Oct 27, 2026 · @catalystih1
For more than two decades, many people were told hormone therapy was too risky to consider. That message is changing. In November 2025 the FDA announced it would remove most of the "black box" warning from menopausal hormone therapy, and updated labels began arriving in early 2026.¹,² This post covers the symptoms that may make hormone therapy worth discussing, what the Women's Health Initiative actually showed, and what the best current evidence says. Our companion post covers the specific options and what professional guidelines recommend.
Symptoms in women that may point to hormone therapy
The average age of menopause in the US is 51, but symptoms often begin years earlier, in perimenopause.¹ Hormone therapy is worth discussing when symptoms like these are affecting your sleep, work, relationships or quality of life:
Hot flashes and night sweats. These affect 50% to 92% of women going through menopause.³
Sleep disruption. Between 16% and 66% of US women report menopause-related sleep problems.³
Mood changes. About 36% of perimenopausal and postmenopausal women report depressive symptoms.³
Vaginal and urinary changes. Dryness, painful intercourse, urinary urgency and recurrent urinary tract infections are part of the genitourinary syndrome of menopause.⁴
Bone loss. Falling estrogen speeds bone loss, and hormone therapy has been shown to prevent bone loss and fracture.⁴
Timing matters. Both ACOG and The Menopause Society favor starting hormone therapy before age 60 or within 10 years of menopause, when benefits most clearly outweigh risks.³,⁴
A note on testosterone for women. Women make testosterone too, and low sexual desire that causes distress is a common midlife concern. A 2019 systematic review of 36 randomized trials found testosterone modestly improved desire, arousal, orgasm and the number of satisfying sexual experiences in postmenopausal women.⁵ Creams and gels are preferred over pills, which worsened cholesterol, and acne and extra hair growth were the main side effects.⁵ Testosterone is not a treatment for hot flashes.³ Most available products are dosed for men, so women need much lower, carefully monitored doses.⁵
Symptoms in men that may point to low testosterone
The American Urological Association lists these symptoms and signs of testosterone deficiency:⁵
Sexual: reduced sex drive and reduced erectile function
Physical: low energy, fatigue, reduced endurance, loss of lean muscle mass, weight gain, and loss of body or beard hair
Mood and thinking: depressive symptoms, irritability, low motivation, and poor concentration or memory
Symptoms alone aren't enough. Diagnosis requires two early-morning blood tests showing low total testosterone, with below 300 ng/dL as a reasonable cutoff, plus symptoms or signs.⁵
Set realistic expectations. Treatment may improve erectile function, sex drive, anemia, bone density, lean body mass and depressive symptoms. The evidence is inconclusive on energy, fatigue, memory and overall quality of life.⁵
The Women's Health Initiative: what it did and didn't show
The WHI was a landmark study, but it answered a different question than most women ask today. It tested whether hormones could prevent chronic disease in postmenopausal women aged 50–79, with an average age of 63.¹ Most women start therapy for symptoms around age 51.
What happened in 2002. The estrogen-plus-progestin arm stopped early in 2002 because of increased breast cancer, and the estrogen-alone arm stopped in 2004 over stroke risk and no heart benefit.¹ Headlines followed, prescriptions plummeted, and the FDA added a boxed warning in 2003.⁶
Relative versus absolute risk. Relative risk tells you how much a risk changes compared with a starting point. Absolute risk tells you how many people are actually affected. If a risk rises from 1 in 1,000 to 2 in 1,000, that is a 100% relative increase, or "double the risk," but only 1 extra case per 1,000 people. When the starting risk is low, a large-sounding relative change can mean a very small absolute change.
How the WHI results were reported. The WHI found a 26% relative increase in breast cancer with estrogen plus progestin.⁷ In absolute terms, that meant about 8 extra breast cancers per 10,000 women per year of use.⁷ The same arm saw about 7 more heart events, 8 more strokes and 8 more blood clots in the lungs per 10,000 women per year, along with 6 fewer colorectal cancers and 5 fewer hip fractures.⁷ Media coverage focused on the relative figure. Expressed another way, the breast cancer finding amounted to about 4 additional cases per 1,000 women over 5 years.⁸ These risks are real, but for an individual woman each one is small.
Fear and confusion followed. Within a year, prescriptions for the combined pill used in the WHI fell by 66%.⁹ Six to eight months after the results, 56% of regular users in one large California health plan had tried to stop hormone therapy, yet only 20% could correctly answer five basic questions about its risks.¹⁰ Overall hormone therapy use fell by 40% to 80% in the years that followed, and many women went without relief from significant symptoms.⁸
Why the findings don't transfer neatly to today's patients:
Age and timing. Nearly two-thirds of participants were 60 or older, and many were a decade or more past menopause.³
One formulation. The study used only oral conjugated equine estrogen, with or without medroxyprogesterone acetate. It did not test transdermal estradiol or micronized progesterone.¹¹
Estrogen alone behaved differently. In women without a uterus, estrogen alone did not raise breast cancer risk.¹¹
The long view. After 18 years of follow-up of 27,347 WHI participants, death from any cause was 27.1% with hormones versus 27.6% with placebo. Cardiovascular and cancer deaths were also similar, with a trend toward lower mortality in women who started in their 50s.¹²
The timing hypothesis. A 2015 Cochrane review of cardiovascular outcomes found no heart protection overall. However, women who started within 10 years of menopause had lower mortality and less coronary heart disease. For every 1,000 women under 60 who started, the authors estimated six fewer deaths, eight fewer cases of heart disease and five extra blood clots over about seven years. This was a subgroup finding, so it supports the timing hypothesis without proving it.¹³
What's changed recently
The FDA removed most of the boxed warning. On November 10, 2025, the FDA announced it would remove boxed-warning language on cardiovascular disease, breast cancer and probable dementia.¹,⁶ Its requested changes also drop the "lowest dose for the shortest time" recommendation and add guidance to consider starting therapy for moderate to severe hot flashes before age 60 or within 10 years of menopause.¹ On February 12, 2026, the FDA approved the first six updated labels, including vaginal estrogen, with 29 manufacturers submitting revisions.²
One warning stays. The boxed warning for endometrial cancer with systemic estrogen-alone products remains.¹ If you have a uterus, you still need a progestogen with systemic estrogen.
Cochrane updated its long-term review. The 2025 update pooled 24 randomized trials, but most data still came from the WHI, and the mean age in most studies was over 60.¹¹ For combined estrogen plus progestin, it found a 27% relative increase in breast cancer (RR 1.27) and fewer fractures.¹¹ That estimate comes from the same WHI combined-therapy arm, so in absolute terms it reflects the roughly 8 extra cases per 10,000 women per year described above.⁷,¹¹
Again, the results it highlighted came from oral pills: conjugated equine estrogen, with or without medroxyprogesterone acetate. They did not involve transdermal estradiol or vaginal estrogen. The authors cautioned that these oral regimens may not reflect the hormone therapy used in practice today.¹¹
Underuse is now the concern. The FDA noted that in 2020 roughly 41 million US women were aged 45–64, yet only about 2 million received a prescription for hormone therapy.²
What the evidence shows for testosterone in men
Heart safety is more reassuring than once feared. The TRAVERSE trial randomized 5,246 men aged 45–80 with low testosterone and existing or high cardiovascular risk. Major cardiac events occurred in 7.0% on testosterone gel versus 7.3% on placebo.¹⁴ A 2022 individual-participant meta-analysis of 35 randomized trials likewise found similar cardiovascular event rates with testosterone and placebo.¹⁵
The caveats are real. TRAVERSE saw more atrial fibrillation, blood clots in the lungs and, unexpectedly, more fractures in the testosterone group.¹⁴,¹⁶ These results apply only to men with documented deficiency, not to men with normal levels seeking a boost. Long-term data beyond a few years remain limited.¹⁵,¹⁶
The bottom line
Hormone therapy is not right for everyone, but for many people it is safer and more helpful than the past 20 years suggested. Your symptoms, age, time since menopause, personal and family history, and goals all shape the decision. For men, testosterone is appropriate when deficiency is confirmed and monitored, not as a general energy boost.
If any of these symptoms sound familiar, schedule a consultation to talk through your options. We'll review your history and labs and build a plan that fits you.
This post is for education only and is not a substitute for individualized medical advice.
References
FDA. Requested labeling changes for menopausal hormone therapies, November 10, 2025 (via Drugs.com).
FDA. FDA approves labeling changes to menopausal hormone therapy products, February 12, 2026 (via ASCO Post).
American College of Obstetricians and Gynecologists. Management of menopause-related vasomotor, sleep, and mood symptoms. Clinical Practice Guideline No. 13. Obstet Gynecol. 2026;148:e345–e369. (ACOG news release; summary)
The North American Menopause Society. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767–794.
Islam RM, et al. 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. (plain-language summary)
Mulhall JP, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423–432 (reviewed and validity confirmed 2024). (Table 5: Symptoms and signs)
Elimination of the black box warning on menopausal hormone therapy. Obstet Gynecol. 2026;147(5):642–646.
Writing Group for the Women's Health Initiative Investigators. 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.
Misreporting and poorly presented results shrouded benefits of HRT. Contemporary OB/GYN.
Hersh AL, Stefanick ML, Stafford RS. National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA. 2004;291(1):47–53. (AHRQ summary)
Ettinger B, Grady D, Tosteson AN, Pressman A, Macer JL. Effect of the Women's Health Initiative on women's decisions to discontinue postmenopausal hormone therapy. Obstet Gynecol. 2003;102(6):1225–1232. (summary)
Bofill Rodriguez M, et al. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2025;11:CD004143.
Manson JE, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the WHI randomized trials. JAMA. 2017;318(10):927–938.
Boardman HM, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev. 2015;3:CD002229.
Lincoff AM, et al. Cardiovascular safety of testosterone-replacement therapy (TRAVERSE). N Engl J Med. 2023;389:107–117.
Hudson J, et al. Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis. Lancet Healthy Longev. 2022;3(6):e381–e393.
Big trial reassures on heart safety of testosterone in men. MDedge. 2023 (report of TRAVERSE results, including fracture findings, presented at ENDO 2023).