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.
Introduction
The incidence of gestational diabetes mellitus (GDM) is globally increasing, and it has been associated with later type 2 diabetes, metabolic syndrome (MetS), and cardiovascular disease ...(CVD). However, long‐term population‐based studies investigating common CVD risk factors years after pregnancy are lacking. To evaluate the future mortality and morbidity in cardiovascular and metabolic diseases, we conducted a thorough investigation of midlife risk factors in women with and without previous GDM.
Material and Methods
A prospective population‐based cohort study was conducted of 3173 parous women from the Northern Finland Birth Cohort, 1966. Study participants were obtained from the national register or patient records. Those with a GDM diagnosis formed the GDM cohort (n = 271), and those without a previous GDM diagnosis formed the control cohort (n = 2902). Clinical examinations were performed on participants at the age of 46 and included anthropometric measurements, oral glucose tolerance test (OGTT), biochemical measurements, and cardiovascular assessment.
Results
At the age of 46, women in the GDM cohort had a higher body mass index (BMI, 29.0 kg/m2 vs 26.3 kg/m2, p < 0.001) and greater waist circumference (94.1 cm vs 86.5 cm, p < 0.001) than the control cohort. In the GDM cohort, a higher incidence of impaired glucose tolerance (12.6% vs 7.3%, p = 0.002), more previously diagnosed and OGTT‐detected type 2 diabetes (23.3% vs 3.9%, p < 0.001), lower high‐density lipoprotein (1.53 mmol/L vs 1.67 mmol/L, p = 0.011), higher triglycerides (1.26 mmol/L vs 1.05 mmol/L, p = 0.002) and a higher fatty liver index (6.82 vs 2.47, p < 0.001), were observed even after adjusting for BMI, polycystic ovary syndrome, parity, level of education, physical activity, smoking, and alcohol consumption. The women in the GDM cohort also had more MetS (42.6% vs 21.9%, p < 0.001) and higher risk scores for CVD and fatal events (Framingham 4.95 vs 3.60, p < 0.001; FINRISK 1.71 vs 1.08, p < 0.001).
Conclusions
Women with a previous diagnosis of GDM exhibit more risk factors for CVD in midlife and are at a higher risk for cardiovascular events later in life.
Previous gestational diabetes is associated with unfavorable metabolic alterations and an accumulation of risk factors for cardiovascular disease (CVD) in midlife. Assessment of CVD risk factors should be considered as part of the follow‐up program to prevent cardiovascular morbidity and mortality.
Introduction
This population‐based follow‐up study investigated the comorbidities, medication use, and healthcare services among women with polycystic ovary syndrome (PCOS) at age 46 years.
Material ...and methods
The study population derived from the Northern Finland Birth Cohort 1966 and consisted of women reporting oligo/amenorrhea and hirsutism at age 31 years and/or a PCOS diagnosis by age 46 years (n = 246) and controls without PCOS symptoms or diagnosis (n = 1573), referred to as non‐PCOS women. The main outcome measures were self‐reported data on symptoms, diagnosed diseases, and medication and healthcare service use at the age of 46 years.
Results
Overall morbidity risk was increased by 35% (risk ratio RR 1.35, 95% confidence interval CI 1.16–1.57) and medication use by 27% RR 1.27, 95% CI 1.08–1.50) compared with non‐PCOS women, and the risk remained after adjusting for body mass index. Diagnoses with increased prevalence in women with PCOS were migraine, hypertension, tendinitis, osteoarthritis, fractures, and endometriosis. PCOS was also associated with autoimmune diseases and recurrent upper respiratory tract infections and symptoms. Interestingly, healthcare service use did not differ between the study groups after adjusting for body mass index.
Conclusions
Women with PCOS are burdened with multimorbidity and higher medication use, independent of body mass index.
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.
Previous studies have shown good correlation between polycystic ovarian morphology (PCOM) and serum anti-Müllerian hormone (AMH) levels. We evaluated the utility of AMH as a surrogate for PCOM as a ...part of the polycystic ovary syndrome (PCOS) diagnosis by describing how the use of different AMH cut-off values would change the prevalence of PCOS.
A general population-based birth cohort study. Anti-Müllerian hormone concentrations were measured from serum samples taken at age 31 years (n = 2917) using the electrochemiluminescence immunoassay (Elecsys). Anti-Müllerian hormone data were combined with data on oligo/amenorrhoea and hyperandrogenism to identify women with PCOS.
The addition of AMH as a surrogate marker for PCOM increased the number of women fulfilling at least two PCOS features in accordance with the Rotterdam criteria. The prevalence of PCOS was 5.9% when using the AMH cut-off based on the 97.5% quartile (10.35 ng/mL) and 13.6% when using the recently proposed cut-off of 3.2 ng/mL. When using the latter cut-off value, the distribution of PCOS phenotypes A, B, C, and D was 23.9%, 4.7%, 36.6%, and 34.8%, respectively. Compared with the controls, all PCOS groups with different AMH concentration cut-offs showed significantly elevated testosterone (T), free androgen index (FAI), luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH) ratio, body mass index (BMI), waist circumference, and homoeostatic model assessment of insulin resistance (HOMA-IR) values, as well as significantly decreased sex hormone-binding globulin (SHBG) values.
Anti-Müllerian hormone could be useful surrogate for PCOM in large data sets, where transvaginal ultrasound is not feasible, to aid the capturing of women with typical PCOS characteristics. Anti-Müllerian hormone measurement from archived samples enables retrospective PCOS diagnosis when combined with oligo/amenorrhoea or hyperandrogenism.
Aims
We studied whether androgen excess and low sex hormone‐binding globulin (SHBG) measured in early pregnancy are independently associated with fasting and post‐prandial hyperglycaemia, gestational ...diabetes (GDM), and its severity.
Materials and Methods
This nationwide case–control study included 1045 women with GDM and 963 non‐diabetic pregnant controls. We measured testosterone (T) and SHBG from biobanked serum samples (mean 10.7 gestational weeks) and calculated the free androgen index (FAI). We first studied their associations with GDM and secondly with the type of hyperglycaemia (fasting, 1 and 2 h glucose concentrations during the oral glucose tolerance test), early‐onset GDM (<20 gestational weeks) and the need for anti‐diabetic medication.
Results
After adjustments for gestational weeks at sampling, pre‐pregnancy BMI, and age, women with GDM had 3.7% (95% CI 0.1%–7.3%) lower SHBG levels, 3.1% (95% CI 0.1%–6.2%) higher T levels, and 4.6% (95% CI 1.9%–7.3%) higher FAI levels than controls. SHBG was inversely associated with fasting glucose, whereas higher FAI and T were associated with higher post‐prandial glucose concentrations. Women with early‐onset GDM had 6.7% (95% CI 0.7%–12.7%) lower SHBG levels and women who needed insulin for fasting hyperglycaemia 8.7% (95% CI 1.8%–14.8%) lower SHBG levels than other women with GDM.
Conclusions
Lower SHBG levels were associated especially with early‐onset GDM, higher fasting glucose and insulin treatment, whereas androgen excess was associated with higher post‐prandial glucose values. Thus, a low SHBG level may reflect the degree of existing insulin resistance, while androgen excess might impair post‐prandial insulin secretion.
Introduction
Current use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on ...the risk of glucose metabolism disorders is still controversial.
Material and methods
This was a prospective, longitudinal birth cohort study with long‐term follow‐up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2‐h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin‐only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253).
Results
Compared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio OR 3.9, 95% confidence interval CI: 1.6–9.2) but not of type 2 diabetes mellitus. Former progestin‐only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol‐lowering medication.
Conclusions
Former long‐term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women.
Former long‐term use of CHCs was associated with prediabetes in perimenopausal women, which potentially indicates a need of glucose metabolism screening in these women and emphasizes the importance of considering contraception alternatives other than CHCs at later fertile age.
Introduction
The aim of the study was to determine the association of body mass index (BMI), self‐reported symptoms or diagnosis of polycystic ovary syndrome (PCOS), and hyperandrogenemia with the ...occurrence of gestational diabetes mellitus (GDM) through reproductive life.
Material and methods
A cohort of women born in 1966 were investigated at ages 14, 31 and 46. Women with self‐reported PCOS symptoms (presence of both oligo‐amenorrhea and hirsutism) at age 31 or with formally diagnosed polycystic ovaries (PCO)/PCOS by age 46 formed the group of self‐reported PCOS (srPCOS, n = 222) and were compared with women without self‐reported PCOS symptoms or diagnosis (n = 1357). We investigated also the association of hyperandrogenism (hirsutism or biochemical hyperandrogenism) at age 31 with the occurrence of GDM throughout reproductive life.
Results
Self‐reported PCOS alone was not a risk factor for GDM, but combined with overweight at age 31 (odds ratio OR 2.43, 95% confidence interval CI 1.22‐4.86) or 46 (OR 3.04, 95% CI 1.58‐5.83) srPCOS was associated with GDM when compared with normal weight controls. The association disappeared when comparing overweight srPCOS women with overweight controls. However, hyperandrogenemia at age 31, but not hirsutism, was associated with GDM even after adjustment for BMI.
Conclusions
The increased risk of GDM in women with srPCOS was mostly attributed to overweight or obesity. Importantly, normal weight women with srPCOS did not seem to be at increased risk for developing GDM. However, hyperandrogenemia was associated with GDM even after adjustment for BMI. These findings strengthen the importance of weight management in reproductive‐age women and suggest a noteworthy role of hyperandrogenemia in the pathophysiology of GDM.
Objective
Up to 70% of women with polycystic ovary syndrome (PCOS) have pre‐obesity or obesity. The aim of this study was to investigate whether women with PCOS have more weight‐loss attempts than ...women without PCOS, regardless of BMI. Moreover, women's weight perceptions in relation to previous weight‐loss attempts were evaluated.
Methods
A population‐based birth cohort study included women with (n = 278) and without PCOS (control individuals, n = 1560) who were examined at ages 31 and 46 years with questionnaires and clinical examinations.
Results
Women with PCOS had more weight‐loss attempts compared with control individuals at age 31 (47% vs. 34%, p < 0.001) and 46 years (63% vs. 47%, p < 0.001). At age 46 years, PCOS was associated with multiple weight‐loss attempts in the adjusted model (odds ratio: 1.43 95% CI: 1.00‐2.03, p = 0.05). The perception of having overweight was more prevalent in those with PCOS, even among participants with normal weight, at age 31 (PCOS 47% vs. control 34%, p = 0.014) and 46 years (PCOS 60% vs. control 39%, p = 0.001).
Conclusions
Women with PCOS were more likely to have experienced multiple weight‐loss attempts and a perception of having overweight compared with control individuals, regardless of obesity status.
Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances ...including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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