Follicle-Stimulating Hormone Exacerbates Cardiovascular Disease in the Presence of Low or Castrate Testosterone Levels.

Low testosterone (T), common in aging men, associates with cardiovascular disease. We investigated whether follicle-stimulating hormone (FSH), which is affected by T, modulates the cardiovascular effects associated with low T or castration. FSHβ:low-density lipoprotein receptor (LDLR) mice, untreated or castrated (orchiectomy, gonadotropin-releasing hormone agonist or antagonist), demonstrated significantly less atherogenesis compared with similarly treated LDLR mice, but not following FSH delivery. Smaller plaque burden in LDLR mice receiving gonadotropin-releasing hormone antagonists vs agonists were nullified in FSHβ:LDLR mice. Atherosclerotic and necrotic plaque size and macrophage infiltration correlated with serum FSH/T. In patients with prostate cancer, FSH/T following androgen-deprivation therapy initiation predicted cardiovascular events. FSH facilitates cardiovascular disease when T is low or eliminated.