Madhusmita Misra, M.P.H., M.B.B.S., M.D.


Chief of Pediatric Endocrinology
Pediatrics, Massachusetts General Hospital
Fritz Bradley Talbot and Nathan Bill Talbot Professor of Pediatrics, Emerita
Harvard Medical School
Physician Investigator (Cl)
Pediatric Endocrinology Program and Diabetes Center, Mass General Research Institute
MBBS SCB Medical College 1986
MPH 2005
amenorrhea; anorexia nervosa; athletes; body composition; bone and bones; bone density; ghrelin; human growth hormone; hydrocortisone

Female Athletes with Oligo-amenorrhea

Our group aims to further medical research and knowledge about common endocrine issues facing athletes today, including the female athlete triad. We have reported on the impact of exercise induced amenorrhea on bone density, structure and strength estimates, and the beneficial effects of transdermal estradiol (with cyclic progesterone), but not a combined hormonal contraceptive pill, on bone density and structure in these women. We have also demonstrated beneficial effects of transdermal estradiol on verbal memory, executive function, and eating behaviors in female oligo-amenorrheic athletes. A current study is assessing the impact of transdermal estradiol on cognitive flexibility and reward responsiveness in amenorrheic athletes and young women with restrictive eating behavior 16-26 years old.

Anorexia Nervosa

Our group has demonstrated that low bone density, impaired bone structure and reduced bone strength are prevalent in adolescent girls and boys with anorexia nervosa and are associated with decreased bone turnover. Hormonal alterations that predict low bone density in this disorder include hypogonadism, a nutritionally acquired resistance to growth hormone effects, and high cortisol levels. 

Weight gain and resumption of menses are associated with some improvement in bone parameters, however, residual deficits persist, raising concerns regarding inadequate catch-up and suboptimal peak bone mass acquisition. As in athletes, we have demonstrated the beneficial effects of transdermal estradiol (with cyclic progesterone) on bone density in these women. We have also demonstrated beneficial effects of transdermal estradiol on trait anxiety measures in adolescents with anorexia nervosa. A current study is assessing the impact of transdermal estradiol on cognitive flexibility and reward responsiveness in amenorrheic athletes and young women with restrictive eating behavior 16-26 years old. Another study is examining homoestatic and hedonic food motivation pathways in the brain in young women with low weight eating disorders.

Obesity

Our group has demonstrated that growth hormone and cortisol status are important determinants of visceral fat, cardiometabolic risk, and bone outcomes in adolescent girls with obesity, and that low dose growth hormone administration improves markers of cardiometabolic risk in these girls. We are currently examining the impact of weight loss surgery (gastric bypass vs. sleeve gastrectomy vs. no surgery) on bone outcomes in youth with obesity 14-25 years old, and also the effect of weight loss surgery on insulin secretion and resistance.

Type 1 Diabetes

We have demonstrated that an elevated HbA1C is a predictor of impaired bone structure in girls with type 1 diabetes 10-16 years old vs. controls. We are now examining bone accrual in these girls over a one-year period, and are beginning a study of bone outcomes in adolescent and young adult males with type 1 diabetes.