| 1. |
- Comasco, Erika, 1982-, et al.
(författare)
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Ulipristal Acetate for Treatment of Premenstrual Dysphoric Disorder : A Proof-of-Concept Randomized Controlled Trial
- 2021
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 178:3, s. 256-265
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Premenstrual dysphoric disorder (PMDD) is a common mood disorder, characterized by distressing affective, behavioral, and somatic symptoms in the late luteal phase of the menstrual cycle. The authors investigated continuous treatment with a selective progesterone receptor modulator, ulipristal acetate (UPA), as a potential treatment for PMDD. Methods: The authors conducted an investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial in which women with PMDD (N=95) were treated with either 5 mg/day of UPA or placebo during three 28-day treatment cycles. The primary outcome was the change in premenstrual total score on the Daily Record of Severity of Problems (DRSP) from baseline to end of treatment. DRSP scores were captured by daily ratings using a smartphone application and were analyzed with linear mixed models for repeated measures. Results: The mean improvement in DR SP score after 3 months was 41% (SD=18) in the UPA group, compared with 22% (SD=27) in the placebo group (mean difference 18%; 95% CI = -29, -8). Treatment effects were also noted for the DRSP depressive symptom subscale (42% [SD=22]compared with 22% [SD=32]) and the DRSP anger/irritability subscale (47% ISD=21) compared with 23% (SD=35I), but not for the DRSP physical symptom subscale. Remission based on DRSP score was attained by 20 women in the UPA group (50.0%) and eight women in the placebo group (21.1%) (a statistically significant difference). Conclusions: If these results are replicated, UPA could be a useful treatment for PMDD, particularly for the psychological symptoms associated with the disorder.
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| 2. |
- Ekenros, Linda, et al.
(författare)
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The perceived influence of menstrual cycle and hormonal contraceptives on training and performance: Comparison between football, handball, and orienteering
- 2023
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Ingår i: International journal of sports science & coaching. - : Sage Publications. - 1747-9541 .- 2048-397X.
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we published self-reported data concerning the perceived effects of the menstrual cycle and hormonal contraceptives on the training and performance of 1086 female athletes participating in 57 sports. However, studies comparing differences between sports with large sample sizes are lacking. The aim of this ancillary study was to compare the impact of the menstrual cycle and hormonal contraceptives on training and performance between the three largest sports in the cohort, that is, football, handball, and orienteering, as well as the knowledge and support provided to the female athletes engaged in these sports. The results are from a web-based questionnaire completed by 312 football players, 243 handball players, and 93 orienteers. A total of 54% of the orienteers planned their training based on the menstrual cycle, which was a higher proportion compared to football (45%) and handball (29%) players (p < 0.05). Fewer football players believed that the menstrual cycle had an impact on their performance during training and competition compared to the two other sports. A high proportion of the athletes used hormonal contraceptives in all three sports, but a lower proportion of the orienteers (40%) used hormonal contraceptives compared to football (76%) and handball players (66%) (p < 0.05). Football and handball players received overall more support than orienteers, and the support was mostly provided by a physiotherapist and/or a strength and conditioner coach besides the main coach. These findings demonstrate that the perceived influence of the menstrual cycle and hormonal contraceptives on training and performance differs between endurance athletes in orienteering compared to team-sport athletes in football and handball.
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| 3. |
- Falhammar, Henrik, et al.
(författare)
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Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency : a Swedish population-based national cohort study
- 2015
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Ingår i: The Journal of Clinical Endocrinology & Metabolism. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0021-972X. ; 100:9, s. 3520-3528
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. OBJECTIVE: This study aimed to study cardiovascular and metabolic morbidity in CAH. DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. MAIN OUTCOME MEASURES: To study cardiovascular and metabolic morbidity in CAH. RESULTS: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1-5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9-3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. CONCLUSIONS: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.
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| 4. |
- Falhammar, Henrik, et al.
(författare)
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Increased mortality in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
- 2014
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Ingår i: The Journal of Clinical Endocrinology & Metabolism. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0021-972X .- 1945-7197.
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Tidskriftsartikel (refereegranskat)abstract
- Context: Reports on mortality in patients with congenital adrenal hyperplasia (CAH) are lacking. Objective: To study mortality and causes of death in CAH. Design, Setting and Participants: We studied patients with CAH (21-hydroxylase deficiency, n=588; CYP21A2 mutations known, >80%), and compared them with controls (n=58800). Data were derived through linkage of national population-based registers. Main Outcome Measures: Mortality and causes of death. Results: The mean age of death was 41.2±26.9 years in CAH patients and 47.7±27.7 years in controls (P<0.001). Among CAH patients 23 (3.9%) had deceased compared to 942 (1.6%) of controls. The hazard ratio (and 95% confidence interval) of death was 2.3(1.2-4.3) in CAH males and 3.5(2.0-6.0) in CAH females. Including only patients born 1952-2009, gave similar total results but only patients with salt-wasting or with unclear phenotype had an increased mortality. The causes of death in CAH patients were adrenal crisis (42%), cardiovascular (32%), cancer (16%), and suicide (10%). There were seven additional deaths in CAH individuals with incomplete or reused personal identification number that could not be analyzed using linkage of registers. Of the latter all except one were deceased before the introduction of neonatal screening in 1986 and most of them in the first weeks of life, probably in an adrenal crisis. Conclusions: CAH is a potentially lethal condition and was associated with excess mortality due to adrenal crisis. The salt-wasting phenotype seemed to have worse outcome also in children and adults due to adrenal crisis and not only before the introduction of neonatal screening.
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| 6. |
- Løvvik, Tone S., et al.
(författare)
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Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2) : a randomised, double-blind, placebo-controlled trial
- 2019
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 7:4, s. 256-266
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy complications. Epi-analysis of two previous randomised controlled trials that compared metformin with placebo during pregnancy in women with PCOS showed a significant reduction in late miscarriages and preterm births in the metformin group. The aim of this third randomised trial (PregMet2) was to test the hypothesis that metformin prevents late miscarriage and preterm birth in women with PCOS.Methods: PregMet2 was a randomised, placebo-controlled, double-blind, multicentre trial done at 14 hospitals in Norway, Sweden, and Iceland. Singleton pregnant women with PCOS aged 18-45 years were eligible for inclusion. After receiving information about the study at their first antenatal visit or from the internet, women signed up individually to participate in the study. Participants were randomly assigned (1: 1) to receive metformin or placebo by computer-generated random numbers. Randomisation was in blocks of ten for each country and centre; the first block had a random size between one and ten to assure masking. Participants were assigned to receive oral metformin 500 mg twice daily or placebo during the first week of treatment, which increased to 1000 mg twice daily or placebo from week 2 until delivery. Placebo tablets and metformin tablets were identical and participants and study personnel were masked to treatment allocation. The primary outcome was the composite incidence of late miscarriage (between week 13 and week 22 and 6 days) and preterm birth (between week 23 and week 36 and 6 days), analysed in the intention-to-treat population. Secondary endpoints included the incidence of gestational diabetes, preeclampsia, pregnancy-induced hypertension, and admission of the neonate to the neonatal intensive care unit. We also did a post-hoc individual participant data analysis of pregnancy outcomes, pooling data from the two previous trials with the present study. The study was registered with ClinicalTrials. gov, number NCT01587378, and EudraCT, number 2011-002203-15.Findings: The study took place between Oct 19, 2012, and Sept 1, 2017. We randomly assigned 487 women to metformin (n=244) or placebo (n=243). In the intention-to-treat analysis, our composite primary outcome of late miscarriage and preterm birth occurred in 12 (5%) of 238 women in the metformin group and 23 (10%) of 240 women in the placebo group (odds ratio [OR] 0.50, 95% CI 0.22- 1.08; p = 0.08). We found no significant differences for our secondary endpoints, including incidence of gestational diabetes (60 [25%] of 238 women in the metformin group vs 57 [24%] of 240 women in the placebo group; OR 1.09, 95% CI 0.69-1.66; p=0.75). We noted no substantial between-group differences in serious adverse events in either mothers or offspring, and no serious adverse events were considered drug-related by principal investigators. In the post-hoc pooled analysis of individual participant data from the present trial and two previous trials, 18 (5%) of 397 women had late miscarriage or preterm delivery in the metformin group ]compared with 40 (10%) of 399 women in the placebo group (OR 0.43, 95% CI 0.23-0.79; p=0.004).Interpretation: In pregnant women with PCOS, metformin treatment from the late first trimester until delivery might reduce the risk of late miscarriage and preterm birth, but does not prevent gestational diabetes.
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| 7. |
- Naessen, Sabine, et al.
(författare)
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Women with bulimia nervosa exhibit attenuated secretion of glucagon-like peptide 1, pancreatic polypeptide, and insulin in response to a meal
- 2011
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 94:4, s. 967-972
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Tidskriftsartikel (refereegranskat)abstract
- Background: The eating disorder bulimia nervosa (BN) is characterized by frequent episodes of binge eating, followed regularly by inappropriate compensatory behavior, such as self-induced vomiting. Objective: The current investigation was designed to examine possible alterations in the secretion of the gastrointestinal satiety peptides glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP) in women with BN. Design: Twenty-one women with BN and 17 healthy control subjects of comparable age and BMI were recruited. After fasting overnight, the subjects provided blood samples during ingestion of a standardized meal and self-rated their appetite on a visual analog scale. Fasting and meal-related secretion of the incretin GLP-1 and the meal-related feedback signal PP and insulin and glucose as indicators of the metabolic homeostasis were analyzed. Results: Women with BN had significantly lower fasting and postprandial serum concentrations of GLP-1 (P < 0.01) and PP (P < 0.05) than did the control subjects. Furthermore, both the basal (P < 0.001) and peak (P < 0.05) concentrations of insulin were significantly attenuated in the bulimic subjects, whereas glucose concentrations were normal. As a consequence, the bulimic homeostasis model assessment of insulin index values were also lower (P < 0.001). Conclusions: Women with BN secrete abnormally low amounts of GLP-1 and PP, possibly because of the adaption to large meals in the form of enlarged gastric capacity and reduced muscle tone in the gastric wall. Attenuated secretion of these gastrointestinal satiety peptides may play a role in the maintenance of bulimic behavior.
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| 8. |
- Nordenström, Anna, et al.
(författare)
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Are carriers of CYP21A2 mutations less vulnerable to psychological stress? A population-based national cohort study
- 2016
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Ingår i: Clinical Endocrinology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0300-0664 .- 1365-2265.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Congenital adrenal hyperplasia (CAH) is one of the most common monogenic autosomal recessive disorders with an incidence of one in 15 000. About one in 70 individuals in the general population are carriers of a severe CYP21A2 mutation. It has been suggested that this confers a survival advantage, perhaps as a result of increased activity in the hypothalamic–pituitary–adrenal axis. We investigated vulnerability to psychological stress in obligate carriers. Method: The Swedish CAH Registry encompasses more than 600 patients. Parents, that is obligate carriers of the CYP21A2 mutation, were identified through the Multigeneration Register. The diagnosis of the child was used as the psychological stressor. Psychiatric diagnoses before and after the birth of a child with CAH were compared to those of controls derived from (i) the general population, (ii) parents of children with hypospadias and (iii) parents of children with diabetes mellitus type 1 (T1DM). Results: Parents of children with CAH had less risk of being diagnosed with any psychiatric disorder (OR, 0 6), an affective disorder (OR, 0 5) or substance misuse (OR, 0 5) after the diagnosis of the child, compared to the general population. Their risk was also decreased compared to parents of a child with hypospadias (OR, 0 6, 0 4 and 0 2, respectively) and parents of a child with T1DM (OR 0 7, 0 6 and 0 2, respectively). The CYP21A2 carriers had a lower risk of developing mood and stress-related disorders after the diagnosis of the child. Conclusion: Obligate CYP21A2 carriers had a reduced risk of a psychiatric diagnosis and were less vulnerable to a psychologically stressful situation, at least with respect to receiving a psychiatric diagnosis. This indicates a better ability to cope with psychological stress among heterozygous carriers of severe CYP21A2 mutations, which may contribute to the apparent survival advantage
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| 9. |
- Nybacka, Åsa, et al.
(författare)
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Increased fibre and reduced trans fatty acid intake are primary predictors of metabolic improvement in overweight polycystic ovary syndromeSubstudy of randomized trial between diet, exercise and diet plus exercise for weight control
- 2017
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Ingår i: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265. ; 87:6, s. 680-688
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Polycystic ovary syndrome (PCOS) is commonly affected by obesity. PCOS phenotypes are prone to increased waist/hip ratio, insulin resistance and dyslipidaemia. This substudy was undertaken to evaluate the effects of lifestyle interventions on metabolic biomarkers in overweight/obese PCOS women and the interventional effects of dietary components related to metabolic outcomes.Design: Randomized three-arm parallel study.Patients: Fifty-seven PCOS women body mass index (BMI >27kg/m(2), age 18-40) were randomly assigned to diet (D, n=19), exercise (E, n=19) or diet plus exercise (DE, n=19) in three-arm fashion over 16weeks. The D group received nutritional counselling by a dietician to reduce their energy intake by at least 600kcal/d. The E group received an ambulatory exercise regimen from a physiotherapist. The DE group had both interventions.Measurements: Self-reported food intake over 4days, exercise pedometers, BMI, waist/hip ratio, blood pressure, body composition and oral glucose tolerance test were performed before and at the end of intervention.Results: BMI, waist circumference and total cholesterol were significantly reduced in the D and DE groups, as well as low-density lipoprotein and Homeostasis Model of Assessment index in the D group. In the E group, exercise was increased along with a decrease in BMI and waist circumference. The strongest predictor of reduced BMI was increased fibre intake (-0.44, P=.03), while a decrease in trans fatty acid intake predicted reduced insulinogenic index (0.44, P<.01).Conclusions: Nutritional counselling with dieting is clearly effective to improve metabolic disturbances in overweight/obese women with PCOS. Increased fibre and reduced trans fatty acid intake are primary predictors of metabolic improvement and weight control.
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| 10. |
- Piltonen, Terhi T., et al.
(författare)
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Awareness of polycystic ovary syndrome among obstetrician-gynecologists and endocrinologists in Northern Europe
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To date, little is known about differences in the knowledge, diagnosis making and treatment strategies of health care providers regarding polycystic ovary syndrome (PCOS) across different disciplines in countries with similar health care systems. To inform guideline translation, we aimed to study physician reported awareness, diagnosis and management of PCOS and to explore differences between medical disciplines in the Nordic countries and Estonia.Methods: This cross-sectional survey was conducted among 382 endocrinologists and obstetrician gynaecologists in the Nordic countries and Estonia in 2015-2016. Of the participating physicians, 43% resided in Finland, 18% in Denmark, 16% in Norway, 13% in Estonia, and 10% in Sweden or Iceland, and 75% were obstetrician-gynaecologists. Multivariable logistic regression models were run to identify health care provider characteristics for awareness, diagnosis and treatment of PCOS.Results: Clinical features, lifestyle management and comorbidity were commonly recognized in women with PCOS, while impairment in psychosocial wellbeing was not well acknowledged. Over two-thirds of the physicians used the Rotterdam diagnostic criteria for PCOS. Medical endocrinologists more often recommended lifestyle management (OR = 3.6, CI 1.6-8.1) or metformin (OR = 5.0, CI 2.5-10.2), but less frequently OCP (OR = 0.5, CI 0.2-0.9) for non fertility concerns than general obstetrician-gynaecologists. The physicians aged <35 years were 2.2 times (95% CI 1.1-4.3) more likely than older physicians to recommend lifestyle management for patients with PCOS for fertility concerns. Physicians aged 46-55 years were less likely to recommend oral contraceptive pills (OCP) for patients with PCOS than physicians aged >56 (adjusted odds ratio (OR) = 0.4, 95% CI 0.2-0.8).Conclusion: Despite well-organized healthcare, awareness, diagnosis and management of PCOS is suboptimal, especially in relation to psychosocial comorbidities, among physicians in the Nordic countries and Estonia. Physicians need more education on PCOS and evidence based information on Rotterdam diagnostic criteria, psychosocial features and treatment of PCOS, with the recently published international PCOS guideline well needed and welcomed.
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