Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men

Journal of Clinical Endocrinology and Metabolism

Volumn 94, Issue 7, 2009, Pages 2313-2320

  Mahabadi, Vahid ^a   Amory, John K ^b   Swerdloff, Ronald S ^a   Bremner, William J ^b   Page, Stephanie T ^b   Sitruk Ware, Regine ^c   Christensen, Peter D ^a   Kumar, Narender ^c   Tsong, Yun Yen ^c   Blithe, Diana ^d   Wang, Christina ^a,e  

^a HARBOR UCLA MEDICAL CENTER   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

^c POPULATION COUNCIL   (United States)

^d EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^e General Clinical Research Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ELCOMETRINE; FOLLITROPIN; GONADOTROPIN; LUTEINIZING HORMONE; MALE CONTRACEPTIVE AGENT; SEX HORMONE BINDING GLOBULIN; TESTOSTERONE;

ACNE; ADULT; APPLICATION SITE ERYTHEMA; ARTICLE; BLOOD SAMPLING; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; ERYTHEMA; FOLLITROPIN BLOOD LEVEL; GEL; GONADOTROPIN BLOOD LEVEL; HEADACHE; HORMONAL CONTRACEPTION; HORMONE ACTION; HORMONE DETERMINATION; HORMONE INHIBITION; HORMONE RELEASE; HUMAN; LIBIDO; LUTEINIZING HORMONE BLOOD LEVEL; MALE; MULTICENTER STUDY; NAUSEA; NORMAL HUMAN; OUTCOME ASSESSMENT; PANIC; PATIENT COMPLIANCE; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; SEMEN ANALYSIS; SIDE EFFECT; SPERMATOGENESIS; TREATMENT DURATION; UNIVERSITY HOSPITAL;

EID: 67650224522     PISSN: 0021972X     EISSN: 0021972X     Source Type: Journal    
DOI: 10.1210/jc.2008-2604     Document Type: Article

References (44)

1. Page ST, Amory JK, Bremner WJ 2008 Advances in male contraception. Endocr Rev 29:465-493
2. Nieschlag E, Henke A 2005 Hopes for male contraception. Lancet 365:554-556
3. Liu PY, McLachlan RI 2008 Male hormonal contraception: so near and yet so far. J Clin Endocrinol Metab 93:2474-2476
4. Gu YQ, Wang XH, Xu D, Peng L, Cheng LF, Huang MK, Huang ZJ, Zhang GY 2003 A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men. J Clin Endocrinol Metab 88:562-568
5. Turner L, Conway AJ, Jimenez M, Liu PY, Forbes E, McLachlan RI, Handelsman DJ 2003 Contraceptive efficacy of a depot progestin and androgen combination in men. J Clin Endocrinol Metab 88:4659-4667
6. 1990 Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility. Lancet 336:955-959
7. 1996 Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril [Erratum (1996) 65:1267] 65:821-829
8. Liu PY, Swerdloff RS, Anawalt BD, Anderson RA, Bremner WJ, Elliesen J, Gu YQ, Kersemaekers WM, McLachlan RI, Meriggiola MC, Nieschlag E, Sitruk-Ware R, Vogelsong K, Wang XH, Wu FC, Zitzmann M, Handelsman DJ, Wang C 2008 Determinants of the rate and extent of spermatogenic suppression during hormonal male contraception: an integrated analysis. J Clin Endocrinol Metab 93:1774-1783
9. Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C 2006 Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet 367:1412-1420
10. Handelsman DJ, Conway AJ, Boylan LM 1992 Suppression of human spermatogenesis by testosterone implants. J Clin Endocrinol Metab 75:1326-1332
11. Meriggiola MC, Farley TM, Mbizvo MT 2003 A review of androgen-progestin regimens for male contraception. J Androl 24:466-483
12. Nieschlag E, Zitzmann M, Kamischke A 2003 Use of progestins in male contraception. Steroids 68:965-972
13. Wang C, Swerdloff RS 2004 Male hormonal contraception. Am J Obstet Gynecol 190:S60-S68
14. Gu YQ, Tong JS, Ma DZ, Wang XH, Yuan D, Tang WH, Bremner WJ 2004 Male hormonal contraception: effects of injections of testosterone undecanoate and depot medroxyprogesterone acetate at eight-week intervals in Chinese men. J Clin Endocrinol Metab 89:2254-2262
15. Handelsman DJ, Conway AJ, Howe CJ, Turner L, Mackey MA 1996 Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot. J Clin Endocrinol Metab 81:4113-4121
16. Kamischke A, Ploger D, Venherm S, von Eckardstein S, von Eckardstein A, Nieschlag E 2000 Intramuscular testosterone undecanoate with or without oral levonorgestrel: a randomized placebo-controlled feasibility study for male contraception. Clin Endocrinol (Oxf) 53:43-52
17. Kamischke A, Venherm S, Ploger D, von Eckardstein S, Nieschlag E 2001 Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception. J Clin Endocrinol Metab 86:303-309
18. Meriggiola MC, Costantino A, Saad F, D'Emidio L, Morselli Labate AM, Bertaccini A, Bremner WJ, Rudolph I, Ernst M, Kirsch B, Martorana G, Pelusi G 2005 Norethisterone enanthate plus testosterone undecanoate for male contraception: effects of various injection intervals on spermatogenesis, reproductive hormones, testis, and prostate. J Clin Endocrinol Metab 90:2005-2014
19. Wang C, Wang XH, Nelson AL, Lee KK, Cui YG, Tong JS, Berman N, Lumbreras L, Leung A, Hull L, Desai S, Swerdloff RS 2006 Levonorgestrel implants enhanced the suppression of spermatogenesis by testosterone implants: comparison between Chinese and non-Chinese men. J Clin Endocrinol Metab 91:460-470
20. Wu FC, Aitken RJ 1989 Suppression of sperm function by depot medroxyprogesterone acetate and testosterone enanthate in steroid male contraception. Fertil Steril 51:691-698
21. Mommers E, Kersemaekers WM, Elliesen J, Kepers M, Apter D, Behre HM, Beynon J, Bouloux PM, Costantino A, Gerbershagen HP, Gronlund L, Heger-Mahn D, Huhtaniemi I, Koldewijn EL, Lange C, Lindenberg S, Meriggiola MC, Meuleman E, Mulders PF, Nieschlag E, Perheentupa A, Solomon A, Vaisala L, Wu FC, Zitzmann M 2008 Male hormonal contraception: a double-blind, placebo-controlled study. J Clin Endocrinol Metab 93:2572-2580
22. Page ST, Amory JK, Anawalt BD, Irwig MS, Brockenbrough AT, Matsumoto AM, Bremner WJ 2006 Testosterone gel combined with depomedroxyprogesterone acetate is an effective male hormonal contraceptive regimen and is not enhanced by the addition of a GnRH antagonist. J Clin Endocrinol Metab 91:4374-4380
23. Buchter D, von Eckardstein S, von Eckardstein A, Kamischke A, Simoni M, Behre HM, Nieschlag E 1999 Clinical trial of transdermal testosterone and oral levonorgestrel for male contraception. J Clin Endocrinol Metab 84:1244-1249
24. Gonzalo IT, Swerdloff RS, Nelson AL, Clevenger B, Garcia R, Berman N, Wang C 2002 Levonorgestrel implants (Norplant II) for male contraception clinical trials: combination with transdermal and injectable testosterone. J Clin Endocrinol Metab 87:3562-3572
25. Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R 2003 AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 88:2673-2681
26. Swerdloff RS, Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Longstreth J, Berman N 2000 Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 85:4500-4510
27. Wang C, Swerdloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G, Matsumoto AM, Weber T, Berman N 2000 Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. Testosterone Gel Study Group. J Clin Endocrinol Metab 85:2839-2853
28. Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS 2004 Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 89:2085-2098
29. Kumar N, Koide SS, Tsong Y, Sundaram K 2000 Nestorone: a progestin with a unique pharmacological profile. Steroids 65:629-636
30. Li F, Kumar N, Tsong YY, Monder C, Bardin CW 1997 Synthesis and progestational activity of 16-methylene-17α-hydroxy-19-norpregn-4-ene-3, 20-dione and its derivatives. Steroids 62:403-408
31. Sitruk-Ware R 2006 New progestagens for contraceptive use. Hum Reprod Update 12:169-178
32. Fraser IS, Weisberg E, Brache V, Alvarez F, Massai R, Mishell Jr DR, Apter D, Gale J, Tsong YY, Sivin I 2005 Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen. Contraception 72:40-45
33. Sivin I, Mishell Jr DR, Alvarez F, Brache V, Elomaa K, Lahteenmaki P, Massai R, Miranda P, Croxatto H, Dean C, Small M, Nash H, Jackanicz TM 2005 Contraceptive vaginal rings releasing Nestorone and ethinylestradiol: a 1-year dose-finding trial. Contraception 71:122-129
34. Fraser IS, Weisberg E, Kumar N, Kumar S, Humberstone AJ, McCrossin L, Shaw D, Tsong YY, Sitruk-Ware R 2007 An initial pharmacokinetic study with a metered dose transdermal system for delivery of the progestogen Nestorone as a possible future contraceptive. Contraception 76:432-438
35. World Health Organization 1999 Laboratory manual for the examination of human semen and sperm cervical mucus interaction. 4th ed. Cambridge, UK: Cambridge University Press
36. Qoubaitary A, Meriggiola C, Ng CM, Lumbreras L, Cerpolini S, Pelusi G, Christensen PD, Hull L, Swerdloff RS, Wang C 2006 Pharmacokinetics of testosterone undecanoate injected alone or in combination with norethisterone enanthate in healthy men. J Androl 27:853-867
37. Agresti A 2002 Categorical data analysis. New York: John Wiley & Sons
38. Amory JK, Anawalt BD, Bremner WJ, Matsumoto AM 2001 Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: implications for male contraceptive development. J Androl 22:1053-1060
39. Anawalt BD, Amory JK, Herbst KL, Coviello AD, Page ST, Bremner WJ, Matsumoto AM 2005 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 26:405-413
40. Aaltonen P, Amory JK, Anderson RA, Behre HM, Bialy G, Blithe D, Bone W, Bremner WJ, Colvard D, Cooper TG, Elliesen J, Gabelnick HL, Gu YQ, Handelsman DJ, Johansson EA, Kersemaekers W, Liu P, MacKay T, Matlin S, Mbizvo M, McLachlan RI, Meriggiola MC, Mletzko S, Mommers E, Muermans H, Nieschlag E, Odlind V, Page ST, Radlmaier A, Sitruk-Ware R, Swerdloff R, Wang C, Wu F, Zitzmann M 2007 10th Summit Meeting consensus: recommendations for regulatory approval for hormonal male contraception. J Androl 28:362-363
41. Sitruk-Ware R 2004 Pharmacological profile of progestins. Maturitas 47:277-283
42. Wang C, Catlin DH, Starcevic B, Leung A, DiStefano E, Lucas G, Hull L, Swerdloff RS 2004 Testosterone metabolic clearance and production rates determined by stable isotope dilution/tandem mass spectrometry in normal men: influence of ethnicity and age. J Clin Endocrinol Metab 89:2936-2941
43. Liu PY, Death AK, Handelsman DJ 2003 Androgens and cardiovascular disease. Endocr Rev 24:313-340
44. Wu FC, von Eckardstein A 2003 Androgens and coronary artery disease. Endocr Rev 24:183-217