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COMPARATIVE STUDY
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
The pituitary-testicular axis in Klinefelter's syndrome and in oligo-azoospermic patients with and without deletions of the Y chromosome long arm.
Clinical Endocrinology 2003 August
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.
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.
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