| 1. |
- Coviello, Andrea D, et al.
(författare)
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4×10(-11)), GCKR (rs780093, 2p23.3, p = 2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5×10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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| 2. |
- Lingaiah, Shilpa, et al.
(författare)
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Bone markers in polycystic ovary syndrome : A multicentre study
- 2017
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Ingår i: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265. ; 87:6, s. 673-679
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hyperandrogenism, hyperinsulinaemia and obesity, known characteristics of polycystic ovary syndrome (PCOS), may influence bone mineral density and biochemical markers of bone turnover (BTMs) can provide a noninvasive assessment of bone turnover. To this end, the serum concentrations of BTMs and 25-hydroxyvitamin D (25OHD) were analysed in women with PCOS, and their possible associations with metabolic parameters of PCOS were determined.Subjects and methods: Bone formation markers procollagen type I amino-terminal propeptide (PINP) and osteocalcin (OC), and bone resorption marker carboxy-terminal cross-linking telopeptide of type I collagen (CTX), along with 25OHD, were measured in 298 women with PCOS and 194 healthy controls.Results: Serum levels of PINP (47.020.2 vs 58.1 +/- 28.6g/L, P<.001) and OC (18.2 +/- 7.5 vs 20.6 +/- 9.8g/L, P<.001) were decreased in women with PCOS compared with controls, whereas no significant differences were found in CTX and 25OHD levels. Age-stratified analyses suggested that PINP (50.5 +/- 21.7 vs 68.2 +/- 26.6g/L, P<.001) and OC levels (20.4 +/- 7.6 vs 25.5 +/- 9.6g/L, P<.001) were decreased only in the younger age group (30years) women with PCOS compared with controls. The formation markers and resorption marker decreased with age in both study groups.Conclusions: Bone formation markers were decreased in younger women with PCOS when compared with healthy women, which may affect bone mass in these women.
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| 3. |
- Lingaiah, Shilpa, et al.
(författare)
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Serum retinol-binding protein 4 levels in polycystic ovary syndrome
- 2019
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 8:6, s. 709-717
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Serum levels of retinol-binding protein 4 (RBP4), an adipokine thought to affect systemic insulin sensitivity, were compared between women with polycystic ovary syndrome (PCOS) and non-PCOS controls to evaluate the association of RBP4 with clinical, hormonal and metabolic parameters of PCOS. Subjects and methods: Serum RBP4 levels were analysed in 278 women with PCOS (age range 18-57 years) and 191 non-PCOS controls (age 20-53 years) by enzyme-linked immunosorbent assay. Results: Serum levels of RBP4 were increased in women with PCOS compared with control women in the whole population (45.1 +/- 24.0 (S.D.) vs 33.5 +/- 18.3 mg/L, P < 0.001). Age-stratified analysis showed that serum RBP4 levels were increased in women with PCOS aged <= 30 years compared with controls (47.7 +/- 23.5 vs 27.1 +/- 10.4 mg/L, P < 0.001), whereas no significant differences were seen in the other age groups. No significant correlations of RBP4 were seen with either steroids or indices of insulin resistance. Conclusions: Although serum RBP4 levels were increased in younger women with PCOS compared with age-matched non-PCOS controls, RBP4 does not seem to be a good marker of insulin resistance or other metabolic derangements in women with PCOS.
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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. |
- Pelanis, Rasa, et al.
(författare)
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The prevalence of Type 2 diabetes is not increased in normal-weight women with PCOS
- 2017
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Ingår i: Human Reproduction. - : OXFORD UNIV PRESS. - 0268-1161 .- 1460-2350. ; 32:11, s. 2279-2286
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is oral glucose tolerance test (OGTT) needed in all women with polycystic ovary syndrome (PCOS)? SUMMARY QNSWER: OGTT is not routinely needed in women with PCOS and BMI < 25 kg/m(2). WHAT IS KNOWN ALREADY: PCOS is associated with insulin resistance and increased prevalence of prediabetes and Type 2 diabetes (T2D) which is closely linked to obesity and possibly age, ethnicity and PCOS phenotype. Several guidelines recommend OGTT upon diagnosis of PCOS and during follow-up. STUDY DESIGN, SIZE, DURATION: A Nordic cross-sectional study including 876 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 876 Nordic women with PCOS, aged 14-57 years, were examined for T2D and prediabetes (impaired glucose tolerance [IGT] or impaired fasting glucose (IFG) by OGTT. MAIN RESULT AND THE ROLE OF CHANCE: Of all study subjects 3% (23/876) had T2D, 23% (204/876) prediabetes and 74% (649/876) had normal glucose tolerance (NGT). Increased BMI and waist circumference were significantly (P < 0.001) associated with prevalence of prediabetes and T2D. No normal-weight woman (BMI < 25 kg/m(2)) was diagnosed with (TD)-D-2. The prevalence of BMI >= 25 kg/m(2) was 66% (578/876). 91% of women (21/23) with T2D had BMI >= 30 kg/m(2). Testosterone levels and PCOS phenotype did not predict 2-h glucose levels during OGTT after adjustment for BMI and age. LIMITATIONS, REASONS FOR CAUTION: The present study included cross-sectional data and prospective studies are needed to confirm our results. These results may not apply to populations of other ethnic origin. WIDER IMPLICATIONS OF THE FINDINGS: Routine OGTT may not be indicated in normal-weight women with PCOS.
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| 6. |
- 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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| 7. |
- Piltonen, Terhi T., et al.
(författare)
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Circulating antimüllerian hormone and steroid hormone levels remain high in pregnant women with polycystic ovary syndrome at term
- 2019
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 111:3, s. 588-596.e1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate plasma antimullerian hormone (AMH) concentration and its relation to steroid hormone levels in pregnant women with polycystic ovary syndrome (PCOS) and controls at term.Design: Case-control study.Setting: University-affiliated hospital.Patient(s): A total of 74 pregnant women at term: 25 women with PCOS (aged 31.6 ± 3.9 years [mean ± standard deviation], body mass index 24.0 ± 3.9 kg/m2, mean gestational length 279 ± 9 days) and 49 controls (aged 31.7 ± 3.3 years, body mass index 24.0 ± 3.3 kg/m2, mean gestational length 281 ± 9 days).Intervention(s): None.Main Outcome Measure(s): Plasma AMH and steroid hormone levels.Result(s): Antimullerian hormone, T, and androstenedione levels were higher in women with PCOS at term compared with controls, whereas estrogen and P levels were similar. The differences were pronounced in women carrying a female fetus. Testosterone and AMH levels correlated positively in both groups, but E2 levels only in women with PCOS.Conclusion(s): Pregnant women with PCOS present with elevated AMH and androgen levels even at term, suggesting a hormonal imbalance during PCOS pregnancy. Differences were detected especially in pregnancies with a female fetus, raising the question of whether female pregnancies are more susceptible to AMH and steroid hormone actions.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Rodriguez-Wallberg, Kenny A., et al.
(författare)
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Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries - compilation of 20 years of multicenter experience
- 2016
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY-BLACKWELL. - 0001-6349 .- 1600-0412. ; 95:9, s. 1015-1026
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. The aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries. Material and methods. A questionnaire was sent to 14 Nordic academic reproductive centers with established fertility preservation programs. It covered fertility preservation cases performed up to December 2014, standard procedures for ovarian tissue cryopreservation and oocyte cryopreservation and reproductive outcomes following ovarian tissue transplantation. Results. Among the Nordic countries, Denmark and Norway practice ovarian tissue cryopreservation as a clinical treatment (822 and 164 cases, respectively) and their programs are centralized. In Sweden (457 cases), ovarian tissue cryopreservation is practiced at five of six centers and in Finland at all five centers (145 cases). Nearly all considered ovarian tissue cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow-freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue was predominantly retrieved laparoscopically by unilateral oophorectomy. Only minor complications were reported. In total, 46 women have undergone ovarian tissue transplantation aiming at recovering fertility, 17 healthy children have been born and several additional pregnancies are currently ongoing. Whenever patients' clinical condition is permissive, oocyte cryopreservation after hormonal stimulation is preferred for fertility preservation. Between 2012 and 2014, a smaller proportion of females have undergone fertility preservation in the Nordic centers, in comparison to males (1: 3). Conclusions. Overall, ovarian tissue cryopreservation was reported to be safe. Slow freezing methods are still preferred. Promising results of recovery of fertility have been reported in Nordic countries that have initiated ovarian tissue transplantation procedures.
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