@article{54301bdab41f4a8792603ab61432e85d,
title = "Ovulation suppression following subcutaneous administration of depot medroxyprogesterone acetate",
abstract = "Objectives: To characterize the relationship between serum medroxyprogesterone acetate (MPA) concentrations and ovulation suppression, and to estimate the risk of ovulation for investigational subcutaneous regimens of Depo-Provera CI (Depo-Provera) and Depo-subQ Provera 104 (Depo-subQ). Study Design: We performed a secondary analysis of 2 studies that assessed the pharmacokinetics and pharmacodynamics of MPA when Depo-Provera is administered subcutaneously rather than by the labeled intramuscular route. Each woman received a single 45 mg to 300 mg subcutaneous injection of Depo-Provera, a single 104 mg subcutaneous injection of Depo-subQ, or 2 injections of Depo-subQ at 3-month intervals. We used an elevation of serum progesterone ≥4.7 ng/mL as a surrogate for ovulation and non-parametric statistical methods to assess pharmacokinetic and pharmacodynamic relationships. Results: This analysis included 101 women with body mass index (BMI) 18 to 34 kg/m2. Return of ovulation occurred at a median MPA concentration of 0.07 ng/mL (95% CI: 0.06–0.08) and the 90th percentile was 0.10 ng/mL (95% CI: 0.09–0.14). Neither age, race, nor BMI significantly influenced this relationship. The estimated probabilities of ovulation within 4 months of a 104 mg subcutaneous injection and within 7 months of a 150 mg subcutaneous injection (6 plus a 1-month grace) were each below 2.2%. Conclusions: The typical MPA concentration associated with loss of ovulation suppression is substantially less than the commonly cited threshold of 0.2 ng/mL. Based on our results, MPA levels would rarely be low enough to permit ovulation if the Depo-subQ reinjection interval were extended to four months or if 150 mg Depo-Provera were injected subcutaneously every 6 months. Implications: Extending the three-month Depo-subQ reinjection interval by one month would result in a 25% reduction in yearly MPA exposure, with little risk of pregnancy. Off-label subcutaneous administration of 150 mg Depo-Provera every 6 months would be a highly effective repurposing of an excellent product, with a similar reduction in cumulative exposure.",
keywords = "Depo-Provera, Depo-subQ Provera, DMPA, Pharmacodynamics, Pharmacokinetics",
author = "Taylor, {Douglas J.} and Vera Halpern and Vivian Brache and Luis Bahamondes and Jensen, {Jeffrey T.} and Dorflinger, {Laneta J.}",
note = "Funding Information: Role of the funding source: This work is made possible by the generous support of the American people through the U.S. Agency for International Development (USAID), provided to FHI 360 through Cooperative Agreement AID-OAA-A-15–00045, and through grant number OPP 1055878 from The Bill & Melinda Gates Foundation (BMGF), which funded one of the trials included in the analysis. The funders were not involved in the analysis, interpretation, or writing of this report. The contents are the responsibility of FHI 360, and do not necessarily reflect the views of USAID, the United States Government, or BMGF. Nor does any mention of trade names, commercial products, or organizations imply endorsement by FHI 360, USAID, the United States Government, or BMGF. Funding Information: We are grateful to the study participants and research staff at PROFAMILIA (Dominican Republic), Universidade Estadual de Campinas (Brazil), Instituto Chileno de Medicina Reproductiva (Chile), and Oregon Health and Science University (USA) for contributing the study data used in our analyses. Data sharing: After de-identification, Individual participant data from both studies analyzed here will be submitted to the Development Data Library (DDL), USAID's publicly available repository for Agency-funded data-on-demand. Declaration of Competing Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Role of the funding source: This work is made possible by the generous support of the American people through the U.S. Agency for International Development (USAID), provided to FHI 360 through Cooperative Agreement AID-OAA-A-15?00045, and through grant number OPP 1055878 from The Bill & Melinda Gates Foundation (BMGF), which funded one of the trials included in the analysis. The funders were not involved in the analysis, interpretation, or writing of this report. The contents are the responsibility of FHI 360, and do not necessarily reflect the views of USAID, the United States Government, or BMGF. Nor does any mention of trade names, commercial products, or organizations imply endorsement by FHI 360, USAID, the United States Government, or BMGF. Publisher Copyright: {\textcopyright} 2022",
year = "2022",
month = jan,
doi = "10.1016/j.conx.2022.100073",
language = "English (US)",
volume = "4",
journal = "Contraception: X",
issn = "2590-1516",
publisher = "Elsevier Inc.",
}