Magnetic resonance imaging and spectroscopy evidence of efficacy for adrenal and gonadal hormone replacement therapy in anorexia nervosa

Abstract

Purpose: Dehydroepiandrosterone (DHEA)+estrogen/progestin therapy for adolescent girls with anorexia nervosa (AN) has the potential to arrest bone loss. The primary aim of this study was to test the effects of DHEA+estrogen/progestin therapy in adolescent girls with AN on bone marrow in the distal femur using magnetic resonance imaging (MRI) and spectroscopy.

Methods: Seventy adolescent girls with AN were enrolled in a double blind, randomized, placebo-controlled trial at two urban hospital-based programs.

Intervention: Seventy-six girls were randomly assigned to receive 12months of either oral micronized DHEA or placebo. DHEA was administered with conjugated equine estrogens (0.3mg daily) for 3months, then an oral contraceptive (20μg ethinyl estradiol/ 0.1mg levonorgestrel) for 9months. The primary outcome measure was bone marrow fat by MRI and magnetic resonance spectroscopy (MRS).

Results: T2 of the water resonance dropped significantly less in the active vs. placebo group over 12months at both the medial and lateral distal femur (p=0.02). Body mass index (BMI) was a significant effect modifier for T1 and for T2 of unsaturated (T2unsat) and saturated fat (T2sat) in the lateral distal femur. Positive effects of the treatment of DHEA+estrogen/progestin were seen primarily for girls above a BMI of about 18kg/m2.

Conclusions: These findings suggest treatment with oral DHEA+estrogen/progestin arrests the age- and disease-related changes in marrow fat composition in the lateral distal femur reported previously in this population.

Keywords: Adolescence; Bone marrow; Dehydroepiandrosterone; Eating disorders; Hormone replacement therapy.

Copyright © 2018. Published by Elsevier Inc.

Figures

Figure 1. Subject Recruitment (depicted through consort diagram for clinical trial)

The study was a two-site, double blind, randomized, placebo-controlled trial. The hospital pharmacy dispensed drug or placebo in identical gelatin capsules. Assignments (computerized blocked randomization) were not revealed aside from the pharmacist and statistician until the trial’s conclusion. The treatment arm received 12 months of oral micronized DHEA (50 mg daily; Belmar Pharmacy; IND 52192) with conjugated equine estrogens (0.3mg daily; Premarin®, Wyeth) for the first 3 months, followed by an oral contraceptive (20μg ethinyl estradiol/0.1mg levonorgestrel; Alesse®, Wyeth) for 9 months. The other group received placebo.

Figure 2

Figure 2A shows the baseline T1-weighted image of the right knee of a 16-year-old girl with anorexia nervosa. The MR spectroscopic voxels are shown as black (medial) and white (lateral) rectangles. Figures 2B and 2C show the spectra from the lateral voxel with TE=30 msec and TE=60 msec respectively. The 5 relevant lipid peaks along with the water peak are seen, along with the fits and peak areas measured by the vendor-supplied software.

Figure 3. 12-Month Change in T1, T2unsat and T2sat:

Figure 3 shows the adjusted 12-month change in T1, T2unsat, and T2sat in the lateral distal femur, plotted as a function of BMI. BMI was a significant effect modifier for all 3 variables. The top row shows the changes in T1 in the active cohort, the middle row shows the placebo cohort, and the bottom row plots the difference between them. The gray shaded area in the bottom row shows 95% confidence limits for the difference. T2unsat and T2sat are plotted on a log10 scale, and therefore the dashed lines at 1 on the y-axis (Figures 3F and 3I) correspond to a raw value of 0, which denotes no difference between active and placebo groups. Positive effects of the treatment of DHEA + E/P are seen primarily for girls above a BMI of about 18 kg/m2. As seen from the graphs, our sample is skewed toward higher BMI girls, leading to a larger standard error at low BMI.