Tag: FDA

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Why Can’t You Get an Estrogen Patch? The 2026 Estradiol Shortage, Explained

On By Dr. Scott RennieIn Menopause & Women's HealthLeave a comment

Several of my patients are having a hard time filling their estradiol patches right now. Not one pharmacy being out for a week. Calling four places, getting a different strength than was prescribed, driving across town, running out before the next box arrives.

So let us go through the explanations people are offering, in order, and then what the evidence actually supports.

Hypothesis one: everyone started using them at once

This one is true, and the numbers are not subtle.

Estradiol patch prescriptions went from about 594,000 in June 2024 to 1.6 million in May 2026 (1). Among women aged 45 to 54, prescribing rose 184 percent, and by February 2026 roughly one in twenty women in that age group had an estrogen prescription (2). Patches now account for a large share of all estrogen prescriptions, and they were never the volume product the supply chain was built around.

The accelerant was regulatory. On November 10, 2025, the FDA announced it was removing the boxed warnings about cardiovascular disease, breast cancer and dementia from menopausal hormone therapy, with Commissioner Marty Makary saying the agency intended to “stop the fear machine steering women away from this life-changing, even lifesaving, treatment” (3). Those warnings had suppressed use for two decades. Pull them off, and a very large number of women who had been told no for years hear a different answer in the same month.

I wrote about that decision when it happened and I thought it was defensible. I did not expect it to empty the shelves.

Hypothesis two: something broke in manufacturing

This one is mostly false, and it is worth saying so clearly because it is the version that frightens people.

There is no recall behind this. No contamination finding, no plant shutdown, no safety problem with the patches that are reaching pharmacies. The FDA’s position, repeated through the summer, is that all the manufacturers are producing at full capacity (4).

What is true is that patches are hard to make more of quickly. A transdermal patch is a drug-in-adhesive matrix that has to deliver a precise dose through skin for three or four days. The production lines are specialized, and companies describe expansion timelines in years rather than months. Add thin generic margins, and nobody is rushing to build a new line for a product that might be a fad.

So: not a manufacturing failure. A manufacturing capacity ceiling, which is a different thing and gets solved on a much slower clock.

Hypothesis three: RFK Jr. and the administration did this

This is the one I keep seeing in comment sections, and the honest answer is more interesting than either the accusation or the denial.

There was no sabotage. Nobody restricted estrogen. If anything, this administration’s FDA pushed hormone therapy harder than any in twenty years, and the demand surge is a direct downstream consequence of that push. You cannot simultaneously argue that they suppressed access and that they promoted the drug into a shortage.

Where policy does have fingerprints is slower and less dramatic. HHS cut roughly 3,500 FDA positions in 2025 as part of a larger restructuring (5). The agency said reviewers and inspectors were protected. Reporting since has described reviewers absorbing administrative work and longer, less predictable timelines. None of that caused the shortage. All of it makes a nimble response harder, and a nimble response is exactly what a demand shock requires.

And there is a specific, consequential decision sitting right in the middle of this.

The part that actually matters: the FDA has not declared a shortage

Pharmacists have been listing estradiol patches as short since January 30, 2026. ASHP’s bulletin has grown to roughly 17 affected packages across five manufacturers, including Dotti, Lyllana, and the Noven, Sandoz, Viatris and Zydus generics (6).

The FDA has acknowledged that women are having trouble and says it is working with manufacturers to expand supply (7). It has not added the patches to its official shortage list.

That gap is not bureaucratic trivia. A formal shortage designation changes what other parties are allowed and incentivized to do. It can ease the path for additional manufacturers, it supports compounding in some circumstances, and it affects how insurers handle a prescription that has to be split across strengths or pharmacies. An Arizona gynecologist, Dr. Suzanne Hackenmiller, started a petition asking for the declaration, and Democratic members of the House have written to the agency asking the same (8).

So the fair summary of the policy question is this. The administration did not cause a shortage by restricting anything. It drove demand deliberately and then declined to use the one administrative tool that would most directly help the women it told to ask for treatment.

Two more explanations worth naming

Fragmentation makes it worse. When a patient cannot get one 0.1 mg patch, the workaround is often two 0.05 mg patches, or a different brand at a different pharmacy. Every one of those workarounds consumes more units of a constrained product and can generate a second copay. Scarcity plus substitution produces more scarcity.

Stockpiling is rational and corrosive. A woman who has been told to ration her patches will fill three months when she can get three months. I do not blame anybody for that. It also means supply reaches fewer people in any given week.

What to do if you are caught in this

First, do not simply stop. Vasomotor symptoms come back fast once estrogen is withdrawn, and the people who suffer most in a shortage are the ones who quietly go without and assume there was no alternative.

There are several, and most of them keep you on transdermal delivery, which matters if the reason you were on a patch in the first place was migraine with aura, a clot history, or anything else that argued against oral estrogen.

Gels and sprays are the closest substitute: EstroGel, Divigel, Evamist. Same route, same avoidance of first-pass liver metabolism, different daily routine. Oral estradiol is reasonable for many women and is widely available and cheap, though it is not the right swap for everyone. A different patch brand or a weekly patch instead of a twice-weekly one is often available when your usual one is not. If your symptoms are limited to vaginal dryness and painful sex, local vaginal estrogen is a different supply chain entirely and is not caught up in this.

Practical things that work: ask the pharmacy to check the strengths they do have rather than just saying no, call independent pharmacies because they order through different channels than the big chains, ask for a 90-day fill when you find stock, and have your clinician send the prescription with the substitution permitted so the pharmacist can act without a second call.

For clinicians

Write the alternative into the prescription up front. A patch prescription with no permitted substitution turns every stockout into a phone call, and in a shortage that is where the days get lost.

Know which of your patients actually need transdermal delivery rather than merely prefer it, because that determines whether oral is an acceptable bridge or a bad idea.

And counsel on the rebound explicitly. A patient who runs out and waits two weeks does not experience that as a supply problem. She experiences it as hormone therapy failing, and some of them do not come back.

The Bottom Line

The estrogen patch shortage is a demand shock, not a manufacturing failure and not a conspiracy.

The FDA removed a twenty-year-old warning, prescriptions nearly tripled in two years, and a small, low-margin, slow-to-expand corner of the generic industry could not absorb it. The policy criticism that holds up is not that anyone blocked access. It is that the agency drove the demand and has still not declared the shortage that would help unlock supply.

If you are affected, you have options, and most of them keep you on the same route of delivery. Call before you run out rather than after.

Related Reading

FDA Removes Black Box Warning From Menopause Hormone Therapy
Menopause Care by Telemedicine: What a Virtual Visit Can and Cannot Do
Perimenopause and Menopause Symptoms and How to Manage Them
Menopause and Sleep: What Is Actually Waking You Up
Vaginal Dryness After Menopause: Why It Doesn’t Go Away
More on Menopause & Women’s Health

Scott Rennie, D.O.
Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

Sources

  1. Estrogen patch shortage prompts doctors, lawmakers to seek FDA action. CBS News, September 3, 2026. https://www.cbsnews.com/news/estrogen-patch-shortage-fda-declaration-hormone-replacement-therapy/
  2. Menopause Estrogen Patches Are in Short Supply. What Are the Alternatives? Healthline, April 15, 2026. https://www.healthline.com/health-news/menopause-estrogen-patch-shortage-after-fda-endorsement
  3. HHS. HHS Advances Women’s Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy. November 10, 2025. https://www.hhs.gov/press-room/hhs-advances-womens-health-removes-misleading-fda-warnings-hormone-replacement-therapy.html
  4. Estrogen patches are in short supply as women seek menopause support. CNBC, June 26, 2026. https://www.cnbc.com/2026/06/26/estrogen-patches-are-in-short-supply-as-women-seek-menopause-support.html
  5. HHS to cut 10,000 staff in major restructuring. BioPharma Dive. https://www.biopharmadive.com/news/hhs-layoffs-restructuring-kennedy-fda-cms-trump/743694/
  6. ASHP Drug Shortage Detail: Estradiol Transdermal System. https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=1206
  7. FDA acknowledges estrogen patch shortage, says it’s working to increase supply. Stateline, September 16, 2026. https://stateline.org/2026/09/16/fda-acknowledges-estrogen-patch-shortage-says-its-working-to-increase-supply/
  8. FDA claims there’s no estrogen patch shortage as women struggle to get prescriptions filled. NBC News. https://www.nbcnews.com/health/womens-health/fda-estrogen-patch-shortage-hormone-therapy-alternatives-rcna344233
  9. FDA removes menopause hormone therapy black box warnings. Harvard Health. https://www.health.harvard.edu/womens-health/fda-removes-menopause-hormone-therapy-black-box-warnings
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Does Mounjaro Lower Your Risk of Heart Attack and Stroke?

On By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

On August 28, 2026, the FDA approved a new use for Mounjaro (tirzepatide): lowering the risk of cardiovascular death, nonfatal heart attack, and nonfatal stroke in adults with type 2 diabetes who are at high risk for those events (1). That is a real change written into the drug’s FDA-approved label. The short version is this: tirzepatide matched, but did not beat, a diabetes drug that already had proven heart benefits of its own. Whether that counts as exciting news depends on what you were expecting going in.

What the Label Now Says

Mounjaro’s original approval covered blood sugar control in adults, later extended to children age 10 and up with type 2 diabetes in December 2025 (3). The new cardiovascular indication sits on top of that one. It reads, in the FDA’s language, as lowering the risk of major adverse cardiovascular events, meaning cardiovascular death, nonfatal heart attack, or nonfatal stroke, in adults with type 2 diabetes who are already at high risk for those events (1, 2). That population matters: this approval is specific to people with type 2 diabetes who already carry meaningful cardiovascular risk, largely established atherosclerotic disease.

An outcomes indication like this one is a different category of claim than glycemic control. It says the drug changed what happens to a person’s heart and vessels over years, something a lab value at three months cannot tell you on its own. That distinction is the entire reason a cardiovascular outcomes trial exists.

The Trial Behind It

The approval rests on SURPASS-CVOT, a randomized, double-blind trial that enrolled more than 13,000 adults with type 2 diabetes and established atherosclerotic cardiovascular disease across 640 sites in 30 countries (4). Participants were assigned to tirzepatide, titrated up to 15 mg weekly or their highest tolerated dose, or dulaglutide (Trulicity) 1.5 mg weekly, followed for a median of roughly four years. Dulaglutide was not a placebo. A drug with its own proven cardiovascular track record from the REWIND trial, chosen deliberately as a harder comparator than sugar water.

The primary outcome, a composite of cardiovascular death, heart attack, or stroke known as three-point MACE, occurred in 12.2 percent of the tirzepatide group and 13.1 percent of the dulaglutide group. That is a hazard ratio of 0.92, with a 95.3 percent confidence interval of 0.83 to 1.01 (4). Tirzepatide met the prespecified bar for noninferiority (p=0.003). It did not meet the bar for superiority (p=0.09). Read plainly: tirzepatide did not fall behind a drug already known to protect the heart, and it numerically edged ahead, but the trial cannot say with statistical confidence that it beat dulaglutide on this endpoint.

Two other numbers are worth knowing even though they sit outside the approved claim. All-cause mortality was 16 percent lower with tirzepatide than with dulaglutide, hazard ratio 0.84, 95 percent confidence interval 0.75 to 0.94, per Lilly’s topline results release (5). And the weight difference was large: about 11.6 percent body weight reduction with tirzepatide against 4.5 percent with dulaglutide (4), which tracks with everything already known about how the two drugs differ on that front. Neither of those numbers was the tested primary endpoint, so treat them as suggestive rather than proven.

I do not read this trial as evidence that tirzepatide is the better heart drug. I read it as evidence that choosing tirzepatide over an active cardioprotective comparator costs you nothing on the cardiovascular side, while it still outperforms on weight and blood sugar. That is a useful thing to know, and it is a smaller claim than the headlines will make it sound.

Where This Leaves Ozempic, Wegovy, and Zepbound

Semaglutide already has cardiovascular outcomes data of its own, built from different comparators and different populations, which matters when you start comparing hazard ratios across trials. SUSTAIN-6 tested injectable Ozempic against placebo in type 2 diabetes at high cardiovascular risk and found a hazard ratio of 0.74 (6). Ozempic tablets, oral semaglutide, picked up their own cardiovascular indication in October 2025 based on the SOUL trial, hazard ratio 0.86, in a population with type 2 diabetes and atherosclerotic disease, chronic kidney disease, or both, broader than “established cardiovascular disease” alone (7). Wegovy’s SELECT trial went further still: adults with overweight or obesity and established cardiovascular disease, no diabetes required at all, hazard ratio 0.80 against placebo (8).

Four trials went into these numbers, each built around its own comparator and its own patient population. Lining the hazard ratios up side by side and picking a winner overstates what any single number can tell you. SURPASS-CVOT is the only one of the four tested against an active drug with its own proven benefit, a harder bar to clear even when the resulting number looks smaller.

Zepbound carries no such indication yet. Zepbound and Mounjaro are the same molecule, tirzepatide, at the same doses. The difference is entirely regulatory. Mounjaro is approved for type 2 diabetes, and its new cardiovascular claim comes from a trial that specifically enrolled people with diabetes. Zepbound is approved for obesity and, separately, moderate to severe obstructive sleep apnea. Its own cardiovascular outcomes trial, SURMOUNT-MMO, is still enrolling, expected to include roughly 15,000 adults with obesity who do not have diabetes, and has not reported results (9). Tirzepatide’s heart benefit currently exists on the books only under the Mounjaro name, for a population that has diabetes.

For Patients

If you have type 2 diabetes and known heart disease and you are already doing well on dulaglutide, this trial should reassure you. Superiority was not shown, so nothing in the data requires a change if your current regimen is working. If your blood sugar or weight has been harder to manage, this approval gives your clinician a documented, FDA-recognized reason to discuss tirzepatide.

Coverage is worth asking about directly. An outcomes-based indication sometimes changes how an insurer’s prior authorization process treats a drug, because it can be framed as reducing a documented risk of death rather than only managing a lab value. That is not guaranteed, and formularies vary by plan. Ask specifically whether this new indication affects your prior authorization, rather than assuming it automatically will.

Patients on my video visits do ask about switching from semaglutide to tirzepatide after news like this. I tell them to stay on semaglutide if it’s working. Superiority was not shown here, so a regimen that is already working has no data forcing a change.

The Practical Question for Prescribers

For a patient with type 2 diabetes and established cardiovascular disease, tirzepatide’s larger effect on weight and A1c, paired with a trial showing it keeps pace on cardiovascular safety against an already-protective drug, makes a reasonable case for choosing it first. That is my opinion, and it deserves the caveat the superiority test earned: the point estimate favored tirzepatide, but the confidence interval did not exclude the possibility of no difference at all.

The active-comparator design is also worth sitting with. Because there was no placebo arm, SURPASS-CVOT cannot independently quantify tirzepatide’s benefit against doing nothing. It borrows dulaglutide’s REWIND-established benefit and shows tirzepatide keeps that benefit intact. Proving a brand new benefit from scratch would have required a placebo arm, and this trial did not have one.

When type 2 diabetes is the indication, I prescribe Mounjaro.

The Bottom Line

Tirzepatide gives up nothing on heart safety when measured against a drug that already protects the heart, and it does more for weight and A1c along the way. That is the real result of SURPASS-CVOT, even though the trial stopped short of proving superiority: the noninferiority bar was met (p=0.003), the superiority bar was not (p=0.09). If you have type 2 diabetes and heart disease, ask your prescriber whether tirzepatide fits your regimen better than what you are on now, and ask whether this new indication changes what your insurer will approve. The August 28, 2026 approval gives that conversation a documented reason to happen (1).

Related Reading

Do Ozempic and Zepbound Cause Muscle Loss?

Foundayo vs. the Wegovy Pill: Comparing the Two New Weight Loss Pills

Wegovy and Zepbound Cash Pay Prices Without Insurance (2026 Update)

More on Weight Loss & Metabolic Health

Scott Rennie, D.O.
Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

Sources

1. FDA approves Lilly’s Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes. Eli Lilly and Company, August 28, 2026. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-mounjaro-tirzepatide-reduce-cardiovascular

2. FDA Expands Tirzepatide Label to Reduce Cardiovascular Risk in Type 2 Diabetes. AJMC. https://www.ajmc.com/view/fda-expands-tirzepatide-label-to-reduce-cardiovascular-risk-in-t2d

3. FDA approval letter, supplement 215866/S-039 (pediatric type 2 diabetes indication, age 10 and older). U.S. Food and Drug Administration, December 19, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215866Orig1s039ltr.pdf

4. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT). New England Journal of Medicine, December 2025. PMID 41406444. https://pubmed.ncbi.nlm.nih.gov/41406444/

5. Lilly’s Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist, demonstrated cardiovascular protection in landmark head-to-head trial. Eli Lilly and Company, July 31, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated

6. Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6). N Engl J Med. 2016;375:1834-1844. https://www.nejm.org/doi/full/10.1056/NEJMoa1607141

7. McGuire DK, Marx N, Mulvagh SL, et al. Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes (SOUL). N Engl J Med. 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2501006

8. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389:2221-2232. PMID 37952131. https://pubmed.ncbi.nlm.nih.gov/37952131/

9. Tirzepatide for Reduction of Morbidity and Mortality in Adults with Obesity (SURMOUNT-MMO). ClinicalTrials.gov, NCT05556512. https://clinicaltrials.gov/study/NCT05556512

A wooden bedside table with a closed notebook, reading glasses, and a mug beside an unmade linen bed in soft morning window light

Should Women Take Testosterone After Menopause?

On By Dr. Scott RennieIn Menopause & Women's HealthLeave a comment

Update, September 18, 2026: What Came Out of the FDA Workshop

The workshop happened yesterday. Nothing was approved, and approval was never on the table. What changed was the tone. Admiral Brian Christine, the Assistant Secretary for Health, opened by calling the lack of an FDA-approved testosterone product for women “unacceptable” when Australia has one. The FDA’s own position was more measured: the approval standard is the same for every drug, data from other countries will be judged case by case, and the agency says it stands ready to review an application (10).

That last point matters most. Nothing changes for patients until a company actually files. Products made for women are already approved in the UK, Australia, New Zealand and South Africa, so the data exists. The question is whether anyone brings it here.

The science presented matched what I wrote below. Dr. Rajita Patil of UCLA’s menopause program said the evidence supports testosterone for postmenopausal women with low sexual desire and is insufficient for mood, cognition or general well-being. She also cautioned against oral testosterone because of what it does to cholesterol (10).

My own practice hasn’t changed. Until there’s an approved product I can prescribe, I refer patients out. Public comments are open until October 19, 2026.

On September 17, 2026, the FDA holds its first public workshop on testosterone use in menopausal women. It is a hybrid session, in person at the agency’s White Oak campus and online at the same time, filed under docket FDA-2026-N-5479, with the public comment period open through October 19 (1). Right now, no testosterone product is FDA-approved for use in women in the United States. Every prescription written for a woman is off-label, borrowed from a product built and dosed for men. When I think a patient would benefit, my role right now is to refer her to someone who can prescribe it, not to write it myself.

That gap has been widening for a decade, and the FDA is only now catching up to it.

Why the Agency Is Paying Attention Now

Prescribing tells the story better than any regulatory notice could. Testosterone prescriptions to women in the US rose roughly 2.6-fold between 2016 and 2025, from 50.0 to 130.8 per 100,000 eligible women (2). In 2025 alone, 90,482 prescriptions went out, up 58.7 percent from the year before. About three in five, 62.2 percent, went to women between 45 and 64. More than half, 51.2 percent, already carried at least one documented cardiometabolic risk factor (2).

Rapid off-label growth in a population that already carries meaningful cardiovascular risk, for a drug whose long-term safety in women is still not established: that combination is what put a federal workshop on the calendar.

The Evidence That Actually Holds Up

Low sexual desire is where testosterone has real trial support. A 2019 systematic review and meta-analysis by Islam and colleagues in The Lancet Diabetes & Endocrinology pooled 36 randomized controlled trials and 8,480 women (3). In postmenopausal women, testosterone significantly improved desire, arousal, orgasm, and sexual pleasure, and reduced the distress that comes with low libido. The Global Consensus Position Statement, released the same year, reached the same conclusion from a different angle: the only evidence-based indication for testosterone therapy in women is hypoactive sexual desire disorder, confirmed only after a genuine biopsychosocial assessment rules out the other usual explanations, a strained relationship, untreated depression, a medication doing this to her (4).

I put it this way when the subject came up this week:

“Low desire is where the evidence is strongest, and that alone is reason not to dismiss it. A lot of women also just feel better on it. We cannot fully explain why yet, but at a physiologic dose with honest counseling about what is proven, that is a reasonable place to stand.”

What the Data Still Cannot Explain

The same Islam review found no measurable effect of testosterone on general wellbeing, cognition, body composition, or musculoskeletal outcomes. No real change in bone density. No change in lean mass or strength. The consensus statement says it plainly: no effect on general wellbeing has been demonstrated in trials to date.

That sits awkwardly next to what a lot of women report once they are actually on it: more energy, sharper focus, a sense of being back in their own body. That reported experience deserves to be taken seriously rather than waved off, and I am not going to claim an energy or cognition benefit I cannot point to a trial for either. The evidence has not caught up to the experience yet.

What a Reasonable Dose Looks Like

The goal is a physiologic premenopausal testosterone level. The dose I would want a patient on is about one-tenth of the standard male dose of a regulated 1 percent testosterone gel, roughly 5 mg applied to the skin daily, off-label since nothing is approved for women. Pellets and high-dose injections push levels into supraphysiologic territory that a properly dosed gel does not reach. Compounded products are a different problem: no consistent evidence backs their dosing, efficacy, or safety, whatever the label promises (4).

Monitoring is not complicated. Check a baseline total testosterone level, recheck at three to six weeks to confirm the dose landed where it should, and stop by six months if there is no symptomatic benefit. Formulation matters for one specific reason: oral testosterone raises LDL cholesterol, while a transdermal patch or gel leaves the lipid panel essentially untouched. Side effects run mild and cosmetic more often than dangerous, acne and unwanted hair growth chief among them. The same 2019 review also recorded an overall increase in weight with testosterone treatment. Worth knowing if weight is already part of the conversation.

Where Estrogen Usually Fits First

Estrogen treats hot flashes, night sweats, disrupted sleep, and vaginal dryness, none of which testosterone has been shown to fix, and it has a much longer safety record behind it. When I treat patients, estrogen usually comes before testosterone.

Without a need for contraception, the regimen I reach for is transdermal 17-beta-estradiol 0.025 to 0.05 mg per day, paired with micronized progesterone 100 mg nightly, continuously, if she still has a uterus. With a need for contraception, I use continuous ethinyl estradiol 20 mcg with levonorgestrel 100 mcg daily instead. About a quarter of the women I see on video visits arrive already started on hormone therapy from somewhere else, so a fair amount of my job is auditing a regimen I did not write.

Flibanserin, sold as Addyi, is worth knowing about too. On December 15, 2025, the FDA expanded its approval to cover postmenopausal women under 65 with HSDD; before that it had only been approved for premenopausal women, since 2015 (5). It is a separate, FDA-approved option aimed specifically at low desire rather than at hormone levels.

Getting Any of This Through a Screen

Testosterone is a Schedule III controlled substance. Under the DEA and HHS telemedicine flexibilities extended through December 31, 2026, a DEA-registered practitioner can currently prescribe it after a video visit alone, with no prior in-person exam, and generally without a separate DEA registration in the patient’s state, as long as both states’ laws allow it (6, 7). That is temporary: it rests on an extension already renewed four times, and the permanent replacement, a special-registration system that would keep Schedule III drugs like this one in an easier tier than Schedule II, has been in White House OMB review since August 25, 2026 with no final version yet (8, 9).

So federal law is not what stops me right now. Some telemedicine platforms do let a DEA-registered clinician prescribe controlled substances after a video visit. The platforms I work through don’t give me that ability at the moment, so when I think a patient would genuinely benefit, I refer her to an in-person clinician who can prescribe it. If that changes, or the DEA’s pending rule settles things for good, I may be able to write it myself.

For Patients

Before a video visit about this, bring your current medications and any hormone therapy already written down. Know what has changed for you, specifically, rather than a general “I don’t feel like myself.” And say what you want treatment to do: “I want my desire back” and “I want more energy” point toward different conversations, and only one has real trial data behind it.

One red flag worth knowing: pellets. The consensus statement is direct about this. Any testosterone preparation that produces supraphysiologic levels, pellets and high-dose injections included, is not recommended, in part because there is no way to adjust or remove the dose once a pellet is implanted. If a clinic is pitching pellets alongside language about restoring youthful vitality, that is worth questioning.

For Colleagues

A total testosterone level should never be the test that diagnoses HSDD. It does not correlate reliably with symptoms; this is a clinical diagnosis built on history and distress, other causes ruled out along the way. There is no data supporting use in premenopausal women, so keep the indication where the evidence lives, and screen for cardiometabolic risk before starting anything, given how much of the current prescribing population already carries it (2).

The Bottom Line

Low desire is where the evidence for testosterone is strongest in postmenopausal women, and that alone is reason not to dismiss it. Many women report feeling better on it, and nobody can fully explain why yet. If I were prescribing, the dose would be physiologic: about one-tenth of the standard male dose of a regulated 1 percent gel, roughly 5 mg on the skin daily, and estrogen usually comes first. Right now I am not the one writing that prescription. Testosterone is a Schedule III controlled substance, and the platforms I work through don’t currently let me prescribe it, so when a patient would benefit, I refer her to an in-person clinician who can. That could change once the DEA finalizes its pending rule or my platforms add the capability. The comment window on the FDA’s workshop closes October 19, 2026.

Related Reading

FDA Removes Black Box Warning From Menopause Hormone Therapy

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

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

More on Menopause & Women’s Health

Scott Rennie, D.O.
Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

Sources

1. FDA. Public Meeting: Testosterone Use in Menopausal Women. September 17, 2026. Docket FDA-2026-N-5479. https://www.fda.gov/consumers/womens-health-events/fda-public-meeting-testosterone-use-menopausal-women-09172026

2. Avivi I, Stuenkel CA, Sampath-Kumar R, Ben-Yehuda O. Accelerating Testosterone Prescribing for U.S. Women: Implications for Cardiovascular Safety. JACC Adv. 2026;5(6 Pt 1):102724. PMID 42095794. https://pmc.ncbi.nlm.nih.gov/articles/PMC13309321/

3. Islam RM, Bell RJ, Green S, Page MJ, Davis SR. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes Endocrinol. 2019;7(10):754-766. PMID 31353194. https://pubmed.ncbi.nlm.nih.gov/31353194/

4. Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019;104(10):4660-4666. PMID 31498871. https://pmc.ncbi.nlm.nih.gov/articles/PMC6821450/

5. Historic First in Women’s Sexual Health: FDA Grants Approval for Addyi (flibanserin) in Postmenopausal Women. BioSpace, December 15, 2025. https://www.biospace.com/press-releases/historic-first-in-womens-sexual-health-fda-grants-approval-for-addyi-flibanserin-in-postmenopausal-women

6. Fourth Temporary Extension of COVID-19 Telemedicine Flexibilities for Prescription of Controlled Substances. Federal Register, December 31, 2025. https://www.federalregister.gov/documents/2025/12/31/2025-24123/fourth-temporary-extension-of-covid-19-telemedicine-flexibilities-for-prescription-of-controlled

7. Drug Enforcement Administration, Diversion Control Division. Telemedicine: State Registration Q&A (EO-DEA192, DEA-DC-044). https://www.deadiversion.usdoj.gov/GDP/(DEA-DC-044)(EO-DEA192)_Telemed_State_Reg_QA_(Final).pdf

8. Special Registrations for Telemedicine and Limited State Telemedicine Registrations. Federal Register, January 17, 2025. https://www.federalregister.gov/documents/2025/01/17/2025-01099/special-registrations-for-telemedicine-and-limited-state-telemedicine-registrations

9. DEA Prescribing of Controlled Substances via Telemedicine. Alliance for Connected Care. https://connectwithcare.org/dea-prescribing-of-controlled-substances/

10. Mahatole S, Ananthan P. US regulators urge more research on testosterone therapy for women. Reuters (via GV Wire), September 17, 2026. https://gvwire.com/2026/09/17/us-regulators-urge-more-research-on-testosterone-therapy-for-women/

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

On 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.

Related Reading

FDA Removes Black Box Warning From Menopause Hormone Therapy Perimenopause and Menopause Symptoms and How to Manage Them Menopause Treatment by Telemedicine: How It Works Vaginal Yeast Infections: Symptoms, Causes, Treatment Bacterial Vaginosis: Most Common Cause of Vaginal Discharge UTI (Bladder Infection): Common Questions Answered

Scott Rennie, D.O.
Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

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/

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FDA Removes Black Box Warning From Menopause Hormone Therapy

On By Dr. Scott RennieIn Menopause & Women's HealthLeave a comment

Since the headlines ran, some version of the same question has been opening my video visits. “So it’s safe now, right? I saw it on the news.”

The women asking are usually a few years past their last period, sleeping badly, foggy at work, and frustrated. Somewhere along the way they were told hormones would give them breast cancer, and that was the end of the conversation. Something did change this summer. What changed is not what most people think.

The FDA did not run a new trial. No fresh outcome data landed on anyone’s desk. What happened is better described as a labeling correction: a regulatory acknowledgment that a warning written for one population had been applied, for more than twenty years, to a completely different one. That distinction is the whole story. It tells you how much permission this gives us, and it tells you exactly where the permission stops.

What Actually Happened

On November 10, 2025, HHS and the FDA announced they were initiating removal of the boxed warning from menopausal hormone therapy products containing estrogen. The specific language coming out covered cardiovascular disease, breast cancer, and probable dementia. (1) The move followed a public expert panel the agency convened in July 2025 and a comment period after that.

Then came the slower part, the part that got almost no coverage. Removing a boxed warning is not a press release. It is a product-by-product labeling supplement for every manufacturer. In February 2026, the FDA approved the first batch: labeling changes for six products spanning all four categories of menopausal hormone therapy, including systemic combination therapy, systemic estrogen alone, systemic progestogen for women with a uterus, and topical vaginal estrogen. (2) Twenty-nine companies had submitted proposed changes by that point. (2) More have been approved since.

The new labels also add something that wasn’t there before: age-specific framing, pointing toward initiation within ten years of menopause onset or before age 60 for systemic therapy. (2)

So the headline “HRT is safe now” is doing a lot of work it can’t support. The accurate version is that a warning which never fit a healthy 52-year-old with hot flashes has finally been taken off her prescription.

Why That Warning Was There In The First Place

You cannot understand the correction without understanding the error.

In July 2002, the Women’s Health Initiative stopped its estrogen plus progestin arm early. That trial had randomized 16,608 postmenopausal women with an intact uterus to conjugated equine estrogens plus medroxyprogesterone acetate or placebo. (3) The data safety monitoring board pulled the plug at 5.2 years because the global index crossed a predetermined boundary.

The relative risks made every front page in the country. Invasive breast cancer, hazard ratio 1.26. Coronary heart disease, 1.29. Stroke, 1.41. Pulmonary embolism, 2.13. (3)

What ran in far smaller type, if it ran at all, were the absolute numbers. Per 10,000 women per year of treatment: seven more coronary events, eight more strokes, eight more pulmonary emboli, eight more invasive breast cancers. Also five fewer hip fractures and six fewer colorectal cancers. (3) These are small absolute differences. “A twenty-six percent increase in breast cancer” and “eight additional cases per ten thousand women per year” describe the same finding, and only one of them ended a generation of treatment.

The estrogen-alone arm, which enrolled 10,739 women who had already had a hysterectomy, was stopped separately in 2004. That arm never showed an increase in breast cancer at all. If anything it trended the other direction. (4) The boxed warning went on both.

The dementia language came from WHIMS, the memory substudy. WHIMS enrolled women aged 65 to 79. (5) That is worth reading twice. A finding generated exclusively in women 65 and older became a printed warning handed to women in their early fifties for the next two decades.

The Trial Didn’t Study The Women Who Got The Warning

Mean age at enrollment in WHI was 63.3 years. (3)

Think about who that is. The average American woman reaches menopause around 51. A 63-year-old enrolling in the mid-1990s was, on average, more than a decade out from her final period. Many were two decades out. Most were not symptomatic, which was by design, because WHI was built as a chronic disease prevention trial and not a symptom trial. Participants were also carrying the cardiovascular risk you would expect at that age, including a substantial proportion with hypertension, obesity, and subclinical atherosclerosis nobody had imaged.

Put estrogen into an artery that already has established, possibly unstable plaque and you are not doing the same thing you do when you put estrogen into a 52-year-old’s relatively clean vasculature. That is the biological core of what became known as the timing hypothesis: estrogen appears to be protective, or at least neutral, in healthy endothelium, and potentially destabilizing in diseased endothelium.

The evidence for it isn’t a hunch.

The ELITE trial randomized 643 postmenopausal women to oral estradiol or placebo, stratified by how far out from menopause they were. In women less than six years postmenopause, estradiol significantly slowed carotid intima-media thickness progression. In women ten or more years out, it did nothing. (6) Same drug, same trial, opposite vascular story depending on when you started it.

The Danish Osteoporosis Prevention Study randomized about 1,000 recently postmenopausal women to hormone therapy or no treatment and followed them for ten years. The treated group had a lower composite rate of death, heart failure hospitalization, and myocardial infarction, with no increase in cancer, stroke, or venous thromboembolism. (7) It was open-label, which limits it, and it wasn’t powered as a cardiovascular outcomes trial. But it points the same direction.

And WHI’s own investigators, when they went back and stratified by age, found the pattern sitting in their own data. Women who started in their fifties looked different from women who started in their seventies. (8) The 18-year follow-up of both WHI arms, published in 2017, found no increase in all-cause mortality, cardiovascular mortality, or cancer mortality in either treatment group. (9)

None of this is new. ELITE published in 2016. The mortality follow-up published in 2017. The FDA’s 2025 action was a review of literature that already existed, which is exactly why calling it a labeling correction is fair. The evidence got there long before the label did.

Now The Part Nobody Is Covering: What This Does Not Do

Here is where I want to slow down, because the celebratory version of this story is going to get people hurt.

The endometrial cancer warning did not go away

The FDA explicitly did not seek removal of the boxed warning regarding endometrial cancer for systemic estrogen-alone products. (1) Unopposed systemic estrogen in a woman with a uterus causes endometrial hyperplasia and carcinoma, and the PEPI trial put hard numbers on how fast. Over three years on unopposed conjugated estrogen, 22.7 percent of women developed complex hyperplasia and 11.8 percent developed atypical hyperplasia. Every arm that included a progestogen held hyperplasia under 1 percent. (14) That risk is dose and duration dependent, it is real, and it is almost entirely preventable. Nothing in this label change touched it.

The word doing all the work in that paragraph is systemic, and it is worth slowing down on, because this is the single most muddled point in the entire subject.

Low-dose vaginal estrogen does not need a progestogen. Not for the cream, not for the ring, not for the tablet. A systematic review of 20 randomized trials covering nearly 3,000 women found endometrial cancer in 0.03 percent and hyperplasia in 0.4 percent, which is background noise, and the WHI Observational Study found no association either. (15) The Menopause Society does not recommend adding a progestogen to low-dose vaginal estrogen therapy. Neither do I. If you have a patient on Estring or a small twice-weekly dab of vaginal estradiol cream for dryness and recurrent UTIs, she does not need progesterone, and putting her on it adds side effects for no endometrial benefit.

Here is the part that trips people up. The dividing line is not oral versus topical. It is systemic versus local. A patch, a pump gel, a spray, and a compounded body cream are all systemic estrogen, and they all raise endometrial risk the same way a pill does. Transdermal delivery changes the clot risk, which I will get to in a minute. It does nothing for the endometrium. If she has a uterus and the estrogen is reaching her bloodstream at systemic levels, she needs a progestogen at an adequate dose for as long as she is on it, no matter what the delivery device looks like.

I bring it up because the compounded and direct-to-consumer market blurs exactly that line, and “cream” gets used to mean two completely different products. I have picked up patients well into a compounded systemic estradiol cream, rubbed on the inner arm at a real systemic dose, with no progestogen prescribed and nobody having mentioned that they needed one.

Removing a warning does not remove a risk

Venous thromboembolism with oral estrogen is the cleanest example. The large UK nested case-control analysis of more than 80,000 VTE cases found oral hormone therapy carried an adjusted odds ratio of 1.58 overall, with oral conjugated equine estrogen plus medroxyprogesterone acetate at 2.10. Transdermal preparations showed no increased risk. Head to head, oral was associated with roughly 70 percent higher VTE risk than transdermal. (10)

That finding should change your prescription pad, not your enthusiasm. The route matters here, and this is the one place it does. First-pass hepatic metabolism drives the procoagulant shift, and transdermal estradiol bypasses it. For a woman with obesity, a prior clot, a thrombophilia, migraine with aura, or a family history that makes you uneasy, transdermal isn’t a preference. It’s the answer.

Breast cancer risk was overstated, not erased

The 2019 Lancet collaborative reanalysis of the worldwide epidemiological evidence put it in numbers a patient can actually hold onto. For a woman of average weight starting at age 50 and using therapy for five years, the excess breast cancer incidence through age 69 is roughly one additional case per 50 users of estrogen plus daily progestogen, and about one per 200 users of estrogen alone. (11) Small. Not zero. And dose and duration dependent, which means the conversation at year eight is a different conversation than the one at year two.

For context I give patients, because context is what they are usually missing: that magnitude sits in the same neighborhood as two alcoholic drinks a day, or carrying significant excess weight after menopause. Nobody puts a black box on either of those.

This is still not a primary prevention drug

The approved indications didn’t change. Systemic hormone therapy is indicated for moderate to severe vasomotor symptoms, for moderate to severe genitourinary symptoms of menopause, for prevention of postmenopausal osteoporosis in appropriate candidates, and for hypoestrogenism from hypogonadism or primary ovarian insufficiency. That’s the list.

The USPSTF continues to recommend against menopausal hormone therapy for the primary prevention of chronic conditions, a grade D recommendation. (12) You do not start a 58-year-old on estradiol to prevent her heart attack. If the timing hypothesis eventually earns a prevention indication, it will do so through a trial designed to answer that question, and that trial has not been run.

A boxed warning coming off is not new evidence coming in

There were no new randomized trials behind the November 2025 action. The FDA reviewed what already existed and concluded the label misrepresented it. That is a real and overdue fix. It is not a discovery, and anyone selling it to you as one is probably selling you something else too.

If You’re A Patient: You Can Reopen This

If you were told no in 2009, or 2015, or honestly even in 2023, the answer you got was shaped by a warning that has since been withdrawn. You are allowed to ask again.

A few things worth knowing before that appointment.

The window matters. The risk-benefit math is most favorable for women who are generally healthy, under 60, and within about ten years of their final menstrual period. The further out from that window you are, the more carefully the decision has to be individualized, and for some women the answer will still be no.

Vaginal estrogen is a separate conversation entirely. Low-dose vaginal estrogen for genitourinary symptoms, meaning dryness, painful sex, recurrent urinary tract infections, urgency, has minimal systemic absorption. The Menopause Society specifically welcomed the boxed warning removal for these products, describing them as safe and effective for a condition that affects most menopausal women. (13) If vaginal symptoms are your issue, the systemic risk conversation largely doesn’t apply to you, and you almost certainly do not need to take progesterone alongside it.

There are still real contraindications. A history of breast cancer, an estrogen-dependent tumor, prior stroke or heart attack, active or prior venous thromboembolism, a known thrombophilia, significant liver disease, or unexplained vaginal bleeding that hasn’t been worked up. If any of those apply to you, the answer may genuinely be no, and there are non-hormonal options worth discussing, including the newer neurokinin receptor antagonists for hot flashes.

And bring specifics, even to a twenty minute video visit. How many nights a week you wake up. Whether you have stopped exercising. Whether sex hurts. Whether you are thinking about leaving a job you used to like. A recent blood pressure reading, when your last mammogram was, and what your mother’s and sister’s history looks like. Symptom burden is half the equation, and “I’m having some hot flashes” badly undersells what is usually going on.

If You’re A Colleague: How I’m Counseling Now

I practice entirely by telemedicine, so everything below happens over video, usually in one visit and a follow-up. Here is how I run it in 2026.

I start by asking what she was told before, and by whom. Roughly half of my perimenopausal and postmenopausal patients are carrying a specific prior refusal, and if I don’t surface it, it sits there and quietly undermines everything I say next.

Then I frame the decision around three questions instead of one. Is she in the window? What is her baseline cardiovascular and thrombotic risk? And what is her symptom burden, honestly measured? A woman at 52 with severe vasomotor symptoms and no risk factors is a different patient than a woman at 64 with controlled hypertension and mild night sweats. The label change does not collapse that difference.

The remote setting changes the logistics of that second question, not the standard. Before I start systemic therapy I want a blood pressure I trust, which usually means a home cuff and a few readings rather than one number she remembers from a year ago. I want her mammogram status current, her personal and family history of clot and breast cancer taken carefully rather than checkbox-style, and any abnormal bleeding evaluated in person before we go anywhere near estrogen. None of that requires me to be in the room. All of it requires me to actually ask.

Route selection is where I have gotten more opinionated. Transdermal estradiol is my default for anyone with obesity, hypertriglyceridemia, migraine with aura, gallbladder disease, or any thrombotic history, personal or family. (10) The oral versus transdermal difference in VTE risk is one of the few places in this entire discussion where we can meaningfully reduce absolute harm by changing one line on the prescription.

Progestogen goes with every uterus on systemic estrogen, and only with systemic estrogen. Micronized progesterone is my preference for the metabolic profile and possibly the breast profile, though I will say plainly that the comparative data across progestogens is observational and not as strong as some of the marketing suggests. If she is on vaginal estrogen alone, she does not get a progestogen from me.

I still ask about duration out loud, every year. Not because there is a hard stop at five years, because there isn’t one, and the old “lowest dose for the shortest duration” language has aged badly. But breast cancer risk is duration dependent (11), and the woman who has been on therapy for nine years should be making that choice consciously rather than by inertia.

And I document the shared decision making. Symptom burden, risk factors reviewed, route and rationale, progestogen plan, alternatives discussed. That note protected me before the label change and it protects me now.

One more thing, and it matters more in this setting than any other. The current news cycle is producing a wave of patients who want hormones for reasons that are not on the label. Longevity. Body composition. Cognitive performance. Telemedicine is where most of that demand is landing, and a lot of it is landing on platforms that will ship estradiol after a four-question intake form and never once ask about the uterus. I would much rather have the honest conversation about what the evidence does and does not support than have someone go around me to get a worse version of the same drug.

The Bottom Line

A warning that should never have been applied to a healthy 52-year-old with hot flashes has been removed. That is a genuine correction, and the women who were denied treatment for twenty years deserved it a long time ago.

What did not happen is a change in the underlying biology. Oral estrogen still raises clot risk. Unopposed systemic estrogen still endangers the endometrium, whatever it is delivered in. Breast cancer risk is still small, still real, still duration dependent. Hormone therapy still isn’t a preventive medication.

The label was wrong. The nuance was always right. We just get to have the conversation now without a black box sitting in the middle of the table.

Related Reading

Perimenopause and Menopause Symptoms and How to Manage Them Menopause Treatment by Telemedicine: How It Works Osteoporosis: How to Prevent It and How It’s Treated Mammograms: When to Get One and What to Expect Why Does High Cholesterol Matter? A Doctor Explains Vaginal Dryness After Menopause: Why It Doesn’t Go Away Does Menopause Cause Weight Gain, or Is It Just Aging?

Scott Rennie, D.O.
Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

Sources:

  1. U.S. Food and Drug Administration. HHS Advances Women’s Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy. November 10, 2025. https://www.fda.gov/news-events/press-announcements/hhs-advances-womens-health-removes-misleading-fda-warnings-hormone-replacement-therapy
  2. U.S. Food and Drug Administration. FDA Approves Labeling Changes to Menopausal Hormone Therapy Products. February 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-labeling-changes-menopausal-hormone-therapy-products
  3. Rossouw JE, et al. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled Trial. JAMA. 2002;288(3):321-333. https://pubmed.ncbi.nlm.nih.gov/12117397/
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  6. Hodis HN, et al. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med. 2016;374(13):1221-1231. https://www.nejm.org/doi/full/10.1056/NEJMoa1505241
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  10. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810. https://pubmed.ncbi.nlm.nih.gov/30626577/
  11. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019;394(10204):1159-1168. https://pubmed.ncbi.nlm.nih.gov/31474332/
  12. US Preventive Services Task Force. Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: USPSTF Recommendation Statement. JAMA. 2022;328(17):1740-1746. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/menopausal-hormone-therapy-preventive-medication
  13. The Menopause Society. The Menopause Society Comments on the FDA Announcement on Hormone Therapy. November 2025. https://menopause.org/press-releases/the-menopause-society-comments-on-the-fda-announcement-on-hormone-therapy
  14. The Writing Group for the PEPI Trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1996;275(5):370-375. https://pubmed.ncbi.nlm.nih.gov/8569016/
  15. Constantine GD, et al. Endometrial safety of low-dose vaginal estrogens in menopausal women: a systematic evidence review. Menopause. 2019;26(7):800-807. https://journals.lww.com/menopausejournal/fulltext/2019/07000/endometrial_safety_of_low_dose_vaginal_estrogens.18.aspx