Life lessons learned from post-menopausal hormone therapy


The overview underscores the importance of considering a woman’s age and time since menopause.

The timing of postmenopausal hormone therapy (HT) significantly impacts coronary risk and overall benefit-to-risk profile, according to an overview of Women’s Health Initiative (WHI) results in the journal Menopause.

WHI evaluated oral conjugated equine estrogens (CEE) taken with or without medroxyprogesterone acetate (MPA) for prevention of chronic disease in postmenopausal women aged 50 to 79 at enrollment.

The key findings were that women younger than age 60 or no more than 10 years since the onset of menopause achieved better outcomes from HT than older women or those further past the menopausal transition.

A total of 16,608 women with an intact uterus were randomized to either CEE + MPA therapy or placebo for a median of 5.6 years, while 10,739 women with hysterectomy were randomized to either CEE-alone therapy or placebo for a median of 7.2 years. Both cohorts, with a combined initial average age of 63, have been followed for 18 years.

“We find that there are significant age-related trends for coronary heart disease and for all-cause mortality with HT,” said JoAnn Manson, MD, DrPH, NCMP, a professor of medicine at Harvard Medical School, who is the principal investigator of the Boston site of WHI.

“This is particularly true in the estrogen-alone trial. Estrogen therapy had more favorable effects on heart disease and all-cause mortality among younger and more recently menopausal women.”

For example, women who were younger than age 60 had about a 40% lower risk of heart attack or coronary heart disease with estrogen-alone therapy compared to no reduction or a slight increase in risk among women aged 70 and older.

Similarly, for all-cause mortality, women below age 60 had roughly a 30% risk reduction, whereas older women did not have a reduction in mortality risk.

Comparable results were observed for the number of years since menopause. “The women who were within 10 years of the onset of menopause tended to have more favorable results from HT on coronary heart disease and all-cause mortality than women who were more than 10 years past the onset of menopause,” Dr. Manson told Contemporary OB/GYN.

In addition, the combination of CEE and MPA was linked to an approximately 24% to 30% increased risk of breast cancer, with risk elevation emerging after 4 to 5 years of treatment.

“But estrogen alone was not associated with an increased risk of breast cancer; in fact, with long-term follow-up there was close to a 20% reduction,” Dr. Manson said.

Women younger than age 60 with prior bilateral oophorectomy particularly benefited from estrogen-alone therapy, resulting in a 32% reduction in all-cause mortality over long-term follow-up.

The overview underscores the importance of considering a woman’s age and time since menopause for clinical decision-making about the use of hormone therapy.

“Systemic HT has an acceptable, even favorable, safety profile for menopause management when initiated among healthy women who are younger or recently menopausal and not at elevated risk for cardiovascular disease or breast cancer,” Dr. Manson said.

However, she believes more research is needed on the clinical effects and risk:benefit profiles of other formulations of HT therapy, particularly transdermal estradiol and low-dose products.


Dr. Manson reports no relevant financial disclosures.


  1. Manson JE, Bassuk SS, Kaunitz AM, Pinkerton JV. The Women's Health Initiative trials of menopausal hormone therapy: lessons learned [published online ahead of print, 2020 Apr 27]. Menopause. 2020;10.1097/GME.0000000000001553. doi:10.1097/GME.0000000000001553
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