{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:49:30Z","timestamp":1785854970208,"version":"3.56.0"},"reference-count":36,"publisher":"JMIR Publications Inc.","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JMIR Res Protoc"],"abstract":"\n Background<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n ClinicalTrials.gov NCT06067256; https:\/\/clinicaltrials.gov\/study\/NCT06067256 and EudraCT 2021-003027-15; https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/trial\/2021-003027-15\/IT<\/jats:p>\n <\/jats:sec>\n \n International Registered Report Identifier (IRRID)<\/jats:title>\n DERR1-10.2196\/63683<\/jats:p>\n 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