Hormonally induced azoospermia is an effective, reversible form of male contraception; however, some men treated with weekly im testosterone enanthate (TE) injections fail to become azoospermic. As weekly injections cause widely fluctuating and supraphysiological testosterone levels, we tested the hypothesis that more stable, physiological testosterone levels would consistently produce azoospermia. Using a depot testosterone formulation which provides stable, physiological range testosterone levels for up to 6 months, we studied nine men before and after insertion of six 200 mg testosterone implants under the abdominal wall skin and compared the results with 38 men treated in a previous study with weekly im injections of 200 mg TE. Testosterone implants suppressed sperm output to near-azoospermia between the second to fourth postimplant months returning to normal by the sixth postimplant month. The fall in sperm output at the first month was greater after testosterone implants than TE injections (58% vs. 17%, P = 0.011) but similar proportions of men became azoospermic (5/9 vs. 25/38) or severely oligozoospermic (< 1 million/ml; 9/9 vs. 37/38). Plasma testosterone and estradiol levels remained mostly within the eugonadal range after implants but were markedly supraphysiological during TE injections. Both treatments suppressed immunoreactive LH and FSH to undetectable levels by ultrasensitive fluoroimmunoassay. Sex hormone-binding globulin levels were decreased and PRL levels increased by TE injections but neither was changed by testosterone implants. Prostate-specific antigen demonstrated a small rise of marginal significance (P = 0.065) after testosterone implants. Fewer men experienced acne after implants (0/9 vs. 25/38, p = 0.0004). Therefore a depot testosterone preparation with quasi-zero-order release demonstrates higher dose efficiency with similar (but not uniform) efficacy at inducing azoospermia but may cause fewer androgenic side-effects than weekly TE injections.
PIP: In Sydney, Australia, researchers analyzed data on 9 healthy men aged 21-50 to determine the effects of 6 long acting depot testosterone (200 mg) implants under the abdominal wall on spermatogenesis. They also compared these data with retrospective data on 38 healthy men who had received weekly testosterone (200 mg) injections to determine whether steady-state testosterone levels within the physiological range might achieve azoospermia uniformly in fertile men. The implants dramatically decreased sperm output to near 0 levels between the 2nd and 4th month after implantation. By 6 months postimplant the sperm density had returned to normal. The injections produced similar reductions in sperm output, but the rate of decrease was significantly greater at the first month in men with the implants (58% vs. 17%; p = 0.011). Similar proportions of men in the implant group and the injection group had achieved azoospermia (56% vs. 66%) or severe oligospermia (1 million sperm/ml; 100% vs. 97%). Plasma testosterone and estradiol levels largely stayed within the eugonadal range after insertion of implants. They were considerably supraphysiological during testosterone injections, however. Both testosterone implants and testosterone injections inhibited immunoreactive luteinizing hormone and follicle stimulating hormone (p 0.05). Testosterone injections reduced sex hormone binding globulin levels but increased PRL levels (p 0.05). Testosterone implants increased prostate-specific antigen by about 20% (p = 0.065). Acne was more prevalent after injections than after implants (0/9 vs. 25/38; p = 0.0004). Both testosterone treatments had biochemical effects of similar magnitude. These findings suggest that the testosterone implants with quasi-zero-order release have a higher dose efficiency than the injections with similar efficacy at achieving azoospermia, but may result in fewer androgenic side effects than the injections.