Alexa C O Medica1, Brian W Whitcomb2, Ksenya Shliakhsitsava3, Andrew C Dietz4, Kelsey Pinson1, Christina Lam1, Sally A D Romero5, Patrick Sluss6, Mary D Sammel7, H Irene Su8. 1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, California. 2. Department of Biostatistics & Epidemiology, School of Public Health & Health Sciences, University of Massachusetts, Amherst, Massachusetts. 3. Division of Pediatric Hematology and Oncology, University of Texas Southwestern, Dallas, Texas. 4. Moores Cancer Center, University of California, San Diego, La Jolla, California. 5. Moores Cancer Center and Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, California. 6. Ansh Labs, Webster, Texas. 7. Division of Biostatistics and Bioinformatics, School of Public Health, University of Colorado, Denver, Colorado. 8. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences and Moores Cancer Center, University of California, San Diego, La Jolla, California.
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.
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.
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