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Semin Reprod Med 2013; 31(04): 245-250
DOI: 10.1055/s-0033-1345271
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Clomiphene Citrate in the Management of Male Infertility

Lauren W. Roth
1   Department of Obstetrics and Gynecology
,
Amanda R. Ryan
1   Department of Obstetrics and Gynecology
,
Randall B. Meacham
2   Division of Urology, University of Colorado, Denver, Colorado
› Author Affiliations
Further Information

Publication History

Publication Date:
17 June 2013 (online)

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Abstract

Clomiphene citrate, a selective estrogen receptor modulator, has been used to treat infertility in women and men for 50 years. In men, clomiphene citrate has been employed in the management of unexplained infertility, oligo and asthenospermia, hypogonadism, and nonobstructive azoospermia. The available evidence reveals mixed results and suggests that clomiphene citrate may be appropriate for the management of male infertility in specific clinical scenarios. Further research is needed to clarify when clomiphene citrate is indicated in the treatment of male infertility.

Keywords

clomiphene citrate - male infertility

Note

There was no funding for this article.


 

  • References

  • 1 Greenblatt RB, Roy S, Mahesh VB, Barfield WE, Jungck EC. Induction of ovulation. Am J Obstet Gynecol 1962; 84: 900-912
    PubMedGoogle Scholar
  • 2 Sorbie PJ, Perez-Marrero R. The use of clomiphene citrate in male infertility. J Urol 1984; 131 (3) 425-429
    PubMedGoogle Scholar
  • 3 Kumar R, Gautam G, Gupta NP. Drug therapy for idiopathic male infertility: rationale versus evidence. J Urol 2006; 176 (4, Pt 1) 1307-1312
    CrossrefPubMedGoogle Scholar
  • 4 Rittenberg V, El-Toukhy T. Medical treatment of male infertility. Hum Fertil (Camb) 2010; 13 (4) 208-216
    CrossrefPubMedGoogle Scholar
  • 5 Check JH, Chase JS, Nowroozi K, Wu CH, Adelson HG. Empirical therapy of the male with clomiphene in couples with unexplained infertility. Int J Fertil 1989; 34 (2) 120-122
    PubMedGoogle Scholar
  • 6 Cocuzza M, Agarwal A. Nonsurgical treatment of male infertility: specific and empiric therapy. Biologics 2007; 1 (3) 259-269
    PubMedGoogle Scholar
  • 7 Wieland RG, Ansari AH, Klein DE, Doshi NS, Hallberg MC, Chen JC. Idiopathic oligospermia: control observations and response to cisclomiphene. Fertil Steril 1972; 23 (7) 471-474
    PubMedGoogle Scholar
  • 8 Ghanem H, Shamloul R. An evidence-based perspective to the medical treatment of male infertility: a short review. Urol Int 2009; 82 (2) 125-129
    CrossrefPubMedGoogle Scholar
  • 9 Ghanem H, Shaeer O, El-Segini A. Combination clomiphene citrate and antioxidant therapy for idiopathic male infertility: a randomized controlled trial. Fertil Steril 2010; 93 (7) 2232-2235
    CrossrefPubMedGoogle Scholar
  • 10 World Health Organization. A double-blind trial of clomiphene citrate for the treatment of idiopathic male infertility. Int J Androl 1992; 15 (4) 299-307
    CrossrefPubMedGoogle Scholar
  • 11 Patankar SS, Kaore SB, Sawane MV, Mishra NV, Deshkar AM. Effect of clomiphene citrate on sperm density in male partners of infertile couples. Indian J Physiol Pharmacol 2007; 51 (2) 195-198
    PubMedGoogle Scholar
  • 12 Matsumiya K, Kitamura M, Kishikawa H , et al. A prospective comparative trial of a gonadotropin-releasing hormone analogue with clomiphene citrate for the treatment of oligoasthenozoospermia. Int J Urol 1998; 5 (4) 361-363
    CrossrefPubMedGoogle Scholar
  • 13 Moradi M, Moradi A, Alemi M , et al. Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility: a comparative study. Urol J 2010; 7 (3) 188-193
    PubMedGoogle Scholar
  • 14 Ko EY, Siddiqi K, Brannigan RE, Sabanegh Jr ES. Empirical medical therapy for idiopathic male infertility: a survey of the American Urological Association. J Urol 2012; 187 (3) 973-978
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 16 Kaminetsky J, Hemani ML. Clomiphene citrate and enclomiphene for the treatment of hypogonadal androgen deficiency. Expert Opin Investig Drugs 2009; 18 (12) 1947-1955
    CrossrefPubMedGoogle Scholar
  • 17 Luboshitzky R, Dickstein G, Barzilai D. Induction of spermatogenesis in isolated hypogonadotropic hypogonadism with exogenous human chorionic gonadotropin. J Endocrinol Invest 1981; 4 (2) 217-219
    PubMedGoogle Scholar
  • 18 Weinstein RL, Reitz RE. Pituitary-testicular responsiveness in male hypogonadotropic hypogonadism. J Clin Invest 1974; 53 (2) 408-415
    CrossrefPubMedGoogle Scholar
  • 19 Schroffner WG, Furth ED. Hypogonadotropic hypogonadism with anosmia (Kallmann's syndrome) unresponsive to clomiphene citrate. J Clin Endocrinol Metab 1970; 31 (3) 267-270
    CrossrefPubMedGoogle Scholar
  • 20 Burge MR, Lanzi RA, Skarda ST, Eaton RP. Idiopathic hypogonadotropic hypogonadism in a male runner is reversed by clomiphene citrate. Fertil Steril 1997; 67 (4) 783-785
    CrossrefPubMedGoogle Scholar
  • 21 Ioannidou-Kadis S, Wright PJ, Neely RD, Quinton R. Complete reversal of adult-onset isolated hypogonadotropic hypogonadism with clomiphene citrate. Fertil Steril 2006; 86 (5) e5-e9
    PubMedGoogle Scholar
  • 22 Ribeiro RS, Abucham J. Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas. Arq Bras Endocrinol Metabol 2011; 55 (4) 266-271
    CrossrefPubMedGoogle Scholar
  • 23 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
    CrossrefPubMedGoogle Scholar
  • 24 Ramasamy R, Ricci JA, Palermo GD, Gosden LV, Rosenwaks Z, Schlegel PN. Successful fertility treatment for Klinefelter's syndrome. J Urol 2009; 182 (3) 1108-1113
    CrossrefPubMedGoogle Scholar
  • 25 Akin JW. The use of clomiphene citrate in the treatment of azoospermia secondary to incomplete androgen resistance. Fertil Steril 1993; 59 (1) 223-224
    PubMedGoogle Scholar
  • 26 Silber SJ. Microsurgical TESE and the distribution of spermatogenesis in non-obstructive azoospermia. Hum Reprod 2000; 15 (11) 2278-2284
    CrossrefPubMedGoogle Scholar
  • 27 Okada H, Dobashi M, Yamazaki T , et al. Conventional versus microdissection testicular sperm extraction for nonobstructive azoospermia. J Urol 2002; 168 (3) 1063-1067
    CrossrefPubMedGoogle Scholar
  • 28 Hussein A, Ozgok Y, Ross L, Niederberger C. Clomiphene administration for cases of nonobstructive azoospermia: a multicenter study. J Androl 2005; 26 (6) 787-791 , discussion 792–793
    CrossrefPubMedGoogle Scholar
  • 29 Check JH, Murdock MG, Caro JF, Hermel MB. Case report: cystic gynecomastia in a male treated with clomiphene citrate. Fertil Steril 1978; 30 (6) 713-715
    PubMedGoogle Scholar
  • 30 Viola MI, Meyer D, Kruger T. Association between clomiphene citrate and visual disturbances with special emphasis on central retinal vein occlusion: a review. Gynecol Obstet Invest 2011; 71 (2) 73-76
    CrossrefPubMedGoogle Scholar
  • 31 Politou M, Gialeraki A, Merkouri E, Travlou A, Baltatzis S. Central retinal vein occlusion secondary to clomiphene treatment in a male carrier of factor V Leiden. Genet Test Mol Biomarkers 2009; 13 (2) 155-157
    CrossrefPubMedGoogle Scholar
  • 32 LeRoith D, Sobel R, Glick SM. The effect of clomiphene citrate on pubertal gynaecomastia. Acta Endocrinol (Copenh) 1980; 95 (2) 177-180
    PubMedGoogle Scholar
  • 33 Bujan L, Mieusset R, De Zong Z, Mansat A, Pontonnier F. Development of Leydig cell tumour in association with clomiphene treatment for oligozoospermia. Br J Urol 1992; 69 (6) 659-660
    CrossrefPubMedGoogle Scholar
  • 34 Nilsson A, Nilsson S. Testicular germ cell tumors after clomiphene therapy for subfertility. J Urol 1985; 134 (3) 560-562
    PubMedGoogle Scholar
  • 35 Landefeld CS, Schambelan M, Kaplan SL, Embury SH. Clomiphene-responsive hypogonadism in sickle cell anemia. Ann Intern Med 1983; 99 (4) 480-483
    CrossrefPubMedGoogle Scholar
  • 36 Matthews GJ, Goldstein M, Henry JM, Schlegel PN. Nonbacterial pyospermia: a consequence of clomiphene citrate therapy. Int J Fertil Menopausal Stud 1995; 40 (4) 187-191
    PubMedGoogle Scholar
  • 37 Shanis B, Check JH, Bollendorf A. Adverse effect of clomiphene citrate on sperm morphology. Arch Androl 1991; 27 (2) 109-111
    CrossrefPubMedGoogle Scholar
  • 38 Pasqualotto FF, Fonseca GP, Pasqualotto EB. Azoospermia after treatment with clomiphene citrate in patients with oligospermia. Fertil Steril 2008; 90 (5) e11-e12
    PubMedGoogle Scholar