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SPHHP dean contributes to JAMA paper on Women’s Health Initiative

Menopause concept featuring a small female figure, a calendar, a clock and the female symbol.


Published June 5, 2024

Jean Wactawski-Wende.
“We continue to learn so much from these women. They’re a remarkable cohort. ”
Jean Wactawski-Wende, dean
School of Public Health and Health Professions

The headlines around coverage of a paper published last month in the Journal of the American Medical Association (JAMA) about the Women’s Health Initiative (WHI) hormone trials didn’t quite capture the intent of the study, according to a UB investigator and longtime WHI researcher.

The JAMA paper was intended to assist clinicians in interpreting the trial findings according to type of medication and personal factors that might help with understanding absolute risk of several, concerning, negative outcomes, including heart disease, stroke, blood clots and breast cancer, including age at administration. The goal of the JAMA publication was to provide further detail, clarity and longer-term assessment of risks and benefits, says Jean Wactawski-Wende, dean of the School of Public Health and Health Professions and a co-author on the JAMA paper.

The trials started in 1993 to determine risks and benefits of longer-term use of hormone therapy (HT) after menopause. One misnomer, Wactawski-Wende says, was that WHI was assessing menopausal symptoms, but it wasn’t. That was already understood. WHI was designed to determine the balance of risks and benefits on chronic disease in postmenopausal women.

The estrogen-plus-progestin trial was stopped early in 2002 amid fears over the safety of combination hormone therapy for women randomized to active drug compared to placebo. Overall the results indicated increases in risk of breast cancer, heart disease, stroke and blood clots. The estrogen-only trial compared to placebo showed an increase in stroke and elevated blood clots, with lower breast cancer risk.

The most recent JAMA paper, a long-term follow-up of the WHI, reports that for menopausal women under age 60, the benefits of hormone therapy for those on estrogen alone likely outweigh the risks.

For women taking estrogen plus progestin, the risk outweighed the benefits, but in women under age 60, the absolute risk was quite small. This detail by type of formulation and age at which it was started indicates that some women who are experiencing moderate to severe symptoms may consider use, as long as the drugs are taken using the smallest effective dose for the least amount of time to manage menopausal symptoms. These decisions should only be made in consultation with a clinician, Wactawski-Wende says.

Wactawski-Wende says there’s an important nuance in the messaging WHI researchers have tried getting out to both clinicians prescribing and women considering taking hormone therapy. She wants to set the record straight on some of the misinterpretations people have of the most recent WHI data, including news reports stating WHI was flawed and that initial fears related to the combination hormone therapy trial were overblown.

“The WHI trials were never flawed. The purpose of the WHI trials was to learn more about chronic disease risk and benefit in menopausal women. The focus of WHI was never about symptoms of menopause,” says Wactawski-Wende, who is also a SUNY Distinguished Professor in the Department of Epidemiology and Environmental Health.

“This paper is not a turnaround on WHI,” Wactawski-Wende adds. “The new information it presents is extending out 20 years from the start of the trial and looking at the initial and long-term risks of hormone therapy. The longer you go out from active treatment, the more the risks reduce.”

The initial WHI study consisted of three randomized clinical trials: the Hormone Therapy (HT) Trial, the Diet Modification (DM) Trial and the Calcium and Vitamin D (CaD) Trial.

The Hormone Trial focused on estrogen alone for women who had a hysterectomy and a combination of estrogen plus progestin, which was added as a protective effect for women who still had a uterus. Researchers halted the estrogen-plus-progestin arm early, in 2002, amid concerns that women who took combination hormone therapy had increased risk of coronary heart disease, stroke, pulmonary embolism and breast cancer.

“What tends to get lost is that at the time the WHI trials were started, there was no trial to say estrogen alone or estrogen plus progestin protected against heart disease, and there were increasing concerns about breast cancer risk,” Wactawski-Wende says. “Many women were being put on estrogen hormone therapy for prevention of heart disease when those studies had been done. Women were often starting HT in their 60s or later assuming it would be beneficial to the heart,” she says.

The U.S. Department of Health and Human Services reports that the WHI results in 2002 found that postmenopausal women taking estrogen plus progestin for menopause symptoms had a higher risk of breast cancer, heart disease, stroke and blood clots. While their risk of fractures and colorectal cancer were lower, these benefits did not outweigh the risks and, as a result, many women stopped taking hormone therapy worldwide. That, in turn, led to a sharp decline in breast cancer that has been shown in published reports from many countries.

The JAMA paper concludes: “For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy.”

Wactawski-Wende says it’s important to recognize that the WHI continues to provide researchers with valuable information on chronic disease in postmenopausal women, and particularly women in the 80- to 100-year-old age group. She notes there are still 50,000 active WHI participants 30 years after the start of the study.

“We continue to learn so much from these women,” she says. “They’re a remarkable cohort.”