This is an application for a competing continuation to R01 HD39100 """"""""Depo-provera and Bone Density in Premenopausal Women."""""""" Because depot-medroxyprogesterone (Depo Provera, DMPA) suppresses estradiol concentrations, concern has been raised that use of the drug would adversely affect bone mineral density. The ongoing parent study is longitudinal, comparing changes in bone mineral density (BMD) every 3 months for 24 months between women newly initiating DMPA for contraception and women using no hormonal method of contraception. The study evaluates the effect of DMPA on bone loss, and whether DMPA-related BMD loss is attenuated by higher calcium intakes, or predicted by estradiol levels, patterns of irregular bleeding or weight gain. At baseline, participants have BMD, height, weight, and percent body fat measured, and blood collected for estradiol concentrations. Enrollees also completed an interview detailing nutritional, lifestyle, demographic, medical, reproductive and behavioral factors that may influence BMD. BMD and physical measurements are repeated and the nutrition and physical activity components of the interview updated at each follow-up visit. Our data demonstrate that hip and spine BMD decline after one DMPA injection and continued with each subsequent injection for 24 months. After two years there was an average of 5.8% BMD loss at the hip and 5.7% loss at the spine. BMD continues to decline after two years, thus the magnitude of BMD loss and its potential consequences are not yet known. Whether BMD is regained following DMPA discontinuation is of primary importance. We are developing a rich pool of participants who have discontinued DMPA. Extending the observation from 24 to 48 months will allow us to determine whether and how rapidly DMPA-related loss of BMD is reversed. There are few published longitudinal studies of BMD changes in women using DMPA for contraception and those studies are limited by lack of baseline data, lack of control groups, short observation periods and small sample sizes. DMPA is used by approximately 10% of women choosing hormonal contraception and approximately 30% will use DMPA for more than 24 months. The manufacturer's label on Depo-Provera warns of potential bone loss yet the magnitude and impact of that loss is not known, leaving clinicians and consumers with little information on which to make sound evidence-based decision. Extending the observational period of this study will be an efficient and cost effective means of more fully understanding DMPA-related bone changes over a period of time that, realistically, reflects the length of DMPA use by a substantial proportion of women choosing DMPA for contraception. It will also provide information on the reversibility of DMPA-related bone loss. This competing continuation will extend the observation period of the parent study from 24 months per enrollee to 48 months per enrollee. The longitudinal design will be continued, maintaining all methods and protocols employed in the parent study.
