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Introduction: There is a paucity of objectively verified data on substance use among Danish pregnant women. We estimated the prevalence of substance use including alcohol and nicotine among the general population of Danish pregnant women., Material and Methods: In this anonymous, national, cross-sectional, descriptive study, pregnant women were invited when attending an ultrasound scan between November 2019 and December 2020 at nine Danish hospitals. Women submitted a urine sample and filled out a questionnaire. Urine samples were screened on-site with a qualitative urine dipstick for 15 substances including alcohol, nicotine, opioids, amphetamines, cannabis, and benzodiazepines. All screen-positive urine samples underwent secondary quantitative analyses with gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results were compared to questionnaire information to analyze the validity of self-reporting and to examine possible cross-reactions., Results: A total of 1903 of 2154 invited pregnant women participated (88.3%). The prevalence of dipstick-positive urine samples was 25.0%. 44.0% of these were confirmed positive, resulting in a total confirmed prevalence of 10.8%. The prevalence of nicotine use was 10.1%-and for all other substances, <0.5%. Nicotine use was more prevalent among younger pregnant women, while other substance use appeared evenly distributed over age groups. Self-reporting of use of nicotine products was high (71.1%), but low for cannabis and alcohol intake (0% and 33.3%, respectively). Prescription medication explained almost all cases of oxycodone, methylphenidate, and benzodiazepine use., Conclusions: Substance use among pregnant women consisted mainly of nicotine. Dipstick screening involved risks of false negatives and false positives. Except for alcohol intake and cannabis use, dipstick analyses did not seem to provide further information than self-reporting. LC-MS/MS analyses remain gold standard, and future role of dipstick screenings should be discussed., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Opioid use during pregnancy has serious consequences for mother and baby. The true extent of the problem is unknown and there is a need for better screening. Existing guidelines with respect to the management of pregnant women with opioid use are based on limited evidence. To improve recommendations for optimal identification, management, and treatment, publications on opioids in pregnancy were reviewed. Published literature from 2007 to 2017 was searched in PubMed, Cochrane and Embase databases. The review employed 60 publications from 210 studies identified, that were of varying quality and included randomized controlled trials, systematic reviews, meta-analyses, and Cochrane reviews. The prevalence of opioid use in pregnancy is underestimated. Screening by urine testing and self-reporting is acceptable to identify fetal exposure. To minimize risk, opioid agonist pharmacotherapy should replace the continued use of opioids or detoxification. Current guidelines recommend methadone and buprenorphine equally. However, recent studies indicate that buprenorphine has advantages over methadone. Accordingly, we suggest buprenorphine as first-line therapy. Future studies should elaborate on better objective screening methods to prevent the consequences of fetomaternal opioid exposure., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Polycystic ovary syndrome (PCOS) is characterized by obesity and insulin resistance. Measures of regional obesity may be used to predict insulin resistance. In the present study we compared fat distribution in patients with PCOS vs. controls and established the best measure of fat mass to predict insulin resistance in patients with PCOS., Material and Methods: The study was cross-sectional in an academic tertiary-care medical center with 167 premenopausal women with PCOS and 110 controls matched for ethnicity, BMI and age. Total and regional fat and lean body mass were assessed by whole body dual-energy X-ray absorptiometry (DXA) scans. Anthropometric measures (BMI, waist) and fasting metabolic analyses [insulin, glucose, lipids, Homeostasis model assessment (HOMA-IR), lipid accumulation product, and visceral adiposity index] were determined. Trial registration numbers: NCT00451568, NCT00145340., Results: Women with PCOS had higher central fat mass (waist, waist-hip ratio, and upper/lower fat ratio) compared with controls. In bivariate associations, the strongest associations were found between HOMA-IR and the fat mass measures trunk fat (r = 0.59), waist (r = 0.57) and BMI (r = 0.56), all p < 0.001. During multiple regression analyses, trunk fat, waist and BMI were the best predictors of HOMA-IR (R 2  = 0.48, 0.49, and 0.47, respectively)., Conclusions: Women with PCOS were characterized by central obesity. Trunk fat, waist and BMI were the best predictors of HOMA-IR in PCOS, but only limited information regarding insulin resistance was gained by whole body DXA scan., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: The aim of this study was to determine the proportion of patients who were referred to specialist care after reporting gynecological cancer alarm symptoms to their general practitioner. We sought to investigate whether contact with specialist care was associated with lifestyle factors or socioeconomic status., Material and Methods: Nationwide population-based prospective cohort study in Denmark, based on a random sample of 51 090 women aged 20 years or older from the general population. A web-based questionnaire regarding gynecological alarm symptoms and lifestyle was distributed to the invited individuals. Data about contact with specialist care were obtained from the National Patient Register and the National Health Insurance Service Registry, whereas information about socioeconomic status was collected from Statistics Denmark. Main outcome measures were percentages of patients having contact with specialist care and odds ratios (ORs) for associations between specialist care contact, lifestyle factors and socioeconomic status., Results: The study included 25 866 nonpregnant women; 2957 reported the onset of at least one gynecological cancer alarm symptom, and 683 of these (23.1%) reported symptoms to their general practitioner. The proportion of individuals having contact with specialist care ranged from 39.3% (pain during intercourse) to 47.8% (bleeding during intercourse). Individuals with higher educational level had significantly higher odds of contact with a specialist (OR 1.86, 95% CI 1.17-2.95)., Conclusions: Educational level influences contact with specialist care among patients with gynecological cancer alarm symptoms. Future studies should investigate inequalities in access to the secondary healthcare system., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objectives: To investigate obstetric outcomes in Danish women with different phenotypes of polycystic ovary syndrome (PCOS) and isolated hyperandrogenism (HA) and describe the risk of adverse obstetric outcomes in women with PCOS and HA compared to controls., Design: Cohort study., Setting: Odense University Hospital, Denmark., Population: Women with PCOS were identified prospectively starting in 1997. Singleton pregnancies in women with PCOS and HA during 2003-2011 were included (n = 199). A control group was matched to the patient cohort according to date of childbirth (n = 995)., Methods: Data on clinical characteristics and obstetric outcomes were collected in patients with PCOS and HA and controls. In PCOS and HA, total and free testosterone, sex hormone binding globulin, and hemoglobin A1c were measured outside pregnancy. During pregnancy, oral glucose tolerance tests were performed in 39 patients and 123 controls according to Danish national guidelines. PCOS phenotypes were based on the Rotterdam criteria., Main Outcome Measures: Gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, delivery by emergency cesarean section, preterm delivery and anthropometric measures in the newborn., Results: The incidence of adverse obstetric outcomes and anthropometric measures among the newborns were comparable between different phenotypes of PCOS and patients with HA. In the oral glucose tolerance test, patients had a higher risk of gestational diabetes mellitus compared with controls; the odds ratio (95% confidence interval) was 3.3 (1.5-6.9) after adjustment for age, parity, and body mass index (p = 0.002). The incidence of other adverse obstetric outcomes was similar in patients and controls., Conclusions: Obstetric outcomes were comparable in women with different PCOS phenotypes., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To determine prevalence estimates of gynecological alarm symptoms in different age groups and to describe common patterns of gynecological symptoms., Design: Web-based cross-sectional survey study., Setting: Nationwide in Denmark., Population: A random sample of 51,090 women aged 20 years or above from the general population., Methods: An internet-based questionnaire study regarding the prevalence estimates of symptom experiences. A total of 18 symptoms of cervical, endometrial and ovarian cancer were selected through an extensive literature search, which included national and international guidelines., Main Outcome Measures: Prevalence estimates of self-reported experience of gynecological alarm symptoms within the preceding 4 weeks., Results: A total of 26,466 women (54.5%) participated in the study. Some 80.3% had experienced at least one of the alarm symptoms within the preceding 4 weeks, and the median number of experienced symptoms was 2 (interquartile range 1-4). The most common symptoms were tiredness (53.0%) and abdominal bloating (36.7%); postmenopausal bleeding (2.3%) and involuntary weight loss (2.8%) were least frequent. Most of the symptoms were more prevalent among younger women, whereas only dyspnea and increased urgency of urination were more frequent among older women. Among younger women, multiple abdominal symptoms often occurred simultaneously and frequently in combination with pelvic pain, whereas older women were more likely to report single symptoms., Conclusions: Gynecological alarm symptoms are frequent in the general population, mostly among younger women. Older women reported fewer symptoms, and these often appeared as single symptoms., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

There are few recent data on the prevalence of substance abuse among Danish pregnant women. During 2013, in the Region of Southern Denmark, a cross-sectional, anonymous, screening-based study was conducted among pregnant women attending for routine ultrasound scan at 12 weeks gestation. The women submitted a urine sample and completed a short questionnaire. Urine samples were tested for opiates, cannabis, benzodiazepines, cocaine, methadone, amphetamine and methamphetamine. Positive samples underwent repeat analysis for confirmation. Of 690 pregnant women, 88.1% participated. Overall, 3.6% of women had a positive urine sample confirmed by repeated analysis. The age distribution in women with positive samples did not differ from the entire cohort. Our findings indicate a larger prevalence than anticipated, and that a substantial number of pregnant women with substance abuse are not appropriately referred to the focused specialist center for such women at risk., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Polycystic ovary syndrome (PCOS) is often associated with an increased waist circumference and with lower cardio-respiratory fitness as a consequence of obesity, which may be improved by physical activity., Objective: To investigate the effect of high-intensity aerobic training combined with group counselling sessions on anthropometry and cardio-respiratory fitness in women with PCOS., Design: Seventeen sedentary, overweight women with PCOS were randomized in a cross-over design to 16 weeks of intervention: eight weeks high-intensity aerobic exercise was followed by eight weeks of group counselling (n = 8) or vice versa (n = 9). Fourteen of the women completed the tests., Main Outcome Measures: Waist circumference, body mass index and maximal aerobic capacity (VO(2max) ) were measured at baseline, cross-over and post-intervention., Results: There was a decrease in waist circumference (119.9 vs. 106.5 cm) and body mass index (34.9 vs. 34.4 kg/m(2) ) and an increase in VO(2max) (2554.9 vs. 2807.9 mL/min) during the intervention period (t = 16 weeks, n = 14), all p < 0.05. Weight loss tended to be highest in the group which started with group counselling (2.9 vs. 0.6 kg, t = 16 weeks, n = 14, p = 0.055)., Conclusion: Exercise in groups followed by counselling or vice versa had beneficial effects on waist circumference, weight, and VO(2max) in women with PCOS. Future studies should examine possible beneficial effects of combined group counselling and exercise on weight loss and adherence to exercise protocols among women with PCOS., (© 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: Polycystic ovary syndrome may be associated with an increased risk of endometrial hyperplasia and endometrial cancer, but substantial evidence for this remains to be established. We investigated the prevalence of endometrial hyperplasia and endometrial cancer in a well characterized group of women with polycystic ovary syndrome and/or clinical/biochemical hyperandrogenism., Design: Retrospective observational trans-sectional study., Setting: Out-patient clinic at the Departments of Endocrinology and Gynecology, Odense University Hospital, Denmark., Population: In all, 963 premenopausal women consecutively referred with the diagnoses polycystic ovary syndrome and/or hirsutism during 1997-2008., Methods: All women underwent a standardized evaluation program. In 2011, The Danish Data Bank of Pathology was used to identify women with endometrial histology diagnoses (year range of diagnosis 1982-2011). Main outcome measures. Histology diagnoses, demographic variables., Results: Endometrial hyperplasia was diagnosed in 10 (1.0%) women and endometrial cancer in one (0.1%) woman. The median body mass index of these women was 30.6 kg/m(2) compared with 26.8 kg/m(2) in the total cohort. There were no differences between the cases and total cohort in terms of individual Rotterdam Criteria. In Denmark, 70 cases of endometrial cancer are diagnosed yearly in women 40-55 years, a prevalence of 0.4% in the corresponding period., Conclusion: The results of the present study do not suggest a higher prevalence of endometrial cancer in women with polycystic ovary syndrome and/or clinical/biochemical hyperandrogenism than in the general population., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Uterine artery embolization is one of the established treatment options for symptomatic uterine leiomyomas, with a proven effect on the size of leiomyomas and providing short-term relief of symptoms. Only few studies have addressed long-term satisfaction with the treatment. We conducted a historical cohort study of 96 patients. The patients were treated at a median age of 43years (range 23-59years). The median size of the largest myoma was 69mm (range 20-170mm). By use of a postal questionnaire (response rate 86%) and audit of patient files, we found that 53% reported full recovery of symptoms and 36% some effect on symptoms after a median of 8.9years (range 8-9.4years). Overall, 25% of the women reported a need for further treatment. The rate of eventual hysterectomy was 22%. We confirm that uterine artery embolization is a safe and well-tolerated procedure with a high long-term satisfaction rate., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Postmenopausal endometriosis is rare. The purpose of this presentation is to give a review of the topic based on existing literature., Methods: A Medline search concerning postmenopausal endometriosis was carried out. Hormone therapy and risk of malignancy in these patients are discussed., Results: Some 32 case reports on postmenopausal endometriosis were found. The most common location is in the ovaries. Estrogens stimulate endometriosis. There is a risk of recurrence or de novo occurrence of endometriosis after the menopause in patients who take hormone therapy (HT); especially estrogen only therapy (ET). So far, treatment has primarily been surgery (hysterectomy (TAH) and bilateral oophorectomy (BSO)).There is little experience with medical treatment (aromatase inhibitors). The risk of malignant transformation of premenopausal endometriosis is around 1%. Furthermore, patients with endometriosis have an increased risk of ovarian cancer, and, apparently, other malignancies. The risk of malignant transformation appears to be further elevated in patients who take ET, although this subject is not fully elucidated., Conclusions: Although the condition is rare, it is important to be aware of endometriosis after the menopause. Postmenopausal endometriosis infers a risk of recurrence and malignant transformation. Although solid evidence is lacking, the risk of malignant transformation appears to be lower during combined HT compared to ET. Thus, hormone replacement therapy should generally be reserved for patients with severe climacteric complaints, and if indicated, combined therapy should be used.

Levormeloxifene is a selective estrogen receptor modulator that was developed as an alternative to estrogen replacement therapy for the treatment and prevention of postmenopausal bone loss. In animal models, levormeloxifene prevented increased bone turnover and vertebral bone loss following ovariectomy. Studies of healthy postmenopausal women showed that levormeloxifene 1.25-20 mg/day decreased bone turnover and increased bone mineral density to a comparable extent to that observed during conventional hormone replacement therapy. However, in the phase II and III studies, the effect on bone turnover and bone mineral density was similar for each dose of levormeloxifene and the minimal effective dose was never established. The development of levormeloxifene was discontinued during the phase III trial due to a significant incidence of gynecologic adverse events in the levormeloxifene-treated groups. This article reviews the preclinical and clinical studies of levormeloxifene and the circumstances for the premature termination of the development of the drug. Other selective estrogen receptor modulators such as tamoxifen and raloxifene and the perspectives for selective estrogen receptor modulators in development are furthermore discussed.

Aim: To evaluate the success rate of medical abortion using an outpatient regimen of oral mifepristone 400 mg and oral misoprostol 400 microg for legal abortion in women < 56 days pregnant., Methods: Successful abortion was defined as an endometrial thickness < 20 mm evaluated by transvaginal ultrasound and minimal vaginal bleeding at a control examination performed 14 days after administration of misoprostol. Over a 6-month period in 2003, a questionnaire (completion rate 70%) was used for a spot check of the patients' evaluation of the method., Results: Six hundred and sixty women underwent the procedure over a 3-year period and 606 (92%) experienced successful medical abortion. The remaining 8% had vacuum aspiration performed mainly due to uterine retention (70%). Other reasons were vaginal bleeding (25%), vomiting (2%), or pelvic infection (4%). Most women reported no days with severe pain (67%), 0--1 days with moderate pain (82%), and 0--1 days with light pain (62%). In terms of gastrointestinal side effects, 68% reported nausea, 33% vomiting, and 27% diarrhea. Most women (90%) felt that the information given at the hospital prior to the abortion was sufficient, 74% would prefer medical abortion again in case of a future unwanted pregnancy, and 85% would prefer to abort at home again., Conclusion: A high acceptance and success rate was seen using this outpatient oral regimen of mifepristone and misoprostol.

The obstetrical complications preeclampsia, intrauterine growth restriction (IUGR), placental abruption and fetal loss are major causes of maternal and fetal morbidity and mortality. Much recent research has focused on to what extent congenital thrombophilia contributes to these obstetrical complications. Combined with the hypercoagulable state of pregnancy, thrombophilia has the potential to induce placental thrombosis and cause placental insufficiency with subsequent obstetrical complications. This article aims to review and discuss published clinical studies of the relationship between congenital thrombophilia and preeclampsia, IUGR, placental abruption and fetal loss. In addition, the few published clinical trials of prophylactic antithrombotic treatment to prevent severe obstetrical complications in thrombophilic women are discussed. The studies have shown variable results evaluated mainly as a result of the limited number of case reports published. However, the strongest association was found to be between congenital thrombophilia and preeclampsia and late fetal loss. Early fetal loss was not found to be associated with congenital thrombophilia. At present, the question remains open as to whether IUGR and placental abruption is directly associated with thrombophilia or mediated through preeclampsia. In conclusion, the associations between congenital thrombophilia and preeclampsia, IUGR, placental abruption and fetal loss only reaches evidence grade 4. Present recommendations and clinical guidelines are thus based on weak scientific proof.