Extra-Gonadal and Non-Canonical Effects of FSH in Males

Abstract

Recombinant follicle-stimulating hormone (FSH) is commonly used for the treatment of female infertility and is increasingly being used in males as well, as recommended by notable guidelines. FSH is composed of an α subunit, shared with other hormones, and a β subunit, which confers specificity of biological action by interacting with its surface receptor (FSHR), predominantly located in granulosa and Sertoli cells. However, FSHRs also exist in extra-gonadal tissues, indicating potential effects beyond male fertility. Emerging evidence suggests that FSH may have extra-gonadal effects, including on bone metabolism, where it appears to stimulate bone resorption by binding to specific receptors on osteoclasts. Additionally, higher FSH levels have been associated with worse metabolic and cardiovascular outcomes, suggesting a possible impact on the cardiovascular system. FSH has also been implicated in immune response modulation, as FSHRs are expressed on immune cells and may influence inflammatory response. Furthermore, there is growing interest in the role of FSH in prostate cancer progression. This paper aims to provide a comprehensive analysis of the literature on the extra-gonadal effects of FSH in men, with a focus on the often-conflicting results reported in this field. Despite the contradictory findings, the potential for future development in this area is substantial, and further research is needed to elucidate the mechanisms underlying these effects and their clinical implications.

Keywords: FSH; bone; cardiovascular system; extra-gonadal; immune system; infertility; metabolism; prostate cancer.

Figure 1

Extragonadal effects of FSH. Established and potential FSH effects on organs and systems. Abbreviations: TNF (tumor necrosis factor), IL (interleukin), UCP (uncoupling protein), IFN (interferon), RANK (Receptor activator of nuclear factor κ B), RANKL (Receptor activator of nuclear factor kappa-Β ligand), FSH (follicle-stimulating hormone). Figures made under Creative Commons License by using the Adobe Stock platform.