Elisabeth Wehr

Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome

OBJECTIVES Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances, in particular from insulin resistance. Accumulating evidence suggests that vitamin D deficiency may contribute to the development of the metabolic syndrome (MS). Hence, the aim of our study was to investigate the association of 25(OH)D levels and the components of the MS in PCOS women. METHODS 25(OH)D levels were measured by means of ELISA in 206 women affected by PCOS. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed. RESULTS The prevalence of insufficient 25(OH)D levels (<30 ng/ml) was 72.8% in women with PCOS. PCOS women with the MS had lower 25(OH)D levels than PCOS women without these features (17.3 vs 25.8 ng/ml respectively; P<0.05). In multivariate regression analysis including 25(OH)D, season, body mass index (BMI), and age, 25(OH)D and BMI were independent predictors of homeostatic model assessment-insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI; P<0.05 for all). In binary logistic regression analyses, 25(OH)D (OR 0.86, P=0.019) and BMI (OR 1.28, P<0.001) were independent predictors of the MS in PCOS women. We found significantly negative correlations of 25(OH)D levels with BMI, waist circumference, waist-to-hip ratio, systolic and diastolic blood pressure, fasting and stimulated glucose, area under the glucose response curve, fasting insulin, HOMA-IR, HOMA-beta, triglycerides, and quotient total cholesterol/high-density lipoprotein (HDL) and positive correlations of 25(OH)D levels with QUICKI and HDL (P<0.05 for all). CONCLUSION We demonstrate that low 25(OH)D levels are associated with features of the MS in PCOS women. Large intervention trials are warranted to evaluate the effect of vitamin D supplementation on metabolic disturbances in PCOS women.

Association of vitamin D status with serum androgen levels in men.

Objective  Studies in rodents indicate a role of vitamin D in male reproduction, but the relationship between vitamin D and androgen levels in men is largely unexplored. We aimed to investigate the association of 25‐hydroxyvitamin D [25(OH)D] levels with testosterone, free androgen index (FAI) and SHBG. Moreover, we examined whether androgen levels show a similar seasonal variation to 25(OH)D.

Effect of vitamin D supplementation on testosterone levels in men.

The male reproductive tract has been identified as a target tissue for vitamin D, and previous data suggest an association of 25-hydroxyvitamin D [25(OH)D] with testosterone levels in men. We therefore aimed to evaluate whether vitamin D supplementation influences testosterone levels in men. Healthy overweight men undergoing a weight reduction program who participated in a randomized controlled trial were analyzed for testosterone levels. The entire study included 200 nondiabetic subjects, of whom 165 participants (54 men) completed the trial. Participants received either 83 μg (3,332 IU) vitamin D daily for 1 year (n = 31) or placebo (n =2 3). Initial 25(OH)D concentrations were in the deficiency range (< 50 nmol/l) and testosterone values were at the lower end of the reference range (9.09-55.28 nmol/l for males aged 20-49 years) in both groups. Mean circulating 25(OH)D concentrations increased significantly by 53.5 nmol/l in the vitamin D group, but remained almost constant in the placebo group. Compared to baseline values, a significant increase in total testosterone levels (from 10.7 ± 3.9 nmol/l to 13.4 ± 4.7 nmol/l; p < 0.001), bioactive testosterone (from 5.21 ± 1.87 nmol/l to 6.25 ± 2.01 nmol/l; p = 0.001), and free testosterone levels (from 0.222 ± 0.080 nmol/l to 0.267 ± 0.087 nmol/l; p = 0.001) were observed in the vitamin D supplemented group. By contrast, there was no significant change in any testosterone measure in the placebo group. Our results suggest that vitamin D supplementation might increase testosterone levels. Further randomized controlled trials are warranted to confirm this hypothesis.

Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: A pilot study

Background: Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances, in particular from insulin resistance. Accumulating evidence suggests that vitamin D deficiency may contribute to the development of insulin resistance. Hence, we aimed to examine the effect of vitamin D supplementation on metabolic and endocrine parameters in PCOS women. Methods: Fifty-seven PCOS women were included in the study. PCOS women received 20,000 IU cholecalciferol weekly for 24 weeks. Anthropometric measures, oral glucose tolerance test, and blood analyses of endocrine parameters were performed at baseline and after 12 weeks (V2) and 24 weeks (V3). Results: Forty-six PCOS women finished the study. 25-hydroxyvitamin D [25(OH)D] levels significantly increased from 28.0±11.0 ng/ml at baseline to 51.3±17.3 and 52.4±21.5 at V2 and V3, respectively (p<0.001). We observed a significant decrease of fasting and stimulated glucose (V3, p<0.05) and C-peptide levels (V2 and 3, p<0.001) after vitamin D treatment. Moreover, triglyceride and estradiol levels significantly decreased at V3 (p=0.001) and V2 (p=0.022), respectively, whereas total cholesterol (V2, p=0.008) and LDL cholesterol levels (V2, p=0.005; V3, p=0.026) significantly increased after vitamin D treatment. There were no changes in androgens. At V2, 14 out of 46 PCOS women previously affected by menstrual disturbances (30.4%) reported improvement of menstrual frequency; at V3, 23 out of 46 women (50.0%), who were oligo- or amenorrheic at baseline reported improvement. Discussion: Our results suggest that vitamin D treatment might improve glucose metabolism and menstrual frequency in PCOS women. Further randomized controlled trails are warranted to confirm our findings.

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

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.

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.

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.

Sex steroids and mortality in men referred for coronary angiography.

Objective  Accumulating evidence suggests that sex steroids are associated with various chronic diseases. We aimed at evaluating whether total testosterone (TT), free testosterone (FT) and sex hormone–binding globulin (SHBG) are associated with all‐cause mortality and specific fatal events.

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.

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.