Introduction. Depot medroxyprogesterone acetate (DMPA, Depo-Provera®) contraception is used by over nine million women worldwide and has a high usage among teenagers in Britain and the USA. Previous studies have found that DMPA use is associated with a bone density deficit.

Objectives. This case-control matched study aims to eliminate potential confounding factors, to identify if the effect of DMPA on the skeleton is age-specific and to determine the effects of DMPA on hormones and bone turnover.

Design/participants. We measured bone density, bone turnover and hormones in individually matched case-control pairs of women; 50 pairs aged 18–25 and 50 pairs aged 35–45.

Results. DMPA use was associated with a five percent bone density deficit at the lumbar spine and hip in women who started DMPA use before age 20, but not after age 34. Bone turnover was increased in DMPA users in both age groups. DMPA users had lower estradiol and higher IGF-1 than controls, and younger DMPA users had higher DHEAS than controls. In a multiple regression model estradiol and IGF-1 were associated with bone turnover, but addition of DMPA to the model made the association with estradiol non-significant.

Conclusions. DMPA use is associated with a bone density deficit at the spine and the hip when used before peak bone mass. DMPA acts on the skeleton mainly through estrogen deficiency.