SAN FRANCISCO – Teenage girls with anorexia have less anxiety about gaining weight if their estrogen levels have been returned to normal, according to a small, randomized study, researchers from Massachusetts General Hospital and Harvard Medical School in Boston reported.
If confirmed in additional studies, it is an important finding, because anxiety about weight gain can sabotage anorexia nervosa treatment. "Physiological estrogen replacement is a potential strategy to reduce ... anxiety and improve chances of successful treatment," said lead investigator Dr. Madhusmita Misra, a pediatric endocrinologist and associate professor of pediatrics at Harvard Medical School in Boston.
Her team randomized female patients aged 13-18 years to 100-mcg transdermal estradiol twice weekly with cyclic progesterone 10 days/month, or to placebo patches and pills.
After 18 months, 20 girls on active treatment, when compared with 17 on placebo, had a significant decrease in trait anxiety, the tendency to experience anxiety as assessed by the State-Trait Anxiety Inventory for Children (–3.05 vs. 2.07, P = .01). Patients with the greatest estrogen level increases had the greatest reductions in trait anxiety scores (P = .001).
The girls were amenorrheic, with baseline estrogen levels far below normal; the intervention restored them to physiologic levels. They all met DSM-IV anorexia criteria, had bone ages of at least 15 years old, and were under treatment.
There were no significant between-group baseline differences in body mass index, psychotropic medication use, age, estrogen levels, questionnaire scores, and other factors, including weight gain over the 18 months. "We did various multiple adjustments to be sure there were not any confounders driving this association," Dr. Misra said.
Estrogen replacement did not directly affect eating attitudes assessed by the Eating Disorders Inventory II questionnaire, or body-shape perceptions assessed by the Body Shape Questionnaire (BSQ-34). However, it did seem to prevent an increase in body dissatisfaction and state anxiety – current anxiety – with weight gain, something noted in the placebo group and common in anorexia nervosa treatment.
"We have shown" before "that physiologic estrogen replacement is very important for normalizing the rate of bone accrual" in teenage girls with the condition (J. Bone. Miner. Res. 2011;26:2430-8). "This seems to be an additional benefit. These findings have the potential to [affect] therapy in anorexia nervosa with early implementation of estrogen replacement in girls who are estrogen deficient. [But,] more studies are necessary to confirm these findings; it would be premature to advise estrogen replacement just for anxiety issues," Dr. Misra said.
Estradiol levels during the study increased a mean of 117.0 pg/mL in treated girls, and 22.4 pg/mL in the placebo group.
The investigators said they have nothing to disclose. The National Institutes of Health funded the work.