Effect of aromatase inhibitor, letrozole on semen parameters in eugonadotropic hypoandrogenic men with oligozoospermia
Keywords:Aromatase inhibitor, Estradiol, Letrozole, Male infertility, Oligozoospermia, Testosterone
Background: Some men with severely defective sperm production commonly have excess aromatase activity, reflected by low serum testosterone and relatively elevated estradiol levels. Elevated levels of estrogen lead to feedback inhibition of the hypothalamic -pituitary-gonadal axis, and the end result is a decrease in LH necessary for the production of testosterone, and FSH to optimize sperm production. The aim of this study was to evaluate the effect of aromatase inhibitor, letrozole on the semen parameters of infertile male having oligozoospermia, low serum testosterone level and testosterone to estradiol ratio <10.
Methods: This Prospective study was conducted in the Department of Reproductive Endocrinology and Infertility at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh during the period from May 2019 to April 2020. The sample size was 30 subfertile men with oligozoospermia (≤ 10 million/ml), low serum testosterone level (<300 ng/dl) and low testosterone to estradiol ratio (<10). All patients were treated with letrozole 2.5 mg daily for 4 months. At the end of the 4 months the semen analysis was performed. Statistical analysis was carried out by using IBM Statistical Package for Social Sciences version 25 for windows (SPSS version 25.0).
Results: The sperm concentration, sperm motility and total motile sperm count significantly increased after letrozole treatment. The side effects were mild and well tolerated.
Conclusions: This study suggests that some men with oligozoospermia, low serum testosterone levels and normal gonadotropin concentration may have a treatable endocrinopathy. Letrozole may be used to improve sperm parameters in infertile men with low serum testosterone to estradiol ratio.
Agarwal A, Mulgund A, Hamada A, Chytte MR, A unique view on male infertility around the globe. Reproductive Biology and Endocrinol. 2015;13:37.
Esteves SC, Miyaoka R, Agarwal A. An update on the clinical assessment of the infertile male. Clinics. 2011;66:691-700.
Jarow JP, Zirkin BR. The androgen microenvironment of the human testis and hormonal control of spermatogenesis. Ann N Y Acad Sci. 2005;1061:208-20.
Bharti S, Misro, MM, Rai U. Clomiphene citrate potentiates the adverse effects of estrogens on rat testis and down-regulates the expression of steroidogenic enzyme genes. Fertil Steril. 2013;99:140-8.
Pavlovich CP, King P, Goldstein M, Schlegel PN. Evidence of a treatable endocrinopathy in infertile men. J Urol. 2001;165:837-41.
Santen RJ. Feedback control of luteinizing hormone and follicle- stimulating hormone secretion by testosterone and estradiol in men: physiological and clinical implications. Clin Biochem. 1981;14:243-51.
Inkster S, Yue W, Brodie A, Human testicular aromatase: immunocytochemical and biochemical studies. J Clin Endocrinol Metab. 1995;80:1941-7.
McArthur HL, Morris PG. Aromatase inhibitor strategies in metastatic breast cancer. Int J Women’s Health. 2010;1:67-72.
Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol. 2002;167:624-9.
Peivandi S, Hamed J, Mina A, Ebadi A. Effect of letrozole on spermogram parameters and hormonal profile in infertile men: A clinical trial study. Endocrine Regulations. 2019;53:231-6.
Shoshany O, Abhyankar N, Mufarreh N, Daniel G, Niederberger C. Outcomes of anastrazole in oligozoospermic hypoandrogenic subfertile men. Fertil Steril. 2017;107(3):589-94.
Saylam B, Efesoy O, Cayan S. The effect of aromatase inhibitor letrozole on body mass index, serum hormones, and sperm parameters in infertile men. Fertil Steril. 2011;95:809-11.
Gregoriou O, Bakas P, Grigoriadis C, Creatsa M, Hassiakos D, Creatsas G. Changes in hormonal profile and seminal parameters with use of aromatase inhibitors in management of infertile men with low testosterone to estradiol ratios. Fertil Steril. 2012;98:48-51.
Patry G, Jarvi K, Grober ED, Lo KC. Use of the aromatase inhibitor letrozole to treat male Infertility. Fertil Steril. 2009;92:892.
Vigersky RA, Glass AR. Effects of testolactone on the pituitary-testicular axis in oligozoospermic men. J Clin Endocrinol Metab. 1981;52:897-902.
Clark RV, Sherins RJ. Treatment of men with idiopathic oligozoospermic infertility using the aromatase inhibitor, testolactone. Results of a double-blinded, randomized, placebo-controlled trial with crossover. J Androl. 1989;10:240-7.
Smith IE, Norton A. Fadrozole and letrozole in advanced breast cancer: clinical and biochemical effects. Breast cancer Res Treat. 1998;49:67-77.
Helo S, Ellen J, Mechlin C, Feustel P, Grossman M, Ditkoff E, et al. A randomized prospective double-blind comparison trial of clomiphene citrate and anastrazole in raising testosterone in hypogonadal infertile men. J Sex Med. 2015;12:1761-9.
Shuling L, Sie KUi. ML, Saffari SE, et al. Do men with normal testosterone-estyradiol ratios benefit from letrozole for the treatment of male infertility? Reproductive Biomed Online. 2019;38(1):39-45.
Cavallini G, Biagiotti G, Bolzon E. Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients: A pilot study. Asian J Androl. 2013;15:806-11.
de Ronde W, de Jong FH. Aromatase inhibitors in men: effects and therapeutic options. Reprod Biol Endocrinol. 2011;9:93.