking. So does physical inactivity. So does depression.

Here is my opinion, and I hold it firmly. A criteria list that broad is not functioning as a clinical gate. It is functioning as paperwork. If you are an adult in the United States, the odds are strong that you already qualify under a criterion you would not have thought to claim, and the honest thing for the system to do would be to say so out loud instead of making each person audit themselves at a kiosk.

Do you need a note from your doctor?

Short answer: almost certainly not, and you should not assume you do.

On September 19, 2025, ACIP voted to recommend COVID-19 vaccination for everyone 6 months and older through individual-based decision-making. In the same meeting it took up a proposal that would have let jurisdictions require a prescription, and that proposal failed on a tiebreaker cast by the committee chair (8, 11). CDC’s position is that the required conversation can happen with a pharmacist, a nurse practitioner, or a PA standing right there at the counter. No written order from your physician.

What tripped people up last fall was state law rather than federal policy. Several states had written pharmacist vaccination authority so that it tracked ACIP’s recommendation language directly, and when that language narrowed, pharmacists in those states abruptly lost standing authority to vaccinate without a prescription. By late September 2025, 26 states had issued standing orders or executive actions restoring broader access (12). The rest had not, and store-level policy varied inside states that had.

Two phone calls save you an afternoon. Call the pharmacy, ask whether they need a prescription for someone your age and situation, and ask whether the 2026-2027 formula is physically on their shelf yet. Then call the number on the back of your insurance card and ask what your plan covers this season. Your state health department’s immunization page is worth two minutes as well, since that is where a new standing order would appear first.

And if a pharmacy does turn you away for want of an order, that is a five-minute problem for your physician to solve, not a reason to abandon the shot. Call the office. Do not walk out and let it go until spring.

Why I think the restrictions backfire

Because the numbers are already bad, and friction is the best explanation for them.

Only 17.5 percent of American adults received the 2025-2026 COVID vaccine, measured at the close of the season in February 2026 across a survey sample of roughly 197,000 people (13). Among adults 65 and older, the group with the clearest, least-debatable benefit, coverage reached 33.5 percent (13). Two-thirds of the highest-risk group in the country did not get vaccinated.

I do not believe most of that gap is ideological. Some of it is. Most of it is drag. Every additional step you insert between a mildly willing person and a needle removes some of them, and the removal is silent. An eligibility attestation form removes a few. A phone call to confirm the pharmacy will actually do it removes a few more. An uncertain bill removes more still. None of those people write a letter explaining why they gave up. They just do not come.

There is a second cost that gets less attention. When the government tells healthy adults they no longer qualify, the message the public hears is that the shot is not worth much. That message does not stay inside its intended audience. It reaches the 68-year-old with COPD who did qualify, who now assumes the whole thing has been downgraded, and who skips it.

If you decided back in 2021 or 2022 that two doses were enough and you have not thought about it since, I would ask you to reconsider on narrow, unromantic grounds. Not because the pandemic is back. Because protection fades, this year’s formula is matched to what is circulating now, and the downside of a sore arm for two days is very small next to a week of illness you did not need to have.

Has the virus changed?

Not in the way people fear. Severity has not meaningfully increased. WHO and ECDC have continued to rate the currently circulating variants as low risk for severe outcomes, and the mutations driving the current lineages are the immune-evasion kind rather than the tissue-damage kind. Laboratory work on XFG published in 2025 found roughly a two-fold drop in neutralizing antibody effectiveness compared with the then-dominant lineage, which explains reinfection without implying worse disease (14).

Symptoms are the familiar Omicron picture. Sore throat, often genuinely severe. Hoarseness. Congestion, cough, fatigue, headache, body aches, and sometimes nausea or loose stools. Loss of smell is far less common than it was in 2020. The “razor blade throat” description that attached itself to NB.1.8.1 in 2025 has stuck around in press coverage, and it is a real complaint, though it is also just a bad Omicron sore throat rather than a diagnostic sign.

What to monitor: shortness of breath at rest or on minimal exertion, chest pain, confusion or unusual difficulty staying awake, bluish lips, and an inability to keep fluids down. Watch for the pattern where someone improves for several days and then clearly worsens around day seven to ten. If you own a fingertip pulse oximeter, a resting reading that keeps coming back at 94 percent or below deserves a same-day call, not a wait-and-see.

Treatment still exists and is still underused. Nirmatrelvir-ritonavir has to be started within five days of symptom onset in adults at high risk of progression, which as we established covers a very large share of adults (15). Day six is too late. If you are in a risk category, know before you are sick how you would reach a clinician quickly.

How long do you stay home?

CDC no longer has a five-day isolation rule, and has not since 2024. The current guidance is symptom-based. Stay home and away from others while you are sick. You can return to normal activities once both of the following have been true for at least 24 hours: your symptoms are improving overall, and you have had no fever without using fever-reducing medication (16).

Then take added precautions for the next five days. Mask well, keep some distance, improve ventilation, and test before you spend time around anyone vulnerable. If a fever returns or you get worse after going back out, go home again and restart the same clock (16).

On work: CDC does not recommend a fixed number of days off, and there is no federal number for your employer to enforce. Your workplace policy is its own creature, and so is your child’s school district. If HR asks for a return-to-work note, that is a workplace requirement rather than a public health one, and it is worth saying so plainly when you ask your physician for it. Healthcare workers and staff in long-term care facilities are the exception and should follow their facility’s occupational health rules instead.

What else lowers your risk

The vaccine is the biggest lever. Metabolic health is the second one, and it is the one you have some control over between now and January.

CDC’s own analysis of 148,494 adults treated at 238 US hospitals found risk of COVID-19 hospitalization was lowest at a BMI of 24.2, ICU admission lowest at 25.9, and death lowest at 23.7, with risk climbing sharply above those points (17). That is a dose-response curve, not a threshold effect, which means movement in the right direction counts even if you do not reach a target number.

Two other findings are worth putting side by side, because together they say something more useful than either does alone.

In a Scottish study of 3.6 million people, vaccinated adults with a BMI over 40 were 76 percent more likely to be hospitalized or die from COVID-19 than vaccinated adults at a normal BMI (adjusted rate ratio 1.76, 95% CI 1.60 to 1.94). In the prospective arm of the same work, 55 percent of people with severe obesity had unquantifiable neutralizing antibody titers six months after their second dose, compared with 12 percent of people at a normal BMI. A third dose restored neutralizing capacity, and then it declined faster again (18).

Meanwhile, in a cohort of 9.17 million adults in England, protection against hospitalization two weeks after the second dose was essentially identical across BMI categories, with an odds ratio of 0.32 in people with obesity against 0.34 in people at a healthy weight. Protection against death was actually stronger in the obesity group, 0.26 against 0.39 (19).

Put those together and the conclusion is not the one people expect. The vaccine works in people with obesity. Its protection simply fades faster. That is an argument for getting the seasonal dose rather than skipping it, and it is the single clearest reason I push seasonal vaccination hardest in my obesity medicine patients.

If you are working on weight for metabolic reasons, this belongs on the list of reasons alongside the ones you already know. I have written about the current medication options in New Weight Loss Pills Foundayo and Wegovy Explained, and about what sustains loss over years in Doctor Supervised Weight Loss: What Works Long Term. For the version of this discussion from last season, including how the eligibility fight started, see.

Two smaller things. You can get the COVID vaccine and the flu vaccine at the same visit, one in each arm, and doing so is the single easiest way to make sure both actually happen (20). And CDC’s risk list includes physical inactivity as its own line item, which is a quiet reminder that the walk you keep meaning to start is doing more than one job.

For patients

Check the wastewater page for your state before you decide how careful to be this month. Call your pharmacy, ask about stock and about whether they need a prescription where you live, and book the appointment while you are on the phone. If you are 65 or older, or you have any condition on that list, do not let a form at the counter end the attempt. If you have been waiting since your first two doses in 2021, this is a reasonable year to restart.

For colleagues

Three practical notes. First, expect the FDA-license-versus-CDC-recommendation gap to generate pharmacy callbacks again this fall, and consider building a standing message your staff can send rather than routing each one to you. Second, screen for eligibility criteria your patients will not volunteer: former smoking status, physical inactivity, and a documented mental health condition all qualify under the CDC list and are all commonly missing from problem lists. Third, if you practice by video as I do, the eligibility conversation is straightforward to complete in a visit that is already happening for something else, and it takes about ninety seconds.

The Bottom Line

The 2026-2027 vaccines are approved, matched to XFG, and shipping now. There is no statewide rollout date to wait for, so call your pharmacy. You very likely qualify under criteria broader than you assume, and you almost certainly do not need a note from me or anyone else, though it is worth one phone call to confirm before you drive over. COVID activity is low nationally and rising, with Texas and the South well ahead of everyone else. And if you stopped after your first two doses because the emergency ended, the case for one more is quiet and practical rather than dramatic: your protection has faded, this formula matches what is going around, and the shot is easier to get than the illness is to sit through.

Sources

Pfizer and BioNTech Receive U.S. FDA Approval for XFG-adapted COVID-19 Vaccine. August 27, 2026. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-receive-us-fda-approval-xfg-adapted
Moderna Receives U.S. FDA Approval for Updated 2026-2027 COVID-19 Vaccines. August 2026. https://www.biospace.com/press-releases/moderna-receives-u-s-fda-approval-for-updated-2026-2027-covid-19-vaccines
Novavax’s Partnership Strategy Continues to Deliver with XFG-adapted Nuvaxovid Approvals in the U.S., EU and Japan for the 2026-2027 Vaccination Season. August 28, 2026. https://www.biospace.com/press-releases/novavaxs-partnership-strategy-continues-to-deliver-with-xfg-adapted-nuvaxovid-approvals-in-the-u-s-eu-and-japan-for-2026-2027-vaccination-season
U.S. Food and Drug Administration. COVID-19 Vaccines (2026-2027 Formula) for Use in the United States Beginning in Fall 2026. https://www.fda.gov/vaccines-blood-biologics/industry-biologics/covid-19-vaccines-2026-2027-formula-use-united-states-beginning-fall-2026
CDC. National Wastewater Data for Respiratory Viruses. Data for the week ending August 22, 2026; updated August 27, 2026. https://www.cdc.gov/wastewater/respiratory-viruses/national.html
CDC. State and Territory Wastewater Data for Respiratory Viruses. Data for the week ending August 22, 2026. https://www.cdc.gov/wastewater/respiratory-viruses/state.html
CDC. SARS-CoV-2 Variant Proportions. National estimates, four-week period ending August 1, 2026; published August 28, 2026. https://data.cdc.gov/Laboratory-Surveillance/SARS-CoV-2-Variant-Proportions/jr58-6ysp
U.S. Department of Health and Human Services. ACIP Recommends COVID-19 Immunization Based on Individual Decision-making. September 19, 2025. https://www.hhs.gov/press-room/acip-recommends-covid19-vaccination-individual-decision-making.html
CDC. People with Certain Medical Conditions and COVID-19 Risk Factors. https://www.cdc.gov/covid/risk-factors/index.html
National Center for Health Statistics. Prevalence of Overweight, Obesity, and Severe Obesity Among Adults Age 20 and Older: United States, 1960-1962 Through August 2021-August 2023. https://www.ncbi.nlm.nih.gov/books/NBK621182/
CDC advisers vote that patients must consult a health care provider for Covid-19 vaccination, but no prescription required. CNN, September 19, 2025. https://www.cnn.com/2025/09/19/health/cdc-acip-hepatitis-mmrv-covid-vaccine
Kates J, Bell C, Michaud J, Williams E, Tolbert J. Tracking State Actions on Vaccine Policy and Access. KFF, September 24, 2025. https://www.kff.org/state-health-policy-data/tracking-state-actions-on-vaccine-policy-and-access/
CDC. COVID-19 Vaccination Coverage, Overall and by Selected Demographics and Jurisdiction, Among Adults 18 Years and Older, by Season. National Immunization Survey-Fall Respiratory Virus Module, week ending February 21, 2026. https://data.cdc.gov/d/ksfb-ug5d
Gavi. Eight things you need to know about the new “Nimbus” and “Stratus” COVID-19 variants. June 16, 2025. https://www.gavi.org/vaccineswork/eight-things-you-need-know-about-new-nimbus-and-stratus-covid-variants
U.S. Food and Drug Administration. PAXLOVID Patient Eligibility Screening Checklist Tool for Prescribers. https://www.fda.gov/media/158165/download
CDC. Preventing Spread of Respiratory Viruses When You’re Sick. https://www.cdc.gov/respiratory-viruses/prevention/precautions-when-sick.html
Kompaniyets L, Goodman AB, Belay B, et al. Body Mass Index and Risk for COVID-19-Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death, United States, March-December 2020. MMWR Morb Mortal Wkly Rep. 2021;70(10):355-361. PMID 33705371. https://pubmed.ncbi.nlm.nih.gov/33705371/
van der Klaauw AA, Horner EC, Pereyra-Gerber P, et al. Accelerated waning of the humoral response to COVID-19 vaccines in obesity. Nat Med. 2023;29(5):1146-1154. PMID 37169862. https://www.nature.com/articles/s41591-023-02343-2
Piernas C, Patone M, Astbury NM, et al. Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study. Lancet Diabetes Endocrinol. 2022;10(8):571-580. PMID 35780805. https://doi.org/10.1016/S2213-8587(22)00158-9
CDC. Staying Up to Date with COVID-19 Vaccines. https://www.cdc.gov/covid/vaccines/stay-up-to-date.html

Plain grey canvas walking shoes, a smooth stone and an unlabeled clear glass bottle on a wooden floor in daylight.

Longevity Medicine: What Actually Works, and What Doesn’t

On August 24, 2026August 30, 2026 By Dr. Scott RennieIn Longevity & Healthy AgingLeave a comment

Longevity medicine is a wide field, and most of it is not what gets marketed. This is a review of what the evidence actually supports, from fitness and blood pressure to the drugs and supplements patients ask about by name.

Patients bring me longevity questions on video, which is how every visit I do happens. It usually arrives as a general question about what I recommend for living longer, followed by one specific thing they read about online. Phosphatidylcholine. Rapamycin. GLP-1 medications.

Here is the part that disappoints almost everybody. The things with the largest measured effect on how long you live are cheap, boring, and nobody can patent them, so nobody sells them. The drugs people ask about by name sit lower on the list, and several sit there with no human results at all. That does not make them worthless. I prescribe GLP-1 receptor agonists and think they are the most important thing to happen to metabolic medicine in my working life. The point is ordering.

What actually works, and it is not a close call

Start with cardiorespiratory fitness, which means how well your heart and lungs move oxygen while you work hard. Nothing else here comes close to it.

Mandsager’s team at Cleveland Clinic followed 122,007 patients who had treadmill tests between 1991 and 2014. The fittest group came out at an adjusted hazard ratio of 0.20 against the least fit (1). A hazard ratio compares the risk in one group against another. Anything under 1.00 means less risk, so 0.20 means the fittest people died at roughly a fifth the rate of the least fit. That is an enormous gap.

That paper also produced the line that being unfit is worse than smoking, and here is the correction. It reported hazard ratios of 1.41 for smoking and 1.40 for diabetes sitting next to 1.41 for below-average fitness (1). Those are similar sizes inside one model. Nobody raced them against each other, and a poor treadmill result is partly a measure of disease nobody has found yet. The pattern does hold up elsewhere, at roughly 14 percent lower death rates for each one-MET gain in fitness (2). A MET is a unit of effort, and one MET is about what your body burns sitting still, so gaining one is real training.

Resistance training is the second lever, and the useful finding is where it stops. Momma pooled dozens of studies and found that any muscle-strengthening work was linked to a 10 to 17 percent lower risk of death, heart disease, cancer and diabetes. The benefit peaks at 30 to 60 minutes a week and flattens after 60 (3). Two half-hour sessions. That is the whole prescription, and the flattening is the part fitness content never mentions, because there is no business in telling somebody they are done.

Grip strength comes at it sideways. In PURE, across 139,691 adults in 17 countries, the death rate rose with a hazard ratio of 1.16 for every 5-kg drop in grip (4). Grip stands in for how much muscle you carry. Nobody should go train their hands.

Nobody ever counted to ten thousand

Paluch pooled 15 cohorts and found the benefit of daily steps levels off around 6,000 to 8,000 for adults 60 and older, and 8,000 to 10,000 under 60 (5).

Here is my one digression. The 10,000 figure has no medical origin whatsoever. It came from a pedometer sold in Japan in 1965, the manpo-kei or ten-thousand-step meter, named partly because the Japanese character for ten thousand looks a bit like a person walking. A marketing name became a health target millions of people feel guilty about missing. Nobody ever checked the math.

The interventions with no sales force

SPRINT assigned people at random to a tight blood pressure goal, under 120 on the top number, against the usual goal of under 140. All-cause mortality, meaning death from any cause, came out at a hazard ratio of 0.73, with an NNT of about 90 over a median of 3.26 years (6). NNT is the number needed to treat. Hold 90 people to the tighter goal for a bit over three years and one of them lives who otherwise would not have. Nothing sold as a longevity supplement has an NNT, because none of them has ever been tested against death.

Quitting smoking gives back more life still. From Jha’s 201,248 US adults, quitting between 25 and 34 gets back about ten years, and quitting in your late fifties still returns four (7).

Sleep follows a U-shaped curve, with the lowest risk near seven hours and the risk climbing faster on the long side, up to a relative risk of 1.37 at ten hours (8). What I want people to stop expecting is a heart benefit from CPAP. SAVE assigned 2,717 adults with moderate-to-severe sleep apnea and known heart disease at random, and the main result came back at HR 1.10, flatly null, which means no difference at all (9). None. CPAP treats symptoms. Say that out loud when you prescribe it.

Then the one physicians skip. Holt-Lunstad’s pooled work put the odds of dying at 1.29 for social isolation and 1.26 for loneliness, with living alone at 1.32 (10). The line about loneliness equalling fifteen cigarettes a day restates those same odds rather than adding a calculation, so hold it loosely.

Diet belongs here too, and PREDIMED is where the honest version lives. Its Mediterranean groups cut the main heart outcome by roughly 30 percent, which is a real result, though the trial was never built to measure death from any cause, and it was pulled and republished in 2018 after an audit found problems with how 1,588 of 7,447 people were assigned (11). Eat that way for your heart. It does not follow that it buys you years.

Weight loss, and what SELECT actually settled

For years there was no good answer on whether losing weight on purpose lowers the death rate. Look AHEAD assigned 5,145 adults with type 2 diabetes at random to an intensive diet and exercise program, held weight loss near 6 percent, and returned a heart outcome of HR 0.95 before stopping for futility (12). Well conducted. Well powered. Null.

SELECT changed that without finishing it. 17,604 adults with overweight or obesity and known heart disease, no diabetes; major heart events hit 6.5 percent on semaglutide against 8.0 on placebo, HR 0.80 (13). All-cause mortality came in at HR 0.81, 95% CI 0.71 to 0.93, and gets quoted everywhere as proof. It is not, and the reason is worth knowing. The trial used hierarchical testing, which means the questions were ranked in advance and answered in order, and once one of them fails, nothing below it counts as proof anymore. That chain broke a step earlier, at heart-related death, HR 0.85, CI 0.71 to 1.01, P=0.07. So the rule bit. So the death result is a strong hint. I think the effect is probably real. I will not tell you it has been proven.

The prescriptions people ask me for by name

GLP-1 receptor agonists are the only drugs here I reach for gladly, and I use them for obesity and its complications. FLOW cut its main kidney outcome to HR 0.76 in 3,533 patients with type 2 diabetes and chronic kidney disease, stopped early because the drug was plainly working, and turned up roughly 20 percent lower all-cause mortality among the secondary results, though I could not confirm the exact confidence interval on that one (14). SURMOUNT-MMO is testing tirzepatide against a combined outcome that includes death from any cause, and it has reported nothing (15). Orforglipron, approved April 2026 as the first pill in the class, has no death data either (16). I prescribe it. I do not pretend it has evidence it does not have.

The catch is muscle. Across these trials, lean tissue was about 45 percent of the weight lost with semaglutide in STEP-1 and about 26 percent with high-dose tirzepatide in SURMOUNT-1 (17). Lean tissue is mostly muscle. Losing close to half your weight as muscle matters in a 68-year-old whose grip is already borderline. It matters a lot. Protein at 1.0 to 1.2 g/kg/day is the geriatric target, and in older patients that is the number I use (18). For most other adults the adequate intake sits higher, and I aim for 80 to 120 grams a day, or 1.6 g/kg/day. Resistance training two to three days a week, covering all major muscle groups, is what decides how much of that muscle survives the loss.

Metformin I would not prescribe to a person without diabetes for longevity. The famous claim is Bannister’s 2014 comparison, which adjusted for nothing: 14.4 deaths per 1,000 person-years among metformin-treated diabetics against 15.2 in matched non-diabetic controls (19). A twenty-year reanalysis found the reverse (20). Most of that first result is confounding by indication, meaning the people who stay on metformin alone were healthier to begin with, in better shape before anyone handed them a pill, so the drug quietly takes credit for a head start it never gave them. TAME was meant to settle it, and as of August 2026 AFAR’s own page still describes it as seeking funding, enrollment not begun (21). Two randomized trials meanwhile found metformin blunting the gains older adults get from exercise, cutting improvements in how well muscle cells make energy and in fitness (22), and losing to placebo on lean mass at 1,700 mg/day over 14 weeks of resistance training (23). Fitness and muscle are the two biggest levers in this piece. Dulling both to chase a result nobody has repeated is a bad trade.

Rapamycin. PEARL assigned 114 adults aged 50 to 85 at random to placebo or 5 or 10 mg of weekly compounded rapamycin for 48 weeks and found it tolerable, with side gains in lean tissue and self-reported pain in women at the higher dose (24). The trial was funded and run by AgelessRx, a longevity telehealth company that sells the thing being studied. Human data on living longer does not exist. I would not write it for this. Senolytics have less. A senolytic is a drug built to clear out worn-out cells that have stopped dividing but keep irritating the tissue around them, and no senolytic has produced any human data on health or lifespan. Everything published so far is safety work (25).

Statins I treat as cholesterol drugs, which is what the guidelines say they are; PREVENTABLE reports in December 2026 on adults over 75 without heart disease (26).

Aspirin is the cleanest example of a longevity assumption failing once somebody randomized it. ASPREE tested low-dose aspirin in healthy older adults for primary prevention, meaning people who had never had a heart attack or a stroke. They died at a higher rate on aspirin, HR 1.14, driven mainly by cancer death, with more major hemorrhage, meaning serious bleeding, and no heart benefit (27). The primary endpoint, which is the single question a trial is built to answer, was years lived without disability, and it showed nothing (28). If you take a daily aspirin with no vascular disease because someone suggested it in 2006, raise it at your next visit.

The supplement aisle, and phosphatidylcholine in particular

NAD+ precursors sell on a mechanism and a biomarker. A biomarker is something you can measure in blood that may or may not track with how you feel or how long you live. Nicotinamide riboside raises whole-blood NAD+ up to 142 percent at 1,000 mg over two weeks, in an open-label study with no clinical endpoint (29). A review of ten NMN trials found the same shape: NAD+ rises, a thin signal on physical performance, nothing resembling a disease or death outcome (30). Tested against thinking and memory in people with mild cognitive impairment, it moved the blood chemistry and nothing else (31).

The ones people tell me they are already on are NAD+ precursors, NMN or NR, and resveratrol. Resveratrol has its own long and contested story, which this post is not going to settle, so read its absence from the rest of this as scope rather than a verdict.

NMN’s legal status is a mess. FDA ruled in November 2022 that it does not count as a dietary supplement, and trade reporting says two FDA letters dated September 29, 2025 reversed that. I have not confirmed those letters against FDA’s own text, so treat the status as unsettled.

Taurine is the most interesting fight in the field. Singh’s 2023 Science paper stretched the median mouse lifespan by 10 to 12 percent and reported that taurine in the blood falls with age in humans, monkeys and mice (32). That second claim is what created the product. An NIA-led group then found taurine flat or rising with age across three human groups plus primates and mice (33), and a separate group measuring 137 men aged 20 to 93 found no link between taurine and age, muscle, strength or how well muscle cells make energy (34). The mouse result stands unchallenged. The human claim underneath the marketing failed to repeat. Twice. No trial has tested taurine against a real human outcome. Anyone selling you certainty either way has not read all three papers.

Phosphatidylcholine earns its own answer, because the real story beats the marketing one. It is a fat molecule and one of the main ways we get choline from food, sold in pills for memory and cell health, and injected as a fat-dissolving product. Pill trials of phosphatidylcholine and lecithin have not helped memory in Alzheimer’s disease, the supporting work on lifespan sits in worms and mice, and no human trial measures anything that matters.

The case against it is better built than the case for it. Choline, phosphatidylcholine and carnitine feed gut bacteria that make a compound called trimethylamine, which the liver turns into TMAO. Tang followed 4,007 heart patients and found that high TMAO went with more heart attacks and strokes (35), building on Wang’s 2011 Nature paper showing that gut bacteria breaking down phosphatidylcholine drives artery disease in animals (36). Read that honestly and the research against phosphatidylcholine pills is stronger than the research for them. I would not take it. The injected version is worse. FDA warns about phosphatidylcholine and sodium deoxycholate products sold online as Aqualyx, Lipodissolve and Kabelline, and the only approved injection for fat reduction is deoxycholic acid on its own, for fat under the chin (37).

The money I would rather you did not spend

Injectable peptides bought online are the clearest line I draw. FDA put several, BPC-157 and epitalon among them, into category 2 of its bulk drug substances list in September 2023, which flags a real safety risk and blocks pharmacies from mixing them up for patients (38). There has been plenty of trade reporting that HHS moved to pull most of them back off that list. I have not confirmed any of it against FDA’s own text, so I am not going to tell you the rules changed. Coming off a restricted list would not be approval anyway. It never was.

I have seen videos online of people advocating injecting peptides, and it makes me uneasy.

Stem cell and exosome clinics have a legal record anyone can read. A federal court ruled against US Stem Cell Clinic in 2019, finding its product adulterated and misbranded, which are the legal terms for failing quality standards and being sold under a false label, and the reported harms include blindness. FDA states there is no approved exosome product for any medical use in this country (39). Young plasma got its own February 2019 FDA notice: no convincing evidence of benefit, against risks including fluid overload, TRALI, which is a serious lung injury, and catching an infection from the donor (40).

Growth hormone marketed for aging can put you in criminal court. 21 U.S.C. §333(e) makes it a federal felony to hand out hGH for anything other than an FDA-approved use in a diagnosed disease, and FDA counts writing the prescription as handing it out (41). It is the only drug in the code carrying that rule. The pitch still traces to Rudman’s 1990 NEJM paper: 21 men, six months, no placebo group, an 8.8 percent rise in lean body mass (42). Nobody counted deaths, and nobody was blinded. NEJM said in 2003 that consumers who meet those citations are being misled (43). Still doing sales work.

Consumer epigenetic age tests belong in the entertainment column. A 2025 preprint reports that running one sample twice can give answers as much as nine years apart on some clocks, and the reliability problem shows up in peer-reviewed work too (44). If your number moves three years after you start a supplement, you measured the test.

Full-body MRI in people with no symptoms is the expensive one. Scans turn up a confirmed cancer roughly 1.1 to 1.5 percent of the time, while about 95 percent of healthy adults show an incidental finding, meaning something the scan spots by accident, and around 91 percent of those turn out to mean nothing (45). Nine in ten. Nothing. What it reliably produces is a repeat MRI, a biopsy of something harmless, and months of fear. Skip it.

For patients, and for the clinicians reading over their shoulder

If you are a patient, work the list in the order the effect sizes come in. Blood pressure to target, which on my end means you own a cuff and bring me the readings, since I cannot take them from here. Quit smoking at any age, because the payoff is measured in years rather than percentage points. Build an aerobic base and lift something twice a week. Then, with whatever money and attention is left over, consider a supplement, and ask one question before you buy it: what did the trial actually measure? If the answer is a blood level, a clock or a marker, it did not measure your life. That question alone empties most of the aisle.

If you are a clinician, the awkward part of this field is that our best-evidenced longevity drugs are ones we already prescribe under other names. Blood pressure drugs, statins, GLP-1 receptor agonists, quit-smoking therapy. Patients arrive on video already carrying things they bought from direct-to-consumer platforms, so ask what they are taking without an eyebrow, because a patient who feels judged stops telling you. Get the compounded rapamycin, the peptide vial and the NMN into the chart and screen interactions properly. When you quote SELECT, quote the hierarchical testing failure along with it.

The Bottom Line

The gap between the best-proven ways to live longer and the most heavily marketed ones runs opposite to the ad money. Cardiorespiratory fitness, blood pressure control, and never picking up another cigarette sit at the top, with effects no capsule has come near.

GLP-1 receptor agonists have real outcome data and a real reason to use them. Metformin for longevity in people without diabetes rests on a weak comparison nobody randomized, plus two randomized trials showing it gets in the way of exercise. Rapamycin is interesting and unproven in humans. Senolytics have nothing at all. Aspirin in healthy older adults who had never had a heart attack made things measurably worse. NAD+ precursors move a blood level nobody has shown you should care about, the human claim behind taurine failed to repeat, and phosphatidylcholine has better research against it than for it.

Buy the used bike before you buy the peptide. If you want one thing to do this week, it does not cost anything.

Sources

Mandsager K, Harb S, Cremer P, et al. Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Network Open. 2018;1(6):e183605. PMID 30646252. https://pubmed.ncbi.nlm.nih.gov/30646252/
Singh B, et al. Comparison of objectively measured and estimated cardiorespiratory fitness to predict all-cause and cardiovascular mortality: systematic review and meta-analysis. Journal of Sport and Health Science. 2025;14:100986. PMID 39271056. https://pubmed.ncbi.nlm.nih.gov/39271056/
Momma H, Kawakami R, Honda T, Sawada SS. Muscle-strengthening activities are associated with lower risk and mortality in major non-communicable diseases. British Journal of Sports Medicine. 2022;56(13):755-763. PMID 35228201. https://pubmed.ncbi.nlm.nih.gov/35228201/
Leong DP, Teo KK, Rangarajan S, et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. The Lancet. 2015;386(9990):266-273. PMID 25982160. https://pubmed.ncbi.nlm.nih.gov/25982160/
Paluch AE, Bajpai S, Bassett DR, et al. Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts. The Lancet Public Health. 2022;7(3):e219-e228. https://doi.org/10.1016/S2468-2667(21)00302-9
SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. New England Journal of Medicine. 2015;373:2103-2116. PMID 26551272. https://pubmed.ncbi.nlm.nih.gov/26551272/
Jha P, Ramasundarahettige C, Landsman V, et al. 21st-Century Hazards of Smoking and Benefits of Cessation in the United States. New England Journal of Medicine. 2013;368(4):341-350. PMID 23343063. https://pubmed.ncbi.nlm.nih.gov/23343063/
Yin J, Jin X, Shan Z, et al. Relationship of Sleep Duration With All-Cause Mortality and Cardiovascular Events. Journal of the American Heart Association. 2017;6(9):e005947. PMID 28889101. https://pubmed.ncbi.nlm.nih.gov/28889101/
McEvoy RD, Antic NA, Heeley E, et al. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea (SAVE). New England Journal of Medicine. 2016;375:919-931. PMID 27571048. https://pubmed.ncbi.nlm.nih.gov/27571048/
Holt-Lunstad J, Smith TB, Layton JB. Social Relationships and Mortality Risk: A Meta-analytic Review. PLoS Medicine. 2010;7(7):e1000316. PMID 20668659. https://pubmed.ncbi.nlm.nih.gov/20668659/ (companion analysis: Holt-Lunstad J, et al. Perspectives on Psychological Science. 2015;10(2):227-237. PMID 25910392)
Estruch R, Ros E, Salas-Salvadó J, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. New England Journal of Medicine. 2018;378(25):e34. PMID 29897866. https://pubmed.ncbi.nlm.nih.gov/29897866/
Look AHEAD Research Group. Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes. New England Journal of Medicine. 2013;369:145-154. PMID 23796131. https://pubmed.ncbi.nlm.nih.gov/23796131/
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). New England Journal of Medicine. 2023;389(24):2221-2232. PMID 37952131. https://pubmed.ncbi.nlm.nih.gov/37952131/
Perkovic V, Tuttle KR, Rossing P, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW). New England Journal of Medicine. 2024;391(2):109-121. PMID 38785209. https://pubmed.ncbi.nlm.nih.gov/38785209/
Lam CSP, et al. Tirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of SURMOUNT-MMO. Obesity (Silver Spring). 2025;33:1645-1656. PMID 40545827. https://pubmed.ncbi.nlm.nih.gov/40545827/
Shirley M. Orforglipron: First Approval. Drugs. 2026. PMID 42479349. https://pubmed.ncbi.nlm.nih.gov/42479349/
Neeland IJ, et al. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes, Obesity and Metabolism. 2024. https://doi.org/10.1111/dom.15728
Bauer J, Biolo G, Cederholm T, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. Journal of the American Medical Directors Association. 2013;14(8):542-559. PMID 23867520. https://pubmed.ncbi.nlm.nih.gov/23867520/
Bannister CA, Holden SE, Jenkins-Jones S, et al. Can people with type 2 diabetes live longer than those without? Diabetes, Obesity and Metabolism. 2014;16(11):1165-1173. https://doi.org/10.1111/dom.12354
Stevenson-Hoare J, et al. Comparison of long-term effects of metformin on longevity between people with type 2 diabetes and matched non-diabetic controls. BMC Public Health. 2023;23:804. https://doi.org/10.1186/s12889-023-15764-y
American Federation for Aging Research. TAME (Targeting Aging with Metformin) trial page. Accessed August 2026. https://www.afar.org/tame-trial
Konopka AR, Laurin JL, Schoenberg HM, et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell. 2019;18(1):e12880. PMID 30548390. https://pubmed.ncbi.nlm.nih.gov/30548390/
Walton RG, Dungan CM, Long DE, et al. Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults (MASTERS). Aging Cell. 2019;18(6):e13039. PMID 31557380. https://pubmed.ncbi.nlm.nih.gov/31557380/
Moel M, et al. Participant-reported and objective outcomes of low-dose rapamycin in healthy adults: the PEARL trial. Aging (Albany NY). 2025;17:908-936. https://doi.org/10.18632/aging.206235
Justice JN, Nambiar AM, Tchkonia T, et al. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine. 2019;40:554-563. PMID 30616998. https://pubmed.ncbi.nlm.nih.gov/30616998/
PREVENTABLE: Pragmatic Evaluation of Events and Benefits of Lipid-Lowering in Older Adults. ClinicalTrials.gov NCT04262206. https://clinicaltrials.gov/study/NCT04262206
McNeil JJ, Nelson MR, Woods RL, et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly (ASPREE). New England Journal of Medicine. 2018;379:1519-1528. PMID 30221595. https://pubmed.ncbi.nlm.nih.gov/30221595/
McNeil JJ, Woods RL, Nelson MR, et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. New England Journal of Medicine. 2018;379:1499-1508. https://doi.org/10.1056/NEJMoa1800722
Airhart SE, Shireman LM, Risler LJ, et al. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside and its effects on blood NAD+ levels in healthy volunteers. PLoS One. 2017;12(12):e0186459. PMID 29211728. https://pubmed.ncbi.nlm.nih.gov/29211728/
Systematic review and meta-analysis of nicotinamide mononucleotide randomized controlled trials. PMC11365583. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365583/
Orr ME, et al. A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. GeroScience. 2024;46:665-682. PMID 37994989. https://pubmed.ncbi.nlm.nih.gov/37994989/
Singh P, Gollapalli K, Mangiola S, et al. Taurine deficiency as a driver of aging. Science. 2023;380(6649):eabn9257. PMID 37289866. https://pubmed.ncbi.nlm.nih.gov/37289866/
Santos-Dias A, et al. Taurine concentrations in humans and nonhuman primates do not decline with age. Science. 2025;388(6751). https://doi.org/10.1126/science.adl2116
Marcangeli V, et al. Experimental Evidence Against Taurine Deficiency as a Driver of Aging in Humans. Aging Cell. 2025;24(10):e70191. PMID 41061678. https://pubmed.ncbi.nlm.nih.gov/41061678/
Tang WHW, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. New England Journal of Medicine. 2013;368(17):1575-1584. PMID 23614584. https://pubmed.ncbi.nlm.nih.gov/23614584/
Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57-63. PMID 21475195. https://pubmed.ncbi.nlm.nih.gov/21475195/
US Food and Drug Administration. Using Fat-Dissolving Injections That Are Not FDA Approved Can Be Harmful. https://www.fda.gov/drugs/buying-using-medicine-safely/using-fat-dissolving-injections-are-not-fda-approved-can-be-harmful
US Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks (category 2 list, September 2023). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
US Food and Drug Administration. Public Safety Alert Due to Marketing of Unapproved Stem Cell and Exosome Products. https://www.fda.gov/safety/medical-product-safety-information/public-safety-alert-due-marketing-unapproved-stem-cell-and-exosome-products
US Food and Drug Administration. Important Information about Young Donor Plasma Infusions for Profit (February 19, 2019). https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-information-about-young-donor-plasma-infusions-profit
21 U.S.C. §333(e), Offenses involving human growth hormone. https://www.law.cornell.edu/uscode/text/21/333
Rudman D, Feller AG, Nagraj HS, et al. Effects of human growth hormone in men over 60 years old. New England Journal of Medicine. 1990;323(1):1-6. PMID 2355952. https://pubmed.ncbi.nlm.nih.gov/2355952/
Perls TT. Anti-aging quackery: human growth hormone and tricks of the trade. New England Journal of Medicine. 2003. https://doi.org/10.1056/NEJMp020186
Technical reliability and reproducibility of epigenetic clock measurements. PMC9586209. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9586209/ (nine-year replicate-variability figure is from a 2025 bioRxiv preprint that has not been peer reviewed)
Whole-body MRI screening in asymptomatic adults: diagnostic yield and incidental findings, systematic review. PMC6249611. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249611/

Where the label usually comes from

The label is not free

There is a score for this, and it runs on history alone

What I actually do with this on a video visit

What a real reaction looks like, and what has changed about treating it

For patients

For colleagues

The Bottom Line

Related Reading

Sources

Start with the boring part, because it is the part that matters

The dementia finding, and the catch

What I actually think about it

The part that belongs to my day job

If you already have it, the clock is the thing

For patients

For colleagues

The Bottom Line

Related Reading

Sources

Location does most of the diagnostic work

The one that gets missed for years

What actually treats an abscess

Why they keep coming back

The part that belongs to my day job

For patients

For colleagues

The Bottom Line

Related Reading

Sources

Itching is not the same as infestation

How to tell persistent itch from actual failure

Failure is more common than people think

The boring reasons treatment fails

The lumps that stay for months

When the itch is not scabies at all

What I ask for on a video visit

For patients

For colleagues

The Bottom Line

Related Reading

Sources

A healing wound is a construction project

What glucose does to the machinery

The protein number

Arginine, and how good the evidence actually is

Vitamin C and zinc

What matters more than any of it

For patients

For colleagues

The Bottom Line

Related Reading

Sources

The velvet patch on the back of the neck

Skin tags carry information

What high glucose actually does to a wound

The infections that come with the territory

Hidradenitis suppurativa, and what changed

The foot

What I ask for on video

For patients

For colleagues

The Bottom Line

Related Reading

Sources

Why the name changed in 2014

Somewhere between 27% and 84%

What I can settle over video. What I can’t.

Start in the drugstore aisle

Low-dose vaginal estrogen

About that boxed warning, precisely

DHEA, ospemifene, and the limits of systemic therapy

Lasers

The best evidence here is about UTIs

After breast cancer, especially on an aromatase inhibitor

If you are the patient

Notes for clinicians

The Bottom Line

Related Reading

Sources