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Women’s Health Initiative - Update 2013

Hormone replacement therapy (HRT) has been under considerable scrutiny since 2002 when a large US government study, the Women’s Health Initiative (WHI) reported that HRT, specifically the combination of estrogen and progestin together, increased the risk for blood clots, stroke, breast cancer and heart attacks.

The WHI, which consisted of three clinical trials and an observational study, was conducted to address major health issues causing morbidity and mortality in postmenopausal women. The study was stopped early by the researchers and they concluded that the risks of HRT outweighed the benefits.

Although the WHI study was designed to evaluate the role of HRT in the prevention of diseases related to aging, many women and their doctors also abandoned HRT as therapy for menopausal symptoms.

Additional research over the past 10 years, has found shown that the level of risk with HRT depends on the individual woman, her health history, age, and the number of years since her menopause began. It is women below the age 60 years and recently started menopause, who are at a lower risk when taking low doses of HRT compared with women over 60.

The paper by Manson JE, Chlebowski RT, Stefanick ML, et al.(1) published in the October 3, 2013 issue of the Journal of the American Medical Association, sets out to report a comprehensive, integrated overview of findings from the two WHI hormone therapy trials with extended postintervention follow-up.


1 Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013;310(13):1353-1368

Expert Comment

International Menopause Society (IMS)

The North American Menopause Society (NAMS)

Note: Access to full comments is available to AMS Members once logged in.

International Menopause Society (IMS)

Menopause Live
Menopausal hormone therapy and prevention of chronic diseases: IMS members react to the recent JAMA paper

Comment 1

... It must be emphasized that WHI data cannot inform about chronic disease prevention since benefits and risks of HT when initiated in a 70–80-year-old women cannot be assumed to equate to the benefits and risks of women 20–30 years after initiating HT at 50–60 years of age. The contrary, however, is that which follows known preventive therapy logic in which risk is reduced initially and is followed by reduction in adverse events, such as bone fracture prevention. There is absolutely no evidence to indicate that HT operates differently from this well-known paradigm of chronic disease prevention. The fact that '…the risk reductions dissipated post-intervention', as stated on page 1366 of the newest WHI manuscript, clearly indicates that chronic disease prevention will only be appreciated with continuous HT, as seen with the prevention of bone fractures.

Howard N. Hodis 
Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Keck School of Medicine, 
University of Southern California, USA

Comment 2

... WHI investigators, with their unbalanced conclusions, have already caused much damage to women who have been deprived of appropriate and needed hormone therapy and thus of the resulting preventive effects at the level of the cardiovascular system and bones.

Manuel Neves-e-Castro 
Lisbon, Portugal 

The North American Menopause Society (NAMS)

First to Know
Outcomes during and after stopping HT: a comprehensive look at WHI data

Comment 1

...These longterm observations regarding participants in the WHI HT trials remind us that the risk: benefit ratio of menopausal hormone therapy (HT) is most favorable when initiated in younger rather than in older menopausal women, and for estrogen-only compared with estrogen-progestin therapy.

Andrew M. Kaunitz, MD, NCMP
Professor and Associate Chairman Department of Obstetrics and Gynecology University of Florida College of Medicine-Jacksonville Jacksonville, FL
NAMS Board Member 

Comment 2

... It is equally reassuring and should be stressed that the younger menopausal woman is at low risk with estrogen therapy, and even when the treated patient’s risk is greater than placebo, the risk ratios are very small. Perhaps we should be stressing that 9,900 women per 10,000 had almost 7 years of exceptional health.

Lila E. Nachtigall, MD, NCMP
Professor of Obstetrics and Gynecology NYU School of Medicine New York, NY
Past NAMS President, 2000

Comment 3

... Short-term hormone therapy remains useful for women with bothersome hot flashes, particularly if under age 60 ....

... For women who are not candidates for hormone therapy, nonhormonal treatment options may be helpful. The FDA has just approved 7.5 mg of paroxetine salt for treatment of hot flashes. Other SSRIS such as escitalopram, SSNRs such as desvenlafaxine and venlafaxine, and gabapentin have been found in large, randomized, double-blind trials to relieve hot flash frequency and severity more than placebo.

JoAnn V. Pinkerton, MD, NCMP
Professor of Obstetrics and Gynecology Director Midlife Health University of Virginia Health Center Charlottesville, VA
Past NAMS President, 2008

Comment 4 

... At the end of the day, this report provides a much-needed summary of the WHI experience to date. As in the past, however, remain mindful that this updated chapter may not be the end of the HT story.

Cynthia A. Stuenkel, MD, NCMP
Clinical Professor of Medicine School of Medicine University of California, San Diego La Jolla, CA
Past NAMS President, 2009 

Content updated October 2013