What is menopausal hormone therapy, and who is it for?

Evidence: does menopausal hormone therapy help with hot flashes?

In a systematic review of 24 double-blind, placebo-controlled trials of oral hormone therapy (3,329 women), hormone therapy reduced hot-flash frequency by about three-quarters compared with placebo, and placebo groups also improved.[1]

Which menopausal hormone therapy products carry a boxed warning?

In November 2025, FDA requested labeling changes for menopausal hormone therapy products, including removing boxed-warning language related to 'cardiovascular diseases, breast cancer, and probable dementia' and keeping 'the Boxed Warning about endometrial cancer in the systemic estrogen-alone products'. As of February 12, 2026, FDA listed six products with revised prescribing information; labels for other products may still carry the earlier wording.

The boxed-warning table shows, for each product listed, the latest prescribing information we found on Drugs@FDA and the boxed warning it carries, if any.

Estrace vaginal cream is not in this table because the prescribing information we found for it prints no revision date. The version on DailyMed, read October 14, 2026, carries a boxed warning headed 'WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA'.

Regulatory status checked October 14, 2026. Sources: www.fda.gov/…/fda-requests-labeling-changes-related-safety-information-clarify-benefitrisk-considerations; www.fda.gov/…/fda-approves-labeling-changes-menopausal-hormone-therapy-products; www.fda.gov/…/menopausal-hormone-therapies-updated-prescribing-information; www.fda.gov/…/menopause; www.fda.gov/…/compounding-and-fda-questions-and-answers; www.fda.gov/…/download; www.fda.gov/…/download; www.accessdata.fda.gov/…/022038s017lbl.pdf; www.accessdata.fda.gov/…/021166Orig1s020lbl.pdf; www.accessdata.fda.gov/…/004782s179lbl.pdf

Potential benefits

Evidence levels in this table follow our grading key: Established means consistent results from randomized trials, a systematic review of them, or that a guideline or label says something; Emerging means some controlled human evidence that falls short of that, such as a single small trial or mixed results; and Evidence against means large trials tested the claim on its main result and did not find it.

Vaginal and urinary symptoms

The Menopause Society recommends low-dose vaginal estrogen for bothersome vaginal and urinary symptoms of menopause that don't improve with over-the-counter products, in women who don't need systemic hormone therapy, and says it is effective and generally safe, with only minimal absorption into the bloodstream.[2] We did not read a clinical trial or systematic review specifically testing vaginal estrogen for these symptoms for this page; this section states the guideline's recommendation, which is based on the guideline's own review of the evidence. The Menopause Society says a progestogen is not required alongside low-dose vaginal estrogen, though randomized trial data beyond one year are lacking, and that any postmenopausal vaginal bleeding needs a thorough medical evaluation.[2]

Bone loss and fractures

In the Women's Health Initiative, both estrogen plus progestin and estrogen alone lowered the rate of hip and total fractures during treatment: hip fracture risk fell by about a third with each regimen, and a Cochrane review found fracture reduction was the one outcome with the strongest evidence of benefit from hormone therapy.[3] This protection lasted only while hormone therapy was being taken, and bone loss resumed quickly after stopping. For women who were 50 to 59 when they started, The Menopause Society reports that neither regimen was shown to reduce hip fracture during the Women's Health Initiative treatment period, which it says may partly reflect the low fracture risk at that age.[2]

A 2021 analysis of the same trials over a median of 18 years, using a statistical model that draws on data from older participants, reported "nominally significant reductions" in hip fracture and three other outcomes with estrogen alone in women who started at ages 50 to 59. We read its abstract, which gives no hip-fracture figure.[4]

Sleep

The Menopause Society says hormone therapy improves sleep in women with bothersome nighttime hot flashes, mainly by reducing nighttime awakenings, and that oral micronized progesterone at bedtime also significantly reduces hot flashes and night sweats and improves sleep.[2]

A 2017 systematic review pooled 7 randomized trials with 15,468 women.[5] It found that hormone therapy improved self-reported sleep quality in women who had hot flashes at the start, and it found no difference in women who did not; the authors rated the pooled trials at moderate to high risk of bias.[5] In a separate 2-month trial of 40 postmenopausal women with insomnia and no severe hot flashes, an estradiol patch did not improve sleep efficiency compared with placebo (85.7% vs 85.2%).[6] The Menopause Society says estrogen may have some effect on sleep independent of hot flashes.[2]

Slowing aging or extending lifespan

In PubMed, Europe PMC and ClinicalTrials.gov searches on October 1, 2026, we found no randomized trial that reported significantly fewer deaths from any cause, across all of its participants, among women assigned to menopausal hormone therapy than among women assigned to placebo or no treatment. On aging, we found two small randomized studies in postmenopausal women, both of blood markers linked to cell aging, and their results were mixed.

Across both arms of the Women's Health Initiative, hormone therapy did not change the rate of death from any cause, cardiovascular disease or cancer over 18 years of combined follow-up.[7]

The Menopause Society reports that, with the two Women's Health Initiative trials combined, death rates during treatment were lower with hormone therapy than with placebo in women who started at ages 50 to 59 (hazard ratio 0.69, 95% CI 0.51 to 0.94) and not in women who started in their 60s or 70s. Pooled analyses of other trials disagree on deaths in younger starters: a 2015 Cochrane review found fewer, and a 2020 review found no effect.[2] These are subgroup results.

In the first of the two marker studies, 63 postmenopausal women (average age 58) who had used hormone therapy for at least a year were randomly assigned to stay on it or stop for about two years. Telomere length in white blood cells, a marker of cell aging, could be compared in 42 of them, and stopping did not significantly change the odds of telomere shortening. Results differed by APOE gene type: carriers of the APOE-ε4 variant who stopped lost telomere length and carriers who continued did not, and the pattern was reversed in non-carriers. The study was funded by the U.S. National Institutes of Health, and three of its authors co-founded a telomere-testing company.[8]

In the second, researchers measured four blood proteins linked with cell senescence in 109 women from the KEEPS trial who had been randomly assigned to an estrogen pill, an estradiol patch or placebo, each active treatment with progesterone. At 36 months, three of the four proteins were lower with the pill than with placebo. With the patch the differences were smaller: the paper's abstract gives a p value of .036 for one of the three and above .05 for the other two, and its results table, which corrects for multiple comparisons, shows no patch comparison below the .05 level (adjusted p values from .055 to .21). The comparison used one blood sample, taken at 36 months, from a subset of the 727 women in the trial, and the authors wrote that the data generate new hypotheses. The work was funded by the Aurora Foundation, the U.S. National Institutes of Health and the Mayo Foundation.[9]

None of the menopausal hormone therapy labels we reviewed lists anti-aging, longevity or healthy aging as an approved use; those products are approved for specific menopause-related uses (checked October 14, 2026).

Limitations

In the Women's Health Initiative, oral estrogen plus progestin did not lower the rate of coronary heart disease, and a Cochrane review concluded that hormone therapy is not indicated for preventing heart disease, stroke, dementia or cognitive decline.[3] In women who started estrogen plus progestin at age 65 or older, the Women's Health Initiative Memory Study found a doubled rate of probable dementia (45 vs 22 cases per 10,000 women per year).[10] Estrogen alone did not show a statistically significant increase in the same age group.[11] The Menopause Society says that, in the absence of more definitive findings, hormone therapy is not recommended at any age to prevent or treat a decline in cognitive function or dementia.[2]

Larger analyses of these and other trials give mixed results for women who start hormone therapy before 60 or within 10 years of menopause. The Menopause Society reports that a 2015 Cochrane review found fewer coronary events and fewer deaths but more blood clots; that a 2019 analysis found lower odds of coronary events and death, which weakened once open-label trials were excluded, and higher odds of stroke and related events; and that a 2020 review found no effect on death, stroke or blood clots.[2]

Breast cancer risk

In the Women's Health Initiative, estrogen plus progestin raised the rate of invasive breast cancer: about 9 more cases per 10,000 women per year than with placebo. After more than 20 years of follow-up, the rate was 0.45% per year with estrogen plus progestin versus 0.36% with placebo.[12] In the same trial, estrogen alone, taken by women after a hysterectomy, did not raise breast cancer rates and was linked with fewer cases over more than 20 years of follow-up (238 vs 296 cases), though separate observational studies of estrogen-only use found a higher rate with longer use.[12] The Menopause Society frames the breast cancer risk from hormone therapy as low: fewer than one additional case per 1,000 women per year of use, or about three additional cases per 1,000 women when estrogen plus progestin is used for 5 years.[2]

Blood clots and stroke; patches vs. pills

In the WHI, oral estrogen plus progestin raised the risk of blood clots in the veins (DVT: 1.87 times as likely; pulmonary embolism: 1.98 times as likely). Oral estrogen alone raised the risk of DVT by less (1.48 times as likely), and its higher rate of pulmonary embolism (1.35 times) was not statistically significant.[13] In the WHI, both oral estrogen plus progestin and oral estrogen alone raised the risk of stroke: about 9 to 11 more strokes per 10,000 women per year, though in women who started between ages 50 and 59, neither trial found a statistically significant difference in stroke.[13] Observational studies have found a lower risk of blood clots with skin patches and gels than with pills.[14][15] The randomized trials we found that compared estrogen pills with patches (PubMed, Europe PMC and ClinicalTrials.gov searches, October 1, 2026) were too small to compare how often blood clots occurred, and The Menopause Society says comparative randomized trial data are lacking.[2]

Two of the trials we found measured clotting markers in blood (blood tests, not clot events). In one, 152 postmenopausal women who had had a hysterectomy took an estradiol pill with or without a progestin, an estradiol patch or placebo for about a year; resistance to activated protein C, which the authors call a risk factor for vein clots, rose in every treated group and rose more with the pills than with the patch.[16] In the other, 45 postmenopausal women were assigned to an estradiol pill, an estradiol patch (each with progesterone) or no treatment for 6 months; a marker of clotting activation rose with the pills and did not change significantly with the patch.[17] Another trial, KEEPS, assigned 727 recently menopausal women to an estrogen pill, an estradiol patch or placebo for 4 years and reported that it was too small to compare clinical events; it lists the Aurora Foundation as its primary funder.[18]

Why a progestogen is added to estrogen

The Menopause Society says that women with a uterus taking systemic estrogen should receive adequate progestogen, because unopposed estrogen increases the risk of endometrial cancer.[2]

Common side effects

The Menopause Society lists nausea, bloating, weight gain, fluid retention, mood swings linked to the progestogen, breakthrough bleeding, headaches and breast tenderness among the common side effects of hormone therapy.[2]

In a 12-week placebo-controlled trial of 495 women using an estradiol gel, side effects reported in more than 5% of users in any group included nasopharyngitis, upper respiratory infection, vaginal yeast infection, breast tenderness and irregular spotting; the label notes that these rates cannot be directly compared with rates from trials of other hormone-therapy products.

Sources: Divigel gel prescribing information, Revised 2/2026.

Hormone therapy raises the risk of gallbladder disease requiring surgery: a Cochrane review found the risk of gallbladder disease rose from about 27 per 1,000 women to between 38 and 60 per 1,000 with combined hormone therapy over about 5.6 years.[3]

If you have severe symptoms, call 911 or seek emergency care. Report side effects to FDA MedWatch.

Is menopausal hormone therapy FDA-approved, and for which uses?

FDA has approved specific estrogen and progestogen products for certain menopause-related uses, such as moderate to severe vasomotor symptoms (hot flashes) due to menopause; approved uses differ by product and route (checked October 14, 2026).

The FDA status table lists each menopausal hormone therapy product whose label we reviewed, with its route and the uses in its prescribing information.

Each menopausal hormone therapy product in the FDA status table is available only with a prescription (checked October 14, 2026).

Completing an intake form or making a payment does not guarantee a prescription.

Whether a product is appropriate for a specific person is decided by a licensed clinician using that product's prescribing information.

The menopausal hormone therapy products whose labels we reviewed are FDA-approved only for specific uses, such as moderate to severe vasomotor symptoms due to menopause, moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, or prevention of postmenopausal osteoporosis, and not for anti-aging, longevity or healthy aging. Using them for anti-aging, longevity or healthy aging is off-label. FDA has not reviewed whether they are safe and effective for that purpose.

Are compounded "bioidentical" hormones FDA-approved?

Compounded hormone therapy is a different product from the hormone therapy products listed in the FDA status table.

In PubMed, Europe PMC and ClinicalTrials.gov searches on October 1, 2026, we found two randomized studies with results that compared compounded estrogen with a conventional hormone therapy product: a 16-day study of blood hormone levels and a one-year trial that ended early. Neither could show whether compounded hormones relieve menopause symptoms as well as a conventional hormone therapy product or are as safe. A third randomized study, registered on ClinicalTrials.gov in 2026 and run in Brazil, compares estradiol implants, a compounded estradiol gel and a brand-name estradiol gel in 50 women; it was still under way and had reported no results as of October 1, 2026.[19] A 2020 report from the National Academies of Sciences, Engineering, and Medicine concluded there is insufficient evidence to support the overall clinical benefit of compounded bioidentical hormone therapy for menopause symptoms, and recommended restricting its use.[20] The Menopause Society says compounded bioidentical hormone therapy raises safety concerns, including minimal regulation and monitoring, overdosing and underdosing, impurities, lack of sterility, and a lack of scientific efficacy and safety data, and that patient preference alone should not justify using it when government-regulated options exist.[2] ACOG says compounded bioidentical menopausal hormone therapy should not be prescribed routinely when other options exist, and that evidence to support marketing claims of its safety and effectiveness is lacking.[21]

The one-year trial of compounded hormones that ended early was run at the University of Kansas Medical Center. It randomly assigned 21 women within 7 years of menopause to one of three compounded estrogen and progesterone capsules or to a conventional pill of conjugated estrogens with medroxyprogesterone acetate; 40 women had been planned and 9 finished. The results posted on ClinicalTrials.gov cover cholesterol, uterine-lining thickness, mammograms and bone density, with no statistical comparison between groups. No serious side effects were recorded, and abnormal vaginal bleeding was recorded in 3 of the 15 women on compounded capsules and none of the 6 on the conventional pill. The investigators wrote that the small sample and the high dropout rate make the data of marginal value. In PubMed and Europe PMC searches on October 1, 2026, by the trial's registration number and by words from its title and subject, we found no journal article reporting the trial.[22]

Compounded menopausal hormone therapy, including compounded products marketed as 'bioidentical' hormones, is not FDA-approved. FDA states: 'Compounded drugs are not FDA-approved. This means that FDA does not verify the safety, effectiveness or quality of compounded drugs before they are marketed.' As of FDA's list updated March 21, 2025, estradiol, estradiol cypionate, estriol, estrone, progesterone and medroxyprogesterone acetate are on FDA's list of substances under evaluation for use by outsourcing facilities (503B Category 1), and this listing is not an FDA approval of any compounded product.

Do saliva or blood hormone tests help set hormone therapy doses?

One hormone-therapy label states that blood levels of FSH and estradiol are not useful for managing hot flashes, and The Menopause Society says saliva and urine hormone testing to guide dosing are unreliable and not recommended.[2]

Is estriol FDA-approved?

There is no FDA-approved estriol drug product for any use, according to FDA's 'Menopause' page (FDA page content current as of December 14, 2023; checked September 28, 2026).

On its 'Menopause' page, FDA says it does not have evidence that drugs containing estriol are safe and effective, or are 'safer forms of estrogen' (FDA page content current as of December 14, 2023; checked September 28, 2026).

Compounded estriol is not FDA-approved. FDA states: 'Compounded drugs are not FDA-approved. This means that FDA does not verify the safety, effectiveness or quality of compounded drugs before they are marketed.' As of FDA's list updated March 21, 2025, estriol is on FDA's list of substances under evaluation for use by outsourcing facilities (503B Category 1), and this listing is not an FDA approval of any compounded product.

Regulatory status checked October 14, 2026. Sources: www.fda.gov/…/fda-requests-labeling-changes-related-safety-information-clarify-benefitrisk-considerations; www.fda.gov/…/fda-approves-labeling-changes-menopausal-hormone-therapy-products; www.fda.gov/…/menopausal-hormone-therapies-updated-prescribing-information; www.fda.gov/…/menopause; www.fda.gov/…/compounding-and-fda-questions-and-answers; www.fda.gov/…/download; www.fda.gov/…/download; www.accessdata.fda.gov/…/022038s017lbl.pdf; www.accessdata.fda.gov/…/021166Orig1s020lbl.pdf; www.accessdata.fda.gov/…/004782s179lbl.pdf

Regulatory status checked September 28, 2026. Sources: www.fda.gov/…/menopause; www.fda.gov/…/compounding-and-fda-questions-and-answers; www.fda.gov/…/download; www.fda.gov/…/download

Provider directory

Both links below open the Hormone health category of the provider directory.

Compounded menopausal hormone therapy is not FDA-approved. See FDA's statement.

Compounded estriol is not FDA-approved. See FDA's statement.

There is no FDA-approved drug containing estriol, according to FDA's 'Menopause' page (FDA page content current as of December 14, 2023; checked September 28, 2026).

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