ESTABLISHING THE MINIMUM EFFECTIVE DOSE AND ADDITIVE EFFECTS OF DEPOTPROGESTIN IN SUPPRESSION OF HUMAN SPERMATOGENESIS BY A TESTOSTERONE DEPOT

Hormonally induced azoospermia induced by weekly im injections of test osterone enanthate provides effective and reversible male contraceptio n, but more practical regimens are needed. Given our previous findings that six 200-mg pellets implanted subdermally produced more stable, p hysiological T levels and reduced the delivered T dose by more than 50 % while maintaining equally effective suppression of sperm output with fewer metabolic side-effects than weekly 200-mg testosterone enanthat e injections, we sought in this study to determine I)whether further d ose-sparing could be achieved by lower testosterone doses while mainta ining efficacy and 2) the efficacy of adding a depot progestin to a su boptimally suppressive depot testosterone dose as a model depot proges tin/androgen combination male contraceptive. Healthy volunteers were r andomized into groups (n = 10) who received either of two lower T dose s (two or four 200-mg T pellets) or four 200-mg T pellets plus a singl e im injection of 300 mg depot medroxyprogesterone acetate (DMPA). Two T pellets (400 mg, 3 mg/day) had a negligible effect on sperm output. Four T pellets (800 mg, 6 mg/day) suppressed sperm output between the second to fourth postimplant months; output returned to normal by the seventh postimplant month, although only 4 of 10 men became azoosperm ic or severely oligozoospermic (<3 mol/L/mL). The addition of a depot progestin markedly increased the extent, but not the rate, of sperm ou tput suppression, with 9 of 10 becoming azoospermic and 10 of 10 becom ing severely oligozoospermic. There were no serious adverse effects du ring the study. Plasma total and free testosterone levels remained wit hin the eugonadal range at all times with each treatment. Plasma epite stosterone was suppressed by all 3 regimens, consistent with a dose-de pendent inhibition of endogenous Leydig cell steroidogenesis. Plasma L H and FSH measured by a two-site immunoassay were suppressed in a dose -dependent fashion by T and further suppressed by the addition of DMPA . Sex hormone-binding globulin levels were decreased by DMPA, but not by either T dose. Prostate-specific antigen and lipids (total, low or high density lipoprotein cholesterol, and triglycerides) were not sign ificantly changed in any group. Thus, a depot testosterone preparation with zero order release must be delivered at between 6-9 mg/day to pr ovide optimal (but not uniform) efficacy at inducing azoospermia. The addition of a single depot dose of a progestin to a suboptimal testost erone dose (6 mg/day) markedly enhances the extent, but not the rate, of spermatogenic suppression, with negligible biochemical androgenic s ide-effects. These findings provide a basis for the use of a progestin /androgen combination depot for hormonal male contraception.