Hormone Therapy for Women : Research

The debate about the benefits versus the risks of hormone replacement therapy (HRT) has raged for over a decade, since data from the Women’s Health Initiative (WHI) was first published in July, 2002. Several articles published in the June 2012 issue of Climacteric, the journal of the International Menopause Society, have concluded that the benefits of hormone replacement therapy outweigh the risks for women who begin HRT near menopause.

Recently, the U.S. Preventive Services Task Force examined the use of hormone replacement therapy, and issued the draft guidelines on the use of estrogen and progestin after considering findings from the WHI. The WHI, a large government-sponsored trial, studied only conjugated equine estrogens (“CEE”, derived from the urine of pregnant horses) and the progestin medroxyprogesterone acetate (“MPA”, a synthetic derivative of the natural hormone progesterone). CEE and MPA are non-bio-identical hormones—they are not the same as hormones made by the human body. The WHI recruited women aged 50 to 79 years, and the average woman in the study was 12 years past menopause when hormone therapy was initiated. The latest USPSTF recommendations don’t apply to women who are menopausal or who use hormones to treat hot flashes and other symptoms related to menopause.

Unfortunately, in response to the WHI, the lay media and even medical professionals including the USPSTF extrapolated the WHI results to include all forms of estrogen and progesterone.
Since the WHI, hundreds of articles have discussed the risks of using “estrogen” without stating that the study dealt exclusively with CEE. And, reviews still continue to use the terms “progestin” and “progesterone” interchangeably, while in fact, the structures and activity are very different. Progestin and progesterone have both been shown to decrease the risk of endometrial hyperplasia, a precursor to uterine cancer. Many of the body’s organs and tissues - such as the brain, heart and bones - have progesterone receptors, and when progesterone levels decline as a result of aging, the body suffers: women experience memory loss, cardiovascular disease, and bone fractures. These are problems that synthetic derivatives of progesterone, i.e. progestins, do not help.

Bio-identical hormones include estrogens such as estradiol, progesterone, testosterone or DHEA, and natural thyroid hormones. Bio-identical hormones have been prescribed in Europe since the 1950s and have been widely used in North America since the 1990s. Many studies have described the benefits and advantages of bio-identical hormones. For example, a study conducted at three prestigious locations, including Yale University School of Medicine, concluded that natural progesterone, but not MPA, enhances estrogen’s beneficial effects on heart muscle in postmenopausal women. At Oregon Health Sciences University and USC School of Medicine, synthetic MPA was compared with natural progesterone in primate studies. MPA was shown to constrict coronary arteries, leading to vasospasm and myocardial infarction, while natural progesterone dilated coronary arteries. Progesterone plus estradiol protected against vasospasm, but MPA plus estradiol did not. In addition, the group treated with bio-identical estrogen had 50% less arterial plaque formation than the control group. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a 3-year multicenter, randomized, double-blind, placebo-controlled study of 875 healthy post-menopausal women, confirmed that synthetic progestins partially negate the beneficial effects on cholesterol levels that result from taking estrogen. Natural progesterone, on the other hand, maintains all the benefits of estrogen on cholesterol without any of the side effects associated with synthetic progestins.

Researchers at Keck School of Medicine, University of Southern California, report that cumulative data supports a “window-of-opportunity” for maximal reduction of coronary heart disease and overall mortality, with minimization of risks when HRT is initiated before 60 years of age and/or within 10 years of menopause and continued for 6 years or more. Results showed a substantial increase in quality of life (adjusted for age) over a 5 to 30-year period in women who initiated HRT in close proximity to menopause, supporting HRT as a highly cost-effective strategy for improving quality of life in menopausal and post-menopausal women.