Endocrine Abstracts

Background: Follicle stimulating hormone (FSH), a dimeric glycoprotein hormone, stimulates Sertoli cell proliferation and spermatogenesis in males. Azoospermia is defined as the absence of sperm in the ejaculate. The majority of patients with non-obstructive azoospermia have high FSH levels. Isolated FSH deficiency has been reported in a few patients.

Case Presentation: A 22-yr-old, 172-cm-tall male presented with azoospermia. He was born at full term with normal delivery of non-consanguineous parents. He had normal pubertal development with normal erections and potency. Upon physical examination he had normal virilization, normal sense of smell and no gynecomastia. His testes were both palpable in the scrotum measuring 25ml. No sperm was observed in the semen analysis twice. Semen fructose levels were normal. Urine analysis for retrograde ejaculation and testicular ultrasound revealed no abnormalities. His chromosomal karyotype was 46, XY. His testosterone, luteinizing hormone (LH), inhibin B (INHB) and anti-mullerian hormone (AMH) levels were normal, whereas FSH was low. Hypothalamic-pituitary magnetic resonance imaging (MRI) demonstrated no abnormalities. FSH levels remained low after intravenous injection of 100μg of gonadotropin-releasing hormone (GnRH), whereas LH levels rose. Sequencing of the β-subunit of FSH (FSHβ) gene did not reveal any mutation.

Discussion: Reports on isolated FSH deficiency are very rare with a prevalence of 0.89% in a retrospective study. The first observations of isolated FSH deficiency in males were described in 1998. Since then ten more case reports have been published, half of which were caused by an inactivating mutation of FSHβ gene. The patients presented with azoospermia, testicular hypotrophy, but with normal levels of testosterone and virilization. It appears that in cases of no FSHβ gene mutation there is milder phenotype, with oligo-astheno-teratospermia and even normal testicular volume. In cases where testicular biopsy was performed, spermatogenesis arrest, Sertoli cell hypoplasia and Leydig cell hyperplasia were reported. Hypothalamic-pituitary MRI and karyotype were normal. Remarkably, despite low INHB and AMH levels in patients with FSHβ gene mutations, cases without the mutation exhibited normal levels. Exogenous FSH led to an increase in testicular volume, spermatogenesis and in some cases in successful pregnancies.

Conclusion: Isolated FSH deficiency represents a rare form of male infertility which may be restored and therefore carries a high diagnostic value.