► PCOS, a heritable yet common cause of ovarian infertility is an evolutionary paradox. ► This paradox has spawned a number of evolutionary hypotheses, which here are appraised. ► The concurrence of ...metabolic and reproductive elements in PCOS is the key to evolutionary understanding. ► Human reproductive ecology and nutritional history have shaped vulnerability to PCOS. ► Fertility selection has the power to rapidly reduce PCOS prevalence.
The Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder characterised both by reproductive and metabolic disturbance, and is the most common cause globally of ovarian infertility. It is also a familial polygenic condition, linked genetically to both Type 2 diabetes and the metabolic syndrome. The striking evolutionary paradox of this prominent genetically-based condition, which impairs fertility, is that not only should it have diminished in prevalence, but it should have done so rapidly – unless there has been some form of balancing selection. The emerging discipline of evolutionary medicine can provide important insights into the causes and patterns of occurrence of common diseases such as PCOS. In this paper we review the impacts of PCOS on infertility, fecundability and lifetime reproductive success and then critically appraise published hypotheses about the evolutionary origins of PCOS and related conditions.
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.
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.
OBJECTIVEThe aim of the study was to investigate are there associations between common female sex-specific health conditions (oligo/amenorrhea, hyperandrogenism, menopause and polycystic ovary ...syndrome PCOS) and high-sensitivity troponin-T (hs-TnT) levels.METHODSCross-sectional and longitudinal analyses of a general population-based prospective cohort study were performed. The hs-TnT levels of 3146 women aged 46 were measured using an Elecsys® Troponin T high-sensitivity assay. Median hs-TnT levels and 25 and 75 percentiles of the cases and controls were compared. Also, a logistic regression analysis using a binary outcome - undetectable hs-TnT (< 3.0 ng/L) versus detectable hs-TnT (≥ 3.0 ng/L) - was performed.RESULTSWomen with oligo/amenorrhea at age 31 had significantly higher hs-TnT levels at age 46 than women without oligo/amenorrhea (4.06 3.59; 4.86 vs 3.98 3.44; 4.71 ng/L, p = .042). Menopausal women had significantly higher hs-TnT levels than premenopausal women (4.15 3.54; 4.91 vs 3.95 3.45; 4.68 ng/L, p = .012) at age 46. Women with PCOS or hyperandrogenism had comparable hs-TnT levels with their controls. In the adjusted logistic regression analysis, oligo/amenorrhea (odds ratio OR = 1.52 0.90-2.57), hyperandrogenism (OR = 1.20 0.75-1.92), PCOS (OR = 1.51 0.81-2.84) and menopause (OR = 1.05 0.63-1.74) were not significantly associated with detectable hs-TnT.CONCLUSIONSThis study was the first to investigate how oligo/amenorrhea, hyperandrogenism, PCOS and menopause are associated with hs-TnT. Although women with oligo/amenorrhea and menopause had higher hs-TnT levels than women without these conditions, the difference was small. Larger studies are required to better understand the effects of oligo/amenorrhea on cardiovascular health.
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.
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.
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.
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).
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective To investigate whether the systemic inflammation induced by chlamydial infections might be associated with symptoms of polycystic ovary syndrome (PCOS). Design Nested case-control study. ...Setting A questionnaire including questions about hirsutism and oligo-amenorrhea was distributed to a representative sample of women (at age 31) from the general population-based Northern Finland Birth Cohort. Those who reported both symptoms were defined as symptomatic (n = 81). Patient(s) A representative sample of women (at age 31) from the general population-based Northern Finland Birth Cohort. Intervention(s) None. Main Outcome Measure(s) To test the presence of serum antibodies to Chlamydia pneumoniae (IgG titers ≥32) and Chlamydia trachomatis (IgG titers ≥8) by microimmunofluorescence in symptomatic and control women. Result(s) Antibodies were investigated in 79 symptomatic and 1427 control women ( C. pneumoniae ) and in 79 symptomatic and 425 control women ( C trachomatis ). C. trachomatis antibodies (odds ratio OR, 2.4; 95% confidence interval CI, 1.3–4.6) and C. pneumoniae antibodies (OR, 1.5; 95% CI, 1.0–2.4) were more commonly present in symptomatic women, and the simultaneous presence of elevated highly sensitive C-reactive protein levels strengthened this association. Conclusion(s) Chronic inflammation, which is associated with chlamydial infections, could contribute to the pathogenetic processes that lead to the metabolic and hormonal disorders of PCOS.
Abstract
Ceramides contribute to the development of type 2 diabetes but it is uncertain whether they predict gestational diabetes (GDM). In this multicentre case–control study including 1040 women ...with GDM and 958 non-diabetic controls, early pregnancy (mean 10.7 gestational weeks) concentrations of four ceramides—Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)—were determined by a validated mass-spectrometric method from biobanked serum samples. Traditional lipids including total cholesterol, LDL, HDL and triglycerides were measured. Logistic and linear regression and the LASSO logistic regression were used to analyse lipids and clinical risk factors in the prediction of GDM. The concentrations of four targeted ceramides and total cholesterol, LDL and triglycerides were higher and HDL was lower among women with subsequent GDM than among controls. After adjustments, Cer(d18:1/24:0), triglycerides and LDL were independent predictors of GDM, women in their highest quartile had 1.44-fold (95% CI 1.07–1.95), 2.17-fold (95% CI 1.57–3.00) and 1.63-fold (95% CI 1.19–2.24) odds for GDM when compared to their lowest quartiles, respectively. In the LASSO regression modelling ceramides did not appear to markedly improve the predictive performance for GDM alongside with clinical risk factors and triglycerides. However, their adverse alterations highlight the extent of metabolic disturbances involved in GDM.
Background Polycystic ovary syndrome is a heterogeneous disorder and its presentation varies with race and ethnicity. Reproductive-age women with polycystic ovary syndrome are at increased risk of ...metabolic syndrome; however, it is not clear if prevalence of metabolic syndrome and clustering of its components differs based on race and ethnicity. Moreover, the majority of these women do not undergo routine screening for metabolic syndrome. Objective We sought to compare the prevalence of metabolic syndrome and clustering of its components in women with polycystic ovary syndrome in the United States with women in India, Brazil, Finland, and Norway. Study Design This is a cross-sectional study performed in 1089 women with polycystic ovary syndrome from 1999 through 2016 in 5 outpatient clinics in the United States, India, Brazil, Finland, and Norway. Polycystic ovary syndrome was defined by the Rotterdam criteria. Main outcome measures were: metabolic syndrome prevalence, blood pressure, body mass index, fasting high-density lipoprotein cholesterol, fasting triglycerides, and fasting glucose. Data from all sites were reevaluated for appropriate application of diagnostic criteria for polycystic ovary syndrome, identification of polycystic ovary syndrome phenotype, and complete metabolic workup. The US white women with polycystic ovary syndrome were used as the referent group. Logistic regression models were used to evaluate associations between race and metabolic syndrome prevalence and its components and to adjust for potential confounders, including age and body mass index. Results The median age of the entire cohort was 28 years. Women from India had the highest mean Ferriman-Gallwey score for clinical hyperandrogenism (15.6 ± 6.5, P < .001). The age-adjusted odds ratio for metabolic syndrome was highest in US black women at 4.52 (95% confidence interval, 2.46–8.35) compared with US white women. When adjusted for age and body mass index, the prevalence was similar in the 2 groups. Significantly more black women met body mass index and blood pressure criteria ( P < .001), and fewer met fasting triglycerides criteria ( P < .05). The age- and body mass index–adjusted prevalence of metabolic syndrome was highest in Indian women (odds ratio, 6.53; 95% confidence interval, 3.47–12.30) with abnormalities in glucose and fasting high-density lipoprotein cholesterol criterion and in Norwegian women (odds ratio, 2.16; 95% confidence interval, 1.17–3.98) with abnormalities in blood pressure, glucose, and fasting high-density lipoprotein cholesterol criterion. The Brazilian and Finnish cohorts had similar prevalence of metabolic syndrome and its components compared to US white women. Conclusion Despite a unifying diagnosis of polycystic ovary syndrome, there are significant differences in the prevalence of metabolic syndrome and clustering of its components based on race and ethnicity, which may reflect contributions from both racial and environmental factors. Our findings indicate the prevalence of metabolic syndrome components varies in women with polycystic ovary syndrome, such that compared to Caucasian women from the United States, black US women had the highest prevalence, whereas women from India and Norway had a higher prevalence of metabolic syndrome independent of obesity. The differences in clustering of components of metabolic syndrome based on ethnicity highlight the need to routinely perform complete metabolic screening to identify specific targets for cardiovascular risk reduction strategies in these reproductive-age women.
The purpose of this prospective, population-based cohort study was to evaluate the roles of polycystic ovary syndrome (PCOS), obesity, weight gain, and hyperandrogenemia in the development of ...hypertensive disorders of pregnancy (HDP) through fertile age both in PCOS and in non-PCOS women. The study population-NFBC1966 (Northern Finland Birth Cohort 1966)-allowed a long-term follow-up of women from age 14 until 46 years who developed HDP (n=408) or did not (n=3373). HDP diagnosis was confirmed by combining hospital discharge records, data from Finnish Medical Birth Registers, and the questionnaire data at age 46. Women with self-reported PCOS (srPCOS; n=279), defined by both oligo-amenorrhea and hirsutism at age 31 or with PCOS diagnosis by age 46, were compared with women without reported PCOS (n=1577). Women with srPCOS had an increased HDP risk (odds ratio, 1.56 95% CI, 1.03-2.37), but the association disappeared after adjustment for body mass index. In women with srPCOS and HDP, body mass index increased from age 14 to 46 significantly more than in srPCOS women without HDP (median interquartile range, 9.82 6.23-14.6 and 7.21 4.16-10.5 kg/m
, respectively;
<0.001). Also, in non-PCOS women, the increase was higher in women with (7.54 5.32-11.62 kg/m
;
<0.001) than without HDP (6.33 3.90-9.33 kg/m
;
<0.001). Increase in waist circumference between ages 31 and 46 years was associated with HDP but not with PCOS. Hyperandrogenemia at 31 or 46 years did not associate with HDP (1.44 0.98-2.11). In conclusion, obesity, especially abdominal obesity, and weight gain from adolescence to age 46, but not srPCOS or hyperandrogenemia, were associated with an increased risk of HDP.
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