Current and emerging drug treatment strategies for polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common hormonal, metabolic, and reproductive disorder with a heterogeneous phenotype. As the exact etiology of PCOS is still unclear, available pharmacotherapies are mostly directed toward alleviating symptoms and associated metabolic abnormalities. AREAS COVERED: Herein, we present an overview of the current and emerging pharmacotherapies for the management of women with PCOS who do not seek pregnancy. We performed a literature search in PubMed database up to January 2022 and reviewed papers assessing drug treatments for PCOS. We aimed to outline the most recent evidence to support treatment recommendations in these patients. EXPERT OPINION: Targets for medical treatment include hormonal, reproductive, and metabolic abnormalities in PCOS. However, none of the available pharmacological options can cover the entire spectrum of clinical manifestations observed in these patients. Considering the heterogeneity of PCOS, treatment should be individualized and adapted to specific needs of each patient. Better understanding of the molecular mechanisms underlying the pathogenesis of PCOS would help development of novel, safer, and more effective multi-targeted therapeutic strategies for the syndrome.

The impact of ageing and menopause in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common hormonal, metabolic and reproductive disorder. Women with PCOS at reproductive age have increased risk and prevalence of prediabetes and diabetes and have multiple risk factors for cardiometabolic disease and other comorbidities such as obstructive sleep apnoea, endometrial cancer and mood disorders, which contribute to the overall health burden of the syndrome. However, little is known about the impact of PCOS on long-term health in ageing women. In this review, we aimed to give an updated overview regarding the long-term health outcomes of PCOS and their clinical implications in peri- and postmenopause. The PCOS phenotype ameliorates with ageing and limited available data suggest that there is no further deterioration in cardiometabolic profile in women with PCOS after menopause. Accordingly, the risk of cardiovascular disease in ageing women with PCOS seems to be no different from those without PCOS and lower than previously anticipated based on their risk during reproductive years. Regarding other comorbidities including sleep apnoea, mood disorders and endometrial cancer, it is difficult to determine the true risk in older women with PCOS due to the confounding factors and lack of long-term cohort studies. Large, prospective studies on community-based and well-phenotyped PCOS cohorts with extended follow-up into late menopause are needed to confirm these findings.

Prevalence of Obesity and Its Impact on Outcome in Patients With COVID-19: A Systematic Review and Meta-Analysis.

Background and Objective: Obesity has been reported as a risk factor for adverse outcomes in COVID-19. However, available studies presenting data on obesity prevalence in patients with COVID-19 have conflicting results. The objective of this systematic review and meta-analysis is to evaluate the prevalence of obesity in these patients and to stratify the estimates by illness severity. Methods: We performed a literature search with the use of Medline/PubMed and Google Scholar database from December 1, 2019 to June 27, 2020 and systematically reviewed studies reporting the number of obese patients with real-time reverse transcriptase polymerase chain reaction (rRT-PCR)-confirmed SARS-CoV-2 infection. Results: Nineteen studies were identified. The pooled obesity prevalence rates were 0.32 (95% CI: 0.24-0.41) in hospitalized patients, 0.41 (95% CI: 0.36-0.45) in patients admitted to intensive care unit, 0.43 (95% CI: 0.36-0.51) in patients needing invasive mechanic ventilation (IMV), and 0.33 (95% CI: 0.26-0.41) in those who died. Obesity was associated with a higher risk for hospitalization [Odds ratio (OR): 1.3, 95% CI: 1.00-1.69; I2 52%, p = 0.05], ICU admission (OR: 1.51, 95% CI: 1.16-1.97; I2 72%, p = 0.002), and IMV requirement (OR: 1.77, 95% CI: 1.34-2.35; I2 0%, p < 0.001). The increase in risk of death did not reach statistical significance (OR: 1.28, 95% CI: 0.76-2.16, p = 0.35) which might be due to obesity survival paradox and/or unidentified factors. Conclusions: Our data indicate that obese subjects may be at higher risk for serious illness if infected and obesity may play a role in the progression of COVID-19.

Klotho gene G395A and C1818T polymorphisms in acromegaly: Association with clinical presentation and comorbidities.

BACKGROUND: Klotho is a new identified anti-ageing gene with tumour suppressor activities. Current data suggest that there is a tight relationship between Klotho protein and growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. PURPOSE: This study aimed to investigate the possible association of Klotho gene polymorphisms with acromegaly and to assess whether these polymorphisms contribute to clinical characteristics, comorbidities and biochemical variables in these patients. METHODS: The study included 52 patients with acromegaly and 52 unrelated healthy subjects. The Klotho G395A and C1818T polymorphisms were assessed by Sanger sequencing. Serum levels of sKlotho were determined by ELISA method. RESULTS: Subjects carrying GA genotype of Klotho G395A polymorphism had 3.27 times higher risk of developing acromegaly [odds ratio (OR), 3.27; 95% confidence interval (CI): 1.37-7.81; p = .023]. The A allele of G395A was significantly associated with acromegaly risk (OR, 2.27; 95% CI: 1.1-4.72; p = .022). No association was observed between the studied polymorphisms and disease characteristics including age at acromegaly diagnosis, size of adenoma, baseline GH and IGF-1 concentrations, and final outcome. G395A polymorphism was associated with the presence of malignancy (OR, 2.24, 95% CI: 1.63-3.08; p = .019) and colorectal polyps (OR, 1.99; 95% CI: 1.02-3.88; p = .047) in patients with acromegaly. Serum sKlotho levels were significantly higher and correlated with GH and IGF-1 levels among acromegaly patients. There was no association between the studied polymorphisms and sKlotho levels. CONCLUSIONS: Klotho G395A polymorphism is associated with acromegaly susceptibility and increased risk of malignancy and colorectal polyps in these patients.

Polycystic ovary syndrome and aging: Health implications after menopause.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with heterogenous clinical manifestations. The evidence indicates that PCOS is associated with long-term health risks including type 2 diabetes, metabolic syndrome, obstructive sleep apnea, endometrial cancer, and mood disorders. Although cardiometabolic risk factors are more common among women with PCOS, currently there is no strong evidence for increased cardiovascular morbidity and mortality in these patients. The effect of menopausal transition on the long-term health consequences of PCOS is mostly uncertain. The PCOS phenotype improves with aging in affected women. Accordingly, the differences in the cardiometabolic risk profiles of PCOS patients and of the general population seem to disappear after menopause. However, it is not clear whether this phenotype amelioration is associated with changes in other long-term health risks after the menopause. There are also gaps in our knowledge about the impact of long-term use of oral contraceptives on the prevalence of PCOS-related comorbidities. This review summarizes the current knowledge regarding the long-term health consequences of PCOS and their clinical implications in peri- and postmenopause, and highlights areas for future research.

Tissue fat quantification by magnetic resonance imaging: proton density fat fraction in polycystic ovary syndrome.

RESEARCH QUESTION: What are the potential differences between lean women with and without polycystic ovary syndrome (PCOS) in fat content in liver, vertebrae, paraspinal muscles, pancreas, subcutaneous (SCAT) and visceral adipose tissue (VAT)? Magnetic resonance imaging proton density fat fraction (PDFF) was used to establish these differences. This is a novel, non-invasive, operator-independent method with comparable diagnostic sensitivity and specificity to histologic examination for fatty liver disease, and strong correlation with muscle strength in neuromuscular studies. DESIGN: Twenty lean women with PCOS (mean age 23.9 ± 2.3; body mass index [BMI] 22.4 ± 2.0) and 20 age- and BMI-matched healthy women (mean age 24.9 ± 1.5; BMI 21.5 ± 1.9) were enrolled in this cross-sectional study. Anthropometric, biochemical and hormonal evaluations along with magnetic resonance imaging proton density fat fraction were carried out. RESULTS: PDFF% measurements of liver, SCAT and VAT were higher in the PCOS group, indicating increased fat content in these areas in lean women with PCOS compared with controls (P = 0.045, 0.030 and 0.037, respectively). In contrast, PDFF% values of vertebrae and paraspinal muscles in the PCOS group were lower than controls (P = 0.038 and 0.05, respectively). Pancreatic PDFF% measurements were similar between the groups. In the PCOS group, PDFF% of VAT was positively correlated with free androgen index (r = 0.69, P = 0.002). CONCLUSIONS: PDFF% measurement, an MRI-based novel biomarker, reveals increased fat in liver, SCAT and VAT, and decreased fat in vertebral bones and paraspinal muscles of lean women with PCOS.

Cardiovascular health and menopause in aging women with polycystic ovary syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with heterogeneous clinical manifestations. Current evidence suggests that women with PCOS exhibit an unfavorable metabolic profile which may pose them at increased risk for cardiovascular events later in life.Areas covered: Herein, we present a review of the existing literature relating to PCOS and long-term cardiovascular (CV) health risks in women after menopause. We performed an electronic-based search with the use of PubMed from 1990 to August 2019 and systematically reviewed studies assessing CV events in women with PCOS. We aimed to outline the gaps in the current evidence and suggest areas for future research.Expert opinion: Although there is a clear association between PCOS and cardiometabolic dysfunction, data on actual cardiovascular disease (CVD) events are conflicting. Additional large, prospective cohort studies of well-phenotyped women with PCOS and long-term follow-up into the late menopause are needed to elucidate the true CVD risk in this population.

The tendency of reduced periodontal destruction in acromegalic patients showing similar inflammatory status with periodontitis patients.

PURPOSE: Evaluate periodontal status of acromegalics through clinical and biochemical variables. METHODS: Demographics, hormone and metabolic variables, periodontal variables, gingival crevicular fluid (GCF) volume, and content data were collected from 30 patients with acromegaly, 30 patients with periodontitis, and 20 healthy subjects and comparatively analyzed. RESULTS: GH differences between acromegaly (2.56 ± 4.86) and periodontitis (0.53 ± 0.95) (p < 0.001) were statistically significant. IGF-1 was lowest at periodontitis (113.31 ± 45.01) and lower (152.11 ± 45.56) at healthy group compared with acromegalics (220.38 ± 167.62) (p < 0.05). GH and IGF-1 had positive correlation (p < 0.05). IGF-1 and CAL had negative (p < 0.01) correlation except healthy group that showed the same correlation at the opposite direction (p < 0.05). Besides similar plaque and gingival indices with periodontitis, acromegalics showed relatively less CAL and GCF volume but except CAL, all their periodontal variables were higher than healthy subjects. GCF GH and prolactin showed higher values in acromegalics while healthy subjects showed relatively high interleukin-1, -10 and carboxyterminal telopeptide of type I collagen compared with others. CONCLUSION: Acromegalics have a tendency of slowed periodontal destruction with an influence of GH and IGF-1 to the inflammation- and collage metabolism-related mechanisms rather than bone-associated ones. However, this information must be confirmed with further studies exploring the mechanisms possibly bonded to others.

Clock gene PERIOD3 polymorphism is associated with susceptibility to Graves' disease but not to Hashimoto's thyroiditis.

Circadian disruption has been linked with immune-related morbidities including autoimmune diseases. PERIOD3 (PER3) clock gene is a key player in the mammalian circadian system. This study evaluated the possible association of PER3 rs2797685 (G/A) polymorphism and susceptibility of autoimmune thyroid diseases (AITD) and assessed if this SNP contributes to disease characteristics and serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The PER3 rs2797685 (G/A) polymorphism was assessed in 125 patients with AITD [Graves' disease (GD), 69; Hashimoto's thyroiditis (HT), 56] and 115 unrelated healthy controls. Subjects carrying at least one variant allele of PER3 rs2797685 (GA+AA) had increased risk for GD (OR 1.9, 95% CI 1-3.61, p= .05). There were no differences in the frequencies of genotypes and alleles of the PER3 rs2797685 polymorphism between HT patients and control subjects. No association was observed between genotypes of the studied SNP and any of the disease characteristics in GD and HT patients. The GA+AA genotype of PER3 rs2797685 was associated with lower levels of IL-6 in patients with Graves' disease. There were no differences between genotypes of the studied SNP regarding TNF-α levels in GD, HT or control groups. In conclusion, this study provides the first evidence for a genetic association between GD and the PER3 gene, highlighting the possible relevance of polymorphisms in clock genes in the etiopathogenesis of AITD. However, functional studies to identify the underlying molecular mechanisms of this association are needed to translate these findings to clinical applications.

Polycystic ovary syndrome and the risk of obstructive sleep apnea: a meta-analysis and review of the literature.

BACKGROUND AND OBJECTIVE: Polycystic ovary syndrome (PCOS) has been reported to be associated with the development of obstructive sleep apnea (OSA). The objective of this meta-analysis is to assess the relationship between PCOS and OSA. METHODS: A literature search was conducted to identify studies linking PCOS with the risk of OSA. Studies in which the presence of OSA was confirmed with overnight polysomnography were included. Random effects models were used to calculate pooled relative risks. RESULTS: Eight studies conducted in adults and five studies conducted in adolescents were identified. The pooled OSA prevalence was 0.22 (95% confidence interval (CI): 0.08-0.40) in PCOS patients. The pooled prevalence of OSA was higher in adults (0.32, 95% CI: 0.13-0.55) than adolescents (0.08, 95% CI: 0.00-0.30). Risk of OSA was significantly increased in adult patients with PCOS (odds ratio (OR) 9.74, 95% CI: 2.76-34.41). Risk of OSA was not significantly increased in adolescents (OR: 4.54, 95% CI:0.56-36.43). CONCLUSIONS: These findings demonstrate a significant association between PCOS and OSA in adult patients. Considering the increased risk for long-term cardiometabolic disorders associated with both PCOS and OSA, it is important to diagnose and treat OSA in patients with PCOS.

Serum transforming growth factor-beta levels in patients with vitamin D deficiency.

BACKGROUND: Transforming growth factor-beta 1 (TGF-ß1) contributes to tissue repair by promoting tissue fibrosis, and elevations have been reported in patients with bone marrow fibrosis. The aim of this study was to evaluate the relationship between TGF-ß1 levels and vitamin D deficiency. METHODS: All patients presenting to the outpatient Endocrinology and Metabolic Diseases clinic between June and September of 2008 were approached, and consenting patients who were deemed suitable candidates were enrolled. Hematological parameters were measured, along with serum levels of total and ionized calcium, phosphorus, parathyroid hormone, iron, folic acid vitamin B12 levels, 25 OH vitamin D3 (25OHD(3)) and TGF-ß1. RESULTS: A total of 132 patients were included in the study. Patients were divided into 4 groups based on levels of 25OHD(3) [group 1 (<5 ng/ml), 20 patients; group 2 (5-15 ng/ml), 38 patients; group 3 (16-30 ng/ml); and group 4 (>30 ng/ml), 28 patients]. TGF-ß1 levels were higher in patients in group 1 compared to the other groups. Transforming growth factor-beta levels correlated negatively with vitamin D3 and positively with leukocyte count, platelet count, of MCV and MCH. Multiple regression analyses revealed TGF-ß1 levels to be associated with 25OHD(3) as well as with platelet count. CONCLUSIONS: Results of this study are suggestive of the presence of a significant relationship between TGF-ß and vitamin D deficiency. Increased TGF-ß1 and platelet count may be an early indicator of bone marrow fibrosis in patients with vitamin D deficiency.

An overlooked indicator of disease activity in ulcerative colitis: mean platelet volume.

Many non-invasive tests have been studied for diagnosis and determining the activation degree of inflammatory bowel disease (IBD). Nevertheless, an ideal test has not been found yet. Mean platelet volume (MPV) is influenced by the inflammation. In a few study, decreased platelet volume have been reported in IBD. The aim of this study is to determine whether platelet volume would be useful in ulcerative colitis (UC) activity. Additionally we have analyzed overall accuracy of MPV in disease activity and compared with other inflammatory markers. A total of 61 UC patients (male/female : 41/20), and 27 healthy subjects (male/female : 18/9) were enrolled into the study. For all subjects following tests were performed; ESR, CRP, white blood cell count and mean platelet volume. A statistically significant decrease in MPV was noted in patients with UC (8.29 +/- 1.02 fL) compared with healthy controls (8.65 +/- 0.79 fL). MPV of active UC (8.06 +/- 1.19 fL) patients were significantly lower than that of inactive UC (8.45 +/- 0.87 fL). Overall accuracy of MPV in determination of active UC was 71% (with sensitivity 67%, specificity 73%). A negative correlation was found between MPV and endoscopic activity index (r : -0.358 p : 0.005). In UC, MPV did not correlate with ESR, CRP and white blood cell. Our study showed that MPV reduced in UC, particularly in patients with active UC. Decreased MPV may be an indicator for increased disease activity in patients with UC.