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,
P. MICHAEL CONN and
CARL M. HERBERT
Departments of Medicine Vanderbilt University School of Medicine Nashville, Tennessee 37232
Obstetrics and Gynecology Vanderbilt University School of Medicine Nashville, Tennessee 37232
Pathology Vanderbilt University School of Medicine Nashville, Tennessee 37232
Department of Pharmacology, University of Iowa College of Medici CJ, Iowa City, Iowa 52242
The Salk Institute La Jolla, California 92037
Address all correspondence and requests for reprints to: Spyros N. Pavlou, M.D., Division of Endocrinology, AA-4206 MCN, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
GnRH antagonists suppress pituitary and gonadal function by competing with endogenous GnRH for binding to receptors on pituitary gonadotrophs. We studied the effects of GnRH antagonist administration to men in a protocol simulating a likely male contraceptive regimen combined with a low dose of testosterone. The GnRH antagonist Nal-Glu was given daily (10 mg, sc) for 20 weeks to eight normal men, and a low dose of testosterone enanthate (25 mg, sc) was given every week. Sperm counts started declining during week 4, and complete azoospermia was reached within 6–12 weeks in six of the eight subjects. Subjects 7 and 8, whose sperm counts and serum gonadotropin levels were not suppressed after 10 weeks, were given 20 mg Nal-Glu starting at week 10. One became azoospermic at week 16, while the other's total sperm counts continued declining and reached a nadir of 1.4 million by week 20. Sperm motility and viability in this subject were completely suppressed after week 14. Sperm counts returned to baseline levels 12–14 weeks after the end of Nal-Glu administration. The mean serum LH level of the first six subjects decreased from 3 ± 03. U/L at baseline to less than 0.1 U/L until week 20, and then levels returned to baseline. FSH levels similarly decreased from a combined mean of 3.6 ± 0.9 U/L at baseline to below 0.3 U/L after 4 weeks of Nal-Glu administration. Serum mean testosterone levels between weekly injections of testosterone enanthate ranged from 27.4 ± 5.9 to 4.8 ± 1.4 nmol/L, but remained in the hypogonadal range (<10 nmol/L) for 4 of the 7 days. None of the subjects, however, complained of decreased libido or potency, as assessed by a questionnaire. No systemic or significant local side-effects were observed, other than a minimal reaction at the injection site. These data suggest that complete sustained azoospermia can be achieved in man, without loss of libido, by chronic administration of a GnRH antagonist plus testosterone.
* This work was supported by the Contraceptive Research and Development Program (CONRAD, CSA–87–013), Eastern Virginia Medical School, under a Cooperative Agreement with the United States Agency for International Development (AID, DPE–3044–A–00–6063– 00). The views expressed by the authors do not necessarily reflect the view of AID or CONRAD. Supported also by the following grants and grants-in-aid: Clinical Research Center Grant-in-Aid 5–M01–RR–95, Population Center Grant-in-Aid HD–05797, DK–26657, NIH Grant HD–13527 (to W.W.V. and J.E.R.), and HD–19899 (to P.M.C.). The Nal-Glu was synthesized at The Salk Institute under Contract N01–HD–7–2907 and made available by the Contraceptive Development Branch, Center for Population Research, NICHHD. Research was conducted in part by the Clayton Foundation for Research, California division.
Clayton Foundation Investigator.
Received January 14, 1991.
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