Reprinted with permission From Alternative Medicine Review, Vol. 11, #3 2006, pp. 208-223, Thorne Research, Inc. Bioidentical Hormones Review A Comprehensive Review of the Safety and Efficacy of Bioidentical Hormones for the Management of Menopause and Related Health Risks Deborah Moskowitz, ND Abstract in addressing menopausal symptoms. The Numerous forms of estrogens and progestins author advocates for continued research on are utilized for the treatment of menopausal bioidentical hormones and concludes there is complaints and associated conditions that currently sufficient evidence to support their occur temporally. Although known to be different preferred use over that of their synthetic cousins. with respect to molecular structure, receptor (Altern Med Rev 2006;11(3):208-223) affinity, metabolism, and other physiological traits, most have been treated as if they were Introduction clinically identical. The majority of these hormone Over the last decade, women and their physi- preparations, commonly referred to as hormone cians have in increasing numbers been opting for the replacement therapy (HRT), should perhaps be use of natural, bioidentical hormones for treatment of more aptly referred to as hormone substitution symptoms of menopause and to support bone and heart therapy, as most of the therapies utilized do health.1 The trend away from the use of conventional not exactly match those produced in the body. synthetic hormones, toward those specifically match- Research indicates these synthetic hormones ing the hormones produced in humans (bioidentical) vary clinically in safety and efficacy. As such, has been driven by several factors, including a global women and their physicians have, in increasing trend toward everything “natural” as seen in the in- numbers, been opting for the use of bioidentical creased interest in organic foods and complementary hormones; i.e., those that match the structure and alternative medicine (CAM). Perhaps the most and function of hormones produced in the body. significant factor driving the increased interest in bi- With greater utilization and research surrounding oidentical hormones is the rising fear or suspicion bioidentical hormones, the differences can now of the “synthetic” hormones used in conventional begin to be fully assessed and appreciated. This hormone replacement therapy (HRT). Over the last article reviews the disparities between synthetic decade, research-based media reports of risks associ- and bioidentical estrogens and progestins/ ated with conventional HRT have prompted women’s progesterone with respect to safety and efficacy; concerns and altered the approach to hormone use.2,3 special attention is devoted to clinical outcomes This has been most evident following the results of in the breast, endometrium, bone, cardiovascular the U.S. government-sponsored Women’s Health Ini- system, and brain. The studies reviewed suggest tiative (WHI) study in 2002. The WHI study results bioidentical progesterone does not have a negative effect on blood lipids or vasculature as do many synthetic progestins, and may carry less risk with Deb Moskowitz, ND – President of Wellness Designed, LLC, a consulting respect to breast cancer incidence. Studies of both company that focuses on natural health product development and research; advisor to Women in Balance, a national non-profit association dedicated bioidentical estrogens and progesterone suggest to helping women achieve optimal health, wellness and hormone balance a reduced risk of blood clots compared to non- (www.womeninbalance.org). Correspondence address: 2407 NE 17th Ave, Portland, OR 97212 bioidentical preparations. Bioidentical hormone Email: [email protected]. preparations have demonstrated effectiveness Page 208 Alternative Medicine Review u Volume 11, Number 3 u 2006 Copyright © 2006 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 11, Number 3 September 2006 Review Bioidentical Hormones led to the conclusion of experts in the field that the levels and provide feedback inhibition to FSH.6 risk of using conventional HRT (non-bioidentical Significant variability may occur in estradiol and in- hormones), specifically Premarin® and Provera®, out- hibin (a hormone that inhibits FSH), and gonadotro- weighed the benefits provided.4 This report was fol- pins may rise abruptly.5,6,9 Testosterone levels decline lowed by a significant decline in the use of synthetic with age and do not appear to change significantly hormones at menopause, and a growing number of with natural menopause. By menopause, few follicles women and their physicians utilizing and advocating remain, yet intermittent estradiol production from the the use of bioidentical hormones. The question, with- ovaries may still occur.8,9 Adrenal androstenedione is out the value of a similar long-term study looking at the primary source of estrogen after menopause; sex- bioidentical hormones, is whether or not the evidence hormone-binding globulin falls slightly.10 FSH levels exists to support their preferred use over their syn- remain high for several years after menopause, after thetic cousins. which levels decline considerably.10,11 Although FSH is commonly used, there are Hormone Changes Surrounding no consistently reliable endocrine markers to estab- 9 Natural (Non-induced) Menopause lish a woman’s menopausal status. Shifts in hor- mones contribute significantly to a sense of physical, Menopause is defined as the cessation of mental, and emotional imbalance that may character- menstruation occurring as a result of the loss of ovar- ize a woman’s experience of menopause. As a clini- ian follicular activity. At birth, a woman has a million cian, it is important to note the changes that occur, eggs, by puberty a mere 300,000. This loss of eggs is link them to the physiology of the various hormones, referred to as atresia, a natural, albeit incompletely and address imbalances individually. Addressing oth- understood, process whereby the follicles enter an er aspects of endocrine health is also necessary and incomplete growth phase. This process continues may involve assessing adrenal and liver function, as throughout a woman’s life. Thousands of follicles well as diet, exercise, and other lifestyle factors. are lost to atresia compared to one or a few lost each month to ovulation. As a woman ages and as a result of the decreasing follicles, follicle-stimulating hor- Problems with Conventional HRT mone (FSH) levels gradually increase and the cycle In July 2002, after determining that estrogen begins to shift, with a shortening of the follicular in combination with progestin increased a woman’s phase that can begin as early as a woman’s 20s.5,6 In risk of breast cancer, coronary events, stroke, and the 10-15 years prior to menopause, this rate of fol- blood clots, the National Institutes of Health (NIH) licular atresia begins to accelerate.7,8 Perimenopause prematurely halted the first part of the WHI, a study is the term used to describe the time of transition be- designed to identify the risks and benefits associated tween a woman’s reproductive years and cessation of with long-term hormone use. In this study, 16,608 menstruation. Typically perimenopause occurs be- healthy postmenopausal women with a uterus, ages tween the ages of 40 and 51 and can last anywhere 50-79, were randomized to either test or placebo 4 from six months to 10 years. During this time, hor- group. The test group received a combination of ® mone levels fluctuate and decline naturally, although equine estrogen and synthetic progestin (PremPro ); not necessarily in an orderly manner. no bioidentical hormones were used. At the time the Perimenopause often begins with an altera- study was halted, PremPro compared to placebo re- tion in cycle and bleeding regularity due to fluctuating sulted in: t hormones, anovulatory cycles, and changes in timing 26-percent increased risk of invasive breast of ovulation. Cycles may be long or short, ovulatory cancer (eight additional cases per 10,000 or anovulatory.8 Even women who cycle regularly women per year); during perimenopause can have significant variabil- t ity in hormone levels.7 Progesterone levels drop with 29-percent increased risk of myocardial anovulatory cycles and a decline in luteal function. infarction (MI) or death from coronary heart Estrogen levels fluctuate in response to rising FSH disease (CHD) (seven additional cases per 10,000 women per year); Alternative Medicine Review u Volume 11, Number 3 u 2006 Page 209 Copyright © 2006 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 11, Number 3 September 2006 Bioidentical Hormones Review menopause is a natural event.2,3,14,20 Use of HRT was t 41-percent increased risk of stroke (eight correlated with older women’s wishes to reduce os- additional cases per 10,000 women per year); teoporosis risk, while younger women sought relief and from menopausal symptoms, predominantly vasomo- tor flushing.2,19 t 200-percent increased risk of blood clots (18 Given this information, it should follow that additional cases per 10,000 women per year). utilizing hormones that have fewer side effects and risks, correlate with a woman’s perception of “natu- The WHI study also confirmed benefits seen ral,” and address long-term health benefits could in- in previous studies, most notably: crease hormone use and therefore improve a woman’s t 33-percent decreased risk of hip fracture