title: Testosterone:estradiol ratio changes associated with long-term tadalafil administration: a pilot study.
abstract: BACKGROUND
  It has been reported that lack of sexual activity due to erectile dysfunction (ED) may be associated with testosterone (T) decline.
  
  
  OBJECTIVE
  To investigate whether the known changes in sex hormones associated with resumption of sexual activity are sustained in the long term.
  
  
  METHODS
  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/m2) 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.
authors.affiliation: Internal Medicine, Department of Medical Pathophysiology, University of Roma "La Sapienza," Rome, Italy.
authors.forename: Emanuela A
authors.initials: EA
authors.lastname: Greco
authors.affiliation: Internal Medicine, Department of Medical Pathophysiology, University of Roma "La Sapienza," Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Pili
authors.affiliation: Internal Medicine, Department of Medical Pathophysiology, University of Roma "La Sapienza," Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bruzziches
authors.affiliation: Andrology Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corona
authors.affiliation: Internal Medicine, Department of Medical Pathophysiology, University of Roma "La Sapienza," Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Spera
authors.affiliation: Internal Medicine, Department of Medical Pathophysiology, University of Roma "La Sapienza," Rome, Italy;. Electronic address: antonio.aversa@uniroma1.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Aversa
mesh_terms: D000328:Adult; D000368:Aged; D002243:Carbolines / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007172:Erectile Dysfunction / Q000097:blood* / Q000188:drug therapy*; D004958:Estradiol / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D010410:Penile Erection / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D010865:Pilot Projects; D000068581:Tadalafil; D013739:Testosterone / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D013739:Testosterone; D004958:Estradiol; D000068581:Tadalafil