Hormone Therapy for Wellness and Disease Prevention
[Acknowledgement – An article produced by PCNZ – Pharmaceutical Compounding New Zealand]
Introduction
Endocrinology primarily focuses on pathology related to hormone imbalance, but “no specific field in medicine has been designated to study and analyze the effects of hormones on wellness and disease prevention.” Hormones are integral to the maintenance of cellular function and homeostasis. We know that hormone levels undergo diurnal variation and levels change in response to our environment, thought processes, stress levels, food intake, and medications, and when hormone levels decline as part of the normal aging process, problems with health arise. Supplemental hormones should be considered to relieve symptoms, improve quality of life, prevent chronic illnesses, and maintain wellness. The type of hormone therapy that is selected to restore hormone balance for each patient “is what makes the difference and must be carefully considered”.1
Confusion
Controversy and confusion surrounding use of estrogen, progesterone, testosterone and thyroid hormones for hormone therapy is perpetuated by the terminology used by both the scientific and lay communities. For example, the term progesterone is often used to describe the human hormone as well as synthetic derivatives which should be called progestins; and the three components of human estrogen are frequently referred to as simply one estrogen. This “oversimplification leads to errors in separating the individual function of the estrogens. Although their actions are perceived and often recorded as one, the component molecules of estrogen have different potencies and effects.” 1, 2-6
   “In humans, the three main identified estrogen molecules are estriol, estradiol, and estrone. Estradiol is the most active form of estrogen made by the ovaries, adrenals, and fat cells postmenopause. Estradiol directly affects a wide range of cellular functions, as estrogen receptors are ubiquitous.” Estriol is the weakest of estrogens, and is primarily made by the placenta during pregnancy. “Recorded data on estriol’s function demonstrate that estriol’s effects are limited mainly to the vaginal walls with a little effect on the heart and bones in nonpregnant women. In the nonpregnant, young, and premenopausal woman, estriol is made in the liver in small doses. Studies on the use of estriol in menopausal women and women with multiple sclerosis have demonstrated promising results7… Estrone is manufactured in fat cells after menopause primarily from testosterone derivatives (androstenedione). Estrone levels tend to rise after menopause and the increase in estrone has been implicated in an increased incidence of breast tumors but most data have been obtained from animal studies. Overweight older women have high circulating levels of estrone.” 1
Progesterone
Progesterone is a precursor to most sex hormones, including estrogen, testosterone and other androgens, and adrenal hormones. Therefore, progesterone’s utility is not limited to its role as a sex hormone or preventing endometrial hyperplasia in women who are receiving estrogen. Progesterone also counteracts the stimulation of cell growth in breast tissue by down-regulating the estrogen receptor. Because progesterone suppresses estrogen-driven cell proliferation, progesterone in the natural state helps keep breast cell growth in healthy balance.8
women    Bioidentical hormone replacement therapy is the main type of hormone supplementation in menopausal women in Europe, where large-scale studies have repeatedly demonstrated effective elimination of menopausal symptoms and a lack of long-term negative side effects with the use of bioidentical preparations. Foidart et al. demonstrated in a small study that, within 14 days, progesterone reduced the estradiol-induced proliferation of breast epithelial cells in vivo in 40 postmenopausal women, and that estradiol and progesterone had less proliferative effects on breast tissue cancer cell lines than did progestins and conjugated estrogens.9 E3N, a large prospective French cohort study that investigated breast cancer risk factors in 98,997 women, concluded that micronized progesterone regimens were associated with significantly lower breast cancer risks when compared to synthetic progestin regimens.10 Franke and Vermes showed that progesterone induces apoptosis in breast cancer cell lines that are stimulated by synthetic progestins and other androgenic progestins.11 DeLignieres and colleagues reported the results of an 8.9-year study of 3175 postmenopausal women using mainly transdermal estradiol and progesterone. No increased risk of breast cancer was found.12
   Place et al. conducted a double-blind comparison of transdermal estradiol and conjugated equine estrogens (CEE) that demonstrated improved relief of postmenopausal symptoms in the patient group on estradiol with no side effects.13 Riis et al. demonstrated in a double-blind clinical controlled study that bioidentical estradiol and micronized progesterone helped improve bone density in postmenopausal women.14 Moorjani and colleagues reported that the lipoprotein profile improved in patients receiving oral bioidentical estrogen with progesterone15 compared to those taking progestins with androgenic action. The Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, a government-sponsored randomized trial of hormone replacement therapy, demonstrated a significant reduction in high-density lipoprotein cholesterol when synthetic progestin was added to CEE (significantly reducing the beneficial effects of estrogen). However, when bioidentical progesterone was added, there appeared to be statistically significant endometrial sparing and the bulk of estrogen’s favorable effects on risk factors, including high-density lipoprotein cholesterol, were also preserved.16  Rosano et al. showed that natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women.17
HRT Study
The Women’s Health Initiative (WHI), a large-scale prospective double-blind placebo-controlled study, evaluated the long-term effect of hormone-replacement therapy versus placebo in the prevention of heart disease, osteoporosis, cancer, and strokes in postmenopausal women. The only hormones used in the study were conjugated equine estrogens (CEE) and the progestin medroxyprogesterone acetate (MPA). The study was halted in July 2002 when interim data demonstrated increased risk of myocardial infarction, stroke, and breast cancer in the CEE-MPA arm of the study, with the media frenzy raising fears and doubts for millions of women and their healthcare providers, who began to seek other options. Subsequent re-evaluations of the results of the WHI have raised many questions about the validity of the findings and soundness of the study; however, the study itself still provides grounds for caution concerning the use of CEE and progestin for hormone therapy.1, 18
   Testosterone is produced by the ovaries and adrenals in young women in low amounts, and has been coined “The Hormone of Desire” after a book by Susan Rako, MD. But, testosterone and dehydroepiandrosterone (DHEA) offer many benefits in addition to enhancing libido in aging women. “The addition of testosterone to conjugated estrogen results in an increase in fat-free body mass and mitigates central fat deposition associated with estrogen use. Further evaluation and research must be conducted as we address the possibility of usage of testosterone in the aging female to help improve muscle mass and decrease central adiposity.” 1, 19, 20  “A growing number of physicians involved with menopausal women’s wellness are using testosterone supplementation to provide improvement in libido and mood simply based on clinical findings and blood levels.”1 Commercially available testosterone preparations designed for use in men should not be used in women as the dose is too high. Testosterone can be compounded in topical and sublingual dosage forms in doses that are appropriate for women.
   We compound customised preparations of bio-identical hormones for women and men in the most appropriate strength and dosage form to meet individual patient needs, based on a prescription from a licensed practitioner. 
References:
1 Hormones in Wellness and Disease Prevention: Common Practices, Current State of the Evidence, and Questions for the Future by Erika  T. Schwartz, MD, and Kent Holtorf, MD.