Psychiatric disorders and mortality due to external causes following diagnosis of endometriosis at a young age: a longitudinal register-based cohort study in Finland.

BACKGROUND: Endometriosis diagnosed in adults is associated with increased risk of various psychiatric disorders. However, little is known concerning psychiatric comorbidity and mortality due to external causes associated with endometriosis diagnosed at a young age. OBJECTIVE: This longitudinal cohort study aimed to investigate the link between surgical diagnosis of endometriosis at a young age and subsequent psychiatric disorders and mortality due to external causes. In addition, we compared the occurrence of the most common psychiatric disorders between different sites of surgically confirmed endometriosis (ovarian vs other) because of possible differences in pain manifestations. STUDY DESIGN: We conducted a retrospective register-based cohort study. Altogether 4532 women with surgically confirmed diagnosis of endometriosis before the age of 25 years from 1987 to 2012 were identified from the Finnish Hospital Discharge Register. They were matched with women without surgically diagnosed endometriosis for age and municipality on the index day (n=9014). Women were followed up from the index day until the end of 2019 for the outcomes of interest, which included 9 groups of psychiatric disorders (inpatient episodes since 1987, outpatient episodes since 1998) and death due to external causes, including deaths due to accidents, suicides, and violence (Finnish Register of Causes of Death). Cox proportional hazard models were applied to assess the crude and parity-adjusted hazard ratios and 95% confidence intervals. RESULTS: The cohort's median age was 22.9 years (interquartile range, 21.3-24.1) at the beginning and 42.5 years (36.7-48.3) after a median follow-up time of 20.0 years (14.5-25.7). We observed a higher hazard of depressive, anxiety, and bipolar disorders in women with endometriosis compared with the reference cohort, with depressive and anxiety disorders being the two most common psychiatric disorders. These differences appeared early and remained the same during the entire follow-up, irrespective of whether assessed from the data on inpatient episodes only or the data on both in- and outpatient episodes. The corresponding adjusted hazard ratios were 2.57 (95% confidence interval, 2.11-3.14) and 1.87 (1.65-2.12) for depressive disorders, 2.40 (1.81-3.17) and 2.09 (1.84-2.37) for anxiety disorders, and 1.71 (1.30-2.26) and 1.66 (1.28-2.15) for bipolar disorders, respectively. A higher hazard was observed for nonorganic sleeping disorders for the first 10 years only (3.83; 2.01-7.30) when assessed using the data on both in- and outpatient episodes. When based on inpatient records, a higher hazard for alcohol/drug dependence after 15 years of follow-up (2.07; 1.21-3.54) was observed. The difference in hazard for personality disorders tended to increase during follow-up (<10 years, 2.12 [1.28-3.52]; ≥10 years, 3.08 [1.44-6.57]). Depressive and anxiety disorders occurred more frequently in women with types of endometriosis other than ovarian endometriosis. No difference in deaths due to external causes was observed between the endometriosis and reference cohorts. CONCLUSION: Surgical diagnosis of endometriosis at a young age was associated with increased incidence of several psychiatric disorders. Moreover, within the endometriosis population, psychiatric comorbidity was more common in women with types of endometriosis other than ovarian endometriosis. We speculate that chronic pain is essential in the development of these psychiatric disorders, and that early and effective pain management is important in reducing the risk of psychiatric morbidity in young women. More research concerning the associations and management of endometriosis and associated psychiatric disorders is warranted.

Surgically confirmed endometriosis in adolescents in Finland-A register-based cross-sectional cohort study.

INTRODUCTION: Increasing awareness of endometriosis in adolescents requires data on the nature of the disease and its management. Our objective was to investigate the subtypes of surgically confirmed endometriosis in adolescents (aged <20 years) and trends in the incidence rates and endometriosis-related procedures during the study period, 1987-2012. MATERIAL AND METHODS: In this register-based cohort study, we identified 526 adolescents receiving their initial surgical diagnosis of endometriosis between 1987 and 2012 from the Finnish Hospital Discharge Register. The age-specific incidence rate of surgically confirmed endometriosis was calculated by dividing the number of adolescents during specific periods by person-years. We calculated the relative differences in incidence rates between the periods using crude incidence ratios. RESULTS: Adolescents were divided into three age groups, <17, 17-18, and 19 years, which comprised 8.2% (43/526), 39.7% (209/526), and 52.1% (274/526) of the study cohort, respectively. Peritoneal endometriosis and ovarian endometriosis were the most common types (379/526 [72%] and 119/526 [23%], respectively). The incidence rate of surgically confirmed endometriosis per 100 000 person-years varied from 5.63 (95% confidence interval [CI] 4.24-7.33) to 11.42 (95% CI 9.64-13.44). The incidence rate in 2001-2005 was significantly higher and was 1.6- to 2.0-fold that of the periods 1987-1990 and 2006-2012, respectively. Comparing the periods in which International Classification of Diseases, Ninth Revision (ICD-9; 1987-1995) and Tenth Revision (ICD-10; 1996-2012) codes were used, the use of laparoscopy (78.2% vs 88.9%), day surgery (10.3% vs 31.6%), and procedures for ovarian (18.8% vs 34.1%) and deep (0.6% vs 10.8%) endometriosis increased. The types of endometriosis and procedures did not differ between the age groups. CONCLUSIONS: Peritoneal endometriosis was the most common type of endometriosis overall and by age group. During the 26-year period, the incidence rate of initial surgical diagnosis of endometriosis peaked in 2001-2005 and decreased thereafter. The proportion of procedures performed for ovarian and deep endometriosis increased, as did the use of laparoscopy and day surgery.

A cohort study of 49 933 women with surgically verified endometriosis: Increased incidence of breast cancer below the age of 40.

INTRODUCTION: The association between endometriosis and breast cancer is unclear. We assessed the risk of breast cancer in women with surgically verified endometriosis, with special focus on the age at cancer diagnosis, time from endometriosis diagnosis and breast cancer histology. MATERIAL AND METHODS: All women with first endometriosis-associated diagnoses occurring concomitantly with relevant surgical codes during 1987-2012 were retrieved from the Finnish Hospital Discharge Register in Finland. Breast cancers diagnosed after the endometriosis diagnosis were identified from the Finnish Cancer Registry. The Finnish female population served as the reference. The endometriosis cohort consisted of 49 933 women (23 210 cases of ovarian, 20 187 peritoneal and 2372 deep infiltrating endometriosis). The outcome measure was the standardized incidence ratio (SIR) with 95% confidence interval (95% CI) of breast cancer calculated for the whole cohort and for the subtypes of endometriosis, stratified by the age at breast cancer diagnosis, histology and time from endometriosis diagnosis. RESULTS: The overall risk of breast cancer (1555 cases) was similar to the reference population (SIR 0.99; 95% CI 0.94-1.03), did not differ in types of endometriosis, and was similar for ductal and lobular breast cancer. However, the SIR of breast cancer was increased in the age group of 20-29 years (SIR 4.44; 95% CI 2.22-7.94) and in the age group of 30-39 years (SIR 1.28; 95% CI 1.03-1.57). The risk of in situ breast cancer (170 cases) was increased in the entire endometriosis cohort (SIR 1.25; 95% CI 1.07-1.44). CONCLUSIONS: The overall risk of breast cancer in women with surgically verified endometriosis was similar to that of general population. However, the risk of breast cancer at young age was increased. Young women with surgically verified endometriosis represent highly symptomatic patients with more frequent surgeries and additional therapies that might also contribute to the risk of breast cancer.

A Nationwide Cohort Study on the risk of non-gynecological cancers in women with surgically verified endometriosis.

We assessed the association of surgically verified endometriosis and risk of non-gynecological cancers according to the type of endometriosis (i.e., ovarian, peritoneal and deep infiltrating endometriosis). All diagnoses of endometriosis combined with relevant procedural codes were identified from the Finnish Hospital Discharge Register 1987-2012. Non-gynecological cancers diagnosed after the endometriosis diagnosis were obtained from the Finnish Cancer Registry. The cohort of 49,933 women with surgically verified endometriosis and the sub-cohorts of ovarian (n = 23,210), peritoneal (n = 20,187), and deep infiltrating (n = 2,372) endometriosis were analyzed separately. The endometriosis cohort contributed 838,685 person-years of follow-up and the Finnish female population served as the reference cohort. The standardized incidence ratio (SIR) and 95% confidence interval (95%CI) was calculated for each cancer separately. The follow-up ended at emigration, death or on the 31st of December 2014. The non-gynecological cancer risk was not increased among women with endometriosis (SIR 1.03, 95%CI 0.98-1.08). Endometriosis was associated with an increased risk of thyroid cancer in the entire cohort (SIR 1.43, 95%CI 1.23-1.64) and in the sub-cohorts of ovarian and peritoneal endometriosis. We found a decreased risk of mouth and pharynx cancer (SIR 0.60, 95%CI 0.41-0.80), and of pancreatic cancer (SIR 0.76, 95%CI 0.58-0.96). The incidence of basal cell carcinoma was elevated in the entire cohort (SIR 1.18, 95%CI 1.10-1.25) and in the sub-cohorts of ovarian and peritoneal endometriosis. In conclusion, women with surgically verified endometriosis have an altered risk of only few non-gynecological cancers.

Trends in the incidence rate, type and treatment of surgically verified endometriosis - a nationwide cohort study.

INTRODUCTION: To study the trends in incidence rate, type and surgical treatment, and patient characteristics of surgically verified endometriosis during 1987-2012. MATERIAL AND METHODS: This is a register-based cohort study. We identified women receiving their first diagnosis of endometriosis in surgery from the Finnish Hospital Discharge Register (FHDR). Quality of the FHDR records was assessed bidirectionally. The age-standardized incidence rates of the first surgically verified endometriosis was assessed by calendar year. RESULTS: The cohort comprises 49 956 women. The quality assessment suggested the FHDR data to be of good quality. The most common diagnosis, ovarian endometriosis (46%), was associated with highest median age 38.5 years (interquartile range 31.0-44.8) and the second most common diagnosis, peritoneal endometriosis (40%), with median age 34.9 years (28.6-41.7). Between 1987 and 2012, a decrease was observed in the median age, from 38.8 (32.3-43.6) to 34.0 (28.9-41.0) years, and in the age-standardized incidence rate from 116 [95% confidence interval (CI) 112-121] to 45 (42-48) per 100 000 women. The proportion of hysterectomy as a first surgical treatment decreased from 38 to 19%, whereas that of laparoscopy increased from 42 to 73% when comparing 1987-1995 with 1996-2012. CONCLUSIONS: This nationwide cohort of surgically verified endometriosis showed a decrease in the incidence rate and in the patient age at the time of first diagnosis, even though the proportion of laparoscopy has increased. The number of hysterectomies has decreased. These changes are likely to reflect the evolving diagnostics, increasing awareness of endometriosis, and effective use of medical treatment before surgery.

Pregnancy and delivery outcomes in women with rectovaginal endometriosis treated either conservatively or operatively.

OBJECTIVE: To study reproductive outcomes, and pregnancy and delivery complications after conservative or operative treatment of rectovaginal endometriosis during long-term follow-up. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Women with rectovaginal endometriosis referred to hospital due to any indication from 2004 to 2013 (N = 543) who were treated initially either conservatively (group CONS, n = 183), or operatively (OPER, n = 360) either with resection of rectovaginal nodule (RVR, n = 192) or with concomitant bowel resection (BR, n = 132). INTERVENTION(S): Conservative or operative management. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live-birth rate, and assessment of the complications during pregnancy and delivery. RESULTS(S): Between women in the CONS group or OPER group, no differences were found in either clinical pregnancy rate (56%, n = 102 vs. 50%, n = 181) or live-birth rate (48%, n = 87 vs. 42%, n = 153). Of the pregnancies, 64% (n = 65) and 49% (n = 89), respectively, started after medically assisted reproduction. No differences emerge in the subanalysis of women <40 years-old who wished to conceive. The most common pregnancy complication was preterm birth: 15% (n = 13) in the CONS group and 20% (n = 30) in the OPER group. The cesarean delivery rate also was high (46%, n = 40 vs. 49%, n = 76). Complications emerged in 21% (n = 10) versus 29% (n = 23) of vaginal deliveries and 45% (n = 18) versus 53% (n = 40) of cesarean deliveries. The most common delivery complication was excessive bleeding. The follow-up period was 4.9 years in the CONS group and 5.6 years in the OPER group. CONCLUSION(S): Women with rectovaginal endometriosis have comparable and good reproductive prognosis regardless of the treatment method.

Incidence of extraovarian clear cell cancers in women with surgically diagnosed endometriosis: A cohort study.

BACKGROUND: Endometriosis is associated with increased risk of clear cell ovarian cancer and has even suggested being an etiological factor for this cancer. Association between endometriosis and extraovarian clear cell cancers is unclear. This study aimed to assess the association between surgically diagnosed endometriosis and risk of extraovarian clear cell cancers according to the type of endometriosis (i.e., ovarian, peritoneal, and other endometriosis) and the site of clear cell cancer. METHODS: In this register-based historic cohort study we identified all women with surgically diagnosed endometriosis from the Finnish Hospital Discharge Registry 1987-2012. Data on extraovarian clear cell cancers of these women were obtained from the Finnish Cancer Registry. The follow-up started January 1st, 2007 or at endometriosis diagnosis (if later), and ended at emigration, death or on the December 31st, 2014. Standardized incidence ratios were calculated for each site of clear cell carcinoma (intestine, kidney, urinary tract, gynecological organs other than ovary), using the Finnish female population as reference. RESULTS: The endometriosis cohort consisted of 48,996 women, including 22,745 women with ovarian and 19,809 women with peritoneal endometriosis. Altogether 23 extraovarian clear cell cancers were observed during 367,386 person-years of follow-up. The risk of extraovarian clear cell cancer was not increased among all women with surgically diagnosed endometriosis (standardized incidence ratio 0.89, 95% confidence interval 0.56-1.33) nor in different types of endometriosis. The incidence of clear cell cancer in any specific site was not increased either. CONCLUSIONS: The risk of extraovarian clear cell cancers in women with surgically diagnosed endometriosis is similar to that in the general population in Finland.

Risk of Gynecologic Cancer According to the Type of Endometriosis.

OBJECTIVE: To assess the risks of gynecologic cancer according to the type of endometriosis in women with surgically verified endometriosis. METHODS: This is a population-based study of women with surgically verified endometriosis retrieved from the Finnish Hospital Discharge Register 1987-2012 (N=49,933); the subtypes of ovarian (n=23,210), peritoneal (n=20,187), and deep infiltrating (n=2,372) endometriosis were analyzed separately. Gynecologic cancers were obtained from the Finnish Cancer Registry. The outcome measure was the standardized incidence ratio (95% CI) calculated as the ratio between the observed to the expected number of cancers and defined for each gynecologic cancer and further stratified according to the histology, follow-up time since surgery, and age at follow-up. The follow-up was 838,685 person-years, and the Finnish female population served as the reference. RESULTS: Endometriosis was associated with increased risk of ovarian cancer (standardized incidence ratio 1.76 [95% CI 1.47-2.08]), especially with endometrioid (3.12 [2.15-4.38]) and clear cell (5.17 [3.20-7.89]) histologic type and to a lesser extent with serous type (1.37 [1.02-1.80]). The risk of ovarian cancer was highest among women with ovarian endometriosis and especially for endometrioid (4.72 [2.75-7.56]) and clear cell (10.1 [5.50-16.9]) ovarian cancer, occurring 5-10 years after the index surgery. The overall risk of ovarian cancer was not increased among women with peritoneal and deep infiltrating endometriosis. However, peritoneal endometriosis was associated with a twofold increase in risk of endometrioid histology. The risk of endometrial cancer was not altered in the entire cohort. The standardized incidence ratio for precancerous cervical lesions was 0.81 (0.71-0.92) and for invasive squamous cell carcinoma of the cervical cancer 0.46 (0.20-0.91). CONCLUSION: The excess risk of ovarian cancer among women with ovarian endometriosis translates into two excess cases per 1,000 patients followed for 10 years. Acknowledging these risks is important when planning long-term management of women with endometriosis.

Deep infiltrating endometriosis affecting the urinary tract-surgical treatment and fertility outcomes in 2004-2013.

Urinary tract endometriosis (UTE) is a rare form of deep infiltrating endometriosis. We studied the operative treatment of UTE and evaluated postoperative recurrences and fertility outcomes. This is a retrospective cohort study of 53 women who underwent operative treatment for UTE in 2004-2013 at Helsinki University Hospital, and were followed-up until the end of 2014. The data were gathered from the hospital's electronic database. The main outcome measures were complications, reoperations, postoperative pregnancies, and deliveries. Preoperative diagnosis was accurate in 72 % with bladder endometriosis and in 93 % with ureteral disease. Thirty-one (58 %) of the 53 operations were performed via laparoscopy. Postoperative complications requiring re-intervention occurred in five cases (9 %). Five reoperations were performed in four cases due to endometriosis recurrence, only two due to recurrence of UTE (4 %). Twenty-eight women wished for pregnancy; 18 (64 %) of them conceived. Infertility treatment was needed in 20 (71 %) cases. Twelve (75 %) women delivered via cesarean section; intraoperative difficulties occurred in ten (83 %). The complication rate with UTE operations is acceptable and recurrences are rare. Infertility is common, but 57 % of those who wished for a child succeeded. A majority of the deliveries involved unplanned and complicated cesarean section.