Madhusmita (Madhu) Misra, MD
Madhusmita (Madhu) Misra, MD, MPH, the Benjamin Armistead Shepherd Chair and Professor of Pediatrics at the University of Virginia and physician-in-chief of UVA Health Children’s, has been awarded a $3.5 million grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The grant will support her research project titled “Role of estrogen formulation and route of delivery on skeletal outcomes in functional hypothalamic amenorrhea.”
Functional hypothalamic amenorrhea is a condition where the reproductive axis shuts down in teenagers and young adult women as a consequence of excessive stress or more commonly from an energy deficit state, as seen in anorexia nervosa and in hyperexercising athletes, when energy intake is not sufficient to meet the needs of exercise energy expenditure.
A major complication of this condition is impaired skeletal health and an increased risk of fracture. In teenagers who develop functional hypothalamic amenorrhea, there is a reduced rate of bone accrual resulting in suboptimal peak bone mass (the maximum amount of bone achieved in an individual’s lifetime), typically achieved in the third decade of life. This results in a lifelong increased risk of low bone density and fracture. Low estrogen levels are a key contributor to impaired skeletal health in individuals with functional hypothalamic amenorrhea. Thus, estrogen replacement is an important strategy to restore estrogen levels and optimize bone accrual in these young women.
However, not all formulations and modes of delivery of estrogen are equally effective in improving bone density. For example, Dr. Misra and her colleagues have previously shown that while 17-beta estradiol (the natural form of estrogen in the body) administered as the transdermal patch is effective in improving bone density by 2-5%, the commonly used oral contraceptive pills containing ethinyl estradiol (a synthetic form of estrogen) and a progestin are not effective in improving skeletal health in functional hypothalamic amenorrhea because of the impact of oral ethinyl estradiol on certain hormones and chemicals that impact bone. But the transdermal 17-beta estradiol patch does not have contraceptive efficacy, and some women prefer an estrogen pill to the patch.
This grant will extend earlier observations by comparing the efficacy of three forms of estrogen in improving bone density, structure and strength in young women 14-25 years old with functional hypothalamic amenorrhea: the oral 17-beta estradiol pill given with a cyclic oral progestin, the transdermal 17-beta estradiol patch given with a cyclic oral progestin, and the transdermal contraceptive patch containing ethinyl estradiol and a progestin.
UVA Department of Pediatrics collaborators on this research include: Christine Burt-Solorzano, MD, Division of Pediatric Endocrinology; Sara Groff Stephens, PhD, Division of Adolescent Medicine and Teen Health; Laura Shaffer, PhD, Child Psychology. Additional collaborators from Virginia Commonwealth University include Alexandra F. Dejong Lempke, Department of Physical Medicine and Rehabilitation and Kelsey Hagan, PhD, Department of Psychiatry.
Filed Under: Research