Abstract P184: Aging Male Offspring Of Polycystic Ovary Syndrome Rat Model Have Normal Blood Pressure And Exaggerated Pressor Response To Angiotensin II

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Noha M Shawky ◽  
Jane F Reckelhoff

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia and elevated blood pressure (BP). Male offspring of hyperandrogenemic female (HAF) rats, PCOS model, have low birth weight, with normal BP, but exaggerated pressor response to Angiotensin (Ang) II as adults. The present study tested the hypothesis that with aging, male HAF offspring are at increased risk of developing hypertension (HT). Methods: Hyperandrogenemia was induced in female SD rats (5α-dihydrotestosterone pellets 7.5 mg/90 d, s.c. at 4 wks of age and throughout life). HAF and controls (10-12 wks of age) were mated, allowed to deliver and lactate. HAF and control male offspring (F1 HAF and F1 Contr. ) were left untreated until 16-20 mos of age. Body composition (echoMRI) and proteinuria were measured in aging offspring. BP was measured (baseline; 9 d, enalapril (25 mg/kg/d); 7d) by telemetry. Rats were then given Ang II (50 ng/kg/min, s.c. minipumps) or saline (No Ang II) for 13 d. High salt (4%) diet (HSD) was started for both Ang II and No Ang II groups on day 8 of Ang II. Results: Aging male F1 HAF had similar fat mass, but lower lean mass (433.7 ± 6 vs 453.6 ± 7 g, p< 0.05) and body weight (552.3 ± 11 vs 590.4 ± 11 g, n = 8-16, p<0.05) than F1 Contr. . Despite higher proteinuria in F1 HAF (412 ± 42 mg/24h vs 292 ± 47 mg/24h, n = 11-13, p<0.05), baseline mean arterial pressure (MAP) was similar between F1 HAF and F1 Contr. (130 ± 1 mmHg vs 126 ± 4 mmHg, respectively, n = 8, p=NS). Enalapril decreased MAP similarly in both F1 HAF and F1 Contr. (110 ± 2 mmHg vs 107 ± 3 mmHg, respectively). On low salt, Ang II increased MAP to higher levels in F1 HAF than F1 contr., saline-treated>F1 HAF and F1 Contr. (140 ± 11 mmHg vs 119 ± 10 mmHg, 105 ± 3 mmHg and 103 ± 4 mmHg, respectively, n = 4, p<0.05 F 1 HAF vs other grps). With 6 days of HSD, MAP was similar between F1 HAF and F1 Contr. not treated with Ang II (142 ± 6 mmHg and 132 ± 9 mmHg, respectively). MAP was also similar between F1 HAF and F1 Contr. with Ang II (169 ± 1 mmHg and 159 ± 9 mmHg, respectively). However, both Ang II-treated groups had significantly higher MAP compared to their respective No Ang II control groups. Conclusion: Aging male HAF offspring do not develop hypertension, but are at increased risk of renal injury and cardiovascular disease due to enhanced pressor sensitivity to Ang II.

2020 ◽  
Vol 16 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Djuro Macut ◽  
Violeta Mladenović ◽  
Jelica Bjekić-Macut ◽  
Sarantis Livadas ◽  
Olivera Stanojlović ◽  
...  

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women during reproductive age. It was shown that PCOS women are with high risk for dyslipidemia, glucose intolerance, type 2 diabetes and metabolic syndrome. These factors are considered to represent traditional risk factors for the occurrence of cardiovascular disease. Observed increased risk for hypertension in PCOS women seems to be associated with insulin resistance and hyperinsulinemia. Both conditions interfere with the endothelium-dependent vasodilatation mechanisms causing vascular muscle wall hypertrophy. Obesity and insulin resistance are considered key factors for the alteration of blood pressure in PCOS women. Higher cardiovascular risk is implicated in PCOS with aging and its consequent association with both systolic and diastolic blood pressure. The elements of renin-angiotensin-aldosterone system (RAAS) have an impact on endothelial dysfunction as a marker of cardiovascular damage that could be modified is women with PCOS. Androgens and components of RAAS are involved in the process of atherogenesis in PCOS women. Therefore, it is hypothesized that spironolactone treatment could ameliorate endothelial dysfunction in PCOS women. Recently it was shown that telmisartan, angiotensin II receptor antagonist poses insulinsensitizing capacity to activate PPAR gamma and mediate favorable metabolic and reproductive effects in hypertensive PCOS women.


2019 ◽  
Vol 51 (01) ◽  
pp. 22-34 ◽  
Author(s):  
Mina Amiri ◽  
Fahimeh Tehrani ◽  
Razieh Bidhendi-Yarandi ◽  
Samira Behboudi-Gandevani ◽  
Fereidoun Azizi ◽  
...  

AbstractWhile several studies have documented an increased risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS), associations between androgenic and metabolic parameters in these patients are unclear. We aimed to investigate the relationships between biochemical markers of hyperandrogenism (HA) and metabolic parameters in women with PCOS. In this systematic review and meta-analysis, a literature search was performed in the PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science from 2000 to 2018 for assessing androgenic and metabolic parameters in PCOS patients. To assess the relationships between androgenic and metabolic parameters, meta-regression analysis was used. A total number of 33 studies involving 9905 patients with PCOS were included in this analysis. The associations of total testosterone (tT) with metabolic parameters were not significant; after adjustment for age and BMI, we detected associations of this androgen with low-density lipoproteins cholesterol (LDL-C) (β=0.006; 95% CI: 0.002, 0.01), high-density lipoproteins cholesterol (HDL-C) (β=–0.009; 95% CI: –0.02, –0.001), and systolic blood pressure (SBP) (β=–0.01; 95% CI: –0.03, –0.00). We observed a positive significant association between free testosterone (fT) and fasting insulin (β=0.49; 95% CI: 0.05, 0.91); this association remained significant after adjustment for confounders. We also detected a reverse association between fT and HDL-C (β=–0.41; 95% CI: –0.70, –0.12). There was a positive significant association between A4 and TG (β=0.02; 95% CI: 0.00, 0.04) after adjustment for PCOS diagnosis criteria. We also found significant negative associations between A4, TC, and LDL-C. Dehydroepiandrosterone sulfate (DHEAS) had a positive association with LDL-C (β=0.02; 95% CI: 0.001, 0.03) and a reverse significant association with HDL-C (β=–0.03; 95% CI: –0.06, –0.001). This meta-analysis confirmed the associations of some androgenic and metabolic parameters, indicating that measurement of these parameters may be useful for predicting metabolic risk in PCOS patients.


2017 ◽  
Vol 107 (3) ◽  
pp. 796-802 ◽  
Author(s):  
Iris Lee ◽  
Laura G. Cooney ◽  
Shailly Saini ◽  
Maria E. Smith ◽  
Mary D. Sammel ◽  
...  

2021 ◽  
Vol 15 (5) ◽  
pp. 1522-1525
Author(s):  
S. Inayat ◽  
H. F. Khattak ◽  
M. G. Muhammad ◽  
K. Robeen ◽  
A. Inayat ◽  
...  

Objective: The main objective of this study is to determine the efficacy of metformin therapy on clinical and hormonal indices of patients with polycystic ovary syndrome. Study Design: Randomized control trial Place and Duration: Study was conducted at Obstetrics & Gynaecology department of Northwest General Hospital and Research Center, Peshawar and Mian Rashid Hussain Shaheed Memorial Hospital, Pabbi for duration of nine months from March 2020 to November 2020. Methods: Total 100 patients of polycystic ovary syndrome were presented in this study. Patients were aged between 18 to 45years. Patients detailed demographics including age, body mass index and socio-economicstatus were recorded after taking informed written consent. Patients were divided into 2-groups, group I had 50 patients and received metformin (500 mg) three times a day and group II had 50 patients and received pioglitazone (30 mg) three times a day for 3months.Clinical (body weight, blood pressure (BP), and body mass index) and indices fasting blood sugar (FBS), serum triglyceride (TG), cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone (DHEA) were measured before and after therapy. Complete data was analyzed by SPSS 22.0 version. Results: Mean age of the patients in group I was 29.18 ± 2.25 years with mean BMI 26.14 ± 8.86 kg/m2 and in group II mean age was 29.8 ± 2.52 years with mean BMI 27.64 ± 7.68 kg/m2.Significantly decrease in blood pressure (systolic 105.41±8.57, diastolic 67.19±8.9), hair loss 20 (40%),oligomenorrhea 23 (46%), body weight 74.45±9.72, waist circumference and dehydroepiandrosterone (DHEA) 2.35±0.67 and as compared to group II. Only triglycerides gave results of reduction in group II 115.39±64.11. Among both groups serum insulin, acne, menstrual disturbance and fasting blood sugar were controlled after treatment. Conclusion: We concluded in this study that use of metformin in patients with polycystic ovary syndrome resulted in to decrease clinical body weight, blood pressure (BP), body mass index and hormonal indices with reduction of serum insulin, acne, menstrual disturbance and fasting blood sugar but pioglitazone was an alternative effective and reliable method in PCOS patients. Keywords: Polycystic ovary syndrome, Insulin resistance, Metformin, Pioglitazone


2021 ◽  
Author(s):  
Ky'Era V. Actkins ◽  
Genevieve Jean-Pierre ◽  
Melinda C. Aldrich ◽  
Digna R. Velez Edwards ◽  
Lea K. Davis

Females with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, have an increased risk of developing metabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). Furthermore, while only diagnosable in females, males with a family history of PCOS can also exhibit a poor cardiometabolic profile. Therefore, we aimed to elucidate the role of sex in the relationship between PCOS and its comorbidities by conducting bidirectional genetic risk score analyses in both sexes. We conducted a phenome-wide association study (PheWAS) using PCOS polygenic risk scores (PCOSPRS) to understand the pleiotropic effects of PCOS genetic liability across 1,380 medical conditions in females and males recorded in the Vanderbilt University Medical Center electronic health record (EHR) database. After adjusting for age and genetic ancestry, we found that European descent males with higher PCOSPRS were significantly more likely to develop cardiovascular diseases than females at the same level of genetic risk, while females had a higher odds of developing T2D. Based on observed significant associations, we tested the relationship between PRS for comorbid conditions (e.g., T2D, body mass index, hypertension, etc.) and found that only PRS generated for BMI and T2D were associated with a PCOS diagnosis. We then further decomposed the T2DPRS association with PCOS by adjusting the model for measured BMI and BMIresidual (enriched for the environmental contribution to BMI). Results demonstrated that genetically regulated BMI primarily accounted for the relationship between T2DPRS and PCOS. This was further supported in a mediation analysis, which only revealed clinical BMI measurements, but not BMIresidual, as a strong mediator for both sexes. Overall, our findings show that the genetic architecture of PCOS has distinct metabolic sex differences, but these associations are only apparent when PCOSPRS is explicitly modeled. It is possible that these pathways are less explained by the direct genetic risk of metabolic traits than they are by the risk factors shared between them, which can be influenced by biological variables such as sex.


2018 ◽  
Vol 7 (5) ◽  
pp. R187-R195 ◽  
Author(s):  
Yao Chen ◽  
Shu-ying Fang

Polycystic ovary syndrome (PCOS) is a heterogenous endocrine disorder with typical symptoms of oligomenorrhoea, hyperandrogenism, hirsutism, obesity, insulin resistance and increased risk of type 2 diabetes mellitus. Extensive evidence indicates that PCOS is a genetic disease and numerous biochemical pathways have been linked with its pathogenesis. A number of genes from these pathways have been investigated, which include those involved with steroid hormone biosynthesis and metabolism, action of gonadotropin and gonadal hormones, folliculogenesis, obesity and energy regulation, insulin secretion and action and many others. In this review, we summarize the historical and recent findings in genetic polymorphisms of PCOS from the relevant publications and outline some genetic polymorphisms that are potentially associated with the risk of PCOS. This information could uncover candidate genes associating with PCOS, which will be valuable for the development of novel diagnostic and treatment platforms for PCOS patients.


2021 ◽  
Vol 27 ◽  
Author(s):  
Jelica Bjekić-Macut ◽  
Tamara Vukašin ◽  
Zelija Velija-Ašimi ◽  
Azra Bureković ◽  
Marija Zdravković ◽  
...  

: Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women during reproductive period. It is considered a complex metabolic disorder with long-term metabolic, as well as reproductive consequences. Main pathophysiological pathways are related to the increased androgen levels and insulin resistance. Nowadays, genetic origins of PCOS are acknowledged, with numerous genes involved in the pathogenesis of hyperandrogenemia, insulin resistance, inflammation and disturbed folliculogenesis. Rotterdam diagnostic criteria are most widely accepted and four PCOS phenotypes have been recognized. Metabolic abnormalities are more common in phenotypes 1 and 2. Women with classic PCOS are more obese and typically have central type of obesity, more prevalently displaying dyslipidemia, insulin resistance and metabolic syndrome that could be associated with an increased risk of cardiovascular complications during life. Heterogeneity of phenotypes demands an individualized approach in the treatment of women with PCOS. Metabolic therapies involve a lifestyle intervention followed by the introduction of insulin sensitizers including metformin and inositols, glucagon-like peptide 1 receptor agonists (GLP-1 RA), as recently sodium glucose contransporter-2 (SGLT2) inhibitors. Addition of an insulin sensitizer to the standard infertility therapy such as CC improves ovulation and pregnancy rates. Our current review analyzes the contemporary knowledge of PCOS etiology and etiopathogenesis, its cardiometabolic risks and their outcomes, as well as therapeutic advances for women with PCOS.


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