Decreased ovarian function is associated with obesity in very long-term female survivors of childhood cancer

Objective: Obesity and gonadal dysfunction are known major side effects of treatment in adult childhood cancer survivors (CCS). In the general population, obesity has a negative influence on female fertility. We aimed to evaluate whether obesity and serum insulin are associated with decreased ovarian reserve markers in CCS. Design: Retrospective single-center cohort study. Methods: Data of 191 female survivors of childhood cancer were analyzed. Median follow-up time was 18.8 (2.3-48.8) years. Outcome measures were serum anti-Mullerian hormone (AMH) and total follicle count (FC). Potential risk factors were: BMI; body composition measures, determined by dual-energy X-ray absorptiometry (total fat percentage, lean body mass, and visceral fat percentage); and fasting insulin. Results: Lower serum AMH was found in obese subjects (beta (%) -49, P=0.007) and in subjects with fasting insulin in the highest tertile (beta (%) -43, P=0.039). Total fat percentage tends to be associated with serum AMH (beta (%) -2.1, P-0.06). Survivors in the highest tertile of insulin had significantly lower FC than survivors in the lowest tertile (beta -6.3, P=0.013). BMI and other measures of body composition were not associated with FC. Correlation between serum AMH and antral follicle count (AFC) was rho=0.32 (P=0.08). Conclusions: Obesity and insulin resistance are associated with gonadal damage, as reflected by decreased AMH and reduced FC in adult survivors of childhood cancer. In contrast to its highly predictive value for AFC in the healthy female population, serum AMH does not seem to correlate as well with AFC in CCS.