biostudies-literatureUnknown9(3)Duivenvoorden WCMLow 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.JACC. Basic to translational science364-379https://www.ebi.ac.uk/biostudies/studies/S-EPMC10978407biostudies-literatureFollicle-Stimulating Hormone Exacerbates Cardiovascular Disease in the Presence of Low or Castrate Testosterone Levels.PMC10978407Khajehei MPinthus JHSubramony Gayathri VMargel DDuivenvoorden WCMDuceppe EYousef SNaeim MHopmans SDevereaux PJBer YPopovic SHeels-Ansdell DfalseFollicle-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.2024-01-01T00:00:00Z2024 Mar2025-04-25T18:56:46.774Z2025-04-06T07:46:07.047ZS-EPMC109784073855962210.1016/j.jacbts.2023.10.010