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Objective: Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure.Methods: We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics.Results: Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years.Conclusion: The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase. [ABSTRACT FROM AUTHOR]

Objective: Lymphovascular space invasion (LVSI) is a known prognostic factor for oncological outcome in endometrial cancer patients. However, little is known about the prognostic value of LVSI among the different molecular subgroups. The aim of this study was to determine the prognostic dependence of LVSI from the molecular signature., Methods: This study included endometrial cancer patients who underwent primary surgical treatment between February 2004 and February 2016 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort). All cases had complete molecular analysis performed on the primary tumor according to the WHO Classification of Tumors, 5th edition. LVSI was reviewed by reference pathologists for all pathology slides., Results: A total of 589 endometrial cancer patients were included in this study, consisting of 40 POLE mut (polymerase epsilon ultramutated), 198 MMRd (mismatch repair deficient), 83 p53abn (p53 abnormal), and 268 NSMP (non-specific molecular profile) cases. Altogether, 17% of tumors showed LVSI: 25% of the POLE mut, 19% of the MMRd, 30% of the p53abn, and 10% of the NSMP cases. There was a significant correlation of LVSI with lymph node metastasis in the entire study cohort (p<0.001), remaining significant in the MMRd (p=0.020), p53abn (p<0.001), and NSMP (p<0.001) subgroups. Mean follow-up was 89 months (95% CI 86 to 93). The presence of LVSI significantly decreased recurrence-free survival among patients with MMRd, p53abn, and NSMP endometrial cancer, and overall survival in patients with p53abn and NSMP tumors. In patients with NSMP endometrial cancer, evidence of substantial LVSI remained a significant independent predictor of recurrence in multivariable Cox regression analysis including tumor stage and grade (HR 7.5, 95% CI 2.2 to 25.5, p=o.001)., Conclusion: The presence of LVSI was associated with recurrence in each subgroup of patients with MMRd, p53abn, and NSMP endometrial cancer, and LVSI remained an independent predictor of recurrence in NSMP endometrial cancer patients., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objectives: To describe the sonographic characteristics of post-molar gestational trophoblastic neoplasia (GTN) at diagnosis and during follow-up, and to assess their association with methotrexate (MTX) resistance (R) as first-line chemotherapy., Methods: This was a retrospective study of all women treated for post-molar GTN at Karolinska University Hospital, Stockholm, Sweden, between October 2010 and December 2017, who had undergone expert transvaginal ultrasound assessment ≤ 2 weeks prior to, or ≤ 1 week after, the start of first-line MTX treatment. Women with a detectable uterine lesion were followed up with repeat scans during treatment, as well as after treatment in cases of persistent lesions. The association between MTX-R and sonographic findings at inclusion was assessed., Results: Of 47 eligible women, 36 were included in the analysis after excluding those who had not undergone structured transvaginal ultrasound assessment and those who started treatment at another center. The median age at diagnosis was 33 (interquartile range (IQR), 27-43) years and 35/36 (97%) women were in the FIGO low-risk group (risk score, 0-6). At inclusion, no uterine lesions were found in eight (22%) women, focal lesions in 24 (67%) women and global lesions in four (11%) women. Median maximum lesion diameter was 40.4 (IQR, 31.3-49.4) mm and 26/28 (93%) lesions had a color score of 3 or 4. Arteriovenous fistulas were found in 9/28 (32%) women and theca lutein cysts in 4/36 (11%) women. Four women with GTN lesion at inclusion underwent hysterectomy prior to the first follow-up ultrasound scan and a fifth woman with a growing lesion underwent hysterectomy, which revealed persistent viable trophoblastic tissue. All remaining women reached complete remission and median time to human chorionic gonadotropin normalization was 2.7 (IQR, 1.4-3.7) months. During ultrasound follow-up, 88% (21/24) of lesions resolved completely. Two women with a persisting lesion remained in complete remission. Median time to disappearance of vascularity was 5.8 (IQR, 3.7-9.3) months and median time to resolution of the lesion was 6.8 (IQR, 3.7-9.3) months. MTX-R developed in 12/31 (39%) women. Uterine tumors ≥ 4 cm (73% vs 17%; P = 0.008) and global lesions (25% vs 0%; P = 0.03) were significantly more common in women with compared to those without MTX-R., Conclusion: Uterine lesions were detected at the time of diagnosis in 78% of women with post-molar GTN. The vast majority of the lesions resolved completely during follow-up, after a median of 7 months. MTX-R was more common in uterine tumors of 4 cm, or larger, and in global lesions. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Sun exposure in combination with skin pigmentation is the main determinant for vitamin D status. Human skin color seems to be adapted and optimized for regional sun ultraviolet (UV) intensity. However, we do not know if fair, UV-sensitive skin is a survival advantage in regions with low UV radiation., Methods: A population-based nested case-control study of 29,518 Caucasian women, ages 25 to 64 years from Southern Sweden who responded to a questionnaire regarding risk-factors for malignant melanoma in 1990 and followed for 25 years. For each fair woman, defined as having red hair or freckles (n = 11,993), a control was randomly selected from all non-fair women from within the cohort of similar age, smoking habits, education, marital status, income, and comorbidity, i.e., 11,993 pairs. The main outcome was the difference in all-cause mortality between fair and non-fair women in a low UV milieu, defined as living in Sweden and having low-to-moderate sun exposure habits. Secondary outcomes were mortality by sun exposure, and among those non-overweight., Results: In a low UV milieu, fair women were at a significantly lower all-cause mortality risk as compared to non-fair women (log rank test p = 0.04) with an 8% lower all-cause mortality rate (hazard ratio [HR] = 0.92, 95% CI 0.84‒1.0), including a 59% greater risk of dying from skin cancer among fair women (HR 1.59, 95% CI 1.26‒2.0). Thus, it seem that the beneficial health effect from low skin coloration outweigh the risk of skin cancer at high latitudes., Conclusion: In a region with low UV milieu, evolution seems to improve all-cause survival by selecting a fair skin phenotype, i.e., comprising fair women with a survival advantage., Competing Interests: The authors have declared that no competing interests exist.

Background: Sunlight exposure and fair skin are major determinants of human vitamin D production, but they are also risk factors for cutaneous malignant melanoma (MM). There is epidemiological evidence that all-cause mortality is related to low vitamin D levels., Methods: We assessed the avoidance of sun exposure as a risk factor for all-cause mortality for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 and were aged 25 to 64 years at the start of the study. We obtained detailed information at baseline on their sun exposure habits and potential confounders. Multivariable flexible parametric survival analysis was applied to the data., Results: There were 2545 deaths amongst the 29 518 women who responded to the initial questionnaire. We found that all-cause mortality was inversely related to sun exposure habits. The mortality rate amongst avoiders of sun exposure was approximately twofold higher compared with the highest sun exposure group, resulting in excess mortality with a population attributable risk of 3%., Conclusion: The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health., (© 2014 The Association for the Publication of the Journal of Internal Medicine.)

Our aim was to determine the risk of endometrial cancer associated with long-term use of combined hormone therapy (HT) and low-potency estrogens. In this prospective population-based cohort, 40,000 women aged 25-64 years, without prior cancer or hysterectomy, were included. The women answered 2 questionnaires at a 10-year interval regarding HT use and personal details. Women were followed up for an average of 15.5 years through the National Cancer and Causes of Death Registry, representing 236,611 women years. Among the 17,822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. Only use of combined HT was related to a decreased risk of endometrial cancer (OR 0.3, 95% CI 0.1-0.8), the protective effect was found after 2 years, and increased with extended duration of use. "Only use" of low-potency estrogens increased the risk of endometrial cancer almost to the same extent as use of high-potency estrogens (OR 2.0, 95% CI 1.1-3.6 vs. OR 2.5, 95% CI 1.3-4.8), the increased risk was confined to non-obese women in both groups. The risk was significantly increased for oral but not for local low-potency estrogen users (OR 2.1, 95% CI 1.1-3.6 vs. OR 1.5, 95% CI 0.4-6.2, respectively). In long-term estrogen users the risk was highest during the first 2 years, dropping slightly thereafter. Since low-potency estrogen use increases the risk of endometrial cancer almost as much as high-potency estrogen use, they should only be given if medically indicated., (Copyright 2009 UICC.)

Background: Venous and arterial thrombotic complications exhibit a seasonal variation, with risk peaking in winter and dropping to a nadir in summer. We sought a possible correlation between sun exposure habits and venous thromboembolism (VTE) events., Methods: This was a cohort study comprising 40,000 women (1000 per year of age from 25 to 64 years) who were drawn from the southern Swedish population registry for 1990 and followed for a mean of 11 years. Seventy-four per cent answered an inquiry at the inception of the study (n=29,518), and provided detailed information on their sun exposure habits. Cox regression analysis was used with the presence of VTE as a dependent variable and selected demographics as independent variables. The main outcome was the relationship between VTE and sun exposure habits., Results: Swedish women who sunbathed during the summer, on winter vacations, or when abroad, or used a tanning bed, were at 30% lower risk of VTE than those who did not. Risk estimates did not change substantially after adjustment for demographic variables. The risk of VTE increased by 50% in winter as compared to the other seasons; the lowest risk was found in the summer., Conclusions: Women with more active sun exposure habits were at a significantly lower risk of VTE. We speculate that greater ultraviolet B light exposure improves a person's vitamin D status, which in turn enhances anticoagulant properties and enhances the cytokine profile.

There has been a great advance in our knowledge of the role that thrombophilic factors play in the risk of venous thromboembolic events (VTE). However, the effect of lifestyle factors on VTE has been inadequately explored in large scale studies of women. This cohort study comprised one thousand native Swedish women for each age year between 25 and 64 inclusive (total = 40,000) drawn from the South Swedish population registry for 1990 (n = 40,000), who were followed for a mean of eleven years. Seventy-four percent completed a questionnaire at the inception of the study (n = 29,518) and 24,098 women responded to a follow-up inquiry between the years 2000-2002. The main outcome was the relationship between VTE and physical exercise, smoking habits, and alcohol consumption. Moderate drinkers of alcohol (10-15 g/d) and women engaged in strenuous exercise were at half the risk of VTE compared to those who consumed little or no alcohol or lived a sedentary life. Heavy smoking was associated with a 30% increased risk of VTE. Lifestyle factors have a major impact on the risk of VTE. Women non-smokers who were physically active and who consumed alcohol in moderation were at a lower risk of VTE.

Background: To determine the risk of endometrial and cervical pathology during long-term follow-up in women with postmenopausal bleeding and thin endometrium (