Over‐the‐Counter Provision of Oral Contraceptive Pills for Patients With Dysmenorrhea, Suspected or Confirmed Endometriosis or Chronic Pelvic Pain: A Systematic Review and Evidence Gaps

Objective To evaluate the effectiveness, values and preferences, and cost associated with over-the-counter oral contraceptive pills for self-managing dysmenorrhea, including symptoms related to suspected or confirmed endometriosis or chronic pelvic pain.

Comprehensive searches of peer-reviewed and grey literature were conducted across multiple databases (PubMed, CINAHL, LILACS and EMBASE) from inception through to April 2025 and screened using predefined eligibility criteria.

No eligible studies were identified. We found no evidence evaluating the effectiveness, values and preferences, or cost of over-the-counter oral contraceptive pills compared to standard of care for managing dysmenorrhea.

The absence of evidence highlights an important research gap in the use of self-management strategies for dysmenorrhea. Future studies could evaluate comparative outcomes, implementation models, and preferences of women affected by dysmenorrhea, including in low- and middle-income settings and among underserved communities. A phased approach, such as pharmacist-led over-the-counter access, could address current access barriers while providing critical data to guide future policy decisions. PROSPERO Registration Number CRD42024616792. 1 Introduction Dysmenorrhea—pain associated with menstruation—is the most frequently reported menstrual health issue among adolescent girls and young women, with prevalence estimates ranging from 50% to 90% [1]. Dysmenorrhea may occur in women with or without the presence of specific pathologic conditions such as endometriosis, adenomyosis or fibroids [2]. It is typically categorised as primary when it occurs without identifiable pelvic pathology and as secondary when it is associated with an underlying condition, often involving structural or inflammatory processes within the reproductive tract [1]. Chronic pelvic pain (CPP) refers to intermittent or constant pain in the lower abdomen or pelvis of a woman, lasting for at least 6 months, not occurring exclusively with menstruation or intercourse, and not associated with pregnancy [3] and can affect as many as one in four individuals in their lifetime [4]. Endometriosis, a condition that can double the risk of infertility in women under 35 [5], involves the growth of endometrial tissue outside the uterus [6] and affects about 10% of reproductive-age women, leading to chronic, sometimes debilitating pain, abnormal bleeding, and dyspareunia, or pain during intercourse [7-9]. Endometriosis and CPP are increasingly acknowledged to be under-studied and under-diagnosed. The global burden of dysmenorrhea is further compounded by limited access to effective therapies and analgesia, including oral contraceptive pills (OCPs), intrauterine devices and GnRH agonists. Consequently, many women and girls endure debilitating pain or reduced quality of life, to the detriment of their sexual and reproductive health and rights [10]. In this article, the term ‘women’ is used inclusively to refer to all women, girls, trans men and gender-diverse individuals who menstruate at some point their life course and the diversity of lived experiences, including but not limited to women with disabilities, experiencing homelessness, undergoing incarceration and/or institutionalisation, displaced due to conflicts, climate change or other humanitarian crises, living with human immunodeficiency virus (HIV), belonging to minority, racial or ethnic groups, and Indigenous women. The World Health Organization (WHO) emphasises the transformative potential of self-care interventions for sexual and reproductive health and rights in improving health coverage, equity and individual empowerment [11]. WHO recommends over-the-counter (OTC) access to OCPs to prevent unintended pregnancy for individuals using OCPs, including both full OTC and pharmacy-access (behind-the-counter, in which eligibility screening is conducted by trained pharmacy staff before dispensation) models [11]. OCPs are an effective treatment option for some etiologies of dysmenorrhea, reducing the frequency and/or severity of pain in some women [12]. However, in many settings, OCPs and other treatment options for dysmenorrhea are only accessible or available through prescription, potentially imposing a barrier to timely care [11, 13]. In a 2021 Danish cohort study involving over 24 000 women, for example, 69% of participants reported menstrual pain; pain was ‘pronounced’ or ‘insufferable’ in 20.1% of women with dysmenorrhea. Of 3673 women (15.3%) who reported having dysmenorrhea so severe that they sought treatment, 17.6% received no care while OCPs were the most commonly prescribed intervention (25%) [14]. While the study did not assess reasons for the treatment gap, OCPs are not available OTC in Denmark [16]. A 2015 review of access to oral contraception across 147 countries found that just 35 countries allowed full OTC access [15]. A more recent review of 47 European countries found that only 11 legally permit OTC access to OCPs [16], suggesting little global progress over the past decade. The United States Food and Drug Administration approved OTC access to certain contraceptives in 2023 [17], but the cost of OCPs purchased OTC may or may not be covered by US health insurance companies, potentially limiting their affordability. Although the evidence of efficacy of OCPs for managing CPP [18] and other pain associated with endometriosis [19] mainly emanates from high-income settings, existing data indicates that OCPs are effective and a valued option for many women [20]. Making OCPs available OTC could enhance treatment access, improve pain management, and increase the quality of life for women with dysmenorrhea. This systematic review aims to assess the evidence base regarding OTC provision of OCPs for women self-managing dysmenorrhea, including suspected or confirmed endometriosis, or chronic pelvic pain. We sought to expand the evidence on self-care interventions [11] by assessing the impact of both behind-the-counter/pharmacy-access and true OTC availability of OCPs on sexual and reproductive health outcomes. 2 Methods We sought to answer the following question: Should OCPs be made available OTC to patients with dysmenorrhea, suspected or confirmed endometriosis, or CPP? To address this question, we conducted complementary reviews of effectiveness, values and preferences, and cost. We followed PRISMA guidelines for systematic reviews [21] and registered our review on PROSPERO (CRD42024616792). 2.1 Effectiveness Review: PICO Question and Inclusion Criteria Our effectiveness review followed the PICO question format: 2.2 Population Women with dysmenorrhea, suspected or (surgically or radiologically) confirmed endometriosis, or CPP, and who do not wish to become pregnant. 2.3 Intervention OTC OCPs (any formulation). This could include either true OTC availability, behind-the-counter, or pharmacy access. 2.4 Comparison Standard of care/no OTC availability. 2.5 Outcomes - 1. Pain management (e.g., for conditions associated with dysmenorrhea (dichotomous), dyspareunia (pain during sexual intercourse) (dichotomous), CPP (dichotomous), pain scores (continuous), and endometriosis). - 2. Symptom management (e.g., menstrual irregularities, heavy menstrual bleeding, non-menstrual pelvic pain assessed through continuous or other pain measurement scales). - 3. Quality of life (either general or specific to CPP and suspected or confirmed endometriosis). - 4. Side effects or adverse events (e.g., hormonal side effects (e.g., nausea, breast tenderness, headaches), thromboembolic events (e.g., transient ischaemic attack), changes in mood or libido). - 5. Self-efficacy, self-determination, and autonomy in managing CPP and suspected or confirmed endometriosis, - 6. Health service usage for pelvic pain management, - 7. Stigma (internalised, anticipated, enacted, or structural) and discrimination related to CPP and suspected or confirmed endometriosis, - 1. Study design that compares OTC, behind-the-counter, or pharmacy access of availability of oral contraception to prescription-only availability of oral contraception for women with dysmenorrhea, confirmed or suspected endometriosis or CPP. This includes randomised controlled trials (RCTs), non-randomised controlled trials and comparative observational studies (including prospective controlled cohort studies, cross-sectional studies, controlled before-after studies and interrupted time series) that compare individuals who received the intervention to those who did not. - 2. Measures one or more of the outcomes listed above. - 3. Published in a peer-reviewed journal, conference abstract, or grey literature. Before–after OTC transition studies without extractable subgroup data for individuals with dysmenorrhea, suspected or confirmed endometriosis, or chronic pelvic pain were also excluded, as these did not address our pre-specified PICO question. No restrictions were placed based on location of the intervention. No language restrictions were used in the search. The full search strategy combined terms for OTC and OCP and dysmenorrhea, endometriosis or CPP health topics (Supporting Information S1: Appendix A). The following electronic databases were searched from inception through the search date of April 7, 2025: PubMed, CINAHL, LILACS and EMBASE. We also searched for ongoing RCTs through clinicaltrials.gov, the WHO ICTRP, PACTR, and the Australian New Zealand Clinical Trials Registry. We searched websites for conference abstracts and grey literature (full list in Supporting Information S1: Appendix A). Secondary reference searching was also conducted on all included studies and four previously published systematic reviews (one on self-management strategies for females with endometriosis [22] and three on contraceptive use for menstrual health/dysmenorrhea [12, 18, 23]). Finally, selected experts in the field were contacted to identify additional articles not identified through other search methods. Titles, abstracts, citation information, and descriptor terms of citations identified through the search strategy were screened by a senior member of the study team. Full text articles were obtained for all selected abstracts, and two independent reviewers assessed all full-text articles for eligibility to determine final study selection. We kept track of screening results in Covidence. Differences were resolved through consensus. We planned to extract data independently by having two reviewers using standardised data extraction forms and resolve differences through consensus and referral to a senior study team member when necessary. - Study identification: Author(s); type of citation; year of publication. - Study description: Study objectives; location; population characteristics (including clinical characteristics of dysmenorrhea, suspected or confirmed endometriosis or CPP); type of oral contraception; description of OTC access; description of any additional intervention components (e.g. any education, training, support provided); study design; sample size; follow-up periods and loss to follow-up. - Outcomes: Analytic approach; outcome measures; comparison groups; effect sizes; confidence intervals; significance levels; conclusions; limitations. 2.6 Values and Preferences Review The same search strategy was used to search and screen for studies to be included in the values and preferences review. Studies would have been included in this review if they presented primary data examining preferences of individuals with dysmenorrhea, suspected or confirmed endometriosis or CPP regarding OTC access to OCPs. We planned to include studies examining the values and preferences of individuals who have used or potentially would use oral contraceptives themselves, and studies examining the values and preferences of health and care workers, particularly pharmacists. We planned to consider issues around OTC access to OCPs as they relate to age of availability and marital status (both in law and in practice), broader social/structural factors that affect values and preferences, informed decision-making, coercion and seeking redress in this section. These studies could have been qualitative or quantitative in nature but would have had to present primary data collection—think pieces and review articles were not going to be included. We planned to summarise values and preferences literature qualitatively with consideration of study design and methodology, location, and population. 2.7 Cost Review The same search terms were used to search and screen for studies to be included in the cost review. Studies would have been included in this review if they presented primary data comparing costing, cost-effectiveness, cost-utility, or cost–benefit of the intervention and comparison listed in the PICO above, or if they presented cost-effectiveness of the intervention as it relates to the PICO outcomes listed above. Cost literature was going to be classified into four categories (health sector costs, other sector costs, patient/family costs, and productivity impacts) and summarised qualitatively. 3 Results Our search yielded a total of 185 records through database searches (Figure 1). After removing duplicates, we screened 172 records. Of these, 15 full-text articles were assessed for eligibility, along with 17 articles from other search methods. We excluded all 32 articles for the following reasons: not primary research (n = 11), case reports without relevant OTC OCP information (n = 1), clinical guidelines lacking OTC information (n = 1), prevalence studies without specific outcome data (n = 1), studies not mentioning OCPs (n = 1), studies discussing OCPs but not OTC provision (n = 16), and studies discussing OTC OCP discussed but no focus on pain or endometriosis (n = 1) (Supporting Information S1: Appendix B). Ultimately, we found no studies that met the eligibility criteria for the effectiveness review, the values and preferences review, nor the cost review. 4 Discussion Our review identified no studies on effectiveness of OTC OCPs on dysmenorrhea, suspected or confirmed endometriosis or CPP. This absence of evidence likely reflects structural research gaps, including the siloing of contraceptive versus pain management research, regulatory barriers, and diagnostic challenges in endometriosis detection [24]. Some before-after OTC transition studies were identified in the broader literature [25, 26], but these did not provide subgroup data on dysmenorrhea or endometriosis outcomes and were therefore excluded, in line with our pre-specified eligibility criteria. The lack of comparative effectiveness data means that the development of global normative guidelines on women's health, including self-care interventions for sexual and reproductive health, must rely on indirect evidence and expert opinion when appraising the benefits of making OCPs available OTC for individuals with dysmenorrhea, suspected or confirmed endometriosis, or CPP. We also identified no studies on values and preferences of women regarding their ability to obtain OCPs OTC for dysmenorrhea, suspected or confirmed endometriosis, or CPP. The lack of values and preferences data suggests a critical gap in understanding the varied perspectives of women affected by dysmenorrhea, including when they develop a clinical need for OCPs, as well as the perspectives of health and care workers, especially pharmacists, on OTC access to OCPs for pain management. However, evidence from broader literature on access to contraception indicates that many adolescents are interested in direct pharmacy or OTC access to OCPs as a way to reduce barriers to care [13, 27]. Pharmacists have also reported that structured OTC or pharmacy-access models for OCPs are feasible and acceptable, provided adequate training and guidance are available [28]. These findings suggest that while pain-specific data are absent, lessons from contraceptive access can help contextualise likely values, preferences, and acceptability in this domain. Similarly, the absence of studies evaluating the cost-effectiveness of OTC OCP access presents a major challenge for developing normative guidance. Without economic data, it is difficult to assess whether the potential benefits of OTC access to OCPs would outweigh the costs, both for individuals and health systems, making it challenging to incorporate cost considerations into policy decisions. Furthermore, the majority of full-text articles reviewed for eligibility were conducted in high-income settings, and there is a lack of data both from low- and middle-income countries, and among underserved communities where access to healthcare, education, and socioeconomic status affect understanding and use of self-management options to alleviate dysmenorrhea, pain related to endometriosis or CPP. While OTC access to OCPs for contraceptive purposes has been relatively well-studied, OTC access to OCPs for their role in managing dysmenorrhea, endometriosis or CPP has received less attention. Several factors may explain the lack of literature on this topic. First, the historical separation between contraceptive care and pain management may have led to siloed research approaches. This lack of focus may be due to the complexity of diagnosing endometriosis and the broader range of treatment options typically considered to require physician consultation. Second, as noted by Sturpe [29], the highest incidence of dysmenorrhea occurs in adolescence, a population for whom OTC access to hormonal medications has traditionally been influenced—and, frequently, restricted—by legal, cultural and societal factors. As Upadhya et al. [27] highlight, while OCPs are considered safe and effective for adolescents, the regulatory concerns about adolescent self-administration may have further limited exploration of OTC solutions for managing CPP in younger populations. Third, the complex nature of diagnosing endometriosis and the broader range of treatment options typically considered to require physician consultation, as described by Saunders and Horne [6], may have deterred research into OTC interventions for suspected cases, although there is increased focus on developing noninvasive self-diagnostic tests for endometriosis [30, 31]. Finally, although dyspareunia was included in our search terms, none of the articles that were assessed at full-text review addressed dyspareunia, suggesting a more generalised lack of research (due to low prioritisation, insufficient funding, or both) on self-care strategies for women's gynaecological pain conditions. In sum, despite evidence regarding OTC access to OCPs for contraception [28] and randomized trials showing OCP efficacy for dysmenorrhea [18] and endometriosis-related pain [19]—in other words, biological plausibility and potential applicability to pain management, limited pharmaceutical industry investment in menstrual pain and endometriosis research, together with broader legal and cultural restrictions on contraceptive access in some settings, has likely limited the generation of primary evidence. WHO recommended OTC availability of OCPs [11] based on general evidence supporting its feasibility and acceptability [28] as a self-care option for women to enhance their sexual and reproductive health and reduce unintended pregnancy. The transition to OTC availability has demonstrated benefits for medications like emergency contraception, improving access, usage, and user satisfaction without increasing adverse events [25, 26, 32]. Modelling suggests that OTC access to progestin-only pills could prevent up to 104 000 unintended pregnancies annually in the United States. [33], and that cost plays a critical role in determining uptake and impact [34]. To date, however, no real-world pregnancy-related outcomes data are available regarding OTC availability of OCPs. This lack of direct evidence highlights the need for further research on self-management options for women with dysmenorrhea, suspected or confirmed endometriosis, or CPP to expand overall access to care and to improve women's quality of life. Indeed, there are significant barriers to care for women with endometriosis. A study by Ghai et al. [35] found that patients often face delays of 8 years before receiving appropriate treatment for endometriosis, with prescription requirements cited as a common obstacle [35]. These delays are particularly concerning given that early intervention with hormonal contraceptives may prevent disease progression and improve long-term outcomes [36-38]. OTC access to OCPs will not address all access barriers for individuals with endometriosis. As emphasised by Upadhya et al., [27] and as with all self-care options [11], OTC OCP access should be viewed as a complementary approach rather than a substitute for timely and comprehensive medical care, ensuring continued access to diagnostic evaluations and personalised treatment. The goal is to expand access to care, including self-care options, especially for those facing systemic or logistical prescription barriers. Based on the gaps identified in our systematic review, several research priorities emerge. Given the complete absence of effectiveness studies, and the burden of dysmenorrhea affecting one in two women over their lifetime, comparative research examining health outcomes between prescription-only and OTC access models is needed. Our review also highlighted a lack of data on patient and provider preferences regarding OTC access to OCPs for pain management in women with dysmenorrhea. Implementation research should explore different OTC delivery models to identify approaches that are both feasible and acceptable to patients and providers. Mixed-methods studies incorporating quantitative outcomes and qualitative experiences would help build a more comprehensive evidence base for policy decisions. We distinguish between evidence-based conclusions (OCP efficacy for menstrual pain management) and hypothetical implications (the potential impact of OTC provision on pain outcomes). To move forward, we recommend phased research agendas: short-term (pilot pharmacist-led OTC studies), medium-term (comparative effectiveness research), and long-term (implementation and equity-focused evaluations). The substantial evidence gaps identified in this review clearly highlight the need for further research. While there is a sizable gap between current evident of OCP efficacy for menstrual pain management and the potential impact of OTC provision of OCPs on pain outcomes, policy considerations are not entirely precluded. In the absence of direct evidence, a cautious and phased approach to increasing access, tailored to context, such as piloting behind-the-counter availability through pharmacists, could help address barriers to care while generating valuable effectiveness and safety data. For instance, the Direct Access study in Washington State demonstrated that pharmacists could effectively prescribe OCPs, with high satisfaction rates among users and continued use over time [39]. This approach would enable systematic monitoring and evaluation, providing a foundation for future evidence-based policy decisions. Other policy steps might include: developing standardised pharmacist training; considering the integration of digital or telehealth support; and adopting equity-focused strategies that differ for high-, middle-, and low-income settings. These actions would facilitate careful expansion of self-care options while generating evidence to inform future normative guidance. The strengths of this review include its global scope and comprehensive search strategy, which encompasses a wide range of issues related to OTC OCPs for dysmenorrhea, suspected or confirmed endometriosis or CPP, such as effectiveness, values and preferences, and cost. However, our conclusions are limited by the lack of studies that met our inclusion criteria. 5 Conclusion There is limited literature on OTC availability of OCPs for managing dysmenorrhea, suspected or confirmed endometriosis or CPP. While OCPs are known to be effective for preventing pregnancy and may reduce pain associated with menstruation in some women, studies regarding the impacts of making OCPs available OTC are limited, and more research is needed to explore the impact of OTC availability of OCPs for dysmenorrhea. Subsequent policy development should be informed by that research as well as a commitment to addressing the significant unmet needs of affected individuals. Increasing OTC availability of OCPs may help address current gaps in pain management for women with dysmenorrhea and improve self-care options for sexual and reproductive health and rights. Author Contributions Amarachi Ijeoma: data curation, writing – original draft preparation. Ping Teresa Yeh: conceptualisation, data curation, methodology, project administration, supervision, writing – review and editing. Caitlin Elizabeth Kennedy: conceptualisation, data curation, methodology, project administration, supervision, writing – review and editing. Jennifer J.K. Rasanathan: writing – review and editing. Manjulaa Narasimhan: conceptualisation, funding acquisition, writing – review and editing. All authors gave approval of the version to be published, agreed on the journal to which the article had been submitted, and agreed to be accountable for all aspects of the work.

We thank the Johns Hopkins Bloomberg School of Public Health graduate students who assisted with this review: Maclaine Barre-Quick, Linda Umutoni Nzabamwita. We gratefully acknowledge financial support from the Children's Investment Fund Foundation (CIFF). The funders played no part in the study design, decision to submit the article for publication, nor in the collection, analysis, and interpretation of data. Disclosure The named authors alone are responsible for the views expressed in this publication and do not necessarily represent the decisions or the policies of the World Health Organisation (WHO) nor the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). Ethics Statement This study was not required to receive IRB approval because all data comes from published records. Conflicts of Interest The authors declare no conflicts of interest. Peer Review The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1002/rfc2.70040. Data Availability Statement All data included in this systematic review are available in the manuscript and were derived from publications available in the literature.