Suppression of spermatogenesis in man induced by Nal-Glu gonadotropin releasing hormone antagonist and testosterone enanthate (TE) is maintained by TE alone.
GnRH antagonists plus testosterone (T) suppress LH and FSH levels and inhibit spermatogenesis to azoospermia or severe oligozoospermia. High-dose T treatment alone has been shown to be an effective male contraceptive (contraceptive efficacy rate of 1.4 per 100 person yr). Combined GnRH antagonist and T induces azoospermia more rapidly and at a higher incidence than T alone; this combination has therefore been proposed as a prototype male contraceptive. However, because GnRH antagonists are expensive to synthesize and difficult to deliver, it would be desirable to rapidly suppress sperm counts to low levels with GnRH antagonist plus T and maintain azoospermia or severe oligozoospermia with T alone. In this study, 15 healthy men (age 21-41 yr) with normal semen analyses were treated with T enanthate (TE) 100 mg im/week plus 10 mg Nal-Glu GnRH antagonist sc daily for 12 weeks to induce azoospermia or severe oligozoospermia. At 12-16 weeks, 10 of 15 subjects had zero sperm counts, and 14 of 15 had sperm counts less than 3 x 10(6)/mL. The 14 who were suppressed on combined treatment were maintained on TE alone (100 mg/week im) for an additional 20 weeks. Thirteen of 14 subjects in the TE alone phase had sperm counts maintained at less than 3 x 10(6)/mL for 20 weeks. Ten remained persistently azoospermic or had sperm concentration of 0.1 x 10(6)/mL once during maintenance. Mean LH and FSH levels in the subjects were suppressed to 0.4+/-0.2 IU/L and 0.5+/-0.2 IU/L in the induction phase, which was maintained in the maintenance phase. The 1 subject who failed to suppress sperm counts during induction had serum LH and FSH reduced to 0.3 and 0.5 IU/L, respectively. The subject who failed to maintenance had LH and FSH suppressed to 1.0 and 0.2 IU/L, respectively, during the induction phase but these rose to 1.6 and 2.1 IU/L, respectively, during maintenance. Failure to suppress or maintain low sperm counts may be related to incomplete suppression of serum LH and FSH levels. We conclude that sperm counts suppressed with GnRH antagonist plus T can be maintained with relatively low dose TE treatment alone. This concept should be explored further in the development of effective, safe, and affordable hormonal male contraceptives.
Swerdloff
R S
RS
Department of Medicine, Harbor-University of California, Los Angeles Medical Center, Torrance 90509, USA. Swerdloff@gcrc.humc.edu
Bagatell
C J
CJ
Wang
C
C
Anawalt
B D
BD
Berman
N
N
Steiner
B
B
Bremner
W J
WJ
D000328:Adult; D003272:Contraceptive Agents, Male / Q000009:adverse effects / Q000494:pharmacology*; D004151:Dipeptides / Q000009:adverse effects / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007989:Libido / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D012725:Sexual Behavior / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013739:Testosterone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology
C102118:2-naphthylalanyl-glutamic acid; D003272:Contraceptive Agents, Male; D004151:Dipeptides; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C004648:testosterone enanthate; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone