| 1. |
- Forslund, Maria, 1978, et al.
(författare)
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International evidence-based guideline on assessment and management of PCOS-A Nordic perspective.
- 2024
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - 1600-0412. ; 103:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) affects about 12% of women of reproductive age. In 2018, the first evidence-based guideline on assessment and management of PCOS was published, and an updated extended guideline was released in August 2023. These guidelines followed best practice and are endorsed by 39 organizations worldwide, making them the most robust source of evidence to guide clinical practice. In the 2023 guideline, diagnostic criteria have been further refined as polycystic ovary morphology can now be assessed with gynecological ultrasound or elevated anti-Müllerian hormone levels. A healthy lifestyle should be at the focus of care for all women with PCOS; however, with no specific diet or physical exercise recommended. The latest evidence on medical treatments and fertility management are reviewed, including special considerations regarding long-term follow-up of metabolic and psychiatric comorbidities and pregnancy in women with PCOS. Here we summarize the recommendations from a Nordic perspective.
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| 2. |
- Lønnebotn, Marianne, et al.
(författare)
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Polycystic ovary syndrome, body mass index and hypertensive disorders in pregnancy
- 2018
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Ingår i: Pregnancy Hypertension. - : Elsevier. - 2210-7789 .- 2210-7797. ; 11, s. 32-37
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Some studies of women with polycystic ovary syndrome (PCOS) report increased prevalence of hypertensive disorders in pregnancy, while others do not. Several of these studies do not control for obesity. We aimed to study whether PCOS is associated with hypertensive disorders in pregnancy and whether it is dependent on body mass index (BMI).Study design: We present a cross-sectional analysis of 3732 women from Denmark, Estonia, Iceland, Norway and Sweden, born in 1945-72, who participated in the Respiratory Health In Northern Europe (RHINE) study and answered an extensive women's health questionnaire on menstruation, PCOS, infertility, pregnancy history and childbirth. The main outcome measurement was hypertensive disorders of pregnancy. We adjusted for smoking, age, infertility treatment and study center. Effect modification by BMI was assessed.Results: PCOS was related to hypertensive disorders in pregnancy with a relative risk (RR) of 1.62 (95% CI 1.09-2.42). This relationship was found among underweight women with a BMI of <18.5 kg/m(2) [RR=5.2 (95% CI 1.66-16.5)] and obese women with a BMI of >= 30 kg/m(2) [RR=2.36 (95% CI 1.29-4.31)], but not among normal-weight women, BMI 18.5-25 kg/m(2) [1.08 (0.53-2.20)], or overweight women, BMI 25-30 kg/m(2) [1.24 (0.50-3.08)] (p-interaction=0.041).Conclusion: Polycystic ovary syndrome is associated with hypertensive disorders in pregnancy. This association only occurs among underweight and obese women and not among normal-weight and slightly overweight women.
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| 3. |
- 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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| 4. |
- Mellembakken, Jan Roar, et al.
(författare)
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Higher blood pressure in normal weight women with PCOS compared to controls
- 2021
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 10:2, s. 154-163
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Obesity is considered to be the strongest predictive factor for cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The aim of the study was to compare blood pressure (BP) in normal weight women with PCOS and controls matched for age and BMI. Methods: From a Nordic cross-sectional base of 2615 individuals of Nordic ethnicity, we studied a sub cohort of 793 normal weight women with BMI < 25 k g/m(2) (512 women with PCOS according to Rotterdam criteria and 281 age and BMI-matched controls). Participants underwent measurement of BP and body composition (BMI, waist-hip ratio), lipid status, and fasting BG. Data were presented as median (quartiles). Results: The median age for women with PCOS were 28 (25, 32) years and median BMI was 22.2 (20.7, 23.4) kg/m(2). Systolic BP was 118 (109, 128) mmHg in women with PCOS compared to 110 (105, 120) mmHg in controls and diastolic BP was 74 ( 67, 81) vs 70 (64, 75) mmHg, both P < 0.001. The prevalence of women with BP >= 140/90 mmHg was 11.1% (57/ 512) in women with PCOS vs 1.8% (5/281) in controls, P < 0.001. In women >= 35 years the prevalence of BP >= 140/90 mmHg was comparable in women with PCOS and controls (12.7% vs 9.8%, P = 0.6). Using multiple regression analyses, the strongest association with BP was found for age, waist circumference, and total cholesterol in women with PCOS. Conclusions: Normal weight women with PCOS have higher BP than controls. BP and metabolic screening are relevant also in young normal weight women with PCOS.
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| 5. |
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| 6. |
- Molin, Johanna, et al.
(författare)
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Gestational weight gain, appetite regulating hormones, and metformin treatment in polycystic ovary syndrome : A longitudinal, placebo-controlled study
- 2022
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Ingår i: British Journal of Obstetrics and Gynecology. - : John Wiley & Sons. - 1470-0328 .- 1471-0528. ; 129:7, s. 1112-1121
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore mechanisms that modulate gestational weight gain (GWG) in women with polycystic ovary syndrome (PCOS) and healthy controls.Design: Sub-sample of randomised controlled trials (PCOS) combined with a prospective cohort (controls).Setting: Eleven Norwegian, Swedish, and Icelandic hospitals.Population: Pregnant women with PCOS treated with metformin (PCOS-M, n = 36) or placebo (PCOS-P, n = 37), and healthy pregnant women (HC, n = 15).Methods: Serum levels of the appetite regulating hormones leptin, ghrelin, allopregnanolone, and soluble leptin receptor (sOB-R) were determined in the first and third trimesters.Main Outcome Measures: Excessive GWG (eGWG) relative to body mass index according to Institute of Medicine (IOM) guideline. Serum leptin/sOB-R ratio, or free-leptin-index (FLI), as biomarker of leptin sensitivity. Serum ghrelin and allopregnanolone levels.Results: The overall prevalence of eGWG was 44% (38/86). Women with eGWG had higher first and third trimester FLI (P < 0.001), and lower third trimester allopregnanolone levels (P = 0.003) versus women with non-eGWG. The prevalence of eGWG was lower in PCOS-M versus PCOS-P (28% versus 62%, odds ratio = 0.4, 95% CI 0.2–0.8, P = 0.005). FLI decreased during pregnancy in PCOS-M (P = 0.01), but remained unaltered in PCOS-P and HC. Ghrelin and allopregnanolone levels were comparable in PCOS-M, PCOS-P and HC throughout pregnancy.Conclusion: Excessive GWG is associated with enhanced leptin resistance, and attenuated physiological increase in serum allopregnanolone levels during pregnancy. Metformin reduces the risk for eGWG and improves leptin sensitivity in pregnant women with PCOS.
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| 7. |
- Molin, Johanna, et al.
(författare)
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Neonatal outcome following metformin-treated gestational diabetes mellitus : a population-based cohort study
- 2024
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 103:5, s. 992-1007
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Neonatal hypoglycemia is a common complication associated with gestational diabetes and therefore relevant to consider in evaluations of maternal treatment. We aimed to investigate the risk of neonatal hypoglycemia in offspring exposed to metformin treatment alone (MT) or combined with insulin (MIT) in comparison with nutrition therapy alone (NT), and insulin treatment alone (IT). In addition, we investigated MT in comparison with MIT. Secondary outcomes included neonatal anthropometrics, respiratory morbidity, hyperbilirubinemia, 5-min Apgar score, and preterm birth.Material and methods: This Swedish population-based cohort included 16 181 women diagnosed with gestational diabetes, and their singleton offspring born in 2019–2021. We estimated risk as adjusted odds ratio (aOR) with 95% confidence interval (CI), using individual-level, linkage register-data in multivariable logistic regression models.Results: In the main analysis, MT was associated with a lower risk of neonatal hypoglycemia versus NT (aOR 0.85, 95% CI: 0.74–0.96), versus MIT (0.74 [0.64–0.87]), and versus IT (0.47 [0.40–0.55]), whereas MIT was associated with a similar risk of neonatal hypoglycemia versus NT (1.14 [0.99–1.30]) and with lower risk versus IT (0.63 [0.53–0.75]). However, supplemental feeding rates were lower for NT versus pharmacological treatments (p < 0.001). In post hoc subgroup analyses including only exclusively breastfed offspring, the risk of neonatal hypoglycemia was modified and similar among MT and NT, and higher in MIT versus NT. Insulin exposure, alone or combined with metformin, was associated with increased risk of being large for gestational age. Compared with NT, exposure to any pharmacological treatment was associated with significantly lower risk of 5-min Apgar score < 4. All other secondary outcomes were comparable among the treatment categories.Conclusions: The risk of neonatal hypoglycemia appears to be comparable among offspring exposed to single metformin treatment and nutrition therapy alone, and the lower risk that we observed in favor of metformin is probably explained by a difference in supplemental feeding practices rather than metformin per se. By contrast, the lower risk favoring metformin exposure over insulin exposure was not explained by supplemental feeding. However, further investigations are required to determine whether the difference is an effect of metformin per se or mediated by other external factors.
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| 8. |
- 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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| 9. |
- Pinola, Pekka, et al.
(författare)
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Androgen Profile Through Life in Women With Polycystic Ovary Syndrome : A Nordic Multicenter Collaboration Study
- 2015
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 100:9, s. 3400-3407
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Tidskriftsartikel (refereegranskat)abstract
- Context: Women with polycystic ovary syndrome (PCOS) have increased androgen secretion throughout fertile life; however, the data on the effect of menopause on hyperandrogenemia in these women are scarce. Nevertheless, large comprehensive comparative studies on age-related androgen levels in women with PCOS are lacking. Objective: The objective of the study was to investigate the effect of age on serum androgen levels in women with PCOS and to determine cutoff values for androgens and SHBG associated with a PCOS diagnosis. Design: This was a case-control study. Setting: The study was conducted in five university sites in the Nordic countries. Patients: In all, 681 women with PCOS and 230 referent women were grouped according to age into seven age groups (18 to > 50 y). Interventions: There were no interventions. Main Outcome measures: T, SHBG, free androgen index (FAI), calculated free T (cFT), androstenedione (A4), and dehydroepiandrosterone sulfate were measured. Results: Androgen levels in women with PCOS decreased with age toward menopause. The difference between women with PCOS and the referent women narrowed and individual variation increased as they approached menopause. T levels, FAI, and cFT were significantly higher in women with PCOS aged 18-44 years (P <.001, adjusted for body mass index). The best predictive factors for having PCOS were cFT (>= 0.40 ng/dL, odds ratio [OR] 7.90), FAI (>= 2.0, OR 6.71), and A4 (>= 277.94 ng/dL, OR 6.16). Conclusions: Women with PCOS had elevated serum androgen levels also after menopause. The parameters that best predicted PCOS at all ages were cFT, A4, and FAI.
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| 10. |
- Pinola, Pekka, et al.
(författare)
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Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life
- 2017
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Ingår i: Fertility and Sterility. - : ELSEVIER SCIENCE INC. - 0015-0282 .- 1556-5653. ; 107:3, s. 788-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Design: Case-control study. Setting: Not applicable. Patient(s): In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: < 30, 30-39, and > 39 years). Interventions(s): None. Main Outcome Measure(s): Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Result(s): Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two-to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. Conclusion(s): When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on.
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