Hormone replacement therapy was the answer for women, until it wasn't

Women spend about a third of their lives after the menopause transition, and about 6,000 women reach menopause every day in the United States. While menopause is a natural process for most women — marking the end of their childbearing years around age 52 — for some, it occurs years earlier due to surgical removal of the ovaries or the effects of cancer therapies on the ovaries.

Symptoms of menopause include a general decrease in ovarian hormone production, sleep disturbances, mood changes, sexual dysfunction, and a general decrease in quality of life. Vasomotor symptoms, or hot flashes and night sweats, are the most common symptoms of menopause and are experienced by approximately 75% of postmenopausal women.

For years, menopausal hormone replacement therapy has been widely prescribed to women, not only for the treatment of vasomotor symptoms, but also for disease prevention, based on the results of observational studies that showed a reduction in the risk of cardiovascular disease, osteoporosis, and even mortality. In 2002, the first publication of the Women’s Health Initiative Hormone Therapy Trial was published in the Journal of the American Medical Association. The study, a randomized controlled trial and therefore more conclusive than previous studies, caused a dramatic change in public and professional perception of the safety of menopausal hormone therapy.

The study demonstrated an increased risk of adverse cardiovascular events, blood clots, stroke, and breast cancer in women aged 50 to 79 who were taking a single fixed-dose oral pill of estrogen and progestin, which was also the most widely used treatment in the United States at the time. The study was stopped early because of the excessive risks associated with taking menopausal hormone therapy.

As a result, thousands of women stopped taking their hormones, and most health care professionals also became reluctant to treat their patients with hormone therapy. Prescriptions declined worldwide. A few years later, a subanalysis of the original study was published, analyzing risks by age subgroups and finding that some risks, such as cardiovascular disease, were not increased in the subgroup of younger women, aged 50 to 59. However, the damage had already been done: the message that hormone therapy was too risky for postmenopausal women had faded into the background.

Two groups of women are most affected by the consequences of the initial Women’s Health Initiative release: symptomatic “younger” women, typically in their 50s, and older women over 60 who are asymptomatic and have never used hormone therapy. While both age groups have experienced negative effects, the younger group has been most affected because their menopausal symptoms have gone untreated or, in some cases, received less safe treatment options, including untested formulations of “custom” compounded hormones.

More than 20 years later, public and professional perceptions about menopause and hormone therapy have finally changed, as our understanding of the risks and benefits of hormone therapy has improved. Subsequent post-intervention analyses by the Women’s Health Initiative and studies exploring treatments, such as transdermal estrogen delivery routes or skin patches, and the benefits of using progesterone have contributed to a safer and more individualized approach to prescribing hormones to postmenopausal women.

Further research demonstrating the lack of education of medical students and resident physicians about menopause has been highlighted, leading to the expansion of menopause curricula in medical education.

So, in a risk-averse culture, how did the message that hormones are not as risky as previously thought get through to the public?

In February 2023, journalist Susan Dominus published an article in the New York Times titled, “Women Have Been Misled About Menopause,” and the article quickly went viral. The comments section alone had hundreds of entries adding personal details from readers about their experiences with menopause.

And with that, along with social media, the rise of telehealth platforms, and celebrities themselves going through menopause and using their status to amplify a message: menopause is finally getting the attention it deserves.

Macaulay, MD, is an obstetrician/gynecologist and director of the Menopause Health Program at UC San Diego Health. She lives in San Diego.