The pituitary-testicular axis in Klinefelter's syndrome and in oligo-azoospermic patients with and without deletions of the Y chromosome long arm

• Published in: Clinical endocrinology (Oxford) Vol. 59; no. 2; pp. 214 - 222
• Main Authors: Tomasi, Paolo A., Oates, Robert, Brown, Laura, Delitala, Giuseppe, Page, David C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2003; Blackwell; Wiley Subscription Services, Inc
• Subjects: Analysis of Variance; Biological and medical sciences; Case-Control Studies; Chi-Square Distribution; Chromosome aberrations; Chromosomes, Human, Y; Endocrinopathies; Estradiol - blood; Follicle Stimulating Hormone - blood; Gene Deletion; Gynecology. Andrology. Obstetrics; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Inhibins - blood; Klinefelter Syndrome - complications; Klinefelter Syndrome - genetics; Klinefelter Syndrome - metabolism; Luteinizing Hormone - blood; Male; Male and female genital diseases. Gonadal dysgenesis. Hermaphroditism. Sex hormones resistance; Medical genetics; Medical sciences; Multivariate Analysis; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oligospermia - etiology; Oligospermia - genetics; Oligospermia - metabolism; Pituitary Gland - metabolism; Testis - metabolism; Testosterone - blood; Chromosomal aberration; Endocrinopathy; Human; Klinefelter syndrome; Endocrine gland; Long arm; Hypothalamohypophysotesticular axis; Aneuploidy; Sexual differentiation disorder; Supernumerary X chromosome; Y-Chromosome; Male genital system; Oligospermia; Azoospermia; Malformation; Deletion; Abnormal chromosome; Male sterility; Male genital diseases
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1046/j.1365-2265.2003.01828.x

Summary objective The most frequent known genetic causes of severe oligospermia (< 5 million sperm/ml) or azoospermia in men are Klinefelter's syndrome (KS), and deletions in the Y chromosome long arm (Yq). We aimed to compare the function of the pituitary–testicular axis in patients with severe oligospermia or azoospermia, idiopathic or associated with Y chromosome deletions or Klinefelter's syndrome (KS) and in control subjects. patients We studied 47 men with idiopathic oligo‐azoospermia, 42 with Yq deletions (27 AZFc, 13 AZFb and two AZFa) and oligo‐azoospermia, 14 with KS and 39 control subjects (total 143). measurements We analysed levels of FSH, inhibin‐B, LH, free testosterone and oestradiol in all subjects, and we calculated indexes based on those hormones. results Inhibin‐B levels were indistinguishable between patients with idiopathic and Y deletion‐associated oligo‐azoospermia, lowest in the Klinefelter's patients and highest in controls. FSH levels followed the reverse pattern: indistinguishable between patients with idiopathic and deletion‐associated oligo‐azoospermia, highest in Klinefelter's patients and lowest in controls. Oestradiol, free testosterone and the derived indeces were not different in subjects with Yq deletions compared to those with idiopathic oligo‐azoospermia. Among the Yq‐deleted patients, no measured or derived parameter differed between the subjects with AZFc deletion and those with AZFb deletion. When non‐KS oligo‐azoospermic patients were classified according to histology [Sertoli cell‐only (SCO), n = 18 or non‐Sertoli cell only (non‐SCO), n= 18] and compared to KS patients, the hormonal pattern did not differ between SCO and non‐SCO subjects, but levels in KS patients were significantly different for FSH, inhibin‐B and the FSH/inhibin‐B ratio. KS patients not only had lower inhibin‐B than SCO and non‐SCO oligo‐azoospermic men, but also higher FSH levels for any given inhibin‐B concentration. conclusion Our data show that Y‐deleted patients do not have a lesser impairment of Sertoli cell function than patients with idiopathic oligo‐azoospermia, and support the concept that the main determinant of inhibin‐B production is the germ cell mass. Also, our results suggest that one or more other factors, apart from inhibin‐B, may contribute to increased pituitary secretion of FSH in KS patients.