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Drug Insight: recent advances in male hormonal contraception

Abstract

As there are limitations to current methods of male contraception, research has been undertaken to develop hormonal contraceptives for men, analogous to the methods for women based on estrogen and progestogens. When testosterone is administered to a man, it functions as a contraceptive by suppressing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. Since these hormones are the main stimulatory signals for spermatogenesis, low levels of LH and FSH markedly impair sperm production. After 3–4 months of testosterone treatment, 60–70% of men no longer have sperm in their ejaculate, and most other men exhibit markedly diminished sperm counts. Male hormonal contraception is well tolerated, free of serious adverse side effects, and 95% effective in the prevention of pregnancy. Importantly, male hormonal contraception is reversible, with sperm counts usually recovering within 4 months of the discontinuation of hormone treatment. Because exogenous testosterone administration alone does not completely suppress sperm production in all men, researchers have combined testosterone with second agents, such as progestogens or gonadotropin-releasing-hormone antagonists, to further suppress secretion of LH and FSH and improve suppression of spermatogenesis. Recent trials have used combinations of long-acting injectable or implantable forms of testosterone with progestogens, which can be administered orally, by injection or by a long-acting implant. Such combinations suppress spermatogenesis to zero without severe side effects in 80–90% of men, with near-complete suppression in the remainder of individuals. One of these testosterone and progestogen combination regimens might soon bring the promise of male hormonal contraception to fruition.

Key Points

  • The administration of exogenous testosterone and progestogens results in suppression of sperm production that might allow their use in a male contraceptive

  • The tolerability and side-effect profiles of these regimens are favorable

  • Such regimens are currently 95% effective at pregnancy prevention

  • Improved potency and methods of drug delivery might allow for the introduction of such a hormonally based male contraceptive in the next 10 years

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Figure 1: The endocrinology of spermatogenesis and male hormonal contraception.
Figure 2: Mean sperm counts in men treated with 1,000 mg of testosterone undecanoate every 8 weeks alone (diamonds) or with 150 mg (squares) or 300 mg (triangles) of medroxyprogesterone acetate every 8 weeks (arrows).

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Acknowledgements

JK Amory is supported, in part, by the National Institute of Child Health and Human Development, a division of the National Institutes of Health, by grant 1K23 HD45386-10A1, and has research funding from Schering AG and GlaxoSmithKline. WJ Bremner and JK Amory are also supported by the National Institute of Child Health and Human Development through cooperative agreements U54-HD-12629 and U54 HD42454 as part of the specialized Cooperative Centers Program in Reproductive Research and the Cooperative Contraceptive Research Centers Program.

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JK Amory has research funding from Schering AG and GlaxoSmithKline.

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Amory, J., Page, S. & Bremner, W. Drug Insight: recent advances in male hormonal contraception. Nat Rev Endocrinol 2, 32–41 (2006). https://doi.org/10.1038/ncpendmet0069

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