The Impact of Metformin on Plasma Prolactin Levels in Antipsychotics-Treated Men With Hyperprolactinemia and...

Metformin decreases elevated levels of pituitary hormones. Little is known about the association between the reproductive axis and hormonal effects of this drug. The purpose of our study was to investigate whether activity of the hypothalamic-pituitary-gonadal axis determines metformin action on prolactin levels in men with prolactin excess.

This prospective cohort study included two groups of men with drug-induced hyperprolactinemia and type 2 diabetes or prediabetes: men with normal hair growth (group A, n = 23) and men with late-onset androgenic alopecia (group B; n = 22). Both groups, matched for age, HOMA-IR, and prolactin concentration, were treated for 6 months with metformin. The outcomes of interest included glucose homeostasis markers (fasting glucose, glycated hemoglobin and HOMA-IR), plasma prolactin (both total and monomeric), other pituitary hormones (gonadotropins, TSH and ACTH), and peripheral hormones (testosterone, DHEAS and IGF-1).

Before metformin treatment, group B was characterized by higher values of LH, LH/FSH ratio, testosterone (total, free and bioavailable) and DHEAS compared to group A. Six-month metformin treatment reduced fasting glucose, glycated hemoglobin and HOMA-IR in both groups, though this effect was more pronounced in group A. The decrease in total and monomeric prolactin was observed only in group A. Their degree correlated inversely with total, free and bioavailable testosterone, positively with baseline prolactin levels, and positively with the impact on HOMA-IR. Compared to baseline values, follow-up LH was higher in group A and lower in group B.

These findings suggest that androgen excess may attenuate metformin action on overactive lactotrophs in men with early-onset androgenic alopecia.