FSH for the Treatment of Male Infertility

Abstract

Follicle-stimulating hormone (FSH) supports spermatogenesis acting via its receptor (FSHR), which activates trophic effects in gonadal Sertoli cells. These pathways are targeted by hormonal drugs used for clinical treatment of infertile men, mainly belonging to sub-groups defined as hypogonadotropic hypogonadism or idiopathic infertility. While, in the first case, fertility may be efficiently restored by specific treatments, such as pulsatile gonadotropin releasing hormone (GnRH) or choriogonadotropin (hCG) alone or in combination with FSH, less is known about the efficacy of FSH in supporting the treatment of male idiopathic infertility. This review focuses on the role of FSH in the clinical approach to male reproduction, addressing the state-of-the-art from the little data available and discussing the pharmacological evidence. New compounds, such as allosteric ligands, dually active, chimeric gonadotropins and immunoglobulins, may represent interesting avenues for future personalized, pharmacological approaches to male infertility.

PTPN5 promotes follicle‐stimulating hormone secretion through regulating intracellular calcium homeostasis

“…In men, it is used to promote testicular growth, spermatogenesis, and to treat oligoasthenozoospermia. [43][44][45] However, although it is common to use FSH and its biosimilar preparation to treat infertility, in practice, due to the short biological half-life of FSH, only 1 day, 46 some FSH preparations on the market require patients to receive subcutaneous injection every day, which brings a lot of inconvenience to patients' daily life. Although there are a small number of long-acting FSH agents on the market,…”

Recent advances in understanding gonadotropin signaling

“…Among these immunoglobulins, nanobodies against the FSHR, with small molecular weight and low predicted immunogenicity in humans, can inhibit cAMP production 129 . In conclusion, immunoglobulins are promising compounds for future therapeutic purposes, such as infertility 130 , 131 and cancer 132 treatment.…”

“…A number of activating and inactivating FSHR mutations have been described within the receptor regions encoded by exons 7 and 10 184 . Loss-of-function FSHR mutations may lead to pathological conditions, such as amenorrhea, in women 186 and may be linked to infertile or subfertile phenotypes in men 131 , 195 , 196 . FSHR mutations overall are rare, and several FSHR SNPs may have been characterized and analyzed for their associations with the gonadal response.…”

The Impact of Estrogen and Estrogen-Like Molecules in Neurogenesis and Neurodegeneration: Beneficial or Harmful?

“…Currently, the applications of sex hormone and gonadotropin therapies are rather broad and versatile, being used in several cases of female and male infertility ( Lunenfeld et al, 2019 ; Casarini et al, 2020 ). On the other hand, the most extensive uses of estrogens correspond to the modulation of reproductive capacity by hormonal contraceptives, and hormone replacement therapy (HRT), aiming to reverse the estrogen deficit during post-menopause.…”