Human Identical Hormones for Hormone Replacement Therapy

by Phillip Warner, MD and Paul Hueseman, RPh, PharmD
October 2002

brought to you by Bellevue Pharmacy, a ProjectAWARE sponsor

The abrupt cessation of a branch of the Women's Health Initiative Randomized Controlled Trial (WHI), a study funded by the National Institute of Health (NIH), caused a media frenzy and raised concerns regarding Hormone Replacement Therapy (HRT) by both the professional and lay community. Interestingly, this WHI study was actually one of two studies which had results published at approximately the same time. The other study was the Heart and Estrogen / Progestin Replacement Study Follow-up (HERS II) study.

The WHI trial consisted of 16,608 post-menopausal women age 50-79 years with an intact uterus at baseline who were recruited by 40 US clinical centers from 1993-1998. The women took Premarin 0.625 milligrams plus Provera 2.5 milligrams (a combination called PremPro) each day, or they took a placebo (a similar pill with no medication) each day, and were unaware of which pill they were taking. The Women's Health Initiative was asking the question "Does hormone replacement with PremPro decrease the risk of chronic disease in healthy women who have their uterus and ovaries?"

This study was ended early on May 31, 2002 after 5 years due to an increase in the risk of breast cancer of 26% in the group receiving PremPro. Because this study was ended early, it is difficult to interpret the results for heart disease. However, preliminary results (those that were seen with the amount of time that elapsed during the study) demonstrated that there was an increased risk for non-fatal heart attacks, stroke, and blood clots (deep vein thrombosis (DVT) and pulmonary embolism (PE)). Again, it is important to note that because this study was ended early, it is difficult to determine whether these "heart effects" would have been reduced with continued treatment once the "initial high risk period" of treatment is complete. Benefits from treatment in this study included a reduction in fractures, conferring protection from osteoporosis or "bone disease". The authors of this study commented that "the results of this study do not necessarily apply to other formulations of oral estrogens and progestins (natural progesterone)." In addition, they stated that "it remains possible that estradiol with progesterone, which more closely mimics the normal physiology and metabolism of endogenous sex hormones, may provide a different risk-benefit profile".

The recently published HERS II study consisted of 2,321 post-menopausal women in which treatment with hormones (most patients received Premarin 0.625 mg) was compared to no hormone treatment to evaluate the benefit on coronary heart disease, as well as non-cardiovascular effects such as cancer. This study demonstrated no differences with regard to cardiovascular (heart) effects for patients who were treated with hormones versus patients who received no treatment with hormones. Additionally, this study showed that after an initial treatment period of 2 years with hormones, the risk of blood clots declined to a non-significant difference. Therefore, long-term there is no increased risk of blood clots. The HERS II study also demonstrated that there were no differences between the hormone group and the placebo (sugar pill) group in the incidence or occurrence of any types of cancer.

Both of these studies strengthen the idea that Hormone Replacement Therapy (HRT) should be in the form of Human Identical Hormones (HIH), and not products like PremPro and Premarin that are totally foreign to the human female. The concept that estrogens and progesterone coming from horse placentas or created in the laboratory will have positive long-term benefits in the human female simply makes no sense. The Human Identical Hormones (HIH) match exactly the estrogens and progesterone made by the ovary, and therefore fit exactly on the cell receptors as nature intended. These hormones are extracted from various plants and have been available by prescription for many years.

There have been some studies with positive benefits of HIH in reducing the risk of heart disease, osteoporosis, stroke, cancer and Alzheimer's disease. Generally, these studies showed no increased risk of breast or endometrial cancer. Clearly, there have been contrasting results with PremPro, and the authors of the WHI trial have even alluded that the results may have been different with HIH. The bottom line conclusion is that continued clinical research is needed to further prove the benefits of HIH in preventing heart disease, stroke, cancer, and Alzheimer’s disease in absence of an increased risk of breast cancer. In the interim, however, hormone replacement therapy with HIH continues to help women in many ways, including improvement in quality of life, by treating various symptoms associated with menopause.

For questions and further information, contact Bellevue Pharmacy.