Isolated follicle-stimulating hormone (FSH) deficiency in a young man with normal virilization who did not have mutations in the FSHβ gene

Toward a pharmacogenetic approach to male infertility: polymorphism of follicle-stimulating hormone beta-subunit promoter

“…Therefore, our findings confirmed the association between FSHB À211 carrier status and FSH levels and better elucidated the possible contribution of genetically determined abnormalities in FSH secretion to specific forms of male infertility. In this light, we can now, e.g., better understand an earlier case report describing a 19-year-old male TT homozygote for the FSHB À211 polymorphism with normal virilization, azoospermia, and isolated FSH deficiency (23).…”

“…Genotype frequency, GG/GT/TT Allele frequency, G/T response to the reduced negative feedback exerted by inhibin B as a consequence of the primary testicular damage and for the lack on FSH increase after GnRH stimulation test (23). Such a condition could therefore be included in the recent definition of ''functional hypogonadotropic hypogonadism,'' distinct from the classic forms of hypogonadotropic and hypergonadotropic hypogonadism (spermatogenic damage, low-normal testosterone levels associated with low or high gonadotropin levels, respectively), because gonadotropins levels are in the low-normal range but inadequate for testicular stimulation (11).…”

Isolated follicle-stimulating hormone (FSH) deficiency without mutation of the FSHβ gene and successful treatment with human menopausal gonadotropin

“…Mantovani et al reported an infertile male with isolated FSH deficiency but with no evidence of mutations; however, they could not perform testicular biopsy (10). Here, we report a case of isolated FSH deficiency without mutations in the FSHb gene, as confirmed by immunohistochemistry.…”

Mechanisms of FSH synthesis: what we know, what we don't, and why you should care

“…However, men with inactivating mutations in the FSHB subunit gene, who are unable to produce the dimeric ligand, are azoospermic (8)(9)(10)(11). Other cases of idiopathic isolated FSH deficiency have also been reported and are similarly associated with azoospermia or oligoteratozoospermia and infertility (12,13). In contrast, male Fshb-deficient mice have similar phenotypes to Fshr knockout animals and are fertile (4).…”

“…Though rare, clinical cases have been reported of isolated FSH deficiency without associated mutations in the FSHB coding sequence (12,13). These idiopathic cases and others like them afford a potential opportunity to discover novel transcriptional regulators and/or cis-regulatory elements.…”