Combination therapy with clomiphene citrate and anastrozole is a safe and effective alternative for hypoandrogenic subfertile men

Objectives To assess the efficacy and safety of combination therapy with clomiphene citrate (CC) and anastrozole (AZ) for male hypoandrogenism. Patients and Methods We identified patients treated with a combination of CC + AZ in the period 2014 to 2017. Data were gathered on patient characteristics and laboratory values at baseline. Total testosterone, bioavailable testosterone, oestradiol and testosterone:oestradiol ratio were measured before combination therapy (treatment with CC only) and at CC + AZ combination therapy follow-ups. Treatment side effects were recorded; prostatic-specific antigen and haematocrit levels were measured to assess safety after 6 months. As a secondary outcome, semen characteristics were compared at baseline and after at least 3 months of combination therapy when these data were available. Data were analysed using a paired t-test and Wilcoxon's signed-rank test. Results A total of 51 men were included, with a mean age of 35.4 +/- 7.4 years and a mean body mass index of 35.0 +/- 8.0 kg/m(2). After CC treatment, total testosterone, bioavailable testosterone, and oestradiol levels all significantly increased. AZ was added in all patients with hyperoestrogenaemia (oestradiol >50 pg/mL) or a testosterone:oestradiol ratio <10. CC + AZ therapy maintained therapeutic total testosterone and bioavailable testosterone levels while also normalizing oestradiol levels and testosterone:oestradiol ratio. Eleven patients experienced side effects: anxiety/irritability, n = 5; decreased libido, n = 4; elevated (>54%) haematocrit, n = 2. Conclusion Combination therapy with CC + AZ is an effective and safe alternative for patients with elevated oestradiol level or low testosterone:oestradiol ratio.