Polycystic Ovary Syndrome Females Research Articles

Effect of cyproterone acetate/ethinyl estradiol combination on periodontal status and high-sensitivity C-reactive protein levels in women with polycystic ovary syndrome: a cross-sectional study.

Polycystic ovary syndrome (PCOS) is widely reported among young females, and anti-androgens are used for treating hirsutism and acne in these patients. The protective effects of myo-inositol, oral contraceptives, and insulin sensitizers have been reported on the periodontium and high-sensitivity C-reactive protein (hsCRP) levels in PCOS females. However, cyproterone acetate/ethinyl estradiol (CPA/EE) has not yet been studied. This cross-sectional study explores the periodontal status and systemic inflammation in PCOS women on CPA/EE drug combination compared to females not on medication. A total of 150 participants were enrolled into three groups: 50 newly diagnosed PCOS females not on medication (N-PCOS); 50 PCOS females consuming CPA/EE combination for the last 6 months (PCOS+CPA/EE); and 50 systemically healthy females (control group). Anthropometric, biochemical, periodontal parameters, and health-related quality of life questionnaires were recorded. N-PCOS and PCOS+CPA/EE groups showed a nonsignificant difference in hsCRP levels, Gingival Index, bleeding on probing, waist circumference, and waist-hip ratio (P > .05). Gingival thickness and keratinized tissue width were significantly greater in the PCOS+CPA/EE than the N-PCOS group (P ≤ .05); however, these were comparable with the control group (P > .05). Regression analysis showed significant association of bleeding on probing with Gingival Index, clinical attachment level, and hsCRP (P ≤ .05). CPA/EE combination does not influence the periodontal and systemic inflammatory status in PCOS females, as similar levels of local and systemic inflammation were observed in CPA/EE consumers compared with PCOS females not on medication. However, it might play a role in increasing gingival thickness and keratinized tissue width in these patients.

Unraveling PCOS: Exploring its causes and diagnostic challenges

Abstract Women in the reproductive age range are usually affected with Polycystic Ovary Syndrome (PCOS), a complex and multifaceted condition. Anovulation, hyperandrogenism, and metabolic difficulties like hyperglycemia, hypertension, and obesity in women are all manifestations of this condition, which also affects the reproductive system. The National Institutes of Health in the 1990s, Rotterdam in 2003, and Androgen Excess Polycystic Ovary Syndrome in 2009 all contributed to the evolution of the diagnostic criteria for PCOS. The 2003 Rotterdam criteria are currently the most generally used criteria. They call for at least two of the three criteria – irregular menstrual periods, polycystic ovary morphology on imaging, and hyperandrogenism – either clinically or biochemically – to be present in order to diagnose PCOS. It is currently being suggested that the anti-Müllerian hormone in serum be used instead of follicular count as an official indicator of polycystic ovarian morphology/PCOS. Hyperandrogenism and irregular periods are essential components in determining PCOS in adolescent patients. More recently, it has been shown that artificial intelligence, especially machine learning, holds great promise for detecting and predicting PCOS with high accuracy, potentially assisting in early management and treatment decisions. Examining the underlying mechanisms, clinical symptoms, and challenges involved in making a diagnosis of PCOS in females is the premise of this review article.

Effects of Gender and Vitamin D on Vascular Reactivity of the Carotid Artery on a Testosterone-Induced PCOS Model

The negative cardiovascular effects of polycystic ovary syndrome (PCOS) and vitamin D deficiency (VDD) have been discussed previously; however, the sex differences between PCOS females and males are not yet known. Our aim was to investigate the effect of PCOS and VDD in the carotid artery of male and female Wistar rats. Females were treated with transdermal testosterone (Androgel) for 8 weeks, which caused PCOS. VDD and vitamin D supplementation were accomplished via diet. The carotid arteries’ contraction and relaxation were examined using myography. Receptor density was investigated using immunohistochemistry. In PCOS females, angiotensin receptor density, angiotensin II-induced contraction, androgen receptor optical density, and testosterone-induced relaxation increased. The increased contractile response may increase cardiovascular vulnerability in women with PCOS. As an effect of VDD, estrogen receptor density increased in all our groups, which probably compensated for the reduced relaxation caused by VDD. Testosterone-induced relaxation was decreased as a result of VDD in males and non-PCOS females, whereas this reduction was absent in PCOS females. Male sex is associated with increased contraction ability compared with non-PCOS and PCOS females. VDD and Androgel treatment show significant gender differences in their effects on carotid artery reactivity. Both VDD and PCOS result in a dysfunctional vascular response, which can contribute to cardiovascular diseases.

Effectiveness of Myoinositol alone or in Companion with Metformin in Improving Hormonal, Metabolic, and Clinical Features of PCOS Women

Polycystic ovary syndrome (PCOS) referring to a syndrome that is recognized as a life-course disease and has both metabolic and reproductive signs; main pathophysiological cause includes insulin resistance, hyperandrogenism, and oxidative stress state. The study aimed to assess the impact of combining Myoinositol and Metformin, the main insulin-sensitizing drugs, on improving clinical, metabolic, and hormonal parameters in females with PCOS. A clinical trial that was prospective, randomized, and comparative on 54 patients (aged 18-40 y) are divided into three groups: group1 patients allocated to receive Myo-inositol(4g), group2 patients assigned to receive Metformin(1g) and group3 patients assigned to receive Myo-inositol(4g) + Metformin(1g) all for three months. Baseline and post-intervention fasting blood samples were collected to evaluate hormonal, metabolic parameters, and oxidative stress biomarkers. Metformin and Myoinositol together lead to a significant drop free testosterone (P = 0.002), LH (P 0.003), LH to FSH ratio(P=0.004), FSI (P 0.012), the HOMA IR (p 0.019), hirsutism score (p=<0.001) and acne score (p= 0.003), besides substantial increase in GPX (P 0.02). Meanwhile, Myoinositol supplement causes a substantial drop in free testosterone (p=0.013), FSI (P 0.02), and HOMA – IR (P value=0.025) also a substantial rise in GPX (P=0.005). Combining Myoinositol with metformin results in improving clinical, metabolic, hormonal parameters, as well as oxidative indicators for PCOS females.

Assessment of Cardiac Autonomic Function in Women With Polycystic Ovary Syndrome Through Ewing's Battery, Heart Rate Variability Analysis, and Composite Autonomic Symptom Score-31 Scale.

Introduction Polycystic ovary syndrome (PCOS) is a frequently occurringendocrine condition prevalent in women of reproductive age characterized by chronic anovulation, hyperandrogenism, insulin resistance, and a low-grade inflammatory state. Patients with PCOS are more vulnerable to developing cardiac and metabolic co-morbidities. Sympathetic overactivity is also reported in PCOS patients. Objective This study aimed to assess cardiac autonomic function in PCOS by Heart Rate Variability Analysis, Ewing's Test, and Composite Autonomic Symptom Scale-31 (COMPASS-31). Methods Thirty female PCOS patients and 30 age-matched control females were enrolled in the study. Both cases and controls were subdivided into sub-groups based on body mass index (BMI) and waist-to-hip ratio (WHR). The cardiac autonomic functions were assessed by the COMPASS-31 questionnaire, Ewing's battery tests, and short-term heart rate variability analysis. Results There was no significant difference in age, BMI, and WHR of both groups. Additionally, cases had a significantly higher low frequency to high frequency (LF/HF) ratio and COMPASS-31 score andalsoreported more derangement in Ewing's battery test, indicating cardiac autonomic dysfunction in PCOS patients. Conclusion Patients with PCOS are more prone to developing cardiac and metabolic co-morbidities.Early assessment of cardiac autonomic function can prevent future complications with timely interventions. Altered autonomic function in PCOS patients can be due to hyperandrogenism and insulin resistance.

Effect of C-reactive protein deficiency on insulin resistance reversal in rats with polycystic ovary syndrome through augmented leptin action

BackgroundC-reactive protein(CRP), is an inflammatory marker that weaken leptin bioavailability and insulin sensitivity to disturb energy and glucose metabolism. Polycystic ovary syndrome (PCOS) exhibit a metabolic component consisting of higher plasma CRP levels, hyperinsulinemic and hyperleptinemia. The ability of leptin to regulation of hepatic glucose production (HGP) in the absence of CRP in PCOS remain unknown.MethodsDehydroepiandrosterone (DHEA) was used to induce PCOS in rats. We assessed the effects of CRP gene knockout in PCOS model rats on body weight, energy expenditure glucose metabolism and insulin sensitivity. We conducted experiments involving the administration of leptin to both the peripheral and central systems in PCOS model rats with CRP knockout, and studied the effects on changes in glucose kinetics during hyperinsulinemic-euglycemic clamps.ResultsIn female PCOS rats, the lack of CRP resulted in decreased leptin resistance and weight gain, increased energy expenditure, and improved insulin sensitivity. Additionally, the deletion of the CRP gene strengthened the HGP-lowering effects of leptin when administered peripherally or centrally. This effect was accompanied by a decrease in the expression of hepatic gluconeogenic enzymes and an increase in hepatic insulin signaling. Finally, inhibition of glucose production was also enhanced for central leptin administration during lipid infusion in PCOS rats.ConclusionsOur findings highlight the therapeutic potential of targeting CRP to restore glucose homeostasis and insulin sensitivity for leptin in PCOS.

Role of Sestrin 1 in Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that affects at least 10% of women of reproductive age. Cystic ovaries, low or absent ovulation, and high circulating testosterone levels are the the group of symptoms that define polycystic ovary syndrome (PCOS).The aim of study: To investigate whether sestrin 1 can serve a prognostic indicator in polycystic ovary syndrome. The study included 100 women with age ranged between (18 – 44) years involving 70 PCOS patients and 30 apparently healthy women as a control in reproductive age, at the reproductive fertility consultant of gynecological and obstetric teaching hospital, Kerbala health directorate Iraq and College of Applied Medical Sciences, University of Kerbala Iraq during the duration from October ., 2022 to April, 2023. The Rotterdam criteriOn-2003 was presumed to PCOS females. The result showed there were highly significant decreasing in woman with PCOS in contrast to woman without PCOS. According to BMI showed highly significant in the overweight at( P =0.001) whereas in the obesity at( P= 0.004) and normal weight at (P= 0.004). According to age showed highly significant in age group (18_23) while in the age group( 24_29)at (P =0.000) and age group (30_35) at (P=0.006) whereas age group (36_41) at( P=0.274) The conclusion indicated that reduced serum sestrin 1 levels may be has potential as a new PCOS diagnostic biomarker .

Levonorgestrel-releasing intrauterine system effects on metabolic variables in PCOS

Background We aimed to determine and compare the reproductive hormone level and metabolic of patients with polycystic ovary syndrome (PCOS) when treated with a levonorgestrel-releasing intrauterine system (LNG-IUS). Objectives Sixty-four women with PCOS (Group A) and sixty-six healthy women inserted with a LNG-IUS for conception (Group B) were recruited from the Department of Obstetrics and Gynecology in Jinhua Hospital Zhejiang University School of Medicine. Method We compared the general characteristics of the cases between the two groups, including age, body mass index (BMI), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), abdominal circumference (AC) and waist circumference (WC). Each patient was evaluated by transvaginal ultrasonography (TVS) to determine the number of oocytes and ovarian volume, and the intima-media thickness (IMT) of the common carotid artery was measured on an ECG image from the left common carotid artery before and six months, 12 months and 24 months after patients were inserted with the LNG-IUS. Hormone levels (follicle stimulating hormone, luteinizing hormone, serum estradiol and total testosterone), serum insulin, sex hormone binding globulin (SHBG), total cholesterol (TC), high density lipoprotein (HDL), and triglyceride (TG), were evaluated before and six months, 12 months and 24 months after patients were inserted with an LNG-IUS. The levels of testosterone (T) in the non-HA (hyperandrogenemia) group and HA group in PCOS group were compared with the baseline. We also compared cases without insulin resistance in the PCOS group with their baseline. Results Prior to LNG-IUS insertion, the PCOS group had significantly higher total testosterone levels (p < 0.05), lower HDL levels (p < 0.05), and a greater ovarian volume (p < 0.05) than the control group. Compared to baseline values, there was a significant increase in fasting glycemia at six months after LNG-IUS insertion (p < 0.05). Mean ovarian volume was significantly smaller than the volume prior to LNG-IUS insertion (p < 0.05); LDL and TC were significantly reduced when compared to baseline evaluation in the PCOS group. The remaining variables did not differ significantly during the 24 months follow-up period. The control group did not show any significant changes when compared to the period before LNG-IUS insertion. When the groups were compared after the 24-month follow-up, WC, AC, FSH, LH, T, SHBG, HDL, FINs, FAI and ovarian volume were significantly different when compared between the two groups (p < 0.05) . Conclusion The LNG-IUS is an effective and safe non-surgical device and the use of this system for 24 months did not result in significant changes in the clinical and metabolic variables in women with PCOS and healthy control females.

Effect of COVID-19 on the Role of Renin Enzyme and ACE2 and Hormones in PCOS Females

Polycystic ovary syndrome (PCOS) is the most endocrine problem in women of regenerative age. PCOS women typically belong to an age and sex group which is at higher risk for severe coronavirus disease (COVID-19). COVID-19 targets cells through angiotensin-converting enzyme 2 (ACE2) receptor presents on cells in veins, lungs, heart, digestion tracts, and kidneys. Renin-Angiotensin System (RAS) over activity has likewise been described in metabolic disorders; type 2 diabetes mellitus (T2DM), and conditions shared by women with polycystic ovary condition. The point of this study is to know the job of renin and ACE2 in PCOS and coronavirus and its relationship with hormones and other metabolic parameters related. The study groups consist of 120 sample subjects consisting of 80 PCOS-women divided into two groups: - (40 PCOS-women infected with COVID-19 and 40 PCOS-women non-infected with COVID-19) and 40 healthy-women divided into two groups: - 20 women-COVID-19 infected, and 20 women non-COVID-19 infected, ranging in age from 15–40 years old. Renin and ACE2, FBS, lipid profile, level of insulin, HOMA IR, FSH, LH, and testosterone, were measured for all participants. There was an increase in the levels of renin, ACE2, insulin, HOMA-IR, LH, LH / FSH ratio, and testosterone, except HDL and FSH were low when comparing PCOS patients groups with healthy groups. There was a decrease in renin and ACE2 in PCOS women infected with COVID-19 compared with PCOS women non-infection with COVID-19. Infection of COVID-19 and low ACE2 levels lead to respiratory damage and problem in reproductive in PCOS patients. Also, at the same time ACE2 high level in PCOS makes them more risk for coronavirus and is not involved in the cause of PCOS, however renin enzyme may be affected by BMI associated with PCOS.

Effectiveness of combined seeds (pumpkin, sunflower, sesame, flaxseed): As adjacent therapy to treat polycystic ovary syndrome in females.

The formation and release of eggs during ovulation are impacted by high amounts of androgens. Seed cycling is powerful in the treatment of polycystic ovary syndrome (PCOS). For efficacy studies, 90 women with PCOS, between 15 and 40 years were selected from the department of gynecology, Tertiary care unit. Women with PCOS were divided into three groups (T0, T1, T2) (20 women/group). Among these three groups, the first was the control group (T0). The second group was the experimental group (T1). In T1, 20 women with PCOS were treated with a portion control diet and METFORMIN 500 mg tab/day for 90 days. The third group was also an experimental group (T2). In this group, 20 women with PCOS were also treated with another treatment plan for 90 days, in which portion control diet and seed cycling were included. During the 12-week efficacy trial, the highest follicle stimulating hormone (FSH) levels were found in the control group T0 (8.18 ± 0.13 mIU/mL). In T2, FSH falls from 6.545 ± 0.16 mIU/mL to 3.51 ± 0.13 mIU/mL throughout a 12-week period. Overall, a portion-controlled diet and seed cycling reduced FSH levels by 1.2% to 2.5%. LH value was 10.118 ± 0.1874 IU/L in the control group (T0), which climbed 12.82 ± 0.15 IU/L, but decreased from 10.62 ± 0.26 IU/L to 9.79 ± 0.17 U/L and 11.015 ± 0.24 IU/L 6.217 ± 0.167 IU/L in the other groups (T1, T2). It was determined that the LH levels were reduced by 1.5%-2% in T2. Conclusively, the seed cycling approach is effective and has significant results in women with PCOS. Seed cycling improves hormonal disturbance in women which promotes a healthy life.

The Clinical Manifestations of Polycystic Ovary Syndrome (PCOS) and The Treatment Options

Polycystic Ovary Syndrome is one of the most common endocrine disorders in females. It is important to diagnose early using the correct diagnostic criteria to ensure proper management and to reduce the long-term effects.To aggregate data on females diagnosed with PCOS and study the prevalence, symptoms, diagnostic criteria, and treatment options available till date for this syndrome.A thorough literature search of PubMed, Medline, and Google Scholar for data sources mentioning the symptoms and diagnostic criteria for PCOS in females to date is included in the study. A total of 61 articles were used and a total of 10 were excluded due to repetition of data or studies with sample sizes less than 70.Women clinically diagnosed with PCOS. The prevalence of PCOS was more common in woman aged 21-34 years and varied from 2.2% to 20% in different parts of the world. The most common symptoms found for PCOS were menstrual irregularities, hirsutism, weight gain, and insulin resistance. There are 3 diagnostic criteria currently being used to diagnose PCOS namely Ovulatory Dysfunction, Hyperandrogenism, and Polycystic Ovarian . The symptoms of PCOS vary greatly among women and so treatment is largely based on the presentation of symptoms and prevention of long-term effect. Therefore, the main treatment options for menstrual irregularities areClomiphene Citrate, Letrozole, Oral Contraceptive Pills (OCPs) a second-line therapy includes Gonadotropins, Metformin and Laparoscopic Ovarian Drilling (LOD). Hyperandrogenism treatment options are Finasteride, Isotretinoin, Spironolactone and Flutamide. Simultaneously weight reduction therapy, lifestyle changes can be used to reduce a weight gain.The prevalence of PCOS is influenced the diagnostic criteria used. The Clinical presentations of PCOS vary greatly among women. Rotterdam criteria, most widely used to diagnose PCOS, include the presence of at least two of these three conditions: polycystic ovaries on ultrasound imagining; hyperandrogenism; and chronic ovulatory dysfunction. The treatment of PCOS is not specific. Lifestyle modifications, pharmacotherapy and some surgical approaches have been successfully used to manage the symptoms.

Mitochondrial Uncoupler BAM15 Ameliorates Associated Metabolic PCOS Traits in a Hyperandrogenic PCOS Mouse Model

Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition characterized by endocrine, reproductive and metabolic abnormalities. There is no cure for PCOS and existing treatments are suboptimal. Obesity and adverse metabolic features are prevalent in PCOS patients, but weight loss has a beneficial effect on PCOS features. However, dietary interventions aimed at weight loss are difficult to sustain long-term. Interestingly, recent data from animal studies has shown that a mitochondrial uncoupler, BAM15, is an effective approach to pharmacologically treat obesity and metabolic diseases. Aim: To investigate the efficacy of BAM15 to ameliorate PCOS-traits in a PCOS mouse model. Method: The effect of BAM15 treatment on metabolic and reproductive PCOS features were evaluated in dihydrotestosterone (DHT)-induced PCOS mice fed a standard chow diet ± BAM15 for 10 weeks. Results: As expected, exposure of female mice to DHT induced the PCOS metabolic features of increased body weight (P&lt;0.05), lean mass (P&lt;0.001), increased parametrial and mesenteric fat pad weights (P&lt;0.05) and adipocyte hypertrophy (P&lt;0.05). DHT-induced PCOS mice also exhibited increased HOMA-IR, cholesterol and fasting triglyceride levels and hepatic steatosis (all P&lt;0.05). Conversely, DHT-induced PCOS females treated with BAM15 displayed lowered body weights similar with controls, a significant decrease in parametrial and mesenteric fat depot weights (P&lt;0.05) and reduced adipocyte hypertrophy. Likewise, BAM15 treatment decreased HOMA-IR, cholesterol and fasting triglyceride levels and the degree of hepatic steatosis observed in PCOS females, to levels comparable with control females. Lastly, PCOS mice presented the reproductive PCOS traits of irregular cycles and ovulatory dysfunction, though BAM15 treatment did not improve these PCOS features. Conclusion: These findings demonstrate that the pharmacologic mitochondrial uncoupler BAM15 is able to ameliorate metabolic PCOS features in a PCOS mouse model. These data provide evidence to support BAM15 as a potential innovative therapeutic approach to manage associated metabolic PCOS features.

Androgen Actions in Adipose Tissue, But Not Skeletal Muscle, are Involved in the Development of Metabolic PCOS Features in a Mouse Model

Background: Polycystic ovary syndrome (PCOS) is a common disorder characterised by endocrine, reproductive and metabolic dysfunction. Hyperandrogenism is a key diagnostic trait and evidence supports a role for androgen receptor (AR) mediated actions in PCOS pathogenesis. Aberrant AR signalling in adipose tissue and muscle have been proposed as being involved in PCOS pathogenesis, but their importance and the precise AR signalling mechanisms involved remain undefined. Aim: To investigate the role of AR signalling in white adipose tissue (WAT), brown adipose tissue (BAT) and skeletal muscle in the development of PCOS. Method: WT, global androgen receptor knockout (ARKO) and skeletal muscle-specific (SkMARKO) mice were exposed to DHT to induce PCOS. ARKO (AR−/−) WAT/BAT was transplanted into WT (AR+/+) DHT-induced PCOS females, and WT WAT/BAT was transplanted into ARKO DHT-induced PCOS females. After 12 weeks of DHT exposure all mice were assessed for the presence of reproductive and metabolic PCOS traits. Results: DHT exposure in WT females induced key reproductive and metabolic PCOS traits. SkMARKO mice treated with DHT displayed a similar phenotype to DHT-treated WT females, with full development of reproductive and metabolic PCOS traits. Transplantation of ARKO WAT/BAT into DHT-treated WT females prevented the development of some metabolic PCOS features, as mice exhibited a significantly lower body weight (P&lt;0.05), decreased visceral adiposity (P&lt;0.05), and smaller adipocyte size (P&lt;0.05) compared to DHT-treated WT females with sham surgery. In contrast, reproductive PCOS traits were not ameliorated by WAT or BAT transplantation. Furthermore, DHT exposure in ARKO female mice transplanted with WT WAT/BAT did not lead to the development of PCOS traits. Conclusion: WAT and BAT, but not skeletal muscle, are key sites of AR-mediated actions involved in the development of metabolic PCOS traits. These data support targeting adipocyte AR-driven pathways in future research aimed at developing novel therapeutic interventions for PCOS.

PCOS model: Apoptotic changes and role of vitamin D

Aim: This research was aimed to observe apoptotic marker (caspase 3) levels in different groups after treatment with vitamin D in an animal model after inducing polycystic ovary syndrome (PCOS) with dehydroepiandrosterone (DHEA). Materials and Methods: 30 pre-pubertal female sprague dawley dams were recruited. The animals were distributed 10 each in control, PCOS and vitamin D treated groups. In control group, 0.2 ml of sesame oil was given. PCOS group was administered DHEA by the daily dose of 6 mg/kg for 30 days. In vitamin D treated group, animals were injected 6 mg/ kg/day DHEA daily and 120 ng 1, 25(OH) 2D3/100 g subcutaneously once a week. The occurrence of programmed cell death in PCOS by apoptotic marker (caspase 3) levels. Results: The results of this study showed significant weight gain, obesity, changes in caspase 3 levels in PCOS group as compared to control and vitamin D treated group. Conclusion: Administration of vitamin D (120 ng 1, 25(OH) 2D3/100) reduced body weight as well as improved the caspase 3 levels in PCOS induced animals. The results support the effect of vitamin D treatment for metabolic and reproductive characteristic features in PCOS females.

The Correlation of BMI and Age to Some Hormonal Indices in Iraqi Women with the Polycystic Ovarian Syndrome

Only a few researchers have looked at the link between age and the occurrence of polycystic ovary syndrome (PCOS). The goal of this study was to see if there was a link between age and body mass index (BMI) and the prevalence of PCOS and to compare the levels of certain endocrine profiles in PCOS and healthy females. In this study, 75 random females participate, 75 healthy females, and fifty are patients in PCOS. Age has no significant difference among females with PCOS as compared with females with normal ovaries. Otherwise, thirty cases of PCOS group occurred in a high percentage (64%) at (18–26) years. Also, highly significant differences in BMI of the PCOS group as compared with a control group, in which in 30 cases (60%) of total study cases, 50 (100%) of females diagnosed with PCOS were obese, and their BMI over 30. On the other hand, the results of the control group (healthy females) were categorized mostly under an average weight 24 (96.0%) from a total study count of 25 (100%). Finally, highly significant differences in serum levels of luteinizing hormone (LH) and testosterone of the PCOS group compared with the control group and non-significant differences in follicle stimulating hormone (FSH) serum levels of the PCOS group compared with the control group. In summary, we observed that women with PCOS with signs and symptoms of PCOS represented mainly in obesity, menstrual irregularity, and hirsutism had higher body mass index, LH levels, and testosterone than women with normal ovaries.

Derailed peripheral circadian genes in polycystic ovary syndrome patients alters peripheral conversion of androgens synthesis.

Do circadian genes exhibit an altered profile in peripheral blood mononuclear cells (PBMCs) of polycystic ovary syndrome (PCOS) patients and do they have a potential role in androgen excess? Our findings revealed that an impaired circadian clock could hamper the regulation of peripheral steroid metabolism in PCOS women. PCOS patients exhibit features of metabolic syndrome. Circadian rhythm disruption is involved in the development of metabolic diseases and subfertility. An association between shift work and the incidence of PCOS in females was recently reported. This is a retrospective case-referent study in which peripheral blood samples were obtained from 101 control and 101 PCOS subjects. PCOS diagnoses were based on Rotterdam Consensus criteria. This study comprised 101 women with PCOS and 101 control volunteers, as well as Swiss albino mice treated with dehydroepiandrosterone (DHEA) to induce PCOS development. Gene expression analyses of circadian and steroidogenesis genes in human PBMC and mice ovaries and blood were executed by quantitative real-time PCR. We observed aberrant expression of peripheral circadian clock genes in PCOS, with a significant reduction in the core clock genes, circadian locomotor output cycles kaput (CLOCK) (P ≤ 0.00001), brain and muscle ARNT-like 1 (BMAL1) (P ≤ 0.00001) and NPAS2 (P ≤ 0.001), and upregulation of their negative feedback loop genes, CRY1 (P ≤ 0.00003), CRY2 (P ≤ 0.00006), PER1 (P ≤ 0.003), PER2 (P ≤ 0.002), DEC1 (P ≤ 0.0001) and DEC2 (P ≤ 0.00005). Transcript levels of an additional feedback loop regulating BMAL1 showed varied expression, with reduced RORA (P ≤ 0.008) and increased NR1D1 (P ≤ 0.02) in PCOS patients in comparison with the control group. We also demonstrated the expression pattern of clock genes in PBMCs of PCOS women at three different time points. PCOS patients also exhibited increased mRNA levels of steroidogenic enzymes like StAR (P ≤ 0.0005), CYP17A1 (P ≤ 0.005), SRD5A1 (P ≤ 0.00006) and SRD5A2 (P ≤ 0.009). Knockdown of CLOCK/BMAL1 in PBMCs resulted in a significant reduction in estradiol production, by reducing CYP19A1 and a significant increase in dihydrotestosterone production, by upregulating SRD5A1 and SRD5A2 in PBMCs. Our data also showed that CYP17A1 as a direct CLOCK-BMAL1 target in PBMCs. Phenotypic classification of PCOS subgroups showed a higher variation in expression of clock genes and steroidogenesis genes with phenotype A of PCOS. In alignment with the above results, altered expression of ovarian core clock genes (Clock, Bmal1 and Per2) was found in DHEA-treated PCOS mice. The expression of peripheral blood core clock genes in DHEA-induced PCOS mice was less robust and showed a loss of periodicity in comparison with that of control mice. N/A. We could not evaluate the circadian oscillation of clock genes and clock-controlled genes over a 24-h period in the peripheral blood of control versus PCOS subjects. Additionally, circadian genes in the ovaries of PCOS women could not be evaluated due to limitations in sample availability, hence we employed the androgen excess mouse model of PCOS for ovarian circadian assessment. Clock genes were assessed in the whole ovary of the androgen excess mouse model of PCOS rather than in granulosa cells, which is another limitation of the present work. Our observations suggest that the biological clock is one of the contributing factors in androgen excess in PCOS, owing to its potential role in modulating peripheral androgen metabolism. Considering the increasing prevalence of PCOS and the rising frequency of delayed circadian rhythms and insufficient sleep among women, our study emphasizes the potential in modulating circadian rhythm as an important strategy in PCOS management, and further research on this aspect is highly warranted. This work was supported by the RGCB-DBT Core Funds and a grant (#BT/PR29996/MED/97/472/2020) from the Department of Biotechnology (DBT), India, to M.L. B.S.J. was supported by a DST/INSPIRE Fellowship/2015/IF150361 and M.B.K. was supported by the Research Fellowship from Council of Scientific & Industrial Research (CSIR) (10.2(5)/2007(ii).E.U.II). The authors declare no competing interests. N/A.

Post‐Pubertal Testosterone Implants Induce Hypertension in Female‐to‐Male Trans‐Sex Rat Model

IntroductionAndrogens induce increases in blood pressure (BP) and risk of cardiovascular diseases (CVDs) in females, as seen in polycystic ovary syndrome females. However, it is not clear whether treatment with gender‐affirming hormone therapy in trans‐men have an impact on their BP or risk of CVD. Therefore, the present study was undertaken to test the hypothesis that chronic androgen supplements (starting post pubertal) in a rodent model of transgender men, will increase BP and promote metabolic dysfunction.MethodsFemale SD rats were implanted with testosterone propionate (TP, 7.5 mg in 5 mm silastic tubes, replaced every 3 wks, n = 10) starting at 7 wks of age (post‐puberty) and compared to controls (empty silastic implants, n = 10). Rats were weighed weekly. Radiotelemetry transmitters were implanted at 13 wks of age (n = 5‐6/group) and mean arterial pressure (MAP) was measured at 15, 21 and 25 wks of age. Body composition was determined at 15, 21 and 23 wks of age and proteinuria was determined at 15 and 21 wks of age (n = 4/group). Serum testosterone was measured by LC/MS at 15 wks of age (n = 4/group). Oral glucose tolerance test was performed at 11 and 22 wks of age (n = 4/group).ResultsTP supplements increased serum testosterone at 15 wks of age by 30‐fold compared to female controls (6.4 ± 1.5 vs 0.2 ± 0.05 ng/ml, respectively; p&lt;0.005). Body weight (BW) increased significantly in TP group compared to controls by 10 wks of age (241 ± 4 g vs 220 ± 2 g, respectively; p&lt;0.05) and was sustained through 26 wks of age (311 ± 7 g vs 276 ± 5 g, respectively; p&lt;0.05). Fat mass and fat mass/BW were similar between TP and controls. Lean mass was significantly higher in TP group compared to controls at 15, 21 and 23 wks of age (254 ± 7, 268 ± 12 and 273 ± 12 g vs 218 ± 6, 227 ± 5 and 229 ± 5 g, respectively; p&lt;0.01); however, when factored for BW, there were no differences between TP and controls. Proteinuria was significantly higher in TP group compared to controls at 15 wks of age (4.9 ± 1.2 vs 2.1 ± 0.3 mg/24 h, respectively, p&lt;0.05) and 21 wks of age (7.6 ± 1.1 vs 2.4 ± 0.5 mg/24 h, respectively, p&lt;0.005). Importantly, MAP was increased significantly in TP group at 15 wks of age (112 ± 3 vs 106 ± 4 mmHg, p&lt;0.05), 21 wks of age (114 ± 3 vs 105 ± 2 mmHg; p&lt;0.05) and 24 wks of age (115 ± 3 vs 104 ± 2 mmHg, p&lt;0.05), compared to controls, respectively. Oral glucose tolerance test at 11 and 22 wks of age was similar between groups.ConclusionTestosterone used in a form of sex‐affirming therapy in female rats induced increases in BP that are independent of adiposity or Insulin resistance and maybe associated to renal injury. Future studies should determine whether these changes are sustained with aging, and the mechanisms responsible for the increase in BP in the female‐to‐male trans‐sex model.

A Case-Control Study of the Luteinizing Hormone Level in Luteinizing Hormone Receptor Gene (rs2293275) Polymorphism in Polycystic Ovarian Syndrome Females

Background: Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder characterized by chronic anovulation, infertility, polycystic ovaries, and hyperandrogenic signs. Objective: The aim of this study was to determine the association of luteinizing hormone/chorionic gonadotropin hormone receptor LHCGR polymorphism (rs2293275) with oligomenorrhea, amenorrhea, hirsutism, acne, infertility, LH, LH/FSH ratio, and body mass index (BMI) among PCOS females. Methods: This genetic case-control study recruited 55 PCOS and 55 control females, diagnosed based on the Rotterdam criteria. LH and FSH were measured by the Roche cobas c 502 automated analyzer. Genotypic analysis was carried out using the polymerase chain reaction-restriction fragment length polymorphism and restriction endonuclease digestion. Results: BMI was higher for PCOS patients (28.5 ± 6.59) compared to controls (25.1 ± 5.77), and ovulatory dysfunction was seen among 90% of PCOS females. Oligomenorrhea was common in PCOS (73%), and hirsutism and acne were detected in PCOS (80% and 40%; respectively). LH ≥10 were recoded among 51%, while LH/FSH ≥1.5 was recorded among 33% PCOS females. There is a statistical difference between rs2293275 polymorphism in the AG genotype between PCOS patients and controls. PCOS patients have a significantly higher mean LH level compared to controls (8.36 ± 4.86 and 5.67 ± 2.51, respectively) and showed higher LH/FSH value (1.46 ± 0.81) compared to (0.87 ± 0.30) controls. GG and AG genotypes of LHCGR showed statistically significant higher LH (8.22 ± 4.11; 9.02 ± 3.87) and LH/FSH values (1.57 ± 0.56; 1.64 ± 0.89) compared to controls. Conclusion: LHCGR (rs2293275) GA and GG genetic variants could modulate the hormonal levels of PCOS LH levels and the LH/FSH ratio and associated with hirsutism, oligomenorrhea, BMI, and LH/FSH ratio as risk factors.

Effect of KISS1 gene variants (rs372790354 G&gt;A and rs4889 G&gt;A) on kisspeptin in patients with polycystic ovary syndrome in Iraq.

Polycystic ovary syndrome (PCOS) is a heterogeneous genetic disorder categorized by hyperandrogenism that affects early reproductive age in females, KISS1 has play role in regulating the hypothalamic-pituitary-gonad axis, it plays a key role in human reproductive function. In patients with polycystic ovarian syndrome, imbalance-of-function mutations in this gene have been found often. blood samples were collected from 120 patients (60 control are divided into 30 normal weight and 30 obese) and (60 PCOS) females are divided into 30 normal weight and 30 obese). DNA was extracted and genotyped for KISS1 variants by HRM-PCR and measured level of kisspeptin by ELIAS, while LH, FSH, DHEA and free testosterone by CLIA. The value of LH, Testosterone, DHEA-S and kisspeptin is elevated in the patient group, while the decline of FSH in serum level patients value, rs372790354 G &gt; A and rs4889 G&gt;A was associated with PCOS in dominant, recessive, co-dominant (P-value&lt; 0.05), rs37279054 AA was not found the effect of obese group and linked with normal weight PCOS put present study no effect on the parameters, rs4889 GG/GA was the effect on all subgroups except the genotype GA not effected on obese female, the highly significant ( P-value&lt;0.05) of rs4889 GA influenced on measured of WHR, LH/FSH ratio and DHEA-S in the patient compared to control, rs4889 GG/AA was influenced on normal-weight patient compare to an obese patient, the WHR was higher in an obese patient in both genotype. While the level of kisspeptin in normal weight with genotype AA was higher level compared to obese and (P-value&lt;0.05). We concluded that the KISS1 levels were higher in PCOS females compared to controls and decreased with increasing BMI, Kiss1 polymorphism rs372790354 G&gt;A and rs4889 G&gt;A may be associated with the pathophysiology of PCOS and lead to increase serum level of LH that due to hyperandrogenism.

Crocus sativus (saffron) petals extract and its active ingredient, anthocyanin improves ovarian dysfunction, regulation of inflammatory genes and antioxidant factors in testosterone-induced PCOS mice

Ethnopharmacological relevanceSaffron petal has traditionally been used to treat a variety of diseases, such as gynecological disease such as primary dysmenorrhea and premenstrual tension. Polycystic Ovary Syndrome (PCOS) is a form of gynecological disease that causes amenorrhea, infertility, menopausal and urogenital disorders. This disease may be treated with saffron petals. Aim of the studyIn this study, the effects of saffron petal extract (SPE) and saffron petal anthocyanins (SPA) on ovarian hormones, steroidogenic enzymes, ovarian dysfunction, regulation of anti-inflammatory genes, and antioxidant factors in female PCOS mice were studied. Methods and resultsThe PCOS mouse model was induced by testosterone enanthate (TE), and an in vivo evaluation of whether the dietary consumption of SPE and SPA improved the PCOS-like symptoms was conducted. The luteinizing hormone (LH), testosterone, and estrogen levels increased in PCOS mice, but decreased following SPE and SPA treatment. In the PCOS mice, the reduced follicular-stimulating hormone (FSH) progesterone levels were restored to that of normal controls with SPE and SPA treatment in serum. The transcription level(s) of gonadotropin receptors (Fshr and Lhr), steroid receptors (Pgr, and Esr1), inflammatory markers (TNFα, IL1ß, IL6 and IL18), inflammatory-related factors (NF-κB, NF-κB p65, IκB) and antioxidant enzymes (GPx, SOD, CAT, GST, and GSH) changed under the PCOS condition. Moreover, they were regulated by SPE and SPA treatment in PCOS mice ovaries. The reproductive tissues of TE induced PCOS mice were restored into estrogenic conditions from androgen environments. The study of antioxidant activity of SPE and SPA using FRAP and DPPH tests showed high antioxidant activity. ConclusionThese results suggest that SPE and SPA ameliorates symptoms of PCOS by improving dysregulation of ovarian steroids, steroidogenic, antioxidant enzymes and inflammatory markers in PCOS mice.