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1.
Arch Gynecol Obstet ; 306(2): 547-555, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1813667

ABSTRACT

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is global pandemic with more than 5 million deaths so far. Female reproductive tract organs express coronavirus-associated receptors and factors (SCARFs), suggesting they may be susceptible to SARS-CoV-2 infection; however, the susceptibility of ovary/follicle/oocyte to the same is still elusive. Co-morbidities like obesity, type-2 diabetes mellitus, cardiovascular disease, etc. increase the risk of SARS-CoV-2 infection. These features are common in women with polycystic ovary syndrome (PCOS), warranting further scope to study SCARFs expression in ovary of these women. MATERIALS AND METHODS: SCARFs expression in ovary and ovarian tissues of women with PCOS and healthy women was explored by analyzing publically available microarray datasets. Transcript expressions of SCARFs were investigated in mural and cumulus granulosa cells (MGCs and CGCs) from control and PCOS women undergoing in vitro fertilization (IVF). RESULTS: Microarray data revealed that ovary expresses all genes necessary for SARS-CoV-2 infection. PCOS women mostly showed down-regulated/unchanged levels of SCARFs. MGCs and CGCs from PCOS women showed lower expression of receptors ACE2, BSG and DPP4 and protease CTSB than in controls. MGCs showed lower expression of protease CTSL in PCOS than in controls. Expression of TMPRSS2 was not detected in both cell types. CONCLUSION: Human ovarian follicle may be susceptible to SARS-CoV-2 infection. Lower expression of SCARFs in PCOS indicates that the risk of SARS-CoV-2 infection to the ovary may be lesser in these women than controls. This knowledge may help in safe practices at IVF settings in the current pandemic.


Subject(s)
COVID-19 , Polycystic Ovary Syndrome , Female , Granulosa Cells/metabolism , Humans , Peptide Hydrolases/metabolism , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism , SARS-CoV-2
2.
Reprod Health ; 18(1): 156, 2021 Jul 26.
Article in English | MEDLINE | ID: covidwho-1779653

ABSTRACT

BACKGROUND: The most common endocrine and metabolic disorders in premenopausal women is polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, chronic anovulation, and/or ultrasound evidence of small ovarian cysts. Obesity and insulin resistance are also the main factors influencing the clinical manifestations of this syndrome. Alzheimer's disease (AD) is the most typical progressive neurodegenerative disorder of the brain, and recent studies suggest a relationship between endocrinal dysregulation and neuronal loss during AD pathology. AIM: This study aimed to evaluate the common risk factors for Alzheimer's and PCOS based on previous studies. Knowing the common risk factors and eliminating them may prevent neurodegenerative Alzheimer's disease in the future. METHOD: In this narrative review, international databases, including Google Scholar, Scopus, PubMed, and the Web of Science, were searched to retrieve the relevant studies. The relevant studies' summaries were categorized to discuss the possible pathways that may explain the association between Alzheimer's and PCOS signs/symptoms and complications. RESULTS: According to our research, the factors involved in Alzheimer's and PCOS disorders may share some common risk factors. In patients with PCOS, increased LH to FSH ratio, decreased vitamin D, insulin resistance, and obesity are some of the most important factors that may increase the risk of Alzheimer's disease.


Polycystic ovary syndrome is a disorder of the female reproductive system that can be caused by hormonal disorders. The disease is detected by an ultrasound of the ovaries with small ovarian cysts. Obesity and insulin resistance are among the factors that can affect the clinical symptoms of this disease. Obesity due to high-fat consumption can affect cognitive functions with age. Alzheimer's is the most common disease associated with disorders in brain cells; a link between hormonal disorders and Alzheimer's has recently been reported. We conducted a review of reports and articles published in connection with polycystic ovary syndrome and neurodegenerative disorders in reputable scientific databases. Studies have shown that the factors involved in polycystic ovary syndrome and Alzheimer's disease may indicate that both diseases have common risk factors. It may be linked to the symptoms and/or complications of Alzheimer's disease and polycystic ovary syndrome. Future preclinical studies are needed to closely examine the mechanisms associated with polycystic ovary syndrome and the association with Alzheimer's. The novelty of our study is from the fact that the PCOS may be to some extent considered as a cause (exposure) among others of AD's (outcome) and the association might be confounded by some or all the risk factors assessed in this review. The nature of the method­the narrative review­is relatively subjective (in the determination of which studies to include, the way the studies are analyzed, and the conclusions drawn) and hence may not help mitigate bias.


Subject(s)
Alzheimer Disease , Anovulation , Hyperandrogenism , Insulin Resistance , Polycystic Ovary Syndrome , Alzheimer Disease/epidemiology , Alzheimer Disease/etiology , Female , Humans , Polycystic Ovary Syndrome/complications , Risk Factors
3.
Arch Immunol Ther Exp (Warsz) ; 70(1): 13, 2022 Mar 24.
Article in English | MEDLINE | ID: covidwho-1756768

ABSTRACT

Increased androgen level, hyperinsulinemia, diabetes, impaired fibrinolysis, obesity, hypertension, chronic inflammation, abnormal immune response to infections and hyperhomocysteinemia are the most common abnormalities related to polycystic ovary syndrome (PCOS) women and are the factors predisposing to the severe course of COVID-19. The SARS-Cov-2 infection during pregnancy is associated with an increased risk of complications (spontaneous abortion), similar to those in PCOS. The treatment of PCOS pregnant women with a history of fertility failures raises many doubts, especially during the COVID pandemic. However, due to the increasing incidence of infections among reproductive people and the potentially more serious course in pregnant women, numerous questions about the safety and effectiveness of the treatment are still very current. In our study we presented a series of cases of recurrent miscarriages or recurrent implantation failure PCOS pregnant women with confirmed COVID-19. The diagnosis of infertility confirmed the presence of plasminogen activator inhibitor type 1 and/or 5,10-methylenetetrahydrofolate reductase polymorphisms in each of them. Moreover, some of the women presented immune dysfunction associated with infertility. We have described the personalized treatments of each pregnant patient included: metformin, enoxaparin and tacrolimus. The treatment applied had the expected effect, supporting the implantation processes. Furthermore, despite the ambiguous data according to immunological therapy of infertile women during the COVID pandemic, we observed a mild or asymptomatic COVID-19 course and we noticed no pregnancy complications.


Subject(s)
Abortion, Spontaneous , COVID-19 , Infertility, Female , Polycystic Ovary Syndrome , Abortion, Spontaneous/epidemiology , Female , Humans , Infertility, Female/complications , Infertility, Female/epidemiology , Infertility, Female/therapy , Pandemics , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/epidemiology , Pregnancy , Pregnant Women , SARS-CoV-2
4.
Medicina (Kaunas) ; 58(3)2022 Mar 16.
Article in English | MEDLINE | ID: covidwho-1742545

ABSTRACT

Metformin (MTF) occupies a major and fundamental position in the therapeutic management of type 2 diabetes mellitus (T2DM). Gender differences in some effects and actions of MTF have been reported. Women are usually prescribed lower MTF doses compared to men and report more gastrointestinal side effects. The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, most robust meta-analyses have yet to confirm such beneficial effects.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Metformin , Polycystic Ovary Syndrome , COVID-19/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Hypoglycemic Agents/adverse effects , Male , Metformin/pharmacology , Metformin/therapeutic use , Pregnancy , Sex Factors
5.
Rev Endocr Metab Disord ; 23(2): 251-264, 2022 04.
Article in English | MEDLINE | ID: covidwho-1718865

ABSTRACT

This comprehensive review aimed to evaluate the relationship between SARS-CoV-2 infection (the cause of coronavirus disease 2019, or COVID-19) and the metabolic and endocrine characteristics frequently found in women with polycystic ovary syndrome (PCOS). In the general population, COVID-19 is more severe in subjects with dyslipidemia, obesity, diabetes mellitus, and arterial hypertension. Because these conditions are comorbidities commonly associated with PCOS, it was hypothesized that women with PCOS would be at higher risk for acquiring COVID-19 and developing more severe clinical presentations. This hypothesis was confirmed in several epidemiological studies. The present review shows that women with PCOS are at 28%-50% higher risk of being infected with the SARS-CoV-2 virus at all ages and that, in these women, COVID-19 is associated with increased rates of hospitalization, morbidity, and mortality. We summarize the mechanisms of the higher risk of COVID-19 infection in women with PCOS, particularly in those with carbohydrate and lipid abnormal metabolism, hyperandrogenism, and central obesity.


Subject(s)
COVID-19 , Hyperandrogenism , Insulin Resistance , Polycystic Ovary Syndrome , COVID-19/epidemiology , Female , Humans , Hyperandrogenism/epidemiology , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/epidemiology , Polycystic Ovary Syndrome/metabolism , SARS-CoV-2
6.
Clin Endocrinol (Oxf) ; 96(4): 443-459, 2022 04.
Article in English | MEDLINE | ID: covidwho-1518007

ABSTRACT

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD). OBJECTIVE: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021. STUDY SELECTION: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). DATA EXTRACTION: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection. DATA SYNTHESIS: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I2 = 75%, very low-grade evidence). CONCLUSION: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.


Subject(s)
Metformin , Polycystic Ovary Syndrome , Atorvastatin/therapeutic use , C-Reactive Protein , Cholesterol, LDL , Female , Humans , Metformin/therapeutic use
7.
Obes Facts ; 14(6): 650-657, 2021.
Article in English | MEDLINE | ID: covidwho-1495755

ABSTRACT

INTRODUCTION: Lockdown due to the COVID-19 pandemic has caused gym closures and adjustments to ongoing weight loss programs were needed in order to keep the programs running. Little is known whether adjustments affected the success of weight reduction. Weight reduction of at least 5% is related to improved fertility and better pregnancy outcomes in obese women. This study compared success of the weight loss program in infertile polycystic ovary syndrome women with obesity who attended the program before and during lockdown due to COVID-19 pandemic. Furthermore, we checked whether there were any differences in spontaneous pregnancy rates between both groups at the end of the program. METHODS: Altogether, 27 women were prospectively included to the weight loss program. Twelve women attended the 8 - week program before COVID-19 pandemic. Fifteen women began the program before the lockdown and ended it during lockdown. Due to lockdown, the program was prolonged for 4 weeks and taken online. RESULTS: On average, prior to lockdown women achieved a BMI reduction of 6.8% whereas women that attended the program during the lockdown reduced their BMI for 3.7%. This difference was not statistically significant. No significant differences were seen in other measured anthropometric and endocrine parameters between both groups. Furthermore, there were no differences in spontaneous pregnancy rates between both groups. In women who reduced their BMI for 5% or more, spontaneous pregnancy rate was 29.4%. DISCUSSION/CONCLUSIONS: Although statistical significance has not been reached in the present study, we have shown that lockdown due to COVID-19 pandemic has led to almost half lower BMI reduction despite adaptations and longer duration of the weight loss program. On average, BMI in the group of women that attended the program during lockdown was 3.7% lower after the end of the weight loss program. This means they did not reach the wanted 5% reduction which is known to improve fertility. We have also shown that weight reduction is the correct approach for treating infertile women with obesity, as almost 30% of those who reduced their body weight by 5% or more conceived spontaneously.


Subject(s)
COVID-19 , Infertility, Female , Polycystic Ovary Syndrome , Weight Reduction Programs , Communicable Disease Control , Female , Humans , Infertility, Female/therapy , Obesity/complications , Obesity/epidemiology , Obesity/therapy , Pandemics , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/epidemiology , Polycystic Ovary Syndrome/therapy , Pregnancy , SARS-CoV-2
8.
J Steroid Biochem Mol Biol ; 214: 105965, 2021 11.
Article in English | MEDLINE | ID: covidwho-1454329

ABSTRACT

Vitamin D deficiency is a negative endocrine renin-angiotensin system (RAS) modulator and PCOS women are often vitamin D deficient, leading to RAS overactivation in PCOS. A cross-sectional study was performed in 99 PCOS and 68 control women who presented sequentially. Circulating plasma levels of RAS proteins (Angiotensin-converting enzyme 2 (ACE2), renin and angiotensinogen) were measured by Slow Off-rate Modified Aptamer (SOMA)-scan and 25-hydroxyvitamin D [25(OH)D] was measured by tandem mass spectroscopy. The RAS system was found to be overactivated in the PCOS women compared to non-PCOS control women with increased renin and decreased angiotensinogen (p < 0.05); 25-hydroxyvitamin D was also significantly lower in the PCOS group (p < 0.0001). In PCOS women, plasma renin was increased in vitamin D deficient and insufficient groups compared with the vitamin D sufficient group (p < 0.005), but did not differ across non-PCOS control subgroups. In non-PCOS controls, plasma ACE2 decreased from vitamin D insufficiency to deficiency (p < 0.05). Angiotensinogen was not different across the vitamin D sufficiency, insufficiency and deficiency strata for either PCOS or non-PCOS controls. These data show that RAS activation through increased plasma renin levels was seen in vitamin D insufficient and deficient PCOS subjects compared to non-PCOS control women. In addition, decreased plasma ACE2 levels were seen in vitamin D deficiency in non-PCOS controls, which may predispose these vitamin D deficient subjects to increased cardiovascular risk and susceptibility to infectious agents such as COVID-19 where this is a risk factor.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , Angiotensinogen/blood , Polycystic Ovary Syndrome/blood , Renin/blood , Vitamin D Deficiency/blood , Adult , Blood Pressure , Female , Humans , Polycystic Ovary Syndrome/physiopathology , Renin-Angiotensin System , Vitamin D/blood , Vitamin D Deficiency/physiopathology , Vitamins/blood , Young Adult
9.
Int J Mol Sci ; 22(18)2021 Sep 09.
Article in English | MEDLINE | ID: covidwho-1409706

ABSTRACT

The susceptibility and the severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with hyperandrogenism, obesity, and preexisting pulmonary, metabolic, renal, and cardiac conditions. Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with obesity, hyperandrogenism, and cardiometabolic dysregulations. We analyzed cardiac, renal, circulatory, and urinary SARS-CoV-2 viral entry proteins (ACE2, TMPRSS2, TMPRSS4, furin, cathepsin L, and ADAM17) and androgen receptor (AR) expression, in a peripubertal androgen exposure model of PCOS. Peripubertal female mice were treated with dihydrotestosterone (DHT) and low (LFD) or high (HFD) fat diet for 90 days. HFD exacerbated DHT-induced increase in body weight, fat mass, and cardiac and renal hypertrophy. In the heart, DHT upregulated AR protein in both LFD and HFD, ACE2 in HFD, and ADAM17 in LFD. In the kidney, AR protein expression was upregulated by both DHT and HFD. Moreover, ACE2 and ADAM17 were upregulated by DHT in both diets. Renal TMPRSS2, furin, and cathepsin L were upregulated by DHT and differentially modulated by the diet. DHT upregulated urinary ACE2 in both diets, while neither treatment modified serum ACE2. Renal AR mRNA expression positively correlated with Ace2, Tmprss2, furin, cathepsin L, and ADAM17. Our findings suggest that women with PCOS could be a population with a high risk of COVID-19-associated cardiac and renal complications. Furthermore, our study suggests that weight loss by lifestyle modifications (i.e., diet) could potentially mitigate COVID-19-associated deleterious cardiorenal outcomes in women with PCOS.


Subject(s)
COVID-19 , Obesity , Polycystic Ovary Syndrome/virology , Receptors, Coronavirus/immunology , SARS-CoV-2/physiology , Virus Internalization , Animals , COVID-19/immunology , COVID-19/virology , Female , Heart , Kidney , Mice , Mice, Inbred C57BL , Obesity/immunology , Obesity/virology
10.
J Endocrinol ; 249(1): 57-70, 2021 04.
Article in English | MEDLINE | ID: covidwho-1314460

ABSTRACT

Vaspin is a novel adipokine mainly expressed in visceral adipose tissue and closely related to obesity and insulin-resistance. Currently, data about its ovarian expression are limited to animal models and its role in human reproduction is largely unexplored. Our study's aims were then to characterise vaspin expression in the human ovary and to study in vitro its effects on granulosa cells physiology. Secondly, we assessed vaspin and its receptor GRP78 variations in granulosa cells and follicular fluid of a cohort of 112 infertile women undergoing an in vitro fertilisation procedure and allocated to three groups, each including normal-weight and obese subjects: 34 PCOS patients, 33 women with isolated polycystic ovary morphology (ECHO group) and 45 controls. Vaspin and GRP78 expression in the ovary was assessed by immunohistochemistry, RT-qPCR and Western blot. Granulosa cells and follicular fluid were analysed by RT-qPCR and ELISA, respectively. In vitro, granulosa cells metabolism was studied after stimulation with recombinant human vaspin, with and without a siRNA directed against GRP78. Vaspin was highly expressed in the human ovary and concentration-dependently enhanced granulosa cells steroidogenesis, proliferation and viability through GRP78 (P < 0.0001). Vaspin levels in both granulosa cells and follicular fluid were significantly higher in obese women (P < 0.0001) and in the normal-weight ECHO group (P < 0.001), which also had the highest expression rates of GRP78 (P < 0.05). Although further investigation is needed, vaspin appears as a novel modulator of human granulosa cells physiology and possibly plays a role in PCOS pathogenesis, notably protecting from insulin-resistance induced complications.


Subject(s)
Granulosa Cells/physiology , Heat-Shock Proteins/physiology , Polycystic Ovary Syndrome/physiopathology , Serpins/physiology , Adult , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Fertilization in Vitro , Follicular Fluid/chemistry , France , Gene Expression , Granulosa Cells/chemistry , Granulosa Cells/drug effects , Heat-Shock Proteins/analysis , Heat-Shock Proteins/genetics , Humans , Infertility, Female/therapy , Insulin Resistance/physiology , Obesity/metabolism , Ovary/chemistry , Ovary/metabolism , RNA, Messenger/analysis , Serpins/genetics , Serpins/pharmacology , Steroids/biosynthesis
11.
Br Dent J ; 229(2): 125, 2020 07.
Article in English | MEDLINE | ID: covidwho-1241851
12.
Int J Mol Sci ; 22(9)2021 Apr 25.
Article in English | MEDLINE | ID: covidwho-1202187

ABSTRACT

SARS-CoV-2, the causative agent of COVID-19, infects host cells using the angiotensin I converting enzyme 2 (ACE2) as its receptor after priming by host proteases, including TMPRSS2. COVID-19 affects multiple organ systems, and male patients suffer increased severity and mortality. Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive-age women and is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS is associated with obesity and cardiometabolic comorbidities, both being risk factors associated with severe COVID-19 pathology. We hypothesize that elevated androgens in PCOS regulate SARS-CoV-2 entry proteins in multiple tissues increasing the risk for this population. Female mice were treated with dihydrotestosterone (DHT) for 90 days. Body composition was measured by EchoMRI. Fasting glucose was determined by an enzymatic method. mRNA and protein levels of ACE2, Tmprss2, Cathepsin L, Furin, Tmprss4, and Adam17 were quantified by RT-qPCR, Western-blot, or ELISA in tissues, serum, and urine. DHT treatment increased body weight, fat and lean mass, and fasting glucose. Ace2 mRNA was upregulated in the lung, cecum, heart, and kidney, while downregulated in the brain by DHT. ACE2 protein was upregulated by DHT in the small intestine, heart, and kidney. The SARS-CoV-2 priming proteases Tmprss2, Cathepsin L, and Furin mRNA were upregulated by DHT in the kidney. ACE2 sheddase Adam17 mRNA was upregulated by DHT in the kidney, which corresponded with increased urinary ACE2 in DHT treated mice. Our results highlight the potential for increased cardiac, renal, and gastrointestinal dysfunction in PCOS women with COVID-19.


Subject(s)
COVID-19/pathology , Hyperandrogenism/pathology , Polycystic Ovary Syndrome/pathology , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/blood , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/urine , Animals , Blood Glucose/analysis , Body Weight/drug effects , COVID-19/complications , COVID-19/virology , Cathepsin L/genetics , Cathepsin L/metabolism , Dihydrotestosterone/pharmacology , Female , Humans , Kidney/metabolism , Mice , Mice, Inbred C57BL , Polycystic Ovary Syndrome/complications , SARS-CoV-2/isolation & purification , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Up-Regulation/drug effects , Virus Internalization
14.
Eur J Endocrinol ; 184(5): 637-645, 2021 May.
Article in English | MEDLINE | ID: covidwho-1175452

ABSTRACT

OBJECTIVE: Several recent observational studies have linked metabolic comorbidities to an increased risk from COVID-19. Here we investigated whether women with PCOS are at an increased risk of COVID-19 infection. DESIGN: Population-based closed cohort study between 31 January 2020 and 22 July 2020 in the setting of a UK primary care database (The Health Improvement Network, THIN). METHODS: The main outcome was the incidence of COVID-19 coded as suspected or confirmed by the primary care provider. We used Cox proportional hazards regression model with stepwise inclusion of explanatory variables (age, BMI, impaired glucose regulation, androgen excess, anovulation, vitamin D deficiency, hypertension, and cardiovascular disease) to provide unadjusted and adjusted hazard risks (HR) of COVID-19 infection among women with PCOS compared to women without PCOS. RESULTS: We identified 21 292 women with a coded diagnosis of PCO/PCOS and randomly selected 78 310 aged and general practice matched control women. The crude COVID-19 incidence was 18.1 and 11.9 per 1000 person-years among women with and without PCOS, respectively. Age-adjusted Cox regression analysis suggested a 51% higher risk of COVID-19 among women with PCOS compared to women without PCOS (HR: 1.51 (95% CI: 1.27-1.80), P < 0.001). After adjusting for age and BMI, HR reduced to 1.36 (1.14-1.63)], P = 0.001. In the fully adjusted model, women with PCOS had a 28% increased risk of COVID-19 (aHR: 1.28 (1.05-1.56), P = 0.015). CONCLUSION: Women with PCOS are at an increased risk of COVID-19 infection and should be specifically encouraged to adhere to infection control measures during the COVID-19 pandemic. SIGNIFICANCE STATEMENT: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardio-metabolic disease, which have been identified as a risk factor for COVID-19. To investigate whether the increased metabolic risk in PCOS translates into an increased risk of COVID-19 infection, we carried out a population-based closed cohort study in the UK during its first wave of the SARS-CoV-2 pandemic (January to July 2020), including 21 292 women with PCOS and 78 310 controls matched for sex, age and general practice location. Results revealed a 52% increased risk of COVID-19 infection in women with PCOS, which remained increased at 28% above controls after adjustment for age, BMI, impaired glucose regulation and other explanatory variables.


Subject(s)
COVID-19/epidemiology , Polycystic Ovary Syndrome/epidemiology , Adult , Age Factors , Body Mass Index , Cardiovascular Diseases/epidemiology , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , Middle Aged , Obesity/epidemiology , Polycystic Ovary Syndrome/metabolism , Prediabetic State/epidemiology , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2 , Testosterone/metabolism , United Kingdom/epidemiology , Vitamin D Deficiency/epidemiology
15.
Front Endocrinol (Lausanne) ; 12: 638621, 2021.
Article in English | MEDLINE | ID: covidwho-1133905

ABSTRACT

Background: Women with polycystic ovary syndrome (PCOS) often have vitamin D deficiency, a known risk factor for severe COVID-19 disease. Alveolar macrophage-derived cytokines contribute to the inflammation underlying pulmonary disease in COVID-19. We sought to determine if basal macrophage activation, as a risk factor for COVID-19 infection, was present in PCOS and, if so, was further enhanced by vitamin D deficiency. Methods: A cross-sectional study in 99 PCOS and 68 control women who presented sequentially. Plasma levels of a macrophage-derived cytokine panel were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Vitamin D was measured by tandem mass spectroscopy. Results: Vitamin D was lower in PCOS women (p<0.0001) and correlated negatively with body mass index (BMI) in PCOS (r=0.28, p=0.0046). Basal macrophage activation markers CXCL5, CD163 and MMP9 were elevated, whilst protective CD200 was decreased (p<0.05); changes in these variables were related to, and fully accounted for, by BMI. PCOS and control women were then stratified according to vitamin D concentration. Vitamin D deficiency was associated with decreased CD80 and IFN-γ in PCOS and IL-12 in both groups (p<0.05). These factors, important in initiating and maintaining the immune response, were again accounted for by BMI. Conclusion: Basal macrophage activation was higher in PCOS with macrophage changes related with increased infection risk associating with vitamin D; all changes were BMI dependent, suggesting that obese PCOS with vitamin D deficiency may be at greater risk of more severe COVID-19 infection, but that it is obesity-related rather than an independent PCOS factor.


Subject(s)
COVID-19/epidemiology , Cytokines/metabolism , Macrophages/metabolism , Polycystic Ovary Syndrome/epidemiology , Vitamin D Deficiency/epidemiology , Adult , Biomarkers/analysis , Blood Proteins/analysis , Body Mass Index , COVID-19/complications , COVID-19/immunology , Cross-Sectional Studies , Female , Humans , Macrophage Activation , Macrophages/chemistry , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/immunology , Risk Assessment , Tandem Mass Spectrometry , Vitamin D/blood , Vitamin D Deficiency/complications
17.
Eur J Pharmacol ; 898: 173934, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1086916

ABSTRACT

Metformin is the most commonly prescribed oral antidiabetic medication. Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin. Metformin is an established insulin receptor sensitising antihyperglycemic agent, is highly affordable, and has superior safety and efficacy profiles. Emerging experimental and clinical evidence suggests that metformin has pleiotropic non-glycemic effects. Metformin appears to have weight stabilising, renoprotective, neuroprotective, cardio-vascular protective, and antineoplastic effects and mitigates polycystic ovarian syndrome. Anti-inflammatory and antioxidant effects of metformin seem to qualify it as an adjunct therapy in treating infectious diseases such as tuberculosis, viral hepatitis, and the current novel Covid-19 infections. So far, metformin is the only prescription medicine relevant to the emerging field of senotherapeutics. Non-glycemic effects of metformin favourable to its repurposing in therapeutic use are hereby discussed.


Subject(s)
Anti-Infective Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Hypoglycemic Agents/therapeutic use , Immunologic Factors/therapeutic use , Metformin/therapeutic use , Protective Agents/therapeutic use , Animals , Anti-Infective Agents/adverse effects , Antineoplastic Agents/adverse effects , COVID-19/drug therapy , COVID-19/epidemiology , Cardiovascular Diseases/prevention & control , Female , Humans , Hypoglycemic Agents/adverse effects , Immunologic Factors/adverse effects , Kidney Diseases/prevention & control , Metabolic Syndrome/drug therapy , Metformin/adverse effects , Obesity/drug therapy , Pandemics , Polycystic Ovary Syndrome/drug therapy , Protective Agents/adverse effects , SARS-CoV-2
19.
Obstet Gynecol ; 137(3): 423-429, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1066430

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), uses two primary receptors, type II transmembrane serine protease and angiotensin-converting enzyme-2, for priming and cellular invasion, respectively. Both proteins have been demonstrated to be present in different concentrations in females and males, which may explain a mechanism for the reported higher case-fatality rate in males. Despite the known sex difference in COVID-19 disease mortality, preliminary data suggest there are certain female populations, including pregnant and menopausal women and possibly polycystic ovarian syndrome patients who are more susceptible to COVID-19-related morbidity. This commentary analyzes the interplay between sex differences, hormones, and the immune function in each of these populations with respect to the risk and severity of COVID-19 and proposes biological rationales to explain these differences.


Subject(s)
COVID-19/epidemiology , COVID-19/genetics , Genetic Predisposition to Disease , Angiotensin-Converting Enzyme 2/genetics , Chromosomes, Human, X , Disease Susceptibility , Female , Humans , Male , Menopause/physiology , Morbidity , Polycystic Ovary Syndrome/epidemiology , Pregnancy , SARS-CoV-2/physiology , Serine Endopeptidases/genetics , Sex Factors
20.
Am J Physiol Renal Physiol ; 320(2): F243-F248, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1035216

ABSTRACT

Coronavirus disease 2019 (COVID-19) has reached pandemic proportions, affecting millions of people worldwide. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of COVID-19. Epidemiological reports have shown that the severity of SARS-CoV-2 infection is associated with preexisting comorbidities such as hypertension, diabetes mellitus, cardiovascular diseases, and chronic kidney diseases, all of which are also risk factors for acute kidney injury (AKI). The kidney has emerged as a key organ affected by SARS-CoV-2. AKI is associated with increased morbidity and mortality in patients with COVID-19. Male sex is an independent predictor for AKI, and an increased death rate has been reported in male patients with COVID-19 worldwide. The mechanism(s) that mediate the sex discrepancy in mortality due to COVID-19 remain(s) unknown. Angiotensin-converting enzyme (ACE)2 is the receptor for SARS-CoV-2. Alterations in the ACE-to-ACE2 ratio have been implicated in renal diseases. This perspective aims to discuss data that suggest that androgens, via alterations in the intrarenal renin-angiotensin system, impair renal hemodynamics, predisposing patients to AKI during COVID-19 infection, which could explain the higher mortality observed in men with COVID-19. Clinicians should ensure early and effective cardiometabolic control for all patients to ameliorate the compensatory elevation of ACE2 and alterations in the ACE-to-ACE2 ratio. A better understanding of the role of androgens in SARS-CoV-2-associated AKI and mortality is imperative. The kidney could constitute a key organ that may explain the sex disparities of the higher mortality and worst outcomes associated with COVID-19 in men.


Subject(s)
Acute Kidney Injury/virology , Androgens/metabolism , COVID-19/mortality , COVID-19/pathology , Kidney/metabolism , SARS-CoV-2 , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Angiotensin-Converting Enzyme 2/metabolism , Female , Gene Expression Regulation , Humans , Male , Polycystic Ovary Syndrome , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , Sex Factors , Transgender Persons
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