If hot flashes and night sweats around menopause affect your life, ask a gynecologist to assess hormone therapy — don’t just endure it, don’t buy the drugs yourself, and don’t use them to prevent heart disease

Around menopause, hormone therapy cuts hot flashes by about 75% compared with placebo. The price is slightly more breast cancer, blood clots and stroke: roughly 8 extra cases of each per 10,000 women per year. For women who start at 50 to 59, overall mortality does not go up. It cannot be used to prevent heart disease or dementia.

Cost

One visit to a gynecology or menopause clinic. The doctor takes your history, checks whether you have any condition that rules hormones out, and prescribes only if appropriate. Once you start, you return for follow-up as instructed. The hard part is letting go of the fear that “hormones mean cancer,” and also not buying them yourself because someone says they slow aging.

Benefit

A Cochrane review pooled 24 randomized trials with 3,329 participants, comparing oral hormones with placebo. Women on hormones had about 75% fewer hot flashes per week than on placebo (95% CI 64.3–82.3). Severity also fell clearly (OR 0.13, 0.07–0.23). Women on placebo also had about 57.7% fewer hot flashes, which is why anything claimed to treat hot flashes has to be compared against placebo to count. The risks come from the U.S. WHI randomized trial. It included 16,608 women aged 50 to 79 with a uterus, who took estrogen plus progestin and were followed for an average of 5.2 years. Coronary heart disease was about 29% higher (HR 1.29, 1.02–1.63). Invasive breast cancer was about 26% higher (HR 1.26, 1.00–1.59). Stroke was about 41% higher (HR 1.41, 1.07–1.85). Pulmonary embolism was about 2.13 times as high (HR 2.13, 1.39–3.25). In absolute terms, per 10,000 women per year there were 7 more cases of coronary heart disease, 8 more strokes, 8 more pulmonary emboli and 8 more invasive breast cancers, along with 6 fewer colorectal cancers and 5 fewer hip fractures. Among women who had had a hysterectomy and took estrogen alone, followed for a cumulative 13 years, breast cancer was actually about 21% lower (HR 0.79, 0.65–0.97). Pooling the two trials with 18 years of follow-up, overall mortality did not change (HR 0.99, 0.94–1.03). By age at starting, the 50-to-59 group had about 31% lower overall mortality during the years on treatment (HR 0.69, 0.51–0.94). The 60-to-69 group was 1.04 (0.87–1.25) and the 70-to-79 group 1.13 (0.94–1.36), neither significant. At 18 years of follow-up the 50-to-59 group was 0.89 (0.79–1.01), no longer significant. The 2017 Cochrane review, looking only at women aged 50 to 59, found the only clear increase was blood clots with combined estrogen-progestin therapy, with an absolute risk below 1/500. Among women over 65 on combined therapy, dementia rose from 9 per 1,000 to 11–30 per 1,000 over 4 years. In 2022 the U.S. Preventive Services Task Force recommended against hormone therapy for preventing chronic conditions (grade D) and concluded there is no net benefit.

Notes

Contested: the WHI women were 63 years old on average and took one fixed oral regimen. Most women today start around 50, just after menopause, for symptoms, so they are not quite like the trial participants. The lower mortality in the 50-to-59 group came from an age-group split and was no longer significant at 18 years, so it cannot be said that hormones extend life. Cochrane also states that the trials were too small to show the risks for women within 10 years of menopause. These groups are generally not suitable: women who have had breast cancer, who have had blood clots, who have a high cardiovascular risk, or who are very overweight; the doctor decides case by case. Women with a uterus who take estrogen alone have more endometrial cancer, so a progestogen is added at the same time; only women who have had a hysterectomy may take estrogen alone. Hormones also reduce fractures, but are normally considered only when other osteoporosis drugs are unsuitable. For osteoporosis, see Section 1, item 39 (bone density test) and Section 1, item 40 (treat if osteoporosis is found). The benefit size is set to large from the roughly 75% fewer hot flashes; the endpoint is symptoms, not overall mortality. The main beneficiary of this item is you, and also your mother and spouse.

Sources · 6

1. MacLennan AH, Broadbent JL, Lester S, Moore V (2004). Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database of Systematic Reviews, (4), CD002978. doi.org/10.1002/14651858.CD002978.pub2
2. Writing Group for the Women's Health Initiative Investigators, Rossouw JE, Anderson GL, Prentice RL, 等 (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA, 288(3), 321-333. doi.org/10.1001/jama.288.3.321
3. Manson JE, Chlebowski RT, Stefanick ML, 等 (2013). Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA, 310(13), 1353-1368. doi.org/10.1001/jama.2013.278040
4. Manson JE, Aragaki AK, Rossouw JE, 等 (2017). Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women's Health Initiative randomized trials. JAMA, 318(10), 927-938. doi.org/10.1001/jama.2017.11217
5. Marjoribanks J, Farquhar C, Roberts H, 等 (2017). Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews, (1), CD004143. doi.org/10.1002/14651858.CD004143.pub5
6. US Preventive Services Task Force, Mangione CM, Barry MJ, 等 (2022). Hormone therapy for the primary prevention of chronic conditions in postmenopausal persons: US Preventive Services Task Force recommendation statement. JAMA, 328(17), 1740-1746. doi.org/10.1001/jama.2022.18625