Emergence of polycystic ovary syndrome (PCOS) during adolescence - PROJECT SUMMARY. Polycystic ovary syndrome (PCOS) affects 1 in 8 women of reproductive age imparting reproductive, cardiometabolic and psychological health complications for patients across the lifespan. PCOS is defined by the presence of 2 or more cardinal features including ovulatory dysfunction, hyperandrogenism and polycystic ovarian morphology (PCOM). Although PCOS manifests during adolescence, delays in diagnosis are common as the cardinal features are said to overlap with characteristics of the normal adolescent reproductive transition. Current standards to define PCOS in adolescence differ from those in adulthood – they do not include PCOM owing to a lack of data. This exclusion results in a narrow spectrum of PCOS during adolescence which may not fully capture all with PCOS until 8y post-menarche when adult-criteria for PCOM are available. Our preliminary data support that ovarian morphology has diagnostic accuracy for PCOS in adolescents and reflects the severity of reproductive and metabolic symptoms in a manner similar to adults. Further, in a longitudinal pilot evaluation of ovarian morphology in healthy adolescents, we show that ovarian markers in the first post-menarcheal year, including anti-Müllerian hormone, predict persistent menstrual cycle irregularity at 2y post-menarche suggesting that morphologic indicators precede in the timeline to aberrant reproductive maturation. We propose that an understanding of the natural history of PCOS during adolescence can provide a framework for the earliest detection and mitigation of this highly prevalent disorder. To that end, this project will define the trajectory of PCOS symptoms during early adolescence (Aim 1) and develop a nomogram of ovarian form and function during the first 8 gynecological years (Aim 2). Our approach involves elucidating the time course of divergences in ovarian morphology, androgen concentrations and menstrual cyclicity in adolescent cohorts who develop PCOS versus those who establish regular menstrual cycles in the first 3y post-menarche. Further, we will conduct a cross-sectional analysis of sonographic and serum markers of PCOM across gynecological ages <1y– 8y in order to define PCOM during this developmental period. The hypotheses to be tested are that changes in ovarian morphology that occur in association with the establishment of regular menstrual cycles differ from those seen in adolescents with persistent cycle irregularity, hyperandrogenism and/or PCOS, and that early and distinct aspects of ovarian morphology predict the likelihood of PCOS in early gynecological life. By defining the normal limits of ovarian form and function during adolescence, we also expect to generate developmental-stage specific criteria for PCOM that reveal the actual clinical spectrum of PCOS during this life stage. This research will immediately improve diagnostic experiences for patients and families by resolving the ambiguity related to the role of ovarian morphology in the early detection of PCOS. Likewise, a new understanding of the emergence of PCOS in adolescence will usher opportunities for the timely intervention, and possible prevention, of this major problem in women’s health.
