Evaluation of extended use and return of ovulation (pharmacokinetics and pharmacodynamics) after the application of an ampoule of Cyclofem up to 90 days after injection.

• Grant number: 25/06715-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Luis Guillermo Bahamondes
• Grantee: Maria Júlia Bottura
• Host Institution: Centro de Atenção Integral à Saúde da Mulher (CAISM). Hospital da Mulher Professor Doutor José Aristodemo Pinotti. Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 23/13279-5 - Clinical aspects of new and current users of long-acting reversible contraceptives (intrauterine devices and implants) and once-a-month injectable contraceptives, AP.TEM

Abstract

Objectives: To assess whether the administration of one ampoule of the monthly combined injection with 5mg of oestradiol cypionate (CyE) and 25mg of medroxyproesterone (MPA) (Cyclofemina) is capable of inhibiting ovulation up to three months after its administration.Material and methods: This study will evaluate the pharmacokinetics (PK) of the use of the monthly combined injectable with 5mg oestradiol cypionate (CyE) and 25mg medroxyprogesterone (MPA) (Cyclofemina) up to three months after an injection in women. A total of 20 women aged between 18 and 36, healthy, protected from pregnancy by having undergone tubal ligation or using a copper IUD, with a Body Mass Index of less than 25, with regular menstrual cycles and without the use of any hormonal contraceptive in the last 12 months will be enrolled in the study. In the menstrual cycle prior to Cyclofemina administration, a blood sample will be taken between days 20-25 of the cycle to determine the serum progesterone level and check for the possibility of ovulation. If the progesterone level is less than or equal to 3 ng/ml, ovulation will be considered to have occurred on the date the sample was taken. The study drug will be administered at the CAISM/UNICAMP Family Planning Outpatient Clinic by a nurse in the arm (deltoids) or buttock (gluteus). The aim is to verify ovulation activity by taking a blood sample between days 15 and 20 after administration of the contraceptive to measure progesterone.For the PK study, weekly blood samples will be taken to determine progesterone and MPA levels. If progesterone levels are greater than or equal to 3 ng/ml, the participant will be discontinued on evidence of ovulation and a comparison will be made with that day's MPA levels. If ovulation does not occur, we will continue to take weekly blood samples until 90 days after the injection date. The lowest detectable MPA level is 0.02 ng/ml, with inter-assay variability of <11%, intra-assay variability with accuracy of -0.4 to 4.0%, and an average intra-assay coefficient of <8%. Statistical analysis: Sociodemographic data will be presented and analysis of variance will be performed to compare the time of ovulation with the MPA levels obtained on the same day, estimating the return to ovulation after injection according to Kaplan-Meier analysis with 95% CI after log-log transformation. We will calculate the area under the curve (AUC) using the linear/log trapezoidal norm using two samples obtained close to the previously specified date. The geometric means (GMs) and coefficients of variation will be calculated for each PK parameter.