Blog of the Society for Menstrual Cycle Research

Revisiting postmenopausal hormone therapy

July 4th, 2013 by Alice Dan

On June 24, the Journal of the American Medical Association (JAMA) released a report on the Women’s Health Initiative Memory Study of Younger Women (WHIMSY) in the JAMA Network publication JAMA Internal Medicine.

This study is of particular interest because hormone therapy caused significant deficits in cognitive functioning in women aged 65 and older, as documented in the Women’s Health Initiative Memory Study (WHIMS). The “Timing Hypothesis” proposes that, despite the serious risks of hormone therapy demonstrated in the Women’s Health Initiative (WHI) research, therapy with conjugated equine estrogens can benefit women when it is started during the menopausal transition and in early menopause. Last year, a position paper endorsed by 14 medical societies made that claim (Stuenkel, et al, 2012).

Why would so many in the medical profession continue to prescribe hormone therapy, and to believe that hormone therapy is beneficial, in the face of powerful evidence that the risks of such therapy far outweigh the benefits? Probably several reasons:

1) Few other therapies are as effective in relieving women who suffer from distressing symptoms during and after the menopausal transition.

2) Animal and laboratory studies strongly support a positive role for estrogen in cognitive function.

3) The pharmaceutical industry wields tremendous power, and provides financial support to most of the medical societies and research studies in this area.

 It is, as the authors state, “reassuring” that this latest WHIMSY study found neither increased risk nor increased benefit in cognitive assessments an average of 7 years after the study was halted, among the 1,272 participants in the WHI who were 50 to 55 years old when the hormonal therapy was started. However, the lack of cognitive benefit makes one wonder why women would want to risk the serious consequences associated with hormone therapy.

Advocates for women’s health must continue to challenge the ethical and scientific basis for medical practices that can potentially be harmful to women. We need to support research on the mechanisms underlying the effects of hormones on women’s bodies, but also on the sociopolitical forces influencing medical practice.


Stuenkel, Cynthia A., Margery L. S. Gass, JoAnn E. Manson, Rogerio A. Lobo, Lubna Pal, Robert W. Rebar, and Janet E. Hall. “A decade after the Women’s Health Initiative—the experts do agree.” Menopause: The Journal of the North American Menopause Society 19.8 (2012): 846–847.

3 responses to “Revisiting postmenopausal hormone therapy”

  1. Jonathan Raymond says:

    This new study is FAR from reassuring as you rightly pointed out. Of course they’re not going to find increased dementia in this age group, because the women are, on average, too young. But what worries me was that they DID find some evidence that estrogen alone in women with hysterectomy caused a slight decline in verbal fluency, even up to 7 years after cessation of therapy. Though they may dismiss that finding as “small” or hardly noticeable, this same adverse effect was seen in older women in WHIMS, along with other domain-specific decrements. Does this presage dementia? Who knows. But any long lasting adverse effects should be taken seriously.

    I’m also personally concerned about the early reports from KEEPS, which suggested that transdermal estradiol may have adversely affected recall ability. Again, very slight, but also nothing even close to a benefit that would support this silly timing hypothesis, which is based on obstinance rather than science!

  2. Alice Dan says:

    Thanks very much, Jonathan, this is important additional information!

  3. Jonathan Raymond says:

    Oh you’re welcome!

    I find it appalling that “experts” are continuing to question the validity of WHI and other trials this many years later. It seems like “HRT” is the only drug that has pushed back against the science. Other interventions that were tested and failed in the past (antioxidants, cancer treatments) were different – we accepted the negative results and moved on. Not the case with estrogen, and the only reason I can think of is that it revolves around the millions of lost customers (and billions of lost dollars in profits). Has nothing to do with science and women’s health.

    That being said, given that many women still use these drugs, I remain concerned about estrogen’s risks, which are still being elucidated. And I don’t buy into the hypothesis that “early” estrogen prevents heart disease. And though Premarin alone may have slightly lowered breast cancer risk, this may not apply to estradiol, which in theory, could be worse, as it is more potent. (KEEPS has already suggested this as women who got estradiol had more abnormal mammograms, vaginal bleeding, and *slightly* more memory problems.)

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