Premature ovarian insufficiency in female adolescent and young adult survivors of cancer: a population-based cohort study

Abstract

Objectives To assess the risk of premature ovarian Insufficiency (POI) in female adolescent and young adult (AYA) survivors of non-gynecologic cancers, using a population-based approach. Methods Provincial healthcare databases were used to identify women 15-39 years old diagnosed with selected cancers (breast, hematological, thyroid, and melanoma) from 1995-2015. Those who lived ≥3 years after diagnosis were included (n=21,666). Each cancer survivor was matched by birth year and census subdivision to 5 randomly selected cancer-free women (n=108,330). Women with bilateral oophorectomy or previous menopause were excluded. Participants were followed until December 2018, bilateral oophorectomy, loss of health insurance or death. POI was identified through physician billing claims coded as a diagnosis of menopause before age 40 (ICD-9 code 627). Modified Poisson regression models were used to calculate the adjusted relative risk (aRR) of POI for AYA cancer survivors, adjusted for income, parity, and immigration status. Results The mean age at cancer diagnosis was 32.12 years (SD 5.59). There was a higher frequency (5.4% vs. 2.2%) and increasedrisk (aRR 2.47, 95% CI 2.30–2.65) of POI amongst the AYA cancer survivors in comparison to controls. Risk varied by type of cancer: breast (4.37; 3.88–4.93), non-Hodgkin's lymphoma (3.72; 2.87–4.83), Hodgkin's lymphoma (2.38; 1.92–2.96), leukemia (14.01; 10.16–19.32), thyroid (1.25; 1.08–1.44) and melanoma (1.05; 0.83–1.33). Conclusions This study identifies significant increased risk of POI in female AYA cancer survivors. Female AYAs with cancer should be counselled about, tested for, and when confirmed, treated for POI.