EFFECTIVENESS OF HYPOCALORIC DIETARY INTERVENTION ON CHANGES IN BODY COMPOSITION AND REPRODUCTIVE FUNCTION IN WOMEN WITH POLYCYSTIC OVARY SYNDROME
Polycystic ovary syndrome (PCOS) is a broad-spectrum endocrine disorder impacting 1 in 8 women worldwide and is associated with cardiometabolic and reproductive dysfunction. These include an increased risk of obesity, metabolic syndrome, cardiovascular disease, menstrual cycle irregularity, anovulatory infertility, endometrial hyperplasia, and gynecological cancers. Overweight and obesity is highly prevalent in women with PCOS and has been reported to exacerbate reproductive dysfunction in this population. Lifestyle intervention aimed at moderate weight loss of 5 – 10% is the recommended first-line treatment for women with PCOS and excess adiposity given the known benefits of such treatment on cardiometabolic health and overall wellbeing. However, the effectiveness of lifestyle intervention on changes in body composition and reproductive function, and whether PCOS status impacts such changes are unclear. Additionally, baseline clinical characteristics predicting changes in body composition and reproductive function in response to lifestyle intervention remain largely unexplored. In Chapter 1, the effectiveness of short-term hypocaloric dietary intervention on weight loss and body composition changes was contrasted between women with and without PCOS. We showed that women with PCOS experienced clinically meaningful weight loss and favorable body composition changes similar to women without PCOS, albeit weight loss trajectories differed. As such, women with PCOS may be more likely to encounter challenges earlier with continued weight loss compared to their non-PCOS counterparts. Consistent with differences in weight loss trajectories, PCOS status was a significant negative predictor for attainment of 10% weight loss. In Chapter 2, we evaluated the impact PCOS status on changes in reproductive function during short-term hypocaloric dietary intervention. Lifestyle intervention did not impact menstrual cycle length or ovulatory follicle dynamics in either women with and without PCOS. By contrast, we noted that both groups had changes in luteal phase progesterone levels and endometrial development. Women with PCOS had a slower rate of change in endometrial development suggesting a longer intervention may be needed in order to normalize endometrial development to the same degree as in women without PCOS. In Chapter 3, we explored baseline predictors of favorable change in menstrual cycle status with a short-term hypocaloric dietary intervention in women with PCOS. We found that less than half of women with PCOS demonstrated an improvement in menstrual cycle status with lifestyle intervention. Ovarian morphology and the relative abundance of lean muscle to fat mass were positive predictors of improvement in menstrual cyclicity suggesting that the standard diagnostic and risk assessment markers for PCOS may be insufficient to identify characteristics associated with clinically meaningful changes in menstrual cycle status. Collectively, this dissertation provides new knowledge related to the effectiveness of short-term lifestyle intervention on changes in body composition and reproductive function in women with PCOS. Our serial assessment of body weight and reproductive status markers, along with our novel consideration of corresponding changes in women without PCOS, addressed the impact of PCOS status on anthropometric and reproductive outcomes in response to hypocaloric dietary intervention. Further, our evaluation of baseline predictors for achieving moderate weight loss and for improving menstrual cyclicity provides a basis for tailored patient counseling on expected outcomes with lifestyle intervention in PCOS.