The Impact of Ethinyl Estradiol on Metformin Action on Prolactin Levels in Women with Hyperprolactinemia

Abstract

Background Metformin reduced prolactin levels only in women with hyperprolactinemia. Objective The purpose of this case-control study was to compare metformin action on lactoctrope function between women receiving oral contraceptive pills and women not using hormonal contraception. Methods The study included two groups of matched women with elevated prolactin levels and new-onset prediabetes or diabetes. The first group consisted of 20 women using oral contraceptive pills for at least 12 months before entering the study, while the second group included 20 patients not using any hormonal contraception. Over the whole study period, all women were treated with metformin (1.7–3 g daily). Circulating levels of glucose, insulin, prolactin, thyrotropin, free thyroid hormones, adrenocorticotropic hormone, gonadotropins and insulin-like growth factor-1 were measured at the beginning and at the end of the study (16 weeks later). Results Thirty-eight patients completed the study. Metformin reduced plasma glucose levels and improved insulin sensitivity but the latter effect was stronger in women receiving oral contraceptive pills than in women not using any contraception. Although metformin treatment decreased plasma prolactin levels in both study groups, this effect was stronger in women taking oral contraceptive pills. Only in this group of women, metformin increased plasma luteinizing hormone levels. The changes in plasma prolactin correlated with their baseline insulin sensitivity and the effect of metformin on insulin sensitivity. Metformin did not affect plasma levels of thyrotropin, free thyroxine, free triiodothyronine, follicle-stimulating hormone, adrenocorticotropic hormone and insulin-like growth factor-1. Conclusions The obtained results suggest that the effect of metformin on overactive lactotropes depends on estrogen levels.

Macroprolactinaemia modulates cardiometabolic effects of fenofibrate in men with atherogenic dyslipidaemia: A pilot study

“…In line with our recent research, 13 including a younger population of men, male subjects with macroprolactinaemia had higher concentra- 24 the only agent found to reduce macroprolactin content is exogenous vitamin D. 25 However, this effect was at most moderate and observed exclusively in women. 26 The present…”

“…12 Finally, macroprolactinaemia was found to increase cardiometabolic risk but to a lesser extent than monomeric hyperprolactinaemia. 13 These finding may suggest that elevated levels of macroprolactin mimic the action of monomeric prolactin.…”

The impact of metformin on prolactin levels in postmenopausal women

“…However, the most important conclusion of our study was that physiological amounts of estradiol enhanced the inhibitory effect of metformin on lactotrope secretory function, which is in line with previous observations of women receiving oral contraceptive pills. 17 The current…”

“…In line with this explanation, the impact of metformin on prolactin concentrations was less pronounced in testosterone-treated men with late-onset hypogonadism than in untreated hypogonadal men, 16 as well as stronger in women using ethinyl estradiol plus a progestin than in hormonal contraception-naïve women. 17 Unfortunately, participants of the latter study were treated with high doses of synthetic estrogen (30 μg) and additionally received a progestin. Moreover, because of mild prolactin excess, most women in the control group were characterized by intact hypothalamic-pituitary-ovarian axis activity.…”

Plasma gonadotropin levels in metformin‐treated men with prediabetes: a non‐randomized, uncontrolled pilot study

“…Contrary to men with normal testosterone concentrations, metformin administered to subjects with low testosterone levels reduced circulating levels of both hormones [13,14]. These findings and a potentiating effect of oral contraceptive pills containing ethinyl estradiol on metformin action [15,16] indicate that the effect of metformin on thyrotrope and lactotrope secretory function depends on sex steroid levels.…”