Vnitr Lek 2006, 52(11):1077-1084
Male hormonal contraception
- Šilinkův nadační fond, Praha, ředitel prof. MUDr. RNDr. Luboslav Stárka, DrSc.
Human reproduction is a complex phenomenon remaining at the center of interest of many medical and extra-medical disciplines and the search for new contraceptive methods is an important part of research effort. The development of effective forms of male hormonal contraception (MHC) is one of the priorities of the World Health Organization (WHO Task Force on Methods of Regulation of Male Fertility). The principle of MHC consists in the suppression of spermatogenesis while preserving all other functional aspects of the male glands (especially the sexual functions, bone metabolism and lean muscle mass). It is possible to stop spermatogenesis by blocking gonadotrophin (FSH and LH) secretion by testosterone administration (isolated or in combination with other hormones). The currently existing variants of MHC are based on testosterone application (which has in the same time the role of substitutive treatment - the so-called androgen "add-back") either in monotherapy (oral, intramuscular, transdermal and subcutaneous form) or in combination with various progestins (levonorgestrel, norethisterone, desogestrel, etonogestrel, medroxyprogesterone), antiandrogens or GnRH analogues. The most promising, at present, seem to be the methods which use a combination of depot testosterone preparations with long-acting progestins. To what extent will the role of MHC be important in the future - this can only be judged after establishing their effectiveness, full reversibility, safe application, acceptability, and financial accessibility in clinical practice.
Keywords: male hormonal contraception; testosterone; spermatogenesis; progestins
Received: June 14, 2006; Accepted: July 21, 2006; Published: November 1, 2006 Show citation
References
- Anawalt BD, Amory JK, Herbst KL et al. Intramuscular testosterone enanthate plus very low dosage oral levonorgestrel suppresses spermatogenesis without causing weight gain in normal young men: a randomized clinical trial. J Androl 2005; 26: 405-413.
Go to original source...
Go to PubMed...
- Anawalt BD, Bebb RA, Bremner WJ et al. A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations. J Androl 1999; 20: 407-414.
Go to original source...
Go to PubMed...
- Anawalt BD, Herbst KL, Matsumoto AM et al. Desogestrel plus testosterone effectively suppresses spermatogenesis but also causes modest weight gain and high-density lipoprotein suppression. Fertil Steril 2000; 74: 707-714.
Go to original source...
Go to PubMed...
- Anderson RA, Kinninburg D, Baird DT Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception. J Clin Endocrinol Metab 2002; 87: 3640-3649.
Go to original source...
Go to PubMed...
- Anderson RA, Van Der Spuy ZM, Dada OA et al. Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone. Hum Reprod 2002; 17: 2869-2877.
Go to original source...
Go to PubMed...
- Anderson RA, Wallace AM, Wu FC Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. III. Higher 5 alpha-reductase activity in oligozoospermic men administered supraphysiological doses of testosterone. J Clin Endocrinol Metab 1996; 81: 902-908.
Go to original source...
- Aribarg A, Sukcharoen N, Chanprasit Y et al. Suppression of spermatogenesis by testosterone enanthate in Thai men. J Med Assoc Thai 1996; 79: 624-629.
Go to PubMed...
- Bagatell CJ, Matsumoto AM, Christensen RB et al. Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens. J Clin Endocrinol Metab 1993; 77: 427-432.
Go to original source...
- Bebb RA, Anawalt BD, Christensen RB et al. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach. J Clin Endocrinol Metab 1996; 81: 757-762.
Go to original source...
- Behre HM, Kliesch S, Lemcke B et al. Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this non-aromatizable androgen alone. Hum Reprod 2001; 16: 2570-2577.
Go to original source...
Go to PubMed...
- Behre HM, Baus S, Kliesch S et al. Potential of testosterone buciclate for male contraception: endocrinedifferences between responders and nonresponders. J Clin Endocrinol Metab 1995; 80: 2394-2403.
Go to original source...
- Brady BM, Walton M, Hollow N et al. Depot testosterone with etonogestrel implants result in induction of azoospermia in all men for long-term contraception. Hum Reprod 2004; 19: 2658-2667.
Go to original source...
Go to PubMed...
- Brady BM, Amory JK, Perheentupa A et al. A multicentre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive. Hum Reprod 2006; 21: 285-294.
Go to original source...
Go to PubMed...
- von Eckardstein S, Noe G, Brache V et al. A clinical trial of 7 alpha-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men. J Clin Endocrinol Metab 2003; 88: 5232-5239.
Go to original source...
Go to PubMed...
- De Gendt K, Swinnen JV, Saunders PT et al. Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci USA 2004; 101: 1327-1332.
Go to original source...
Go to PubMed...
- Gonzalo IT, Swerdloff RS, Nelson AL et al. Levonorgestrel implants (Norplant II) for male contraception clinical trials: combination with transdermal and injectable testosterone. J Clin Endocrinol Metab 2002; 87: 3562-3572.
Go to original source...
Go to PubMed...
- Gu YQ, Tong JS, Ma DZ et al. Male hormonal contraception: effects of injections of testosterone undecanoate and depot medroxyprogesterone acetate at eight-week intervals in chinese men. J Clin Endocrinol Metab 2004; 89: 2254-2262.
Go to original source...
Go to PubMed...
- Gu YQ, Wang XH, Xu D et al. A multicenter Contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men. J Clin Endocrinol Metab 2003; 88: 562-568.
Go to original source...
Go to PubMed...
- Gui YL, He CH, Amory JK et al. Male hormonal contraception: suppression of spermatogenesis by injectable testosterone undecanoate alone or with levonorgestrel implants in chinese men. J Androl 2004; 25: 720-727.
Go to original source...
Go to PubMed...
- Kamischke A, Ploger D, Venherm S et al. Intramuscular testosterone undecanoate with or without oral levonorgestrel: a randomized placebo-controlled feasibility study for male contraception. Clin Endocrinol (Oxf) 2000; 53: 43-52.
Go to original source...
Go to PubMed...
- Kamischke A, Venherm S, Ploger D et al. Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception. J Clin Endocrinol Metab 2001; 86: 303-309.
Go to original source...
- Kinniburgh D, Zhu H, Cheng L et al. Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men. Hum Reprod 2002; 17: 1490-1501.
Go to original source...
Go to PubMed...
- Martin CW, Riley SC, Everington D et al. Dose-finding study of oral desogestrel with testosterone pellets for suppression of the pituitary-testicular axis in normal men. Hum Reprod 2000; 15: 1515-1524.
Go to original source...
Go to PubMed...
- Matthiesson KL, Amory JK, Berger R et al. Novel male hormonal contraceptive combinations: the hormonal and spermatogenic effects of testosterone and levonorgestrel combined with a 5alpha-reductase inhibitor or gonadotropin-releasing hormone antagonist. J Clin Endocrinol Metab 2005; 90: 91-97.
Go to original source...
Go to PubMed...
- McLachlan RI, O'Donnell L, Meachem SJ et al. Identification of specific sites of hormonal regulation in spermatogenesis in rats, monkeys, and man. Recent Prog Horm Res 2002; 57:149-79.
Go to original source...
Go to PubMed...
- Meriggiola MC, Bremner WJ, Costantino A et al. Low dose of cyproterone acetate and testosterone enanthate for contraception in men. Hum Reprod 1998; 13: 1225-1229.
Go to original source...
Go to PubMed...
- Meriggiola MC, Bremner WJ, Costantino A et al. An oral regimen of cyproterone acetate and testosterone undecanoate for spermatogenic suppression in me. Fertil Steril 1997; 68: 844-850.
Go to original source...
Go to PubMed...
- Meriggiola MC, Bremner WJ, Paulsen CA et al. A combined regimen of cyproterone acetate and testosterone enanthate as a potentially highly effective male contraceptive. J Clin Endocrinol Metab 1996; 81: 3018-3023.
Go to original source...
- Meriggiola MC, Costantino A, Cerpolini S et al. Testosterone undecanoate maintains spermatogenic suppression induced by cyproterone acetate plus testosterone undecanoate in normal men. J Clin Endocrinol Metab 2003; 88: 5818-5826.
Go to original source...
Go to PubMed...
- Meriggiola MC, Costantino A, Saad F et al. Norethisterone enanthate plus testosterone undecanoate for male contraception: effects of various injection intervals on spermatogenesis, reproductive hormones, testis, and prostate J Clin Endocrinol Metab 2005; 90: 2005-2014.
Go to original source...
Go to PubMed...
- Neischlag E, Hoogen H, Bolk M et al. Clinical trial with testosterone undecanoate for male fertility control. Contraception 1978; 18: 607-614.
Go to original source...
Go to PubMed...
- Pavlou SN, Brewer K, Farley MG et al. Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido. J Clin Endocrinol Metab 1991; 73: 1360-1369.
Go to original source...
Go to PubMed...
- Reddy PR Proceedings: Reversible contraceptive action of testosterone in males. J Reprod Fertil 1974; 38: 232.
- Swerdloff RS, Bagatell CJ, Wang C et al. Suppression of spermatogenesis in man induced by Nal-Glu gonadotropin releasing hormone antagonist and testosterone enanthate (TE) is maintained by TE alone. J Clin Endocrinol Metab 1998; 83: 3527-3533.
Go to original source...
- Turner L, Conway AJ, Jimenez M et al. Contraceptive efficacy of a depot progestin and androgen combination in men. J Clin Endocrinol Metab 2003; 88: 4659-4667.
Go to original source...
Go to PubMed...
- Wallace EM, Gow SM, Wu FC Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. I: Plasma luteinizing hormone, follicle stimulating hormone, testosterone, estradiol, and inhibin concentrations. J Clin Endocrinol Metab 1993; 77: 290-293.
Go to original source...
- Wang C, Wang XH, Nelson AL et al. Levonorgestrel implants enhanced the suppression of spermatogenesis by testosterone implants: comparison between Chinese and non-Chinese men. J Clin Endocrinol Metab 2006; 91: 460-470.
Go to original source...
Go to PubMed...
- World Health Organization Task Force on methods for the Regulation of Male Fertility: Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet 1990; 336: 955-959.
Go to original source...
- Wu FC, Farley TM, Peregoudov A et al. Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Fertil Steril 1996; 65: 626-636.
Go to original source...
- Zhang GY, Gu YQ, Wang XH et al. A clinical trial of injectable testosterone undecanoate as a potential male contraceptive in normal Chinese men. J Clin Endocrinol Metab 1999; 84: 3642-3647.
Go to original source...