On the basis of previous studies of the effectiveness of metformin in restoring menstruation in women with polycystic ovarian syndrome (11) and in nonpsychotic patients with amenorrhea (12), Wu and colleagues designed a double-blind study of metformin (1000 mg/day) or matched placebo in antipsychotic-treated schizophrenia patients with amenorrhea. The authors report that 66% of the metformin-treated patients, compared with only 2% of the placebo patients, resumed menstruation during the 6-month study, and the mean time for restoration of menstruation was 2 months. Metformin also decreased levels of prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) and significantly decreased weight, insulin levels, and insulin resistance in these patients. Logistic regression analysis suggested that decreases in body weight, insulin resistance, and levels of prolactin, LH, and FSH were all related to the drug's therapeutic effect of restoring menstruation, although the specific contribution of these effects to the mechanism by which metformin restores menstruation is not clear. Many antipsychotic drugs exert some of their biological or clinical effects by interfering with dopamine transmission through blockade of postsynaptic dopamine receptors; this is believed to be an important mechanism through which these drugs raise prolactin and other hormone levels. Metformin has been shown to increase dopaminergic tone in patients with polycystic ovarian syndrome (13), and this may be one of its mechanisms of action in the clinical effects reported here. It is also important to note that there were no differences in side effects between the metformin and placebo groups, which indicates that metformin was a safe treatment as well as an efficacious one.