The United States has one of the highest adolescent pregnancy rates among industrialized nations. One of the major contributing factors is inadequate contraception. A very effective contraceptive method is depot-medroxyprogesterone acetate (DMPA) which has become increasingly popular in this age group. Recent research in adults has suggested a negative effect of DMPA on bone mineral density (BMD). With decreased BMD, one's risk increases later for osteoporosis, a major public health problem affecting millions of postmenopausal women every year. Compromised BMD would appear to be a particular concern in adolescents, as they normally accrue up to 40% of their total bone mineral content during this period. In preliminary work, the investigators demonstrated a 3.0% decrease in BMD in adolescent DMPA users over 2 years, compared with a 9.0% increase in untreated controls (p<0.0001). A prospective cohort study of the effects of DMPA on adolescent BMD, which will also include a double-blinded randomized prevention component, is proposed. Bone density in 400 adolescent DMPA initiators will be compared to their baseline values and to that of 300 and 120, oral and barrier contraceptive initiators, respectively, frequency matched on age and race. Bone density will be measured every six months for a maximum of two years. Bone density will also be measured at the time of discontinuation of contraceptive method. To evaluate the protective effects of estrogen on bone density, females in the DMPA treatment arm will be randomly assigned to DMPA with estradiol (n=200) and DMPA without estradiol (n=200). To examine the question of whether age modifies the effect of DMPA on bone density, the investigators will evaluate the age-treatment interaction between DMPA use and bone density among females of varying gynecologic ages. Finally, sex hormone levels and indices of calcium metabolism will be compared among the treatment groups in order to explore the biologic mechanisms underlying BMD changes. The statistical analysis will estimate the effect of DMPA on bone density while taking account of constant treatment discontinuation throughout the study period.
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