Male hormonal contraceptives

Minerva Ginecologica

Volumn 58, Issue 3, 2006, Pages 215-226

  Amory, J K ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Male fertility; Progesterone; Spermatogenesis; Testosterone

Indexed keywords

ABARELIX; ACYLINE; ANDROGEN; ANILINE DERIVATIVE; ANTIANDROGEN; CETRORELIX; CONTRACEPTIVE AGENT; CYPROTERONE ACETATE; DECANOIC ACID; DESOGESTREL; DIENOGEST; ESTROGEN; ETONOGESTREL; GESTAGEN; GONADORELIN ANTAGONIST; GONADOTROPIN ANTAGONIST; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LEVONORGESTREL; MEDROXYPROGESTERONE ACETATE; N,N DIMETHYL PARA ANISIDINE; NANDROLONE; NORETHISTERONE ENANTATE; PROGESTERONE; STEROID 5ALPHA REDUCTASE INHIBITOR; TESTOSTERONE; TESTOSTERONE ENANTATE; TESTOSTERONE ESTER; TESTOSTERONE UNDECANOATE; TRESTOLONE; UNCLASSIFIED DRUG;

ALLERGIC REACTION; ATHEROSCLEROSIS; AZOOSPERMIA; BLOOD CLOT; CLINICAL TRIAL; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG EFFECT; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG MARKETING; DRUG SAFETY; DRUG TOLERANCE; ENDOMETRIUM CANCER; HORMONAL CONTRACEPTION; HUMAN; HYPOGONADOTROPIC HYPOGONADISM; HYPOPHYSIS; MALE FERTILITY; MEDICAL INSTRUMENTATION; NONHUMAN; OLIGOSPERMIA; OVARY CANCER; PROSTATE CANCER; PROSTATE DISEASE; REVIEW; SIDE EFFECT; SKIN IRRITATION; SPERMATOGENESIS; SPERMATOZOON COUNT; WEIGHT GAIN;

CONTRACEPTIVE AGENTS, MALE; CONTRACEPTIVES, ORAL, HORMONAL; HUMANS; MALE; SPERMATOGENESIS;

EID: 33745928446     PISSN: 00264784     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (81)

1. Martin CW, Anderson RA, Cheng L, Ho PC, van der Spuy Z, Smith KB et al. Potential impact of hormonal meal contraception: cross-cultural implications for development of novel male preparations. Hum Reprod 2000;15:637-45.
2. Glasier AF, Anakwe R, Everington D, Martin CW, van der Spuy Z, Cheng L et al. Would women trust their partners to use a male pill? Hum Reprod 2000;15:646-9.
3. Amory JK, Bremner WJ. The use of testosterone as a male contraceptive. Balliere's Clin Endocrinol Metab 1998;12:471-84.
4. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril 1996;65:821-9.
5. Handelsman DJ, Farley TM, Peregoudov A, Waites GM. Factors in nonuniform induction of azoospermia by testosterone enanthate in normal men. Fertil Steril 1995;63:125-33.
6. World Health Organization. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet 1990;336:995-9.
7. Bagatell CJ, Heiman JR, Matsumoto AM, Rivier JE, Bremner WJ. Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men. J Clin Endocrinol Metab 1994;79:561-7.
8. Meriggiola MC, Marcovina S, Paulsen CA, Bremner WJ. Testosterone enanthate at the dose 200 mg/week decreases HDL-cholesterol levels in healthy men. Int J Androl 1995;18:237-42.
9. Zitzmann M, Junker R, Kamischke A, Nieschlag E. Contraceptive steroids influence the hemostatic activation state in healthy men. J Androl 2002;23:503-11.
10. Cherrier MM, Anawalt BD, Herbst KL, Amory JK, Craft S, Matsumoto AM et al. Cognitive effects of short-term manipulation of serum sex steroids in healthy young men. J Clin Endocrinol Metab 2002;87:3090-6.
11. Sjogren B, Gottlieb C. Testosterone for male contraception during one year: attitudes, well-being and quality of sex life. Contraception 2001;64:59-65.
12. Ringheim K. Evidence for the acceptability of an injectable hormonal method for men. Fam Plann Perspect 1995;27:123-8.
13. Zhang GY, Gu YQ, Wang XH, Cui YG, Bremner WJ. A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men. J Androl 1998;19: 761-8.
14. Behre AM, Abshagen K, Oettel M, Hubler, Nieschlag E. Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies. Eur J Endrocrinol 1999;140:414-9.
15. Zhang GY, Gu YQ, Wang XH, Cui YG, Bremner WJ. Injectable testosterone undecanoate for contraception in Chinese men. J Clin Endocrinol Metab 1999;84: 3642-7.
16. Kamischke A, Ploger D, Venherm S, von Eckardstein S, von Eckardstein A, Nieschlag E. Intramuscular testosterone undecanoate with or without oral levonorgestrel: a randomized placebo-controlled feasibility study for male contraception. Clin Endocrinol (Oxf) 2000;53:43-52.
17. Erratum in: Clin Endocrinol (Oxf) 2000;53:661.
18. Kamischke A, Venherm S, Ploger D, von Eckardstein S, Nieschlag E. Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception. J Clin Endocrinol Metab 2001;86:303-9.
19. Gu YQ, Wang XH, Xu D, Peng L, Cheng LF, Huang MK et al. A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men. J Clin Endocrinol Metab 2003;88:562-8.
20. Sundaram K, Kumar N, Bardin CW. 7 alpha-Methyl-19-nortestosterone: an ideal androgen for replacement therapy. Recent Prog Horm Res 1994;49:373-6.
21. Speroff L, Glass RH, Kase NG. Oral contraception. In: Speroff L, Glass RH, Kase NG, editors. Clinical gynecologic endocrinology and infertility. 5th ed. Baltimore: Williams and Wilkins; 1994.p.715-64.
22. Cummings DE, Kumar N, Bardin CW, Sundaram K, Bremner WJ. Prostate-sparing tissue specific effects of the potent androgen 7-methyl-19-nortestosterone (MENT) in primates. J Clin Endocrinol Metab 1998;83:4212-9.
23. Suvissari J, Sundaram K, Noe G, Kumar N, Aguillaume C, Tsong YY et al. Pharmacokinetics and pharmacodynamics of 7-methyl-19-nortestosterone and intramuscular administration in healthy men. Hum Reprod 1997;12:967-73.
24. Noe G, Suvisaari J, Martin C, Moo-Young AJ, Sundaram K, Saleh SI et al. Gonadotropin and testosterone suppression by 7-methyl-19-nortestosterone acetate administered by subdermal implant to healthy men. Hum Reprod 1999;14:2200-6.
25. Von Eckardstein S, Noe G, Brache V, Nieschlag E, Croxatto H, Alvarez F et al.; International Committee for Contraceptive Research, The Population Council. A clinical trial of 7 alpha-methyl-19-nor-testosterone implants for possible use as a long-acting contraceptive for men. J Clin Endocrinol Metab 2003;88:5232-9.
26. Soufir JC, Jouannet P, Marson J, Soumah A. Reversible inhibition of sperm production and gonadotrophin secretion in men following combined oral medroxyprogesterone acetate and percutaneous testosterone treatment. Acta Endocrinol (Copenh.) 1983;102:625-32.
27. Buchter D, von Eckardstein S, von Eckardstein A, Kamischke A, Simoni M, Behre HM et al. Clinical trial of transdermal testosterone and oral levonorgestrel for male contraception. J Clin Endocrinol Metab 1999;84:1244-9.
28. Hair WM, Kitteridge K, O'Conner DB, Wu FC. A novel male contraceptive pill-patch combination: oral desogestrel and transdermal testosterone in the suppression of spermatogenesis in normal men. J Clin Endocrinol Metab 2001;86:5201-9.
29. Gonzalo IT, Swerdloff RS, Nelson AL, Clevenger B, Garcia R, Berman N et al. Levonorgestrel implants (Norplant II) for male contraception clinical trials: combination with transdermal and injectable testosterone. J Clin Endocrinol Metab 2002;87:3562-72.
30. Pollanen P, Nikkanen V, Huhtaniemi I. Combination of subcutaneous levonorgestrel implants and transdermal dihydrotestosterone gel for male hormonal contraception. Int J Androl 2001;24:369-80.
31. Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R, North American AA2500 T Gel Study Group. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 2003;88:2673-81.
32. Delanoe D, Fougeyrollas B, Meyer L, Thonneau P. Androgenisation of female partners of men on medroxyprogesterone acetate/percutaneous testosterone contraception. Lancet 1984;1:276.
33. Pavlou SN, Brewer K, Farley MG, Lindner J, Bastias MC, Rogers BJ 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;73:1360-9.
34. Tom L, Bhasin S, Salameh W, Steiner B, Peterson M, Sokol RZ et al. Induction of azoospermia in normal men with combined Nal-Glu gonadotropin-releasing hormone antagonist and testosterone enanthate. J Clin Endocrinol Metab 1992;75:476-83.
35. Bagatell CJ, Matsumoto AM, Christensen RB, Rivier JE, Bremner WJ. Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens. J Clin Endocrinol Metab 1993;77:427-32.
36. Swerdloff RS, Bagatell CJ, Wang C, Anawalt BD, Berman N, Steiner B 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;83:3527-33.
37. Behre HM, Kliesch S, Lemcke B, von Eckardstein S, Neischlag E. 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;16:2570-7.
38. Wong SL, Lau DT, Baughman SA, Fotheringham N, Menchaca D, Garnick MG. Pharmacokinetics and pharmacodynamics of novel depot formulation of Abarelix, a gonadotropin-releasing hormone (GnRH) antagonist, in healthy men, ages 50 to 75. J Clin Pharmacol 2004;44:495-502.
39. Herbst KL, Coviello AD, Page ST, Amory JK, Anawalt BD, Bremner WJ. Acyline, a gonadotropin releasing-hormone antagonist suppresses gonadotropins and testosterone for 15 days after a single dose. J Clin Endocrinol Metab 2004;89:5959-65.
40. Matthiesson KL, Amory JK, Berger R, Ugoni A, McLachlan RI, Bremner WJ. Novel male hormonal contraceptive combinations: the hormonal and spermatogenic effects of testosterone and levonorgestrel combined with a 5-alpha-reductase inhibitor or GnRH Antagonist. J Clin Endocrinol Metab 2005;90:91-7.
41. Cho N, Harada M, Imaeda T, Imada T, Matsumoto H, Hayase Y et al. Discovery of a novel, potent, and orally active nonpeptide antagonist of the human luteinizing hormone-releasing hormone (LHRH) receptor. J Med Chem 1998;41:4190-5.
42. Schearer SB, Alvarez-Sanchez F, Anselmo J, Brenner P, Coutinho E, Latham-Faundes A et al. Hormonal contraception for men. Int J Androl 1978;1 Suppl 2:680-712.
43. Fotherby K, Davies JE, Richards DJ, Bodin M. Effect of low doses of synthetic progestagens on testicular function. Int J Fertil 1972;17:113-9.
44. Barfield A, Melo J, Coutinho E, Alvarez-Sanchez F, Faundes A, Brache V et al. Pregnancies associated with sperm concentrations below 10 million/ml in clinical studies of a potential male contraceptive method, monthly depot medroxyprogesterone acetate and testosterone esters. Contraception 1979;20:121-7.
45. Bebb RA, Anawalt BD, Christensen RB, Paulsen CA, Bremner WJ, Matsumoto AM. 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;81:757-62.
46. Anawalt BD, Bebb RA, Bremner WJ, Matsumoto AM. 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;20:407-14.
47. Anawalt BD, Amory JK, Herbst KL, Coviello AD, Bremner WJ, Matsumoto AM. Very low-dosage oral levonorgestrel plus intramuscular testosterone enanthate suppresses spermatogenesis without causing weight gain in normal young men: a randomized clinical trial. J Androl 2005;26:405-13.
48. Gui YL, He CH, Amory JK, Bremner WJ, Zheng EX, Yang J et al. Male hormonal contraception: suppression of spermatogenesis by injectable testosterone undecanoate alone or with levonorgestrel implants in Chinese men J Androl 2004;25:720-7.
49. Wu FC, Balasubramanian R, Mulders TIM, Coelingh-Bennick HJ. Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism. J Clin Endocrinol Metab 1999;84:112-22.
50. Anawalt BD, Herbst KL, Matsumoto AM, Mulders TM, Coelingh-Bennink HJ, Bremner WJ. Desogestrel plus testosterone effectively suppresses spermatogenesis but also causes modest weight gain and high-density lipoprotein suppression. Fertil Steril 2000;74:707-14.
51. Kinniburgh D, Zhu H, Cheng L, Kicman AT, Baird DT, Anderson RA. Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men. Hum Reprod 2002;17:1490-501.
52. Anderson RA, Van Der Spuy ZM, Dada OA, Tregoning SK, Zinn PM, Adeniji OA et al. Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone. Hum Reprod 2002;17:2869-77.
53. Hay CJ, Brady DM, Zitzmann M, Osmanagaoglu K, Pollanen P, Apter D et al. A multicenter phase Iib study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progstogen (etonogestrel) for male hormonal contraception. J Clin Endocrinol Metab 2005;90:2042-9.
54. Anderson RA, Kinniburgh D, Baird DT. Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception. J Clin Endocrinol Metab 2002;87:3640-9.
55. Brady BM, Walton M, Hollow N, Kicman AT, Baird DT, Anderson RA. Depot testosterone with etonogestrel implants result in induction of azoospermia in all men for long-term contraception. Hum Reprod 2004;11: 2658-67.
56. Brady DM, Amory JK, Perheentupa A, Zitzmann M, Hay C, Apter D et al. A multi-centre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive. Hum Reprod 2006;21:285-94.
57. Meriggiola MC, Bremner WJ, Paulsen CA, Valdiserri A, Incorvaia L, Motta R et al. A combined regimen of cyproterone acetate and testosterone enanthate as a potentially highly effective male contraceptive. J Clin Endocrinol Metab 1996;81:3018-23.
58. Meriggiola MC, Bremner WJ, Constantino A, DiCintio B, Flamigni C. Low dose of cyproterone acetate and testosterone enanthate for contraception in men. Hum Reprod 1998;13:1225-9.
59. Meriggiola MC, Bremner WJ, Constantino A, Pavani A, Capelli M, Flamigni C. An oral regimen of cyproterone acetate and testosterone for spermatogenic suppression in men. Fertil Steril 1997;68:844-50.
60. Meriggiola MC, Bremner WJ, Costantino A, Bertaccini A, Morselli-Labate AM, Huebler D et al. Twenty-one day administration of dienogest reversibly suppresses gonadotropins and testosterone in normal men. J Clin Endocrinol Metab 2002;87:2107-13.
61. Kamischke A, Diebacker J, Nieschlag E. Potential of norethisterone enanthate for male contraception: pharmacokinetics and suppression of pituitary and gonadal function. Clin Endocrinol (Oxf) 2000;53:351-8.
62. Kamischke A, Venherm S, Ploger D, Von Eckardstein S, Nieschlag E. Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception. J Clin Endocrinol Metab 2001;86:303-9.
63. Meriggiola MC, Constantino A, Saad F, D'Emidio L, Morselli Labate AM, Bertaccini A et al. Norethisterone enanthate plus testosterone undecanoate for male contraception: effects of various injection intervals of spermatogenesis, reproductive hormones, testis and prostate. J Clin Endocrinol Metab 2005;90:2005-14.
64. Kamischke A, Heuermann T, Kruger K, von Eckardstein S, Schellschmidt I, Rubig A. An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations. J Clin Endocrinol Metab 2002;87:530-9.
65. Turner L, Conway AJ, Jimenez M, Liu PY, Forbes E, McLachlan RI et al. Contraceptive efficacy of a depot progestin and androgen combination in men. J Clin Endocrinol Metab 2003;88:4659-67.
66. Gu YQ, Tong JS, Ma DZ, Wang XH, Yuan D, Tang WH 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;89:2254-62.
67. Rosen J, Negro-Vilar A. Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile. J Musculoskelet Neuronal Interact 2002;2:222-4.
68. Chen J, Hwang DJ, Bohl CE, Miller DD, Dalton JT. A selective androgen receptor modulator for hormonal male contraception. J Pharmacol Exp Ther 2005;312: 546-53.
69. Amory JK, Bremner WJ. Oral testosterone in oil plus dutasteride: a pharmacokinetic study in men. J Clin Endocrinol Metab 2005;90:2610-7.
70. 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;77:290-3.
71. Amory JK, Anawalt BD, Bremner WJ, Matsumoto AM. Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: implications for male contraceptive development. J Androl 2001;22: 1053-60.
72. McLachlan RI, Robertson DM, Pruysers E, Ugoni A, Matsumoto AM, Anawalt BD et al. Relationship between serum gonadotropins and spermatogenic suppression in men undergoing steroidal contraceptive treatment. J Clin Endocrinol Metab 2004;89:142-9.
73. 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;81:902-8.
74. McLachlan RI, O'Donnell L, Stanton PG, Balourdos G, Frydenberg M, de Kretser DM et al. Effects of testosterone plus medroxyprogesterone acetate on semen quality, reproductive hormones, and germ cell populations in normal young men. J Clin Endocrinol Metab 2002;87:546-56.
75. McLachlan RI, McDonald J, Rushford D, Robertson DM, Garrett C, Baker HW. Efficacy and acceptability of testosterone implants, alone or in combination with a 5alpha-reductase inhibitor, for male hormonal contraception. Contraception 2000;62:73-8.
76. Kinniburgh D, Anderson RA, Baird DT. Suppression of spermatogenesis with desogestrel and testosterone pellets is not enhanced by addition of finasteride. J Androl 2001;22:88-95.
77. Zhang FP, Pakarainen T, Poutanen M, Toppari J, Huhtaniemi I. The low gonadotropin-independent constitutive production of testicular testosterone is sufficient to maintain spermatogenesis. Proc Natl Acad Sci U S A 2003;100:13692-7.
78. Meriggiola MC, Costantino A, Bremner WJ, Morselli-Labate AM. Higher testosterone dose impairs sperm suppression induced by a combined androgen-progestin regimen. J Androl 2002;23:684-90.
79. Yu B, Handelsman DJ. Pharmacogenetic polymorphisms of the AR and metabolism and susceptibility to hormone-induced azoospermia. J Clin Endocrinol Metab 2001;86:4406-11.
80. Eckardstein SV, Schmidt A, Kamischke A, Simoni M, Gromoll J, Nieschlag E. CAG repeat length in the androgen receptor gene and gonadotrophin suppression influence the effectiveness of hormonal male contraception. Clin Endocrinol (Oxf) 2002;57:647-55.
81. Nieschlag E, Anderson RA, Apter D. Sixth Summit Meeting Consensus: recommendations for regulatory-approval for hormonal male contraception. Int J Androl 2002;23:375.