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Volume 22, Issue 4 (July 2020) 22, 360–367; 10.4103/aja.aja_101_19

A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility

Francesco Del Giudice1, Gian Maria Busetto1, Ettore De Berardinis1, Isabella Sperduti2, Matteo Ferro3, Martina Maggi1, Martin S Gross4, Alessandro Sciarra1, Michael L Eisenberg5

1 Department of Urology, Sapienza Rome University, Policlinico Umberto I, Rome 00161, Italy
2 Biostatistical Unit, IRCCS, Regina Elena National Cancer Institute, Rome 00128, Italy
3 Division of Urology, European Institute of Oncology, Milan 20141, Italy
4 Section of Urology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03766, USA
5 Department of Urology, Stanford University, School of Medicine, Stanford, CA 94305, USA

Correspondence: Dr. GM Busetto (gianmaria.busetto@uniroma1.it)

Date of Submission 21-May-2019 Date of Acceptance 18-Jul-2019 Date of Web Publication 15-Oct-2019


Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio. In this subset of patients, and particularly in those with hypogonadism, elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic–pituitary–testicular axis by suppressing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production and impaired spermatogenesis. Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment. We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males. Overall, eight original articles were included and critically evaluated. Either steroidal (Testolactone) or nonsteroidal (Anastrozole and Letrozole) aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile. While the evidence is promising, future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.

Keywords: aromatase inhibitor; hypogonadism; male infertility; meta-analysis; systematic review

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