The Impact of Weight Loss on Ovarian Morphology in Obese Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. The pathogenesis of anovulation involves the hypersecretion of gonadotropins, androgens and insulin. These disruptions interact at the ovaries to stimulate stromal hypertrophy, accumulation of small follicles (2–5mm) and arrest of follicular growth at the 6–9mm stage. Excess weight and visceral adiposity are thought to exacerbate the endocrine and metabolic disruptions that result in chronic anovulation, and as such, represent important therapeutic targets of dietary interventions aimed at weight loss. Modest reductions in weight (5–10%) have been shown to normalize gonadotropin secretion, reduce hyperandrogenism and improve insulin sensitivity in women with PCOS. Yet, it remains unclear whether dietary interventions are an effective means to normalize ovarian morphology and restore ovulatory cyclicity in this population. To that end, our objectives were to: (1) determine the impact of weight loss on ovarian morphology, and (2) evaluate the associations between changes in ovarian morphology and improvements in cardinal endocrine and metabolic features with weight loss. Twenty obese women with PCOS were recruited to a 3‐month hypocaloric dietary intervention involving a commercial meal program. Subjects underwent the following procedures pre‐ and post‐intervention: (a) anthropometry and dual x‐ray absorptiometry; (b) a transvaginal ultrasound scan; (c) fasting blood tests; and (d) an oral glucose tolerance test. Changes in weight, body composition, sonographic markers of ovarian morphology, gonadotropins, androgens and insulin sensitivity were evaluated with paired t‐tests or Wilcoxon signed‐rank tests. Associations between changes in morphologic parameters and changes in clinical, endocrine or metabolic parameters were assessed with linear regression. Due to the exploratory nature of these analyses, statistical significance was set at p<0.10. Subjects experienced significant reductions in weight, total and abdominal fat mass during the intervention (p<0.0001). Changes in circulating concentrations of gonadotropins (p≤0.05), androgens (p<0.01) and indices of insulin sensitivity (p<0.10) were also apparent. Subjects showed a decrease in ovarian area (p=0.02) and volume (p=0.05), and an increased number of large follicles (6–9 mm; p=0.09), with weight loss. Large changes in ovarian size were associated with small changes in percent total fat (β= −1.108, p=0.08), abdominal fat (β= −0.897, p=0.07), and 2‐hour glucose (β= −1.022, p=0.02) and insulin concentrations (β: −0.007, p=0.01). Similarly, large changes in the number of 6–9 mm follicles were associated with small changes in fat mass (β= −0.001, p=0.06) and 2‐hour insulin (β= −0.017, p=0.02), as well as large changes in the homeostatic model of insulin resistance (β= 1.014, p=0.07). All associations remained after adjustment for the degree of weight loss. Together, these findings suggest that changes in visceral adiposity and insulin sensitivity are requisite to improve stromal hypertrophy and follicle arrest in PCOS. Future analyses will elucidate the impact of these changes in ovarian morphology on ovulatory cyclicity. Support or Funding Information This work was supported by the Division of Nutritional Sciences at Cornell University and the National Institutes of Health (T32‐DK007158). The context is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive Kidney Diseases (NIDDK) or the National Institutes of Health. Meal donations were also provided by Nutrisystem, Inc.