FAQ on the risks of HRT

Q. Do the results of the Women's Health Initiative (WHI) apply to bio-identical hormones?

A. The Women's Health Initiative specifically studied a population of women who were broken into 3 separate arms of the study: one arm received premarin, a second received prempro, and a 3rd arm received placebo. Bio-identical hormones were NOT studied in the WHI. Many physicians have extrapolated the results of the WHI to bio-identical hormones, implying varying side effects with all forms of HRT, which cannot be proven at this time, as the WHI did not use bio-identical hormones. Conversely, other practitioners have also claimed that bio-identical hormones are superior and safer based on negative results of the WHI using pharmaceutical agents. This is also extrapolation and cannot be proven at this time. Whether positive or negative, the only hormone regimens for the treatment of menopausal symptoms which have had proven results in large-scale (high statistical power), gold-standard trials of placebo-controlled, randomized, double-blind studies to date include premarin and prempro, but NOT the typical bio-identical skin preparations such as Bi-est, Tri-est, or progesterone creams. Furthermore, most randomized, controlled trials (WHI included) have tested women well past the age of menopause.  For example, the average age of women in the WHI were 63.5 years old, and only slightly over 20% of the studied women had ever been on HRT before entering the trial.  Numerous critiques have ensued in the years following the initial publication of the WHI results, most of which have pointed to the proven protective effects of HRT in women less than the age of 60, indicating a "window of opportunity" to replace hormones quickly after women lose them, rather than waiting 10-15 years AFTER menopause.  In fact, several large organization bodies have revised their guidelines since 2002, indicating the importance of not missing this "window of opportunity" for women less than the age of 60 years old.  For an excellent unbiased critique of the WHI, I recommend readers study the position statements by the Expert Panel of the International Menopause Society (IMS), revised in 2004, and again in 2007, with recent updates from 2008. This is available on-line at www.imsociety.org.

Although there are numerous studies in the scientific literature documenting beneficial effects of estrogens, over 90% of all such studies were done with premarin/prempro products, so once again, extrapolation is rampant. Furthermore, many studies were done on animals and such results cannot necessarily be directly applied to humans with certainty. In recent years, there have been small human trials (compared to the large scale of WHI) looking at low doses of estrogen +/- progesterone or synthetic progestins and their abilities to prevent bone loss and treat menopausal symptoms. Such trials generally use bio-identical FDA-approved name brand estradiol patches and not the bio-identical Bi-est or Tri-est creams, which are commonly prescribed by physicians focusing on anti-aging medicine, and have mostly yielded positive results based on individual physician feedback.

Thankfully, large randomized, placebo-controlled studies are underway now using bio-identical hormones in order to give us vitally-needed information for comparison. These include the KEEPS (Kronos Early Estrogen Prevention Study, a 5 year study funded by the Kronos Longevity Resesarch Institute, results due out in 2011), and BHOT (Bio-identical Hormones On Trial, a study now in its data collection phase, via the University of Texas).

Q. Will using hormone replacement therapy (HRT) increase my risk of heart disease and breast cancer?

A. These types of claims are largely based on the WHI results, and do not necessary apply to everyone. The decision to start HRT or not is a very individualized process, based on each woman's specific situation, risk factors, quality of life, among other factors in weighing the pros and cons. In interpreting the WHI results, I agree with the Expert Panel from the IMS that "the WHI study was not designed, and therefore was not powered, to investigate the consequences of hormone therapy (HT) in women below 60 years of age. Therefore, any attempt to present the results of the study as indicating the HT may inflict damage to the heart in general--a message that was accepted by many medical societies and regulatory authorities--is simply wrong and must be amended". Furthermore, re-analysis of the WHI data actually showed a 25% reduction in the risk of breast cancer in the women given premain only. Once again, falling prey to such comments represents extrapolation of the WHI data, when clearly such data should only be applied to women with the same characteristics and given the same treatment as those who were studied in the WHI. Once again, I refer patients to the position statement by the Expert Panel of the International Menopause Society for a thorough critique of the WHI at www.imsociety.org. Over the past 2 years, more large, European population-based studies have been published looking specifically at cyclical vs. continuous/combined HRT, with reference to the potential of increased cardiovascular side-effects. Such results thus far favor cyclical approach with specific reference to cardiovascular protection. There is also continued varied opinion among more recently published results with reference to breast and ovarian cancers. Once again, risks vs. benefits profile needs to be carefully assessed in each individual patient, based on her own risk factors, and sweeping conclusions can not be given without a thorough evlauation.