Beyond Premature Ovarian Insufficiency: Staging Reproductive Aging in Adolescent and Young Adult Cancer Survivors

Abstract

Context: Although stages of reproductive aging for women in the general population are well described by STRAW+10 criteria, this is largely unknown for female adolescent and young adult cancer survivors (AYA survivors). Objective: This work aimed to evaluate applying STRAW+10 criteria in AYA survivors using bleeding patterns with and without endocrine biomarkers, and to assess how cancer treatment gonadotoxicity is related to reproductive aging stage. Design: The sample (n=338) included AYA survivors from the Reproductive Window Study cohort. Menstrual bleeding data and dried-blood spots for antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) measurements (Ansh DBS enzyme-linked immunosorbent assays) were used for reproductive aging stage assessment. Cancer treatment data were abstracted from medical records. Results: Among participants, mean age 34.0±4.5 years and at a mean of 6.9±4.6 years since cancer treatment, the most common cancers were lymphomas (31%), breast (23%), and thyroid (17%). Twenty-nine percent were unclassifiable by STRAW+10 criteria, occurring more frequently in the first 2 years from treatment. Most unclassifiable survivors exhibited bleeding patterns consistent with the menopausal transition, but had reproductive phase AMH and/or FSH levels. For classifiable survivors (48% peak reproductive, 30% late reproductive, 12% early transition, 3% late transition, and 7% postmenopause), endocrine biomarkers distinguished among peak, early, and late stages within the reproductive and transition phases. Gonadotoxic treatments were associated with more advanced stages. Conclusions: We demonstrate a novel association between gonadotoxic treatments and advanced stages of reproductive aging. Without endocrine biomarkers, bleeding pattern alone can misclassify AYA survivors into more or less advanced stages. Moreover, a large proportion of AYA survivors exhibited combinations of endocrine biomarkers and bleeding patterns that do not fit the STRAW+10 criteria, suggesting the need for modified staging for this population.