Follicle-Stimulating Hormone Exacerbates Cardiovascular Disease in the Presence of Low or Castrate Testosterone Levels
Wilhelmina Duivenvoorden, David Margel, V Gayathri, Emmanuelle Duceppe, Sadiya Yousef, Magda Naeim, Mohammad Khajehei, Sarah Hopmans, Snežana Popović, Yaara Ber, Diane Heels‐Ansdell, P.J. Devereaux, Jehonathan H. Pinthus
Abstract
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.