Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: Comparison with testosterone gel

Journal of Sexual Medicine

Volumn 10, Issue 6, 2013, Pages 1628-1635

  Kaminetsky, Jed ^a   Werner, Michael ^b   Fontenot, Greg ^c   Wiehle, Ronald D ^c  

^a University Urology Associates   (United States)

^b MAZE Laboratories   (United States)

^c Repros Therapeutics Inc   (United States)

Author keywords

Clomid; Clomiphene Citrate; Enclomiphene Citrate; Low Serum Testosterone; Secondary Hypogonadotropic Hypogonadism; Sperm Counts; Testosterone Gel; Testosterone Replacement Therapy

Indexed keywords

ENCLOMIFENE CITRATE; ESTRADIOL; FOLLITROPIN; LUTEINIZING HORMONE; PROLACTIN; SEX HORMONE BINDING GLOBULIN; SOMATOMEDIN C; TESTOSTERONE; THYROTROPIN;

ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG SUBSTITUTION; DRUG WITHDRAWAL; ESTRADIOL BLOOD LEVEL; FOLLITROPIN BLOOD LEVEL; FOLLOW UP; GEL; HORMONE SYNTHESIS; HUMAN; HYPOGONADISM; LUTEINIZING HORMONE BLOOD LEVEL; MALE; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROLACTIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; SPERM; SPERMATOZOON COUNT; TESTOSTERONE BLOOD LEVEL; THYROTROPIN BLOOD LEVEL;

EID: 84878686321     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/jsm.12116     Document Type: Article

References (33)

1. Gray A, Feldman HA, McKinlay JB, Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: Results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991;73:1016-1025.
2. Orwoll E, Lambert LC, Marshall LM, Phipps K, Blank J, Barrett-Connor E, Cauley J, Ensrud K, Cummings S. Testosterone and estradiol among older men. J Clin Endocrinol Metab 2006;91:1336-1344.
3. Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva F, Forti G, Giwercman A, Huhtaniemi IT, Kula K, Punab M, Boonen S, Vanderschueren D. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European Male Aging Study. J Clin Endocrinol Metab 2008;93:2737-2745.
4. Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Lean ME, Pendleton N, Punab M, Boonen S, Vanderschueren D, Labrie F, Huhtaniemi IT; EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010;363:123-135.
5. Tajar A, Forti G, O'Neill TW, Lee DM, Silman AJ, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Vanderschueren D, Huhtaniemi IT, Wu FC; EMAS Group. Characteristics of secondary, primary, and compensated hypogonadism in aging men: Evidence from the European Male Ageing Study. J Clin Endocrinol Metab 2010;95:1810-1818.
6. Snyder PJ. Hypogonadism in elderly men: What to do until the evidence comes. N Engl J Med 2004;350:440-442.
7. Kaltenboeck A, Foster S, Ivanova J, Diener M, Bergman R, Birnbaum H, Kinchen K, Swindle R. The direct and indirect costs among U.S. privately insured employees with hypogonadism. J Sex Med 2012;9:2438-2447.
8. Ribeiro RS, Abu J. Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment. Eur J Endocrinol 2009;161:163-169.
9. Clark JH, Guthrie SC. Agonistic and antagonistic effects of clomiphene citrate and its isomers. Biol Reprod 1981;25:667-672.
10. Mikkelson TJ, Kroboth PD, Cameron WJ, Dittert LW, Chungi V, Manberg PJ. Single-dose pharmacokinetics of clomiphene citrate in normal volunteers. Fertil Steril 1986;46:392-396.
11. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM. Testosterone therapy in adult men with androgen deficiency syndromes: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006;91:1995-2010.
12. Wang C, Swerdloff RS. Practical aspects of testosterone substitution. J Endocrinol Invest 2005;28:109-111.
13. Swerdloff RS, Wang C. Transdermal androgens: pharmacology and applicability to hypogonadal elderly men. J Endocrinol Invest 2005;28:112-116.
14. Patel A, Rivkees SA. Prenatal virilization associated with paternal testosterone gel therapy. Int J Pediatr Endocrinol 2010;867471. doi: 10.1155/2010/867471.
15. Hill S, Arachelvam V, Quninton R. Enclomiphene, an estrogen receptor antagonist for the treatment of testosterone deficiency in men. Idrugs 2009;1292:109-119.
16. Kaminetsky J, Hemani ML. Clomiphene citrate and enclomiphene for the treatment of hypogonadal androgen deficiency. Expert Opin Investig Drugs 2009;18:1947-1955.
17. Kim ED, Crosnoe L, Bar-Charma N, Khera M, Lipshultz LI. The treatment of hypogonadism in men of reproductive age. Fertil Steril 2013;99:718-724.
18. Kacker R, Traish AM, Morgentaler A. Estrogens in men: Clinical implications for sexual function and the treatment of testosterone deficiency. J Sex Med 2012;9:1681-1696.
19. Nachtigall LB, Boepple PA, Pralong FP, Crowley WF, Jr. Adult-onset idiopathic hypogonadotropic hypogonadism-A treatable form of male infertility. N Engl J Med 1997;336:410-415.
20. Fitzpatrick SL, Berrodin TJ, Jenkins SF, Sindoni DM, Deecher DC, Frail DE. Effect of estrogen agonists and antagonists on induction of progesterone receptor in a rat hypothalamic cell line. Endocrinology 1999;140:3928-3937.
21. Burghardt RC, Gaddy-Kurten D, Burghardt RL, Kurten RC, Mitchell PA. Gap junction modulation in rat uterus. III. Structure-activity relationships of estrogen receptor-binding ligands on myometrial and serosal cells. Biol Reprod 1987;36:741-751.
22. Young RL, Goldzieher JW, Chakraborty PK, Panko WB, Bridges CN. Qualitative differences in estrogenic/antiestrogenic effects of clomiphene and zuclomiphene. Int J Fertil 1991;36:291-295.
23. Szutu M, Morgan DJ, McLeish M, Phillipou G, Blackman GL, Cox LW, Dollman W. Pharmacokinetics of intravenous clomiphene isomers. Br J Clin Pharmacol 1989;27:639-640.
24. Young SL, Opsahl MS, Fritz MA. Serum concentrations of enclomiphene and zuclomiphene across consecutive cycles of clomiphene citrate therapy in anovulatory infertile women. Fertil Steril 1999;71:639-644.
25. Guay AT, Bansal S, Heatley GJ. Effect of raising endogenous testosterone levels in impotent men with secondary hypogonadism: Double blind placebo-controlled trial with clomiphene citrate. J Clin Endocrinol Metab 1995;80:3546-3552.
26. Guay AT, Jacobson J, Perez JB, Hodge MB, Velasquez E. Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: Who does and does not benefit? Int J Impot Res 2003;15:156-165.
27. Hussein A, Ozgok Y, Ross L, Niederberger C. Clomiphene administration for cases of nonobstructive azoospermia: A multicenter study. J Androl 2005;26:787-791; discussion 792-3.
28. Shabsigh A, Kang Y, Shabsigh R, Gonzalez M, Liberson G, Fisch H, Goluboff E. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med 2005;2:716-721.
29. Tan RS, Vasudevan D. Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse. Fertil Steril 2003;79:203-205.
30. Cohn L, Feller AG, Draper MW, Rudman IW, Rudman D. Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF-I concentrations. Clin Endocrinol (Oxf) 1993;39:417-425.
31. Blackman MR, Sorkin JD, Münzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, Jayme J, O'Connor KG, Christmas C, Tobin JD, Stewart KJ, Cottrell E, St Clair C, Pabst KM, Harman SM. Growth hormone and sex steroid administration in healthy aged women and men: A randomized controlled trial. JAMA 2002;288:2282-2292.
32. Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005;26:833-876.
33. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86:724-731.