This Article Full Text Full Text (PDF) All Versions of this Article: 28/4/548    most recent Author Manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Amory, J. K. Articles by Bremner, W. J. Search for Related Content PubMed PubMed Citation Articles by Amory, J. K. Articles by Bremner, W. J.

Elevated End-of-Treatment Serum INSL3 Is Associated With Failure to Completely Suppress Spermatogenesis in Men Receiving Male Hormonal Contraception

BRADLEY D. ANAWALT^*,

ANDREA D. COVIELLO

ALVIN M. MATSUMOTO^*,,

From the ^* Department of Medicine, University of Washington, Seattle, Washington; the Department of Medicine, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington; the Department of Medicine, Boston University, Boston, Massachusetts; and the Department of Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.

Correspondence to: Dr John K Amory, University of Washington, Box 356429, 1959 NE Pacific, Seattle, WA 98195 (e-mail: jamory{at}u.washington.edu).

The administration of testosterone plus a progestogen functions as a male contraceptive by inhibiting the release of pituitary gonadotropins. After 3 to 4 months of treatment, most men are azoospermic or severely oligospermic (1 million sperm/mL). However, 10% to 20% of men have persistent sperm production despite profound gonadotropin suppression. Since insulin-like factor 3 (INSL3) has been shown to prevent germ cell apoptosis in mice, we hypothesized that INSL3 might be higher in men with persistent spermatogenesis during treatment with male hormonal contraceptives. In a retrospective analysis, we measured serum INSL3 in 107 men from 3 recent male hormonal contraceptive studies and determined the relationship between suppression of spermatogenesis and serum INSL3. At the end of treatment 63 men (59%) were azoospermic and 44 men (41%) had detectable sperm in their ejaculates. Baseline INSL3 did not predict azoospermia; however, end of treatment serum INSL3 was significantly higher in nonazoospermic men compared with those with azoospermia (median [interquartile range]: 95 [73–127] pg/mL vs 80 [67–101] pg/mL; P = .03). Furthermore, serum INSL3 was positively correlated with sperm concentration (r = .25; P = .009) at the end of treatment and was significantly associated with nonazoospermia by multivariate logistic regression (P = .03). After 6 months of treatment with a hormonal male contraceptive regimen, higher serum INSL3 concentrations were associated with persistent sperm production. INSL3 may play a role in preventing complete suppression of spermatogenesis in some men on hormonal contraceptive regimens. This finding suggests that INSL3 may be a potential target for male contraceptive development.

     Key words: Azoospermia, oligospermia

This article has been cited by other articles:

				R. A. L. Bayne, T. Forster, S. T. G. Burgess, M. Craigon, M. J. Walton, D. T. Baird, P. Ghazal, and R. A. Anderson Molecular Profiling of the Human Testis Reveals Stringent Pathway-Specific Regulation of RNA Expression Following Gonadotropin Suppression and Progestogen Treatment J Androl, July 1, 2008; 29(4): 389 - 403. [Abstract] [Full Text] [PDF]

				S. T. Page, J. K. Amory, and W. J. Bremner Advances in Male Contraception Endocr. Rev., June 1, 2008; 29(4): 465 - 493. [Abstract] [Full Text] [PDF]

				S. T. Page, T. F. Kalhorn, W. J. Bremner, B. D. Anawalt, A. M. Matsumoto, and J. K. Amory Intratesticular Androgens and Spermatogenesis During Severe Gonadotropin Suppression Induced by Male Hormonal Contraceptive Treatment J Androl, September 1, 2007; 28(5): 734 - 741. [Abstract] [Full Text] [PDF]