Isolated follicle-stimulating hormone (FSH) deficiency in two infertile men without FSH ß gene mutation: Case report and literature review.

OBJECTIVE: Congenital FSH deficiency is an exceptional cause of male infertility most often attributed to FSH ß gene mutations. The few published cases report azoospermia, severe testicular hypotrophy and normal testosterone levels associated with normal virilization. We report the exploration of two young men aged 26 and 27 years with severe sperm abnormalities, moderate testicular hypotrophy and isolated FSH deficiency. METHODS: Several FSH, LH, total testosterone and inhibin B assays and FSH ß gene sequencing were performed. RESULTS: FSH was almost undetectable at baseline and poorly responsive to GnRH test, whereas LH was normal at baseline and increased after GnRH test. Testosterone levels were within the adult range, while inhibin B levels were upper-normal to high. No FSH ß gene mutations were found. Exogenous FSH treatment was followed by spontaneous pregnancy in one case and required intra-cytoplasmic sperm injection (ICSI) in the other. CONCLUSIONS: The paradoxical high levels of inhibin B reflect the presence of functional Sertoli cells and may explain the isolated FSH deficiency. An intra-gonadal factor stimulating inhibin B secretion is discussed.

Which origin for polycystic ovaries syndrome: Genetic, environmental or both?

Polycystic ovaries syndrome (PCOS), the most common female endocrine disorder, affects 7-10% of women of childbearing age. It includes ovarian hyperandrogenism, impaired follicular maturation, anovulation and subfertility. Insulin resistance, although present in most cases, is not necessary for diagnosis. It increases hyperandrogenism and long-term metabolic, cardiovascular and oncological risks. The origin of hyperandrogenism and hyperinsulinemia has a genetic component, as demonstrated by familial aggregation studies and recent identification of associated genomic variants, conferring a particular susceptibility to the syndrome. However, experimental and epidemiological evidences also support a developmental origin via a deleterious foetal environment, concerning the endocrine status (foetal hyperandrogenism), the nutritional level (intrauterine growth retardation), or the toxicological exposure (endocrine disruptors). Epigenetic changes recently reported in the literature as associated with PCOS, enhance this hypothesis of foetal reprogramming of the future adult ovarian function by environmental factors. Better characterisation of these genetic, epigenetic, or environmental factors, could lead to earlier prevention and more efficient treatments.