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

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.

Conflict of interest statement

Disclosure Summary: Procter & Gamble provided the study medication at no cost. E.A.L. has served as a consultant for and has a financial interest in OXT Therapeutics, Inc. K.K.M. is the recipient of an investigator-initiated research grant from Amgen and receives study drug at no cost and support for assays from Marinus Pharmaceuticals. The remaining authors have nothing to disclose.

All data generated or analyzed during this study are included in this published article or in the data repositories listed in References.

Copyright © 2019 Endocrine Society.

Figures

Figure 1.

Flow of study participation. *Reasons for discontinuation: increased irritability, relapse of alcohol use disorder, and pregnancy.

Figure 2.

Serum free testosterone in subjects receiving testosterone (black circles) or placebo (black squares). Horizontal dotted lines delineate the normal range of serum free testosterone for women of reproductive age. *P < 0.001 for the difference between groups over 24 wk. Error bars indicate SD.

Figure 3.

(A) Mean BMI increased by 0.0 ± 1.0 kg/m2 in the testosterone group and by 0.5 ± 1.1 kg/m2 in the placebo group over 24 wk (P = 0.03). (B) At 4 wk, there was a trend toward a greater decrease in mean depression severity score by HAM-D in the testosterone (black bars) vs placebo group (white bars) (P = 0.09). There was no difference in change in HAM-D scores between groups at 24 wk. (C) There was no difference in change in mean anxiety severity score by HAM-A between the testosterone (black bars) or placebo group (white bars) at 4 wk or 24 wk. Error bars indicate SD. *P < 0.05; **P < 0.1.