129 Comparison of the Effects of Oral Enclomiphene Citrate and Topical Testosterone Gels Treatment on Serum Hormones, Erythrocytosis, Lipids, and Prostate Specific Antigen

Abstract

INTRODUCTION AND OBJECTIVES: Testosterone therapy (TTh) is often the mainstay for hypogonadism treatment. Adverse effects of TTh include lipid abnormalities, erythrocytosis, and increases in prostate specific antigen (PSA). Enclomiphene citrate (En) can raise T levels, but its effects on lipids, erythrocytosis, and PSA are unknown relative to TTh. Here, we compare effects of topical T gels and oral En in hypogonadal men on serum hormones, lipids, erythrocytosis, and PSA. METHODS: Data from 11 prospective, randomized, blinded Phase 2/3 trials of oral En, placebo, and T gels were analyzed. Men with secondary hypogonadism based on two morning serum evaluations for total T (TT) <300 ng/dL and low-to-normal LH were enrolled; 130 men on T gels, 290 on placebo, and 953 on En completed the study protocols. TT, dihydrotestosterone (DHT), estradiol (E), hemoglobin (Hgb), hematocrit (Hct), PSA, total cholesterol (Tchol), triglycerides (TG), LDLChol, and HDL-Chol were evaluated at baseline (BL) and during regular follow-up for up to 1 year, and compared using a mixed model linear regression for repeated measures. RESULTS: Both T gels and En raised serum TT, DHT and E levels, with a more significant increase in TT and E levels in men on En (En TT: 216+/-64 vs. 450+/-182 mg/dL at BL and 12 months; T gels TT: 231+/-74 vs. 379+/-187 ng/dL at BL and 12 months), and a slower return to baseline after treatment was discontinued. In contrast, Hgb and Hct were higher in men on T gels (Hct 49.3% at 12 months) than En (46.9% at 12 months), although only one patient discontinued T gel due to erythrocytosis (Hct >54%); no erythrocytosis occurred in men taking En. Small, clinically insignificant increases in mean PSA were observed with En (0.8 vs. 1.2 ng/mL at BL and 12 months) that were not observed in men on T gels (0.9 vs. 0.8 ng/mL at BL and 12 months). Decreases in TChol (En: 190 vs. 178 mg/dL; T gel 193 vs. 190 mg/dL at BL and 12 months), HDL-Chol (En: 49 vs. 41 mg/dL; T gel 42 vs. 42 mg/dL at BL and 12 months) and LDL-Chol (En: 106 vs. 101 mg/dL; T gel 115 vs. 117 mg/dL at BL and 12 months) were observed with both En and T gels, with more significant changes with En. Effects on triglycerides were variable and inconsistent for both En and T gels. CONCLUSIONS: En therapy results in more significant and sustained increases in TT and E, as well as more significant and sustained decreases in TChol, HDL-Chol and LDL-Chol, than T gel therapy. Clinically insignificant effects on PSA, Hgb, and Hct are observed. En may represent an effective, low-risk treatment option for androgen deficient men with few adverse effects.