March 15, 2013

Androgens are Optimal for Ovarian Function

Women make and utilize male hormones. These hormones are integral to optimal ovarian function in both natural cycles and stimulated cycles such as in In Vitro Fertilization (IVF). In both men and women, these androgens decrease with age. In women, blood testosterone levels decrease; this diminution is paralleled in the markers used to assess ovarian function (antral follicle count {AFC}, and Anti-mullerian hormone {AMH}). In early studies that evaluated women undergoing IVF procedures, blood testosterone levels correlated to number of eggs retrieved. These data suggest that testosterone levels may play a role in ovarian response to the stimulatory hormones such as Follicle Stimulating Hormone (FSH). It is hypothesized that the presence of the androgen may make the follicles more receptive to the stimulation and consequently produce more follicles. An anticipated progression would be that, if in fact, androgens (testosterone and the family of male hormones) decrease with age, perhaps women who experience diminished ovarian reserve and low egg numbers in an IVF cycle, are deficient in this vital hormone family. Moreover, perhaps its supplementation in a deficient environment, could work to rescue those follicles incapable of responding.

There are multiple studies exploring androgen supplementation and variable ovarian responses. In these studies, it seems that the therapeutic effect on follicular development was variable and may be dependent upon both duration and concentration of androgen exposure. Earlier studies supplemented with both testosterone and DHEA (dehydroepiandrosterone). DHEA has entered the vernacular as a viable option for multiple reasons. Firstly, it is known that natural production decreases by 50% between ages 25 and 45. Secondly, when DHEA supplements are given, low androgen levels in women returned to normal range. Thirdly, it is easily accessible and relatively inexpensive. When DHEA was used as a supplement in an IVF trial there was a modest increase in ovarian response.

However, this point is where the data falls short. To date, there are no randomized controlled trials (RCT), assessing DHEA supplementation and ovarian response. Clearly, well-designed and executed controlled trials of DHEA treatment in women with diminished ovarian reserve are warranted.

Ultimately, treatment efficacy is dependent upon outcome. In women pursuing IVF for diminished ovarian reserve, the favorable and acceptable outcome is the birth of their child. Unfortunately, the data accrued thus far does not support that androgen supplements, whether it be testosterone patches or DHEA, improve a women’s chance of giving birth. The production of more follicles, higher estrogen levels and possible retrieval of an additional egg is inconsequential if the fulfillment of childbirth is not met.

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Danielle Vitiello, Ph.D., M.D.

Danielle Vitiello, Ph.D., M.D. Board-Certified in Obstetrics and Gynecology, Reproductive Endocrinology and Infertility