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

Fundam Clin Pharmacol. 2021 Apr;35(2):466-472. doi: 10.1111/fcp.12600. Epub 2020 Sep 10.


Metformin was found to reduce elevated, but not normal, thyrotropin and prolactin levels. This non-randomized, uncontrolled pilot study investigated hypothalamic-pituitary-testicular axis activity in men with primary hypogonadism receiving metformin. The study population included 29 men with prediabetes, 10 of whom had been diagnosed with primary hypogonadism. Throughout the study, the participants were treated with metformin (2.55-3 g daily). Glucose homeostasis markers (fasting glucose, glycated hemoglobin, and HOMA1-IR), as well as circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, thyrotropin, prolactin, estradiol, and creatinine, were assessed at the beginning of the study and 16 weeks later. Both groups differed in baseline gonadotropin and testosterone levels. Fasting glucose, glycated hemoglobin, and HOMA1-IR were lower after than before metformin treatment. The changes in fasting glucose and HOMA1-IR were more pronounced in hypogonadal men than in subjects with testosterone levels within the reference range. Only in hypogonadal men, plasma concentrations of FSH and LH were lower at the end than at the beginning of the study. Levels of the remaining hormones remained unchanged throughout the study period. The reduction in FSH and LH levels correlated with their baseline levels and with the changes in HOMA1-IR. The results of our study suggest that metformin may decrease FSH and LH levels in men with hypergonadotropic hypogonadism.

Keywords: adenosine 5′-monophosphate-activated protein kinase; follicle-stimulating hormone; hypogonadism; insulin resistance; luteinizing hormone; metformin.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Blood Glucose
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Gonadotropins / blood*
  • Humans
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypogonadism*
  • Male
  • Metformin / blood
  • Metformin / pharmacokinetics*
  • Middle Aged
  • Pilot Projects
  • Prediabetic State


  • Blood Glucose
  • Gonadotropins
  • Hypoglycemic Agents
  • Metformin