Effects of Oral Androstenedione Administration on Serum Testosterone and Estradiol Levels in Postmenopausal Women
Effects of Oral Androstenedione Administration on Serum Testosterone and Estradiol Levels in Postmenopausal Women
Abstract & Commentary
Synopsis: Acute oral administration of 50 mg and 100 mg of androstenedione to postmenopausal women increases serum testosterone and estrone but not estradiol.
Source: Leder BZ, et al. J Clin Endocrinol Metab. 2002;87:5449-5454.
The use of androgenic preparations to support libido and energy in postmenopausal women has been advocated, but few studies on the use of androgenic preparations are available to guide physician practices. Testosterone has poor oral bioavailability, so other preparations have been suggested. Androstenedione is available without a prescription, but its safety and efficacy have not been established. To delineate more about the fate of orally ingested androstenedione, 30 postmenopausal women were randomly assigned to receive 0, 50, or 100 mg of androstenedione as a single oral dose. Hourly measurements were made for androstenedione, estrone, estradiol, and testosterone for 12 hours. There was, not surprisingly, considerable individual variability in the levels achieved. Testosterone levels exceeded the upper limit of normal in 4 of 10 women given the 50-mg dose and in 6 of 10 women given the 100-mg dose. Peak serum androstenedione levels exceeded the upper limit of normal for young reproductive-age women (200 ng/dL) in all subjects given the 100-mg dose and in 8 of 10 given the 50-mg dose. Estrone, but not estradiol, levels were increased, but did not exceed physiological concentrations. All hormone levels had returned to baseline by 12 hours.
Comment by Sarah L. Berga, MD
On a molar basis, the androgen secreted in greatest abundance by the ovaries is androstenedione and not testosterone. However, testosterone binds much more avidly than androstenedione to the androgen receptor. Thus, on a molar basis, testosterone is a more potent androgen. Because adipose tissue, sebaceous glands, and other tissues can convert androstenedione to testosterone, androstenedione is nonetheless an important androgen from a physiological perspective, and too much or too little may have clinical consequences. In women, approximately 50% of the circulating level of androstenedione derives from the adrenal glands, with the other half being secreted by the ovaries. In contrast to testosterone, androstenedione has a long half-life and is not so avidly bound by SHBG. Therefore, it is easier to estimate circulating androstenedione concentrations from a single blood sample than testosterone concentrations. Given these considerations, androstenedione use has been promoted to restore androgen levels, libido, muscle mass, bone density, and well-being in older men and women undergoing "adrenopause." "Andro" use also has been promoted for enhancing athletic performance. Since a large fraction of the circulating testosterone in women is derived from androstenedione, its use has been advocated also for women who undergo natural or surgical menopause to restore libido and boost well-being. There are few data on what would constitute an appropriate dose for women. The present study was designed to address that gap. The data would suggest that a more appropriate dose might be 25 mg, but to maintain testosterone levels around the clock would require twice-daily dosing. Of note, there was a large degree of intersubject variability, so it might be necessary to use both smaller and larger doses to achieve physiological levels in some individuals. Because the use of oral androgens induces hepatic enzymes and binding proteins, one would need to determine levels of androstenedione and its metabolites after several weeks of use to determine steady state, circulating concentrations. No safety data were collected in the present study, and there are no data about how the use of androstenedione would impact coagulation, insulin action, and other important physiological parameters.
It would be interesting to know how topical administration compares to the oral route of delivery in terms of peak levels and the distribution of metabolites (estrone, estradiol, testosterone, and cortisol). Presumably, there would be different levels of metabolites with oral vs topical delivery because when it is given orally, the liver actively metabolizes and alters the androstenedione before it is released into the systemic circulation. Absorption might not be as rapid when applied topically and this would likely be a benefit. Compounding pharmacies make and often promote topical preparations, so this information would be relevant to those of us still struggling with the aftermath of the WHI. Many women have the mistaken belief that over-the-counter, nonprescription products such as androstenedione are safe and well studied. Thus, they may abandon conventional medications in favor of "natural" products. As one can see, there are far too little data to endorse this practice.
Leder and colleagues discuss how androstenedione use might compare to DHEA (dihydroepiandrosterone) use. Androstenedione is derived from DHEA, but DHEA can also be sulfated. DHEA-S circulates in microgram rather than nanogram concentrations. Oral DHEA increases both testosterone and estradiol in women. These levels may be more sustained because the reservoir of DHEAS is available for desulfation and aromatization. There are few studies, however, on the long-term safety of DHEA, although at least 1 long-term study is ongoing. Again, a physiological pattern might result if this pre-androgen is administered topically rather than orally, and it is unlikely to require twice-daily dosing to maintain levels in the "desired" range. Again, the use of androstenedione or DHEA makes more sense if the patient in question has a true hormonal deficiency as a result of adrenalectomy, Addison’s disease, or surgical menopause. The use of androgens to retard the aging process has not been substantiated, although, because of the 1994 Dietary Supplement Health and Education Act, patients are free to conduct their own experiments on themselves without the benefit of medical advice or oversight.
Dr. Berga is Professor and Director, Division of Reproductive Endocrinology and Infertility at the University of Pittsburgh.
Synopsis: Acute oral administration of 50 mg and 100 mg of androstenedione to postmenopausal women increases serum testosterone and estrone but not estradiol.
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