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Heliyon Oct 2023Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with a worldwide prevalence of 6-10 % of women of reproductive age. PCOS is a risk factor for...
Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with a worldwide prevalence of 6-10 % of women of reproductive age. PCOS is a risk factor for cardiometabolic disorders such as type 2 diabetes, myocardial infarction, and stroke in addition to exhibiting signs of hyperandrogenism and anovulation. However, there is no known cure for PCOS, and medications have only ever been used symptomatically, with a variety of adverse effects. Drugs made from natural plant products may help treat PCOS because several plant extracts have been widely recognized to lessen the symptoms of PCOS. In light of this, 72 current studies on natural products with the potential to control PCOS were examined. By controlling the PI3K/AKT signaling pathway and decreasing NF-κB and cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6), certain plant-derived chemicals might reduce inflammation. Other substances altered the HPO axis, which normalized hormones. Additionally, other plant components increased glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels to reduce radiation-induced oxidative stress. The other substances prevented autophagy by impairing beclin 1, autophagy-related 5 (ATG5), and microtubule-associated protein 1A/1B-light chain 3 - II (LC3- II). The main focus of this comprehensive review is the possibility of plant extracts as natural bio-resources of PCOS treatment by regulating inflammation, hormones, reactive oxygen species (ROS), or autophagy.
PubMed: 37867816
DOI: 10.1016/j.heliyon.2023.e20889 -
Cureus Sep 2023Polycystic ovarian syndrome (PCOS), also referred to as Stein-Leventhal syndrome, happens to be one of most common hormonal disorders found in females, causing... (Review)
Review
Polycystic ovarian syndrome (PCOS), also referred to as Stein-Leventhal syndrome, happens to be one of most common hormonal disorders found in females, causing large-sized ovaries with small cysts of non-ovulated oocytes in the outer medulla part of the ovary. Women suffering from PCOS often exhibit symptoms like oligomenorrhoea, elevated testosterone levels, acne, alopecia, hirsutism, sudden weight gain and many more. It can predispose a woman to developing infertility in future, and thus, difficulties in conceiving; due to the cystic changes in the ovaries, it results in anovulation and amenorrhea. The early symptoms of PCOS are being commonly observed nowadays in young women who are in their early 20s and those who are overweight or obese. The metabolic expression of PCOS increases with obesity. Obesity is a factor that is considered to contribute the most in the occurrence of various long-standing and non-transmissible illnesses apart from PCOS such as atherosclerosis, hypertension, diabetes, high blood cholesterol and even certain types of cancers. In obesity, there is an increase in the size and number of fat cells in the body. Obese and overweight young girls have a heightened likelihood of developing PCOS and its corresponding metabolic and reproductive health complications.
PubMed: 37854752
DOI: 10.7759/cureus.45405 -
Frontiers in Endocrinology 2023Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with...
INTRODUCTION
Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with estrogen levels within the normal range and can be characterized by oligo-/anovulation resulting in decreased progesterone levels. It is suggested that decreased progesterone levels may lead to more autoimmune diseases in women with PCOS. In addition, it is often claimed that there is an association between hyperprolactinemia and PCOS. In this large well-phenotyped cohort of women with PCOS, we have studied the prevalence of thyroid dysfunction and hyperprolactinemia compared to controls, and compared this between the four PCOS phenotypes.
METHODS
This retrospective cross-sectional study contains data of 1429 women with PCOS and 299 women without PCOS. Main outcome measures included thyroid stimulating hormone (TSH), Free Thyroxine (FT4), and anti-thyroid peroxidase antibodies (TPOab) levels in serum, the prevalence of thyroid diseases and hyperprolactinemia.
RESULTS
The prevalence of thyroid disease in PCOS women was similar to that of controls (1.9% versus 2.7%; P = 0.39 for hypothyroidism and 0.5% versus 0%; P = 0.99 for hyperthyroidism). TSH levels were also similar (1.55 mIU/L versus 1.48 mIU/L; P = 0.54). FT4 levels were slightly elevated in the PCOS group, although within the normal range (18.1 pmol/L versus 17.7 pmol/L; P < 0.05). The prevalence of positive TPOab was similar in both groups (5.7% versus 8.7%; P = 0.12). The prevalence of hyperprolactinemia was similarly not increased in women with PCOS (1.3%% versus 3%; P = 0.05). In a subanalysis of 235 women with PCOS and 235 age- and BMI-matched controls, we found no differences in thyroid dysfunction or hyperprolactinemia. In according to differences between PCOS phenotypes, only the prevalence of subclinical hypothyroidism was significantly higher in phenotype B (6.3%, n = 6) compared to the other phenotypes.
CONCLUSION
Women with PCOS do not suffer from thyroid dysfunction more often than controls. Also, the prevalence of positive TPOab, being a marker for future risk of thyroid pathology, was similar in both groups. Furthermore, the prevalence of hyperprolactinemia was similar in women with PCOS compared to controls.
Topics: Humans; Female; Polycystic Ovary Syndrome; Hyperprolactinemia; Retrospective Studies; Progesterone; Prevalence; Cross-Sectional Studies; Thyroid Diseases; Hypothyroidism; Thyrotropin
PubMed: 37854182
DOI: 10.3389/fendo.2023.1245106 -
Diagnostics (Basel, Switzerland) Sep 2023(1) Background: Infertility is a prevalent issue that affects 10-18% of couples worldwide, and up to 30% in Eastern Europe. Infertility of unknown etiology is one of the...
(1) Background: Infertility is a prevalent issue that affects 10-18% of couples worldwide, and up to 30% in Eastern Europe. Infertility of unknown etiology is one of the most challenging forms of infertility. Vitamin D has recently been extensively studied and researchers are investigating its possible role in ovulation and pregnancy. While the evidence suggests a positive association between vitamin D and ovulation, more research is needed to understand the role that vitamin D plays in ovulation. (2) Methods: In this study, 86 infertile patients were studied retrospectively in a single center by analyzing their anthropometric (body mass index), biochemical (total cholesterol, insulin resistance) and hormonal data in correlation with their vitamin D status. (3) Results: It was found that the mid-luteal progesterone level was significantly related to the 25-hydroxy vitamin D level in a multivariate linear regression model. An analysis of subgroups of ovulatory and anovulatory patients suggests that serum 25-hydroxy vitamin D levels of approximately 20 ng/mL may be necessary to trigger ovulation or to support progesterone secretion. (4) Conclusions: Vitamin D deficiency should be considered when infertility of unknown etiology and progesterone-related disorders occur.
PubMed: 37835767
DOI: 10.3390/diagnostics13193024 -
Journal of Clinical Medicine Sep 2023Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance and...
Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance and closely linked with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS was likely further selected in humans when scarcity of food in hunter-gatherers of the late Pleistocene additionally programmed for enhanced fat storage to meet the metabolic demands of reproduction in later life. As an evolutionary model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor fat storage through exaggerated lipid accumulation during development to adipocytes in vitro. In turn, fat storage is counterbalanced by reduced insulin sensitivity and preferential accumulation of highly lipolytic intra-abdominal fat in vivo. This metabolic adaptation in PCOS balances energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction; its accompanying oligo-anovulation allowed PCOS women from antiquity sufficient time and strength for childrearing of fewer offspring with a greater likelihood of childhood survival. Heritable PCOS characteristics are affected by today's contemporary environment through epigenetic events that predispose women to lipotoxicity, with excess weight gain and pregnancy complications, calling for an emphasis on preventive healthcare to optimize the long-term, endocrine-metabolic health of PCOS women in today's obesogenic environment.
PubMed: 37834765
DOI: 10.3390/jcm12196120 -
Cureus Aug 2023Polycystic ovarian syndrome (PCOS) is considered the most prevalent endocrinological disorder, which affects some women and it is characterized by anovulation and... (Review)
Review
Polycystic ovarian syndrome (PCOS) is considered the most prevalent endocrinological disorder, which affects some women and it is characterized by anovulation and hyperandrogenism, with morphologic changes in the ovary, inappropriate gonadotropin secretion, and insulin resistance (IR) with accompanying compensatory hyperinsulinemia. PCOS was associated with some degree of IR which probably contributes to hyperandrogenism. Many studies showed that metformin, when used to treat PCOS, significantly reduced serum androgen levels, improved insulin sensitivity, restored menstrual cyclicity, and was successful in triggering ovulation. As a result, metformin may be useful in treating PCOS-related infertility. The aim of this review was to clarify PCOS, its prevalence, particularly in Saudi Arabia, its pathogenesis, its impact on the patient's health, and to explain the uses of metformin, its mechanism of action, and its role in the treatment of PCOS-related infertility.
PubMed: 37791160
DOI: 10.7759/cureus.44493 -
Journal of Clinical Medicine Sep 2023Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. This condition is characterized by hyperandrogenism and either oligo-... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. This condition is characterized by hyperandrogenism and either oligo- or anovulation. PCOS patients often present comorbidities such as obesity, insulin resistance, impaired glucose metabolism, dyslipidemia, hypertension, metabolic syndrome, and an increased risk of diabetes. Given the profound implications of metabolic impairment in PCOS, the accurate diagnosis and management of these facets are imperative. The first-line approach to treatment involves lifestyle modifications, including dietary adjustments and exercise aimed at achieving weight loss, a strategy consistently emphasized across the literature. Supplementation with probiotics, vitamin D, and L-carnitine have also provided additional benefits to patients. In select cases, pharmacological interventions are needed for optimal therapeutic results. The most common medications used in PCOS include metformin, thiazolidinediones, inositols, and two classes of antidiabetic agents: dipeptidyl peptidase-IV (DPP-IV) inhibitors, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new addition to the therapeutic arsenal for the metabolic management of PCOS. GLP-1 receptor agonists cause insulin release in a glucose-dependent manner, yielding clinical benefits such as heightened satiety, reduced appetite, and appetite regulation. GLP-1RAs have demonstrated efficacy in reducing glycated hemoglobin levels and promoting weight loss while ameliorating hyperlipidemia. Prior to initiating GLP-1RA therapy, patients should undergo screening for contraindications, including history of pancreatitis, diabetic retinopathy, or thyroid cancer. The effects of treatment should be monitored using laboratory testing and body weight measurements. Effective communication between clinician and patient should be maintained with regular check-in for a period of 6 to 12 months.
PubMed: 37762856
DOI: 10.3390/jcm12185915 -
Animals : An Open Access Journal From... Sep 2023Cystic ovarian disease (COD) in dairy cattle is characterized by preovulatory follicles that become cysts, fail to ovulate and persist in the ovary; consequently,...
Cystic ovarian disease (COD) in dairy cattle is characterized by preovulatory follicles that become cysts, fail to ovulate and persist in the ovary; consequently, interfering with normal ovarian cyclicity. The intraovarian key players that orchestrate the alterations occurring in the preovulatory follicle and that culminate with cyst formation and persistence, however, remain uncertain. Interestingly, the Hippo pathway effector yes-associated protein (YAP) has been described in humans and mice as a key player of anovulatory cystic disorders. To start elucidating if YAP deregulation in ovarian follicle cells can be also involved in the pathogenesis of COD, we have generated a series of novel results using spontaneously occurring cystic follicles in cattle. We found that mRNA and protein levels of YAP are significantly higher in granulosa (GCs) and theca cells (TCs) isolated from cystic follicles (follicular structures of at least 20 mm in diameter) in comparison to respective cell types isolated from non-cystic large follicles (≥12 mm). In addition, immunohistochemistry and Western blot analyses used to determine YAP phosphorylation pattern suggest that YAP transcriptional activity is augmented is cystic GCs. These results were confirmed by a significant increase in the mRNA levels encoding for the classic YAP-TEAD transcriptional target genes , and in GCs from follicle cysts in comparison to non-cystic large follicles. Taken together, these results provide considerable insight of a completely novel signaling pathway that seems to play an important role in ovarian cystic disease pathogenesis in dairy cattle.
PubMed: 37760251
DOI: 10.3390/ani13182851 -
Animal Reproduction Science Oct 2023The objective of this study was to compare the reproductive performance of lactating dairy cows submitted to first AI after combination of estrus detection and fixed...
Comparison of three reproductive management strategies for lactating dairy cows using combination of estrus detection or ovulation synchronization and Fixed-Timed Artificial Insemination.
The objective of this study was to compare the reproductive performance of lactating dairy cows submitted to first AI after combination of estrus detection and fixed timed AI (FTAI) and FTAI only. Cows were randomly assigned to receive AI at detected estrus between 50 and 70 d in milk (DIM), if not detected in estrus, were enrolled in either Ovsynch (ED-Ov, n = 485) or PRIDsynch (ED-PR, n = 505) protocols; or received FTAI at 80 DIM after Double-Ovsynch protocol (DO, n = 501). Cows were body condition scored (BCS) at calving and at 43 DIM; and evaluated for postpartum disorders within 7 d postpartum; clinical mastitis, lameness and bovine respiratory disease were recorded until first AI. Ovarian cyclicity was monitored at 43 and 50 DIM, and at 70 and 77 DIM. Pregnancy diagnoses (PD) were performed at 32 and 63 d after AI. Overall prevalence of postpartum anovulation was 7.8%. Pregnancy per AI (P/AI) did not differ between reproductive strategies at 32 d PD (ED-Ov = 43.2%; ED-PR = 41.7%; DO= 45.3%). Primiparous cows had greater P/AI than multiparous cows (53.7% vs 36.8%). Cows on farm 1 had lower P/AI compared with their counterparts on farm 2 (42.1% vs 45.4%). Cows with BCS > 2.5 at 43 DIM had greater P/AI compared with cows with BCS ≤ 2.5 (44.5% vs 34.7%). Similar P/AI for cow's receiving AI at detected estrus and FTAI, low prevalence of disease anovulation may have contributed to the similar performance of ED-Ov, ED-PR and DO.
PubMed: 37717491
DOI: 10.1016/j.anireprosci.2023.107331 -
Trials Sep 2023Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5-10% of AYAs worldwide....
SPIOMET4HEALTH-efficacy, tolerability and safety of lifestyle intervention plus a fixed dose combination of spironolactone, pioglitazone and metformin (SPIOMET) for adolescent girls and young women with polycystic ovary syndrome: study protocol for a multicentre, randomised, double-blind,...
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5-10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs.
METHODS
In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO.
DISCUSSION
The present study will be the first to evaluate-in a randomised, double-blind, placebo-controlled way-the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention.
TRIAL REGISTRATION
EudraCT 2021-003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58 .
Topics: Adolescent; Female; Humans; Carotid Intima-Media Thickness; Clinical Trials, Phase II as Topic; Insulin; Life Style; Metformin; Multicenter Studies as Topic; Pioglitazone; Polycystic Ovary Syndrome; Quality of Life; Randomized Controlled Trials as Topic; Spironolactone; Young Adult
PubMed: 37715279
DOI: 10.1186/s13063-023-07593-6