Lina Steinrud Mørch

Association of Hormonal Contraception With Depression.

Importance Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some womens mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed. Objective 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. Design, Setting, and Participants 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. Exposures Use of different types of hormonal contraception. Main Outcomes and Measures 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. Results 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). Conclusions and Relevance 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.

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.)

Hormone Therapy and Different Ovarian Cancers: A National Cohort Study

Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women taking unopposed oral estrogen therapy had increased risks of both serous tumors (incidence rate ratio (IRR) = 1.7, 95% confidence interval: 1.4, 2.2) and endometrioid tumors (IRR = 1.5, 95% confidence interval: 1.0, 2.4) but decreased risk of mucinous tumors (IRR = 0.3, 95% confidence interval: 0.1, 0.8). Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types of ovarian tumors should be given attention in future studies.

Fetal Growth and Preterm Birth in Children Exposed to Maternal or Paternal Rheumatoid Arthritis: A Nationwide Cohort Study

To assess indicators of fetal growth and risk of preterm birth in children of parents with rheumatoid arthritis (RA).

Hormone replacement therapy and the risk of endometrial cancer: A systematic review

BACKGROUND In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account. AIM This systematic literature review assesses the safety of estrogen plus progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin. METHODS PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only, estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio. RESULTS 28 studies were included. The observational literature found an increased risk among users of estrogen alone. Continuous combined therapy showed a lower risk than sequential combined therapy. The newer marketed micronized progesterone increased the risk notably, also when administered continuously. In most studies, tibolone was associated with an increased risk. CONCLUSION Use of unopposed estrogen, tibolone and sequential combined therapy increases the risk of endometrial cancer. Continuous combined therapy seems risk free, but possibly not when micronized progesterone is used.

The influence of hormone therapies on type I and II endometrial cancer: A nationwide cohort study

The influence of hormone therapy (HT) on risk for endometrial cancer is still casting which type of HT the clinicians recommend. It is unrevealed if HT has a differential influence on Type I versus Type II endometrial tumors, and little is known about the influence of, e.g., different routes of administration and about the influence of tibolone. We followed all Danish women aged 50–79 years without previous cancer or hysterectomy (n = 914,595) during 1995–2009. From the National Prescription Register, we computed HT exposures as time‐dependent covariates. Incident endometrial cancers (n = 6,202) were identified from the National Cancer Registry: 4,972 Type I tumors and 500 Type II tumors. Incidence rate ratios (RRs) and 95% confidence intervals (Cls) were estimated by Poisson regression. Compared with women never on HT, the RR of endometrial cancer was increased with conjugated estrogen: 4.27 (1.92–9.52), nonconjugated estrogen: 2.00 (1.87–2.13), long cycle combined therapy: 2.89 (2.27–3.67), cyclic combined therapy: 2.06 (1.88–2.27), tibolone 3.56 (2.94–4.32), transdermal estrogen: 2.77 (2.12–3.62) and vaginal estrogen: 1.96 (1.77–2.17), but not with continuous combined therapy: 1.02 (0.87–1.20). In contrast, the risk of Type II tumors appeared decreased with continuous combined therapy: 0.45 (0.20–1.01), and estrogen therapy implied a nonsignificantly altered risk of 1.43 (0.85–2.41). Our findings support that continuous combined therapy is risk free for Type I tumors, while all other hormone therapies increase risk. In contrast, Type II endometrial cancer was less convincingly associated with hormone use, and continuous combined therapy appeared to decrease the risk.

Reduction in stillbirths at term after new birth induction paradigm: results of a national intervention

Objective The risk of fetal death increases steeply after 42 gestational weeks. Since 2009, Denmark has had a more proactive policy including prevention of prolonged pregnancy, and early intervention in women with diabetes, preeclampsia, high body mass index and of a higher age group. The aim of this study was to describe the development in fetal deaths with this more proactive birth induction practice, and to identify and quantify contributing factors for this development. Design National cohort study. Setting Denmark. Participants Delivering women in Denmark, 1 January 2000 to 31 December 2012. Outcome measures Stillbirths per 1000 women at risk (prospective risk of stillbirth) and per 1000 newborn from 37 and 40 gestational weeks, respectively, through the study period. Results During the study period, 829 165 children were live born and 3770 (0.45%) stillborn. Induction of labour increased from 12.4% in year 2000 to 25.1% in 2012 (p<0.001), and the percentage of children born at or after 42 weeks decreased from 8.0% to 1.5% (p<0.001). Through the same period, the prospective risk of stillbirth after 37 weeks fell from 0.70 to 0.41/1000 ongoing pregnancies (p<0.001), and from 2.4 to 1.4/1000 newborn (p<0.001). The regression analysis confirmed the inverse association between year of birth and risk of stillbirth. The lowest risk was observed in the years 2011–2012 as compared with years 2000–2002 with a fully adjusted HR of 0.69 (95% CI 0.57 to 0.83). The general earlier induction, the focused earlier induction of women with body mass index >30, twins, and of women above 40 years and a halving of smoking pregnant women were all independent contributing factors for the decrease. Conclusions A gradually more proactive and differential earlier labour induction practice is likely to have mainly been responsible for the substantial reduction in stillbirths in Denmark.

Use of baseline and updated information on alcohol intake on risk for breast cancer: importance of latency

BACKGROUND Alcohol intake has been shown to be associated with an increased risk for breast cancer. In the analysis of longitudinal prospective cohort studies, however, the analysis of repeated measurements of alcohol intake might not be straightforward. METHODS In this analysis of the Copenhagen City Heart Study, in which alcohol intake was measured four times, 9318 Danish women with no previous diagnosis of cancer were followed for breast cancer for 27 years, from 1976 to 2002. During follow-up, breast cancer was diagnosed in 476 women. RESULTS The association between alcohol intake at first measurement (baseline alcohol intake) and breast cancer was positive and approximately linear. When alcohol intake was updated during follow-up, no association was observed between breast cancer and alcohol intake. It is suggested that this difference in results may be attributable to long latency time between alcohol intake and breast cancer occurrence, because a markedly increased risk was estimated on the basis of direct lagging of risk time. CONCLUSIONS Our results support the hypothesis that baseline alcohol intake is more strongly associated with breast cancer risk than updated intake, and we suggest that this is due to the long latency between alcohol intake and breast cancer.

The Outcome of Bone Mineral Density Measurements on Patients Referred From General Practice

The incidence of osteoporosis is increasing and the general practitioner is integral to identifying these patients. It is, therefore, of interest to characterize the referral pattern of patients scheduled for determination of bone density by means of dual-energy X-ray absorptiometry scanning. Altogether, 1551 scans from first-time referred women were analyzed with respect to normal bone mineral density (BMD), osteopenia, and osteoporosis as the outcome, and the results were compared with age and body mass index (BMI). Using multiple regression analysis, risk estimates for osteoporosis were calculated with respect to patient characteristics. Only 21% of the referred patients had osteoporosis and 34% had osteopenia. Of these, 24% had osteopenia and a Z-score below -1. Half of the referred patients were women less than 60 yr with a markedly low risk of osteoporosis. A BMI less than 20 kg/m(2) increased the predictive value considerably. A low BMI is a good indicator for referral of women less than 60 yr for measurements of bone density. Forty-five percent of the referred women from general practitioners had a normal BMD.

Association of Hormonal Contraception With Suicide Attempts and Suicides

OBJECTIVE The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception. METHOD The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal contraception as compared with those who never used hormonal contraception. RESULTS Among nearly half a million women followed on average for 8.3 years (3.9 million person-years) with a mean age of 21 years, 6,999 first suicide attempts and 71 suicides were identified. Compared with women who never used hormonal contraceptives, the relative risk among current and recent users was 1.97 (95% CI=1.85-2.10) for suicide attempt and 3.08 (95% CI=1.34-7.08) for suicide. Risk estimates for suicide attempt were 1.91 (95% CI=1.79-2.03) for oral combined products, 2.29 (95% CI=1.77-2.95) for oral progestin-only products, 2.58 (95% CI=2.06-3.22) for vaginal ring, and 3.28 (95% CI=2.08-5.16) for patch. The association between hormonal contraceptive use and a first suicide attempt peaked after 2 months of use. CONCLUSIONS Use of hormonal contraception was positively associated with subsequent suicide attempt and suicide. Adolescent women experienced the highest relative risk.