Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study.

OBJECTIVES: To investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer. DESIGN: Prospective, nationwide cohort study. SETTING: Denmark, 1995-2014. PARTICIPANTS: All women aged 15-49 years during 1995-2014 were eligible. Women were excluded if they immigrated after 1995, had cancer (except non-melanoma skin cancer), had venous thrombosis, or were treated for infertility before entry (final study population included 1 879 227 women). Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (≤1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives. MAIN OUTCOME MEASURES: Poisson regression was used to calculate relative risk of ovarian cancer among users of any contemporary combined hormonal contraceptives and by progestogen type in combined preparations and all progestogen-only products, including non-oral preparations. Separate analyses examined women followed up to their first contraception type switch and those with full contraceptive histories. Duration, time since last use, and tumour histology were examined and the population prevented fraction were calculated. RESULTS: During 21.4 million person years, 1249 incident ovarian cancers occurred. Among ever users of hormonal contraception, 478 ovarian cancers were recorded over 13 344 531 person years. Never users had 771 ovarian cancers during 8 150 250 person years. Compared with never users, reduced risks of ovarian cancer occurred with current or recent use and former use of any hormonal contraception (relative risk 0.58 (95% confidence interval 0.49 to 0.68) and 0.77 (0.66 to 0.91), respectively). Relative risks among current or recent users decreased with increasing duration (from 0.82 (0.59 to 1.12) with ≤1 year use to 0.26 (0.16 to 0.43) with >10 years' use; P<0.001 for trend). Similar results were achieved among women followed up to their first switch in contraceptive type. Little evidence of major differences in risk estimates by tumour type or progestogen content of combined oral contraceptives was seen. Use of progestogen-only products were not associated with ovarian cancer risk. Among ever users of hormonal contraception, the reduction in the age standardised absolute rate of ovarian cancer was 3.2 per 100 000 person years. Based on the relative risk for the never use versus ever use categories of hormonal contraception (0.66), the population prevented fraction was estimated to be 21%-that is, use of hormonal contraception prevented 21% of ovarian cancers in the study population. CONCLUSIONS: Use of contemporary combined hormonal contraceptives is associated with a reduction in ovarian cancer risk in women of reproductive age-an effect related to duration of use, which diminishes after stopping use. These data suggest no protective effect from progestogen-only products.

Contemporary Hormonal Contraception and the Risk of Breast Cancer.

BACKGROUND: Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer. METHODS: We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders. RESULTS: Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year. CONCLUSIONS: The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.).

Somatic health of 2500 women examined at a sexual assault center over 10 years.

INTRODUCTION: Sexual assault is a public health issue with many potential short- and long-term consequences for the victims. We aimed to investigate somatic health of women before and after sexual assault. MATERIAL AND METHODS: We included 2501 women who attended the Centre for Victims of Sexual Assault in Copenhagen, and 10004 women without a known assault experience (controls). Somatic diagnoses were retrieved from the National Health Registry and number of visits to general practitioners from the Danish Health Insurance Registry. Somatic data were assessed during the five-year period before and after the assault. RESULTS: The incidence of several somatic disorders was found to be significantly higher for the exposed women than for controls, both before and after the assault. Rate ratios of main disorders before and after the assault were respectively: disease of circulatory and respiratory system: 3.2 (2.6-4.1) and 2.6 (2.1-3.2); epilepsy: 2.9 (2.2-3.8) and 4.1 (3.0-5.6) and disease of the liver: 3.5 (1.9-6.3) and 7.0 (4.4-11.1), respectively. The rate ratios of laparoscopic surgery: 1.5 (0.9-2.5) and 3.4 (2.3-5.0) and of cervical cancer: 0.8 (0.4-1.7) and 2.0 (1.4-3.0) increased significantly after sexual assault. Likewise, the number of visits to a general practitioner was significantly higher in exposed women both before and after the assault (16 vs. 10/year). Complications associated with childbirth were not statistically different between the groups. CONCLUSIONS: Our results suggest a higher somatic morbidity in women seen at a sexual assault center before as well as after the assault compared with controls.

Reproductive prognosis in endometriosis. A national cohort study.

OBJECTIVE: To assess the reproductive long-term prognosis of women with and without endometriosis, to explore changes over time, and to quantify the contribution of artificial reproductive techniques. DESIGN: Cohort study. SETTING: Denmark 1977-2009. SAMPLE: Data retrieved from four national registries. Among 15-49-year-old women during the period 1977-82, 24 667 were diagnosed with endometriosis and 98 668 (1:4) women without endometriosis were age-matched. METHODS: To assess long-term reproductive prognosis, all pregnancy outcomes were identified among the women with and without endometriosis until the end of 2009. To explore changes over time, the endometriosis cohorts were followed for 15 years from the years 1980, 1986, 1992 and 1998, with the corresponding control cohorts. All pregnancy outcomes were categorized into naturally or artificially conceived pregnancies. MAIN OUTCOME MEASURES: Births, miscarriages, induced abortions, ectopic pregnancies and hydatidiform moles. RESULTS: Compared with women without endometriosis, women with endometriosis had a lowered relative risk for childbirth of 0.93 (95% confidence interval 0.92-0.95), for miscarriages the relative risk was 1.2 (95% confidence interval 1.2-1.3), ectopic pregnancies were almost twice as many (relative risk 1.9, 95% confidence interval 1.8-2.1), while frequencies of induced abortions were equivalent. The chances for childbirth increased over time from 0.82 to 0.92 (p < 0.001) with successive cohorts, but this was restricted to pregnancies from assisted reproduction. CONCLUSION: Women with endometriosis have slightly fewer children, but this lessened over time due to artificially conceived pregnancies. The risk for miscarriages and ectopic pregnancies was increased compared with women without the disease.

Venous thromboembolism in pregnancy and the puerperal period: a study of 1210 events.

OBJECTIVE: The aim of this study was to describe venous thromboembolism (VTE) in pregnancy and the puerperal period, and to validate diagnoses of VTE. DESIGN: Historical cohort study. POPULATION: All pregnancies in Denmark from 1995 to 2009. METHODS: VTE diagnoses were retrieved from national registries. MAIN OUTCOME MEASURES: Positive predictive value of a VTE diagnoses diagnosed during pregnancy or the puerperal period. Location of VTE. Incidence rate of confirmed, validated diagnoses of VTE and on all retrieved diagnoses of VTE. RESULTS: In 1 297 037 pregnancies, 1436 women had a first-ever VTE diagnosis. Hospital records were retrieved for 1210 women (84.3%). Almost all women had relevant clinical symptoms and in 796 (65.8%), the diagnosis were confirmed by a positive diagnostic test or by instituted anticoagulation treatment. In all, 72.6, 53.7, 58.5 and 79.1% of the diagnoses were confirmed in the first, second, third trimester and the puerperal period, respectively. The 796 cases of VTE included 624 women with deep venous thrombosis only and 133 with pulmonary embolisms. Deep venous thrombosis was located in the left lower limb in 83.8% in pregnancy, compared with 67.9% in the puerperal period. CONCLUSIONS: The vast majority of women with a registered diagnosis of VTE had relevant symptoms. Diagnoses of VTE were confirmed in the medical records in two of three women. VTE diagnoses were most often confirmed when made in the first trimester and in the puerperal period. Left-sided deep venous thrombosis was the predominant type of VTE in pregnancy and the puerperal period.