Testosterone: Estradiol Ratio Changes Associated with Long-Term Tadalafil Administration: A Pilot Study

Abstract

Introduction. It has been reported that lack of sexual activity due to erectile dysfunction (ED) may be associated with testosterone (T) decline. Aim. To investigate whether the known changes in sex hormones associated with resumption of sexual activity are sustained in the long term. Main Outcome Measures. Primary endpoints were variations from baseline of steroid hormones: total T, free T (f T), and estradiol (E). Secondary endpoints were variations of erectile function domain scores at International Index of Erectile Function-5 (IIEF-5). Methods. In an open-label fashion, 20 patients (mean age 54.8 ± 8.4 years) received tadalafil 10-20 mg on demand for 12 months. Exclusion criteria were those reported for phosphodiesterase inhibitors, including hypogonadism and hyperprolactinemia. Results. Tadalafil assumption was safe and well tolerated (overall adverse effects in 15% of patients) and none discontinued medication. A significant decrease in E levels occurred at the end of the study (from 19.9 ± 9.6 to 16.6 ± 8.1 ng/dL, P = 0.042 vs. baseline), with parallel increase in the T:E ratio (26.3 ± 15.3 to 32.6 ± 17.7, P = 0.05), whereas no changes in T and f T serum levels were observed, respectively (411.4 ± 131.4 to 434.2 ± 177.1 ng/dL and 47.7 ± 15.3 to 49.9 ± 19.1 pmol/L, not significant). Interestingly, nonparametric subgroup analysis for related samples revealed that E decrease was detectable only in lean (N = 14) but not in obese (N = 6, body mass index > 27.5 kg/m 2 ) subjects (17.8 ± 10.1 vs. 13.5 ± 6.8, P < 0.05). A net increase in IIEF-5 scores was observed at the endpoint (13.7 ± 5.9 vs. 25.7 ± 2.9, P < 0.0001). Conclusions. Sustained improvement in sexual function after 12 months of tadalafil administration is associated with increased T:E ratio mainly related to reduction of E levels. We hypothesize that androgen-estrogen cross-talk and possible inhibition of aromatase activity during chronic exposure to tadalafil might have a role in the regulation of erectile function. Greco EA, Pili M, Bruzziches R, Corona G, Spera G, and Aversa A. Testosterone:estradiol ratio changes associated with long-term tadalafil administration: A pilot study. J Sex Med 2006;3:716-722.