Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 13 percent of reproductive-aged women worldwide. It is characterized by the presence of two or more cardinal features, including irregular menstrual cycles, clinical or biochemical hyperandrogenism, and/or polycystic ovarian morphology. Although the etiology of PCOS is yet undetermined, it is associated with reproductive, metabolic, and psychological complications. Obesity, as one of the metabolic complications, has a bidirectional relationship with PCOS. Excess adiposity can exacerbate PCOS symptoms, while women with PCOS are also more prone to weight gain. Both PCOS and obesity are strongly associated with reduced quality of life. In women with PCOS and comorbid obesity, excess weight, along with factors like emotion, infertility, body hair, and menstrual problems, can reduce the health-related quality of life (HRQoL). Lifestyle intervention such as hypocaloric dietary intervention is considered the first-line treatment for PCOS. Although hypocaloric dietary interventions are commonly recommended for women with PCOS and obesity, limited research has explored their impact on HRQoL. This thesis investigated whether hypocaloric dietary intervention improved HRQoL in women with PCOS and obesity and identified factors associated with changes in HRQoL domains. A secondary analysis of two parent clinical weight loss studies, including a 4-month weight loss study (4MO WLS, N= 18) and a 7-month weight loss study (7MO WLS, N= 10), was conducted. During both interventions, participants consumed similar low calorie, low glycemic index meals through a commercial weight loss program, Nutrisystem®. HRQoL was assessed using the Polycystic Ovary Syndrome Questionnaire (PCOSQ) at baseline, post-intervention, and 6-month follow-up. All analyses were performed in RStudio. Mean HRQoL scores over time were analyzed using linear mixed effects models. Exploratory linear regression models examined associations between changes in physiological variables and changes in HRQoL, as well as associations between baseline reproductive characteristics and PCOS phenotype with changes in HRQoL. Overall HRQoL significantly improved from baseline to post-intervention in the 4MO WLS (estimate = 0.91, SE = 0.20, p < 0.001) but not in the 7MO WLS. At the domain level, the emotion domain improved significantly at post intervention in both groups (estimate = 0.74, SE = 0.21, p < 0.01; estimate = 0.99, SE = 0.28, p < 0.01). In the 4 MO WLS, significant improvements were also observed in the weight, body hair, menstrual problems, and infertility domains at post intervention (all, p<0.05), with improvements in the body hair (p = 0.02) and menstrual problems domains (p = 0.05) sustained at 6-month follow-up. Exploratory analyses showed that improvements in the weight domain were associated with reductions in waist circumference and body fat percentage (Estimate = -0.23, SE = 0.08, p <0.01; Estimate = -0.40, SE = 0.19, p = 0.04). In addition, longer baseline menstrual cycle length was associated with greater improvement in HRQoL body hair domain (Estimate = 0.01, SE = 0.003, p = 0.02). Furthermore, Phenotype D (non-androgenic) relative to Phenotype A (overt presentation) was associated with greater HRQoL improvements in body hair and menstrual problems domain (Estimate = 0.96, SE = 0.37, p = 0.02; Estimate = 1.05, SE = 0.41, p = 0.02). In conclusion, short-term hypocaloric dietary intervention may improve HRQoL in women with PCOS and obesity, with perceptions of emotions being the most responsive to hypocaloric dietary intervention. The extent of improvement was impacted by study duration in that a longer hypocaloric dietary intervention did not necessarily confer additional benefit across HRQoL domains. Improvements in HRQoL are also influenced by physiological changes in responses to the dietary intervention and by baseline reproductive characteristics and clinical phenotype. Larger prospective studies are needed to confirm these findings and to help guide clinical practice and nutritional recommendations by identifying which women with PCOS are more likely to experience meaningful HRQoL benefits from hypocaloric dietary intervention. Key words: Polycystic Ovary Syndrome, Obesity, Health-Related Quality of Life, Weight Loss Studies, Hypocaloric Intervention