Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study

Oncologist. 2011;16(4):424-31. doi: 10.1634/theoncologist.2010-0435. Epub 2011 Mar 8.


Purpose: Controversy exists about whether vaginal estrogens interfere with the efficacy of aromatase inhibitors (AIs) in breast cancer patients. With the greater incidence of vaginal atrophy in patients on AIs, a safe and effective nonestrogen therapy is necessary. We hypothesized that vaginal testosterone cream could safely treat vaginal atrophy in women on AIs.

Methods: Twenty-one postmenopausal breast cancer patients on AIs with symptoms of vaginal atrophy were treated with testosterone cream applied to the vaginal epithelium daily for 28 days. Ten women received a dose of 300 μg, 10 received 150 μg, and one was not evaluable. Estradiol levels, testosterone levels, symptoms of vaginal atrophy, and gynecologic examinations with pH and vaginal cytology were compared before and after therapy.

Results: Estradiol levels remained suppressed after treatment to <8 pg/mL. Mean total symptom scores improved from 2.0 to 0.7 after treatment (p < .001) and remained improved 1 month thereafter (p = .003). Dyspareunia (p = .0014) and vaginal dryness (p <.001) improved. The median vaginal pH decreased from 5.5 to 5.0 (p = .028). The median maturation index rose from 20% to 40% (p < .001). Although improvement in total symptom score was similar for both doses (-1.3 for 300 μg, -0.8 for 150 μg; p = .37), only the 300-μg dose was associated with improved pH and maturation values.

Conclusions: A 4-week course of vaginal testosterone was associated with improved signs and symptoms of vaginal atrophy related to AI therapy without increasing estradiol or testosterone levels. Longer-term trials are warranted.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Administration, Intravaginal
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Aromatase Inhibitors / adverse effects*
  • Aromatase Inhibitors / therapeutic use
  • Atrophy
  • Breast Neoplasms / complications*
  • Breast Neoplasms / drug therapy*
  • Estradiol / blood
  • Estrogens / administration & dosage
  • Female
  • Humans
  • Middle Aged
  • Pilot Projects
  • Testosterone / administration & dosage*
  • Testosterone / adverse effects
  • Vagina / pathology*


  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Estrogens
  • Testosterone
  • Estradiol