Journal of Clinical Endocrinology & Metabolism. First published July 19, 2005 as doi:10.1210/jc.2005-0639
Effects of testosterone and levonorgestrel combined with a 5 alpha reductase inhibitor or GnRH antagonist on spermatogenesis and intratesticular steroid levels in normal men. Kati L. Matthiesson1, Peter G. Stanton1, Liza O’Donnell1, Sarah J. Meachem1, John K. Amory2, Richard Berger2, William J. Bremner2 and Robert I. McLachlan1
1
Prince Henry's Institute of Medical Research & Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, Clayton, Victoria, 3168, Australia and 2The
Center for Research in Reproduction and Contraception, University of Washington, Seattle, Washington, 98195, USA.
Short title:
Spermatogenic effects of gonadotropin and androgen withdrawal.
Keywords:
spermatogenesis, FSH, LH, testosterone
Address for correspondence: Kati Matthiesson, MBBS, FRACP Prince Henry's Institute of Medical Research PO Box 5152, Clayton, Victoria, 3168 Australia Ph. 61-3-9594-3004 Fax 61-3-9594-3558 Email:
[email protected]
This study was supported by the NICHD, Male Contraception Research Center Grant 654 HD42454 and by the Australian
NHMRC, Program Grant #241000 and Post Graduate
Scholarship Grant ID 241031 (KLM).
Copyright (C) 2005 by The Endocrine Society
-2ABSTRACT Context. Combination of a GnRH antagonist (acyline), type I and II, 5α reductase inhibitor (dutasteride) or levonorgestrel (LNG) with testosterone (T) treatment may augment the suppression of spermatogenesis and intratesticular (iT) steroids. Objective. To assess effects of combined hormonal contraceptive regimens on germ cell populations and iT steroids. Design, setting, and participants. Twenty-nine normal health men enrolled in this prospective, randomized, fourteen-week study at the University of Washington. Intervention(s). Twenty-two men (n=5-6/group) received 8 weeks of T enanthate (TE, 100 mg IM wkly) combined with (i) LNG 125mcg orally daily, (ii) LNG 125 mcg + dutasteride 0.5mg orally daily, (iii) acyline 300mcg/kg sc 2 weekly, (iv) LNG 125 mcg orally daily + acyline 300mcg/kg sc 2 weekly. Subjects then underwent a vasectomy and testicular biopsy. Control men (n=7) proceeded directly to surgery. Main Outcome Measure(s). Germ cells and iT steroids (T, dihydrotestosterone (DHT), 3α and β androstanediol (Adiol)) and estradiol (E2)). Results. High iT levels of all androgens (6-123 fold serum) and E2 (407 fold serum) were found in control men. iTT (1.9-2.6% control, p
