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 contrac eptive (contraceptive efficacy rate of 1.4 per 100 person yr). Combine d GnRH antagonist and T induces azoospermia more rapidly and at a high er incidence than T alone; this combination has therefore been propose d as a prototype male contraceptive. However, because GnRH antagonists are expensive to synthesize and difficult to deliver, it would be des irable to rapidly suppress sperm counts to low levels with GnRH antago nist 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 sp erm 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 alo ne (100 mg/week im) for an additional 20 weeks. Thirteen of 14 subject s in the TE alone phase had sperm counts maintained at less than 3 X 1 0(6)/mL for 20 weeks. Ten remained persistently azoospermic or had spe rm concentration of 0.1 x 10(6)/mL once during maintenance. Mean LH an d 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 ma intenance phase. The 1 subject who failed to suppress sperm counts dur ing induction had serum LH and FSH reduced to 0.3 and 0.5 IU/L, respec tively. The subject who failed to maintenance had LH and FSH suppresse d to 1.0 and 0.2 IU/L, respectively, during the induction phase but th ese rose to 1.6 and 2.1 IU/L, respectively, during maintenance. Failur e to suppress or maintain low sperm counts may be related to incomplet e suppression of serum LH and FSH levels. We conclude that sperm count s suppressed with GnRH antagonist plus T can be maintained with relati vely low dose TE treatment alone. This concept should be explored furt her in the development of effective, safe, and affordable hormonal mal e contraceptives.