Polycystic ovary syndrome in type 2 diabetes: does it predict a more severe phenotype?

OBJECTIVE: To examine the prevalence of a history of polycystic ovary syndrome (PCOS) in women with type 2 diabetes (DM2) and to compare metabolic and reproductive outcomes between women with and without PCOS. DESIGN: Cross-sectional study. SETTING: Tertiary hospital. PATIENT(S): Female inpatients age 18-75 years with DM2. INTERVENTION(S): A face-to-face questionnaire was administered. MAIN OUTCOME MEASURE(S): Age at diagnosis of diabetes, history of gestational diabetes, family history of diabetes, and reproductive history, fertility history, number of miscarriages, and morbidity in pregnancy. RESULT(S): One hundred seventy-one inpatients with DM2 participated. The prevalence of a history of PCOS was 37%. Women with PCOS had an earlier mean age of diagnosis of DM2 (44.2 vs. 48.8 years), higher recalled peak body mass index (BMI; 43.1 kg/m2 vs. 36.8 kg/m2), higher rate of gestational diabetes (28% vs. 18%), and higher rate of hypertension in pregnancy (40% vs. 22%). Women with PCOS were less likely to have a family history of DM2 than those without PCOS (45% vs. 67%). CONCLUSION(S): A history of PCOS in women with DM2 is associated with earlier onset of DM2, higher BMI, and a more severe phenotype. Since PCOS subjects were less likely to have a family history of DM2, lack of a family history of DM2 in women with PCOS is not reassuring for DM2 risk. We recommend identifying PCOS in early life and intervening to reduce the risk of diabetes and its comorbidities and suboptimal reproductive outcomes.

Clustering of metabolic and cardiovascular risk factors in the polycystic ovary syndrome: a principal component analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent condition with heterogeneity of clinical features and cardiovascular risk factors that implies multiple aetiological factors and possible outcomes. OBJECTIVE: To reduce a set of correlated variables to a smaller number of uncorrelated and interpretable factors that may delineate subgroups within PCOS or suggest pathogenetic mechanisms. MATERIALS AND METHODS: We used principal component analysis (PCA) to examine the endocrine and cardiometabolic variables associated with PCOS defined by the National Institutes of Health (NIH) criteria. Data were retrieved from the database of a single clinical endocrinologist. We included women with PCOS (N = 378) who were not taking the oral contraceptive pill or other sex hormones, lipid lowering medication, metformin or other medication that could influence the variables of interest. PCA was performed retaining those factors with eigenvalues of at least 1.0. Varimax rotation was used to produce interpretable factors. RESULTS: We identified three principal components. In component 1, the dominant variables were homeostatic model assessment (HOMA) index, body mass index (BMI), high density lipoprotein (HDL) cholesterol and sex hormone binding globulin (SHBG); in component 2, systolic blood pressure, low density lipoprotein (LDL) cholesterol and triglycerides; in component 3, total testosterone and LH/FSH ratio. These components explained 37%, 13% and 11% of the variance in the PCOS cohort respectively. CONCLUSIONS: Multiple correlated variables from patients with PCOS can be reduced to three uncorrelated components characterised by insulin resistance, dyslipidaemia/hypertension or hyperandrogenaemia. Clustering of risk factors is consistent with different pathogenetic pathways within PCOS and/or differing cardiometabolic outcomes.

Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy.

CONTEXT: There is an association between nonalcoholic fatty liver disease (NAFLD) and the polycystic ovary syndrome (PCOS). Marine-derived omega-3 fatty acids have favorable effects on cardiovascular risk and could reduce liver fat in NAFLD. OBJECTIVE: The primary aim of this study was to examine the effects of omega-3 fatty acids on liver fat in PCOS. The secondary aim was to assess their effects on traditional cardiovascular risk factors. DESIGN AND SETTING: We conducted a randomized, crossover study at a tertiary cardiovascular research center. SUBJECTS: Twenty-five women with PCOS (mean age, 32.7 yr; mean body mass index, 34.8 kg/m(2)) participated in the study. INTERVENTION: We compared 4g/d of omega-3 fatty acids with placebo over 8 wk. MAIN OUTCOME MEASURES: The primary outcome measure was hepatic fat content quantified using proton magnetic resonance spectroscopy. Secondary outcome measures included fasting lipids and blood pressure. RESULTS: Omega-3 fatty acids significantly decreased liver fat content compared with placebo [10.2 (1.1) vs. 8.4 (0.9)%; P = 0.022]. There was also a reduction in triglycerides [1.19 (1.03-1.47) vs. 1.02 (0.93-1.18) mmol/liter; P = 0.002], systolic blood pressure [124.1 (12.1) vs. 122.3 (14.5) mm Hg; P = 0.018], and diastolic blood pressure [73.2 (8.4) vs. 69.7 (8.3) mm Hg; P = 0.005] with omega-3 fatty acids compared with placebo. Omega-3 fatty acids particularly decreased hepatic fat in women with hepatic steatosis, defined as liver fat percentage greater than 5% [18.2 (11.1) vs. 14.8 (9.3)%; P = 0.03]. CONCLUSIONS: Omega-3 fatty acid supplementation has a beneficial effect on liver fat content and other cardiovascular risk factors in women with PCOS, including those with hepatic steatosis. Whether this translates into a reduction in cardiometabolic events warrants further study.

Dissociation of endothelial function and arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS).

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with cardiovascular risk but it is not clear if this is independent of obesity and insulin resistance. This study therefore investigates endothelial function and arterial stiffness in nonobese, noninsulin resistant women with PCOS. DESIGN: This is cross-sectional case-control study. PATIENTS: A total of 19 young women with PCOS, with body mass index (BMI) <30 kg/m(2), and 19 healthy controls matched for age and BMI were included in the study. MEASUREMENTS: Endothelial function was assessed with flow mediated dilatation (FMD) of the brachial artery, while arterial stiffness was assessed with pulse wave velocity (PWV) and augmentation index (AI). RESULTS: There were no significant differences between PCOS and control subjects when assessing the following clinical and biochemical variables: blood pressure, homeostasis model assessment insulin-resistance index, lipids and oestradiol. Women with PCOS had higher free androgen index scores (5.14 ± 3.47 vs. 3.25 ± 1.42, P = 0.036). The PCOS subjects had significantly lower FMD of the brachial artery compared with the controls (6.5 ± 2.9%vs. 10.5 ± 4.0%, P < 0.01). There were no significant differences in markers of arterial stiffness (PWV 5.8 ± 1.1 vs. 6.0 ± 1.0, P = 0.58, AI 16.5 ± 10.2 vs. 20.3 ± 10.2, P = 0.25). CONCLUSIONS: Women with polycystic ovary syndrome who are young, nonobese, and have no biochemical evidence of insulin resistance, have abnormal vascular function, but normal arterial stiffness, when compared with age and weight matched control subjects. Whether this leads to a greater risk of cardiovascular disease requires further investigation.

Cardiometabolic risk in polycystic ovary syndrome: a comparison of different approaches to defining the metabolic syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and features in common with the metabolic syndrome (MetS)--factors shown to predict cardiovascular risk and type 2 diabetes. We investigated the prevalence and characteristics of the MetS in PCOS by three definitions-World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III) and International Diabetes Federation (IDF)--and compared that with the background population. METHODS: Cross-sectional study of 168 women with PCOS and 883 age-matched controls from the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. RESULTS: Prevalence of the MetS in PCOS subjects was 33% by WHO, 37% by NCEP-ATP-III and 40% by IDF criteria, compared with 10% by NCEP-ATP-III and 13% by IDF in controls (P < 0.001). MetS by WHO criteria was not calculated in the AusDiab population. Age was an independent predictor of MetS in PCOS and controls. The prevalence of MetS was significantly higher among those with PCOS (P = 0.027) in obese women (BMI > 30 kg/m(2)), and higher but not significantly so in overweight (BMI 25-30 kg/m(2)) women (P = 0.052). Dehydroepiandrosterone sulphate was associated with a lower risk of the MetS--Odds ratio 0.86 (95% confidence interval, 0.77-0.97, P = 0.011). CONCLUSIONS: An approximate 4-fold increase in the prevalence of the MetS in women with PCOS compared with the general population, consistent with the proposed major role of insulin and obesity in the syndrome, implies greater risk of cardiometabolic disease in women with PCOS. However, this estimate is likely to vary according to PCOS definition, ethnicity and different aetiological pathways to PCOS.

Metabolic syndrome and cardiometabolic risk in PCOS.

The cardiovascular risk associated with the polycystic ovary syndrome (PCOS) has recently attracted much interest. Women with PCOS are more likely to fulfill the diagnosis of the metabolic syndrome, a cluster of related cardiometabolic factors known to predict long-term risk of cardiovascular disease and type 2 diabetes. We review the literature pertaining to the link between the metabolic syndrome, cardiovascular disease, and PCOS. We focus on the influence of obesity and hyperandrogenemia, and on strategies for identifying cardiovascular risk in PCOS.

Cardiovascular disease in the polycystic ovary syndrome: new insights and perspectives.

The new millennium has brought intense focus of interest on the risk of cardiovascular disease in women. The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women characterised by hyperandrogenism and oligomenorrhoea. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Echocardiography, imaging of coronary and carotid arteries, and assessments of both endothelial function and arterial stiffness have recently been employed to address this question. These studies have collectively demonstrated both structural and functional abnormalities of the cardiovascular system in PCOS. These alterations, however, appear to be related to the presence of individual cardiovascular risk factors, particularly insulin resistance, rather than to the presence of PCOS and hyperandrogenaemia per se. However, given the inferential nature of the evidence to date, more rigorous cohort studies of long-term cardiovascular outcomes and clinical trials of risk factor modification are required in women with PCOS.

Polycystic ovarian syndrome: marked differences between endocrinologists and gynaecologists in diagnosis and management.

BACKGROUND: Women with polycystic ovarian syndrome (PCOS) commonly consult endocrinologists or gynaecologists and it is not known whether these specialty groups differ in their approach to management. OBJECTIVE: To compare the investigation, diagnosis and treatment practices of endocrinologists and gynaecologists who treat PCOS. DESIGN AND SETTING: A mailed questionnaire containing a hypothetical patient's case history with varying presentations--oligomenorrhoea, hirsutism, infertility and obesity--was sent to Australian clinical endocrinologists and gynaecologists in teaching hospitals and private practice. RESULTS: Evaluable responses were obtained from 138 endocrinologists and 172 gynaecologists. The two specialty groups differed in their choice of essential diagnostic criteria and investigations. Endocrinologists regarded androgenization (81%) and menstrual irregularity (70%) as essential diagnostic criteria, whereas gynaecologists required polycystic ovaries (61%), androgenization (59%), menstrual irregularity (47%) and an elevated LH/FSH ratio (47%) (all P-values < 0.001). In investigation, gynaecologists were more likely to request ovarian ultrasound (91%vs. 44%, P < 0.001) and endocrinologists more likely to measure adrenal androgens (80%vs. 58%, P < 0.001) and lipids (67%vs. 34%, P < 0.001). Gynaecologists were less likely to assess glucose homeostasis but more likely to use a glucose tolerance test to do so. Diet and exercise were chosen by most respondents as first-line treatment for all presentations. However, endocrinologists were more likely to use insulin sensitizers, particularly metformin, for these indications. In particular, for infertility, endocrinologists favoured metformin treatment whereas gynaecologists recommended clomiphene. CONCLUSIONS: There is a lack of consensus between endocrinologists and gynaecologists in the definition, diagnosis and treatment of PCOS. As a consequence, women may receive a different diagnosis or treatment depending on the type of specialist consulted.

Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism.

T(4) is standard treatment for hypothyroidism. A recent study reported that combined T(4)/liothyronine (T(3)) treatment improved well-being and cognitive function compared with T(4) alone. We conducted a double-blind, randomized, controlled trial with a crossover design in 110 patients (101 completers) with primary hypothyroidism in which liothyronine 10 micro g was substituted for 50 micro g of the patients' usual T(4) dose. No significant (P < 0.05) difference between T(4) and combined T(4)/T(3) treatment was demonstrated on cognitive function, quality of life scores, Thyroid Symptom Questionnaire scores, subjective satisfaction with treatment, or eight of 10 visual analog scales assessing symptoms. For the General Health Questionnaire-28 and visual analog scales assessing anxiety and nausea, scores were significantly (P < 0.05) worse for combined treatment than for T(4) alone. Serum TSH was lower during T(4) treatment than during combined T(4)/T(3) treatment (mean +/- SEM, 1.5 +/- 0.2 vs. 3.1 +/- 0.2 mU/liter; P < 0.001), a potentially confounding factor; however, subgroup analysis of subjects with comparable serum TSH concentrations during each treatment showed no benefit from combined treatment compared with T(4) alone. We conclude that in the doses used in this study, combined T(4)/T(3) treatment does not improve well-being, cognitive function, or quality of life compared with T(4) alone.

Brown-Séquard revisited: a lesson from history on the placebo effect of androgen treatment.

BACKGROUND: In 1889, Brown-Séquard, aged 72, reported dramatic rejuvenating effects after self-administering testicular extracts of dogs and guinea-pigs. His report resulted in widespread use of testicular extracts throughout Europe and North America for several decades. More recently, the male ageing process has been attributed to partial androgen deficiency, or "andropause", and testosterone treatment is claimed to improve well-being in middle-aged and elderly men. DESIGN: We prepared extracts from five dog testes using Brown-Séquard's methods and assayed testosterone concentrations. RESULTS: Testosterone concentrations were four orders of magnitude less than that required for a biological effect. CONCLUSIONS: Our study illustrates the marked placebo response that can be evoked by androgen treatment. It cautions against the empirical use of testosterone treatment for older men, unless a diagnosis of hypogonadism has been substantiated.