@Article{info:doi/10.2196/63683,
author="Cagnacci, Angelo
and Grandi, Giovanni
and Capobianco, Giampiero
and Fulghesu, Anna Maria
and Morgante, Giuseppe
and Biondelli, Vincenzo
and Piccolo, Elena
and Casolati, Elena
and Mangrella, Mario",
title="Effects of a Monophasic Hormonal Contraceptive With Norgestimate+Ethinyl Estradiol on Menstrual Bleeding: Protocol and Design of a Multicenter, Prospective, Open-Label, Noncomparative Study in Italy",
journal="JMIR Res Protoc",
year="2025",
month="Mar",
day="31",
volume="14",
pages="e63683",
keywords="combined oral contraceptive; ethinyl estradiol; menstrual cycle; monophasic; norgestimate; hormonal contraceptive; menstrual health; Italy; women's health; patient-reported outcomes; methodology; observational study; reproductive health; data analysis; assessment",
abstract="Background: Norgestimate (NGM) is a progestin with negligible androgenic activity that is available in combination with ethinyl estradiol (EE) as a monophasic combined oral contraceptive (COC). It has been more than 30 years since a clinical study evaluated the effects of monophasic NGM/EE on menstrual cycle characteristics in healthy women, and in the interim, there has been growing recognition that clinical trials of contraceptives should evaluate a wide range of potential positive and negative impacts for users. Objective: The aim of this study is to investigate menstrual cycle control during the use of a monophasic COC formulation containing NGM 0.25 mg and EE 0.035 mg (Effimia; Italfarmaco SpA), using established methodologies as well as patient-reported outcomes. Methods: This is a prospective observational study being undertaken in a target population of 228 healthy Italian women aged 18-35 years who are starting oral contraception for the first time or switching from another COC. The participants are asked to complete a diary for 6 cycles recording information about their menstrual cycles (frequency, duration, regularity, estimated flow volume, and breakthrough bleeding), any unscheduled bleeding, and an evaluation of dysmenorrhea, using a 100-mm visual analog scale from 0=no pain to 100=very severe pain, and any adverse events. Compliance is assessed after 3 and 6 months via returned medication. The primary end point is the change from baseline in the rate of intermenstrual bleeding during the sixth cycle. At baseline, 3 months, and 6 months, acne will also be assessed using the Global Acne Grading Scale, and participants will complete a Profile of Mood State to assess premenstrual syndrome and the Female Sexual Function Index to evaluate the quality of their sex life. A subgroup of 28 participants at 1 site (Genoa) is also providing a blood sample for the assessment of metabolic, endocrine, and coagulation parameters. Results: Study enrollment began in July 2023 and is expected to be complete by December 2024. Data analysis is expected to be complete by October 2025. Conclusions: This study into the effects of monophasic NGM/EE 0.25/0.035 mg on menstrual characteristics in healthy Italian women will provide up-to-date data on these effects and includes assessments of a range of other parameters, such as acne severity and patient-reported outcomes, in line with recent international consensus recommendations. Trial Registration: ClinicalTrials.gov NCT06067256; https://clinicaltrials.gov/study/NCT06067256 and EudraCT 2021-003027-15; https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003027-15/IT International Registered Report Identifier (IRRID): DERR1-10.2196/63683 ",
issn="1929-0748",
doi="10.2196/63683",
url="https://www.researchprotocols.org/2025/1/e63683",
url="https://doi.org/10.2196/63683"
}