Where are we in understanding the natural history of polycystic ovary syndrome? A systematic review of longitudinal cohort studies.

STUDY QUESTION: What is the natural history of reproductive, psychological and oncological features in women with polycystic ovary syndrome (PCOS) in comparison to those without PCOS across the life course? SUMMARY ANSWER: Existing longitudinal data on changes in reproductive, psychological and oncological features in PCOS are inadequate and conflicting, but the limited evidence suggests that total testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) levels decline more significantly in women with PCOS than in those without PCOS, and the risk of gestational diabetes is higher in pregnant women with PCOS compared to their counterparts without PCOS. WHAT IS KNOWN ALREADY: The progression of reproductive, psychological and oncological features in PCOS remains unclear, which limits prevention and early diagnosis strategies across the lifespan. Understanding the natural history of PCOS is one of the overarching priorities in PCOS research. STUDY DESIGN, SIZE, DURATION: This is a systematic review of longitudinal cohort studies with a narrative presentation of findings. Databases MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews were searched between 15 January 2020 and 11 February 2021 with no language restrictions. Only studies published from the year 1990 to February 2021 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: In line with current guidelines for the assessment and management of PCOS, we included studies where participants were females with PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) consensus criteria. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 21 longitudinal studies including 62 123 participants over four continents reported reproductive, psychological and/or oncological outcomes. Participants were females aged between 15 and 49 years at baseline, with follow-up periods ranging from 4 weeks to 32 years. Consistent evidence based on limited studies suggests that total T and DHEAS levels decline to a greater degree in women with PCOS compared to those without PCOS, and the risk gestational diabetes is higher in women with PCOS than in those without PCOS. Evidence reporting changes over time in the majority of the remaining outcomes was unclear due to conflicting and/or insufficient information. LIMITATIONS, REASONS FOR CAUTION: There was extreme heterogeneity between studies in terms of study setting, population characteristics, follow-up period, effect measures used and laboratory testing approaches. WIDER IMPLICATIONS OF THE FINDINGS: Understanding the natural history of PCOS and changes in diagnostic, reproductive, psychological and oncological features of PCOS across the lifespan is still a challenge and the existing literature is both limited and conflicting. It is important that future long-term prospective longitudinal studies are conducted in unselected and well-characterized populations. STUDY FUNDING/COMPETING INTEREST(S): This specific study was not funded. S.K. is supported by scholarships from the Research Training Program of the Commonwealth of Australia and Monash University; H.J.T. is supported by an Australian National Health and Medical Research Council fellowship; and A.E.J. is supported by the Australian National Health and Medical Research Council's Centre for Research Excellence in Women's Health in Reproductive Life. R.A. was employed by the American Society for Reproductive Medicine and is a consultant to Spruce Biosciences and Fortress Biotech. The other authors have no conflicts of interest to declare. REGISTRATION NUMBER: Prospero registration number: CRD42020165546.

Lactogenic hormones in relation to maternal metabolic health in pregnancy and postpartum: protocol for a systematic review.

INTRODUCTION: Maternal metabolic disease states (such as gestational and pregestational diabetes and maternal obesity) are reaching epidemic proportions worldwide and are associated with adverse maternal and fetal outcomes. Despite this, their aetiology remains incompletely understood. Lactogenic hormones, namely, human placental lactogen (hPL) and prolactin (PRL), play often overlooked roles in maternal metabolism and glucose homeostasis during pregnancy and (in the case of PRL) postpartum, and have clinical potential from a diagnostic and therapeutic perspective. This paper presents a protocol for a systematic review which will synthesise the available scientific evidence linking these two hormones to maternal and fetal metabolic conditions/outcomes. METHODS AND ANALYSIS: MEDLINE (via OVID), CINAHL and Embase will be systematically searched for all original observational and interventional research articles, published prior to 8 July 2021, linking hPL and/or PRL levels (in pregnancy and/or up to 12 months postpartum) to key maternal metabolic conditions/outcomes (including pre-existing and gestational diabetes, markers of glucose/insulin metabolism, postpartum glucose status, weight change, obesity and polycystic ovary syndrome). Relevant fetal outcomes (birth weight and placental mass, macrosomia and growth restriction) will also be included. Two reviewers will assess articles for eligibility according to prespecified selection criteria, followed by full-text review, quality appraisal and data extraction. Where possible, meta-analysis will be performed; otherwise, a narrative synthesis of findings will be presented. ETHICS AND DISSEMINATION: Formal ethical approval is not required as no primary data will be collected. The results will be published in a peer-reviewed journal and presented at conference meetings, and will be used to inform future research directions. PROSPERO REGISTRATION NUMBER: CRD42021262771.