Burden of somatic morbidity associated with a surgically verified diagnosis of endometriosis at a young age: a register-based follow-up cohort study in Finland.

study questionHow does the burden of somatic disorders compare between women with surgically verified endometriosis diagnosed in adolescence or early adulthood, and matched women without a history of endometriosis? SUMMARY ANSWER: Women with endometriosis diagnosed at a young age had a higher incidence of several somatic disorders and a higher number of hospital visits compared to women without endometriosis. WHAT IS KNOWN ALREADY: Endometriosis is associated with an increased risk of several somatic disorders, including autoimmune, inflammatory, and pain-related disorders with higher utility of health care resources. There may be differences in the experience of pain relating to the subtypes of endometriosis. Depression and anxiety are linked to endometriosis and increase overall somatic comorbidity. STUDY DESIGN, SIZE, DURATION: Longitudinal retrospective register-based cohort study utilizing episode data from specialized care; 2680 women under 25 years with a surgical of diagnosis endometriosis in 1998-2012, and 5338 reference women of the same age and municipality followed up from the index day to the end of 2019, emigration, death or the outcome of interest. PARTICIPANTS/MATERIALS, SETTING,

methodsWe analysed incidence rates, cumulative incidence rates, and crude hazard rate ratios (HR) with 95% CIs across 15 groups of somatic disorders. Subgroup analyses were conducted among women with endometriosis, by (i) type of endometriosis-ovarian only (n = 601) versus combined types (n = 2079), and (ii) pre-existing diagnosis of depression or anxiety (n = 270) versus those without such diagnoses (n = 2410). MAIN RESULTS AND THE ROLE OF CHANCE: Women reached a median age of 38 (IQR 34-42) years after a median follow-up of almost 16 (12, 19) years. Compared to the reference cohort, women with endometriosis had a higher incidence of several somatic disorders during the follow-up. By the age of 40 years, 38% of women with endometriosis and 9% of the reference cohort had diagnoses of infertility (HR 5.88 [95% CI 5.24-6.61]). The corresponding figures for genital tract infections were 24% and 6% (4.64 [4.03-5.36]), symptoms and signs of pain 62% and 28% (3.27 [3.04-3.51]), migraine 15% and 6.4% (2.49 [2.13-2.92]), and chronic pain conditions 33% and 19% (2.01 [1.83-2.22]), respectively. In women with endometriosis, a higher incidence was seen also for dyspareunia, uterine myomas, celiac disease, asthma, anaemia, high blood pressure, hypercholesterolemia or cardiovascular diseases; autoimmune diseases, and disorders of the thyroid gland. For women with ovarian endometriosis only, we observed a lower HR of high blood pressure, hypercholesterolemia or cardiovascular diseases, asthma, migraine, and pain-related disorders compared to those with other or combined types of endometriosis. Within the endometriosis cohort, women with pre-existing diagnoses of depression or anxiety had higher HRs of several somatic disorders compared to those without such diagnoses. The number of hospital visits after the index day was higher in women with endometriosis when compared to the reference cohort (40 vs 18). LIMITATIONS, REASONS FOR CAUTION: Confounding bias may arise from the reliance on registry-based hospital diagnoses, as women undergoing surgery are already engaged with health care, and, subsequently, more likely to receive new diagnoses. Furthermore, the homogenous population of Finland limits the generalizability of these findings. WIDER IMPLICATIONS OF THE

findingsSurgical diagnosis of endometriosis at a young age is associated with a burden of somatic disorders, emphasizing importance of comprehensive approach to management of endometriosis and endometriosis-related conditions. Further studies are needed to clarify the varying reasons behind these associations. However, the results of this study suggest that pain and mental health may play a key role in the development of subsequent somatic disorders. Therefore, careful management of primary dysmenorrhea and mental health in young women is essential. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from the Hospital District of Helsinki and Uusimaa, and from Finska Läkaresällskapet. E.R. acknowledges financial support from The Finnish Society of Research for Obstetrics and Gynaecology and The Finnish Medical Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. O.H. serves occasionally on advisory boards for Bayer AG, Gedeon Richter, and Roche, has received travel support from Gedeon Richter, has received consulting fees from Orion Pharma and Nordic Pharma, and has helped to organize and lecture at educational events for Bayer AG and Gedeon Richter. The other authors report no conflict of interest concerning the present work. TRIAL REGISTRATION NUMBER: N/A.