Administration of metformin to a diabetic woman with extreme hyperandrogenemia of nontumoral origin: management of infertility and prevention of inadvertent masculinization of a female fetus.

Abstract

The polycystic ovary syndrome (PCOS) is characterized by chronic hyperandrogenemic anovulation and is considered to be a common cause of infertility because it affects 5–15% of premenopausal women (1–3). Metformin has been shown, in several studies, to significantly lower androgen levels and initiate menstrual cyclicity in women with PCOS (4–8). The mechanism of action of metformin in PCOS is unknown, but it is believed to involve the combined effects of decreased insulin action on the ovary (lowering ovarian androgen production rates) and on the liver [resulting in an increase in sex hormone binding globulin (SHBG) levels] (4, 9–11). Though metformin is effective in women with PCOS with mild to moderate elevations of androgen serum levels (2, 4–8), its effects in the considerably smaller subset of PCOS cases associated with extreme hyperandrogenemia [testosterone (T) . 200 ng/dL (6.9 nmol/L)] and maternal virilization have not been studied. Such extreme levels of hyperandrogenemia during pregnancy are usually caused by an ovarian tumor or luteoma of pregnancy and can be treated effectively by surgery (12). However, this is not the case when these high levels are caused by PCOS. In fact, although the possibility of fetal masculinization exists in the presence of severe maternal hyperandrogenism, there are presently no effective preventive measures when this is found in women with PCOS (13).