Testosterone Undecanoate Maintains Spermatogenic Suppression Induced by Cyproterone Acetate Plus Testosterone Undecanoate in Normal Men

University of Washington Seattle, Seattle, Washington, United States
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 01/2004; 88(12):5818-26. DOI: 10.1210/jc.2003-030574
Source: PubMed


In this study we evaluated whether testosterone undecanoate (TU), alone or combined with low dose cyproterone acetate (CPA), can maintain spermatogenic suppression induced by higher doses of CPA plus TU. Twenty-four men received for 12 wk 20 mg/d CPA plus 1000 mg/6 wk TU and then 1000 mg/8 wk TU plus 20 mg/d CPA (n = 8), 2 mg/d CPA (n = 8), or plus placebo (n = 8) for 32 wk. Blood samples, physical examinations, hormones, chemistry, hematology, semen analysis, and sexual/behavioral assessments were performed throughout the study. Sperm counts decreased to less than 1 million/ml in all subjects by wk 12, and 54% of them achieved azoospermia. Suppression of sperm counts was maintained until wk 44. Serum LH and FSH levels were suppressed by wk 12 of hormone administration and remained suppressed until wk 44. No significant changes in any biochemical parameters were detected at wk 44 in any group. There was a slight increase in total prostate volume to within the normal range at wk 44 that returned to baseline 1 yr after stopping hormone administration. In conclusion, TU alone or combined with lower doses of CPA maintains sperm suppression induced by higher dose CPA plus TU for 32 wk. This prototype regimen represents a promising male contraceptive regimen.

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    • "Of the various approaches tried for the purpose, testosterone alone was found to be effective in achieving azoospermia [2] [3] [4] [5], but due to the lack of high efficacy combined with significant side effects [6] [7], alternate protocols using combinations of testosterone and progestins are preferred. These include testosterone plus progestins such as medroxyprogesterone acetate [8], cyproterone acetate [9], desogestrel [10], levonorgestrel [11] and norethisterone enanthate [12]. These combinations have been shown to be highly effective in terms of sperm suppression and do not induce any major changes in clinical and laboratory parameters, thus promising to be safe for long-term use [13]. "
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    ABSTRACT: The potential of using dienogest [DNG, 40 mg/kg body weight (bw)] plus testosterone undecanoate (TU, 25 mg/kg bw) in rats for development of a once-a-month male hormonal contraceptive has been reported earlier in our laboratories. In the present study, we report a separate efficacy evaluation of the same combination, DNG (40 mg/kg bw) and TU (25 mg/kg bw) in which interval of drug administration has been extended further to 45 and 60 days instead of every 30 days. Complete sperm suppression was observed in rats sacrificed either 60 or 90 days after DNG+TU administration, for two injections at 45-day interval. The neutral α-glucosidase activity in these treated rats remained in the normal range. Germ cell loss due to apoptosis was frequently observed both after 60 or 90 days of combination treatment. Significant decline in serum gonadotropin and testosterone, both serum and intratesticular levels, were observed in the treated rats. Following stoppage of treatment (given at 45-day interval) after two (0 and 45 days) or three injections (0, 45 and 90 days), complete restoration of spermatogenesis was observed by 120 and 165 days, respectively. The sperm suppression, however, could not be sustained when the period of combined drug administration was extended from every 45 to 60 days. Dienogest plus testosterone undecanoate in the above doses retained contraceptive effectiveness when administered every 45 days but not 60 days. The spermatogenic arrest was completely reversible once drug treatment is stopped. The dose and the frequency of intervention can be extrapolated in future clinical trials.
    Full-text · Article · Jun 2011 · Contraception
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    • "In Germany, at least 20% of volunteers did not reach undetectable LH and FSH levels following injections of TU 1000 mg given at 6-week intervals (von Eckardstein et al, 2003). In Italian men, this application scheme was sufficient to suppress LH and FSH in all volunteers, and only prolongation of injection intervals led to a rebound (Meriggiola et al, 2003). Our data suggest that differences in body shape and composition could contribute to such differences. "
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    ABSTRACT: Interindividual differences in gonadotropin suppression achieved by short- and long-acting intramuscular testosterone (T) preparations were studied to detect factors hindering complete suppression of gonadotropins as the prerequisites for effective male contraception. Forty healthy men received a single injection of T propionate; 4 weeks later they received 2 injections of 1000 mg of T undecanoate (TU) given 6 weeks apart. Following TU, declines of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were consistent in 17.5% and almost absent in 25% of men. Men showing the most rapid and consistent declines in LH and FSH levels received a slightly higher dose per body weight of TU (13.1 +/- 0.6 vs 11.3 +/- 0.6 mg/kg; P = NS) and reached higher maximal concentrations of total T (40 +/- 4.8 vs 18.4 +/- 2.4 nmol/L; P < .001) and free T as well as estradiol. Men with high fat mass (mean +/- SEM, 10.3 +/- 1.5 vs 23.2 +/- 6.4 kg) had a delayed increase in T levels and an impaired relative decline in LH (12 +/- 2% vs 53 +/- 10%) and FSH (17 +/- 6%. vs 70 +/- 25%) levels within the first 2 weeks after the first TU injection. We conclude that overweight reduces the chance of rapid and profound gonadotropin suppression during treatment with TU. Body weight needs to be considered to avoid failure of hormonal male contraception.
    Full-text · Article · Apr 2009 · Journal of Andrology
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    • "On the final visit to the clinic (on average, 72 weeks after the initiation of the study), all participants of the TXT group who completed the treatment (n = 44) filled in the Final Treatment questionnaire (FTA). For the purposes of this instrument, the investigator cited the time needed to achieve sperm suppression (<1 × 10 6 /ml) or the recovery of the sperm count as based on the results of their previous study of a similar combination of hormones (12 or 18 weeks respectively) (Meriggiola et al., 2003b). The questionnaires (BMB, TMB, RMB and FTA) were developed specifically for this study and included a selection of questions taken from other questionnaires designed for different purposes (Reynolds et al., 1988; O&apos;Leary et al., 1995; Corty et al., 1996; Feiger et al., 1996; Clayton et al., 1997; Derogatis, 1997; Rosen, 1998). "
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    ABSTRACT: We assessed attitudes towards and acceptability of male hormonal contraception among volunteers participating in a clinical trial of a prototype regimen, consisting of progestin and testosterone injections. After completing screening, eligible men were randomly assigned to the no-treatment group (n = 40) or to receive injections of norethisterone enanthate and testosterone undecanoate or placebo at different intervals (n = 50) according to a blocked randomization list. They underwent self-administered questionnaires. The average age of the participants was approximately 28 years; most were involved in a stable relationship and had no children. Ninety-two percentage of the respondents thought that men and women should share responsibility for contraception and 75% said they would try a hormonal contraceptive if available. At the end of the treatment phase, 66% of the participants said that they would use such a method, and most rated its acceptability very highly; none reported it to be unacceptable. The injections themselves were indicated as the biggest disadvantage. No significant changes in sexual function or mood states were detected among the men who underwent hormone injections. The contraceptive tested in this study was well accepted by the participants over the course of 1 year.
    Preview · Article · Sep 2006 · Human Reproduction
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