Abstract
Background: Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for hematologic malignancies, but is associated with negative side effects, including reduced sexual function. It was recently reported that estradiol may exert an effect on sexual desire & erectile function, independent to that of testosterone, in healthy men. We hypothesized that changes in estrogen would be directly associated with changes in sexual function in men undergoing HCT. Methods: Nineteen men planning autologous HCT completed the International Index of Erectile Function (IIEF) & provided a morning, fasted blood sample at Baseline (before initiating preparatory chemotherapy) & 30±10 days post-HCT (FU). IIEF contains sub-categories of Erectile Function (EF), Orgasmic Function (OF), Sexual Desire (SD), Intercourse Satisfaction (IS), & Overall Satisfaction (OS). Plasma samples were analyzed for total testosterone (TT), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), sex-hormone binding globulin (SHBG), 17-OHprogesterone, 17-OHpregnenelone, androstenedione, androsterone, pregnenolone, progesterone, estrone (E1), & estradiol (E2) via LCMS; bioavailable (BT) & free T (FT) were calculated using local laboratory-derived albumin levels. Follicle-stimulating hormone (FSH) was analyzed via ELISA. Non-parametric, paired t-tests compared Baseline to FU & multiple regression identified significant predictors of sexual function changes using forced variables (age, HCT-comorbidity index (CI), cumulative steroid exposure, post-HCT testing day, diagnosis) & conditional variables (change scores for each hormone & relative fat mass change). Data are median ± SEM. Results: Men were 68±3 years of age (multiple myeloma, N=15; leukemia, N=6). Significant changes were observed at FU for E2 (-5.2±1.9 pg/mL, p=0.048), E1 (-6.6±2.2 pg/mL, p=0.002), FSH (4.6±0.9 IUL, p=0.002), TT (1.3±0.4 ng/mL, p=0.02), SHBG (41.2±5.5 nmol/L, p=0.001), DHT (0.06±0.03 ng/mL, p=0.03), androsterone (0.02±0.02 ng/mL, p=0.045), androstenedione (0.54±0.16 ng/mL, p=0.001), progesterone (0.02±0.01 ng/mL, p=0.01), & 17-OHprogesterone (0.27±0.08 ng/mL, p=0.001). Sexual function significantly decreased at FU for EF (p=0.003), OF (p=0.01), SD (p=0.009), IS (p=0.03), & IIEF Total (p=0.004). There were no significant predictors of OF, SD, or OS change scores. Diagnosis, HCT-CI, & change scores for E2 & 17-OHpregnenolone were significant predictors of EF change (F=13.3, p=0.005). Age, diagnosis, HCT-CI, & change scores for E2 androstenedione were significant predictors of IS change (F=14.5, p=0.004). Age, diagnosis, HCT-CI, & change scores for E2 & DHEA were significant predictors of Total IIEF changes (F=20.1, p=0.002). Conclusion: Acute changes in sexual function after HCT are likely influenced by HCT-induced reductions in estradiol, independent of changes in testosterone.
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