Amenorrhea due to anorexia remains difficult to treat

MONTREAL – Clinicians do not have many therapeutic interventions to choose from to help restore ovarian function in adolescent patients with anorexia nervosa, a presenter said at the annual meeting of the Canadian Pediatric Endocrine Group.

“Amenorrhea in anorexia nervosa is an important indicator of the pathology that can result from this condition,” Madhusmita Misra, MD, a pediatric endocrinologist at Massachusetts General Hospital and Associate Professor of Pediatrics at Harvard Medical School in Boston, Mass., said here. “Low energy availability in anorexia nervosa leads to reduction in fat mass and alterations in hormones secreted or regulated by fat, which in turn disrupt gonadotropin secretion causing menstrual dysfunction. The most important consequence in adolescents with anorexia nervosa and amenorrhea is the risk of low bone density and fracture. Adolescence is a critical time for bone accrual.”

Data show that adolescent girls with anorexia have very low rates of bone accrual compared to their normal-weight counterparts, Misra said, adding that the optimal therapy is weight gain.

“It’s important to try to optimize weight gain as early as possible in adults and in adolescents with anorexia,” Misra said. “Particularly in adolescents, the earlier that we can achieve weight gain and resumption of menses, the greater is their ability to optimize bone accrual and attain a reasonable peak bone mass.”

The nature of weight gain is also significant, Misra said, pointing out that fat mass, and not just lead mass, needs to increase to enable resumption of menses.

Research in anorexia in adolescents has focused on optimizing bone accrual by targeting hormones that are dysregulated in anorexia, Misra explained.

Oral estrogen and progesterone have not been effective in elevating bone density in adolescents, but estrogen administered transdermally does increase bone density in adolescent AN patients, she said, citing the literature.

“If estrogen is given transdermally, it does not suppress insulin growth factor-1,” Misra said, noting that IGF-1 (with estrogen) is essential for pubertal bone accrual.

Testosterone replacement over a 1-year period in women with anorexia resulted in increases in lead body mass but not bone density, she noted.

Bone anabolic therapy, such as teriparatide, has demonstrated an increase in bone formation and bone mineral density in adult women with anorexia after 6 months of treatment, but Dr. Misra cautioned against initiation of this therapeutic approach.

“We can’t currently advise teriparatide in adults with anorexia because it was a small study and we need more data, but it was a very promising result,” Misra said in an interview with Endocrine Today.

Bisphosphonate therapy as a means of increasing bone density is effective in adult women but has not shown to be effective in adolescent females, according to Misra. — Louise Gagnon

For more information:

Misra M. Ovarian Function in Anorexia Nervosa. Presented at the Canadian Pediatric Endocrine Group 2014 Scientific Meeting; Feb. 20-22, 2014; Montreal.

Frost ML. J Bone Miner Res. 2011; doi:10.1002/jbmr.305.

Fazeli PK. J Clin Endocrinol Metab. 2014; doi:10.1210/jc.2013-4105.

Disclosure: Misra reports a financial relationship with Genentech.