Osteoporosis and related fractures are growing public health problems. Factors affecting bone loss in later life and those affecting peak bone mass attainment are key to prevention of this condition. Several small studies suggest that depot medroxyprogesterone acetate (Depo-Provera, DMPA), an injectable progesterone-based contraceptive, decreases bone density and may thus increase a woman's later risk of osteoporosis. However, our ongoing evaluation of this association in a large study group provides evidence that DMPA's effects may be more complex, varying by age, duration of use, and anatomic site. In particular, effects on bone may be greater in younger age groups. Preliminary studies also suggest that discontinuation may favorably impact bone mass, but whether any effects are completely reversed and what roles age, duration of prior DMPA use, time since discontinuation, and other covariates may play is, as yet, unclear. We propose to continue our prospective epidemiologic evaluation of the effects of DMPA use on bone mineral density (BMD) in reproductive-age women. The primary aims are: to attain longer-term BMD evaluations in women who continue to use this contraceptive method; to assess the effects of discontinuation in women of varying age and durations of use; and to evaluate DMPA's effects on bone density in adolescents. Members of our established cohort of 457 women 18-39 years of age will be followed to evaluate more fully the effects of continued DMPA use on bone density and to assess changes in BMD after discontinuation. We propose to enrich our cohort with an additional group of adolescent participants. This group will be recruited from the same defined HMO population as our ongoing study group, using automated databases to select DMPA users and randomly-selected age-comparable women not using DMPA. Adolescent women will be followed for 24 to 36 months. For all participants the primary outcome, bone mineral density, will be measured every 6 months at various anatomic sites (hip, spine, and whole body) using dual-energy x-ray absorptiometry. This proposal addresses an area designated as a priority for research by the NIH/NICHD and incorporates a group (adolescents) deemed to be in critical need of adequate study. Moreover, DMPA is an increasingly popular contraceptive among young contracepting women. The size, diversity, and range of DMPA exposure in this study group allow for comprehensive evaluation of the possibly complex association between this effective, convenient and economical contraceptive and bone mass.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Kaufman, Steven
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Center for Health Studies
United States
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Scholes, Delia; Hubbard, Rebecca A; Ichikawa, Laura E et al. (2011) Oral contraceptive use and bone density change in adolescent and young adult women: a prospective study of age, hormone dose, and discontinuation. J Clin Endocrinol Metab 96:E1380-7
Beasley, Jeannette M; Ichikawa, Laura E; Ange, Brett A et al. (2010) Is protein intake associated with bone mineral density in young women? Am J Clin Nutr 91:1311-6
Scholes, Delia; Ichikawa, Laura; LaCroix, Andrea Z et al. (2010) Oral contraceptive use and bone density in adolescent and young adult women. Contraception 81:35-40
Ott, Susan M; Ichikawa, Laura E; LaCroix, Andrea Z et al. (2009) Navel jewelry artifacts and intravertebral variation in spine bone densitometry in adolescents and young women. J Clin Densitom 12:84-8
Ott, Susan M (2008) Reproductive hormones and skeletal health in young women. J Clin Endocrinol Metab 93:1175-7
Wetmore, C M; Ichikawa, L; LaCroix, A Z et al. (2008) Association between caffeine intake and bone mass among young women: potential effect modification by depot medroxyprogesterone acetate use. Osteoporos Int 19:519-27
Scholes, Delia; LaCroix, Andrea Z; Ichikawa, Laura E et al. (2005) Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Arch Pediatr Adolesc Med 159:139-44
Scholes, Delia; LaCroix, Andrea Z; Ichikawa, Laura E et al. (2004) The association between depot medroxyprogesterone acetate contraception and bone mineral density in adolescent women. Contraception 69:99-104
Scholes, Delia; LaCroix, Andrea Z; Ichikawa, Laura E et al. (2002) Injectable hormone contraception and bone density: results from a prospective study. Epidemiology 13:581-7
Ott, S M; Scholes, D; LaCroix, A Z et al. (2001) Effects of contraceptive use on bone biochemical markers in young women. J Clin Endocrinol Metab 86:179-85

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