Testosterone for Poor Ovarian Responders: Lessons From Ovarian Physiology

Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect on reproductive outcome. The rationale for asking this question lies in the existing scientific evidence derived from basic research and animal studies regarding the action of androgens during folliculogenesis, showing that their main effect in follicular development is defined during the earlier developmental stages. In addition, extreme testosterone excess is not only likely to induce adverse events but has also the potential to be ineffective and even detrimental. Thus, evidence from clinical studies is not enough to either "reopen" or "close" the "androgen chapter" in poor responders, mainly because the short administration and the high dose of testosterone is not in line with the ovarian actions of androgens and the presence of androgen receptors during follicular development.