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.

Association of genetic variants in the two isoforms of 5α-reductase, SRD5A1 and SRD5A2, in lean patients with polycystic ovary syndrome.

OBJECTIVE: Given its role in converting testosterone to dihydrotestosterone and cortisol to dihydrocortisol, 5α-reductase may be important in the pathophysiology of the polycystic ovary syndrome (PCOS). Increased activity of this enzyme has already been demonstrated in ovaries of affected women, and might be caused by genetic alterations. The aim of this study was to analyze representative genetic variants of both isoforms of 5α-reductase with regard to PCOS parameters in lean and obese women. STUDY DESIGN: We analyzed one single nucleotide polymorphism (SNP) (rs523349) of the isoform 2 (SRD5A2) and one haplotype of the isoform 1 (SRD5A1), consisting of the two SNPs rs39848 and rs3797179, in 249 women with PCOS and 226 healthy women using a 5'-exonuclease-assay. The genotypes were associated with anthropometric, metabolic and hormonal as well as functional tests in these women. RESULTS: In the investigated haplotype of SRD5A1, the TA variant was associated with an increased frequency of PCOS (P=0.022) and an increased Ferriman-Gallwey Score (hirsutism) (P=0.016) in women with normal weight. The G allele at the examined position of the SRD5A2 showed a decreased frequency of PCOS (P=0.03) in women with normal weight. CONCLUSION: One of the keys in the development of the PCOS is hyperandrogenism, which might be caused by an increased 5α-reductase activity, as it is often seen in obesity. This mechanism might therefore be of importance in lean PCOS patients and contribute to the clinical findings.

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.

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. DESIGN, SETTING AND PARTICIPANTS: We measured TT and SHBG levels in 2078 men who were routinely referred for coronary angiography (1997-2000). FT was calculated according to Vermeulen. MEASUREMENTS: The main outcome measures were Cox proportional hazard ratios (HRs) for mortality from all causes, from cardiovascular and non-cardiovascular causes and from cancer according to SHBG, FT and TT. RESULTS: Multivariable-adjusted HRs (with 95% confidence intervals) in the fourth compared to the first SHBG quartile for all-cause, non-cardiovascular and cancer mortality were 1·61 (1·16-2·23), 2·44 (1·39-4·28), and 2·86 (1·03-7·32), respectively. There was no significant association of SHBG levels with cardiovascular mortality. All-cause mortality was significantly reduced per 1 SD increase in FT in the multivariate-adjusted analyses [0·49 (0·30-0·81)]. We observed no significant associations of FT with cardiovascular and cancer mortality, and TT levels were not independently related to any fatal events. CONCLUSION: High levels of SHBG are associated with adverse health outcomes in a large cohort of older men referred for coronary angiography. Further studies are warranted to confirm our results and to elucidate the underlying mechanisms for our findings.

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. DESIGN: In this cross-sectional study, 25(OH)D, testosterone and SHBG levels were assessed by immunoassay in 2299 men who were routinely referred for coronary angiography (1997-2000). MEASUREMENTS: Main outcome measures were associations of 25(OH)D levels with testosterone, SHBG and FAI. FAI was calculated as testosterone (nmol/l)/SHBG (nmol/l) x 100. RESULTS: Men with sufficient 25(OH)D levels (> or =30 microg/l) had significantly higher levels of testosterone and FAI and significantly lower levels of SHBG when compared to 25(OH)D insufficient (20-29.9 microg/l) and 25(OH)D-deficient (<20 microg/l) men (P < 0.05 for all). In linear regression analyses adjusted for possible confounders, we found significant associations of 25(OH)D levels with testosterone, FAI and SHBG levels (P < 0.05 for all). 25(OH)D, testosterone and FAI levels followed a similar seasonal pattern with a nadir in March (12.2 microg/l, 15.9 nmol/l and 40.8, respectively) and peak levels in August (23.4 microg/l, 18.7 nmol/l and 49.7, respectively) (P < 0.05 for all). CONCLUSION: Androgen levels and 25(OH)D levels are associated in men and reveal a concordant seasonal variation. Randomized controlled trials are warranted to evaluate the effect of vitamin D supplementation on androgen levels.

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.

Evidence-based health care coverage for children: proceed with caution.

Making health care coverage depend on the existence of valid, applicable research data and positive cost-effectiveness analyses, as managed care contracts are beginning to do, is particularly problematic for children. Because of research challenges specific to children, there are relatively few pediatric data and analyses required under such evidence-based coverage standards. It is too soon to expect major increases from federal efforts to stimulate pediatric health care research. But absence of requisite evidence would entitle a managed care organization or other decision maker to deny coverage on the basis of unproven, negative assumptions about an intervention. In general, population-based evidence is an incomplete basis for decisions on coverage for individual patients. Cost-effectiveness analyses are not standardized and may be biased. Purchasers of managed care and policy makers should understand the limits of evidence-based coverage standards. Other uses of evidence may contribute more to systemic improvements of health care.

Disparities in children's oral health and access to dental care.

Dental caries can be prevented by a combination of community, professional, and individual measures including water fluoridation, professionally applied topical fluorides and dental sealants, and use of fluoride toothpastes. Yet, tooth decay is the most common chronic disease of childhood. Dental care is the most prevalent unmet health need in US children with wide disparities existing in oral health and access to care. Only 1 in 5 children covered by Medicaid received preventive oral care for which they are eligible. Children from low income and minority families have poorer oral health outcomes, fewer dental visits, and fewer protective sealants. Water fluoridation is the most effective measure in preventing caries, but only 62% of water supplies are fluoridated, and lack of fluoridation may disproportionately affect poor and minority children. Childhood oral disease has significant medical and financial consequences that may not be appreciated because of the separation of medicine and dentistry. The infectious nature of dental caries, its early onset, and the potential of early interventions require an emphasis on preventive oral care in primary pediatric care to complement existing dental services. However, many pediatricians lack critical knowledge to promote oral health. We recommend financial incentives for prioritizing Medicaid Early and Periodic Screening, Diagnostic, and Treatment dental services; managed care accountability; integration of medical and dental professional training, clinical care, and research; and national leadership. JAMA. 2000;284:2625-2631.