Pharmacokinetic Evaluation of Serum Testosterone Concentrations After Administration of Clomiphene Citrate

Summary

This is a randomized, open-label trial examining two doses of clomiphene citrate in men with low serum testosterone concentrations (total testosterone (TT) \< 300 ng/dl).

Timeline

Start

2022-05-01

Primary completion

2025-01

Completion

2025-01

Publications

• Background Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006 Jul;60(7):762-9. doi: 10.1111/j.1742-1241.2006.00992.x.
• Background Mulhall JP, Trost LW, Brannigan RE, Kurtz EG, Redmon JB, Chiles KA, Lightner DJ, Miner MM, Murad MH, Nelson CJ, Platz EA, Ramanathan LV, Lewis RW. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urol. 2018 Aug;200(2):423-432. doi: 10.1016/j.juro.2018.03.115. Epub 2018 Mar 28.
• Background Wheeler KM, Sharma D, Kavoussi PK, Smith RP, Costabile R. Clomiphene Citrate for the Treatment of Hypogonadism. Sex Med Rev. 2019 Apr;7(2):272-276. doi: 10.1016/j.sxmr.2018.10.001. Epub 2018 Dec 3.
• Background Mazzola CR, Katz DJ, Loghmanieh N, Nelson CJ, Mulhall JP. Predicting biochemical response to clomiphene citrate in men with hypogonadism. J Sex Med. 2014 Sep;11(9):2302-7. doi: 10.1111/jsm.12592. Epub 2014 Jun 5.
• Background Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. 2012 Nov;110(10):1524-8. doi: 10.1111/j.1464-410X.2012.10968.x. Epub 2012 Mar 28.
• Background Katz DJ, Nabulsi O, Tal R, Mulhall JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int. 2012 Aug;110(4):573-8. doi: 10.1111/j.1464-410X.2011.10702.x. Epub 2011 Nov 1.
• Background Tenover JS, Bremner WJ. The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men. J Androl. 1991 Jul-Aug;12(4):258-63.
• Background Bendre SV, Murray PJ, Basaria S. Clomiphene Citrate Effectively Increases Testosterone in Obese, Young, Hypogonadal Men. Reprod Syst Sex Disord. 2015 Dec;4(4):155. doi: 10.4172/2161-038X.1000155. Epub 2015 Nov 13.
• Background Habous M, Giona S, Tealab A, Aziz M, Williamson B, Nassar M, Abdelrahman Z, Remeah A, Abdelkader M, Binsaleh S, Muir G. Clomiphene citrate and human chorionic gonadotropin are both effective in restoring testosterone in hypogonadism: a short-course randomized study. BJU Int. 2018 Nov;122(5):889-897. doi: 10.1111/bju.14401. Epub 2018 Jun 14.
• Background Ramasamy R, Scovell JM, Kovac JR, Lipshultz LI. Testosterone supplementation versus clomiphene citrate for hypogonadism: an age matched comparison of satisfaction and efficacy. J Urol. 2014 Sep;192(3):875-9. doi: 10.1016/j.juro.2014.03.089. Epub 2014 Mar 21.
• Background Krzastek SC, Sharma D, Abdullah N, Sultan M, Machen GL, Wenzel JL, Ells A, Chen X, Kavoussi M, Costabile RA, Smith RP, Kavoussi PK. Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism. J Urol. 2019 Nov;202(5):1029-1035. doi: 10.1097/JU.0000000000000396. Epub 2019 Oct 9.
• Background Knight JC, Pandit AS, Rich AM, Trevisani GT, Rabinowitz T. Clomiphene-Associated Suicide Behavior in a Man Treated for Hypogonadism: Case Report and Review of The Literature. Psychosomatics. 2015 Sep-Oct;56(5):598-602. doi: 10.1016/j.psym.2015.06.003. Epub 2015 Jun 12. No abstract available.
• Background Pasqualotto FF, Fonseca GP, Pasqualotto EB. Azoospermia after treatment with clomiphene citrate in patients with oligospermia. Fertil Steril. 2008 Nov;90(5):2014.e11-2. doi: 10.1016/j.fertnstert.2008.03.036. Epub 2008 Jun 16.
• Background Ernst S, Hite G, Cantrell JS, Richardson A Jr, Benson HD. Stereochemistry of geometric isomers of clomiphene: a correction of the literature and a reexamination of structure-activity relationships. J Pharm Sci. 1976 Jan;65(1):148-50. doi: 10.1002/jps.2600650140. No abstract available.
• Background Murdter TE, Kerb R, Turpeinen M, Schroth W, Ganchev B, Bohmer GM, Igel S, Schaeffeler E, Zanger U, Brauch H, Schwab M. Genetic polymorphism of cytochrome P450 2D6 determines oestrogen receptor activity of the major infertility drug clomiphene via its active metabolites. Hum Mol Genet. 2012 Mar 1;21(5):1145-54. doi: 10.1093/hmg/ddr543. Epub 2011 Nov 22.
• Background Goldstein SR, Siddhanti S, Ciaccia AV, Plouffe L Jr. A pharmacological review of selective oestrogen receptor modulators. Hum Reprod Update. 2000 May-Jun;6(3):212-24. doi: 10.1093/humupd/6.3.212.
• Background Ghobadi C, Mirhosseini N, Shiran MR, Moghadamnia A, Lennard MS, Ledger WL, Rostami-Hodjegan A. Single-dose pharmacokinetic study of clomiphene citrate isomers in anovular patients with polycystic ovary disease. J Clin Pharmacol. 2009 Feb;49(2):147-54. doi: 10.1177/0091270008328096. Epub 2008 Nov 25.
• Background Mikkelson TJ, Kroboth PD, Cameron WJ, Dittert LW, Chungi V, Manberg PJ. Single-dose pharmacokinetics of clomiphene citrate in normal volunteers. Fertil Steril. 1986 Sep;46(3):392-6. doi: 10.1016/s0015-0282(16)49574-9.
• Background Fontenot GK, Wiehle RD, Podolski JS. Differential effects of isomers of clomiphene citrate on reproductive tissues in male mice. BJU Int. 2016 Feb;117(2):344-50. doi: 10.1111/bju.13244. Epub 2015 Sep 7.
• Background Adashi EY. Clomiphene citrate: the case for a monoisomeric preparation. Baillieres Clin Obstet Gynaecol. 1993 Jun;7(2):331-47. doi: 10.1016/s0950-3552(05)80134-8. No abstract available.
• Background Wiehle R, Cunningham GR, Pitteloud N, Wike J, Hsu K, Fontenot GK, Rosner M, Dwyer A, Podolski J. Testosterone Restoration by Enclomiphene Citrate in Men with Secondary Hypogonadism: Pharmacodynamics and Pharmacokinetics. BJU Int. 2013 Jul 12;112(8):1188-200. doi: 10.1111/bju.12363. Online ahead of print.
• Background Kim MJ, Byeon JY, Kim YH, Kim SH, Lee CM, Jung EH, Chae WK, Lee YJ, Jang CG, Lee SY, Choi CI. Effect of the CYP2D6*10 allele on the pharmacokinetics of clomiphene and its active metabolites. Arch Pharm Res. 2018 Mar;41(3):347-353. doi: 10.1007/s12272-018-1005-7. Epub 2018 Mar 7.

Drugs

Indications