A Preliminary Pharmacokinetic and Pharmacodynamic Evaluation of Depot-Medroxyprogesterone Acetate and Norethisterone Oenanthate

Abstract

A comparative pilot study was carried out in two World Health Organization Collaborating Centers on Research and Training in Human Reproduction (New Delhi and Stockholm) to assess the pharmacokinetic and pharmacodynamic properties of two injectable steroidal contraceptives, depot-medroxyprogesterone acetate (DMPA) and norethisterone oenanthate (NET-OEN). The assessment also included a variety of biochemical and hematologic indices. The period during which NET was detectable in the blood following injection of NET-OEN was significantly shorter in Indian women than in Swedish women. No difference was apparent with DMPA. None of the four Swedish women ovulated until more than 156 days after injection of DMPA and until plasma medroxyprogesterone acetate (MPA) levels were undetectable. The four Indian women ovulated within 73 days of injection of DMPA, and MPA levels at this time were above 0.6 ng/ml. There was no difference between the two centers in the time of return of ovulation for subjects receiving NET-OEN. For women receiving DMPA, the number of days on which bleeding and spotting occurred and the number of episodes of bleeding were significantly higher than those of women receiving NET-OEN. There were no significant changes in any of the biochemical or hematologic analyses as a result of injection of the gestagens. This preliminary study suggests that responses to the two injectable contraceptives may vary in different populations and emphasizes the need for more detailed comparative investigations in those countries where the formulations are expected to be in widespread use.