norethindrone-enanthate and Azoospermia

Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so 'add-back' therapy is needed.. To summarize all randomized controlled trials (RCTs) of male hormonal contraception.. In January and February 2012, we searched the computerized databases CENTRAL, MEDLINE, POPLINE, and LILACS. We also searched for recent trials in ClinicalTrials.gov and ICTRP. Previous searches included EMBASE. We wrote to authors of identified trials to seek additional unpublished or published trials.. We included all RCTs that compared a steroid hormone with another contraceptive. We excluded non-steroidal male contraceptives, such as gossypol. We included both placebo and active-regimen control groups.. The primary outcome measure was the absence of spermatozoa on semen examination, often called azoospermia. Data were insufficient to examine pregnancy rates and side effects.. We found 33 trials that met our inclusion criteria. The proportion of men who reportedly achieved azoospermia or had no detectable sperm varied widely. A few important differences emerged. 1) Levonorgestrel implants (160 μg daily) combined with injectable testosterone enanthate (TE) were more effective than levonorgestrel 125 µg daily combined with testosterone patches. 2) Levonorgestrel 500 μg daily improved the effectiveness of TE 100 mg injected weekly. 3) Levonorgestrel 250 μg daily improved the effectiveness of testosterone undecanoate (TU) 1000 mg injection plus TU 500 mg injected at 6 and 12 weeks. 4) Desogestrel 150 μg was less effective than desogestrel 300 μg (with testosterone pellets). 5) TU 500 mg was less likely to produce azoospermia than TU 1000 mg (with levonorgestrel implants). 6) Norethisterone enanthate 200 mg with TU 1000 mg led to more azoospermia when given every 8 weeks versus 12 weeks. 7) Four implants of 7-alpha-methyl-19-nortestosterone (MENT) were more effective than two MENT implants. We did not conduct any meta-analysis due to intervention differences.Several trials showed promising efficacy in percentages with azoospermia. Three examined desogestrel and testosterone preparations or etonogestrel and testosterone, and two examined levonorgestrel and testosterone.. No male hormonal contraceptive is ready for clinical use. Most trials were small exploratory studies. Their power to detect important differences was limited and their results imprecise. In addition, assessment of azoospermia can vary by sensitivity of the method used. Future trials need more attention to the methodological requirements for RCTs. More trials with adequate power would also be helpful.

Topics: Azoospermia; Contraception; Contraceptive Agents, Male; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Synthetic; Desogestrel; Drug Implants; Humans; Levonorgestrel; Male; Norethindrone; Oligospermia; Randomized Controlled Trials as Topic; Testosterone

The principle of male hormonal contraception is based on the suppression of LH and FSH and the replacement of testosterone to maintain androgenicity. The goal can best be achieved by testosterone alone or by testosterone in combination with a gestagen. The five clinical trials using pregnancy rates as end points and the one trial performed by the pharmaceutical industry are reviewed here. An ongoing large multicenter trial launched by WHO and the US CONRAD Programme will decide about the future of male hormonal contraception.

Topics: Azoospermia; Clinical Trials as Topic; Contraception; Contraceptive Agents, Male; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Medroxyprogesterone Acetate; Norethindrone; Pregnancy; Pregnancy Rate; Progesterone Congeners; Progestins; Testosterone