Efficacy, safety and acceptability of once-monthly oral contraceptives containing quinestrol and quingestanol, quinestrol and levonorgestrel or quinestrol and norgestrel: a systematic review

OBJECTIVE: To evaluate the efficacy, safety and acceptability of quinestrol combined with quingestanol (Quin-QUIN), quinestrol combined with levonorgestrel (Quin-LNG) and quinestrol combined with norgestrel (Quin-NG) as contraceptives. METHODS: PubMed, Web of Science Core Collection, Embase, CENTRAL, CINAHL, CNKI, Wanfang, SinoMed and selected supplementary sources were systematically searched to identify randomised controlled trials (RCTs) and non-randomised studies of interventions related to Quin-QUIN, Quin-LNG and Quin-NG. Two investigators independently performed data extraction and risk-of-bias assessment. A random-effects model was used for the meta-analysis and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twelve studies (1 RCT and 11 case series) involving 5355 participants were included. Most studies were published in the 1970s. The only included RCT showed no significant difference in the risk of pregnancy (risk ratio (RR)=0.70, 95% confidence interval (CI) 0.31 to 1.55 for Quin-LNG compared with Quin-NG). Quin-LNG was associated with a lower risk of discontinuation and fewer side effects than Quin-NG. Proportion meta-analyses of the case series, all evaluating Quin-QUIN, found a pooled proportion of pregnancy of 3.6% (95% CI 2.5% to 5.0%) and a pooled discontinuation rate of 47.9% (95% CI 17.4% to 79.4%). Nausea, vomiting, dizziness and headache were the most common side effects. The certainty of evidence for most outcomes was low or very low. CONCLUSIONS: Available evidence is limited; the risk-benefit profile of quinestrol-based once-monthly oral contraceptives remains uncertain. Their clinical use should be cautious, and high-quality studies are needed to clarify their safety and efficacy. © World Health Organization 2026. Licensee BMJ.