Baseline Gonadotropin Levels and Testosterone Response in Hypogonadal Men Treated With Clomiphene Citrate.

OBJECTIVE: To investigate the role of baseline gonadotropins in predicting the biochemical response to clomiphene citrate (CC) treatment. METHODS: We conducted a retrospective review of data from hypogonadal men treated with CC in 2 high-volume fertility centers between 2013 and 2018. Patient age, body mass index, and baseline hormones (follicle stimulating hormone [FSH], luteinizing hormone [LH], and total testosterone [TT]) were obtained. Response to treatment was measured as changes in TT levels within 6 months of initiating CC treatment. Linear regression models adjusted for age, body mass index, and time on CC therapy were fitted to assess the associations between baseline LH and FSH levels with treatment response. RESULTS: A total of 332 men with mean ± standard deviation age of 36.2 ± 8.2 years were included. Median time to initial follow-up was 6 weeks (25th-75th interquartile range [IQR]: 4-9 weeks). TT levels increased significantly on CC treatment (mean change: 329.2 ng/dL, 95% CI: 307.4-351.0) with 73% of men having at least 200 ng/dL increase over baseline TT levels. In univariable linear regression models, only age was significantly associated with TT response. Neither the baseline LH nor FSH significantly predicted TT response in linear regression models. CONCLUSION: CC treatment results in significant increases in testosterone levels in most men. Baseline gonadotropins are not strong predictors for treatment response to CC. Adequate biochemical response with CC trial can be expected in most patients with normal or slightly elevated baseline gonadotropin levels.

Obesity and Baseline Estradiol Levels Are Independent Predictors for Initiation of Anastrozole in Hypogonadal Men on Clomiphene Citrate.

PURPOSE: To assess the conversion rate from clomiphene citrate (CC) monotherapy to combination CC+anastrozole (AZ) therapy in hypogonadal men and the predictors associated with the initiation of AZ. MATERIALS AND METHODS: A retrospective review of records from hypogonadal men treated with CC in a single fertility center was performed from 2013 to 2018. Patient age, body mass index (BMI), blood pressure, and reproductive hormones were obtained at baseline. Obesity was defined as BMI≥30 kg/m². Cox proportional hazards models were used to identify predictors of switching to combination CC+AZ therapy. RESULTS: A total of 318 men on CC were included. Median (interquartile range) age was 34 years (30-39 years) and patients were followed for a median of 9 months (4-17 months). Of these, 97 (30.5%) were started on CC+AZ therapy. These patients had higher baseline BMI and estradiol, which in multivariable regression were significant predictors for switching to CC+AZ therapy. A threshold of 18.5 pg/mL for baseline estradiol provided the highest accuracy for predicting the addition of AZ after adjusting for baseline BMI and total testosterone levels. CONCLUSIONS: In our practice, following CC monotherapy, 30% of men were initiated on CC+AZ. Obesity (BMI≥30 kg/m²) and baseline estradiol ≥18.5 pg/mL can predict the conversion to combination therapy with addition of AZ. This information can be used to counsel patients and also help to identify patients who can be started on combination therapy upfront.

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/m2 . 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.