Male Contraceptive

Discussion in 'Men's Health Forum' started by Michael Scally MD, Oct 27, 2016.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Behre HM, Zitzmann M, Anderson RA, et al. Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2016-2141

    Context: The development of a safe and effective reversible method of male contraception is still an unmet need.

    Objective: Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone.

    Design: Prospective multicentre study.

    Setting: Ten study centers.

    Participants: Healthy men, aged 18–45 years, and their 18- to 38-year-old female partners, both without known fertility problems.

    Intervention: Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks.

    Main Outcomes Measures: Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate.

    Results: Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8–97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method).

    During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59–4.14).

    The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users (95% CI, 91.5–97.1).

    The most common adverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early.

    Conclusions: The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high.
     
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  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Would Male Hormonal Contraceptives Affect Cardiovascular Risk?

    The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives.

    This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years), a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception.

    The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.

    Zitzmann M. Would male hormonal contraceptives affect cardiovascular risk? Asian journal of andrology 2018. Would male hormonal contraceptives affect cardiovascular risk? Zitzmann M, - Asian J Androl
     
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Hormonal Regulation of Spermatogenesis; Mutant Mice Challenging Old Paradigms

    The two pituitary gonadotrophins, luteinising hormone (LH) and follicle-stimulating hormone (FSH), and in particular LH-stimulated high intratesticular (IT) testosterone (T) concentration, are considered crucial for spermatogenesis.

    We have revisited these concepts in genetically modified mice, one being the LH receptor (R) knockout mouse (LuRKO), the other a transgenic mouse expressing in Sertoli cells a highly constitutively active mutated Fshr (Fshr-CAM).

    It was found that full spermatogenesis was induced by exogenous T treatment in LuRKO mice at doses that restored ITT concentration to a level corresponding to normal circulating T levels in wild-type (WT) mice, ≈ 5 nmol/L, which is 1.4% of the normal high ITT concentration.

    When hypogonadal LuRKO and Fshr-CAM mice were crossed, the double mutant mice with strong FSH signaling but minimal T production showed near-normal spermatogenesis, even when their residual androgen action was blocked with the strong antiandrogen flutamide.

    In conclusion, our findings challenge two dogmas of the hormonal regulation of male fertility:
    (1) high ITT concentration is not necessary for spermatogenesis, and
    (2) strong FSH stimulation can maintain spermatogenesis without T.

    These findings have clinical relevance for the development of hormonal male contraception and for the treatment of idiopathic oligozoospermia.

    Huhtaniemi I. MECHANISMS IN ENDOCRINOLOGY: Hormonal regulation of spermatogenesis; mutant mice challenging old paradigms. European journal of endocrinology 2018. MECHANISMS IN ENDOCRINOLOGY: Hormonal regulation of spermatogenesis; mutant mice challenging old paradigms