ABSTRACT
Background: Worldwide, an increasing number of women with cancer are receiving Gonadotropin Releasing Hormone agonist (GnRHa) co-treatment during chemotherapy aiming at ovarian protection. There is divergence among guidelines, and some have recommended GnRHa co-treatment for women with breast cancer, however, the effect of GnRHa on future fertility is uncertain. Methods: In this population-based cohort study we included all women diagnosed with cancer at ages 15-45 between July 2005 and March 2017 in Sweden, identified in the Swedish Cancer Register. Exposure to GnRHa co-treatment was captured using the Prescribed Drug Register. Post-cancer childbirth, extracted from the Medical Birth Register, was the main outcome. Secondary outcomes included childbirths achieved through natural conception (NC), infertility diagnosis and cancer mortality. For each outcome, adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using delayed-entry Cox models, stratified by age and cancer site. Findings: Among 24,922 women diagnosed with cancer, 1.5% had GnRHa co-treatment. Breast cancer diagnoses were found in 80.2% of GnRHa exposed women and the GnRHa exposure was not associated with higher rates of childbirth (aHR 1.23, 95% CI 0.80-1.89), or NC childbirth (aHR 1.02, 95% CI 0.62-1.67), whereas the rate of infertility was significantly higher (aHR 2.42, 95% CI 1.44-4.08). In women with lymphoma and other cancers, GnRHa exposure was not associated with higher rates of childbirth, NC childbirth or infertility. GnRHa exposure was not associated with higher cancer mortality for any cancer type. Interpretation: We did not find evidence of improved or maintained fertility, estimated as childbirth rates post-cancer, in women who received GnRHa during cancer treatment. Funding: This study was financed by research grants from The Swedish Cancer Society (CAN 2017/704; 190249Pj, 200170F), The Swedish Research Council (Dnr 2019-00446), the Nordic Cancer Union NCU (Grant 2017), The Swedish Childhood Cancer Fund (KP2016-0031), Radiumhemmets Forskningsfonder (Dnr: 201313), Stockholm County Council (FoUI-953912) and Karolinska Institutet (Dnr 2020-01963).
ABSTRACT
BACKGROUND: Liver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment. METHODS: Data from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group. RESULTS: Among the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4-73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4-74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3-99.9%). CONCLUSION: Among patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower.