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

Wilhelmina C M Duivenvoorden; David Margel; Vishal Subramony Gayathri; Emmanuelle Duceppe; Sadiya Yousef; Magda Naeim; Mohammad Khajehei; Sarah Hopmans; Snezana Popovic; Yaara Ber; Diane Heels-Ansdell; Philip J Devereaux; Jehonathan H Pinthus

doi:10.1016/j.jacbts.2023.10.010

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

JACC Basic Transl Sci. 2023 Dec 20;9(3):364-379. doi: 10.1016/j.jacbts.2023.10.010. eCollection 2024 Mar.

Authors

Wilhelmina C M Duivenvoorden^{1

2}, David Margel^{3

4}, Vishal Subramony Gayathri², Emmanuelle Duceppe^{5

6}, Sadiya Yousef², Magda Naeim², Mohammad Khajehei¹, Sarah Hopmans¹, Snezana Popovic⁷, Yaara Ber³, Diane Heels-Ansdell⁸, Philip J Devereaux^{5

6}, Jehonathan H Pinthus^{1

2}

Affiliations

¹ Department of Surgery, Division of Urology, Faculty of Medicine, McMaster University, Hamilton, Ontario, Canada.
² Research Institute of St. Joe's Hamilton, Hamilton, Ontario, Canada.
³ Department of Urology, Rabin Medical Center, Petach Tikva, Israel.
⁴ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁵ Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
⁶ Department of Medicine, Centre Hospitalier de l'Universite de Montréal, Montréal, Québec, Canada.
⁷ Department of Pathology and Molecular Medicine, Faculty of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁸ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

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.

Keywords: GnRH-antagonist; androgen-deprivation therapy; cardiovascular disease; follicle-stimulating hormone; prostate cancer.