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Temporal Effects of Clomiphene Citrate on Testosterone and Semen Parameters (2022)
TJiang, JSigalos, ASantamaria, NModiri, MZheng, VOsadchiy, RJayadevan, MIslam, JMills, SEleswarapu
Introduction
In men with secondary hypogonadism or impaired sperm concentrations, clomiphene citrate (CC) is often prescribed off-label to improve testosterone levels and fertility parameters. Prior studies have largely focused on outcomes in the short term (∼3 months). The longer-term efficacy of CC use is less clear, particularly if and when improvement may reach a plateau.
Objective
We sought to determine the magnitude of improvement in total testosterone and sperm concentration in men taking CC for fertility optimization 3, 6, 9, and 12-month interval follow-up.
Methods
With IRB approval, we retrospectively evaluated men presenting to an academic andrology clinic for fertility evaluation who were prescribed CC from January 2016 through May 2021. We identified men with 3, 6, 9, and 12-month follow-up data for total testosterone (TT) and 3, 6, and 9-month follow-up semen analyses. Mean absolute changes in TT and sperm concentration are reported, along with 95% confidence intervals. Men with previous genitourinary procedures or hormone therapy were excluded. Paired t-tests were used to compare changes in TT and sperm concentration at each time point to baseline, and statistical significance was set at p<0.05.
Results
CC (25 mg qd or 50 mg qod) was prescribed to 235 men seeking fertility optimization during the 5-year period. The mean age was 37.7 (SD 6.7, range 24-52). Of these 235, data for TT at 3, 6, 9, and 12 months were available for 25 men, and semen analyses at 3, 6, and 9 months were available for 26 men. Baseline TT at the time of prescription was 358±145 ng/dL, and baseline sperm concentration was 13±17.2 M/mL. In the subset of 25 men with long-term follow-up data, a statistically significant improvement in TT was identified at 3 months (+62.7 ng/dL, 95% CI: 0.49-125.0 ng/dL, p=0.048), an additional benefit was seen at 6 months (+181.8 ng/dL, 95% CI: 114.1-249.5 ng/dL, p<0.01) followed by plateau at 9 and 12 months (Figure A). Improvement in sperm concentration was first noted at 9 months of treatment with CC (+20.7 M/mL, 95% CI: 10.2-31.2 M/mL, p<0.01) (Figure B). At no point were there improvements in semen volume and % motility at any follow-up.
Conclusions
In men prescribed CC for fertility optimization, we observed a maximal improvement in TT at 6 months, followed by a plateau. Sperm concentrations showed a statistically significant improvement at 9 months. Our results suggest that a longer duration of CC therapy may be needed to fully appreciate the benefit of CC treatment. Our study is limited by retrospective analysis, absence of controls, and small sample size. Work is underway to examine long-term follow-up data of CC in men seeking treatment for hypogonadism rather than optimization of fertility.
TJiang, JSigalos, ASantamaria, NModiri, MZheng, VOsadchiy, RJayadevan, MIslam, JMills, SEleswarapu
Introduction
In men with secondary hypogonadism or impaired sperm concentrations, clomiphene citrate (CC) is often prescribed off-label to improve testosterone levels and fertility parameters. Prior studies have largely focused on outcomes in the short term (∼3 months). The longer-term efficacy of CC use is less clear, particularly if and when improvement may reach a plateau.
Objective
We sought to determine the magnitude of improvement in total testosterone and sperm concentration in men taking CC for fertility optimization 3, 6, 9, and 12-month interval follow-up.
Methods
With IRB approval, we retrospectively evaluated men presenting to an academic andrology clinic for fertility evaluation who were prescribed CC from January 2016 through May 2021. We identified men with 3, 6, 9, and 12-month follow-up data for total testosterone (TT) and 3, 6, and 9-month follow-up semen analyses. Mean absolute changes in TT and sperm concentration are reported, along with 95% confidence intervals. Men with previous genitourinary procedures or hormone therapy were excluded. Paired t-tests were used to compare changes in TT and sperm concentration at each time point to baseline, and statistical significance was set at p<0.05.
Results
CC (25 mg qd or 50 mg qod) was prescribed to 235 men seeking fertility optimization during the 5-year period. The mean age was 37.7 (SD 6.7, range 24-52). Of these 235, data for TT at 3, 6, 9, and 12 months were available for 25 men, and semen analyses at 3, 6, and 9 months were available for 26 men. Baseline TT at the time of prescription was 358±145 ng/dL, and baseline sperm concentration was 13±17.2 M/mL. In the subset of 25 men with long-term follow-up data, a statistically significant improvement in TT was identified at 3 months (+62.7 ng/dL, 95% CI: 0.49-125.0 ng/dL, p=0.048), an additional benefit was seen at 6 months (+181.8 ng/dL, 95% CI: 114.1-249.5 ng/dL, p<0.01) followed by plateau at 9 and 12 months (Figure A). Improvement in sperm concentration was first noted at 9 months of treatment with CC (+20.7 M/mL, 95% CI: 10.2-31.2 M/mL, p<0.01) (Figure B). At no point were there improvements in semen volume and % motility at any follow-up.
Conclusions
In men prescribed CC for fertility optimization, we observed a maximal improvement in TT at 6 months, followed by a plateau. Sperm concentrations showed a statistically significant improvement at 9 months. Our results suggest that a longer duration of CC therapy may be needed to fully appreciate the benefit of CC treatment. Our study is limited by retrospective analysis, absence of controls, and small sample size. Work is underway to examine long-term follow-up data of CC in men seeking treatment for hypogonadism rather than optimization of fertility.
