Clomiphene citrate (CC) and anastrozole (AZ) have been used off label to increase testosterone (T) in hypogonadal infertile men (HIM). Both medications have been shown to increase T with different effects on estradiol (E2) and T-to-E2 ratios.
There are no reported randomized trials comparing CC and AZ to improve T levels in HIM. We aimed to establish equivalence of CC vs. AZ with respect to improvement in T levels in HIM.
We randomized 26 HIM (T less than 350 ng/dL and normal luteinizing hormone [LH]). Patients were randomized to CC (25 mg/day) or AZ (1 mg/day) for 12 weeks. Hormones assayed were total T, free T, E2, LH, follicle stimulating hormone (FSH), and sex hormone binding globulin (SHBG). Patient-reported outcomes were the International Index of Erectile Function, Erection Hardness Scale, and the Androgen Deficiency in the Aging Male questionnaires. Blood tests and questionnaires were recorded at baseline, 6 and 12 weeks. Semen analyses were performed at baseline and 12 weeks.
T increased significantly from baseline in both groups at 6 and 12 weeks. There was a significantly larger increase in T and mean increase from baseline in CC vs. AZ (571 vs. 408 ng/dL, respectively). Whereas E-2 levels increased in the CC group, they decreased in the AZ group. Though both groups demonstrated an increase in T-to-E-2 ratio from baseline, statistic significance at 6 and 12 weeks was only achieved with AZ. Neither group demonstrated significant changes in seminal parameters or patient-reported outcomes.
We failed to demonstrate equivalence of CC vs. AZ. CC resulted in significantly higher T levels than AZ. AZ resulted in a significantly larger increase in T/E-2 ratio than CC. No significant differences between CC and AZ on seminal parameters or patient-reported outcomes were demonstrated. Helo S, Ellen J, Mechlin C, Feustel P, Grossman M, Ditkoff E, and McCullough A. A randomized prospective double-blind comparison trial of clomiphene citrate and anastrozole in raising testosterone in hypogonadal infertile men. J Sex Med 2015;12:1761-1769.
The journal of sexual medicine. 2015 Jul 14 [Epub]
Sevann Helo, Joseph Ellen, Clay Mechlin, Paul Feustel, Michael Grossman, Edward Ditkoff, Andrew McCullough
Albany Medical Center, Division of Urology, Albany, NY, USA. , Albany Medical Center, Division of Urology, Albany, NY, USA. , Urology Associates of Central Missouri, Columbia, MO, USA. , Albany Medical College, Center for Neuroscience and Neuropharmacology, Albany, NY, USA. , CNY Fertility Center, Latham, NY, USA. , CNY Fertility Center, Latham, NY, USA. , Albany Medical Center, Division of Urology, Albany, NY, USA.