WHO Reviews Three Contraceptive Methods for Potential Guideline Inclusion

WHO's Contraceptive Review: What Does It Uncover?

The World Health Organization (WHO) has completed a comprehensive scoping review of three contraceptive methods currently used in member states but not included in its Medical Eligibility Criteria (MEC) guidelines. The review examined ormeloxifene (a weekly pill), quinestrol-containing monthly contraceptives, and mifepristone for emergency contraception, analyzing data from 20 studies across multiple countries to determine their efficacy, safety, and acceptability profiles.

The investigation, which surveyed 958 individuals across 141 member states, aimed to address a critical gap in global contraceptive guidance. With an estimated 164 million women worldwide having unmet contraceptive needs, the findings could potentially expand the range of recommended options in future WHO guidelines. The review represents a significant step toward evidence-based assessment of contraceptive methods that have gained regulatory approval in certain countries but lack formal WHO recommendation.

Which Contraceptive Options Show Promise?

Ormeloxifene, a selective estrogen receptor modulator marketed in India as Saheli and Chhaya, demonstrated 96-99% efficacy when taken as a weekly 30mg pill following an initial biweekly induction period. The five included studies, comprising 1,346 participants, reported favorable continuation rates of 75-91% at 12 months. While menstrual disturbances affected up to 50% of users and were cited as the primary reason for discontinuation, systemic side effects were generally mild and self-limiting. The review authors noted that ormeloxifene shows "high potential for more widespread use" given its efficacy and convenience of weekly dosing.

Quinestrol-containing contraceptives, registered for use in China, showed high efficacy in the five included studies (3,322 participants) but raised safety concerns due to estrogen levels 4-5 times higher than standard combined oral contraceptives. These monthly pills demonstrated poor acceptability with discontinuation rates reaching 85% at 12 months, primarily due to side effects including nausea, vomiting, headache, and menstrual irregularities. The review highlighted that member state inquiries to WHO had raised concerns about potential complications including blood pressure elevation, venous thromboembolism, and uterine pre-cancers, though these were not specifically documented in the reviewed studies from 1970-1974.

Mifepristone for emergency contraception emerged as the most extensively studied method, with 10 studies including 18,496 participants. Seven randomized controlled trials demonstrated crude pregnancy rates of 0-1.8% across various dosages (5-600mg), comparable to or better than established emergency contraceptive options. The side effect profile was favorable compared to other emergency contraception regimens, with high patient satisfaction (93-94%) and recommendation rates (94-95%). Mifepristone is already used as an emergency contraceptive in several countries including China, Russia, Vietnam, and Moldova.

Is the Evidence Base Robust and Transparent?

The scoping review methodology followed the Arksey and O'Malley framework, with a comprehensive search strategy developed in collaboration with a medical librarian. Two independent reviewers screened all titles and abstracts, with a third reviewer resolving conflicts. Data extraction covered study location, funding source, study design, intervention details, outcomes, and results related to efficacy, safety, and acceptability. The review process was registered with Open Science Framework to ensure transparency.

Pearl Indices were calculated to assess contraceptive efficacy, with all three methods showing promising results. For ormeloxifene, Pearl Indices ranged from 1.67 to 3.7, while quinestrol-containing contraceptives demonstrated Pearl Indices between 0.83 and 5.9. Mifepristone as emergency contraception prevented pregnancy in 76-100% of cases, with higher doses generally showing greater efficacy.

Laboratory and imaging studies were performed in subsets of participants for both ormeloxifene and quinestrol-containing contraceptives. For ormeloxifene, assessments of liver and kidney function, as well as ovarian morphology, revealed no significant abnormalities. Similarly, endometrial biopsies performed in studies of quinestrol-containing contraceptives showed no concerning changes, though the review authors noted the age of these studies (1970-1974) and recommended updated safety evaluations.

What Do the Findings Mean for the Future?

The review's findings will inform future WHO guideline development, with the authors recommending systematic reviews for all three methods. They acknowledged limitations including the exclusion of non-English literature, particularly affecting assessment of quinestrol-containing contraceptives, as many studies are published exclusively in Chinese. The authors emphasized the need for expanded clinical trials in diverse geographic settings to strengthen the evidence base for these alternative contraceptive options.

Will Market Dynamics Shift with These Changes?

Industry Context: This review highlights the ongoing challenge of balancing innovation in contraceptive technology with rigorous safety evaluation. As pharmaceutical companies increasingly look to emerging markets for growth opportunities, the regulatory landscape for reproductive health products remains complex and fragmented. The potential inclusion of these methods in WHO guidelines could significantly impact market access and uptake, particularly in low- and middle-income countries where WHO recommendations strongly influence national family planning programs. The findings also reflect broader industry trends toward longer-acting and more convenient contraceptive options that address specific patient needs while maintaining high efficacy and acceptable safety profiles.

Summary

The World Health Organization has completed a comprehensive scoping review examining three contraceptive methods—ormeloxifene, quinestrol-containing monthly contraceptives, and mifepristone for emergency contraception—that are currently used in member states but not included in WHO's Medical Eligibility Criteria guidelines. The review analyzed data from 20 studies involving thousands of participants to assess efficacy, safety, and acceptability. Ormeloxifene, a weekly pill marketed in India, demonstrated 96-99% efficacy with favorable continuation rates and mild side effects, showing high potential for wider use. Quinestrol-containing contraceptives, registered in China, showed high efficacy but raised safety concerns due to estrogen levels 4-5 times higher than standard oral contraceptives and poor acceptability with 85% discontinuation rates. Mifepristone for emergency contraception emerged as the most extensively studied method with 18,496 participants, demonstrating pregnancy rates of 0-1.8% and high patient satisfaction. The review followed rigorous methodology including independent screening by multiple reviewers and transparent registration. The findings address a critical gap in global contraceptive guidance for the estimated 164 million women worldwide with unmet contraceptive needs and will inform future WHO guideline development. The authors recommend systematic reviews for all three methods and expanded clinical trials in diverse geographic settings to strengthen the evidence base for these alternative contraceptive options.