A Vision for Improving the Assessment and Management of PCOS through International Collaboration

Helena J. Teede, MBBS, FRACP, PhD

Robert J. Norman, MBBS

In this issue of Seminars in Reproductive Medicine, we address a much neglected area of women's health; polycystic ovary syndrome (PCOS). The condition affects 8 to 13% of reproductive-aged women, with up to 21% of women in high-risk groups affected. It has diverse clinical features, and currently women experience substantive delays in diagnosis and gaps in care, with significant patient dissatisfaction. Key gaps have emerged and PCOS has been prioritized in research, evidence-based guidelines development, and translation by governments and professional societies.

Here, we present a vision for improvement in the assessment and management of PCOS through international collaboration. We summarize the condition and outline the journey from international stakeholder engagement and collaboration to identification of challenges and priorities, to the generation of extensive evidence-based guidelines, available at https://www.monash.edu/medicine/sphpm/mchri/pcos. We also highlight the research, co-design, and outputs of the integrated international guideline translation program.

The guideline objective was to develop and translate rigorous, comprehensive evidence-based diagnosis, assessment, and treatment guidelines, to improve the lives of women with PCOS worldwide. Extensive health professional and patient engagement informed guideline priority areas. International society–nominated panels included consumers, experts in pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, psychiatry, psychology, dietetics, and exercise physiology, public health, project management, evidence synthesis, and translation. Best practice evidence-based guideline development involved extensive evidence synthesis and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework covered evidence quality, feasibility, acceptability, cost, implementation, and, ultimately, recommendation strength. Governance included an international advisory board, a project board, 5 guideline development groups with 63 members, consumer, and translation committees. The Australian Centre for Research Excellence in PCOS, funded by the National Health and Medical Research Council (NHMRC), partnered with European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine to deliver the guideline and translation program. In total, 37 organizations across 71 countries collaborated with 23 face-to-face international meetings over 15 months. Sixty prioritized clinical questions involved 40 systematic and 20 narrative reviews, generating 170 recommendations. Convened committees from partner and collaborating organizations provided peer review and the guideline was approved by the NHMRC.

Overall, we endorse the Rotterdam PCOS diagnostic criteria in adults (two of clinical or biochemical hyperandrogenism, ovulatory dysfunction, or polycystic ovaries on ultrasound) and, where irregular menstrual cycles and hyperandrogenism are present, highlight that ultrasound is not necessary in diagnosis. In adolescents and those within 8 years of menarche, both hyperandrogenism and ovulatory dysfunction are required, with ultrasound not recommended, due to overlap with the normal physiology around puberty. The definition of irregular cycles is more clearly defined based on gynecological age. Androgens to be measured in diagnosis are specified along with optimal assays. Ultrasound criteria are tightened with advancing technology. Antimüllerian hormone levels, although promising, are not recommended for diagnosis. Once diagnosed, assessment and management includes reproductive, metabolic, and psychological features. Education, self-empowerment, and multidisciplinary care are important. Healthy lifestyle is vital for all with PCOS for prevention of excess weight gain, and lifestyle intervention is needed for those who are of unhealthy weight. Depressive and anxiety symptoms should be screened, assessed, and managed with the need for awareness of other impacts on emotional wellbeing. Combined oral contraceptive pills are first-line pharmacological management for menstrual irregularity and hyperandrogenism, with no specific recommended preparations a preference for lower dose preparations. Metformin is recommended in addition or alone, primarily for metabolic features. Letrozole, where permitted by national bodies, is first-line pharmacological infertility therapy with, clomiphene and metformin having a role alone and in combination. Gonadotrophins and laparoscopic surgery are second line and in vitro fertilization third line in isolated PCOS. Overall, evidence is low-to-moderate quality, requiring significant research expansion in this neglected, yet common, condition. Guideline translation is extensive, including a multilingual patient mobile application and health professional training.

We appreciate the opportunity here to bring together a body of work to progress awareness, quality of care, and improved health outcomes for women with PCOS through collaboration, guideline development, and translation. Overall, we propose this strategic international approach with strong partnership between consumers, multidisciplinary health professionals, academics, and professional societies is transferable to other women's health conditions and beyond and would reduce duplication of effort and promote consistency of care. Once completed, guidelines can be adapted to regional health settings based on population needs, health systems, and resource availability.