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Vascular Health and Risk Management 2024Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people... (Review)
Review
Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people worldwide for the treatment of type 2 diabetes (T2D). Metformin is used off-label for the treatment of polycystic ovary syndrome (PCOS) and for pre-diabetes and weight loss. Metformin is a safe, inexpensive drug with side effects mostly limited to gastrointestinal issues. Prospective clinical data from the United Kingdom Prospective Diabetes Study (UKPDS), completed in 1998, demonstrated that metformin not only has excellent therapeutic efficacy as an anti-diabetes drug but also that good glycemic control reduced the risk of micro- and macro-vascular complications, especially in obese patients and thereby reduced the risk of diabetes-associated cardiovascular disease (CVD). Based on a long history of clinical use and an excellent safety record metformin has been investigated to be repurposed for numerous other diseases including as an anti-aging agent, Alzheimer's disease and other dementias, cancer, COVID-19 and also atrial fibrillation (AF). AF is the most frequently diagnosed cardiac arrythmia and its prevalence is increasing globally as the population ages. The argument for repurposing metformin for AF is based on a combination of retrospective clinical data and in vivo and in vitro pre-clinical laboratory studies. In this review, we critically evaluate the evidence that metformin has cardioprotective actions and assess whether the clinical and pre-clinical evidence support the use of metformin to reduce the risk and treat AF.
Topics: Humans; Metformin; Atrial Fibrillation; Drug Repositioning; Hypoglycemic Agents; Animals; COVID-19; Anti-Arrhythmia Agents; Treatment Outcome; Diabetes Mellitus, Type 2
PubMed: 38919471
DOI: 10.2147/VHRM.S391808 -
Nature Medicine Jun 2024
PubMed: 38918607
DOI: 10.1038/d41591-024-00047-9 -
Inflammopharmacology Jun 2024In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress...
Astaxanthin treatment decreases pro-inflammatory cytokines and improves reproductive outcomes in patients with polycystic ovary syndrome undergoing assisted reproductive technology: A randomized clinical trial.
RESEARCH QUESTION
In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and assisted reproductive technology (ART) outcomes in 44 infertile Polycystic Ovary Syndrome (PCOS) patients.
DESIGN
Patients with PCOS were randomly divided into two groups. The intervention group received 6 mg AST, and the control group received placebo daily for 8 weeks. Blood samples were obtained from all patients before and after intervention and follicular fluid (FF) was collected during the ART procedure. Interleukin (IL) -6, IL-1β were evaluated from serum samples and FF and OS markers (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD], and reactive oxygen species [ROS]) were measured from FF. The groups were compared for ART outcomes as well.
RESULTS
A significant decrease in IL-6 and IL-1β concentrations (both, P = < 0.01) serum levels was found following AST treatment. FF cytokine levels and OS markers did not differ significantly between the groups. Reproductive outcomes, including the number of oocytes retrieved (P = 0.01), the MII oocyte count (P = 0.007), oocyte maturity rate (MII %) (P = 0.02) and number of frozen embryos (P = 0.03) significantly improved after intervention. No significant differences were found in chemical, clinical and multiple pregnancies between the groups.
CONCLUSIONS
AST pretreatment may modify inflammation and improve ART outcomes in PCOS infertile patients. Further investigations are recommended to verify these findings.
PubMed: 38916710
DOI: 10.1007/s10787-024-01504-0 -
Journal of Endocrinological... Jun 2024Evidence-based guidelines for the management of polycystic ovary syndrome (PCOS) recommend clinical laboratories use liquid chromatography-tandem mass spectrometry...
PURPOSE
Evidence-based guidelines for the management of polycystic ovary syndrome (PCOS) recommend clinical laboratories use liquid chromatography-tandem mass spectrometry (LC-MS/MS) for diagnosing biochemical hyperandrogenism. However, automated immunoassays are still mostly used in routine laboratories worldwide. Another hurdle for PCOS phenotyping in the clinical setting is ultrasound assessment of polycystic ovarian morphology. We address the impact of using state-of-the-art (LC-MS/MS) and of an anti-müllerian hormone (AMH) assay on the diagnosis of PCOS in routine practice.
METHODS
In a cross-sectional study, we included 359 premenopausal women consecutively evaluated because of symptoms of functional androgen excess or hyperandrogenemia, and finally diagnosed with PCOS. Patients were submitted to routine phenotyping based on serum androgen measurements by immunoassays and an ovarian ultrasound when necessary. Samples of all patients were also assayed by LC-MS/MS for hyperandrogenemia and for circulating AMH.
RESULTS
The observed agreement between immunoassays and LC-MS/MS in identifying hyperandrogenemia was poor [78.0%; k(95%CI): 0.366 (0.283;0.449)]. The observed agreement between ultrasound and increased AMH was 27.3% [(95%CI): 0.060 (0.005; 0.115)]. Using LC-MS/MS changed PCOS phenotypes in 60(15.8%) patients. Fifty-two (18.3%) individuals with hyperandrogenemia by routine immunoassays no longer presented with androgen excess by LC-MS/MS. Overall diagnostic agreement between routine assessment using immunoassays and ultrasound and that derived from LC-MS/MS and the addition of AMH to US was moderate [weighted κ (linear weights): 0.512 (0.416;0.608)].
CONCLUSIONS
Immunoassays used in routine practice are unacceptably inaccurate for phenotyping women with PCOS. Our data cast some doubts upon the interchangeability of serum AMH and ultrasound examination for the diagnosis of PCOS.
PubMed: 38913250
DOI: 10.1007/s40618-024-02416-0 -
Gynecological Endocrinology : the... Dec 2024To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age.
OBJECTIVE
To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age.
METHOD
This was a cross-sectional study in which 288 women with PCOS and 180 women without PCOS between the ages of 20 and 40 years were evaluated. All women had serum total testosterone, androstenedione, DHEA-S, fasting glucose, total cholesterol, HDL-C, LDL-C, and triglyceride levels analyzed. The McCoy Female Sexual Questionnaire (MFSQ) was applied to all studied women. Exploratory factor analysis and reliability analysis were done after data collection. The factor loadings of MFSQ domains were compared between women with PCOS and controls.
RESULTS
Average factor loadings of the MFSQ sexuality domain and MFSQ sexual partner domain were significantly lower in the PCOS group when compared to controls. There was no correlation between the two sexual function domains of the MFSQ and the PCOS features either in the PCOS group or the controls.
CONCLUSION
PCOS is a heterogeneous disease with different metabolic components, such as insulin resistance, obesity, and hyperandrogenism. Although sexual function among women with PCOS was lower than controls, no differences were found in metabolic features of the PCOS and non-PCOS groups with relation to sexual function determined by the MFSQ.
Topics: Humans; Female; Polycystic Ovary Syndrome; Adult; Cross-Sectional Studies; Turkey; Young Adult; Insulin Resistance; Sexual Dysfunction, Physiological; Testosterone; Surveys and Questionnaires; Case-Control Studies; Hyperandrogenism; Sexual Behavior; Androstenedione; Dehydroepiandrosterone Sulfate; Obesity
PubMed: 38913084
DOI: 10.1080/09513590.2024.2362249 -
Iranian Journal of Basic Medical... 2024Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder associated with chronic inflammation. However, the effect of ∆ tetrahydrocannabinol-9...
Revitalizing polycystic ovary syndrome: The therapeutic impact of low-dose ∆ tetrahydrocannabinol-9 through reduction of oxidative stress and modulation of macrophage polarization.
OBJECTIVES
Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder associated with chronic inflammation. However, the effect of ∆ tetrahydrocannabinol-9 (THC) on PCOS has not been evaluated. Therefore, this study aimed to investigate the immunomodulatory effects of THC in an animal model of PCOS.
MATERIALS AND METHODS
Twenty female Sprague-Dawley rats, aged 4 weeks, were divided into four groups. The control group received a normal diet, the sham group received a vehicle (carboxymethyl cellulose), the PCOS group received a high-fat diet (HFD) for 16 weeks followed by letrozole for 4 weeks, and the THC group received an HFD for 16 weeks followed by letrozole+THC (0.02 mg/kg) for 4 weeks.
RESULTS
The PCOS animals exhibited significantly higher levels of testosterone, insulin, triglycerides, and total cholesterol, along with elevated inflammatory and oxidative stress markers compared to the control group. Flow cytometry and real-time PCR analysis revealed an increase in M1 macrophage markers and a decrease in M2 macrophage markers compared to the control group. However, the administration of a low dose of THC mitigated these disturbances.
CONCLUSION
Low-dose THC improved inflammatory responses and shifted the balance of M1/M2 macrophage markers towards M2 macrophages in the animal model of PCOS.
PubMed: 38911246
DOI: 10.22038/IJBMS.2024.73892.16061 -
Iranian Journal of Basic Medical... 2024Polycystic ovary syndrome (PCOS) is one of the main causes of infertility in women. This study was conducted to uncover the effects of lupeol as an anti-androgenic...
OBJECTIVES
Polycystic ovary syndrome (PCOS) is one of the main causes of infertility in women. This study was conducted to uncover the effects of lupeol as an anti-androgenic triterpene on experimentally-induced PCOS in mice.
MATERIALS AND METHODS
Eighty immature female mice were divided into 4 groups: Control (C), PCOS (P), Lupeol (L), and Flutamide (F). PCOS was induced in test groups by injection of Dehydroepiandrosterone (60 mg/kg/day, IP) for twenty days. Following the PCOS induction, the two groups of L and F were treated with lupeol (40 mg/kg/day) and/or flutamide (10 mg/kg/day) respectively and the two groups of C and P received sesame oil (0.1 ml/mouse/day) for 15 days. After the treatment period, ten animals in each group were selected for collecting blood and ovary samples. fertilization assessment was carried out on 10 remaining mice in each group. The hormonal assays and oxidative stress biomarker determination were performed on serum and tissue samples. Moreover, histopathological analyses were conducted on the ovaries.
RESULTS
PCOS-elevated concentration of LH and Testosterone was significantly (<0.05) lowered in lupeol and flutamide-received animals. Lupeol and flutamide both reduced PCOS-induced fibrosis and the number of atretic follicles. Both compounds declined the PCOS-increased lipid peroxidation and protein oxidation in serum and the ovaries. Lupeol increased the PCOS-reduced fertility rate and decreased the number of arrested embryos by 12%.
CONCLUSION
These findings indicate that lupeol could be a novel compound in the treatment of PCOS as it reduced PCOS-induced structural and also functional disorders.
PubMed: 38911242
DOI: 10.22038/IJBMS.2024.77602.16783 -
Frontiers in Endocrinology 2024
PubMed: 38911041
DOI: 10.3389/fendo.2024.1413251 -
Fertility and Sterility Jun 2024To assess whether provision of fertility treatment for patients with polycystic ovary syndrome (PCOS) varies by patient and physician level demographics.
OBJECTIVE
To assess whether provision of fertility treatment for patients with polycystic ovary syndrome (PCOS) varies by patient and physician level demographics.
DESIGN
Retrospective cohort study SUBJECTS: Patients at a university health system seeking care for PCOS and infertility from 2007-2021.
EXPOSURE
Patient age, BMI, race, ethnicity, estimated household income, primary insurance payor, provider sex, and provider medical specialty.
MAIN OUTCOME MEASURES
Prescriptions for fertility treatment, including clomiphene citrate, letrozole, and injectable gonadotropins. Differences in patient and physician demographics between patients who did and did not receive a prescription were identified with univariable analysis. Multilevel mixed-effects logistic regression was performed to determine associations between patient and physician demographics and prescription receipt.
RESULTS
3,435 patients with PCOS and infertility were identified with a mean age of 31.1 +/- 5.7 years. Of the 68.8% of patients who received a prescription, 47.8% of prescriptions were clomiphene citrate, 38.6% letrozole, and 13.7% injectable gonadotropins. There were lower odds of prescription receipt for Black patients compared to White patients (aOR 0.75, 95% CI 0.61-0.93), those with estimated household income below the federal poverty level (FPL) compared to above the national median (aOR 0.71, 95% CI 0.46-0.97), and those with public compared to commercial insurance (aOR 0.53, 95% CI 0.40-0.71). These disparities persisted in a subanalysis of patients prescribed oral medications only with lower odds of prescription receipt for Black compared to White patients (aOR 0.74, 95% CI 0.57-0.95), those with estimated household income below the FPL compared to above the national median (aOR 0.93, 95% CI 0.87-0.98), and those with public compared to commercial insurance (aOR 0.57, 95% CI 0.42-0.76). Black patients waited on average 153.3 days longer than White patients from initial visit to prescription receipt. Patients had lower odds of receiving any prescription from family medicine physicians (aOR 0.36, 95% CI 0.24-0.52) and general internal medicine physicians (aOR 0.55, 95% CI 0.42-0.73) compared to reproductive endocrinologists.
CONCLUSION
Racial and socioeconomic disparities exist in the provision of infertility treatments for patients with PCOS. Fewer primary care physicians engaged in first-line fertility treatment, indicating an opportunity for physician education to improve access to fertility care.
PubMed: 38909670
DOI: 10.1016/j.fertnstert.2024.06.014 -
International Immunopharmacology Jun 2024Polycystic ovary syndrome (PCOS) is a common and complex endocrine disease in women, with a prevalence of 5% to 18% worldwide. HeQi San (HQS) is a Chinese medicine...
Chinese medicine compound prescription HeQi San ameliorates chronic inflammatory states and modulates gut flora in dehydroepiandrosterone-induced polycystic ovary syndrome mouse model.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common and complex endocrine disease in women, with a prevalence of 5% to 18% worldwide. HeQi San (HQS) is a Chinese medicine compound prescription, which has been applied to treat various endocrine and metabolic diseases.
OBJECTIVE
The study was intended to investigate the effect of HQS on PCOS, and clarify the potential mechanism via in vivo and in vitro experiments.
METHODS
The PCOS mouse model was established by injecting the dehydroepiandrosterone (DHEA) subcutaneously and fading high-fat diet for 3 weeks. After making model, PCOS mice were treated with HQS (8.75 g/kg and 17.5 g/kg, ig.) for 4 weeks. Firstly, we assessed the histopathological changes in ovary tissues and detected the hormone level. Subsequently, the study evaluated the capability of anti-inflammatory and regulating macrophage polarization of HQS in vivo and in vitro. The secretion of inflammation indicators was measured with Elisa kits, and the expression level of phosphorylated nuclear factor kappa-B (P-NFκB) and B-lymphocyte activation antigen B7 (CD80) was measured by immunofluorescence and Western blot. Meanwhile, the apoptosis of ovarian granulosa cells was detected via tunel staining and Western blot. The co-culture model in vitro was utilized to assess the effect between macrophage polarization and human ovarian granulosa cells (KGN cells) apoptosis. Furthermore, 16S rDNA sequencing was utilized to elevate gut microbiota change in PCOS mice.
RESULTS
HQS reversed the abnormal hormone increase, ameliorated insulin resistance, and improved histopathological changes of the ovary tissue to exert the therapeutic effect. HQS inhibited the expression of P-NF-κB and decreased the production of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) to further prohibit the macrophage M1 polarization in ovary tissues and macrophages. The apoptosis-positive cells, Bcl-2 Assaciated X protein (BAX), and cleaved-caspase 3 expression were also decreased in the treatment group. The B-cell lymphoma-2 (Bcl2) expression was enhanced after HQS treatment in vivo. The co-culture experiments also verified that HQS could prevent the apoptosis of KGN cells. Furthermore, HQS mediated the abundance of gut flora. The abundance of bifldobacterium and parasutterella was increased and the abundance of lachnoclostridium was decreased.
CONCLUSION
The study verified that HQS has the effect of anti-inflammation and inhibits macrophage M1 polarization. Besides, HQS could mediate the abundance of gut microbiota in mice with PCOS. Thus, this study would provide more reasonable basis of HQS for clinical use. In conclusion, HQS might be a potential candidate for PCOS treatment.
PubMed: 38909499
DOI: 10.1016/j.intimp.2024.112491