Yi-Ting Hsieh1, Jason Y P Ho2,3. 1. Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan. 2. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan. 3. Taipei Fertility Center, Taipei, Taiwan.
Abstract
STUDY QUESTION: Is thyroid autoimmunity associated with a higher risk of low ovarian reserve and POI? SUMMARY ANSWER: Thyroid autoimmunity significantly increases the risk of POI in women. WHAT IS KNOWN ALREADY: POI is closely related with autoimmune disease, and according to some studies, thyroid autoimmunity (TAI) may account for diminished ovarian reserve. However, no large-scale cohort study has demonstrated the association between TAI and POI. STUDY DESIGN, SIZE, DURATION: A longitudinal population-based retrospective cohort study on the National Health Insurance Research Database (NHIRD) was designed. Since 1 March 1995, the National Health Insurance (NHI) programme in Taiwan has included 99.9% of the 23 million population of Taiwan. Patients between 1 January 2000 and 31 December 2012 were eligible for recruitment, and 21 325 subjects were analysed in our study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two cohorts, Hashimoto's and Grave's disease, were composed of patients with autoimmune thyroid disease between 20 and 40 years of age. The comparison cohorts consisted of patients in the NHIRD without autoimmune thyroid disease matched by age at a ratio of 1:4 in subject numbers. MAIN RESULTS AND THE ROLE OF CHANCE: The Hashimoto's disease (HD) cohort, Grave's disease (GD) cohort and two comparison cohorts were followed up until a diagnosis of amenorrhoea, menopausal syndrome, other ovarian failure or infertility due to ovarian failure had been made. Compared statistically with the non-HD cohort, patients with HD exhibited an 89% higher risk of amenorrhoea (95% CI =1.36-2.61). The HD patients exhibited a 2.40-fold higher risk of infertility due to ovarian failure than the non-HD subjects (hazard ratio (HR)=2.40, 95% confidence interval (CI)=1.02-5.68). In comparison with the non-GD cohort, patients with GD exhibited a 68% higher risk of amenorrhoea (95% CI = 1.43-1.98) after adjustment. According to the Kaplan-Meier analysis, the cumulative incidence of amenorrhoea and menopausal syndrome was significantly higher in the TAI groups than in the control groups. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study using ICD-9 disease code analysis to determine the statistical association between two diseases. WIDER IMPLICATIONS OF THE FINDINGS: Given that autoimmune thyroid disease is highly associated with early diminished ovarian reserve or even premature ovarian failure or POI, the options for infertility treatment may be re-directed to more efficient methods in infertile patients diagnosed with the disease. If the ovarian reserve is normal at the time of diagnosis of thyroid autoimmune disease, close follow-up of ovarian reserve may be highly recommended. STUDY FUNDING/COMPETING INTEREST(S): This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center, Grant Number: MOHW109-TDU-B-212-114004. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
STUDY QUESTION: Is thyroid autoimmunity associated with a higher risk of low ovarian reserve and POI? SUMMARY ANSWER: Thyroid autoimmunity significantly increases the risk of POI in women. WHAT IS KNOWN ALREADY: POI is closely related with autoimmune disease, and according to some studies, thyroid autoimmunity (TAI) may account for diminished ovarian reserve. However, no large-scale cohort study has demonstrated the association between TAI and POI. STUDY DESIGN, SIZE, DURATION: A longitudinal population-based retrospective cohort study on the National Health Insurance Research Database (NHIRD) was designed. Since 1 March 1995, the National Health Insurance (NHI) programme in Taiwan has included 99.9% of the 23 million population of Taiwan. Patients between 1 January 2000 and 31 December 2012 were eligible for recruitment, and 21 325 subjects were analysed in our study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two cohorts, Hashimoto's and Grave's disease, were composed of patients with autoimmune thyroid disease between 20 and 40 years of age. The comparison cohorts consisted of patients in the NHIRD without autoimmune thyroid disease matched by age at a ratio of 1:4 in subject numbers. MAIN RESULTS AND THE ROLE OF CHANCE: The Hashimoto's disease (HD) cohort, Grave's disease (GD) cohort and two comparison cohorts were followed up until a diagnosis of amenorrhoea, menopausal syndrome, other ovarian failure or infertility due to ovarian failure had been made. Compared statistically with the non-HD cohort, patients with HD exhibited an 89% higher risk of amenorrhoea (95% CI =1.36-2.61). The HDpatients exhibited a 2.40-fold higher risk of infertility due to ovarian failure than the non-HD subjects (hazard ratio (HR)=2.40, 95% confidence interval (CI)=1.02-5.68). In comparison with the non-GD cohort, patients with GD exhibited a 68% higher risk of amenorrhoea (95% CI = 1.43-1.98) after adjustment. According to the Kaplan-Meier analysis, the cumulative incidence of amenorrhoea and menopausal syndrome was significantly higher in the TAI groups than in the control groups. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study using ICD-9 disease code analysis to determine the statistical association between two diseases. WIDER IMPLICATIONS OF THE FINDINGS: Given that autoimmune thyroid disease is highly associated with early diminished ovarian reserve or even premature ovarian failure or POI, the options for infertility treatment may be re-directed to more efficient methods in infertilepatients diagnosed with the disease. If the ovarian reserve is normal at the time of diagnosis of thyroid autoimmune disease, close follow-up of ovarian reserve may be highly recommended. STUDY FUNDING/COMPETING INTEREST(S): This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center, Grant Number: MOHW109-TDU-B-212-114004. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.