RESUMEN
Purpose: Female childhood cancer survivors (CCSs) risk infertility due to gonadotoxic chemotherapy/radiation. Anti-Müllerian hormone (AMH) helps evaluate ovarian reserve, and the 2020 Oncofertility Pediatric Initiative Network (O-PIN) risk stratification is utilized to counsel risk of gonadal dysfunction/infertility. This study analyzed how AMH levels after cancer treatment differ with age and correlate AMH with O-PIN risk level and clinical outcomes. Methods: A literature review and mega-analysis of individual patient data were performed. Females ages 0-20 years at the time of cancer diagnosis with AMH values post-treatment were included. AMH outcomes were compared by O-PIN risk stratification, age at diagnosis, cyclophosphamide equivalent dose (CED), and hematopoietic stem cell transplant (HSCT). Multivariable random effects mixed models correlated AMH with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), and pregnancy. Results: In 13 studies with 608 CCSs, the median age (years) at diagnosis was 12.0 (interquartile range [IQR] 5.2-16.2) and 21.1 (IQR 17.1-30.0) at AMH measurement. AMH values were higher with time since treatment and correlated with the O-PIN risk level. Patients with HSCT had very low/undetectable AMH levels regardless of CED; when stratified by CED, AMH levels were lower if treated peripubertally or older. AMH was detectable in 54% (34/63) of patients with POI on hormone replacement. Pregnancy did not correspond to the gonadotoxicity risk level (p = 0.70). Conclusion: This study supports utilizing the O-PIN risk stratification system in estimating risk of DOR in CCSs and its categorization by pubertal status. AMH levels may return over time even after receiving the highest risk therapy. These findings may help counsel cancer patients pre- and post-therapy.
RESUMEN
BACKGROUND: Physical activity is associated with reduced risk for breast cancer, perhaps through reductions in circulating reproductive hormones (estrogens and androgens). There may also be a role for physical activity in regulating menopausal symptoms. Few studies have examined associations of physical activity on hormone levels. None have examined the potential effect of the menopausal transition on the associations between physical activity and reproductive hormone levels. MATERIALS AND METHODS: Data from the Penn Ovarian Aging Study were used for this analysis. Self-reported physical activity was assessed in 391 women up to four times over 10 years and extending across the menopausal transition. Other assessments included reproductive hormones via RIA (estradiol, luteinizing hormone, follicle-stimulating hormone, testosterone, DHEA sulfate), body weight, and height. Multivariate repeated measures regression models were developed to compare reproductive hormone levels within physical activity tertiles, adjusting for age, follow-up time, smoking, and ethnicity. RESULTS: Activity level was inversely associated with estradiol in the subgroup in the late transition stage. Adjusted means for estradiol were 24.6 and 37.9, a relative difference of 54% in estradiol when comparing highest to lowest activity tertile (P = 0.02). Similarly, in this subgroup, there was an inverse association between physical activity and testosterone levels (means of 11.1 and 15.94 in the highest and lowest tertile, a 47% relative difference; P = 0.01). There were no significant associations of activity with any other reproductive hormone. CONCLUSIONS: These results identify a particular window of the menopausal transition during which physical activity is associated with reduced estradiol and/or testosterone levels.