Contraceptive Efficacy of a Depot Progestin and Androgen Combination in Men

Abstract

WHO studies provided proof of concept for hormonal male contraception using a prototype androgen-alone regimen. Combined testosterone plus progestin regimens offer more practical promise, but no contraceptive efficacy studies have been completed. The objective of this study was to establish the proof of principle for depot hormonal androgen/progestin combination as a male contraceptive. We performed a contraceptive efficacy study of 55 healthy men in stable fertile relationships seeking a change in contraceptive method. Testosterone (four 200-mg implants, every 4 or 6 months) and 300 mg depot medroxyprogesterone acetate, im, every 3 months were administered. Once sperm output was suppressed (<1 million/ml for 2 consecutive months), men entered a 12-month contraceptive efficacy period, ceasing other contraception. The main outcome measure was contraceptive failure (pregnancy) rate. No pregnancies occurred in 426 person-months (35.5 person-years; 95% confidence limits for contraceptive failure rate, 0-8%/annum), superior to the first year failure rate of condoms, the only reversible male method. Sperm density fell rapidly, so 94% of men entered the efficacy phase by 3 months, with only 2 of 55 (3.6%) men not sufficiently suppressed to enter efficacy. A few men treated with testosterone implants at 6-month intervals demonstrated androgen deficiency symptoms and/or escape of gonadotropin and spermatogenic suppression between months 5 and 6; after a protocol amendment, all men receiving testosterone implants at 4-month intervals avoided androgen deficiency or loss of gonadotropin and sperm output suppression. Recovery was complete (median, 3.6 months to sperm reappearance and 5.0 months to 20 million sperm/ml) in all but one man with an incidental testicular disorder. Discontinuations were for protocol-related reasons (n = 15) or altered personal circumstances (n = 12), but there were no serious adverse effects related to drug exposure. The first male contraceptive efficacy study using a prototype depot androgen/progestin combination demonstrates high contraceptive efficacy with satisfactory short-term safety and recovery of spermatogenesis. Further studies of purpose-developed products are required to extend the overall safety and efficacy experience with depot androgen/progestin combinations, the most promising approach to hormonal male contraception.

Empirical estimation of free testosterone from testosterone and sex hormone-binding globulin immunoassays

“…Hormone assays were performed in a single teaching hospital-based routine diagnostic endocrinology laboratory as described previously (20)(21)(22) using established commercial immunoassays routinely monitored by participation in external quality-control programs. Plasma TT and SHBG were measured by commercial immunoassays (Immulyte, Los Angeles, CA, USA).…”

Update on Male Hormonal Contraception: Is the Vasectomy in Jeopardy?

“…Subsequent studies in 55 men with testosterone implants and depot MPA showed suppression to o1 million sperms per ml in 94% of patients with no pregnancies in this suppression subgroup. 62 Median time to counts returning to 20 million sperms per ml was 5 months, but return to baseline numbers was much longer, suggesting an accumulation of drug in adipose tissue. These studies were conducted in the Asian population only.…”

Does ethnicity matter in male hormonal contraceptive efficacy?

“…[17][18][19] The effect of ethnicity is more evident on the degree of suppression when an androgen alone regime is used. Weekly injection of testosterone enanthate resulted in azoospermia in 91% of Chinese men compared to 60% of Non-Asian men mostly of European origin.…”

“…In particular, reversibility is not influenced by whether or not the regimen includes a progestin. Furthermore, non-recovery of sperm output has only been reported in two men after possible sterilizing processes such as epididymitis 18 and myotonic dystrophy 30 interceded. Nevertheless, these data provide the strongest assurance to date of highly predictable recovery of sperm output, and semen quality, following male hormonal contraceptive.…”

“…15,16 Since then three contraceptive efficacy studies have been conducted that confirmed the effectiveness of hormonal male contraception. [17][18][19] These have been supported by the Chinese Government, WHO and other non-government organizations. However, it should be noted that the majority of men participating in these more recent contraceptive efficacy studies originated from China.…”