madman
Super Moderator
Abstract
INTRODUCTION AND OBJECTIVES:
Clomiphene citrate (CC) is increasingly used off-label to treat male hypogonadism while preserving gonadal function. CC has been associated with dyslipidemia in women treated for ovulatory dysfunction, and preliminary data from our institution previously suggested that short-term CC use may reduce HDL levels in men. This study aimed to evaluate lipid profile changes in a larger cohort of hypogonadal men treated with CC.METHODS:
We performed a retrospective review of hypogonadal men treated with CC between January 2020 and October 2025 at a tertiary men’s health clinic. Pre- and post-treatment (4 weeks) fasting morning labs were compared. Total testosterone (TT) was measured using liquid chromatography–mass spectrometry (LCMS). Variables included TT, free testosterone (fT), estradiol (E2), hematocrit, hemoglobin, triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Patients with incomplete data were excluded.RESULTS:
A total of 352 men (mean age 48 ± 16 years, BMI 32.4 ± 7.9 kg/m2) were included. Following CC initiation, mean TT increased from 297.4 to 535.0 ng/dL (p0.001), and E2 from 25.1 to 42.0 pg/mL (p0.001), confirming biochemical efficacy. Mean TC decreased from 171.2 to 164.8 mg/dL (Δ −6.4 ± 34.2, p=0.038) and TG from 147.0 to 134.5 mg/dL (Δ −12.5 ± 86.4, p=0.101). HDL decreased significantly from 44.5 to 41.8 mg/dL (Δ −2.64 ± 11.0, p=0.008), while LDL showed no meaningful change (97.6 vs 96.8 mg/dL, p=0.761). A decline in HDL occurred in 61% of men, with 14% experiencing >10 mg/dL reductions within 4 weeks. No adverse events or hematologic abnormalities were observed.CONCLUSIONS:
In this expanded cohort, four weeks of CC therapy in hypogonadal men resulted in a statistically significant decrease in HDL, corroborating our prior institutional findings. TC decreased modestly, while E2 rose significantly. These results suggest that CC may have early, unfavorable effects on HDL despite favorable hormonal responses. Given the chronic use of CC in clinical practice, prospective long-term studies are warranted to determine the cardiometabolic implications of extended therapy.
