Nasim Ghafouri; University of California, San Diego Pharm.D.
Alycia Clark; University of California, San Francisco Pharm.D.
I. Background1,2,3
- Estrogens
- The body naturally produces three main forms of estrogen: estrone (E1), estradiol (E2), and estriol (E3). Before menopause, E2 is the most physiologically active form of estrogen and is synthesized primarily by the ovaries. Some E1 is converted reversibly from E2 in the liver and small intestine, but E1 synthesis increases significantly after menopause when the adrenal glands replace the ovaries as the primary source of estrogen. However, it should be noted that some E2 may still be synthesized postmenopausally via aromatization of adrenal androstenedione by fat cells. Lastly, both E1 and E2 can be metabolized to E3, which is the primary urinary metab olite. E3 is considered the “weakest” estrogen, but can antagonize the effects of other stronger estrogens on the endometrium and breast if administered at low daily doses.
- Progesterone versus Progestin
- Progesterone (P4) refers to a single molecular structure that is identical to the progesterone molecule the body synthesizes. Progestin, however, refers to synthetic progestogens, or hormones that act like natural progesterone in the uterus. While synthetic progestins may mimic natural progesterone’s effects on the endometrium, they may also have a variety of different actions elsewhere in the body depending on their affinity for androgen, progesterone, glucocorticoid, and estrogen receptors.
- Testosterone and DHEA
- Testosterone and dihydroepiandrosterone (DHEA) are androgens that contribute to normal ovarian function, bone metabolism, cognition and sexual behavior. Androgens are primarily produced in the adrenal gland, ovaries, and via peripheral conversion of pro-hormones. Androgens are also essential precursors for estrogen synthesis. 8
- There is no consensus as what constitutes biochemical or clinical testosterone deficiency, but mean circulating testosterone levels decline gradually with age, primarily due to decreased production of the precursor androstenedione and decrease in peripheral conversion to testosterone.9 For example, testosterone levels in women in their 40’s are about half of women in their 20’s. Because androgen production declines after menopause, it is reasonable to assume that some menopausal symptoms could be due to androgen deficiency.
- A low testosterone level is closely correlated with reduced coital frequency and loss of sexual desire.9 The addition of testosterone therapy to estrogen replacement results in womenfeelingmorecomposed,elated,energeticwithanincreaseinsexualmotivationalbehaviors.10 Studieshaveshownthathigherdosesoftestosteroneareassociatedwithincreased side effects but no additional benefits, so replacement should given at the lowest possible dose to decrease symptoms.8
II. Menopause
- Menopause marks the end of menstruation, and thus the diminished production of estrogen, progesterone, and testosterone. The physiological effects of each hormone, as well as symptoms of hormone deficiency or excess are outlined in the table below:
|
Estrogen1,2,4,5 |
|
|
|
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Progesterone1,2,4,5 |
|
|
|
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DHEA Testosterone8,9,10 |
|
Decreased libido Fatigue |
|
*has not been shown to increase overall cardiovascular effect8
These statements have not been evaluated by the food and drug administration.
Bioidentical hormone replacement not only serves as an individualized therapeutic option for managing menopausal symptoms, but also poses several advantages over conventional therapy. For instance, while commercial estrogens (see appendix for list of all available products) have demonstrated an increased risk of blood clots, this trend has not been documented with bioidenticals.6 Furthermore, progestins such as medroxyprogesterone acetate have been shown to induce hypertension, increase insulin resistance, and enhance estrogen activity, whereas natural progesterone decreases hypertension and edema, can lead to weight loss, and has favorable effects on lipids and mood.4,6 Testosterone and DHEA has been shown to improve cognitive functiton, feeling of well being, and appetite, and bone density.
III. Monitoring Therapy: Saliva Testing vs. Plasma Levels
Saliva testing provide a non-invasive way to detect levels of free circulating hormones in the body.12 This method can be useful if multiple collections are required, or if a patient has cultural, physical or psychological conditions that make them unable to have blood draws. Saliva testing also minimizes hazard associated with blood collection.
Saliva differs from serum in that it measures only the free physiologically active hormone in saliva, not the inactive protein-bound form.12 There have been many discussions about the accuracy of saliva tests. While saliva testing has been used for a number of years as a fast and reliable method to check hormone levels, some studies have shown saliva testing may not be as reliable as once believed due to the body’s natural diurnal and monthly fluctuations in hormones.13 There are still many improvements required to produce a collection device that combines ideal recovery, stability, and reliable correlation to blood levels for out-patient applications.14 Direct serum levels have been the gold standard to measure hormone levels and monitor treatment, but may be more troublesome due to its invasiveness and requirement for office visits.
Regardless of type of testing, BHRT dosing and monitoring should include both relative lab values and patient’s reports of symptom frequency and intensity. The goal is to keep hormone levels at the lower end of the normal range to minimize potential side effects while decreasing symptoms and allowing the patient to have the best quality of life during these important years.
III. Conclusion
“Bioidentical”referstohormonesthatareidenticalinchemicalstructureandeffecttohormonesproducedbythehumanbody. Theseproductsarederivedfromplant sources and differ from synthetically made commercial products which use a different chemical structure from that which naturally occurs. The advantages of bioidentical hormone replacement therapy (BHRT) when compared to commercially available products include decreased side effects, decreased risks for breast cancer, and improved compliance. 7
Since each formulation is custom made for each individual, treatment is based on one’s symptoms and laboratory values and can be changed accordingly. This essentially customizes the treatment for the patient instead of attempting to fit the patient to a commercially available treatment. Compounding offers a unique therapy option for women who would like to have individualized treatment of menopausal symptoms. Compounding specialists offer a variety of delivery forms based on each individual preference: creams (transdermal), troches/lozenges (buccal), solution (sublingual), suppositories (rectal/vaginal), and capsules (oral).
References:
- Harrison TR. Harrison’s online. New York: McGraw-Hill Health Professions Division; 1998. Available from: http://uclibs.org/PID/21201; http://uclibs.org/PID/112098.
- Gruber CJ, Tschugguel W, Schneeberger C, Huber JC. Production and actions of estrogens. N Engl J Med. 2002;346(5):340-52.
- Wepfer, ST. A Review of Bioidentical Hormone Replacement Therapy. Intl Journal of Pharmaceutical Compounding. 2002;6(1):50-54.
- Wepfer, ST. The Science Behind Bioidentical Hormone Replacement Therapy. Intl Journal of Pharmaceutical Compounding. 2001;5(6):462-464.
- DiPiro JT. Pharmacotherapy : a pathophysiologic approach. New York: McGraw-Hill, 2005.
- Moskowitz D. A comprehensive review of the safety and efficacy of bioidentical hormones for the management of menopause and related health risks. Altern Med Rev.
2006;11(3):208-23.
- Wepfer, S. The Science Behind Bioidentical Hormone Replacement Therapy. International Journal of Pharmaceutical Compounding. 2001: 5; 462-464.
- Udoff, L. Androgen Production and Therapy in Women. Accessed from www.uptodate.com on 1/27/09.
- Davis, S, Tran, J. Testosterone Influences Libido and Well Being in Women. Trends in Endocrinology and Metabolism. 2001:12;33-37.
- Watts, N, Notellovitz, M. Comparison of Oral Estrogens Plus Androgens on Bone Mineral Density, Menopausal Symptoms, and Lipid-Lipoprotein Profiles in Surgical
Menapause. Obstetrics & Gynecology. 1995: 85; 529-537.
- Nieman, L. Measurement of Adrenal Androgens. Accessed from www.uptodate.com on 1/13/09.
- Hofman, L. Human Saliva as a Diagnostic Specimen. Journal of Nutrition. 2001: 131; 1621S-1625S.
- Lewis, J et al. Caution on the use of saliva measurements to monitor absorption of progesterone from transdermal creams in menopausal women. Maturital 2002; 41: 1-6.
- Groschl, M, Kohler, H. Evaluation of saliva collection devices for the analysis
of steroids, peptides and therapeutic drugs. Journal of Pharmaceutical and Biomedical Analysis. 2008:47; 478–486.