Lean mass and associated factors in women with PCOS with different phenotypes.

Although current evidence suggests increased risk of obesity, insulin resistance, and metabolic alterations in patients with polycystic ovary syndrome (PCOS), especially of a hyperandrogenic phenotype, the impact of each one of these variables on muscle mass remains uncertain. In this case-control study, we evaluated clinical and hormonal characteristics related to lean body mass according to the different PCOS phenotypes. We performed clinical, metabolic, and hormonal assessments and evaluated body compartments by dual-energy X-ray absorptiometry in 133 women of reproductive age. Creatinine served as an indirect marker of lean mass. Median age was 28 (range, 17-37) years. Women with phenotypes A and B (n = 59) had higher body mass index (BMI) and metabolic syndrome prevalence than those with phenotype C (n = 23) and controls (n = 51) (p<0.005). Women with phenotypes A and B also had higher Ferriman-Gallwey score (p<0.001), insulin levels (p = 0.006), HOMA-IR (p = 0.008), testosterone (p = 0.008), free androgen index (FAI) (p<0.001), fat mass index (FMI) (p = 0.015), android-to-gynoid fat ratio (p = 0.036), and bone mineral density (BMD) at lumbar spine (p = 0.027) and total femur (p = 0.013) than controls. Median appendicular lean mass index (ALMI) was higher in phenotypes A and B than in controls (7.01 [IQR, 6.33-8.02] vs. 6.69 [IQR, 5.94-7.09], p = 0.024), but it did not differ significantly from that in phenotype C (6.60 [IQR, 6.16-7.22], p = 0.222). Even after adjusting for BMI, ALMI correlated positively with creatinine in women with phenotypes A and B (rho = 0.319, p = 0.023) but not in those with phenotype C (p = 0.238) or controls (p = 0.097). In multivariate linear regression analyses, ALMI was positively associated with insulin, FAI, FMI, and total femur BMD. The present results suggest that fasting insulin, FAI, fat mass, and total femur BMD were positively associated with increased lean mass in women with PCOS phenotypes A and B.

Hirsutism, Normal Androgens and Diagnosis of PCOS.

Hirsutism is defined as the presence of terminal hair with male pattern distribution in women. While in the general population, hirsutism affects around 4-11% of women, it is the main manifestation of hyperandrogenism in women with polycystic ovary syndrome (PCOS), with a prevalence estimated at 65-75%. Hirsutism in PCOS is associated with both androgen excess and individual response of the pilosebaceous unit to androgens. The modified Ferriman-Gallwey (mFG) scoring system has been widely used in clinical practice to visually score excessive terminal hair, thus standardizing hirsutism evaluation and facilitating data comparison. Although a universal mFG score cutoff would be useful for comparisons, ethnic variations, as well as skin type and other factors, should be considered when evaluating hirsutism in distinct populations. In turn, androgen levels, measured by conventional techniques, have been shown to correlate poorly with the severity of hirsutism. Indeed, while most women with PCOS and hirsutism also have higher than reference values for serum androgen levels, some of them may not present with biochemical hyperandrogenism, representing a challenge to the diagnosis of PCOS. In this article, we critically review this not uncommon condition in women with PCOS presenting with hirsutism but normal androgen levels.

Are vitamin D deficiency and VDR gene polymorphisms associated with high blood pressure as defined by the ACC/AHA 2017 criteria in postmenopausal women?

OBJECTIVES: To assess the vitamin D levels, prevalence of vitamin D deficiency and genotypes of Fok-I, Bsm-I, Apa-I and Taq-I polymorphisms in the VDR gene and to determine whether vitamin D deficiency and VDR gene variants are associated with blood pressure levels and systemic arterial hypertension as defined by the 2017 ACC/AHA criteria. STUDY DESIGN: A cross-sectional study of biobanked blood samples from 339 postmenopausal women. MAIN OUTCOME MEASURES: Blood pressure strata were defined according to the 2017 ACC/AHA cutoffs. Circulating 25(OH)D levels were considered deficient if <20 ng/mL. RESULTS: Mean serum total 25(OH)D levels were 22.99 ± 8.54 ng/mL, and 40.1% of participants were deficient in vitamin D. Overall, 7.7% had elevated blood pressure, 36.6% had stage 1 and 37.8% had stage 2 hypertension. Mean total (p = 0.014) and free 25(OH)D levels (p = 0.029) were lower in women with stage 2 hypertension than in those with normal blood pressure. A higher prevalence rate of stage 2 hypertension was associated with age (PR 1.058; 95%CI 1.033-1.083; p < 0.001), BMI (PR 1.046; 95%CI 1.025-1.068; p < 0.001), vitamin D deficiency (PR 1.333; 95%CI 1.016-1.749; p = 0.038) and Taq-I polymorphism (PR 1.764; 95%CI 1.030-3.019; p = 0.039). Women with vitamin D deficiency and the AA+AG genotype of Taq-I polymorphism were 33% and 76% more likely to have stage 2 hypertension, respectively, but these associations lost significance when adjusted for age and BMI. CONCLUSION: The results suggest that vitamin D deficiency and Taq-I polymorphism are associated with stage 2 hypertension, depending on age and BMI, in postmenopausal women.

Prevalence of vitamin D deficiency in women from southern Brazil and association with vitamin D-binding protein levels and GC-DBP gene polymorphisms.

Vitamin D deficiency is highly prevalent worldwide, and vitamin D-binding protein (DBP) a major regulator of serum vitamin D levels. The rs4588 and rs7041 polymorphisms of the GC gene constitute the genetic basis of the three major isoforms of circulating DBP (GC1s, GC1f, and GC2), while the rs2282679 variant is located in an important regulatory region of the GC gene. The aim of this study was to assess the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency and to ascertain whether it is associated with DBP levels and with GC gene variants. Biorepository samples of 443 women aged 20 to 72 years, with no evidence of clinical disease, were analyzed. Circulating levels of 25(OH)D were considered sufficient if ≥20 ng/mL and deficient if <20 ng/mL. Genotype analysis was performed by RT-PCR. Mean age was 53.4±9.4 years; mean BMI was 27.8±5.8 kg/m2. The overall sample had mean 25(OH)D levels of 22.8±8.3 ng/mL; 39.7% of participants had deficient circulating 25(OH)D levels. Higher prevalence ratios (PR) of 25(OH)D deficiency were found for the CC genotype of rs2282679 (PR 1.74; 95%CI 1.30 to 2.24; p<0.001), GC2 isoform (PR 1.66; 95%CI 1.17 to 2.38; p = 0.005), time since menopause (PR 1.02; 95%CI 1.003 to 1.03, p = 0.016), and HOMA-IR (PR 1.02; 95%CI 1.01 to 1.03, p = 0.004). DBP levels (per 30 µg/mL increase in DBP) were associated with lower PR for 25(OH)D deficiency (PR 0.89; 95%CI 0.80;0.99; p = 0.027). Except for HOMA-IR, these prevalence ratios remained significant after adjustment for age and BMI. In conclusion, the rs2282679 polymorphism and the GC2 isoform of DBP were associated with lower serum DBP levels and with susceptibility to 25(OH)D deficiency in Brazilian women with no evidence of clinical disease.

Apa-I polymorphism in VDR gene is related to metabolic syndrome in polycystic ovary syndrome: a cross-sectional study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder determined by polygenic traits as well as environmental factors. Lower vitamin D levels have been detected in PCOS women and related to hormone and metabolic disturbances. Vitamin D acts in tissues through the vitamin D receptor (VDR). VDR gene variants have been associated with worse metabolic profile in the general population. We investigated the genotype and haplotype distribution of the Bsm-I (rs1544410), Apa-I (rs7975232), and Taq-I (rs731236) VDR gene polymorphisms in PCOS and non-hirsute women from southern Brazil. We further investigated the associations of these gene variants and their haplotypes with PCOS, vitamin D levels, and metabolic abnormalities, including the metabolic syndrome (MetS). METHODS: A group of 191 women with PCOS (Rotterdam criteria) and 100 non-hirsute controls with regular ovulatory cycles were genotyped for all polymorphisms by real-time PCR, with allelic discrimination assays. MetS and the cutoffs for its isolated components were defined in accordance with the Joint Scientific Statement. RESULTS: Women with PCOS were younger and had significantly higher BMI and total testosterone levels than controls (p < 0.05). The frequency of MetS in PCOS and controls was 26.5% and 4.8% respectively. The CC genotype of Apa-I entailed higher risk of MetS in PCOS (OR: 2.133; 95% CI 1.020-4.464, p = 0.042), and was associated with higher systolic blood pressure (p = 0.009), total cholesterol (p = 0.040), and LDL-cholesterol (p = 0.038) in both PCOS and control groups (two-way ANOVA). The frequencies of VDR haplotypes were similar in PCOS and control women. CONCLUSIONS: The present results suggest that the Apa-I variant in VDR gene may be associated with MetS in southern Brazilian women with PCOS, and with blood pressure, total cholesterol, and LDL-c in women with and without PCOS.

Impact of vitamin D receptor and binding protein gene polymorphisms in clinical and laboratory data of HCV patients: Cross sectional study.

Potential relationship of vitamin D, vitamin D receptor (VDR), and vitamin D binding protein (DBP) have been suggested in the pathophysiology of hepatitis C virus (HCV) infection. The aim of this observational study is to determine vitamin D levels, and VDR and DBP genetic polymorphism according demographic and laboratory data in chronic HCV patients (CHC).A total of 148 CHC patients gave serum samples for testing 25-hydroxyvitamin D (25 (OH)D) level by immunochemiluminometric assay (<20 ng/mL defined as deficient) and donated blood samples to allelic discrimination analysis using TaqMan assays. Analyzed single nucleotide polymorphisms (SNPs) were: VDR-rs7975232 (ApaI) C>A, rs731236 A>G (TaqI), rs1544410 C>T (BsmI), rs10735810 T>C (FokI) and carrier globulin/binding protein (GC)-rs4588 and rs7041 and the haplotype bAt [CCA]. Hepatic fibrosis was assessed using Fib-4 and Forns index.Eighty-two (54.40%) patients demonstrated deficiency of vitamin D and this was associated to AST (P = .019 [CI: 1.003-1.034]), total cholesterol (P = .038 [CI: 1.004-1.164]), fibrosis grade (P < .001 [CI: 0.000-0.844]), and FokI (P = .028) allele T presence. Association was found between VDR polymorphism and fibrosis (BsmI andTaqI), triglycerides (TaqI), and HDL (FokI). DBP polymorphism was associated to HCV genotype (GC rs7041), previous HCV treatment, and GGT (GC rs4588).In conclusion, low frequency of vitamin D deficiency was found, but VDR polymorphisms were frequently associated to fibrosis grade suggesting that they could be used as disease evaluation markers to understand the mechanisms underlying the virus-host interaction.

Circulating and peritoneal fluid interleukin-6 levels and gene expression in pelvic endometriosis.

Current data are inconsistent regarding the association between interleukin-6 (IL-6), a marker of acute phase inflammation, and pelvic endometriosis. The aim of the present study was to assess IL-6 levels in serum and peritoneal fluid (PF), as well as IL-6 gene expression in adipose tissue (AT) and endometrial samples in pelvic endometriosis. A total of 30 patients with endometriosis and 18 women with a normal pelvis were enrolled in this case-control study. IL-6 levels in PF and serum were determined using a human enzyme-linked immunosorbent assay and IL-6 gene expression was evaluated using reverse transcription-quantitative polymerase chain reaction. It was observed that IL-6 levels in the PF were higher in patients with endometriosis than in the control group (P=0.047) and patients with stage III/IV endometriosis exhibited higher IL-6 levels in the PF than those with stage I/II endometriosis and the control group (P<0.001). Furthermore, a strong correlation between PF IL-6 levels and the revised American Society for Reproductive Medicine score for endometriosis severity was identified (r=0.77; P<0.001). IL-6 gene expression did not differ significantly between endometriosis and control groups in endometrial samples or in AT of both groups. The results of the current study suggest that there may be an association between IL-6 and the presence and severity of pelvic endometriosis. The source of this higher IL-6 seems not to be specifically related to regional AT.

Genetic variant in vitamin D-binding protein is associated with metabolic syndrome and lower 25-hydroxyvitamin D levels in polycystic ovary syndrome: A cross-sectional study.

Vitamin D deficiency has been related to metabolic syndrome (MetS) in polycystic ovary syndrome (PCOS). The vitamin D-binding protein (DBP) is the main protein involved in vitamin D transport. Two single-nucleotide polymorphisms (SNPs) of the DBP gene, rs4588 and rs7041, have been associated with low circulating levels of 25-hydroxyvitamin D [25(OH)D] in various populations, but not in women with PCOS. Therefore, we determined the genotype and haplotype distribution of DBP gene polymorphisms and investigated the associations between these genetic variants and their haplotypes with PCOS, MetS, and 25(OH)D levels in women with PCOS and controls from the South of Brazil. The sample included 291 women (191 with PCOS and 100 controls). All participants were genotyped for polymorphisms rs2282679, rs4588, and rs7041. Serum 25(OH)D levels were determined in a subset of 102 participants. Women with PCOS were younger and had significantly higher body mass index, blood pressure, and insulin resistance than the control group (p<0.05). The prevalence of MetS in PCOS and controls was 26.5% and 4.8% respectively. Levels of 25(OH)D were lower in PCOS women with MetS, even after adjustment for age (p = 0.033). No associations were observed between PCOS and the polymorphisms or their haplotypes. A higher frequency of genotype TT of rs7041 was found in PCOS participants with MetS (OR: 2.21, 95%CI:1.08-4.52; p = 0.027). This same genotype was associated with lower 25(OH)D levels in both PCOS and control women (OR: 4.40, 95%CI:1.62-12.00; p = 0.002). In conclusion, these findings indicate that DBP gene polymorphisms and their haplotypes are not directly associated with PCOS. In contrast, the TT genotype of SNP rs7041 was associated with MetS in PCOS women, and with lower 25(OH)D levels in both PCOS and control groups.