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Relationship between drug exposure and DNA markers with depot medroxyprogesterone acetate-associated side effects in adolescents

Andrea Bonny, Nationwide Children's Hospital, 2011

Project abstract

Depot medroxyprogesterone acetate (DMPA) is a progestin-only, hormonal contraceptive that is extremely effective, obviates the need for daily or weekly compliance, and can be used privately. DMPA is very appealing for the adolescent contraceptive user.

Despite its many advantages, DMPA continuation rates are low in adolescents. Side effects, namely weight gain and bone mineral density (BMD) loss, are major barriers to prolonged DMPA use.

The research questions in this study are whether:

  1. higher circulating levels of medroxyprogesterone acetate (MPA) are related to weight gain and BMD loss, and
  2. whether selected genetic markers are predictive of weight gain and BMD loss.

Specific Aim 1 will assess measures of weight gain and BMD loss on DMPA and their association to MPA drug exposure. A clinical study on 45 adolescents age 12-21 years, enrolled into three DMPA dose cohorts (150, 104, and 75 mg) will be performed to determine a dose of DMPA that mitigates weight gain and BMD loss while maintaining contraceptive efficacy.

Specific Aim 2 will explore genetic markers which predispose adolescent girls to either DMPA-associated weight gain or BMD loss. Gene-specific single nucleotide polymorphisms of genomic DNA from our cohort of girls on DMPA will be performed to identify genetic markers for susceptibility to DMPA-induced weight gain and BMD loss.

Our long-term objectives are to establish a framework for early identification of risk of DMPA side effects and use of pharmacokinetic-pharmacodynamic parameters to individualize DMPA dosing in the future.


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