Safety and Efficacy of Clomiphene Citrate in the Treatment of Secondary Hypogonadism. A Retrospective Study

“Introduction: Clomiphene (Clomid) has an off-label indication to treat hypogonadism in select populations. “Based on clinical practice, this medication in certain types of hypogonadism is equally effective as testosterone in treating hypogonadism. It will lead to less side effects, lower treatment cost, and will decrease rates of infertility in the male veteran population.” Secondary hypogonadism can be most often caused by opioid use, obesity, sleep apnea, and diabetes.” “Aim of Study: To evaluate the safety and efficacy of Clomiphene Citrate in Treatment of Secondary Hypogonadism in comparison with testosterone. “Study Population: Data was obtained from the Veterans Administration Data Warehouse through the Veterans Administration Informatics and Computing Infrastructure. Data was extracted using SQL. There were 405,824 male patients with a diagnosis of hypogonadism (87.1%)and infertility (12.9%). nationally at the VA. Of these, 9566 patients have been treated with clomiphene citrate and 232,123 with various testosterone therapy. “ The two groups were then matched by propensity method to controls at a ratio of about 1:1 for Age, race, BMI and time for follow-up as potential confounding factors hat could have affected inclusion in the study controls. Patients without either Clomiphene or testosterone treatment were excluded. Statistical Analysis: SAS was used for propensity matching (PSM, greedy near) Categorical variables were evaluated as frequency counts with percentage within group, as well as ODDS ratio (OR) and differences were evaluated by a chi-square method. Comparisons of continuous variables were done were done by simple and paired t-test. Kaplan Meier plots and Cox Hazard ratio calculations were used to examine time dependent risk between treatments. Actual p-values are shown and p-values lower than 0.0001 are shown as such. All comparisons used a two-sided assumption. Measurements: Testosterone laboratory measures were recorded for start and end of trial. Survival was taken as the difference in days between start date and date of death. New diagnosis of Osteoporosis and Polycythemia was that which occurred after initiation of therapy. “Results: Clomid treatment normalized testosterone levels in 53.2% versus 46.8% in the testosterone group (OR 1.32 P<0.005). All-cause mortality was in the clomid group 0.16% and 1.62%in the testosterone group (OR 0.16 P<0.001). The incidence of new Osteoporosis for clomid was 3.9 % versus 5.9% for testosterone (OR 0.65 P<0.001)” Conclusion: This is a retrospective study comparing the efficacy and side effects of clomiphene versus testosterone for treatment of hypogonadism. The study showed that clomiphene is more effective than testosterone to treat secondary hypogonadism. We also found decreased overall mortality and incidence of polycythemia and osteoporosis.