Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women's mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed.
To investigate whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital.
This nationwide prospective cohort study combined data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women and adolescents aged 15 to 34 years who were living in Denmark were followed up from January 1, 2000, to December 2013, if they had no prior depression diagnosis, redeemed prescription for antidepressants, other major psychiatric diagnosis, cancer, venous thrombosis, or infertility treatment. Data were collected from January 1, 1995, to December 31, 2013, and analyzed from January 1, 2015, through April 1, 2016.
Use of different types of hormonal contraception.
With time-varying covariates, adjusted incidence rate ratios (RRs) were calculated for first use of an antidepressant and first diagnosis of depression at a psychiatric hospital.
A total of 1?061?997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71).
Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use.
To investigate associations between combined hormonal contraception and progestogen-only contraception and risks of venous thromboembolism by progestogen and carriership of genetic hemostatic variations.
This was a case-control study in Sweden carried out between 2003 and 2009, which included 948 patients with venous thromboembolism and 902 individuals in a control group, all aged 18-54 years. Information was obtained by telephone interviews and DNA analyses of blood samples. Radiologic referrals were used for case ascertainment. For comparisons, odds ratios were estimated by unconditional logistic regression analysis adjusting for smoking, body mass index (BMI), and immobilization.
The odds ratio (OR) for current use of combined hormonal contraception was 5.3 (95% confidence interval [CI] 4.0-7.0). Desogestrel combinations had the highest OR (11.4, 95% CI 6.0-22.0). The OR for injection of medroxyprogesterone acetate was 2.2 (95% CI 1.3-4.0). In users of combined hormonal contraception with the factor V Leiden mutation, the OR was 20.6 (95% CI 8.9-58). In women who used progestogen-only contraception and carried the factor V Leiden mutation, the OR was 5.4 (95% CI 2.5-13).
Risks of venous thromboembolism in association with combined hormonal contraception vary by type of progestogen and independently of BMI and smoking. Thrombophilic genotypes such as factor V Leiden increase risks of venous thromboembolism in users of combined hormonal contraception. Except for injection of medroxyprogesterone acetate, progestin-only contraception seems to be the least thrombogenic hormonal contraception for women carrying genetic hemostatic variations.
Associations of hormone replacement therapy and oral contraceptives with risk of colorectal cancer defined by clinicopathological factors, beta-catenin alterations, expression of cyclin D1, p53, and microsatellite-instability.
Postmenopausal hormone therapy (HRT) and oral contraceptive (OC) use have in several studies been reported to be associated with a decreased colorectal cancer (CRC) risk. However, data on the association between HRT and OC and risk of different clinicopathological and molecular subsets of CRC are lacking. The aim of this molecular pathological epidemiology study was therefore to evaluate the associations between HRT and OC use and risk of specific CRC subgroups, overall and by tumour site.
In the population-based prospective cohort study Mamö Diet and Cancer, including 17035 women, 304 cases of CRC were diagnosed up until 31 December 2008. Immunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status had previously been assessed in tissue microarrays with tumours from 280 cases. HRT was assessed as current use of combined HRT (CHRT) or unopposed oestrogen (ERT), and analysed among 12583 peri-and postmenopausal women. OC use was assessed as ever vs never use among all women in the cohort. A multivariate Cox regression model was applied to determine hazard ratios for risk of CRC, overall and according to molecular subgroups, in relation to HRT and OC use.
There was no significantly reduced risk of CRC by CHRT or ERT use, however a reduced risk of T-stage 1-2 tumours was seen among CHRT users (HR: 0.24; 95% CI: 0.09-0.77).Analysis stratified by tumour location revealed a reduced overall risk of rectal, but not colon, cancer among CHRT and ERT users, including T stage 1-2, lymph node negative, distant metastasis-free, cyclin D1 - and p53 negative tumours.In unadjusted analysis, OC use was significantly associated with a reduced overall risk of CRC (HR: 0.56; 95% CI: 0.44-0.71), but this significance was not retained in adjusted analysis (HR: 1.05: 95% CI: 0.80-1.37). A similar risk reduction was seen for the majority of clinicopathological and molecular subgroups.
Our findings provide information on the relationship between use of HRT and OC and risk of clinicopathological and molecular subsets of CRC.
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The incidence of breast cancer in Denmark has increased about 2-3% every year in the past decades. In this review the established risk factors for the disease are presented and the changes over time in these factors are described. It is concluded that a large part of the rise in incidence can be explained by changes in established risk factors. The potential measures for prevention of the disease seem to be changes in birth patterns and and increased focus on obesity and alcohol use.
The aim of our study was to examine the risk of breast cancer according to specific types of estrogens and progestagens in oral contraceptives (OCs) based on the prospective Norwegian Women and Cancer study (NOWAC). Between 1991-97 women aged 30-70 years were drawn at random from the central person register and mailed an invitation and a questionnaire. Women (102,443) were enrolled with follow-up information collected throughout 1999 by linkage with national registries of cancer, mortality and emigration based on the unique national identification number. Among the 96,362 women included in the present analysis 851 invasive breast cancer were diagnosed. The adjusted risk of breast cancer increased with 25% for ever use of OCs and the risk increased with increasing duration of use (test for trend: p = 0.007). No association between time since last use and breast cancer risk was found after stratification on duration of use. Positive trend was still found for total duration of use among women who used OCs more than 5 years ago. Second generation of OCs had an increased risk with increasing duration of use. Classifying progestagens according to chemical groups, the relative risk increased significantly with increasing cumulative dose of levonorgestrel progestagen. It was difficult to conclude for the other groups due to lack of power. In a multivariate analysis the cumulative dose for all progestagen groups were non-significant, although we observed a significant increased risk with increasing milligram-months of estrogen exposure (p = 0.002). In conclusion, the increased risk of breast cancer related with OC formulations could be due mostly to estrogen component.
On October 29, 2002, Health Canada issued Guidance for Industry: Clinical Development of Steroidal Contraceptives Used by Women. The original draft of this guideline, published July 4, 2001, included recommendations for clinical trials in excess of those required in Europe and the United States. The proposed requirements, which reflected Health Canada's views, had the potential to discourage contraceptive research in Canada and to block registration of new products. To evaluate the impact of Canada's hormonal contraceptive regulation, a comparative analysis of the availability of products in various countries was performed, along with an evaluation of the time required from submission to approval of a new drug. Women in Canada have access to 35% of the contraceptive products available worldwide and to 37% of the hormonal contraceptives available worldwide, compared with 58% and 59% respectively, in the United States; 52% and 54% respectively, in the United Kingdom; 44% and 54%, respectively, in France; and 44% and 50% respectively, in Sweden. Regarding the more recent contraceptive products available worldwide, women in Denmark have the most choices (67% of available products), whereas women in Canada have the least (only 22% of available products). Eleven of 12 oral contraceptive products recently approved in other countries have either not been submitted for approval in Canada or remain in the Canadian regulatory process. Although the time-to-approval period in Canada, for drugs in general, is 6 months longer than in the United States, the mean lag time for 6 contraceptive products is 29.6 months as of January 1, 2004, and no oral contraceptives have been approved in Canada since 1997.
From 1975 to 1984, there were 1,585,000 women-years of oral contraceptive use and 1,975,000 women-years of copper-bearing intrauterine device use in Finland. During this 10-year period, 20 women between 15 and 39 years of age died of pulmonary embolism, 41 of coronary heart disease, and 311 of intracranial hemorrhage. The diagnoses were confirmed in 89% at necropsy examination. The contraceptive method used by patients was determined in 84% by means of inquiry sent to family planning clinics. Among the 20 patients who died of pulmonary embolism, four died while taking the pill, which gives a relative risk of 1.2 (95% confidence limits, 0.37 to 3.62; p = 0.78). The corresponding values for death from myocardial infarction and intracranial hemorrhage were 0.19 (95% confidence limits, 0.05 to 0.70; p = 0.01) and 0.36 (95% confidence limits, 0.18 to 0.70; p = 0.03), respectively. None among the copper intrauterine device users under the age of 40 years died of pulmonary embolism during 1,383,000 women-years of intrauterine device use. The relative risk of death from intracranial hemorrhage among intrauterine device users was 1.18 (95% confidence limits, 0.70 to 1.99, p = 0.25).
The purpose of the cohort study reported here was to investigate the association between oral contraceptive use and risk of benign breast disease (BBD), overall and by histological subtype, within the 56,537 women in the Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 at recruitment. Cases were the 2,116 women in the dietary cohort who were diagnosed with biopsy-confirmed incident BBD. For comparative purposes, a subcohort consisting of a random sample of 5,681 women (including 197 subjects with incident BBD) was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 2,116 cases and 5,338 non-cases. There was an inverse association between use of oral contraceptives and risk of all types of BBD combined. The reduction in risk was confined largely to proliferative forms of BBD (BPED), and in particular, to those forms of BPED without histological atypia, in whom there was a progressive reduction in risk with increasing duration of use (the IRR (95% CI) for use of more than 7 years was 0.64 (0.47-0.87)); risk of BPED with atypia was increased somewhat in association with oral contraceptive use (the IRR (95% CI) for use of more than 7 years was 1.43 (0.68-3.01 )), but not in a dose-dependent manner. The results were similar when examined separately in the screened and control arms of the NBSS and for screen-detected and interval-detected BPED.
493 women were examined over an 8 month period for the incidence of condylomata acuminata (CA) and the presence of the virus candida albicans. The results were correlated to the patients' rate of oral contraceptive use. CA was found in 77 patients; the rest served as a control group. 44% of the women in the CA group used oral contraceptives, compared to 38% in the control group (.05 P .1). Candida albicans was found among 14.7% of the women using oral contraceptives and in 16% of the non-users (.5 P .6). Candida albicans was found in 20% of the CA group and 15% of the control group (.3 P .4). No significant relationship could be demonstrated between any of the 3 parameters.