Early adolescent Depo-Provera exposure increases stillbirths in adult sooty mangabeys

Abstract

The 3-month injectable contraceptive medroxyprogesterone acetate (MPA; Depo-Provera) is a synthetic progestin that protects against pregnancy by suppressing ovulation. Studies have focused on the resumption of ovulation after MPA-treatment cessation but neglected potential long-term effects of MPA exposure on future successful reproduction. MPA is frequently administered to adolescent girls; however, long-term fertility effects of adolescent MPA exposure have not been explored. We investigated fertility after extended MPA exposure in a species of old world primate, the sooty mangabey (Cercocebus atys). Female sooty mangabeys (n=31) received chronic MPA-treatment for 4-8 years. At MPA-treatment onset, subjects were either parous adults (n=14) or nulliparous adolescents (n=17), with adolescent-treated subjects being further divided into those who had reached first ovulation (n=10) and those who had not (n=7). After MPA-treatment cessation, adolescent-treated females had a significantly higher incidence of stillbirth than did age-matched and parity-matched controls, whereas adult-treated females did not differ from their matched controls. Females placed on MPA-treatment prior to first ovulation had a significantly higher incidence of stillbirth post-treatment than did females placed on MPA-treatment after first ovulation. Diabetic females had an increased incidence of stillbirth as compared to nondiabetic females; however, when controlling for diabetes, MPA exposure prior to first ovulation was still a significant positive predictor of stillbirth. These findings suggest that the post-treatment fertility effects of chronic MPA exposure vary with the developmental timing of treatment onset and raise concern about the use of MPA as a contraceptive for adolescent girls.