J Clin Endocrinol Metab. 2021;106: e1002e1013. https://pubmed.ncbi.nlm.nih.gov/33141175/
This cross-sectional study applied a commonly used system to classify reproductive aging (Stages of Reproductive Aging Workshop +10 or STRAW +10) to 338 adolescents and young adult (AYA) cancer survivors (1). The study aimed to evaluate if STRAW +10 correctly identifies premature ovarian failure in this population and to assess the relationship between cancer treatment and reproductive aging stage.
The STRAW classification system was first described in 2001 to stage ovarian aging based on menstrual cycle characteristics and FSH levels. Several studies then highlighted the critical changes in hypothalamic-pituitary and ovarian function that occur before and after the final menstrual period. These advances led to an update in 2011 that expanded the STRAW system from 7 to 10 criteria (STRAW +10). In particular, anti-müllerian hormone (AMH) levels and antral follicle count (AFC) were added as qualitative markers of fertility potential during the late reproductive life (1). Short reproductive lifespan is common in AYA cancer survivors, in particular those who received gonadal irradiation and/or alkylating chemotherapy and were older at the time of cancer treatment. Current guidelines for these patients recommend to monitor ovarian function by menstrual patterns, and to measure endocrine biomarkers only if menstrual changes appear. However, it is well known that ovarian reserve declines before the appearance of menstrual changes.
In this study, patients were initially classified by menstrual pattern, then according to FSH and AMH levels. The proportion of individuals in each reproductive aging stage was compared to evaluate the concordance of these two methods. Within the reproductive phase, the addition of endocrine biomarkers distinguished between peak and late reproductive aging. The agreement between classification by menstrual pattern alone vs menstrual pattern with ovarian reserve testing was high for the reproductive and postmenopausal stages. However, the menopausal transition was highly discrepant between the two approaches. After adjustment for age and cancer recurrence, cyclophosphamide equivalent dosing (CED) remained significantly associated with the risk of menopausal transition and postmenopause.
This study highlights that the STRAW +10 system does not correctly identify premature ovarian failure in AYA survivors. Current guidelines for the evaluation of reproductive health should be revised, in particular for patients in low-risk groups. Large observational studies are needed to understand the timing and progression of reproductive aging in young cancer survivors. Predicting premature ovarian failure is essential to correctly inform patients about the fertility, improve quality of life and prevent disease-related complications (i.e cardiometabolic risk and bone impairment).
Reference: 1. Harlow SD, et al. Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab. 2012; 97: 115968.