This cohort study evaluates the potential association between prenatal acetaminophen exposure and risk of autism in Danish national registers.

OBJECTIVE:To assess the effect of different types of contemporary hormonal contraceptives on the risk of developing colorectal cancer in women of reproductive age. DESIGN:Nationwide cohort study. SETTING:Denmark based on national registers. PARTICIPANTS:The study included women aged 15-49 years living in Denmark between 1995 and 2021, who had at least five years of residence and no history of cancer, hysterectomy, oophorectomy, or sterilisation. MAIN OUTCOME MEASURES:Adjusted incidence rate ratios with 95% confidence intervals (CIs) for a first time diagnosis of colorectal cancer by type and duration of hormonal contraceptive use. RESULTS:Among 1 956 948 women followed for a median of 12.5 years (24.5 million person years in total), 1878 colorectal cancers were detected. Compared to never users, the incidence rate ratio of colorectal cancer among all current and recent users was 0.94 (95% CI 0.83 to 1.06). The incidence rate ratio with less than five years of use was 0.97 (0.85 to 1.11) and 0.86 with more than 10 years of use (0.62 to 1.18). The incidence rate ratio in previous users was similar to never users, however, with some indication for a decreased incidence rate ratio 10 or more years after cessation (0.81, 95% CI 0.66 to 0.99). No consistent differences in risk between newer and older combined oral contraceptives were observed. The most used progestogen-only pills gave an incidence rate ratio of 1.09 (0.74 to 1.61) and the most used progestogen-only non-oral product, the levonorgestrel releasing intrauterine device, gave an incidence rate ratio of 0.96 (0.81 to 1.15). CONCLUSION:The risk of colorectal cancer was not substantially affected by current or recent use of contemporary hormonal contraception, suggesting that modern products neither protect against nor contribute to the rising incidence in young women. Although some subgroup estimates were imprecise, no support was found for an association between hormonal contraceptive use and colorectal cancer.

Importance:No recent study has examined whether method of abortion is associated with psychotropic medication use, an indicator of mild mental health problems. Objective:To examine whether medication or procedural abortions were associated with increased risk of psychotropic medication use. Design, Setting, and Participants:This population-based Danish registry cohort study followed the psychotropic medication redemptions of females aged 12 to 38 years having elective, first first-trimester abortions between January 1, 2000, and December 31, 2018, from 1 year before their medication or procedural abortion until their first psychotropic medication prescription claim (redemption), December 31, 2018, emigration from Denmark, or death, whichever came first. Analyses were conducted between June 2023 and June 2025. Exposure:First abortion method (first medication abortion or first procedural abortion). Main Outcomes and Measures:Any first psychotropic medication prescription redemption, first antidepressant medication redemption, and first antianxiety medication redemption during the study period. Incidence rate ratios (IRRs) were calculated in adjusted regression models. Bonferroni-corrected P values were used to account for multiple tests. Results:Of 67 390 females included in this study (mean [SD] age, 21.8 [4.6] years), 4575 (6.8%) had a prior psychiatric diagnosis; 33 793 had a record of a first medication abortion, 33 597 had a record of a first procedural abortion, and 19 979 (29.6%) had a first psychotropic medication redemption during the study period. In fully adjusted models, using the conventional P value level of .05, compared with the year before a medication or procedural abortion, there were small increased risks of any first psychotropic medication redemption in the first year after medication abortion (IRR, 1.10; 95% CI, 1.02-1.19; P = .01) and procedural abortion (IRR, 1.09; 95% CI, 1.01-1.16; P = .02). There were no statistically significant associations in 1 to 2 years and 2 to 5 years after abortion relative to the year before an abortion for each abortion method. There were decreased risks of any first psychotropic medication redemption more than 5 years after medication abortion (IRR, 0.85; 95% CI, 0.78-0.91; P < .001) and more than 5 years after procedural abortion (IRR, 0.83; 95% CI, 0.78-0.88; P < .001). Using the Bonferroni-corrected P value of .002, the small increased risks of psychotropic medication redemption observed in the first year after an abortion no longer met the criteria for statistical significance, while the lower risks for more than 5 years after abortion continued to meet the criteria for statistical significance. Conclusions and Relevance:In this Danish population-based cohort study, compared with the year before a medication or procedural abortion, small increased risks of psychotropic medication prescription redemptions were observed during the first year after abortion, and decreases in risk of psychotropic medication prescription redemptions were observed more than 5 years after abortion when using conventional levels of statistical significance. The small increased risks observed in the first year after an abortion no longer met the criteria for statistical significance following Bonferroni adjustment for multiple statistical tests. Additional research may be needed to replicate and understand these results.

OBJECTIVE:To determine the prevalence and recurrence of gestational diabetes mellitus (GDM) in Danish live births from 2004 to 2017, to support and expand existing knowledge on prevalence, recurrence and risk factors. METHODS:This registry-based cohort study included all women giving birth in Denmark during the study period. Data from the Danish Medical Birth Registry identified 784,545 singleton deliveries, of which 22,309 (19,559 women) were complicated by GDM. Maternal age, pre-pregnancy BMI, smoking in pregnancy and parity were analyzed as risk factors. Proportions, including recurrence risk, were calculated. RESULTS:The prevalence of GDM increased from 1.8% in 2004 to 4.2% in 2017. Overweight women (BMI 25-29.9) had a threefold increased risk of GDM; OR 3.26 (95% CI 3.15-3.38); while obese women (BMI ≥ 30) had an almost eightfold increased risk; OR 7.78 (95% CI (7.53-8.04). Increasing parity was associated with reduced risk of GDM, though not monotonically. Smoking was not associated with GDM; OR 0.99 (95% CI 0.95-1.04). The overall recurrence risk was 48.5% (95% CI 47.1-49.8); lower in women first diagnosed in their second pregnancy (43.7% (95% CI 40.0-47.4)) than in those diagnosed in their first pregnancy (49.2% (95% CI 47.7-50.6)). CONCLUSIONS:Despite an increasing prevalence of GDM, the recurrence rate remained stable. Higher BMI and maternal age were key factors for GDM, whereas smoking and parity were not consistently associated with risk. This knowledge on recurrent GDM and risk factors for recurrent GDM may contribute to optimization of future treatment strategies.

OBJECTIVE:To assess whether menopausal hormone therapy increases the risk of all cause mortality. DESIGN:Nationwide, registry based cohort study. SETTING:Denmark. PARTICIPANTS:Danish women born between 1950 and 1977 and alive at 45 years. Follow-up began on each woman's 45th birthday and ended on 31 July 2023. Of 969 424 eligible women, 92 619 were excluded because of thrombophilia, liver disease, arterial thrombosis or venous thrombosis, breast cancer, endometrial cancer, ovarian cancer, previous use of menopausal hormone therapy, or previous bilateral oophorectomy. Systemic menopausal hormone therapy was the intervention of interest. MAIN OUTCOME MEASURES:Death as registered in the Central Persons Register. Secondary outcomes were cause specific mortality registered in the cause of death register (cardiovascular, cancer, or other mortality). Hazard ratios were estimated using Cox regression, adjusted for age, calendar year, parity, educational degree, income group quarter (based on quartiles), country of birth, diabetes, hypercholesterolemia, hypertension, atrial fibrillation, valvular disease, heart failure, and three or more hospital contacts between 44 and 45 years of age. RESULTS:Of 876 805 women, 104 086 (11.9%) redeemed a prescription for menopausal hormone therapy, and 47 594 (5.4%) died, with a median follow-up time of 14.3 years (interquartile range (IQR) 7.9-21.0 years). Women who used menopausal hormone therapy had an incidence rate of 54.9 deaths per 10 000 person years compared to 35.5 per 10 000 person years in the unexposed group, corresponding to an adjusted hazard ratio of 0.96 (95% confidence interval (CI) 0.93 to 0.98). Stratifying this by cumulative duration of menopausal hormone therapy use gave an adjusted hazard ratio after <1 years of menopausal hormone therapy of 1.01 (95% CI 0.98 to 1.05), after 1-2.9 years of use 0.94 (0.89 to 0.98), 3-4.9 years of use 0.90 (0.84 to 0.95), 5-9.9 years of use 0.89 (0.84 to 0.95), and over ≥10 years of use 0.98 (0.90 to 1.07). No unequivocal differences in cause-specific mortality were found between groups. Among the 703 women who underwent bilateral oophorectomy between 45-54 years, those who used menopausal hormone therapy experienced a 27-34% lower mortality hazard as compared to women who did not (median age at death for those who had taken menopausal hormone therapy 60.9 years (IQR 55.3-66.6 years) v 56.6 years (52.9-62.0 years) for those who had not). CONCLUSIONS:This nationwide cohort study did not find menopausal hormone therapy was associated with increased mortality.

Importance Hormonal contraceptive (HC) use is associated with depression. It is, however, unknown whether this is also true in the postpartum period when women have a heightened depression risk and are routinely offered HC treatment. Objective To examine whether HC initiation post partum is associated with the development of depression within 12 months post partum. Design, Setting, and Participants A population-based cohort study based on nationwide Danish register data was conducted including all primiparous women who gave birth from January 1, 1997, through December 31, 2022. Women were excluded if they had depression within 24 months before delivery, multiple births or stillbirth, or a diagnosis of breast cancer or liver tumor. Data analysis was conducted between March 20, 2023, and January 17, 2025. Exposure Hormonal contraceptive initiation within 12 months post partum was treated as a time-varying exposure. Hormonal contraceptive types were categorized as combined oral contraceptives (COCs), combined nonoral contraceptives (CNOCs), progestogen-only pills (POPs), and progestogen-only nonoral contraceptives (PNOCs). Main Outcomes and Measures Depression within 12 months post partum, defined as filling an antidepressant prescription or receiving a hospital diagnosis of depression, was the main outcome. Adjusted hazard ratios (AHRs) and average absolute risks of depression within 12 months post partum were estimated using Cox proportional hazards regression and a G-formula estimator. Results Of 610 038 first-time mothers, 248 274 (40.7%) initiated HCs within 12 months post partum (mean [SD] age, 27.6 [4.3] years for HC users vs 29.6 [4.8] years for nonusers). Hormonal contraceptive initiation was associated with subsequent depression, with an AHR of 1.49 (95% CI, 1.42-1.56) compared with no use, resulting in an increase in the 12-month absolute risk from 1.36% (95% CI, 1.32%-1.39%) to 1.54% (95% CI, 1.50%-1.57%). The AHR for COC was 1.72 (95% CI, 1.63-1.82); CNOC, 1.97 (95% CI, 1.64-2.36); and PNOC, 1.40 (95% CI, 1.25-1.56). Progestogen-only pill exposure was associated with an instantaneously reduced risk in the early study period, but it was increased late post partum. The earlier COCs were initiated post partum the higher the associated rate ratio of depression. Conclusions and Relevance In this cohort study, HC initiation post partum was associated with an instantaneous increased risk of developing depression. The associated risk was higher the earlier it was initiated post partum, at least for COC. This finding raises the issue of whether the incidence of depression post partum is increased by routine HC initiation after childbirth.

Background Sampson's theory of Retrograde menstruation is regarded as an important origin of endometriosis but does not explain all cases of endometriosis. Especially, endometriosis occurring before and during puberty, referred to as early-onset endometriosis which might be explained by the phenomenon of neonatal uterine bleeding (NUB), as it is possibly the first retrograde menstrual bleeding and occurring around the 7th day postpartum. As NUB is more often seen in neonates born post term or after hypertension induced complicated pregnancies, endometriosis later in life might be correlated with gestational age and may show a higher prevalence in woman born after a hypertension-related complicated pregnancy. Methods Data were extracted from the Danish Health Register (update 2023) and the Medical Birth Register (Danish new-borns from 1977-1999). Women with and without endometriosis will be compared. Using cross-sectional and longitudinal models we compared the prevalence of the following parameters in both cases and controls: gestational age, birth weight, hypertensive disorders diagnosed in the pregnancy of the mother i.e. pregnancy induced hypertension, preeclampsia, HELLP. Results A total of 681970 daughters could be evaluated divided in two groups: no endometriosis (n=667524) and with endometriosis (n=14446). A significant negative correlation was seen for the parameter post term. Less daughters with endometriosis were born after the gestational age of 41 weeks. RR=0.93 (95% CI 0.90-0.96) and p< 0.001. The prevalence of daughters with and without endometriosis, born after a pregnancy with all hypertensive disorders combined was similar. RR=1,00 (95% CI 0.92-1.08) and p NS. However, in the group with only hypertension or pre-eclampsia there was a slightly higher prevalence of daughters with endometriosis. RR=1.07 (95% CI 1.00-1.15) p=0.0495. This difference was even more clear in the group with hypertension or pre-eclampsia and born postterm showing a higher prevalence of daughters with endometriosis. RR = 1.19 (95% CI 1.02-1.39) p=0.03. These are preliminary results and a full evaluation of the groups is in progress at the moment. Conclusions Preliminary results not directly support the theory of NUB as an origin of endometriosis later in life. Hypertension and preeclampsia might have an association with endometriosis.

Importance: Mental and somatic health is often impaired among transgender persons. Studies regarding coexisting mental and somatic health outcomes among transgender persons are limited. Objective: To assess health diagnoses and medicine use among transgender persons compared with cisgender controls. Design, Setting, and Participants: This register-based national cohort study included data from January 1, 2000, to December 31, 2021. Transgender persons were included on the first date of receipt of a transgender identity contact code. Controls included 10 age-matched cisgender men (n = 5) and women (n = 5) for each transgender person. Statistical analyses were conducted from September to December 2024. Main Outcomes and Measures: The main outcomes were International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes and medicine use in a 5-year period up to the first date of transgender contact code for most commonly occurring mental and physical illnesses. The main outcomes were determined after data collection. Results: The cohort included 3812 transgender persons (1993 transmasculine persons [52.3%] with a median age of 19 years [IQR, 15-24 years] and 1819 transfeminine persons [47.7%] with a median age of 23 years [IQR, 19-33 years]) and 38120 cisgender controls. The odds for a mental health diagnosis was up to 12 times higher among transgender persons compared with cisgender controls. Among transmasculine and transfeminine persons, neurotic, stress-related disorders (transmasculine: adjusted odds ratio [AOR], 4.70 [95% CI, 4.02-5.50]; transfeminine: AOR, 5.27 [95% CI, 4.28-6.49]); developmental disorders, including autism (transmasculine: AOR, 11.67 [95% CI, 8.85-15.39]; transfeminine: AOR, 9.39 [95% CI, 7.05-12.50]); mood (affective) disorders (transmasculine: AOR, 5.41 [95% CI, 4.32-6.77]; transfeminine: AOR, 5.61 [95% CI, 4.16-7.57]); and behavioral disorders (transmasculine: AOR, 4.50 [95% CI, 3.61-5.62]; transfeminine: AOR, 4.15 [95% CI, 3.19-5.39]) were the most frequent mental health diagnoses compared with cisgender controls of the opposite sex at birth. Transmasculine persons had higher odds for somatic diagnosis codes of diabetes (AOR, 2.00 [95% CI, 1.12-3.56]), asthma (including chronic obstructive lung disease; AOR, 1.40 [95% CI, 1.06-1.85]), injury and poisoning (AOR, 1.28 [95% CI, 1.15-1.41]), and pain (AOR, 1.29 [95% CI, 1.12-1.49]) compared with control cisgender women. Among transfeminine persons, somatic diagnosis codes of infection (AOR, 1.68 [95% CI, 1.33-2.13]), anemia (AOR, 3.08 [95% CI, 1.36-6.97]), diabetes (AOR, 1.95 [95% CI, 1.25-3.05]), sleep apnea (AOR, 3.41 [95% CI, 1.84-6.31]), and pain (AOR, 1.31 [95% CI, 1.08-1.58]) were more frequent compared with control cisgender men. Transgender persons had higher use of psychopharmacologic medicine, antacids, and laxatives compared with cisgender controls (transmasculine persons vs control cisgender women, antipsychotics: AOR, 6.20 [95% CI, 5.07-7.59]; hypnotics-sedatives: AOR, 4.45 [95% CI, 3.78-5.23]; antacids: AOR, 1.25 [95% CI, 1.07-1.45]; and laxatives: AOR, 1.53 [95% CI, 1.17-1.99]; transfeminine persons vs control cisgender men, antipsychotics: AOR, 4.74 [95% CI, 3.92-5.74]; hypnotics-sedatives: AOR, 3.01 [95% CI, 2.53-3.57]; and antacids: AOR, 1.32 [95% CI, 1.12-1.56]). Mental health diagnoses and use of psychopharmacologic drugs were coexisting with somatic diagnoses and use of drugs for somatic diseases. Conclusions and Relevance: This cohort study of Danish transgender persons and cisgender controls found significantly higher risks for mental and somatic health diagnoses among transgender persons. Coexistence of mental health outcomes and somatic health outcomes among transgender persons could be associated with stress encountered due to belonging to a gender identity or sexual orientation minority group; mental and physical morbidity should be considered an integrated part of transgender care.

Objective: To provide an overview of postpartum hormonal contraceptive (HC) use in Denmark. Methods: This descriptive study used National health registries to estimate the cumulative incidence of HC initiation one year after delivery by type, calendar year, and age group among all first- and second-time mothers who delivered during 1997-2021 in Denmark. Timing of initiation is reported as the median time from delivery. Results: A total of 676 759 first-time and 552 142 second-time mothers were registered, with a cumulative incidence of HC initiation of 41.0% (95% CI, 40.9-41.1) and 40.5% (40.4-40.6), respectively. From 1997 to 2021, the cumulative incidence of first-time mothers who initially used progestogen-only pills increased from 3.8% (3.5-4.0) to 14.4% (13.9-14.8) and intrauterine levonorgestrel-releasing systems from 0.1% (0.1-0.2) to 12.6% (12.3-13.0). In contrast, combined oral contraception initiation decreased from 31.3% (30.7-31.8) to 7.8% (7.5-8.2). The median time of initiation decreased from 4.7 (Q1-Q3, 2.5-7.5) months during 1997-2001 to 2.5 (2-0-4.0) months during 2017-2021. The cumulative incidence of first-time mothers using combined HC six weeks after delivery decreased from 1.5% (1.5-1.6) during 2007-2011 to 0.5% (0.5-0.5) during 2017-2021. Conclusions: Within the first year after childbirth, 41 % of first- and second-time mothers initiated HC in Denmark. Throughout 1997-2021, mothers started earlier after delivery and more often used progestogen-only contraception. Few started combined HC within 6 weeks after delivery. Taken together, the pattern of HC use over time reflects a change to safer contraceptive methods postpartum which minimizes thromboembolic risk.

Purpose: Gender affirmation surgery (GAS) refers to surgical procedures that align physical appearance with gender identity. Data are limited regarding GAS in national cohort studies and we aimed to assess GAS in Danish transgender persons.Methods: We conducted a national register-based cohort study in Danish transgender persons. Persons with International Classification of Diseases (ICD)-10 diagnosis code of "gender identity disorder" were included during 2000-2021 and surgical procedure codes were identified up to and including June 2022.Results: The cohort included 3812 transgender persons with median age (interquartile range) at study inclusion 19.0 (15.0; 24.0) years for persons assigned female sex at birth (AFAB, N=1993) and 23.0 (19.0; 33.0) years for persons assigned male sex at birth (AMAB, N=1819). The mean (standard deviation) follow-up duration was 4.5 (4.3) years. In persons AFAB, the 5-year cumulative incidence for GAS increased from 14.9 (7.0; 25.6) for persons diagnosed in 2000-2005 to 50.0 (45.9; 53.9) for persons diagnosed in 2014-2018. In persons AMAB, the 5-year cumulative incidence increased from 7.1 (3.5; 12.4) to 17.0 (13.8; 20.4). The mean waiting time from study inclusion to event of any GAS, top surgery or genital surgery, decreased throughout the study period in persons AFAB and persons AMAB. Genital constructive GAS was conducted in 1.4% transgender persons.Conclusions: The incidence of GAS increased and waiting time decreased for transgender persons diagnosed during 2000-2018. Genital constructive GAS was rarely performed in Danish transgender persons.

Are gestational age and a complicated pregnancy, due to hypertensive disorders, predisposing factors for the development of endometriosis and supporting NUB as pathogenetic factor Preliminary results do not directly support the theory of NUB as pathogenetic factor of endometriosis. Hypertension and preeclampsia might have an association with endometriosis. Sampson’s theory of Retrograde menstruation is regarded as an important origin of endometriosis but does not explain all cases of endometriosis. Especially, endometriosis occurring before and during puberty, referred to as early-onset endometriosis (EOE) EOE might be explained by the phenomenon of neonatal uterine bleeding (NUB), as it is possibly the first retrograde menstrual bleeding and occurring around the 7th day postpartum. As NUB is more often seen in neonates born post term or after hypertension induced complicated pregnancies, EOE might be correlated with gestational age and may show a higher prevalence in woman born after a hypertension-related complicated pregnancy. Nationwide case-control study. Data were extracted from the Danish Health Register (update June 2024) and the Medical Birth Register (Danish new-borns from 1977-1999). Women with and without endometriosis will be compared. Using cross-sectional and longitudinal models we will compare the prevalence of the following parameters in both cases and controls: gestational age, hypertensive disorders diagnosed in the pregnancy of the mother i.e. pregnancy induced hypertension, preeclampsia, HELLP Cases : Daughters who were diagnosed with endometriosis. Controls : Daughters without the diagnosis endometriosis during the study period. Exposures : a) Hypertensive and or preeclamptic disorders in their mothers, and b) gestational age at birth. Methods: Relevant exposures were assessed in women with endometriosis and compared to women without having been diagnosed with endometriosis. Odds ratios were calculated for selected exposures with 95% CI. Among 681,970 daughters born during the period 1977-1999, 14,446 (2.12%) were diagnosed with endometriosis, 47% with surgical confirmation. A significant negative correlation was seen for the parameter post term. Less daughters with endometriosis were born after the gestational age of 41 weeks (22.7% in women with and 24.7% in women without endometriosis). RR = 0.93 (95% CI 0.90-0.96) and p < 0.001. The prevalence of daughters with and without endometriosis, born after a pregnancy with all hypertensive disorders combined was similar. RR = 1,00 (95% CI 0.92-1.08) and p NS. However, in the group with only hypertension or preeclampsia there was a slightly higher prevalence of daughters with endometriosis. RR = 1.07 (95% CI 1.00-1.15) p = 0.0495. This difference was even more clear in the group with hypertension or preeclampsia and born postterm showing a higher prevalence of daughter with endometriosis. Among endometriosis daughters born from 41 weeks, the proportion of mothers with hypertensive disorders was 3.6% and with hypertensive or preeclamptic disorders 4.8%. The corresponding percentages in daughters without endometriosis were 3.3% and 4.0%, respectively. The odds ratio for hypertensive disorders was 1.12 (95% CI 0.93-1.34) and for hypertensive or preeclamptic disorders 1.21 (1.03-1.42). There is no documentation of neonatal bleeding in the national database, so no direct relation is evaluated. The database doesn't include private practice. Possibly cases of endometriosis are not included regarding the rather low prevalence of endometriosis in our patientgroup. A possible hereditary factor as confounder will be excluded soon. In several studies a relation is mentioned between hypertension related complications in pregnancies in women with endometriosis. If there is a relation between pregnancies with hypertensive related complications and endometriosis later in life in the newborn, it might develop new ideas for (vascular?) pathogenetic paths or pathophysiological theories on endometriosis. No

Background Asthma is common among women of reproductive age. Prior studies have revealed an association between asthma and fertility by reporting prolonged time to pregnancy and lower fecundability. Objective To investigate fertility in women treated with asthma medication compared with women without asthma. Methods All women born between 1976 and 1999, who were living in Denmark on their 18th birthday, were followed from 1994 to 2017. Asthma was defined as repeated fulfillment of asthma medication prescriptions, and severity was classified according to the Global Initiative for Asthma guidelines (GINA). Outcome was fertility treatment in women with asthma compared with women without asthma, applying a Cox regression model adjusted for age, calendar year, and education. Results The cohort comprised 765,606 women followed up, starting on their 18th birthday, for a median time of 10.8 years (interquartile range: 5.3-17.5 years). Compared with women without asthma, women with asthma had a comparable proportion giving birth during follow-up, slightly more experienced fetal loss (17.0% vs 15.8%), and required fertility treatment (5.6% vs 5.0%). The risk of fertility treatment was significantly higher in women with asthma (hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 1.07-1.14). Women on GINA treatment steps 4 and 5 had an even higher risk of fertility treatment (HR: 1.59, 95% CI: 1.41-1.80) and, likewise, women with ≥3 prior exacerbations of asthma (HR: 1.36, 95% CI: 1.17-1.58). Conclusion Women with asthma have an increased use of fertility treatment, which correlates with asthma severity and exacerbation burden. However, asthma does not seem to affect number of live births.

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.

Background: Uterine leiomyoma may cause pelvic symptoms and may also interfere with the reproductive desires of many women. Consequently, some women may undergo myomectomy as a fertility sparring method to relieve symptoms or as a method to improve their fertility. Objective: We aimed to assess pregnancies and deliveries in women with previously myomectomy both in spontaneous pregnancies and with use of assisting reproductive techniques. Also, we aimed to asses if the reproductive prognosis differed between different surgical approaches. Study design: In this historical cohort study we collected data regarding myomectomies, pregnancies, use of assisting reproductive techniques and births from national health registries. All Danish women were followed from 1996 through 2017. Results: Of 5.281 women undergoing myomectomy, 97% had one and 3% had two or more myomectomies. Median age at first surgery was 38.5 years (interquartile range 34.1-44.6 years). Of 5.430 myomectomies conducted, 71% were done by laparotomy and 29% by laparoscopy. Of the 5.281 women treated with myomectomy, 1.586 (30%) became pregnant and 1.145 (22%) gave birth. In the entire cohort of 5.281 women, 1.056 (20%) were treated with assisting reproductive techniques. Of these 1.056 women, 659 (62%) got pregnant and 461 (44%) delivered. Median time from surgery to pregnancy was 1.2 years. Significantly more women became pregnant and gave birth when treated with laparotomy as compared to laparoscopy. However, the effect was only significant for women younger than 30 years or older than 40 years at first surgery. Conclusion: As the proportion of women attempting pregnancy was unknown, the overall figure of 30% pregnancy rate is a minimum estimate of the real chance of achieving pregnancy after myomectomy.

Background: Hormonal contraceptives are among the most widely used drugs of all time. Reports of the influence of different types of contemporary hormonal contraceptives on the risk of depression are conflicting.Methods: We used the Swedish Prescribed Drug Register and the National Patient Register and designed historical cohort studies covering the period from July 2010 until December 2020. We defined the target "trial" protocol, ensuring eligibility and treatment alignment from the start. To prevent healthy user bias, we excluded prevalent and prior users of hormonal contraception at baseline. Follow-up time was two years. The relation between hormonal contraceptive use and depression risk was modelled using Cox proportional hazards regression. Treatment effects were estimated by comparing initiators and never-users in observational analogues to “intention-to-treat” analyses. Findings: A total of 1 234 303 women were identified and included in the analyses of which 126 889 experienced a depression during follow up. Use of hormonal contraception was positively associated to depression development with adjusted hazard ratio of 1·36 (95% CI: 1·34-1·38) and 1·71 (1·67-1·75) for combined oral contraceptives and progestin-only pills, respectively. Similar effects were observed in adolescent (14-19 years of age) and adults (> 20 years of age). The adjusted hazard ratio of depression with use of pills containing ethinyl estradiol was if combined with norethisterone; 1·50 (1·21-1·87), with levonorgestrel 1·22 (1·19-1·24), norgestimate 1·32 (1·25-1·40), desogestrel 1·57 (1·35-1·82), drospirenone 1·81 (1·76-1·86), and dienogest 2·05 (1·52-2·77). For the levonorgestrel intrauterine system the effect increased with increasing dosages of progestin: 1·50, 1·52, and 1·63 for levonorgestrel dosage of 13·5, 19·5 and 52 mg, respectively (Ptrend = 0·002). Interpretation: Hormonal contraceptive use is positively associated to depression in both adolescents and adults. Different dosages and types of progestins, rather than the route of administration, seems to influence the risk of depression. Funding: ÅJ received funding from Women’s Mental Health During the Reproductive Lifespan (WOMHER). The computations were enabled by resources in project 2018/8-372 and (NAISS) at UPPMAX, funded by the Swedish Research Council through grant agreement no. 2022-06725.Declaration of Interest: The Juliane Marie Centre at Rigshospitalet has received a grant to conduct an EMA requested post marketing safety study focusing on venous thrombosis of a new progestogen only pill with drospirenon. Lidegaard is project leader of this study and received no personal payment for his investigator role. Lidegaard has received honoraria for postgraduate courses for gynaecologists under specialisation from the Danish Health Board.Ethical Approval: The study was approved by the Swedish Ethical Review Authority (Dnr 2021-05649-02).

BackgroundThe proportion of abortions provided by medication in the US and worldwide has increased greatly since FDA-approval of 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.ObjectiveThis study examined whether mental health disorders increased in the shorter and longer-term after a medication or procedural abortion.Study DesignUsing Danish population registers’ data, we conducted a prospective cohort study in which we included 72,424 females born in Denmark between 1980-2006, who were ages 12-38 during the study period and had a first first-trimester abortion before 13 weeks gestation in 2000-2018. Females with no previous psychiatric diagnoses were followed from one 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 one 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.ResultsFemales 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% 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).ConclusionsBecause 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.

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.