title: Effects of aromatase inhibition on sexual function and well-being in postmenopausal women treated with testosterone: a randomized, placebo-controlled trial.
abstract: OBJECTIVE
  The extent to which aromatization of testosterone (T) to estradiol is required for the observed effects of testosterone therapy on sexual function and well-being are not known. Therefore, the authors investigated the effects of aromatase enzyme inhibition on sexual function, well-being, and mood in estrogen- and T-replete postmenopausal women in a double-blind, randomized, placebo-controlled study.
  
  
  METHODS
  Postmenopausal women using transdermal estrogen therapy for at least 8 weeks and reporting low sexual satisfaction (score <42 for the Sabbatsberg Sexual Self-rating Scale [SSS]) with a total T value of less than 1.2 nmol/L were treated with 400 muL of a 0.5% T gel (total dose 2 mg) and were randomly assigned to receive treatment with either 2.5 mg/day of letrozole or an identical placebo tablet. Women were assessed at baseline (week -2) and at 0, 4, 8, and 16 weeks. Sexual function was assessed with the SSS, well-being was assessed with the Psychological General Well-being Index, and mood was assessed with the Beck Depression Inventory at 0 and 16 weeks. Eighty-one women were screened, 76 were randomly assigned to a treatment group, and 30 in each group completed the study. Because this was a mechanistic study, only the 60 women who completed the study per protocol were included in the final analysis.
  
  
  RESULTS
  Total T and calculated free T increased from baseline in both groups, with no difference between groups. At 16 weeks, estradiol, sex hormone-binding globulin, fasting lipids, lipoprotein(a), and C-reactive protein did not differ from baseline or between groups. Significant increases in total Sabbatsberg Sexual Self-rating Scale scores, total Psychological General Well-being Index scores, and a reduction in Beck Depression Inventory scores from baseline to 16 weeks was seen for both treatment groups, with no effect of treatment allocation. No adverse treatment effects were reported.
  
  
  CONCLUSIONS
  Increases in total and free T in the physiologic range in postmenopausal women were associated with improved sexual satisfaction, well-being, and mood. In this study, aromatase inhibition did not influence any of these outcomes. Short-term transdermal T therapy did not modify fasting lipids, lipoprotein(a), or C-reactive protein.
authors.affiliation: Women's Health Program, Department of Medicine, Central and Eastern Clinical School, Monash University, Alfred Hospital, Prahran, Victoria, Australia. susan.davis@med.monash.edu.au
authors.forename: Susan R
authors.initials: SR
authors.lastname: Davis
authors.forename: Rebecca
authors.initials: R
authors.lastname: Goldstat
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Papalia
authors.forename: Sonal
authors.initials: S
authors.lastname: Shah
authors.forename: Jayashri
authors.initials: J
authors.lastname: Kulkarni
authors.forename: Susan
authors.initials: S
authors.lastname: Donath
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Bell
mesh_terms: D000279:Administration, Cutaneous; D000339:Affect / Q000187:drug effects*; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000032:analysis; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood; D015914:Estrogen Replacement Therapy / Q000379:methods; D005260:Female; D006801:Humans; D000077289:Letrozole; D008055:Lipids / Q000097:blood; D017270:Lipoprotein(a) / Q000097:blood; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology; D010919:Placebos; D019529:Sexuality / Q000187:drug effects*; D013739:Testosterone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D008055:Lipids; D017270:Lipoprotein(a); D009570:Nitriles; D010919:Placebos; D014230:Triazoles; D013739:Testosterone; D004958:Estradiol; D000077289:Letrozole; D002097:C-Reactive Protein