Lifetime induced abortions and live births. A 40-year historical cohort study.

OBJECTIVE: Little is known about whether induced abortions are associated with the final lifetime number of live births (life births). The objective of this study was to examine the association of number of life births with number of abortions a female has had in her lifetime. METHODS: In a national cohort design, we followed all Danish females from ages 15 to 44 years through the period 1977-2017 for induced abortions and live births. For each lifetime number of induced abortions, the average number of life births were assessed, and rates with 95% confidence limits calculated. RESULTS: The study included 409 497 females who completed 222 482 induced abortions and 831 742 live births. In 265 573 (64.9%) females who did not have any induced abortion, the average number of life births was 2.09 (95% CI 2.08-2.10). For females with 1 (23.4%), 2 (7.4%), 3 (2.6%), 4 (1.0%), and ≥5 (0.7%) induced abortions during their reproductive lifespan, the average number of life births was 1.88 (1.87-1.89), 1.99 (1.98-2.00), 2.09 (2.06-2.11), 2.13 (2.09-2.15), and 2.25 (2.21-2.29), respectively. The increase in number of life births in females with 1 to females with 5+ induced abortions was 4.7% for each additional induced abortion. CONCLUSION: We found number of induced abortions during a woman's reproductive lifespan to be positively correlated to the number of live births. This association is likely explained by a high fecundity in females with multiple pregnancies including induced abortions, and suggests that even several induced abortions do not compromise a woman's general reproductive end points.

Association Between Intrauterine System Hormone Dosage and Depression Risk.

OBJECTIVE: The authors compared the associated risk of incident depression between first-time users of low-, medium-, and high-dose levonorgestrel-releasing intrauterine systems (LNG-IUSs). METHODS: This national cohort study was based on Danish register data on first-time users of LNG-IUSs, 15-44 years of age, between 2000 and 2022. Cox regression and a G-formula estimator were used to report 1-year average absolute risks, risk differences, and risk ratios of incident depression, defined as initiation of an antidepressant or receipt of a depression diagnosis, standardized for calendar year, age, education level, parental history of mental disorders, endometriosis, menorrhagia, polycystic ovary syndrome, dysmenorrhea, leiomyoma, and postpartum initiation. RESULTS: In total, 149,200 women started using an LNG-IUS, among whom 22,029 started a low-dose one (mean age, 22.9 years [SD=4.5]), 47,712 a medium-dose one (mean age, 25.2 years [SD=6.2]), and 79,459 a high-dose one (mean age, 30.2 years [SD=5.6]). The associated subsequent 1-year adjusted absolute risks of incident depression were 1.21% (95% CI=1.06-1.36), 1.46% (95% CI=1.33-1.59), and 1.84% (95% CI=1.72-1.96), respectively. For the users of high-dose LNG-IUSs, the risk ratios were 1.52 (95% CI=1.30-1.74) and 1.26 (95% CI=1.10-1.41) compared with users of the low- and medium-dose LNG-IUSs, respectively. For users of medium-dose LNG-IUSs, the risk ratio was 1.21 (95% CI=1.03-1.39) compared with users of low-dose LNG-IUSs. CONCLUSIONS: First-time use of an LNG-IUS was positively associated with incident depression in an LNG-dose-dependent manner across low-, medium-, and high-dose LNG-IUSs. Although the observational design of the study does not permit causal inference, the dose-response relationship contributes to the body of evidence suggesting a relationship between levonorgestrel exposure and risk of depression.

Gender affirming treatment and employment rate in 3,812 Danish transgender persons and 38,120 controls.

OBJECTIVE: Gender affirming care could be associated with higher employment rate. We assessed employment rates in transgender persons compared to controls and demographic, health and treatment-related factors associated with employment in transgender persons. METHODS: National register-based cohort study in Danish persons with diagnosis code of gender dysphoria during year 2000-2021. Five age-matched controls of the same sex at birth and five age-matched controls of the other sex at birth were included. The date of study inclusion was the first date of transgender diagnosis. Employment was the primary study outcome. RESULTS: The cohort included 3,812 transgender persons and 38,120 cisgender controls. The median age (interquartile range) was 19 (15; 24) years for transgender men, n = 1,993 and 23 (19; 33) years for transgender women, n = 1,819. In transgender men compared to control cisgender women, the odds ratio (95% confidence interval) for employment was 0.33 (0.29; 0.38) before study inclusion and 0.24 (0.20; 0.29) in the fifth calendar year after index; in transgender women compared to control cisgender men, corresponding ORs were 0.30 (0.70; 0.34) and 0.21 (0.18; 0.25). Similar findings were found between transgender persons and cisgender controls of other sex. Use of gender affirming hormone in transgender men increased probability of employment at all time points with odds ratio after 5 years: 1.61 (1.08; 2.42), p = 0.02 (95% confidence interval). In transgender women, use of hormone treatment was not associated with changed employment rates, 5 years odds ratio 1.31 (0.94; 1.82), p = 0.11. CONCLUSION: Masculinizing hormone treatment was associated with higher probability of employment.

Medication and procedural abortions before 13 weeks gestation and risk of psychiatric disorders.

BACKGROUND: The proportion of abortions provided by medication in the United States and worldwide has increased greatly since the U.S. Food and Drug Administration approved mifepristone in 2000. While existing research has shown that abortion does not increase risk of mental health problems, no population-based study has examined specifically whether a procedural or medication abortion increases risk of mental health disorders. OBJECTIVE: This study examined whether mental health disorders increased in the shorter and longer-term after a medication or procedural abortion. STUDY DESIGN: Using Danish population registers' data, we conducted a prospective cohort study in which we included 72,424 females born in Denmark between 1980 and 2006, who were ages 12 to 38 during the study period and had a first first-trimester abortion before 13 weeks gestation in 2000 to 2018. Females with no previous psychiatric diagnoses were followed from 1 year before their abortion until their first psychiatric diagnosis, December 31, 2018, emigration from Demark, or death, whichever came first. Risk of any first psychiatric disorder was defined as a recorded psychiatric diagnosis at an in- or out-patient facility from the 1 year after to more than 5 years after a medication or procedural abortion relative to the year beforehand. Results were adjusted for calendar year, age, gestational age, partner status, prior mental and physical health, childbirth history, childhood environment, and parental mental health history. RESULTS: Females having medication (n=37,155) and procedural abortions (n=35,269) had the same risk of any first psychiatric diagnosis in the year after their abortion relative to the year before their abortion (medication abortion adjusted incidence rate ratio [MaIRR]=1.02, 95% confidence interval [CI]: 0.93-1.12; procedural abortion adjusted incidence rate ratio [PaIRR]=0.94, 95% CI: 0.86-1.02). Moreover, as more time from the abortion passed, the risk of a psychiatric diagnoses decreased relative to the year before their abortion for each abortion method (MaIRR 1-2 years after=0.89, 95% CI: 0.80-0.98; PaIRR 1-2 years after=0.81, 95% CI: 0.88-1.05; MaIRR 2-5 years after=0.77, 95% CI: 0.71-0.84; PaIRR 2-5 years after=0.72, 95% CI: 0.67-0.78; MaIRR 5+ years after=0.58, 95% CI: 0.53-0.63; PaIRR 5+ years after=0.54, 95% CI: 0.50-0.58). CONCLUSION: Because the risk of psychiatric diagnoses was the same in the year after relative to the year before a medication and procedural abortion and the risk did not increase as more time after the abortion increased, neither abortion method increased risk of mental health disorders in the shorter or longer-term.

School performance and educational achievement in children exposed to maternal cancer in utero.

BACKGROUND: In utero exposure to maternal cancer and cancer treatment might influence the child's cognitive development. This study investigated if exposure to maternal cancer during fetal life impacted school performance and educational achievement as adults. METHODS: This nationwide retrospective cohort study identified all live-born children in Denmark between January 1978 and December 2013. Exposure was defined as maternal cancer diagnosis during pregnancy. Four partly overlapping birth cohorts were constructed depending on the outcome of interest: (1) receiving special educational support for birth years 2001-2013; (2) grade point average (GPA) at the final exams after 10th grade for 1986-2003; (3) educational achievement at 20 years for 1978-1998; and (4) education at 30 years for 1978-1988. Logistic and linear models were adjusted for birth year, maternal age, maternal education and maternal death. RESULTS: The estimated probability of receiving special educational support was similar in the exposed group and the reference (adjusted OR 0.96; 95% CI 0.46 to 1.77, non-significant). The GPA did not statistically differ (0.13 grade points; 95% CI -0.18 to 0.45, non-significant). The achieved educational levels were similar for the exposed group and the reference at 20 years, with an adjusted OR of 1.07 (95% CI 0.82 to 1.40) for low versus medium educational level, and at 30 years with an adjusted OR of 0.73 (95% CI 0.35 to 1.50) for low versus high educational level and of 1.07 (95% CI 0.66 to 1.72) for medium versus high educational level. CONCLUSION: Our findings did not indicate poorer performance in compulsory school nor impairment of adult educational achievement after exposure to maternal cancer in utero.

Gender-affirming treatment and mental health diagnoses in Danish transgender persons: a nationwide register-based cohort study.

IMPORTANCE: Gender affirming treatment aims to improve mental health. OBJECTIVE: To investigate longitudinal mental health outcomes in Danish transgender persons. DESIGN: National register-based cohort study in Danish transgender persons with diagnosis code of "gender identity disorder" during the period 2000-2021. PARTICIPANTS: Five age-matched controls of the same sex at birth and five age-matched controls of the other sex at birth were included for each transgender person. MAIN OUTCOMES: Diagnosis codes of mental and behavioral disorders and/or prescription of psychopharmacological agents until June 2022. RESULTS: The cohort included 3812 transgender persons with median age (interquartile range) 19 (15; 24) years for persons assigned female at birth (AFAB, N = 1993) and 23 (19; 33) years for persons assigned male at birth (AMAB, N = 1819) and 38 120 controls. Follow up duration was up to 10 years with mean (standard deviation) 4.5 (4.3) years. In transgender persons AFAB compared to control women, the odds ratio (OR) (95% confidence interval) for mental and behavioral disorders was 6.7 (5.5; 8.1) before the index date, 9.9 (8.4; 11.7) at 1 year, 5.8 (4.4; 7.7) at 5 years, and 3.4 (2.1; 7.5) at 8 years follow up. In transgender persons AMAB compared to control men, corresponding ORs were 5.0 (4.0; 6.4), 11.3 (9.3; 13.7), 4.8 (3.5; 6.5), and 6.6 (4.2; 10.3) at 8 years follow up (all P < .001). CONCLUSION: The OR for mental health disorders was higher in transgender persons compared to controls and remained elevated throughout follow up, especially in transgender persons AMAB.

Pregnancy Loss and the Risk of Myocardial Infarction, Stroke, and All-Cause Mortality: A Nationwide Partner Comparison Cohort Study.

Background Pregnancy loss has been associated with myocardial infarction, stroke, and all-cause mortality in women through unknown mechanisms. The aim of this study was to examine these associations in women and their male partners. Methods and Results In this register-based cohort study, all people born between 1957 and 1997, residing in Denmark between 1977 and 2017, and with a registered partner of the opposite sex were eligible for inclusion. Male partners through cohabitation, marriage, or paternity constituted the male cohort. Exposure to pregnancy loss was categorized as follows: 0, 1, 2, or ≥3 pregnancy losses. The outcomes of interest were myocardial infarction, stroke, and all-cause mortality. The Cox proportional hazards model estimated hazard ratios (HRs), adjusted for age, calendar year, parity, and parental history of myocardial infarction or stroke. During follow-up, 1 112 507 women experienced 4463 events of myocardial infarction compared with 13 838 events among 1 120 029 male partners. With the no pregnancy loss group as reference, the adjusted HRs of myocardial infarction in the female cohort after 1, 2, and ≥3 pregnancy losses were as follows: 1.1 (95% CI, 1.0-1.2), 1.3 (95% CI, 1.1-1.5), and 1.4 (95% CI, 1.1-1.8), respectively. In the male partner cohort, the corresponding estimates were 1.0 (95% CI, 1.0-1.1), 1.1 (95% CI, 1.0-1.2), and 1.0 (95% CI, 0.8-1.2), respectively. The outcome of stroke showed similar results. Pregnancy loss was not significantly associated with increased mortality in either sex. Conclusions Pregnancy loss or stillbirth was significantly associated with myocardial infarction and stroke in women but not their male partners. Pregnancy loss or stillbirth was not significantly associated with all-cause mortality in women or male partners.

Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for Postpartum Depression.

Importance: Hormonal sensitivity may contribute to the risk of depression in some women, as observed during the premenstrual, postpartum, and perimenopausal phases, and when initiating hormonal contraception (HC). However, little evidence exists to support that such depressive episodes are linked across the reproductive life span. Objective: To determine whether prior depression associated with HC initiation is coupled with a higher risk of postpartum depression (PPD) than prior depression not associated with HC initiation. Design, Setting, and Participants: This cohort study used Danish health registry data collected from January 1, 1995, through December 31, 2017, and analyzed from March 1, 2021, through January 1, 2023. All women living in Denmark born after 1978 with their first delivery between January 1, 1996, and June 30, 2017, were eligible for inclusion; 269 354 met these criteria. Women were then excluded if they had never used HC or if they had a depressive episode before 1996 or within 12 months prior to delivery. Exposures: Prior depression associated with vs not associated with HC initiation, ie, if developed within 6 months after start of an HC exposure or not. Depression was defined as a hospital diagnosis of depression or filling a prescription for antidepressant medication. Main Outcomes and Measures: Crude and adjusted odds ratios (ORs) were calculated for the incidence of PPD defined as the development of depression within 6 months after first delivery. Results: Of 188 648 first-time mothers, 5722 (3.0%) (mean [SD] age, 26.7 [3.9] years) had a history of depression associated with initiation of HC use, and 18 431 (9.8%) (mean [SD] age, 27.1 [3.8] years) had a history of depression not associated with the initiation of HC. Women with HC-associated depression had a higher risk of PPD than women with prior non-HC-associated depression (crude OR, 1.42 [95% CI, 1.24-1.64]; adjusted OR, 1.35 [95% CI, 1.17-1.56]). Conclusions and Relevance: These findings suggest that a history of HC-associated depression may be associated with a higher risk of PPD, supporting that HC-associated depression may indicate PPD susceptibility. This finding offers a novel strategy in clinical PPD risk stratification and points to the existence of a hormone-sensitive subgroup of women.

Ectopic Pregnancy Risk in Users of Levonorgestrel-Releasing Intrauterine Systems With 52, 19.5, and 13.5 mg of Hormone.

This study assesses the association between use of levonorgestrel intrauterine systems containing 52, 19.5, and 13.5 mg of hormone and ectopic pregnancy in a nationwide cohort study.

Endometriosis is associated with pregnancy loss: a nationwide historical cohort study.

OBJECTIVE: To study whether endometriosis is associated with pregnancy loss and recurrent pregnancy loss (RPL). DESIGN: Nationwide historical cohort study with a nested case-control analysis. SETTING: National health registers. PATIENT(S): A total of 29,563 women born between 1957 and 1997 were identified in the national health registers, diagnosed with endometriosis between 1977 and 2017, and age-matched 1:10 with 295,630 women without endometriosis. The number of pregnancy losses was assessed, and data were analyzed with conditional logistic regression. INTERVENTION(S): Endometriosis (International Classification of Diseases, 8th Revision, 62530-62539, and International Classification of Diseases, 10th Revision, DN80.0-9). MAIN OUTCOME MEASURE(S): The primary outcomes of interest were the numbers of pregnancy losses categorized as 0, 1, 2, and ≥ 3 losses, unadjusted and adjusted for gravidity, and RPL. The secondary outcome measures were the predefined types of pregnancy losses. Pregnancy loss was defined as the spontaneous demise of a pregnancy until 22 weeks of gestation. Primary RPL was defined as 3 or more consecutive pregnancy losses with no prior live birth or stillbirth, and secondary RPL was defined as 1 or more births followed by 3 or more consecutive losses. RESULT(S): A total of 18.9%, 3.9%, and 2.1% of ever-pregnant women with endometriosis had 1, 2, and ≥ 3 pregnancy losses compared with 17.3%, 3.5%, and 1.5% of the women without endometriosis, corresponding to the odds ratios of 1.13 (95% confidence interval, 1.09-1.17), 1.18 (1.10-1.26), and 1.44 (1.31-1.59), respectively. When adjusted also for gravidity, the corresponding results were 1.37 (95% confidence interval, 1.32-1.42), 1.75 (1.62-1.89), and 2.57 (2.31-2.85), respectively. The following predefined subgroups of RPL were positively associated with endometriosis: primary; secondary; secondary after giving birth to a boy; after a complicated delivery; and ≥ 3 pregnancy losses before the age of 30 years. Six endometriosis subgroup analyses found an association between endometriosis and pregnancy loss. These analyses were women diagnosed in the 4 decades between 1977 and 2017, women with adenomyosis, and women with adenomyosis only. CONCLUSION(S): This nationwide cohort study found endometriosis to be associated with pregnancy loss and RPL, and the association strengthened with an increasing number of losses.

Does fetal sex influence the risk of venous thrombosis in pregnancy? A cohort study.

BACKGROUND: Venous thromboembolism is a prominent cause of maternal death. OBJECTIVE: As inflammation is a well-known risk factor for venous thromboembolism and several studies have found a higher grade of inflammation in pregnancies bearing a male compared with female fetuses, we investigated the risk of pregnancy-related venous thromboembolism associated with sex of the fetus. METHODS: This cohort study linked data from national registries and compared event rates and hazard ratios of venous thrombosis for pregnancies bearing a male fetus with those bearing a female fetus during pregnancy and in the first 3 months postpartum. National data from 1995 to 2017 were used. All Danish women aged 15 to 49 years with a live or stillbirth were eligible for inclusion; 1 370 583 pregnancies were included. Women with venous thrombosis, ischemic heart disease, cerebrovascular disease, thrombophilia, or cancer before conception were excluded. RESULTS: The event rate for a venous thrombosis was 8.0 per 10.000 pregnancy years with a male fetus compared with 6.8 for a female fetus. The adjusted hazard ratio for venous thrombosis during pregnancies bearing a male was 1.2 (95% CI, 1.1-1.4), whereas in the postpartum period, it was 0.9 (95% CI, 0.7-1.0). The risk was elevated until week 30. CONCLUSION: These findings indicate a slightly greater risk of venous thrombosis during pregnancies bearing a male fetus than during pregnancies bearing a female fetus. There was no increased risk associated with fetal male sex in the postpartum period.

Long-Term Morbidity and Mortality in Children After In Utero Exposure to Maternal Cancer.

PURPOSE: In utero exposure to maternal cancer and cancer treatment might influence the child's short- and long-term health and development. The objective of the study was to investigate short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero. METHODS: This nationwide cohort study identified all liveborn children in Denmark between January 1978 and December 2018. Exposure was defined as maternal cancer diagnosis during pregnancy, and in a subgroup analysis, exposure to chemotherapy in utero. The main outcomes of interest were overall mortality, somatic diagnoses, and psychiatric diagnoses identified in the National Health Registers. Follow-up started at birth and ended at an event, death, emigration, or end of 2018. Hazard ratios of end points adjusted for potential confounders were estimated using Cox regression analysis. RESULTS: Of 2,526,163 included liveborn children, 690 (0.03%) were exposed to maternal cancer in utero. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality, adjusted hazard ratio 0.8 (95% CI, 0.4 to 1.5), nor increased risk of congenital malformations, overall somatic or psychiatric disease. During the period 2002-2018, of 378 (0.03%) children exposed to cancer in utero, 42 (12.5%) were exposed to chemotherapy. Among these 42 children, in utero exposure to chemotherapy was not associated with selected somatic diseases nor to congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy. CONCLUSION: Overall, findings did not indicate excess risk of mortality or severe morbidity among children exposed to cancer in utero. Fetal exposure to chemotherapy was not associated with adverse health outcomes in childhood.

Cardiovascular risk in Danish transgender persons: a matched historical cohort study.

Background: Cardiovascular risk could be increased in transgender persons, but the mechanism is undetermined. Aim: The aim of this study was to assess the risk of cardiovascular outcomes in Danish transgender persons compared to controls. Methods: The study design was a historical register-based cohort study in Danish transgenders and age-matched controls. The main outcome measure was cardiovascular diagnosis (any CVD) including medicine prescriptions for CVD during 2000-2018. The transgender cohort (n = 2671) included persons with International Classification of Diseases-10 diagnosis code of 'gender identity disorder' (n = 1583) and persons with legal sex change (n = 1088), 1270 were assigned female at birth (AFAB) and 1401 were assigned male at birth (AMAB). Controls (n = 26 710) were matched by age (n = 5 controls of same and n = 5 controls of other birth sex) of the respective transgender. Results: The median (interquartile range) age at study inclusion was 22 (18; 29) years for AFAB and 26 (21; 39) years for AMAB. The mean (s.d.) follow-up time was 4.5 (4.2) years for AFAB and 5.7 (4.8) years for AMAB. The hazard ratio (HR) for any CVD was significantly higher in transgenders vs controls of same and other birth sex, with highest adjusted HR in transgenders AFAB vs control men: 2.20 (95% CI: 1.64;2.95), P < 0.001. Gender-affirming hormone treatment (GAHT) explained part of elevated risk of CVD in transgenders AFAB, whereas GAHT did not contribute to the elevated risk of CVD in transgenders AMAB. Conclusions: The risk of cardiovascular diagnosis was increased in transgenders. The mechanism should be further investigated.

Asthma Is Associated With Pregnancy Loss and Recurrent Pregnancy Loss: A Nationwide Cohort Study.

BACKGROUND: Women with asthma appear to have an increased risk of pregnancy loss (PL). The impact of asthma on recurrent pregnancy loss (RPL), defined as 3 consecutive losses, is, however, unknown. OBJECTIVE: The aim of this study was to investigate whether having asthma before or during the fertile age is associated with PL and RPL. METHODS: Based on Danish national health registers, we identified all women aged 6 to 45 years with at least 2 filled prescriptions of an antiasthma drug during the period 1977 to 2019. Women with asthma were compared with women without asthma. Pregnancy outcomes were retrieved for both groups from national health registers. Logistic regression with adjustment for the year of birth and educational level provided odds ratios (ORs) for the number of PLs. Subgroup analyses were conducted for early-onset (age 6-15 years), adult-onset (age 16-39 years), and late-onset (age 40-45 years) asthma. Lastly, we compared uncontrolled asthma (defined as ≥ 400 doses of a short-acting beta-2 agonist in a year) to controlled asthma (defined as < 400 doses of a short-acting beta-2 agonist in a year). RESULTS: In a population of 1,309,786 women, we identified 128,553 women with asthma and 1,297,233 women without asthma. Compared with nonasthmatic women, women with asthma had ORs for 1, 2, and 3 or more PLs of 1.05 (95% CI 1.03-1.07), 1.09 (95% CI 1.05-1.13), and 1.18 (95% CI1.11-1.24), respectively, and for RPL of 1.19 (95% CI 1.12-1.27). In women with early-onset asthma, the OR of 3 or more PLs was 1.47 (95% CI 1.24-1.72). For women classified as having uncontrolled asthma compared with controlled asthma, we found a significant OR of 1.60 (95% CI 1.16-2.16) for 3 or more PLs. CONCLUSIONS: We found a significant positive association between asthma and number of PLs and RPLs. Early-onset asthma and uncontrolled asthma were more strongly associated with PL than adult-onset and late-onset asthma and controlled asthma.

Gender affirming hormonal treatment in Danish transgender persons: A nationwide register-based study.

BACKGROUND: Gender affirming hormonal treatment (GAHT) is a cornerstone in transgender care. National data are sparse regarding use of hormonal treatment by transgender persons. AIM: To assess use of GAHT in transgender persons. DESIGN: National register-based cohort study in Danish transgender persons followed from 2000 until 2018. The main outcome measure was prescription and purchase of GAHT. Persons with ICD-10 diagnosis code of "gender identity disorder" (CGI-cohort) and persons with legal sex change but without diagnosis (CPR-cohort) were included. In the CGI-cohort, transgender women were defined by prescription of estrogen and/or cyproterone acetate and/or testosterone-5-alpha reductase inhibitors, and transgender men were defined by prescription of testosterone after study inclusion. Discontinuation of GAHT was defined as no purchase of GAHT ≥13 months or shift from feminizing to masculinizing hormone treatment, or vice versa. RESULTS: The cohort included 2789 transgender persons (n = 1717, CGI-cohort and n = 1072, CPR-cohort). The median age (interquartile range) at study inclusion was 26.1 (17.7) years for persons assigned male at birth (n = 1447) and 22.5 (10.5) years for persons assigned female at birth (n = 1342). In the CGI-cohort, the event rate for GAHT in transgender women increased from 4.0 (95% confidence interval [CI]: [3.1; 5.2]) events per 100 person in year 2000-2005 to 20.6 (17.8; 23.7) between 2014 and 2018. In transgender men, the event rate of GAHT increased from 4.2 (2.8; 6.2) to 18.8 (16.4; 21.6). The rate of discontinuation of GAHT was 0.06 (95% CI 0.049; 0.071) per person year. CONCLUSIONS: The event rate of GAHT increased during 2000-2018. Our data suggested high adherence to GAHT.

Pregnancy loss and risk of multiple sclerosis and autoimmune neurological disorder: A nationwide cohort study.

BACKGROUND: The loss of one or more pregnancies before viability (i.e. pregnancy loss or miscarriage), has been linked to an increased risk of diseases later in life such as myocardial infarction and stroke. Recurrent pregnancy loss (i.e. three consecutive pregnancy losses) and multiple sclerosis have both been linked to immunological traits, which could predispose to both occurrences. The objective of the current study was to investigate if pregnancy loss is associated with later autoimmune neurological disease. METHODS: This register-based cohort study, included the Danish female population age 12 or older between 1977-2017. Women were grouped hierarchically: 0, 1, 2, ≥3 pregnancy losses, primary recurrent pregnancy loss (i.e. not preceded by a delivery), and secondary recurrent pregnancy loss (i.e. preceded by a delivery). The main outcome was multiple sclerosis and additional outcomes were amyotrophic lateral sclerosis, Guillain-Barré syndrome, and myasthenia gravis. Bayesian Poisson regression estimated incidence rate ratios [IRR] and 95% credible intervals [CI] adjusted for year, age, live births, family history of an outcome, and education. RESULTS: After 40,380,194 years of follow-up, multiple sclerosis was diagnosed among 7,667 out of 1,513,544 included women (0.5%), median age at diagnosis 34.2 years (IQR 27.4-41.4 years), and median age at symptom onset 31.2 years (IQR 24.8-38.2). The adjusted IRR of multiple sclerosis after 1 pregnancy loss was: 1.03 (95% CI 0.95-1.11), 2 losses: 1.02 (95% CI 0.86-1.20), ≥3 non-consecutive losses: 0.81 (95% CI 0.51-1.24), primary recurrent pregnancy loss: 1.18 (95% CI 0.84-1.60), secondary recurrent pregnancy loss: 1.16 (95% CI 0.81-1.63), as compared to women with no pregnancy losses. Seven sensitivity analyses and analyses for additional outcomes did not show significantly elevated adjusted risk estimates. CONCLUSIONS: In this nationwide study, pregnancy loss was not significantly associated with autoimmune neurological disorder.

Hormone therapy and disease activity in Danish women with multiple sclerosis: A population-based cohort study.

BACKGROUND AND PURPOSE: Sex differences in multiple sclerosis (MS) prevalence and disease course are thought to be driven by hormones. Exogenous exposure to estrogens may affect MS disease course. Thus, our aim was to investigate the association between hormone therapy (HT) and disease activity and disability accrual among women with MS. METHODS: A register-based cohort study was conducted with prospectively enrolled cases from the Danish MS registry. Information on hormone exposure was retrieved from the National Prescription Registry. Outcomes were relapse rate, relapse rate ratio, recurrent relapses, 6-month confirmed and sustained Expanded Disability Status Scale (EDSS) milestones 4 and 6, and recurrent EDSS worsening. RESULTS: In all, 3325 women were eligible for analyses, of whom 333 (10%) were ever on HT at some time during follow-up. We found no association between HT and disability accrual, although a trend for increasing risk with increasing length of use was seen. The risk of reaching 6-month confirmed and sustained EDSS 4 among users was 0.6 (95% confidence interval [CI] = 0.3-1.2) after <1 year of use and 1.4 (95% CI = 0.9-2.2) after >5 years of HT compared to never use. The risk of recurrent relapse was increased by 20% (95% CI = 1.0-1.4) among current users of HT compared to nonusers. However, the risk of recurrent relapses was driven by the first calendar period (1996-2005) before the introduction of high-efficacy disease-modifying therapy. CONCLUSIONS: Our findings from this nationwide MS population suggest that HT does not affect disability accrual in women with MS, especially if used for <5 years.

Reproductive changes among women in their 40s: A cross-sectional study.

INTRODUCTION: The aim was to describe and compare changes in the reproductive pattern of women in their 40s observed over a decade in Scandinavia. MATERIAL AND METHODS: Cross-sectional study using the total population of women aged 40-49 years between 2008-2018 in Denmark, Norway and Sweden (on average n = 1.5 million). Aggregated data concerning birth and induced abortion rate were collected and analyzed from national health registers. National data on redeemed prescriptions of hormonal contraceptives in the three countries were collected from prescription registers. Births after spontaneous and assisted conceptions were identified by using cross-linked data on deliveries from the Medical Birth Registers and National Registers of Assisted Reproduction in the three countries. RESULTS: Use of hormonal contraception increased among women aged 40-44 years in Denmark from 24% to 31%, in Sweden from 27% to 30%, and in Norway from 22% to 24%. The levonorgestrel-releasing intrauterine device was the most frequently used method in all countries. Birth rates among women 40-44 years increased continuously from 9.5 to 12/1000 women in Denmark and from 11.7 to 14.3/1000 in Sweden, but remained stable in Norway at ~11/1000 women. There was a doubling of assisted conceptions in Denmark from 0.71 to 1.71/1000 women, Sweden from 0.43 to 0.81/1000 and Norway from 0.25 to 0.53/1000 women 40-49 years of age. Sweden had the highest induced abortion rate (7.7 to 8.1/1000 women) in women aged 40-49 years during the study period. CONCLUSIONS: From 2008 to 2018, birth rates continuously increased among women aged 40-49 years in Denmark and Sweden and births resulting from assisted reproductive technology doubled in all three countries.