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.

Ovarian cancer prognosis in women with endometriosis: a retrospective nationwide cohort study of 32,419 women.

BACKGROUND: Contradicting results regarding ovarian cancer prognosis in women with endometriosis have been reported in the literature. Owing to the small sample size of previous studies, larger studies are required to elucidate the role of endometriosis in ovarian cancer prognosis. OBJECTIVE: This study aimed to evaluate the survival rate in women with ovarian cancer with or without histologically proven endometriosis in a Dutch population-based cohort. STUDY DESIGN: All women with ovarian cancer diagnosed between 1990 and 2015 were identified from the Netherlands Cancer Registry. We linked these women with the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief) to identify all women with histologically proven endometriosis. We compared the prognosis of patients with ovarian cancer with and without histologically proven endometriosis. Primary outcome was the overall survival with subgroup analyses stratified by histologic ovarian cancer subtype and stage. Multivariable Cox proportional hazard analysis was used to estimate hazard ratios with 95% confidence intervals. RESULTS: We included 32,419 patients with ovarian cancer, of whom 1979 (6.1%) had histologically proven endometriosis. The median age of histologic endometriosis diagnosis was 53 years (interquartile range, 46-62). Of all women with ovarian cancer and endometriosis, 81.2% received a diagnosis of synchronous endometriosis and ovarian cancer. The endometriosis cohort was younger at ovarian cancer diagnosis, had more favorable tumor characteristics, and more often had surgical treatment for ovarian cancer than the women without endometriosis. These variables were included in the multivariable model as confounders. Women with histologically proven endometriosis had a significantly better prognosis in both crude and adjusted analyses (hazard ratio, 0.46; 95% confidence interval, 0.43-0.49; P<.0005, and adjusted hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; P<.05, respectively). CONCLUSION: Women with ovarian cancer and histologically proven endometriosis had longer overall survival than women with ovarian cancer without endometriosis, even after adjustment for confounders. Future studies on ovarian cancer treatment and prognosis should consider stratifying by endometriosis status to elucidate its role. Furthermore, women diagnosed as having ovarian cancer and concurrent endometriosis should be explained the role of endometriosis in ovarian cancer survival.

Early Detection of Ovarian Dysfunction by Anti-Mullerian Hormone in Adolescent and Young Adult-Aged Survivors of Childhood Cancer.

PURPOSE: Current guidelines recommend screening at-risk childhood cancer survivors for ovarian dysfunction using follicle-stimulating hormone (FSH). However, FSH identifies diminished ovarian reserve (DOR), a component of ovarian dysfunction, in the later stages when fertility preservation is less likely to succeed. This analysis evaluates the utility of anti-Mullerian hormone (AMH) for the assessment of DOR in adolescent and young adult (AYA)-aged survivors of childhood cancer. METHODS: A retrospective chart review of 13- to 21-year-old female survivors who received gonadotoxic therapy and were ≥2 years off therapy was performed. Gonadotoxic treatments were categorized as low, moderate, or high risk for future infertility. Patients with AMH below the assay's age-specific normal range were identified and stratified by FSH values (normal ≤12 mIU/mL). Prevalence of low AMH and AMH-FSH subgroups was calculated and risk factors were evaluated using logistic regression. RESULTS: AMH was measured in 190 survivors who received gonadotoxic treatment; of them, 35.3% had low AMH. Among survivors who received <30 Gy cranial radiation and were not on hormone therapy (n = 141), 18.4% had normal FSH with low AMH. Stratified by future infertility risk, 10.6% of low-risk, 38.1% of moderate-risk, and 25.7% of high-risk survivors had normal FSH with low AMH (p < 0.01). Within the low-risk group, normal FSH with low AMH was significantly associated with older age at diagnosis (p = 0.02). CONCLUSION: Nearly 20% of AYA-aged at-risk survivors had low AMH and normal FSH. DOR in these patients would have been missed in standard recommended surveillance practices.

The effect of ovarian dysfunction on bone mineral density in breast cancer patients 10 years after adjuvant chemotherapy.

BACKGROUND: Premenopausal patients treated with adjuvant chemotherapy often develop early menopause and thus, may encounter significant bone loss. We studied the long-term effects of chemotherapy-induced ovarian dysfunction on bone mineral density in breast cancer patients. MATERIAL AND METHODS: The effect of menstrual status after adjuvant chemotherapy on bone mineral density (BMD) was examined in 29 premenopausal breast cancer patients. RESULTS: During 10 years of follow-up, nearly 90% of women developed menstrual irregularities or amenorrhea. The total bone loss at the lumbar spine was -5.4% in women with preserved menstruation, -15.3% in those with irregular menses and -13.2% in amenorrheic women 10 years after adjuvant chemotherapy. The changes in lumbar spine BMD correlated significantly with menstrual function. Both amenorrhea and menstrual irregularities shortly after chemotherapy increased the risk of osteoporosis later on: one third of women with ovarian dysfunction developed osteoporosis of the lumbar spine during the follow-up. Osteopenia before adjuvant therapy predicted an increased risk for osteoporosis. CONCLUSION: The present study with a unique follow-up period of 10 years shows that ovarian dysfunction leads to long-term deleterious BMD changes and predisposes breast cancer survivors to osteoporosis.

Long term survival of ovarian endometriosis associated clear cell and endometrioid ovarian cancers.

OBJECTIVE: This study aimed to analyze long-term survival of clear cells (CCs) and endometrioid (E) ovarian cancer cases according to presence of endometriosis in the pathologic report. METHODS: This is a retrospective analysis of 47 CC and 66 E ovarian cancer cases observed consecutively at our center between 1990 and 2010.All cases had first surgery at our center or were referred to it for treatment and follow-up.Cases were identified according to the original diagnosis reported in clinical records.All pathologic reports were reviewed, and cases were classified with or without pathologic evidence of endometriosis on the basis of the pathologic report.Follow-up was updated in March 2011. The follow-up median was 147 months (range, 116-171). RESULTS: Endometriosis-associated ovarian cancer cases were more frequently diagnosed at stage I to II than cases without endometriosis: among the 36 endometriosis-associated ovarian cancer cases, 25 (69%) were at stage I or II, and the corresponding value was 35 (46%) of 77 among cases without endometriosis (P = 0.0173).The presence of endometriosis tended to be associated with a higher 10-year survival rate: after taking the potential confounding effect of stage into account, the finding was not statistically significant (hazards ratio, 0.7; 95% confidence interval, 0.3-1.5). CONCLUSIONS: This analysis shows that EA CCs and E ovarian cases are diagnosed at an earlier stage than cases without endometriosis. No clear association emerged between presence of endometriosis and survival.

Accuracy of intra-operative frozen sections in the diagnosis of ovarian masses.

The accuracy of frozen section diagnosis in the intraoperative evaluation of ovarian masses is very important with regard to surgeon selection of appropriated operating procedures. For evaluation in our institute, the records of 127 patients with ovarian masses submitted for intraoperative frozen sections between January 2001 and December 2005 were reviewed. After exclusion of 4 completely infarcted masses and 11 cases with deferred frozen section diagnoses, 112 were analyzed for diagnostic accuracy by comparing with the final histologic results. We found sensitivity in the diagnosis of benign, borderline and malignant tumors to be 100%, 84%, and 92 %, respectively, with specificities of 92.7%, 97.9%, and 100%, respectively. The overall accuracy with frozen sections was 94 %. Among 18 patients with deferred or discordant diagnoses, mucinous tumors accounted for 72 % of cases. No over-diagnosis of malignancy or misdiagnosis of metastatic lesions as primary ovarian cancer by frozen sections was observed. In conclusion, the accuracy of intraoperative frozen section for the diagnosis of ovarian masses is high. Frozen sections also help in the evaluation of metastatic tumors to the ovary. Mucinous tumors constitute an important group causing diagnostic discrepancies.

Preoperative serum vascular endothelial growth factor (VEGF) in ovarian masses.

PURPOSE OF THE INVESTIGATION: To determine the diagnostic value of serum vascular endothelial growth factor (VEGF) in the preoperative assessment of the nature of ovarian masses. MATERIALS AND METHODS: A prospective cohort study was conducted from August 2001 to September 2002 on 40 premenopausal and 23 postmenopausal patients with ovarian masses. During preoperative workup, patient age, serum Ca-125 levels, serum VEGF levels, and tumor volume based on ultrasonographic examination were determined. Laparoscopic (n=23) or laparotomic (n=39) approaches were undertaken to obtain the final pathologic result. According to the final ovarian pathology, follicular cysts, corpus luteum cysts and endometriomas were grouped as non-neoplastic ovarian masses (n=40, group I). Serous or mucinous cyctadenomas, dermoid tumors and fibromas were allocated into the neoplastic benign ovarian mass group (n=10, group II). Primary malignant ovarian neoplasms were categorized into the neoplastic-malign group (n=12, group III). RESULTS: Mean ages of cases among groups I, II and III were 39.0 +/- 2.0, 42.2 +/- 5.2 and 56.9 +/- 4.2, respectively. As age of the cases enrolled in this sudy increased, the more likely was the occurrence of neoplastic malign ovarian pathologies (p < 0.001). Among postmenopausal cases diagnosed with an ovarian mass, serum Ca-125 levels were 113.5 +/- 20 IU/ml compared to those in premenopausal cases (85.8 +/- 16.0, p = 0.05). The values for serum VEGF values among pre- and postmenopausal ovarian masses were 46.2 +/- 6.7 pg/ml and 68.2 +/- 7.9, respectively (p = 0.04). In group I, serum VEGF levels of endometriomas (56.5 +/- 1.5 pg/ml) were higher compared to those of follicular or corpus luteum cysts (30.6 +/- 2.8, p = 0.05). In contrast, tumor size appeared to be larger in non-endometriotic. non-neoplastic cysts (10.1 +/- 2.0 cm), compared to endometriomas (6.4 +/- 0.6 cm, p < 0.01). Serum VEGF levels of group III were higher than other groups (p < 0.001). With respect to the discriminating benign or malign nature of the mass, with a specific cut-off value of serum VEGF level of 68.7 pg/ml, the sensitivity, specificity, positive and negative likelihood ratios were 92.3%, 88.0%, 3.3 and 0.1, respectively. For serum Ca-125 levels, the sensitivity, specificity, positive and negative likelihood ratio with a statistically relevant cut-off value of 102 IU/ml were, 76.9%, 76.0%, 3.21 and 0.3, respectively. Area under curve (AUC) for serum VEGF and Ca-125 values were 0.938 (95% CI: 0.81-0.96) and 0.769 (95% CI: 0.64-0.86), respectively (p = 0.02). Among the postmenopausal group, AUC for serum VEGF and Ca-125 was detected as 0.902 (95% CI: 0.70-0.98) and 0.873 (95% CI: 0.66-0.91) (p = 0.14). CONCLUSION: Serum VEGF has the potential to be considered as a tumor marker with a good diagnostic relevance in differentiating the nature of ovarian masses.

Ruptured tuboovarian abscess. Is hysterectomy necessary?

The use of conservative pelvic surgery combined with intra- and postoperative antibiotic peritoneal lavage has been evaluated in 113 women with generalized peritonitis due to ruptured tuboovarian abscess. Mortality was 7.1% and hysterectomy was only required in 3% of cases. Hormonal and menstrual functions were retained in 73.5% and the potential for future pregnancy in 42.5%. Further surgery was required in 17.5% of the patients. These results are contrasted with recent series of comparable size in which the mortality and morbidity were similar but the frequency of hysterectomy ranged from 70--100%. It is concluded that hysterectomy is not necessary in the management of ruptured tuboovarian abscess if the major source of sepsis is removed and adequate peritoneal drainage is provided by the use of lavage.