Estrogen Therapy for Hot Flushes Challenged: Progestin as Effective as Risk-laden Estrogen

Women seeking treatment for hot flushes can avoid health risks associated with estrogen by taking medroxyprogesterone, now demonstrated to be equally as effective as estrogen, according to research led by a University of British Columbia endocrinologist, who is also a member of the Vancouver Coastal Health Research Institute (VCHRI).

In the first direct comparison of the two drugs ever undertaken, Dr. Jerilynn Prior and an international research team has shown that medroxyprogesterone, a progestin or synthetic version of the hormone progesterone, initially marketed as Provera®, is equally effective in controlling hot flushes and night sweats as the standard estrogen treatment.

The study has recently been published in Clinical Science. Placebo-controlled studies of medroxyprogesterone from the 1980s showed its effectiveness for treatment of hot flushes, but this knowledge virtually disappeared from clinical wisdom, says Prior. In addition, until now it had not been directly compared to estrogen.

“Women now have a true choice,” says Prior, who is a UBC professor of Endocrinology and Metabolism and founder of the Centre for Menstrual Cycle and Ovulation Research, at Vancouver General Hospital. “Since 2002 when the serious risks of taking estrogen were proven, women with severe flushes had to choose between two evils — potential adverse effects of estrogen or continued and poorly controlled symptoms. Now they can get relief without risking their health.”

Medroxyprogesterone does not cause blood clots, breast cancer or increase migraine headaches, making it safer than estrogen, adds Prior.

In 2002, the Women’s Health Initiative — a clinical trial of 16,600 U.S. women — showed that estrogen with low dose progestin increased risk of blood clots, breast cancer, stroke and heart attack. Another trial of estrogen alone, published in 2004, showed blood clots and strokes were significantly increased. However, estrogen remains the standard for treating women because no other drug has been believed strong enough to control severe VMS.

VMS are caused by changes in estrogen levels in the brain. Symptoms are common in perimenopause and menopause but only about 20 per cent of women experience severe symptoms.

In the one-year, double blind, randomized study, Prior and the research team treated 41 women with a daily dose of either .6 mg. of estrogen or 10 mg. of medroxyprogesterone. Both therapies reduced flushes and sweats — together known as vasomotor symptoms (VMS) — to one flush or sweat every third or fourth day. In addition, no participant experienced blood clots, heart attack, stroke or breast cancer during the study.

Women in the study were menstruating before surgical menopause — menopause induced by removal of ovaries and uterus — a group which typically has the worst VMS. Ages ranged from late 30s to early 50s.

Prior says there is little evidence of harmful effects of medroxyprogesterone whereas the benefits are easily shown. Apart from relieving women of the significant health risks associated with estrogen, the study showed medroxyprogesterone results in less weight gain than estrogen, and less increase in triglyceride levels, a contributor to women’s cardiovascular conditions.

In a follow-up trial, Prior and colleagues are conducting a hot flush study in post-menopausal women to examine whether natural progesterone, like medroxyprogesterone, controls moderate to severe VMS. As part of the study, researchers will examine progesterone’s effects on cholesterol, blood clotting and forearm blood flow. The study is needed because, although current evidence suggests abnormal clotting is not associated with progesterone, conclusive evidence has not been available. Women with moderate to severe flushes who wish to participate can learn more at

VCHRI is the research body of Vancouver Coastal Health and the fourth largest research institute in Canada. In academic partnership with UBC, VCHRI brings innovation and discovery to patient care, advancing healthier lives in healthy communities across British Columbia, Canada, and beyond.

Attn: Editors – a woman who has been treated with medroxyprogesterone is available for print media interviews, on the condition of anonymity.

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