A Randomized Placebo-Controlled Trial of Low-Dose Testosterone Therapy in Women With Anorexia Nervosa

J Clin Endocrinol Metab. 2019 Oct 1;104(10):4347-4355. doi: 10.1210/jc.2019-00828.

Abstract

Context: Anorexia nervosa (AN) is a psychiatric illness with considerable morbidity and no approved medical therapies. We have shown that relative androgen deficiency in AN is associated with greater depression and anxiety symptom severity.

Objective: To determine whether low-dose testosterone therapy is an effective endocrine-targeted therapy for AN.

Design: Double-blind, randomized, placebo-controlled trial.

Setting: Clinical research center.

Participants: Ninety women, 18 to 45 years, with AN and free testosterone levels below the median for healthy women.

Intervention: Transdermal testosterone, 300 μg daily, or placebo patch for 24 weeks.

Main outcome measures: Primary end point: body mass index (BMI). Secondary end points: depression symptom severity [Hamilton Depression Rating Scale (HAM-D)], anxiety symptom severity [Hamilton Anxiety Rating Scale (HAM-A)], and eating disorder psychopathology and behaviors.

Results: Mean BMI increased by 0.0 ± 1.0 kg/m2 in the testosterone group and 0.5 ± 1.1 kg/m2 in the placebo group (P = 0.03) over 24 weeks. At 4 weeks, there was a trend toward a greater decrease in HAM-D score (P = 0.09) in the testosterone vs placebo group. At 24 weeks, mean HAM-D and HAM-A scores decreased similarly in both groups [HAM-D: -2.9 ± 4.9 (testosterone) vs -3.0 ± 5.0 (placebo), P = 0.72; HAM-A: -4.5 ± 5.3 (testosterone) vs -4.3 ± 4.4 (placebo), P = 0.25]. There were no significant differences in eating disorder scores between groups. Testosterone therapy was safe and well tolerated with no increase in androgenic side effects compared with placebo.

Conclusion: Low-dose testosterone therapy for 24 weeks was associated with less weight gain-and did not lead to sustained improvements in depression, anxiety, or disordered eating symptoms-compared with placebo in women with AN.

Trial registration: ClinicalTrials.gov NCT01121211.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Cutaneous
  • Adolescent
  • Adult
  • Age Factors
  • Anorexia Nervosa / diagnosis*
  • Anorexia Nervosa / drug therapy*
  • Anxiety / drug therapy
  • Anxiety / physiopathology
  • Body Mass Index*
  • Depression / drug therapy
  • Depression / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Patient Selection
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Testosterone / therapeutic use*
  • Treatment Failure
  • United States
  • Young Adult

Substances

  • Testosterone

Associated data

  • ClinicalTrials.gov/NCT01121211