Selective estrogen receptor modulators and the management of male hypoandrogenism – a systematic analysis
Authors:
M. Kathrins; H. Wadhwa; C. Niederberger
Authors‘ workplace:
University of Pennsylvania Medical Center
Published in:
Urol List 2015; 13(3): 22-26
Overview
Selective estrogen receptor modulators, such as clomiphene citrate, have been used as an off-label treatment of hypoandrogenism and idiopathic male infertility for over 30 years. We performed a systematic analysis of selective estrogen receptor modulators use in men with hypoandrogenism to examine issues related to dosage, hormonal and symptomatic efficacy, and adverse events. Our analysis indicates that treatment is well-tolerated and efficacious when compared to traditional exogenous testosterone supplementation. However the ideal dosage of clomiphene citrate has yet to be elucidated. We also provide a review of our institutional practices on the use and safety monitoring of clomiphene citrate.
Key words:
clomiphene citratemale infertility hypoandrogenism selective estrogen receptor modulators hormonal therapy
Sources
1. Da Ros CT, Averbeck MA. Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency – a prospective study. Int Braz J Urol 2012; 38(4): 512–518.
2. Moss JL, Crosnoe LE, Kim ED. Effect of rejuvenation hormones on spermatogenesis. Fertil Steril 2013; 99(7): 1814–1820. doi: 10.1016/j.fertnstert.2013.04.003.
3. Ross LS, Kandel GL, Prinz LM et al. Clomiphene treatment of the idiopathic hypofertile male: high-dose, alternate-day therapy. Fertil Steril 1980; 33(6): 618–623.
4. Hussein A, Ozgok Y, Ross L et al. Optimization of spermatogenesis-regulating hormones in patients with non-obstructive azoospermia and its impact on sperm retrieval: a multicentre study. BJU Int 2013; 111 (3 Pt B): E110–114. doi: 10.1111/j.1464-410X.2012.11485.x.
5. Wiehle RD, Fontenot GK, Wike J et al. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertil Steril 2014; 102(3): 720–727. doi: 10.1016/j.fertnstert.2014.06.004.
6. Turpen RM, Fesperman SF, Sultan S et al. Levels of evidence ratings in the urological literature: an assessment of interobserver agreement. BJU Int 2010; 105(5): 602–606. doi: 10.1111/j.1464-410X.2009.09181.x.
7. 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(12): 3546–3552.
8. Mazzola CR, Katz DJ, Loghmanieh N et al. Predicting biochemical response to clomiphene citrate in men with hypogonadism. J Sex Med 2014; 11(9): 2302–2307. doi: 10.1111/jsm.12592.
9. Shabsigh A, Kang Y, Shabsign R et al. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med 2005; 2(5): 716–721.
10. Guay AT, Jacobson J, Perez JB et al. 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(3): 156–165.
11. Ramasamy R, Scovell JM, Kovac JR et al. Testosterone supplementation versus clomiphene citrate for hypogonadism: an age matched comparison of satisfaction and efficacy. J Urol 2014; 192(3): 875–879. doi: 10.1016/j.juro.2014.03.089.
12. Taylor F, Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost. J Sex Med 2010; 7 (1 Pt 1): 269–276. doi: 10.1111/j.1743-6109.2009.01454.x.
13. Katz DJ, Nabulsi O, Tal R et al. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int 2012; 110(4): 573–578. doi: 10.1111/j.1464-410X.2011.10702.x.
14. Kaminetsky J, Werner M, Fontenot G et al. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. J Sex Med 2013; 10(6): 1628–1635. doi: 10.1111/jsm.12116.
15. Whitten SJ, Nangia AK, Kolettis PN. Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril 2006; 86(6): 1664–1668.
16. Ioannidou-Kadis S, Wright PJ, Neely RD et al. Complete reversal of adult-onset isolated hypogonadotropic hypogonadism with clomiphene citrate. Fertil Steril 2006; 86(5): 1513.e5–e9.
17. Ribeiro RS, Abucham J. Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment. Eur J Endocrinol 2009; 161(1): 163–169. doi: 10.1530/EJE-09-0084.
18. Chua ME, Escusa KG, Luna S et al. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis. Andrology 2013; 1(5): 749–757. doi: 10.1111/j.2047-2927.2013.00107.x.
19. Moskovic DJ, Katz DJ, Akhavan A et al. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int 2012; 110(10): 1524–1528. doi: 10.1111/j.1464-410X.2012.10968.x.
20. Ashok S, Sigman M. Bioavailable testosterone should be used for the determination of androgen levels in infertile men. J Urol 2007; 177(4): 1443–1446.
21. Vermeulen A. Hormonal cut-offs of partial androgen deficiency: a survey of androgen assays. J Endocrinol Invest 2005; 28 (Suppl 3): 28–31.
22. Pasqualotto FF, Pasqualotto EB. Is there a special subgroup of males with adult-onset idiopathic hypogonadotrophic hypogonadism who may respond with increases in sperm concentration after clomiphene citrate? Fertil Steril 2007; 88(1): 249.
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