Low free testosterone levels are associated with all-cause and cardiovascular mortality in postmenopausal diabetic women.

OBJECTIVE: Hyperandrogenemia is associated with cardiovascular risk factors in women but evidence about the relationship of testosterone levels with mortality is sparse. We aimed to evaluate whether total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) are associated with all-cause and cardiovascular mortality in a cohort of postmenopausal women. RESEARCH DESIGN AND METHODS: We measured TT and SHBG levels in 875 postmenopausal women who were referred for coronary angiography (during 1997-2000). FT was calculated according to the Vermeulen method. The main outcome measures were Cox proportional hazard ratios (HRs) for mortality from all causes and from cardiovascular causes. RESULTS: After a median follow-up time of 7.7 years, 179 women (20.5%) had died. There were 101 deaths due to cardiovascular disease (56.4% of all deaths). We found no association of FT, TT, and SHBG levels with mortality in all postmenopausal women. In postmenopausal diabetic women, multivariable-adjusted HRs (with 95% CIs) in the fourth compared with the first FT quartile for all-cause and cardiovascular mortality were 0.38 (0.08-0.90), P = 0.025, and 0.28 (0.08-0.90), P = 0.032, respectively. We found no association of TT and SHBG with mortality in diabetic postmenopausal women. CONCLUSIONS: In postmenopausal diabetic women referred for coronary angiography, low FT levels are independently associated with increased all-cause and cardiovascular mortality.

The lipid accumulation product is associated with impaired glucose tolerance in PCOS women.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances. Lipid accumulation product (LAP) is an emerging cardiovascular risk factor. We aimed to investigate the association of LAP with impaired glucose tolerance (IGT) in PCOS and control women. METHODS: The LAP was calculated as [waist circumference (centimeters) - 58] × [triglycerides (millimoles per liter)] in 392 PCOS and 140 body mass index (BMI)-matched control women within the same age range. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed. RESULTS: PCOS women had significantly higher LAP levels than control women in age-adjusted analyses [22.2 (10.9-46.2) and 18.2 (10.7-36.3), respectively, P = 0.001). In PCOS and control women, age, BMI, blood pressure, fasting and stimulated glucose, fasting and stimulated insulin, and free testosterone progressively increased, whereas SHBG decreased across LAP quartiles. In PCOS and control women, receiver operating characteristic curve analysis revealed that the best cutoff value for LAP to define the presence of IGT was 44.1 and 41.8, respectively [sensitivity 79.5%, specificity 80.5%, and area under the curve (AUC) 0.86 and sensitivity 82.3%, specificity 90.5%, and AUC 0.86, respectively]. In PCOS and control women, receiver operating characteristic curve analyses for BMI (0.77 and 0.54, respectively) and waist circumference (0.80 and 0.72, respectively) to define IGT revealed lower AUC. Odds ratios for IGT for PCOS women in the highest LAP, BMI, and waist-to-hip ratio quartile were 41.81 (5.52-316.54), 10.24 (2.94-35.63), and 18.45 (4.19-81.30), respectively, when compared with PCOS women in the lowest LAP, BMI, and WHR quartile, respectively. CONCLUSION: LAP is an easily obtainable and cheap marker associated with IGT in PCOS and control women.

The lipid accumulation product is associated with increased mortality in normal weight postmenopausal women.

Lipid accumulation product (LAP) is an emerging cardiovascular risk factor, which is calculated from waist circumference (WC) and triglyceride (TG) levels. The aim of this study was to elucidate the relationship between LAP and cardiovascular mortality as well as the presence of type 2 diabetes with respect to gender-specific differences. We determined WC and fasting TG levels and the cardiovascular and metabolic phenotypes coronary artery disease (CAD), hypertension, metabolic syndrome, and diabetes mellitus in 2,279 men and 875 postmenopausal women who were routinely referred to coronary angiography. The LAP was calculated as (WC (cm)--65) × (TG (mmol/l)) for men and as (WC (cm)--58) × (TG (mmol/l)) for women. LAP levels were independently associated with congestive heart failure mortality in all postmenopausal women and with all-cause mortality in diabetic postmenopausal women but not in men. Multivariable-adjusted hazard ratios (with 95% confidence intervals) for all-cause, cardiovascular, and congestive heart failure mortality in the third compared to the first LAP tertile were 4.28 (1.94-9.44; P < 0.001), 3.47 (1.28-9.40; P = 0.015), and 10.77 (1.21-95.88; P = 0.033), respectively, in normal weight postmenopausal women, whereas no significant associations were found in men. LAP levels were highly associated with type 2 diabetes in all subjects, postmenopausal women, and men. High LAP values are predictive of mortality independently of other cardiovascular risk factors in normal weight and diabetic postmenopausal women but not in men. Type 2 diabetes (T2DM) was highly associated with LAP in women and men. Our study validates an inexpensive and simple risk profiling that may allow identifying postmenopausal women at high cardiovascular risk.

Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome.

INTRODUCTION: Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances including insulin resistance (IR), which might be related to vitamin D metabolism. We aimed to investigate the association of polymorphisms in the vitamin D receptor (VDR) gene as well as vitamin D level-associated genes with metabolic and endocrine parameters in PCOS women. Moreover, we examined whether there are associations with PCOS susceptibility. METHODS: Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed in 545 PCOS and 145 control women. Genotyping of VDR (Cdx2, Bsm-I, Fok-I, Apa-I, and Taq-I), GC, DHCR7, and CYP2R1 polymorphisms was performed. RESULTS: 25-Hydroxyvitamin D (25(OH)D) levels showed significant negative correlation with IR and positive correlation with insulin sensitivity (P<0.05 for all) in PCOS women. In PCOS women, the VDR Cdx2 'AA' genotype was associated with lower fasting insulin (P=0.039) and homeostatic model assessment-IR (P=0.041) and higher quantitative insulin-sensitivity check index (P=0.012) and MATSUDA index (P=0.003). The VDR Apa-I 'AA' genotype was associated with lower testosterone (P=0.028) levels. In PCOS women, 170 women (31.2%) presented with 25(OH)D levels <20 ng/ml. PCOS women carrying the GC 'GG' genotype and the DHCR7 'GG' genotype had a significantly higher risk for 25(OH)D levels <20 ng/ml (OR 2.53 (1.27-5.06), P=0.009, and OR 2.66 (1.08-6.55), P=0.033 respectively) compared with PCOS women carrying the GC 'TT' genotype and DHCR 'TT' genotype in multivariate analyses. We observed no association of genetic variations and PCOS susceptibility. CONCLUSION: VDR and vitamin D level-related variants are associated with metabolic and endocrine parameters including 25(OH)D levels in PCOS women.

Low free testosterone is associated with heart failure mortality in older men referred for coronary angiography.

AIMS: Accumulating evidence suggests that androgen deficiency is associated with cardiovascular disease. We aimed at evaluating whether total testosterone (TT) and free testosterone (FT) are associated with specific cardiovascular events. METHODS AND RESULTS: We measured TT and sex-hormone-binding globulin levels in 2078 men who were routinely referred for coronary angiography between 1997 and 2000. Free testosterone was calculated according to Vermeulen. Main outcome measures were Cox proportional hazard ratios (HRs) for sudden cardiac death, fatal myocardial infarction, death from congestive heart failure (CHF), as well as other cardiac deaths according to quartiles of TT and FT. The median follow-up time was 7.7 years. Multivariable adjusted HRs (with 95% confidence intervals) in the fourth compared with the first FT quartile and per 1 SD increase in FT for CHF mortality were 0.38 (0.17-0.87) and 0.37 (0.15-0.89), respectively. We observed no independent significant association of FT with sudden cardiac death, fatal myocardial infarction, or other cardiac death. There was no independent association of TT levels with cardiovascular events or cardiac disease. CONCLUSION: Low levels of FT are independently associated with increased CHF mortality.

Endocrinology of hirsutism.

Hirsutism represents a primary clinical indicator of androgen excess. The most common endocrine condition causing hirsutism is polycystic ovary syndrome (PCOS). Diagnosing PCOS is not easy as the signs and symptoms are heterogenous. The newest diagnostic guideline made by the Androgen Excess and PCOS Society in 2006, claims the presence of hyperandrogenism, and ovarian dysfunction (oligo / anovulation and / or polycystic ovaries). Obesity associated reproductive and metabolic dysfunctions may aggravate the symptoms of PCOS. PCOS might be underdiagnosed in non obese women because lean PCOS phenotypes might be underestimated for the syndrome. Effective medical treatment of PCOS and associated hirsutism depends on the endocrinological expertise and experience of the therapist in each individual case. An algorithm for the treatment has not been established yet.

Association of FTO gene with hyperandrogenemia and metabolic parameters in women with polycystic ovary syndrome.

Variants in the fat mass and obesity-associated gene (FTO) are associated with obesity and type 2 diabetes mellitus. Women with polycystic ovary syndrome (PCOS) are frequently affected by obesity and impaired glucose tolerance. The aim of this study was to investigate the impact of FTO variants (rs9939609) on metabolic and endocrine parameters in PCOS women. We genotyped the single nucleotide polymorphism rs9939609 (T/A) in 288 PCOS women and performed metabolic and hormonal measurements, oral glucose tolerance test, hirsutism score, and lipometry. The A/T + A/A genotype showed an increased prevalence in overweight/obese PCOS patients (odds ratio [OR] = 1.91, P = .028) and in PCOS women with impaired glucose tolerance (OR = 3.23, P = .009). The A allele was associated with a significant increase in free testosterone (P = .042), weight (P = .024), body mass index (P = .011), 2-hour glucose (P = .047), 1-hour insulin (P = .032), and AUCins (area under the curve insulin) (P = .038). In a logistic regression analysis, the A allele was associated with free testosterone (P = .025; OR = 1.54; 95% confidence interval, 1.06-2.25; B = 0.86). Total body fat (percentage) (P = .016), total fat mass (P = .013), visceral adipose tissue mass (P = .044), and subcutaneous fat mass (P = .011) were significantly increased in PCOS women carrying the A allele. We demonstrated that variants within the FTO gene influence hyperandrogenemia and anthropometric parameters in women with PCOS, indicating an important role of FTO variants not only in obesity and diabetes but also in hyperandrogenism in women with PCOS.

Subcutaneous adipose tissue topography and metabolic disturbances in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. Central obesity plays a major role in the pathophysiology of PCOS. However, there is little information on the impact of subcutaneous adipose tissue (SAT) on metabolic disturbances in PCOS. The aim of this study was to investigate whether SAT topography influences insulin resistance, impaired glucose tolerance and metabolic parameters in women with PCOS. METHODS: 36 women aged 16-41 years with PCOS and 87 healthy women aged 20-34 years were examined using lipometry, metabolic and hormonal measurements, oral glucose tolerance tests, hirsutism scores, and questionnaires. The homeostasis model assessment (HOMA) index was used for determination of insulin resistance. RESULTS: SAT measurement points on the trunk showed significant positive correlation with the HOMA index. A negative correlation between calf SAT and the HOMA index was seen. Multiple regression analysis detected a positive association between the HOMA index and lower-abdomen SAT and upper-back SAT, whereas hip SAT showed a negative association with the HOMA index. In overweight/obese patients with PCOS, lower-abdomen and upper-back SAT showed significant positive correlations with insulin resistance. There was no correlation of SAT topography with insulin resistance in lean women with PCOS. Compared with PCOS women with normal glucose tolerance, patients with glucose intolerance had significantly increased trunk obesity and decreased leg fat. Increased SAT layers on the trunk were related to an unfavorable serum lipid profile, whereas increased leg fat correlated positively with HDL cholesterol. CONCLUSIONS: Increased SAT layers on the trunk are associated with insulin resistance, impaired glucose tolerance and an unfavorable lipid profile in women suffering from PCOS. Increased thickness of leg SAT emerges as being protective against metabolic disturbances in PCOS.