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IMS Menopause Live

What if?

14 April, 2014

In a recent publication, under the section heading 'Personal Perspectives', Dr James Simon considers hypothetical comparisons between oral conjugated equine estrogens (CEE) and transdermal estradiol and between oral medroxyprogesterone acetate (MPA) and oral micronized progesterone for their effects on four primary outcomes of the Women's Health Initiative (WHI) [1]: cardiovascular disease risk, cerebrovascular disease risk, venous thromboembolism risk, and breast cancer risk. Although the discussion in this article focused on transdermal estradiol delivered through patches, gels, or lotions, it could be broadened to include all forms of non-oral estrogen administration. After a brief review of the WHI and a survey of the relevant literature in which the safety of these various hormone therapies was assessed or compared, the author used statistical methods to ascertain the attributable risk of venous thromboembolism for transdermal estradiol versus oral hormone therapy and imputed those risks into the WHI primary outcomes.


This is not a regular comment for Menopause Live, but rather an appraisal. Although medicine is not accurate as mathematics is, it cannot be based on a 'what if' situation, since the treating physician makes decisions after considering both the individual clinical facts and personal experience. Still, the 'what if' issue here is not purely fiction, but an attempt to extrapolate results from studies in women using transdermal estradiol and progesterone to the WHI arena, where CEE and MPA were the only study medications. The manuscript is built in a very logical way, first bringing the up-to-date information on all available aspects of the WHI study results, then discussing the four risk domains mentioned earlier in regard to current knowledge on the potential relevant adverse effects of non-oral estradiol and progesterone, and finally bringing the author's conclusions. The main message, which is not innovative, but well phrased and referenced, is that 'postmenopausal hormones' should not be regarded as a single entity, and therefore the WHI results should not be the sole basis for guidelines and recommendations.

Hormonal products which do not contain CEE or MPA might have a different risk profile and, in fact, have a more favorable benefit–risk balance. Understanding these important nuances must lead to better implementation of the vast data on postmenopausal hormone therapy and a more rational clinical approach, which truly considers the best options for the individual patient. There is no place for the fear of using hormones which appeared after the first release of the WHI trial results because of mis-interpreted related risks. Appropriate hormonal preparations, especially in healthy women during the first decade postmenopause are safe and effective. I suggest that health-care providers should read Simon's article and use its take-home messages during discussions with women prior to decisions on hormone therapy.
Amos Pines
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel


1. Simon JA. What if the Women's Health Initiative had used transdermal estradiol and oral progesterone instead? Menopause 2014 Jan 6. Epub ahead of print

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