ArticleLiterature Review

The pathogenesis and treatment of polycystic ovary syndrome: What's new?

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Abstract

Polycystic ovary syndrome (PCOS) is currently the leading cause of menstrual complications in women. It is characterized by clinical and/or biochemical hyperandrogenism, ovulation abnormalities and the presence of enlarged and/or polycystic ovaries in ultrasound images (12 or more small bubbles located circumferentially and/or ovarian volume > 10 mL). It is often comorbid with hyperinsulinemia, dyslipidemia, overweight or obesity, and is a risk factor for the development of diabetes and cardiovascular diseases (CVDs). The treatment of patients with PCOS depends on the prevailing symptoms. The aim of this paper is to present the etiopathogenesis, clinical and biochemical implications, and non-pharmacological and pharmacological treatment options - those approved by worldwide scientific organizations as well as new therapies whose initial results are encouraging enough to prompt researchers to explore them further.

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... Gynecological complications include subfertility and a high risk of miscarriage, gestational diabetes, endometrial atypia or carcinoma, and possibly ovarian malignancy. [1][2][3][4] Hence, it is critical that health care professionals understand the complexity of this condition and the need for accurate diagnosis, appropriate management, and coordinated care. ...
... Evaluation of patients suspected of having PCOS includes clinical assessment for the presence of hirsutism, ovarian ultrasonography, and laboratory hormonal assessment to confirm hyperandrogenism and oligo-anovulation and to exclude other similar disorders. [1][2][3][4] Traditionally, the treatment of patients with PCOS has focused on the relief of symptoms and is set according to the management goal: relief of hyperandrogenic symptoms, regulation of menstruation, and restoration of fertility. [1][2][3][4] Despite significant progress in understanding the pathophysiology of PCOS over the past two decades, it remains underdiagnosed by many practitioners. 1 Management of PCOS is complex and should include the relief of symptoms and the screening and treatment of chronic metabolic, atherosclerotic, and gynecological complications. ...
... [1][2][3][4] Traditionally, the treatment of patients with PCOS has focused on the relief of symptoms and is set according to the management goal: relief of hyperandrogenic symptoms, regulation of menstruation, and restoration of fertility. [1][2][3][4] Despite significant progress in understanding the pathophysiology of PCOS over the past two decades, it remains underdiagnosed by many practitioners. 1 Management of PCOS is complex and should include the relief of symptoms and the screening and treatment of chronic metabolic, atherosclerotic, and gynecological complications. 5 Due to the different phenotypes of women with PCOS and the different interests of expert groups, guidelines have pointed physicians in different directions to diagnose and manage PCOS. ...
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Background Studies from several regions examined the approach to diagnosing and managing polycystic ovary syndrome (PCOS). Limited data are available from the Middle East and Africa (MEA). Objective The aim of this study was to understand the practice pattern for diagnosing and managing PCOS by relevant specialists across the MEA region. Methods We used an online survey consisting of an established questionnaire. The questionnaire consisted of 25 questions grouped to capture information on (a) the characteristics of the respondents, (b) patients with PCOS seen by respondents, (c) the diagnostic criteria, (d) biochemical parameters for differential diagnosis of hyperandrogenism, (e) long-term concerns, and, finally (f) management choices. Results A total of 190 questionnaires were available for final analysis; 73.7% of the respondents were senior physicians; 59.5% and 17.4% were endocrinologists and gynecologists, respectively. Menstrual irregularity was the most frequent criterion used for the diagnosis of PCOS (90.5%), followed by hirsutism (75.7%), and biochemical hyperandrogenism (71.4%). Dehydroepiandrosterone was the most frequent biochemical parameter used for the differential diagnosis of hyperandrogenism (52.4%) followed by total testosterone (45.4%). Obesity and type 2 diabetes mellitus were the principal long-term concerns for PCOS (45.1%), followed by infertility (29.9%). Metformin was the most commonly prescribed treatment (43.8%), followed by lifestyle modification (27.0%), and oral contraceptives (18.9%). Infertility treatments include metformin alone, clomiphene citrate alone, or their combination prescribed by 23.1, 9.9, or 52.7%, respectively, whereas only 3.8% contemplated ovulation induction. Some differences and similarities were observed in previous studies, including gynecologists and endocrinologists. Conclusions This survey provides a baseline for the perspective in diagnosing and treating PCOS in the MEA region. Some deviation is observed from mainline recommended practices. More education on PCOS diagnostic criteria and treatment of PCOS is needed in line with the recently published evidence international guideline.
... The paraclinical characteristic of PCOS patients is increased LH serum levels and normal FSH levels. It is considered to be due to increased release frequency of GnRH from the hypothalamus which leads to a hyperfunction of the theca cells [4]. The estradiol serum levels are similar to those of the healthy controls but still of lower values and they remain constant along the duration of the whole menstrual cycle. ...
... Vitamin D plays an extremely important role in calcium-phosphorus (Ca 2+ × HPO 4 2− ) metabolism and provides constant serum levels of both elements for metabolic needs and bone mineralization. Vitamin D deficiency leads to secondary hyperparathyroidism associated with osteoclastogenesis and increased bone resorption exceeding osteoblast-mediated bone formation. ...
... Normal but statistically significant lower levels estradiol -356.94 ± 157.91 pmol/L (p = 0.043) and statistically significant higher values of AMH -10.11 ± 2.67 ng/mL (p < 0.001) are observed. Franks and Bednarska report in their studies that the patients with PCOS are characterized by increased serum levels of androgens, LH and AMH, but by normal or low serum levels of FSH [2,4]. ...
Article
Background: Problems with hormonal changes and the related variations in bone turnover in adolescents with polycystic ovarian syndrome (PCOS) have been of interest in terms of providing these patients with an opportunity to receive a prophylactic and precision-based treatment aiming to prevent early onset of osteoporosis. Materials and methods: Prospective comparative clinical trial—‘case-control’ type in Bulgarian populace of 36 female patients with PCOS and 42 healthy controls aged 12 to 18. The study protocol included a general section of anthropometric patient data, clinical section–including general and Ob/Gyn Medical History, ultrasound exam of the lesser pelvis and a lab section examining the serum levels of Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), estradiol, Anti-Müllerian hormone (AMH) and bone turnover markers–osteocalcin and β-CrossLaps (bCTX), as well as Vitamin D. Results: A statistically significant high serum levels of the gonadotropic hormones were observed (LH — p < 0.001 и FSH — p = 0.017), AMH (p < 0.001) in patients with PCOS compared to the controls, while the estradiol (p = 0.043) and osteocalcin (p < 0.001) levels displayed a statistically significant lower values in patients with PCOS compared to the control group. AMH can be utilized as a surrogate marker for diagnosing patients with PCOS where the marker shows sensitivity — 94% and specificity — 69% with threshold value (cut-off) at ≥5.95 ng/mL (area under the curve 0.854, p < 0.001). Significant variance in Vitamin D serum levels between the two groups was not detected. Conclusion: Despite the hormonal characteristic of normogonadotropic normogonadism in adolescent patients with PCOS, the significantly lower values of osteocalcin demonstrated suppressed bone metabolism–bone formation, in particular–compared to the healthy controls, which can be interpreted as increased risk of insufficient bone accretion and risk of early onset of osteoporosis later in life.
... Entre estas, perfil lipídico anormal (triglicéridos y lipoproteínas de baja densidad elevados), sobrepeso y obesidad, resistencia a la insulina independiente del IMC, por lo tanto, mayor riesgo de diabetes mellitus (4,9). Además, las mujeres con SOP podrían tener afectación de aspectos psiquiátricos, por ejemplo, ansiedad, depresión, desorden bipolar y desórdenes alimenticios (7,10). También se ha visto la presencia de lesiones en la sustancia blanca cerebral de pacientes posmenopáusicas con SOP (7). ...
... En algunas pacientes, debido al estrés oxidativo y el aumento en los marcadores inflamatorios, hay un aumento en la hepcidina, lo que provoca una inhibición de la absorción de hierro por parte de los enterocitos, resultando así en deficiencia de hierro y anemia. Por otro lado, en algunas pacientes ocurre lo contrario, en donde se encuentra una sobrecarga de hierro, manifestada por los niveles de ferritina y hepcidina; esto representa un aumento en el riesgo de resistencia a la insulina y enfermedad cardiovascular, sin embargo, se puede regular reduciendo el consumo de carnes rojas y el uso de quelantes de hierro y zinc (10). Aún no está clara la relación entre SOP y los abortos recurrentes. ...
... Como parte del tratamiento farmacológico, la metformina ha demostrado contribuir con la regularización de los ciclos menstruales y detener la anovulación, además, en las pacientes que desean concebir favorece las tasas de embarazos. Usualmente, esta opción se reserva para las pacientes con IMC >25 kg/m², y suele presentar resultados aproximadamente 6 meses después del inicio del tratamiento (1,4,10). Se debe investigar acerca del deseo de la paciente de concebir, ya que, de ser así, el tratamiento en cuanto al HA clínico consta de medidas cosméticas como la decoloración del vello o terapias de depilación. ...
Article
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El síndrome de ovario poliquístico (SOP) es la patología endocrinometabólica más frecuente que afecta a mujeres en edad fértil, y es la principal causa de infertilidad por anovulación. Uno de los aspectos más importantes del síndrome es el exceso de andrógenos de origen ovárico, que se puede evidenciar en el análisis bioquímico o en las manifestaciones clínicas que induce. La fisiopatología aún no se conoce por completo, por lo que se deben excluir otras causas para realizar el diagnóstico, con 2 de los 3 siguientes criterios: a) hiperandrogenismo, b) oligoovulación, c) patrón polimicrofolicular de ovarios. Según sus manifestaciones, las pacientes se pueden clasificar en 4 diferentes fenotipos, los cuales también se diferencian por su severidad. Además, una evidente relación con la resistencia a la insulina y, por lo tanto, un aumento en el riesgo de enfermedad metabólica y cardiovascular. El tratamiento se basa principalmente en medidas higiénico - dietéticas y el uso de anticonceptivos orales, dependiendo de la clínica de cada paciente y de su deseo de concepción.
... O principal objetivo desse tratamento é tornar o ciclo menstrual regular, reduzir os sintomas de hiperandrogenismo, diminuir as anormalidades metabólicas, induzir a ovulação nas mulheres que desejam gestação, oferecer contracepção para as mulheres que não desejam engravidar, prevenir a hiperplasia e câncer de endométrio (BEDNARSKA & SIJKA, 2017). ...
... Podem também ser utilizados outros métodos hormonais, como os combinados ou os compostos apenas por progesterona. Como exemplos tem-se: injetável mensal, anel vaginal, adesivo, dispositivo intrauterino, injetável trimestral e implante subdérmico (BEDNARSKA & SIJKA, 2017). ...
... Polycystic Ovary Syndrome (PCOS) is the most common disorder affecting this subgroup of patients, with prevalence ranging from 6 to 10% of the global population depending on the classification criteria used (2). It is recognized that PCOS is not a cause of anovulation but rather a symptom of chronic anovulation caused by a range of both endocrinologic and functional abnormalities (3). As opposed to normal cycling hormone concentrations in ovulating women, women with PCOS are often described as being in a "hormonally steady state, " with both gonadotropin and sex steroid concentrations similar to those seen in early follicular phase (4). ...
... A positive feedback of increased ovarian androgens contributes to insulin resistance which in turn inhibits hepatic sex hormone binding globulin production, further increasing androgen levels (17)(18)(19). These changes are responsible for the pathophysiological symptoms of PCOS, such as insulin resistance, which predisposes to type 2 diabetes, obesity, hirsutism, and anovulation (3). A stepwise approach in treating and managing patients diagnosed with PCOS can range from lifestyle interventions to invasive operations such as Laparoscopic Ovarian Drilling (LOD), which is often reserved for medication resistant cases. ...
Article
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Anovulation is very common and has several different clinical manifestations, including amenorrhea, oligomenorrhea and abnormal uterine bleeding. Various mechanisms can cause anovulation. The clinical consequences and commonest chronic anovulatory disorder, polycystic ovary syndrome (PCOS), has a prevalence that ranges between 6 to 10% of the global population. While multiple causes can eventually result in PCOS, various methods have been described in the literature for its management, often without ascertaining the underlying cause. Ovulation Induction (OI) is a group of techniques that is used in women with PCOS who are looking to conceive and are unbale to do so with natural means. This narrative review presents a summary of the current evidence and available techniques for OI in women with PCOS, highlighting their performance and applicability.
... Existing evidence indicates that the elevation of TNF-α and IL-6 levels is directly associated with the occurrence and development of PCOS [30]. Accordingly, the levels of TNF-α and IL-6 in the serum of obese and nonobese PCOS patients were detected using ELISA, followed by analyses of their correlations with serum miR-124-3p and ANGPTL2 mRNA levels. ...
... However, it remains unknown whether ANGPTL2 can be adopted as a new molecular target to treat PCOS by reducing its expression or inhibiting its activity. As elaborated earlier, elevated TNF-α and IL-6 levels are directly associated with PCOS occurrence and development [30]. erefore, we analyzed the correlation between miR-124-3p and ANGPTL2 expressions in serum and TNF-α and IL-6 levels in serum of obese and nonobese PCOS patients and unraveled that miR-124-3p was negatively correlated with TNF-α and IL-6, while ANGPTL2 was positively correlated with TNF-α and IL-6. ...
Article
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Polycystic ovary syndrome (PCOS) is a hormonal disorder that affects 5–20% of women of reproductive age. Interestingly, serum miR-124-3p and ANGPTL2 are differentially expressed in PCOS patients. Accordingly, this study set out to explore the clinical roles of serum miR-124-3p/ANGPTL2 in PCOS. Firstly, miR-124-3p/ANGPTL2 expression patterns were detected in the serum of 102 PCOS patients and 100 healthy subjects. miR-124-3p or/and ANGPTL2 diagnostic efficacy on PCOS was further analyzed, in addition to the measurement of lipid metabolism, glucose metabolism, sex hormone indexes, and inflammation levels. Correlations between serum miR-124-3p/ANGPTL2 expressions and age, BMI, Ferriman–Gallwey score, lipid metabolism, glucose metabolism, sex hormone indexes, TNF-α, and IL-6 in PCOS patients were determined. The expression correlation and binding relationship of ANGPTL2 and miR-124-3p were identified. In addition, miR-124-3p was downregulated and ANGPTL2 was upregulated in the serum of obese and nonobese PCOS patients. miR-124-3p expression was found to be negatively correlated with Ferriman–Gallwey score and serum total testosterone (T), and negatively related to prolactin (PRL). ANGPTL2 expression was positively correlated with FNS and inversely linked with PRL. TNF-α and IL-6 were negatively correlated with miR-124-3p, but positively correlated with ANGPTL2. Furthermore, there was a negative correlation and a targeting relationship between ANGPTL2 and miR-124-3p expression in the serum of obese and nonobese PCOS patients. Collectively, our findings indicated that miR-124-3p might target ANGPTL2 expression in obese and nonobese PCOS patients, and further underscored the diagnostic value of their combination.
... Despite these well-characterized phenotypes, the pathogenesis of PCOS remains unclear; it is a multifactorial disorder that involves genetic, epigenetic and environmental variables [9], as well as immunity disorders [10]. ...
... Insulin and insulin growth factor 1 (IGF-1) trigger some pathways in inner theca cells, directly causing its hypertrophy and the overproduction of androgens [17]. Particularly, they activate CYP17A1 and the steroidogenic factor (SF-1), favoring the adrenal steroidogenesis as well as the ovarian one [9]. In addition, hyperinsulinemia and hyperandrogenism affect pituitary LH pulsatility and worsen the release of male hormones [18]. ...
Article
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Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder mainly characterized by a hormonal and metabolic disbalance that leads to oligo/anovulation, hyperandrogenism and the formation of ovarian cysts. Despite the progress that has been reached in its diagnosis and management, little is known about the molecular mechanisms and signaling pathways underlying the pathogenic mechanisms. In this sense, recent research has suggested that the influence of multiple factors, including age, environment, lifestyle and the disease state environment can change the clinical presentation of PCOS via epigenetic modifications. Variants in the genes encoding for proteins involved in steroidogenesis and glucose homeostasis play a crucial role in the development of the disease. Other genes involved in inflammation and cell proliferation seem to undergo an epigenetic control. Moreover, lifestyle factors influence the PCOS course and prognosis, including diet and physical activity, which are fundamental in reducing oxidative stress, inflammation and in improving metabolic and hormonal parameters. In the present review, literature evidence on molecular and epigenetic mechanisms related to PCOS etiology will be discussed, with a particular attention on the positive influence of diet and physical activity as nonpharmacological ways of intervention in the management of the disease.
... PCOS is a serious medical condition associated with defects in metabolic, reproductive and psychological functions, affecting approximately 5-20% of reproductive-age women (51,52). It manifests as a heterozygous entity of menstrual cycle abnormalities, anovulation, IR, hirsutism and androgenetic alopecia (53). Hyperinsulinemia and IR play an important role in the pathophysiology and metabolic manifestations of PCOS (54). ...
... For the treatment of PCOS women with anovulatory infertility, aromatase inhibitors such as letrozole are the recommended first-line therapy, with clomiphene and metformin alone or in combination. Gonadotrophins are a second-line therapy (53,74,75). ...
Article
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Brown adipose tissue (BAT), a unique tissue, plays a key role in metabolism and energy expenditure through adaptive nonshivering thermogenesis. It has recently become a therapeutic target in the treatment of obesity and metabolic diseases. The thermogenic effect of BAT occurs through uncoupling protein-1 by uncoupling adenosine triphosphate (ATP) synthesis from energy substrate oxidation. The review discusses the recent developments and progress associated with the biology, function, and activation of BAT, with a focus on its therapeutic potential for the treatment of polycystic ovary syndrome (PCOS). The endocrine activity of brown adipocytes affects the energy balance and homeostasis of glucose and lipids, thereby affecting the association of BAT activity and the metabolic profile. PCOS is a complex reproductive and metabolic disorder of reproductive-age women. Functional abnormalities of adipose tissue (AT) have been reported in patients with PCOS. Numerous studies have shown that BAT could regulate the features of PCOS and that increases in BAT mass or activity were effective in the treatment of PCOS through approaches including cold stimulation, BAT transplantation and compound activation in various animal models. Therefore, BAT may be used as a novel management strategy for the patients with PCOS to improve women’s health clinically. It is highly important to identify key brown adipokines for the discovery and development of novel candidates to establish an efficacious therapeutic strategy for patients with PCOS in the future.
... Первоначально существовали две воз можные теории развития СПЯ: с одной сто роны, рассматривалась теория гонадотроп ной дисфункции, которая характеризуется нарушением секреции гонадотропин рили зинг гормона в гипоталамусе, а с другойтеория инсулинорезистентности [10,11,18,[24][25][26][27][28]. Объектом центральной теории, или теории гонадотропной дисфункции, являет ся гипоталамус. ...
... То есть образуется такая концентрация ФСГ, которая недостаточна для подавления активности антимюллерова гормона (АМГ), затрудняющего рост фол ликула за счет ингибирования ФСГ. Все это приводит к гиперандрогении и нерегуляр ному формированию доминантного фол ликула (нарушение овуляции) [15,23,24]. ...
Article
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The polycystic ovary syndrome (POS) is a common hormonal disorder in women all over the world; it is characterized not only by reproductive disturbances but by endocrine and metabolic as well. Women with POS are subjected to an increased risk for the development of type 2 diabetes mellitus, metabolic syndrome and sterility. This article presents information on POS problems, its history. The main etiological factors predisposing to the development of polycystic ovaries syndrome are highlighted. Besides, actual data on pathogenetic theories of POS development are presented.
... Increasing evidence suggests that genetic, epigenetic, and environmental factors contribute to PCOS progression. 13 However, it was generally accepted that IR and hyperandrogenism play key roles in its etiology. 14 ...
... PCOS consists of hyperandrogenemia, ovulatory disorders, hyperinsulinism, and insulin resistance [148]. In addition, the syndrome raises the risk of endometrial cancer [20], as well as diabetes, cardiovascular disease [149] and contributes to reduced female fertility [150]. The role of iron in PCOS appears to be important, if only because iron may have a role as an oxidative factor in the development of insulin resistance in these patients [151]. ...
Article
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Iron and cobalt are micronutrients that play an important role in the regulation of cellular processes, being part of the centre of catalases, peroxidases, cytochromes and metalloproteins such as hemoglobin and myoglobin (Fe). Cobalt primarily functions as a component of hydroxycobalamin, which is essential for regulating red blood cell production. Maintaining normal levels of cobalt and iron in the human body is important, as a deficiency can lead to anaemia. These elements are also involved in reactions during which oxidative stress occurs and are therefore considered to be a cause of tumor formation. This paper will discuss aspects of the influence of cobalt and iron on mechanisms that may contribute to the growth of gynecological tumors, as well as other obstetric-gynecological disease entities, by altering the conditions of the microenvironment. In addition, the following review also highlights the role of cobalt and iron in the treatment of gynecological tumors.
... Measurements of sex hormone levels (particularly testosterone, LH, and E2) is used for diagnosing PCOS [15]. Indeed, elevated serum testosterone and LH concentrations and low E2, progesterone, and FSH levels are the most consistent hormonal features for diagnosing PCOS in women [25]. In this study, the PCOS group showed high LH and testosterone levels but low E2 and progesterone concentrations compared to the control group. ...
Article
Objective: Polycystic ovary syndrome (PCOS) is an endocrine disorder that disrupts the menstrual cycle and causes infertility. Considering the increasing use of medicinal plants, the present study aimed to evaluate the effects of Teucrium polium L. on letrozole-induced PCOS in female rats. Methods: Six groups of rats (n=7 each) were evaluated. The control group received 1% carboxy methyl cellulose as vehicle, while the five other groups received letrozole 1 mg/kg orally for 21 days. After PCOS induction, the rats were orally administered T. polium extract (50, 100, 200 mg/kg) or metformin (200 mg/kg) for 28 days. Subsequently, body and ovarian weights and serum levels of follicle stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, and testosterone were measured. Finally, the ovarian tissues were isolated for histological examination. Results: There were no significant changes in weekly body weight in any group. After 21 days of letrozole administration, PCOS induction was confirmed by estrous cycle irregularities and increased LH and testosterone levels. After treatment with the hydroalcoholic extract of T. polium, testosterone and LH levels were significantly reduced in all groups (P<0.05). Histological studies of ovaries in the metformin and T. polium groups exhibited normal follicular development with fewer and smaller cystic follicles than those in the PCOS group. Conclusion: The hydroalcoholic extract of T. polium improves serum levels of sex hormones, restores ovarian morphology in PCOS-induced rats, and is a good candidate for further clinical trials.
... Although the mechanism of insulin resistance in PCOS is not fully understood, the main defect, as we reported above, occurs in the PI3K post-receptor pathway, which mediates the metabolic effects of insulin [34]. Hyperinsulinemia plays an important role in the development of some of the phenotypic features of PCOS and, together with β-cell dysfunction, increases the risk of developing other metabolic disorders such as type 2 diabetes mellitus (DM2), hypertension, dyslipidemia, and cardiovascular disease, collectively referred to as the metabolic syndrome [35]. By increasing body weight, the post-receptor insulin PI3K pathway becomes resistant to its effects due to the formation of selective dysfunction of this pathway, which leads to compensatory hyperinsulinemia [36]. ...
Article
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Polycystic ovary syndrome is a heterogeneous endocrine disease that affects women of childbearing age. The pathogenesis of polycystic ovary syndrome has not been fully studied to date, its paradigm considers the genetic determinism of the manifestation of hormonal and metabolic disorders, which are considered to be criteria for the verification of the disease (hyperandrogenism, oligo/anovulation and/or polycystic ovarian transformation during ultrasound examination (ultrasound). This review discusses the main ways of interaction between hyperandrogenism, insulin resistance and obesity and their role in the pathogenesis of polycystic ovary syndrome, as well as possible methods of treatment for this category of patients. The review analyzes the role of hyperandrogenism and insulin resistance in the implementation of the genetic scenario of polycystic ovary syndrome and finds out the reasons why women with polycystic ovary syndrome often demonstrate the presence of a «metabolic trio» - hyperinsulinemia, insulin resistance and type 2 diabetes mellitus. It is noted that obesity is not included in the criteria for the diagnosis of polycystic ovary syndrome, but epidemiological data confirm the existence of a relationship between these diseases. Obesity, especially visceral, which is often found in women with polycystic ovary syndrome, enhances and worsens metabolic and reproductive outcomes with polycystic ovary syndrome, as well as increases insulin resistance and compensatory hyperinsulinemia, which, in turn, stimulates adipogenesis and suppresses lipolysis. Obesity increases the sensitivity of tech cells to luteinizing hormone stimulation and enhances functional hyperandrogenism of the ovaries, increasing the production of androgens by the ovaries. Excess body weight is associated with a large number of inflammatory adipokines, which, in turn, contribute to the growth of insulin resistance and adipogenesis. Obesity and insulin resistance exacerbate the symptoms of hyperandrogenism, forming a vicious circle that contributes to the development of polycystic ovary syndrome. These data allow us to conclude that bariatric surgery can become an alternative to drugs (metformin, thiazolidinedione analogs of glucagon-like peptide-1), which has shown positive results in the treatment of patients with polycystic ovary syndrome and obesity.
... At the same time, these small follicles also secrete excessive levels of anti-Mullerian hormone to inhibit the aromatase activity induced by follicle-stimulating hormone (FSH) and hinder follicular development. This leads to ovarian dysfunction [5]. It has also been reported that excessive androgen can induce low level inflammatory reaction in PCOS patients, forming a vicious cycle that ultimately leads to follicle development disorder [6,7]. ...
Article
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Objective: Hyperandrogenemia (HA) is the main pathophysiological change that takes place in polycystic ovary syndrome (PCOS). Cyproterone acetate (CYA) is a drug commonly used to reduce androgen in patients with PCOS. Long-term and continuous exposure to HA can cause ovarian granulosa cells (GCs), pyroptotic death, and follicular dysfunction in PCOS mice. The aim of this study was to investigate whether CYA could ameliorate the hyperandrogenemia-induced pyroptosis of PCOS ovarian GCs by alleviating the activation of the IRE1α signaling pathway. Methods: Firstly, thirty PCOS patients with HA as their main clinical manifestation were selected as the study group, and thirty non-PCOS patients were selected as the control group. The GCs and follicular fluid of the patients were collected, and the expression of pyroptosis-related proteins was detected. Secondly, a PCOS mouse model induced by dehydroepiandrosterone (DHEA) was constructed, and the treatment group model was constructed with the subcutaneous injection of cyproterone acetate in PCOS mice. The expression of pyroptosis-related protein in ovarian GCs was detected to explore the alleviating effect of CYA on the pyroptosis of ovarian GCs in PCOS mice. Thirdly, KGN cells-i.e., from the human GC line-were cultured with dihydrotestosterone, CYA, and ERN1 (IRE1α gene) small interfering RNA in vitro to explore whether CYA can alleviate the activation of the IRE1α signaling pathway and ameliorate the hyperandrogenemia-induced pyroptosis of PCOS ovarian GCs. Results: The expression of pyroptosis-related proteins was significantly increased in ovarian GCs of PCOS patients with HA as the main clinical manifestation, and in the PCOS mouse model induced by DHEA. After treatment with CYA, the expression of pyroptosis-related proteins in the ovarian GCs of mice was significantly lower than that in PCOS mice. In vitro experiments showed that CYA could ameliorate KGN cells’ pyroptosis by alleviating the activation of the IRE1α signaling pathway. Conclusion: This study showed that CYA could ameliorate the activation of the IRE1α signaling pathway in mouse GCs and KGN cells, and also alleviate pyroptosis in ovarian GCs. This study provides a new mechanism and evidential support for CYA in the treatment of PCOS patients.
... [4] Even though the definitive underlying etiology of PCOS did not conclude yet, multiple genetic, nutritional, and environmental factors are intertwined in PCOS pathogenicity, severity, and heterogeneity of its complications. [5,6] To that end, several reports have postulated that 67%-85% of PCOS women have impaired Vitamin D status, and its deficiency has a predominant role in the development and exacerbation of ovarian dysfunctionality, sex hormones irregularities, IR, impaired blood glucose metabolism, and other endocrine-metabolic features of PCOS; [7][8][9][10] assuming the screening essentiality of Vitamin D status in all reproductive women with PCOS. [11,12] In that respect, Vitamin D deficiency in Saudi Arabia is alarmingly high and can affect all human ages with an approximate prevalence rate of 63%. ...
Article
Background: Vitamin D deficiency in Saudi Arabia is alarmingly high and can affect all human ages. However, the characteristic hormonal and metabolic features, and the systemic Vitamin D levels, among Saudi women with polycystic ovarian syndrome (PCOS) remain largely unknown. Aims: This retrospective study aimed to identify the hormonal, metabolic, and Vitamin D status variabilities among infertile Saudi women with PCOS versus those of non-PCOS fertile women as controls. Materials and Methods: The medical records of a total of 99 women (49 PCOS and 50 controls), with matched age and body mass index, were analyzed in this study. For each woman who met the study inclusion criteria, the analyzed parameters included the serum levels of 25-hydroxyvitamin D (25(OH) D), sex hormone-binding globulin (SHBG), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), androgen, total testosterone (TT), estradiol, progesterone, thyroid hormones, the fasting plasma glucose (FPG), and lipid profile concentrations. Results: Compared to the controls, women with PCOS had significantly lower levels of 25(OH) D, SHBG, FSH, and estradiol, but they had significantly higher levels of LH, androgen, TT, FPG, total cholesterol, and low-density lipoprotein cholesterol. There were no differences between the two groups regarding the other parameters. Conclusions: The present findings highlight the prevalence of sex hormones, metabolic, and Vitamin D status disturbances among Saudi women with PCOS. Large-scale retrospective and prospective studies are therefore essential to realize these findings.
... Overall, 6-8% of women of reproductive age suffer from PCOS, making this disorder one of the most common endocrine abnormalities (Moffett and Naughton 2020). The main clinical and diagnostic features of PCOS are menstrual irregularity, biochemical and or clinical hyperandrogenism, and the presence of polycystic ovaries on ultrasound (Bednarska and Siejka 2017). Women with PCOS show an increased prevalence of clinical depression, anxiety, and symptoms of psychological distress, and other sorts of distress compared to women without PCOS (Deeks et al. 2011). ...
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Aim This study was conducted to examine stress and eating disorders in women undergoing in-vitro fertilization (IVF) treatment. Subject and methods This study was carried out on 159 women who applied to the infertility unit. The scales used in the study are the Fertility Adjustment Scale, the Scale for Coping with Infertility Stress, the ORTO-15 Scale, and the Eating Disorders Scale. Results It was found that women's infertility compliance scores were significantly higher for normal weight compared to overweight, obese women. On the ORTO-15 Scale, 75.5% of the women were orthorexic, and 43.5% had an eating disorder. The ORTO-15 scores of obese women were significantly lower than women with normal weight and those who were overweight. A statistically meaningful relationship was detected between the Eating Disorder Scale, active ignoring, and active struggling scores, and subdimensions of the scale of coping with infertility stress. The infertility compliance scale scores of those who did not undergo IVF were considerably higher than those who did (p = 0.005). Conclusion It is recommended to provide appropriate training, information, and counseling services for women to confirm their stress levels and learn active coping methods. It is inferred that body weight loss positively affects fertility and is beneficial in IVF treatment.
... Additionally, it not only improves the lipid profile and antioxidant characteristics and increases the levels of sex hormone binding globulin (SHBG), but also (through its pleiotropic effect on the vascular endothelium) acts to protect the cardiovascular system. [32] CONCLUSIONS Women suffering from PCOS are more prone to insulin resistance, dyslipidemia, hypertension and consequently, cardiovascular complications. Therefore, it is very important not to consider PCOS only in the context of gynecological and endocrine diseases, but also metabolic changes and cardiovascular diseases. ...
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Polycystic ovary syndrome (PCOS) is a heterogeneous disorder in terms of clinical symptoms and laboratory findings. It is one of the most common endocrinopathies in women of childbearing age. The development of symptoms and the degree of severity in the course of the disease are the results of changes in the ovaries which may be caused by many genetic, metabolic, neuroendocrine, and environmental factors. The main clinical manifestations are menstrual disorders, difficulties with becoming pregnant, and changes related to hyperandrogenism, e.g., acne, hirsutism. Recognition is above mainly based on Rotterdam criteria. A comprehensive explanation of pathophysiology is still lacking. Nevertheless, it probably is a multifactorial condition with a genetic component. Women suffering from PCOS experience lipid and carbohydrate metabolism disorders, which lead to insulin resistance, obesity, hypertension, and cardiac complications. Insulin resistance affects 65-70% of women and not only plays a significant role in the development of the disease but also contributes to the development of hypertension and dyslipidemia. Potential mechanisms of hypertension in PCOS include endothelial dysfunction, increased aldosterone, and excess testosterone secretion, whereas lipid abnormalities consist of reduced high-density lipoprotein-cholesterol (HDL-C), increased triglycerides, and low-density lipoprotein-cholesterol (LDL-C). All of these factors cause high cardiovascular risk. Currently, therapy considers both lifestyle improvements and medications and must be tailored on a case-by-case basis. It is very important not to consider PCOS only in the context of gynecological and endocrine diseases, but also metabolic changes and cardiovascular diseases. Treatment of PCOS should be individualized and dependent on the predominant disorders, as well as the short- and long-term goals chosen. It also should take the prevention of cardiovascular diseases into account.
... Women with PCOS are often obese, develop IR and are at risk of developing T2D [187,188]. The pathological mechanism by which PCOS arises is very complex, multifactorial and still remains largely unclear, but appears to be a disbalance in hormones, androgens and insulin in particular [189]. Furthermore, obesity may exacerbate features of PCOS by worsening IR and stimulating hyperandrogenism [190,191]. ...
Article
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According to the free hormone hypothesis, biological activity of a certain hormone is best reflected by free rather than total hormone concentrations. A crucial element in this theory is the presence of binding proteins, which function as gatekeepers for steroid action. For testosterone, tissue exposure is governed by a delicate equilibrium between free and total testosterone which is determined through interaction with the binding proteins sex hormone-binding globulin and albumin. Ageing, genetics and various pathological conditions influence this equilibrium, hereby possibly modulating hormonal exposure to the target tissues. Despite ongoing controversy on the subject, strong evidence from recent in vitro, in vivo and human experiments emphasizes the relevance of free testosterone. Currently, however, clinical possibilities for free hormone diagnostics are limited. Direct immunoassays are inaccurate, while gold standard liquid chromatography with tandem mass spectrometry (LC–MS/MS) coupled equilibrium dialysis is not available for clinical routine. Calculation models for free testosterone, despite intrinsic limitations, provide a suitable alternative, of which the Vermeulen calculator is currently the preferred method. Calculated free testosterone is indeed associated with bone health, frailty and other clinical endpoints. Moreover, the added value of free testosterone in the clinical diagnosis of male hypogonadism is clearly evident. In suspected hypogonadal men in whom borderline low total testosterone and/or altered sex hormone-binding globulin levels are detected, the determination of free testosterone avoids under- and overdiagnosis, facilitating adequate prescription of hormonal replacement therapy. As such, free testosterone should be integrated as a standard biochemical parameter, on top of total testosterone, in the diagnostic workflow of male hypogonadism.
... Uterine fibroids and ovarian cysts are the most common benign gynecological diseases in women with prevalence of 4.5-70% and 7-21% in global, respectively [8,9]. Uterine fibroids are characterized by noncancerous growth in the uterus, which commonly appears during childbearing years; ovarian cysts are a fluid-filled sac or pocket that appears in the ovary or on its surface [10,11]. Laparoscopic surgery is the primary treatment approach for patients with these conditions, especially for symptomatic women. ...
Article
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Aim: Diminished ovarian reserve can be characterized by poor response to ovulation and low number of eggs. The risk factors include endometriosis, receiving cancer treatment, luteal phase deficiency and gynecologic surgery. Uterine fibroids and ovarian cysts are the most common benign gynecological diseases in women globally. This prospective study evaluated the influence of laparoscopic surgery treating benign gynecological diseases on ovarian reserve. Methods: A total of 121 patients with uterine fibroids or benign ovarian cysts who received laparoscopic surgeries (41 with hysterectomy, 36 with myomectomy, 18 with adnexectomy, and 26 with ovarian cystectomy) were included. The ovarian reserve status defined as serum anti-Mullerian hormone concentration was assessed at 1 month before and after surgery, respectively. Results: The anti-Mullerian hormone reduction level was 22.34% in cystectomy, 44.1% in adnexectomy, 24.92% in myomectomy, and 47.61% in hysterectomy (p < 0.001). Multivariate analysis showed that adnexectomy had significantly high risk of high serum anti-Mullerian hormone reduction level (adjusted odds ratio (aOR): 14.90, 95% confidence interval (CI): 2.56-86.93, p = 0.003). Conclusions: These 4 laparoscopic surgeries all reduced the AMH levels 1 month after the procedure. Further prospective studies with longer follow-up are necessary to know the real impact on the ovarian reserve. Adnexectomy was an independent factor of reduced ovarian reserve in 1 month after surgery.
... It is thought that genes that escape from X inactivation in patients with triple X syndrome may cause POI (31). Although most patients with triple X syndrome can achieve pregnancy, the prevalence of sex chromosome anomaly, genitourinary system anomaly, neural tube defects, and cardiac malformation is high compared to the healthy population (31,32). There are many examples of other syndromic diseases that occur with POI, such as galactosemia, Perrault syndrome, ataxia telangiectasia, and McKusick-Kaufman syndrome. ...
Article
İnfertilite, erkek veya kadın üreme sisteminin bir hastalığı olup, 12 ay veya daha uzun süre düzenli ve korunmasız cinsel ilişkiden sonra gebelik elde edilememesi olarak tanımlanır. Veriler, dünya çapında 186 milyondan fazla insanın infertil olduğunu göstermektedir. Üreme çağındaki kadınların yaklaşık %10'u gebe kalamaz veya hamileliğini sürdüremez. Bu çalışmada kadın infertilitesinin nedenleri çeşitli başlıklar altında incelenmiş ve ayrıca infertilitede genetik danışmanlığın önemine de değinilmiştir. Kadın infertilitesinin hem genetik ve hem de genetik olmayan nedenler de dahil olmak üzere birçok farklı nedeni vardır. Bu derlemede kadın infertilitesinin genetik etiyolojisindeki güncel gelişmeler ve yaklaşımlar, kromozom anomalileri, kadın genital sistem bozuklukları, hipogonadotropik hipogonadizm, primer over yetmezliği, polikistik over sendromu ve gonadal disgenezi olmak üzere altı ana başlık altında incelenmiştir. Ayrıca bu hastalıklarda genetik danışmanlığın rolü de tartışılmıştır. Genetik danışmanlığın amacı, kalıtsal bir hastalığı olan veya taşıyıcı olma riski yüksek olan kişileri hastalığın seyri ve tedavi yöntemleri hakkında bilgilendirmek, aynı zamanda gelecek nesillere ve aile bireylerine de riskleri konusunda rehberlik etmektir. Tüm test ve tetkiklerden sonra, üreme sağlığında genetik danışmanlık çok önemli bir yere sahiptir.
... PCOS causes disturbances in the ovulation and an excess production of androgens, the pathogenesis responsible is not yet clear, and currently there is no definitive treatment, it is seems that visceral lipids cause an inflammatory response by releasing cytokines and interleukins, which affect the ovulation process (2). PCOS causes an imbalance in the menstrual cycle and is accompanied by high weight and diabetes, currently the treatment of PCOS depends on the dominant symptoms only (3). It has been proven that iron accumulation in the fatty tissue of PCOS patients is one of the causes of dysfunction in this tissue, and this appears especially in patients who suffer from obesity thus this confirm their metabolic disorder (4). ...
... PCOS causes disturbances in the ovulation and an excess production of androgens, the pathogenesis responsible is not yet clear, and currently there is no definitive treatment, it is seems that visceral lipids cause an inflammatory response by releasing cytokines and interleukins, which affect the ovulation process (2). PCOS causes an imbalance in the menstrual cycle and is accompanied by high weight and diabetes, currently the treatment of PCOS depends on the dominant symptoms only (3). It has been proven that iron accumulation in the fatty tissue of PCOS patients is one of the causes of dysfunction in this tissue, and this appears especially in patients who suffer from obesity thus this confirm their metabolic disorder (4). ...
Article
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Polycystic ovary syndrome (PCOS) is one of the most common gynecological diseases that affect the fertility in women in Basra governorate. The current study was designed in order to assess iron aberrations in PCOS patients by measuring the related parameters and their relationship with sex hormones in patients with PCOS. Serum samples were collected from 45 PCOS patients and 45 controls from a private women’s clinic and were measured by ELISA in a private medical laboratory. The results showed a significant decrease in the level of hepcidin, transferrin and estradiol versus a significant increase in iron, ferritin, progesterone and testosterone. The current study showed a clear imbalance in the level of iron and its serum regulating parameters in in PCOS women, and there is an effective correlation between iron status and sex hormones.
... It is obvious that the elevated serum level of TS and LH and low EST, progesterone, and FSH are the most comparable and consistent hormonal hallmarks to diagnose PCOS in women. 48 In this study, Ltz-induced PCOS rats displayed elevated levels of TS and LH, and low level of EST, compared with control. These results are consistent with the findings of the previous researches that produced PCOS-model by Ltz-administration. ...
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Background: Current therapies for polycystic ovary syndrome (PCOS) are accompanied by unwanted effects. Silibinin; a flavonolignan has pleiotropic activities and favorable safety profile. Purpose: To investigate the efficacy of silibinin on estrous cyclicity, inflammation, oxidative stress and ovarian morphology in letrozole-induced PCOS in rats. Methods: Forty-eight female Wistar albino rats were divided into 2 sets. Rats of the first set (n = 12), assigned as a negative control (NC) received only the vehicle, rats of the second set (n = 36), assigned as PCOS rats, were given letrozole 1mg/Kg orally for 21 days. On day 21, six rats from the first set and six rats from the second set were euthanized for confirmation of PCOS-induction. The remaining animals from the first set assigned as group 1, those in the second set (n = 30) were equally divided into 5 groups and treated daily for 19 days as follows: group 2 (positive control) received only the vehicle, group 3 treated with metformin 300mg/Kg orally, groups 4 and 5 treated respectively with 100 and 200 mg/Kg silibinin intraperitoneally (IP), and group 6 treated with a combination of metformin 300mg/Kg orally and silibinin 100mg/Kg IP. On day 40, blood samples were examined for luteinizing hormone (LH), testosterone (TS) and estradiol (EST) levels, the anti-inflammatory and antioxidant parameters, ovarian and uterine morphology. Results: Silibinin alone or in combination with metformin was found to be effective in restoring the regularity of estrous cycle by ameliorating the abnormal alterations of LH, TS, EST, tumor necrosis factor (TNF)-α, and oxidative status and by resuming the appearance of corpora lutea and decreasing or even total absence of cystic follicles in the ovaries. Conclusion: Silibinin was effective in restoring estrous regularities and alleviating hormonal and histomorphological abnormalities of the ovarian and uterine tissues, this could be due to its anti-androgenic, anti-inflammatory and antioxidant properties.
... Even though PCOS itself may not be a critical condition, it is considered to be associated with a relatively higher risk of developing other diseases, including type 2 diabetes mellitus, cardiovascular disease, and endometrial cancer (8)(9)(10). Clinically applied treatment for PCOS at present is mostly limited to pharmacological therapies targeting anovulatory infertility, menstrual disturbances, or hyperandrogenism, involving clomifene, metformin, and oral contraceptive pills (11). These strategies may be ideal in terms of alleviating the symptoms temporarily; however, an effective approach for comprehensive improvement of ovarian function, particularly polycystic ovarian morphology, remains a clinical challenge and an interest of researchers. ...
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Objectives: Astragaloside IV (AS-IV) is a bioactive saponin with a wide range of pharmacological effects. This study was aimed at investigating its potential effect on polycystic ovary syndrome (PCOS). Materials and methods: Female Sprague-Dawley rats were randomly divided into five groups (control, PCOS, PCOS+AS-IV 20 mg/kg, PCOS+AS-IV 40 mg/kg, and PCOS+AS-IV 80 mg/kg). The pathological injury level of rat ovary was observed with hematoxylin-eosin (H&E) staining; enzyme-linked immunosorbent assay (ELISA) kit was utilized to measure the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone in rat serum; western blot detected autophagy-associated or peroxisome proliferator-activated receptor γ (PPARγ) pathway-related protein expression; immunofluorescence was performed to observe LC3 level in rat ovarian tissue. After co-treatment with AS-IV and PPARγ inhibitor, the proliferation in ovarian granulosa cell line KGN was examined employing cell counting kit-8 (CCK-8), EdU staining, and colony formation; cell apoptosis was observed with TdT-mediated dUTP nick-end labeling (TUNEL); apoptosis-related protein expression was assayed by western blot. Results: Treatment with AS-IV inhibited the ovarian pathological damage in PCOS rats. It also promoted the level of autophagy and activated PPARγ signaling in the rat PCOS model. In KGN cells, the level of autophagy and expression of PPARγ-related proteins were also elevated by AS-IV treatment. Furthermore, AS-IV facilitated autophagy, thus inhibiting KGN cell proliferation and promoting its apoptosis, through activating the PPARγ signaling pathway. Conclusion: AS-IV-activated PPARγ inhibits proliferation and promotes the apoptosis of ovarian granulosa cells, enhancing ovarian function in rats with PCOS.
... To date, a variety of factors have been reported to be involved in the pathogenesis and clinical phenotype of PCOS, such as excessive androgen synthesis, follicular atresia, and insulin resistance [19]. However, the causes of PCOS are still unclear. ...
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Background: Polycystic ovary syndrome (PCOS) is a complex class of endocrine disorders with insulin resistance, compensatory hyperinsulinemia, and obesity. However, the pathogenesis and therapies of PCOS have not been fully elucidated. Exosomal miRNAs have the potential to serve as biomarkers and therapies for a wide range of medical conditions. Method: We collected follicular fluid from 5 PCOS patients and 5 healthy people. High-throughput sequencing technology to identify differentially expressed miRNAs and untargeted metabolome identify differential metabolites in follicular fluid exosomal. RT-qPCR and AUC analysis were performed. Result: miRNA high-throughput sequencing identified 124 differential miRNAs. RT-qPCR analysis confirmed the sequencing results. These differential miRNA target genes are mainly involved in metabolic pathways. Metabolomics studies identified 31 differential metabolites. miRNA and lncRNA coexpression networks in metabolic pathways rigorously screened 28 differentially expressed miRNAs. This network would identify miRNA signatures associated with metabolic processes in PCOS. Meanwhile, the area under curve of receiver operating characteristic revealed that hsa-miR-196a-3p, hsa-miR-143-5p, hsa-miR-106a-3p, hsa-miR-34a-5p, and hsa-miR-20a-5p were potential biomarkers for the diagnosis of PCOS. Conclusion: Collectively, these results demonstrate the potential pathogenesis of PCOS, and follicular fluid exosomal miRNAs may be efficient targets for the diagnosis and treatment of PCOS in long-term clinical studies.
... In addition, hyperinsulinemia caused by insulin resistance increases the risk of obesity, leading to a vicious circle of worsening insulin resistance and its metabolic sequelae (14). Elevated insulin and glucose levels are considered hallmarks of the development of type 2 diabetes, and PCOS plays a key role in the development and progression of diabetes (15). Di et al. have found that glucose metabolism, lipid accumulation, and insulin resistance are closely related (16). ...
Article
Background: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disease in women of childbearing age, and insulin resistance is an important etiological mechanism in PCOS. This study revealed the microRNA (miRNA) expression profile of PCOS with insulin resistance and explored the potential biological functions of differentially expressed miRNA. Methods: A total of 76 patients with PCOS and 30 normal healthy women were recruited in the gynecological clinic of the Second Hospital of Tianjin Medical University. We divided the patients with PCOS into a group with insulin resistance (n=46) and a group without insulin resistance (n=30). Peripheral venous serum samples from each group were used for deep sequencing to identify differentially expressed miRNAs. Hierarchical clustering heat maps were used to show differences in miRNA expression. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and target gene network databases were used to explore the potential target genes of differentially expressed miRNAs and to analyze their specific biological functions. Results: A case-control analysis found that the levels of body mass index (BMI), prolactin (PRL), total testosterone (T), fasting blood glucose (FBG), and fasting insulin (INS) in patients with PCOS were higher than those in healthy controls. High BMI, high blood sugar, and hyperinsulinemia were more significant in the PCOS with insulin resistance group than without insulin resistance group. Among the patients with PCOS, miR-122-5p was found to have more significant differences in the PCOS with insulin resistance group. GO and KEGG pathway analysis showed that the identified miRNAs were involved in the regulation of different biological processes, such as signal transduction, negative regulation of GTPase activity, chloride channel complex. The predicted target genes were related to the citrate cycle (TCA cycle) and the biosynthesis of mucin-type O-glycans. Conclusions: Our research demonstrated the use of miRNAs as new biomarkers for the diagnosis, treatment and presented a new strategy to lessen the symptoms of PCOS with insulin resistance.
... This result is consistent with previously published studies where metformin had no effect on the body and restored the estrous cycle (Huang et al., 2015;Zahoor and Shrivastava, 2022). Sex hormone levels, especially E2, are recommended for diagnosing PCOS (Bednarska and Siejka, 2017). In this study, the PCOS mice had higher E2 concentration than the control mice. ...
Article
Polycystic ovary syndrome (PCOS) is becoming a common pathology among women, yet its pathogenesis remains enigmatic. The chemokine C-X-C motif ligand 13 (CXCL13) and its receptor type 5 (CXCR5) regulate inflammatory responses but their roles in PCOS remain unknown. Metformin is commonly administered to PCOS patients but its mechanism of action remains unclear. Thus, we aimed to determine the expression of CXCL13 and CXCR5 in the ovaries of PCOS mice and to evaluate the therapeutic effect of metformin on them. The study comprised four groups of mice: control, PCOS, PCOS plus metformin, and PCOS plus vehicle. CXCL13 and CXCR5 were found to be elevated in the ovarian tissues of the PCOS mice. Metformin reduced ovarian CXCL13 and CXCR5 expressions in the PCOS mice. Hence, CXCL13 and CXCR5 are potentially involved in PCOS pathogenesis; and metformin may help alleviate the symptoms of PCOS by inhibiting CXCL13 expression and actions.
... Conversely, increased secretion of anti-Müllerian hormones (AMH) and LH, increased Gonadotropin-releasing hormone (GnRH) pulse rate, and decreased FSH levels are signs of the hypothalamic-pituitary-malfunctioning axis. [23] Treatment for this syndrome includes lifestyle changes, surgery, and taking some medicines, including clomiphene citrate and metformin. [24] Due to the unwanted effects of these drugs, the use of herbal medicines and their derivatives, which are less expensive, less invasive, and more valuable than other methods, has been considered. ...
Article
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Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases that affects 5%-10% of women of childbearing age. Several factors contribute to the development of PCOS such as dysfunction of the hypothalamic-pituitary axis and ovarian function, as well as increased insulin levels. The manifestations of the disorder include a wide range of symptoms, including menstrual disorders, acne, infertility, and increased body fat. Currently, the most well-known treatments for PCOS are clomiphene, metformin, letrozole, and tamoxifen. Due to their side effects, the identification of substitute drugs is essential. One of the traditional medicines, which is usually used in different parts of the world, particularly in Western Europe, is Bryonia dioica Jacq. (B. dioica). This plant is used in the treatment of disease due to its active ingredients like polyphenols. Materials and Methods: Induction PCOS in a female rat (3 weeks old) was performed through subcutaneous injection of testosterone enanthate (1 mg/100g) daily for 35 days. The effects of B. dioica (30 and 60 mg/kg) root methanolic extract on PCOS-induced was evaluated after 28-day treatment. On the last day, the serum levels of follicle-stimulating hormone (FSH), glucose, low-density lipoprotein/high-density lipoprotein (LDL/HDL), luteinizing hormone (LH), and testosterone and histological studies (hematoxylin and eosin [H&E] staining) were measured. Results: Results showed that FSH and LH levels (P < 0.05) as well as glucose (P < 0.001) in the B. dioica groups normalized significantly compared to the PCOS group. LDL levels decreased in rats and the LDL/HDL ratio decreased in all treatment groups. In histologic assay, metformin and B. dioica restricted the effects of testosterone in the ovaries of rats. Conclusion: The data indicate that methanolic extract of B. dioica recovers hormonal factors in PCOS.
... dysfunction, and polycystic ovarian morphology (60). It is also associated with metabolic disorders such as insulin resistance (61), type 2 diabetes, and other cardiovascular diseases (62). PCOS is caused by the interaction between numerous genes which affect neuroendocrine and metabolic functions, inducing metabolic endotoxemia and circulation of LPS, causing lowgrade chronic inflammation, cardiometabolic changes, increased NF-KB activation, and oxidative stress (63). ...
Article
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The human intestinal microbiota has been shown to be modulated during inflammatory conditions. Probiotic administration has been shown to affect the immune system and cytokine expression which can affect inflammation and health outcomes. There seems to be an association between the mother's intestinal microbiota and inflammation biomarkers, both of which may contribute to newborn early life immune and metabolic programming and impact short and long-term health outcomes. Probiotic supplementation during pregnancy has been shown to influence metabolic health, immunity, and gastrointestinal health of the mother, and can also have carry-over benefits to infants such as infant allergy risk reduction. Therefore, this review focuses on the evidence of probiotic administration in women of reproductive age, including during pregnancy and its impact on inflammatory markers and on maternal and infant health. We performed a PubMed search for articles published in English in the last 20 years. Immune markers were narrowed to serum and breast milk levels of TNF-α, IL-6 and TGF-β, IgA, and IL-10. Studies that investigated the beneficial effects of interventions in women with gestational diabetes mellitus, polycystic ovarian syndrome, and infant allergy management are summarized. These results show a beneficial or neutral effect on selected health outcomes and that it is safe for woman and their infants. The effect of probiotics on modulation of inflammatory markers was probiotic specific. More research is needed to further our understanding of the mechanisms underlying the effects of probiotics on inflammation and how these effects improve health outcomes.
... It is characterized by ovulatory, metabolic, and endocrine dysfunction [2]. Although the involved pathophysiological mechanisms are poorly understood [3], the different metabolic and endocrine alterations begin during puberty. In adolescent females, low vitamin E levels are associated with changes in fat metabolism, unlike their male counterparts [4]. ...
Article
Aim: This systematic review and meta-analysis assessed the effect of vitamin E supplementation on testosterone, glucose, lipid profile, pregnancy rate, hirsutism, and body mass index (BMI) in women with polycystic ovary syndrome (PCOS). Methods: A multi-database search was performed from inception to January 2022 for randomized controlled trials (RCTs) reporting the effects of vitamin E supplementation with or without another nutritional supplement on women with PCOS. A random-effects model was used to obtain mean differences (MDs) and its 95% confidence intervals (95%CI). Evidence certainty was assessed with GRADE methodology. Results: We meta-analyzed eight RCTs reporting vitamin E supplementation alone or combined with other individual substances like omega-3, vitamin D3, or magnesium oxide in adult women ≤40 years old with PCOS. Vitamin E supplementation reduced fasting glucose (MD: -1.92 mg/dL, 95%CI: -3.80 to -0.05), fasting insulin (MD: -2.24 µIU/mL, 95%CI: -3.34 to -1.14), HOMA-IR (MD: -0.42, 95%CI: -0.65 to -0.19), total cholesterol (MD: -18.12 mg/dL, 95%CI: -34.37 to -1.86), LDL-cholesterol (MD: -15.92 mg/dL, 95%CI: -29.93 to -1.90), triglycerides (MD: -20.95 mg/dL, 95%CI: -37.31 to -4.58), total testosterone (MD: -0.42 ng/mL, 95%CI: -0.55 to -0.29), and increased sex hormone-binding globulin (MD: 7.44 nmol/L, 95%CI: 2.68 to 12.20). However, it had no impact on female sex hormones, HDL-cholesterol, BMI, and hirsutism. Two RCTs assessed pregnancy and implantation rates with inconsistent results. The certainty of the evidence was very low to moderate. Conclusion: Vitamin E supplementation improves glucose, lipid, and androgenic-related biomarkers in women with PCOS.
... [2]. At present, the treatment of PCOS mainly includes surgery, long-term oral contraceptive, and ovulation induction; however, these treatments are limited by their high invasiveness, high recurrence rates, poor long-term results, and many side effects [3]. Recently, complementary and alternative medicine has become a more valuable option for the treatment of PCOS [4]. ...
Article
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Objective: Bushen Huoxue Huatan Decoction (BHHD) is a classic prescription for treating polycystic ovary syndrome (PCOS). This study aims to explore the effects and possible mechanisms of BHHD on PCOS by integrating network pharmacology and clinical study. Methods: The components and potential drug targets of BHHD were analysed using the TCMSP platform, and the potential pathogenesis targets for PCOS were analysed using the GeneCards and OMIM databases. Subsequently, a disease-compound-target network diagram was established to identify the targets of BHHD treatment on PCOS. In addition, protein-protein interaction analysis, KEGG pathway analysis, and Gene Ontology biological analysis were carried out to reveal the mechanisms of BHHD. To further validate the analysis, a clinical trial involving 62 PCOS patients was conducted. All patients were treated with BHHD for 3 months and the ovulation rate, anthropometric indicators, clinical symptoms, and serological indicators were measured and compared before and after treatment. Results: The network pharmacology analysis showed that quercetin, luteolin, and kaempferol are the most significant active components in BHHD; STAT3, Jun, AKT1, MAPK3, MAPK1, and TP53 are the most critical drug targets; regulating hormones, reversing insulin (INS) resistance, exerting anti-inflammatory effects, and improving fertility might be the most important mechanisms of BHHD in the treatment of PCOS. After BHHD administration, the cyclic ovulation rate and the clinical symptoms including acanthosis nigricans and acne of patients were obviously improved. The serum endocrine levels of luteinising hormone (LH), LH/follicle-stimulating hormone, testosterone, dehydroepiandrosterone sulphate, insulin (INS), and area under the INS curve were evidently reversed, and the serum inflammatory factors levels including human interleukin (IL)-18, IL-16, IL-1β, IL-8, macrophage migration inhibitory factor, and human leukocyte differentiation antigen CD40 ligand were greatly reduced. Conclusion: BHHD has a good therapeutic effect on PCOS, and its mechanisms may be related to regulating hormone levels, improving insulin resistance, alleviating inflammation, and promoting pregnancy.
... Polycystic ovary syndrome (PCOS) or Stein-Leventhal syndrome, is one of the most common incurable endocrinopathies among women of reproductive age [1,2]. PCOS characterized by many clinical-biochemical fea-Atoum/Alajlouni/Alzoughool Public Health Genomics 2 DOI: 10.1159/000521971 tures including ovulatory dysfunction which includes oligomenorrhea or amenorrhea [3], hyperandrogenic features which are clinically characterized by the presence of excessive acne or hirsutism, and biochemical features which are characterized by the elevated serum androgen level [4]. ...
Article
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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.
... PCOS is a heterogeneous endocrine disorder that affects women of reproductive age group worldwide. [1] PCOS is having multifactorial pathology which is influenced by genetic, endocrine, and environmental factors. [2] It is the usual cause of menstrual irregularities and infertility among females. ...
Article
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Polycystic ovarian syndrome (PCOS) is a common endocrine disorder that affects multiple aspect of women's health during the reproductive age group. PCOS exerts a negative impact on female identity and contributes to deterioration of Quality of life. Homoeopathy is a complementary system of medicine that can be used safely without any known side-effects. This article mainly highlights the importance of using individualized homoeopathic medicines in PCOS. Three cases of women in reproductive age with PCOS were treated with individualized homeopathic medicines. Each case was reported according to the criteria set out in the HOM-CASE guidelines. The improvement is evaluated from the regularity of the menstrual cycle by assessing with the PCOS questionnaire, Modified Naranjo Criteria for Homoeopathy (MONARCH), and also from the ultrasonography (USG) reports. Marked improvement was observed in all three cases of PCOS. The irregular menstrual cycles and other associated symptoms became normal, along with a resolution of cysts in ovaries as noticed in ultrasonography. All cases improved within 6 to 18 months of treatment. The Modified Naranjo Criteria total score was +8/13, +9/13, +8/13 for the cases, which indicates a positive causal attribution of homeopathy in relieving the symptoms of PCOS. These case reports suggest a significant role of individualized homeopathic medicines in PCOS. The improvement is evident at the symptomatic level, and also in Ultrasonography.
... Negli ultimi anni, Escobar-Morreale e collaboratori hanno ipotizzato che la PCOS derivi da un circolo vizioso di eccesso di androgeni che favorisce la deposizione di tessuto adiposo addominale e l'adiposità viscerale, inducendo IR e, conseguentemente, iperinsulinismo che a sua volta facilita ulteriormente la secrezione di androgeni da parte delle ovaie e dalle ghiandole surrenali nelle donne affette. Secondo questa teoria, le pazienti con disfunzione ovarica più grave dovrebbero pre-sentare anche un'IR più grave [9,18]. Ciò confermerebbe la bidirezionalità del meccanismo e l'importante ruolo dell'insulina nello sviluppo di infertilità femminile da causa ovarica. ...
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Sommario Il fattore femminile costituisce un’alta percentuale delle cause d’infertilità di coppia. Tra le cause più frequenti d’infertilità femminile vi sono quelle correlate a un inadeguato stile di vita e alla presenza di sindrome metabolica. L’insulino-resistenza (IR) è uno dei punti cardine della sindrome metabolica ed è coinvolta anche nell’eziopatogenesi della sindrome dell’ovaio policistico (PCOS), frequente causa d’infertilità anovulatoria. Inoltre, l’IR è alla base di alcune delle complicanze della PCOS, come la malattia epatica non alcolica (NAFLD), a sua volta indirettamente correlata a problematiche di fertilità. In questa rassegna proveremo dunque a fornire al lettore degli spunti di riflessione sul complesso e affascinante ruolo dell’IR e delle disfunzioni a essa correlate, nel campo della fertilità femminile.
... Due to the increasing pressure of women's life and work and the influence of living environment, the clinical incidence of PCOS is on the rise, which seriously affects the physical and mental health and life quality of patients [2]. e pathogenesis of PCOS is unclear but may be related to hyperandrogenemia, hyperinsulinemia, luteinizing hormone/follicle-stimulating hormone ratio imbalance, metabolic abnormalities, inflammation, advanced glycation end products, and endoplasmic reticulum stress [3][4][5]. PCOS is frequently associated with obesity, type 2 diabetes and gestational diabetes, cardiovascular disease, hepatic steatosis, and endometrial cancer [6][7][8]. ese diseases pose a serious threat to women's lives. ...
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Background: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder in women of gestational age and the most common cause of female infertility. This study aimed to investigate the effect of letrozole and metformin combined with targeted nursing on ovarian function, LH, and FSH in infertile patients with PCOS. Methods: A total of 72 infertile patients with PCOS were divided into the control group and combined group. The control group was given metformin tablets combined with targeted nursing therapy. The combined group was treated with letrozole on the basis of the control group. Ovarian function, LH, and FSH were compared between the two groups before and after treatment. Results: After treatment, the total effective rate (94.44%) of the combined group was significantly higher than that of the control group (80.56%). After treatment, the levels of HbA1c, FINS, HOMA-IR, TG, and TC in the two groups were lower than those before treatment, and the HDL-C level was higher than that before treatment. The full-term delivery rate, ovulation rate, and normal menstrual rate in the combined group were higher than those in the control group. After treatment, the LH level in the combined group was lower than that in the control group, and the FSH level was higher than that in the control group. After 1 month, 3 months, and 5 months of treatment, RI, PI, and ovarian volume were decreased, and the endometrial thickness was increased in both groups. Also, after 5 months of treatment, the RI, PI, and ovarian volume in the combined group were significantly lower than those in the control group, and the endometrial thickness was significantly higher than that in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups. Conclusion: The combination of letrozole and metformin with targeted nursing in the treatment of infertility patients with PCOS has better clinical effect and high safety. It can improve endometrial receptivity and ovarian reserve function and regulate LH and FSH levels.
... at present, available PcoS treatment strategies mainly focus on lifestyle changes, maintaining a healthy diet and chemotherapeutic drugs, such as metformin, oral contraceptive pills and spironolactone (6,7). However, the mechanism of PcoS pathogenesis is complex and remains to be fully elucidated (8). Therefore, it is of importance to understand the mechanisms underlying PcoS to provide novel insights into treatment strategies. ...
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Polycystic ovary syndrome is one of the most common endocrine and metabolic gynecological disorders, of which dysfunction of ovarian granulosa cells is a key contributing factor. The aim of the present study was to explore the role of ferrostatin‑1 (Fer‑1), a ferroptosis inhibitor, in a cell injury model established by homocysteine (Hcy)‑induced ovarian granulosa KGN cell line and the potential underlying mechanism. Cell viability was measured using Cell Counting Kit‑8 assay in the presence or absence of Hcy and Fer‑1. Cell apoptosis was assessed using TUNEL staining and the expression levels of apoptosis‑related proteins were measured using western blotting. To explore the effects of Fer‑1 on oxidative stress in Hcy‑treated ovarian granulosa cells, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), lactate dehydrogenase (LDH) and glutathione (GSH) were measured using their corresponding kits. Furthermore, Fe2+ levels were assessed using Phen Green™ SK labeling and western blotting was performed to measure the protein expression levels of ferroptosis‑associated proteins GPX4, SLC7A11, ASCL4 and DMT1. Subsequently, DNA methylation and ten‑eleven translocation (TET) 1/2 demethylase levels were also detected to evaluate the extent of overall DNA methylation in ovarian granulosa cells after Hcy treatment. The TET1/2 inhibitor Bobcat339 hydrochloride was applied to treat ovarian granulosa cells before evaluating the possible effects of Fer‑1 on TET1/2 and DNA methylation. Fer‑1 was found to markedly elevate ovarian granulosa cell viability following Hcy treatment. The apoptosis rate in Fer‑1‑treated groups was also markedly decreased, which was accompanied by downregulated Bax and cleaved caspase‑3 expression and upregulated Bcl‑2 protein expression. In addition, Fer‑1 treatment reduced the levels of ROS, MDA and LDH whilst enhancing the levels of GSH. Fe2+ levels were significantly decreased following Fer‑1 treatment, which also elevated glutathione peroxidase 4 expression whilst reducing solute carrier family 7 member 11, achaete‑scute family BHLH transcription factor 4 and divalent metal transporter 1 protein expression. Fer‑1 significantly inhibited DNA methylation and enhanced TET1/2 levels, which were reversed by treatment with Bobcat339 hydrochloride. Subsequent experiments on cell viability, oxidative stress, Fe2+ content, ferroptosis‑ and apoptosis‑related proteins levels revealed that Bobcat339 hydrochloride reversed the effects of Fer‑1 on ovarian granulosa Hcy‑induced cell injury. These results suggest that Fer‑1 may potentially protect ovarian granulosa cells against Hcy‑induced injury by increasing TET levels and reducing DNA methylation.
... Treatments mainly focus on controlling clinical symptoms and managing the conditions to prevent serious complications [311]. The treatment will vary from woman to woman, depending upon their specific symptoms. ...
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Polycystic ovarian syndrome is an utmost communal endocrine, psychological, reproductive, and metabolic disorder that occurs in women of reproductive age with extensive range of clinical manifestations. This may even lead to long-term multiple morbidities including obesity, diabetes mellitus, insulin resistance, cardiovascular disease, infertility, cerebrovascular diseases, and ovarian and endometrial cancer. Women affliction from PCOS in midst assemblage of manifestations allied with menstrual dysfunction and androgen exorbitance, which considerably affects eminence of life. PCOS is recognized as a multifactorial disorder and systemic syndrome in first-degree family members; therefore, the etiology of PCOS syndrome has not been copiously interpreted. The disorder of PCOS comprehends numerous allied health conditions and has influenced various metabolic processes. Due to multifaceted pathophysiology engaging several pathways and proteins, single genetic diagnostic tests cannot be supportive to determine in straight way. Clarification of cellular and biochemical pathways and various genetic players underlying PCOS could upsurge our consideration of pathophysiology of this syndrome. It is requisite to know pathophysiological relationship between biomarker and their reflection towards PCOS disease. Biomarkers deliver vibrantly and potent ways to apprehend the spectrum of PCOS with applications in screening, diagnosis, characterization, and monitoring. This paper relies on the endeavor to point out many candidates as potential biomarkers based on omics technologies, thus highlighting correlation between PCOS disease with innovative technologies. Therefore, the objective of existing review is to encapsulate more findings towards cutting-edge advances in prospective use of biomarkers for PCOS disease. Discussed biomarkers may be fruitful in guiding therapies, addressing disease risk, and predicting clinical outcomes in future.
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Ethnopharmacological relevance: In the Ayurvedic system of medicine, Cedrus deodara bark has been utilized as a folk medicine to remove ovarian cysts and treat infertility in females. Aim: The present study is the first to investigate ameliorating potential of C. deodara bark on testosterone propionate and high-fat diet-induced polycystic ovarian syndrome in experimental rats. Materials and methods: LC-MS analysis of the fraction selected through bioassay-guided approach employing uterine relaxant activity was performed to determine the bioactive constituents present in it. Further, the identified compounds were docked on the catalytic site of the androgen receptor and insulin receptor substrate-1. Later, the fraction was investigated against testosterone propionate and high-fat diet-induced PCOS in rats. Results: Chloroform fraction (F1) of the plant bark was found most active in uterine smooth muscle relaxant activity. LC-MS analysis of F1 indicated the presence of key flavonoids namely deodarin, cedrin, deodardione, and cedrusinin. Afterward, a molecular docking study of these compounds revealed impressive binding interactions with androgen receptor and insulin receptor substrate-1. Besides, in vivo studies, treatment with F1 significantly restored the estrous cycle in rats from the diestrus phase in a dose-dependent manner. Also, the disturbed metabolic and endocrine profile was markedly improved in rats. Later, histopathological analysis revealed the presence of a large number of mature follicles and corpora lutea in F1-treated rats. Conclusion: In a nutshell, F1 exhibited promising beneficial effects in PCOS and associated conditions via amelioration of metabolic, endocrine, and ovarian dynamics in experimental rats.
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Background Polycystic ovarian syndrome (PCOS) is a common condition of hyperandrogenism, chronic ovulation, and polycystic ovaries in females during the reproduction and maturation of the ovum. Although PCOS has been associated with metabolic disorders, including type 2 diabetes (T2D), obesity (OBE), and cardiovascular disease (CVD), Causal connection and molecular features are still unknown. Purpose Therefore, we investigated the shared common differentially expressed genes (DEGs), pathways, and networks of associated proteins in PCOS and metabolic diseases with therapeutic intervention. Methods We have used a bioinformatics pipeline to analyze transcriptome data for the polycystic ovarian syndrome (PCOS), type 2 diabetes (T2D), obesity (OBE), and cardiovascular diseases (CVD) in female patients. Then we employed gene-disease association network, gene ontology (GO) and signaling pathway analysis, selection of hub genes from protein-protein interaction (PPI) network, molecular docking, and gold benchmarking approach to screen potential hub proteins. Result We discovered 2225 DEGs in PCOS patients relative to healthy controls and 34, 91, and 205 significant DEGs with T2D, Obesity, and CVD, respectively. Gene Ontology analysis revealed several significant shared and metabolic pathways from signaling pathway analysis. Furthermore, we identified ten potential hub proteins from PPI analysis that may serve as a therapeutic intervention in the future. Finally, we targeted one significant hub protein, IGF2R (PDB ID: 2V5O), out of ten hub proteins based on the Maximal clique centrality (MCC) algorithm and literature review for molecular docking study. Enzastaurin (−12.5), Kaempferol (−9.1), Quercetin (−9.0), and Coumestrol (−8.9) kcal/mol showed higher binding affinity in the molecular docking approach than 19 drug compounds. We have also found that the selected four compounds displayed favorable ADMET properties compared to the native ligand. Conclusion Our in-silico research findings identified a shared molecular etiology between PCOS and metabolic diseases that may suggest new therapeutic targets and warrants future experimental validation of the key targets.
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Introduction: The efficacy of selenium supplementation was elusive for polycystic ovary syndrome. This meta-analysis aimed to explore the efficacy of selenium supplementation for polycystic ovary syndrome. Methods: PubMed, EMbase, Web of science, EBSCO, Cochrane library database, CNKI, Chongqing VIP database and Wanfang databases have been searched through July 2022 and we included randomized controlled trials (RCTs) reporting the effect of selenium supplementation versus placebo in patients with polycystic ovary syndrome. Results: Five RCTs were included in the meta-analysis. Compared with placebo group for polycystic ovary syndrome, selenium supplementation was associated with significantly reduced total testosterone (SMD=-0.42; 95% CI=-0.78 to −0.06; p = 0.02) and cholesterol (SMD=-0.71; 95% CI=-1.41 to −0.02; p = 0.04), but revealed no remarkable influence on SHBG (SMD=-0.52; 95% CI=-1.29 to 0.25; p = 0.19), triglyceride (SMD=-1.45; 95% CI=-3.62 to 0.73; p = 0.19), LDL (SMD=-0.17; 95% CI=-0.72 to 0.37; p = 0.53), FPG (SMD=-0.95; 95% CI=-3.72 to 1.82; p = 0.50) or HOMA-IR (SMD=-0.51; 95% CI=-3.79 to 2.77; p = 0.76). Conclusions: Selenium supplementation may be able to improve the metabolic response for polycystic ovary syndrome, and this finding should be interpreted with caution.
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PurposePolycystic ovarian syndrome (PCOS) is a metabolic syndrome associated with mineralocorticoid receptor (MR) activation, which causes infertility in women of reproductive age. Spironolactone (SPL) is a MR blocker with inconclusive effect in the treatment of PCOS. Therefore, the present study hypothesized that low dose SPL would ameliorate metabolic dysfunction associated with PCOS.Methods Female Wistar rats (8-week-old) were divided into 3 groups namely: Control, SPL, Letrozole (LET)-treated and LET + SPL-treated groups. The control group was given vehicle (distilled water), SPL-treated group received 0.25 mg/kg, LET-treated group received 1 mg/kg of LET and LET + SPL-treated group received a combination of LET and SPL. The administrations were done by oral gavage for 21 days uninterruptedly. Biochemical parameters such as lipid profile, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), testosterone, 17-β estradiol and glutathione peroxidase (GPx) were determined with appropriate assay methods.ResultsLetrozole-treated group had a significant increase in ovarian weight, plasma and ovarian triglycerides, MDA/TNF-α, GGT/LDH and plasma testosterone while it decreased plasma 17-β estradiol and plasma/ovarian high-density lipoproteins and GPx when compared with control group. In addition, histomorphological changes were observed in LET-treated group compared with control group. Nevertheless, administration of low dose SPL attenuated these perturbations.Conclusion The present study therefore demonstrates that inhibition of mineralocorticoid receptor by low dose SPL ameliorates hyperandrogenic metabolic dysfunction in a rat model of PCOS. Therefore, low dose SPL is hereby suggested as a promising therapeutic agent in the management of PCOS.
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Background The modified Guishen pill (MGP) has a prominent therapeutic effect on polycystic ovary syndrome (PCOS). However, its mechanism is still unclear. This study aimed to uncover the mechanism of MGP for PCOS treatment through a comprehensive strategy integrating metabolomics and network pharmacology. Methods A letrozole-induced PCOS model was used to evaluate ovarian function in rats. Plasma metabolomics was used to authenticate differential metabolites and enriched related pathways using the MetaboAnalyst platform. Network pharmacology was utilized to explore the endogenous targets of MGP treatment for PCOS. Finally, the potential targets and related biological functions were verified experimentally. Results MGP improved PCOS symptoms by regulating abnormal levels of sex hormones and alleviating ovarian pathological changes in rats; fifty-four potential differential metabolites involved in MGP treatment for PCOS, and the hub genes derived from network pharmacology were consistent with the metabolomic analysis results to varying degrees. The comprehensive analysis identified that a key novel target for endothelial nitric oxide synthase (eNOS/NOS3), five key metabolites (ornithine, citrulline, l-glutamic acid, acetylornithine, and hydroxyproline), and one pathway (arginine and proline metabolism) were related to the therapy of PCOS with MGP. Subsequently, we verified the localization and expression of eNOS in the ovaries, and it significantly improved insulin resistance, apoptosis, and oxidative stress in letrozole-induced PCOS rats. Conclusion Our work reveals the complex mechanism of MGP therapy for PCOS. This study is a successful paradigm for elucidating the pharmacological mechanism of the traditional Chinese medicine compound.
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Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. The present study aimed to evaluate the effects of Rosa damascena (RD) extract in estradiol valerate (EV) induced polycystic ovary syndrome rats. Material and Methods Adult female Wistar rats were divided into control (n = 12) and PCOS groups (n = 36). The PCOS model was induced using EV (4 mg/kg/day), which was confirmed in 6 rats in each control and PCOS group by observation of irregular estrous cycles in vaginal smears and ovarian multiple cystic. Then, the rest of the control group (n = 6) and PCOS rats (n = 30 in 5 divided groups) were treated orally for 28 days with metformin (MET) as a positive control (200 mg/kg/day) and RD extract (400, 800, and 1200 mg/kg/day, respectively). Body and ovary weights, biochemical and histological parameters, and expression of the IGF-1 gene were measured. Results Compared to the PCOS group, metformin and higher doses of RD extract (800 and 1200 mg/kg/day) significantly reduced BW, HOMA-IR, FBS, FINS, TG, LDL, TT, E2, LH, TC, and liver enzymes, and increased HDL and FSH levels. In addition, ovarian weight and CFs decreased, and the findings showed an increment in PFs, CLs, PAFs, AFs, and GFs. IGF-1 gene expression levels were significantly decreased (P < 0.001). Conclusions RD extract seems to have the potential therapeutic effect of alleviating PCOS complications, and IGF-1 signaling may be involved in the beneficial effects of RD on PCOS.
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Endometrioid endometrial adenocarcinoma and its precursor lesion, endometrial intraepithelial neoplasia (EIN), are caused by excessive, unopposed systemic estrogen. As the prevalence of obesity in the United States is increasing, there has been a concomitant rise in endometrial carcinogenesis. Polycystic ovary syndrome is characterized by many of the same hormonal disruptions that are characteristic of uterine cancer including anovulation, hyperandrogenism, and insulin resistance. Numerous epidemiologic studies have demonstrated associations between PCOS and endometrial cancer; however heterogeneity of study design has made it difficult to determine the true magnitude of these associations. The interrelatedness of PCOS and endometrial carcinogenesis is also apparent at the molecular level with early data showing overlap between the genomics, epigenomics, and metabolomics of these two conditions. As our patient population ages and survivorship from endometrial cancer improves, it is crucial to understand the health repercussions at the intersection of PCOS and endometrial cancer to maximize the clinical care these patients receive and improve their long-term health outcomes.KeywordsEndometriumEndometrial hyperplasiaEndometrial cancer/carcinomaPolycystic ovary syndromePCOS
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To verify if in lean polycystic ovary syndrome (PCOS) patients, the smok- ing habitude might increase the risk of cardiovascular (CV) disease. In this prospective observational study, eighty-one women were divided into the following three groups: group I with 27 non-smokers, group II with 26 light-smokers (1-10 cigarettes/day), and group III with 28 heavy smokers (>10 cigarettes/ day). They were submitted to fasting blood sampling; blood measurement of nitrites/ni- trates (NO2-/ NO3), biochemical and hormonal parameters; ovarian ultrasonographic (US) analysis; doppler evaluation of uterine and ophthalmic arteries; brachial artery flow-medi- ated vasodilatation; 24-hour ambulatory blood pressure monitoring; and oral glucose toler- ance test (OGTT). Doppler analysis revealed higher uterine and ophthalmic arteries pulsatility in- dex (PI) and ophthalmic artery back pressure in group III compared with group I. The brachial artery diameter and PI, at baseline, was similar among all groups. After the re- active hyperemia, a more intense vasodilatation was observed in group I in comparison with group III. The 24-hour blood pressure demonstrated that, in group III patients, the 24-hour, day- and night-time diastolic blood pressure (DBP), was higher in comparison with non-smokers. The atherogenic index of plasma (AIP) was higher in heavy smokers than in non-smokers. The leukocytes and homocysteine (HCY) values were increased in group III. The NO2-/ NO3- plasma levels were reduced in heavy smokers in compari- son with non-smokers. The insulin, glucose and C-peptide plasma values were higher in group III than in other groups. In heavy smokers, the estimates of insulin sensitivity (ISI) and pancreatic β-cell function (HOMA-B) were higher compared to the other groups. Smoking habitude in lean PCOS patients may increase the soft markers of CV risk.
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OBJECTIVETHE EFFECT OF METFORMIN ON WEIGHT REDUCTION IN POLYCYSTIC OVARY SYNDROME (PCOS) IS OFTEN UNSATISFACTORY. WE INVESTIGATED THE POTENTIAL ADD-ON EFFECT OF TREATMENT WITH THE GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONIST LIRAGLUTIDE ON WEIGHT LOSS IN OBESE NON-DIABETIC WOMEN WITH PCOS WHO HAD LOST LESS THAN 5% BODY WEIGHT DURING PRE-TREATMENT WITH METFORMIN.METHODS40 OBESE WOMEN WITH PCOS WHO HAD BEEN PRE-TREATED WITH METFORMIN FOR AT LEAST 6 MONTHS, PARTICIPATED IN A 12-WEEK OPEN, PROSPECTIVE STUDY. metformin arm (MET) 1000 mg BID, liraglutide arm (LIRA) 1.2 mg QD sc or combined - MET 1000 mg BID and LIRA 1.2 mg QD sc (COMBI). The primary outcome was change in body weight. RESULTS36 PATIENTS (AGED 31.3 7.1 YEARS, BMI 37.1 4.6 KG/M2) COMPLETED THE STUDY: 14 on MET, 11 on LIRA and 11 on combined treatment. COMBI therapy was superior to LIRA and MET monotherapy in reducing weight, BMI and waist circumference. Subjects treated with COMBI lost on average 6.5 ± 2.8 kg compared with a 3.8 ± 3.7 kg loss in LIRA group and a 1.2±1.4 kg loss in MET group (p<0.001). BMI decreased for 2.4±1.0 in COMBI arm compared to 1.3±1.3 in LIRA and 0.5±0.5 in MET arm (p<0.001). Waist circumference also decreased for 5.5±3.8 cm in COMBI arm compared to 3.2±2.9 cm in LIRA and 1.6±2.9 cm in MET arm (p=0.029). Subjects treated with liraglutide experienced more nausea than those treated with metformin, but severity of nausea decreased over time and did not correlate with weight loss.Conclusions Short-term combined treatment with liraglutide and metformin was associated with significant weight loss and decrease in waist circumference in obese women with PCOS who had been previously poor responders regarding weight reduction on metformin monotherapy.
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Context Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. Objective The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. Data Sources Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). Study Selection We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. Data Extraction Two authors performed the data extraction independently. Data Synthesis We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, −2.3 mg/dL; 95% confidence interval, −4.5 to −0.1, I2 = 72%, P = .04) and fasting blood insulin (weighted mean difference, −2.1 μU/mL, 95% confidence interval, −3.3 to −1.0, I2 = 0%, P < .001). Changes in body mass index were associated with changes in fasting blood glucose (P < .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. Conclusions The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.
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Recently, several studies reported that the cancer incidence in type 2 diabetes patients is higher than in the general population. Although a number of risks are shared between cancer and diabetes patients, there have been few studies of its correlation. We evaluated the influences of several factors including low density lipoprotein cholesterol (LDL-C), albuminuria and use of metformin on the risk of cancer in patients with type 2 diabetes. We enrolled 1,320 patients with at least 5 years of follow-up and 73 patients were diagnosed with cancer during this period. The associations of the risk factors with cancer incidence were evaluated by multiple regression analysis. The subjects were placed into two subgroups based on metformin dosage (<1,000 mg/day, ≥1,000 mg/day) and we compared cancer incidence using analysis of covariance. LDL-C and albuminuria were not significantly correlated with cancer risk. In contrast, metformin showed a reverse correlation with cancer risk (P=0.006; relative risk, 0.574). In the metformin nonadministration group, smoking, male gender, and high triglyceride levels tended to be contributing factors without statistical significance. Cancer occurence was lower in the low dose metformin group (less than 1,000 mg/day) (P=0.00). These results suggest that the administration of low dose metformin in patients with type 2 diabetes may be associated with a reduced risk of cancer.
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Abstract Background: Androgens appear to play a role in the development of acne, and presence of acne is a potential marker of hyperandrogenism. Objective: We evaluated androgens and insulin sensitivity markers before and after treatment with isotretinoin in women with post-adolescent severe acne who do not have hirsutism and/or ovulatory dysfunction. Methods: Androgens, lipids, glucose and insulin levels were measured in 26 patients and 21 controls during oral glucose tolerance test. Homeostasis model assessment for insulin resistance, area under curve (AUC)Glucose and AUCInsulin were calculated. Twenty patients completed a minimum of 6-month isotretinoin treatment. Results: All studied parameters were similar in patients and controls at baseline. Isotretinoin therapy increased body mass index and triglyceride levels without any effect on androgens or insulin sensitivity. Conclusion: Severe acne itself is not associated with hyperandrogenemia and/or insulin resistance. Isotretinoin treatment does not alter serum androgens or insulin sensitivity, although it increases body weight and serum triglycerides.
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Background: It has been shown that there is an increase in oxidative stress in polycystic ovary syndrome (PCOS). Statins are considered to have a pleiotropic effect other than their lipid-lowering effect. These effects may be mediated in part by reducing oxidative stress. Methods: This randomized, double-blind, placebo-controlled study was conducted to assess the effect of atorvastatin on serum malondialdehyde (MDA) concentrations as a marker of oxidative stress in patients with PCOS. Forty medication-naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. Results: There was a significant decrease of MDA concentrations with atorvastatin [mean (sem)] [0.29 (0.04) vs. 0.25 (0.02) μmol/liter; P < 0.01] compared with placebo [0.28 (0.02) vs. 0.29 (0.12) μmol/liter; P = 0.52]. Three months treatment with metformin resulted in further reduction of MDA levels with atorvastatin compared with baseline [0.25 (0.02) baseline vs. 0.23 (0.03) μmol/liter for atorvastatin treated; P = 0.02]. There was also a significant correlation between the reduction in MDA with a reduction in high-sensitivity C-reactive protein (r = 0.71, P < 0.01), an increase in 25-hydroxyvitamin D (25OHD; r = -0.68, P = 0.02), and a reduction in testosterone levels (r = 0.63, P = 0.01). Multiple linear regression analysis revealed Δ25OHD, ΔC-reactive protein, and Δtestosterone were independent predictors of changes in MDA after atorvastatin treatment. No correlation was observed between the reductions in serum MDA concentrations with changes in the lipid parameters. Conclusions: Twelve weeks of atorvastatin led to a significant reduction in oxidative stress as determined by MDA concentrations among patients with polycystic ovary syndrome that was independently predicted by changes in testosterone, 25OHD, and high-sensitivity C-reactive protein.
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Background: Poly cystic ovarian syndrome (PCOS) is the most prevalent endocrinopathy among women and the most common underlying diagnosis for anovulatory infertility. The role of insulin-resistance (IR) and hyperinsulinemia in pathophysiology and clinical manifestations of the syndrome depicts the importance of evaluation of the efficacy of insulin reducing medications. N acetyl cysteine (NAC) inhibits oxidative stress and prevents hyperglycemia induced insulin resistance. This study aims at evaluating the effects of NAC on manifestations of the disease as well as improvement of fertility status. Materials and Methods: Through a prospective double-blind clinical trial, 46 patients were randomly divided into one intervention and one control group. The two groups were treated for six weeks after similarity was allocated. All clinical and biochemical indicators were recorded in the early follicular phase both before and after treatment. Results: From each group, 18 patients were ultimately evaluated. In the first group, ovulation rate increased as compared to the control group. A significant decrease in weight, body mass index (BMI), and waist/hip ratio was also observed. Fast blood sugar (FBS), serum insulin, total cholesterol, low density lipoprotein (LDL) levels, and HOMA-IR index also dropped while high density lipoprotein HDL levels elevated significantly. No significant change was reported in luteinizing hormone (LH), FSH, PRL, LH/FSH levels and glucose/insulin ratio. The control group remained unchanged. Conclusion: N-Acetyl Cysteine improves lipid profile, hormonal levels, ovulation status, and long-term health of women with PCOS. Considering its limited adverse effects, it can be regarded as a substitute for insulin reducing medications in treatment of these patients.
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Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women. To meet PCOS criteria, women must have a combination of hyperandrogenism, anovulation and ultrasound findings. Almost 10% of all reproductive age women worldwide show signs of PCOS. Although women often seek care for gynecological or body image concerns, many PCOS women are at risk for metabolic syndrome (MS). Many of the metabolic consequences are overlooked and undertreated by physicians because these patients tend to be young, reproductive age women. MS and obesity coexist commonly with PCOS. These young women are predisposed to glucose abnormalities and ultimately diabetes mellitus, dyslipidemia and eventually cardiovascular disease. Bariatric surgery can be an effective means of weight loss in PCOS women. Surgical techniques have become safer and less invasive over time and have been found to be effective in achieving significant weight loss. Surgical options have also increased, giving patients more choices. Bariatric surgery may prevent or reverse metabolic syndrome. Bariatric surgery may also have reproductive benefits in PCOS patients. Although bariatric surgery has historically been performed in older, reproductive aged women, it has recently gained favor in adolescents as well. This is of particular importance due to the prevalence of both PCOS and MS in adolescents. Treatment of PCOS and MS certainly requires a combination of medical therapy, psychological support and lifestyle modifications. These treatments are difficult and often frustrating for patients and physicians. Bariatric surgery can be effective in achieving significant weight loss, restoration of the hypothalamic pituitary axis, reduction of cardiovascular risk and even in improving pregnancy outcomes. Ultimately, bariatric surgery should be considered part of the treatment in PCOS women, especially in those with MS.
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Polycystic ovary syndrome (PCOS) is linked to obesity, impaired glucose tolerance and diabetes. Recently, studies have found that preptin enhances insulin secretion in rats and might play a role in the pathogenesis of diabetes and PCOS in humans. The aim of this study was to evaluate the relationship between PCOS, glucose tolerance status, and serum preptin level. This study was conducted in a university-affiliated hospital from October 2010 to August 2011. Anthropometric parameters, sex hormone concentrations, blood pressure, lipid profiles, fasting glucose and insulin, 2-h blood glucose after glucose overloaded (2hOGTT), glycosylated haemoglobin (HbA1c), homeostasis model assessment-insulin resistance index (HOMA-IR), and serum preptin of the samples were analyzed. Sixty-three PCOS patients, including 33 women with normal glucose tolerance (NGT) and 30 women with impaired glucose tolerance (IGT), and 63 patients without PCOS, including 35 women with NGT and 28 women with IGT were recruited in this study. For patients with and without PCOS, women with IGT had higher serum preptin levels compared with women with NGT. Preptin levels in PCOS patients were higher compared with patients without PCOS, but the difference was not significant. Fasting serum preptin levels correlated positively with TG, SBP, DBP, FBG, 2hOGTT, and HOMA-IR in simple regression analysis of the pooled data. While in multiple stepwise regression analysis, preptin levels were independently related with glucose tolerance, but not with PCOS. Irrespective of PCOS status, women with IGT had higher serum preptin levels compared with women with NGT. Preptin levels are related with glucose tolerance status, but not with PCOS status.
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Polycystic ovary syndrome (PCOS) affects 5%-10% of women in reproductive age, and it is the most common cause of infertility due to ovarian dysfunction and menstrual irregularity. Several studies have reported that insulin resistance is common in PCOS women, regardless of the body mass index. The importance of insulin resistance in PCOS is also suggested by the fact that insulin-sensitizing compounds have been proposed as putative treatments to solve the hyperinsulinemia-induced dysfunction of ovarian response to endogenous gonadotropins. Rescuing the ovarian response to endogenous gonadotropins reduces hyperandrogenemia and re-establishes menstrual cyclicity and ovulation, increasing the chance of a spontaneous pregnancy. Among the insulin-sensitizing compounds, there is myo-inosiol (MYO). Previous studies have demonstrated that MYO is capable of restoring spontaneous ovarian activity, and consequently fertility, in most patients with PCOS. With the present review, we aim to provide an overview on the clinical outcomes of the MYO use as a treatment to improve ovarian function and metabolic and hormonal parameters in women with PCOS.
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Polycystic ovary syndrome (PCOS) is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients.
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Polycystic ovary syndrome (PCOS) is a common female endocrine disorder of heterogeneous clinical presentation, high disease burden, and unknown aetiology. The disease and associated conditions cluster in families, suggesting that PCOS may be the reproductive consequence of underlying chronic disease susceptibility. To determine whether parents of young women with PCOS were more likely to have a history of diabetes or cardiovascular disease in later adult life. Structured interviews with 715 members of a cohort constructed by tracing female infants born at a single general hospital in Adelaide between 1973 and 1975. Participants were asked whether they had a pre-existing medical diagnosis of PCOS, and whether each parent had ever had high blood pressure, high cholesterol, diabetes, stroke, or heart disease. Maternal high blood pressure during pregnancy was taken from the medical record of the pregnancy with the study participant. Mothers of women with PCOS were more likely than mothers of other women to have any cardiovascular disease (RR 1.78, 95% CI 1.29, 2.47), and nearly twice as likely to have high blood pressure (RR 1.95, 95% CI 1.38, 2.76). Fathers of women with PCOS were more than twice as likely to have heart disease (RR 2.36, 95% CI 1.44, 3.88) and over four times as likely to have had a stroke (RR 4.37, 95% CI 1.97, 9.70). Occurrence of cardiovascular disease in both mother and father are associated with the risk of PCOS in daughters. Further detailed study is required to elucidate the precise pathways that may be causally related to the observations.
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Polycystic ovarian syndrome (PCOS) is a highly prevalent hormonal and metabolic disorder among reproductive aged women worldwide. Women with PCOS have widely varying phenotypes and seek medical care for differing reasons. In addition to concern for menstrual cycle function, ovulation, hirsutism and acne, many PCOS women have abnormal glucose metabolism. While diabetes mellitus and impaired glucose tolerance are easily diagnosed, the diagnosis of and concern for insulin resistance as a precursor disorder is underappreciated. Insulin resistance may be the first important marker of metabolic disease in PCOS women at risk for metabolic syndrome and coronary artery disease.
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Polycystic ovary syndrome (PCOS) is a common disorder affecting women of reproductive age and it is associated with increased cardiovascular risk. Obesity plays an important role in the pathogenesis of PCOS, and the majority of patients with PCOS are obese. Over the last 20 years, the prevalence of obesity has dramatically increased, with probable associated increase in PCOS. Weight reduction plays an integral part in the management of women with PCOS. In this paper, current available weight reduction therapies in the management of PCOS are discussed.
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Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age group and is associated with a higher cardiovascular risk. Obesity, mainly visceral adiposity, is prevalent in patients with PCOS. Obesity is associated with low-grade inflammation and raised inflammatory cytokines, both of which are also described in patients with PCOS. In this paper, the potential relationships between fat distribution, adipocyte dysfunction and, altered inflammatory markers in patients with PCOS have been discussed.
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Polycystic Ovary Syndrome (PCOS) represents a common endocrinopathy, with anovulation and hyperandrogenism as cardinal symptoms. In recent years it has been recognized that insulin resistance is an intrinsec feature of the disorder and plays a central role in pathogenesis. PCOS is associated with important reproductive morbidity as shown by high prevalence of anovulatory infertility, spontaneous abortion, gestational diabetes and preeclampsia. The association of insulin resistance with this reproductive pathology has been well documented. Due to major implication of insulin resistance in PCOS pathogenesis, insulin reduction strategies were studied as a possible treatment for infertility in PCOS patients. Weight loss, even modest was proved to be a simple and efficient method to improve reproductive parameters in PCOS patients and should be recommended to all overweight and obese patients with infertility. Metformin was showed to induce ovulation, at least in a subset of patients with PCOS, but there are not unequivocal proves concerning its efficacy for pregnancies and live-birth rate, mainly because few trials studied this aspect. Therefore there are not enough evidences to recommend metformin for infertility treatment in PCOS. Few small studies with newer thiazolidindiones suggest their efficacy for ovulation induction, but further extensive studies are needed to confirm these results. In conclusion, reduction of insulin resistance was proved to ameliorate ovulation rate in PCOS patients, but strong evidences to sustain the utility of insulin-sensitizing drugs as a therapeutic option for infertility are lacking. Future studies are needed to elucidate these aspects and to characterize the particular subtype of patients with higher probability to respond to this treatment.
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The polycystic ovary syndrome (PCOS), a common endocrine disorder in women of child-bearing age, mainly characterised by chronic anovulation and hyperandrogenism, is often associated with insulin resistance (IR) and obesity. Its etiology and the role of IR and obesity in PCOS are not fully understood. We examined the influence of validated genetic variants conferring susceptibility to obesity and/or type 2 diabetes mellitus (T2DM) on metabolic and PCOS-specific traits in patients with PCOS. We conducted an association study in 386 patients with PCOS (defined by the Rotterdam-criteria) using single nucleotide polymorphisms (SNPs) in or in proximity to the fat mass and obesity associated gene (FTO), insulin-induced gene-2 (INSIG2), transcription factor 7-like 2 gene (TCF7L2) and melanocortin 4 receptor gene (MC4R). To compare the effect of FTO obesity risk alleles on BMI in patients with PCOS to unselected females of the same age range we genotyped 1,971 females from the population-based KORA-S4 study (Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4). The FTO risk allele was associated with IR traits and measures of increased body weight. In addition, the TCF7L2 SNP was associated with body weight traits. For the SNPs in the vicinity of INSIG2 and MC4R and for the other examined phenotypes there was no evidence for an association. In PCOS the observed per risk allele effect of FTO intron 1 SNP rs9939609 on BMI was +1.56 kg/m2, whereas it was +0.46 kg/m2 in females of the same age range from the general population as shown previously. The stronger effect on body weight of the FTO SNP in PCOS might well have implications for the etiology of the disease.
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It has been reported that women with polycystic ovary syndrome (PCOS) benefit from metformin therapy. A randomized, placebo-controlled, double-blind study of obese (body mass index >30 kg/m2), oligo-/amenorrhoeic women with PCOS. Metformin (850 mg) twice daily was compared with placebo over 6 months. All received the same advice from a dietitian. The primary outcome measures were: (i) change in menstrual cycle; (ii) change in arthropometric measurements; and (iii) changes in the endocrine parameters, insulin sensitivity and lipid profile. A total of 143 subjects was randomized [metformin (MET) = 69; placebo (PL) = 74]. Both groups showed significant improvements in menstrual frequency [median increase (MET = 1, P < 0.001; PL = 1, P < 0.001)] and weight loss [mean (kg) (MET = 2.84; P < 0.001 and PL = 1.46; P = 0.011)]. However, there were no significant differences between the groups. Logistic regression analysis was used to analyse the independent variables (metformin, percentage of weight loss, initial BMI and age) in order to predict the improvement of menses. Only the percentage weight loss correlated with an improvement in menses (regression coefficient = 0.199, P = 0.047, odds ratio = 1.126, 95% CI 1.001, 1.266). There were no significant changes in insulin sensitivity or lipid profiles in either of the groups. Those who received metformin achieved a significant reduction in waist circumference and free androgen index. Metformin does not improve weight loss or menstrual frequency in obese patients with PCOS. Weight loss alone through lifestyle changes improves menstrual frequency.
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Background: Isotretinoin is the most efficacious long-lasting treatment for acne; however, some factors, including polycystic ovary syndrome (PCOS), patient age, family history, and type and number of acne lesions, may lead to treatment resistance or relapse following treatment. The aim of this study was to compare the efficacy and permanence of systemic isotretinoin (SI) in nodulocystic acne patients with and without PCOS and to evaluate the factors associated with relapse during the first and second post-treatment years. Methods and materials: The study included 96 female patients with nodulocystic acne. SI 0.5-1 mg/kg/dl was given, with a total cumulative dose of 120-150 mg/kg. Response to treatment and relapse during the first and second post-treatment years were evaluated. Results: In all, the 50 non-PCOS and 46 PCOS acne patients were similar. SI was similarly efficacious in both groups. In total, eight patients relapsed during the first post-treatment year, versus 16 during the second. Relapse during the first year was associated with the number of nodules at the start of treatment and the number of papulopustular lesions at the end of treatment, whereas PCOS, patient age, and the number of nodules at the start of treatment were associated relapse during the second year. Conclusion: Regardless of its association with PCOS, SI was effective in the treatment of nodulocystic acne. The factors associated with relapse during the 1(st) and 2(nd) post-treatment years differed, except for the number of nodules at the start of treatment.
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Women with polycystic ovary syndrome (PCOS) have a 2.7-fold increased risk for developing endometrial cancer. A major factor for this increased malignancy risk is prolonged exposure of the endometrium to unopposed estrogen that results from anovulation. Additionally, secretory endometrium of some women with PCOS undergoing ovulation induction or receiving exogenous progestin exhibits progesterone resistance accompanied by dysregulation of gene expression controlling steroid action and cell proliferation. Endometrial surveillance includes transvaginal ultrasound and/or endometrial biopsy to assess thickened endometrium, prolonged amenorrhea, unopposed estrogen exposure or abnormal vaginal bleeding. Medical management for abnormal vaginal bleeding or endometrial hyperplasia consists of estrogen-progestin oral contraceptives, cyclic or continuous progestins or a levonorgestrel-releasing (Mirena) intrauterine device. Lifestyle modification with caloric restriction and exercise is appropriate to treat obesity as a concomitant risk factor for developing endometrial disease. An increased risk of ovarian cancer may also exist in some women with PCOS. There are strong data to suggest that oral contraceptive use is protective against ovarian cancer and increases with the duration of therapy. The mechanism of this protection may be through suppression of gonadotropin secretion rather than the prevention of "incessant ovulation". There is no apparent association of PCOS with breast cancer, although the high prevalence of metabolic dysfunction from obesity is a common denominator for both conditions. Recent data suggest that the use of metformin may be protective for both endometrial and breast cancer. There are insufficient data to evaluate any association between PCOS and vaginal, vulvar and cervical cancer or uterine leiomyosarcoma.
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Polycystic ovary syndrome (PCOS) is a widespread reproductive disorder that encompasses many associated health conditions and has an impact on various metabolic processes. PCOS is depicted by hyperandrogenism, polycystic ovaries, and anovulation. It increases the risk of insulin resistance (IR), type 2 diabetes, obesity, and cardiovascular disease. The etiology of the disease remains unclear, and the subjective phenotype makes a united diagnosis difficult among physicians. It seems to be a familial genetic syndrome caused by a combination of environmental and genetic factors. It can be linked with metabolic disorders in first-degree family members. PCOS is the cause of up to 30% of infertility in couples seeking treatment. Currently, there is no cure for PCOS. Despite the growing incidence of this syndrome, limited research has been done that encompasses the entirety of PCOS spectrum. In this review, the current status and possible future perspective will be discussed.
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The latest list of reimbursed medicines includes, as a new addition, metformin for the treatment of polycystic ovary syndrome (PCOS), which is extremely important for practicing physicians. While this paper briefly summarises the current state of knowledge on PCOS, its main aim is to remind the reader about the effectiveness of metformin in women with PCOS in controlling glycaemia, increasing tissue sensitivity to insulin and affecting endothelial function, vascular inflammation, lipid profile and other risk factors of atherosclerosis, which suggests its cardioprotective effects. The paper also discusses the clinical effect of metformin relative to hyperandrogenism, menstrual cycle disorders and ovulation induction. The paper concludes with an algorithm for the diagnosis and management of PCOS. (Endokrynol Pol 2013; 64 (5): 409-414).
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Numerous epidemiological cohort and case-control studies showed that type 2 diabetes is a risk factor for cancer and that metformin therapy is associated with a significant reduction in the incidence of cancer and cancer-related death when compared to other glucose-lowering agents. Such beneficial effect is observed whatever the type of cancer, but seems to be more prominent in case of gastrointestinal and breast cancers. In general, the protective effect was more evident in observational cohort studies (however, more exposed to bias due to confounding factors) than in case-control studies. However, the results of the rather rare controlled clinical trials available are not conclusive, but none of them was performed with the objective to specifically assess cancer risk. Several meta-analyses recently confirmed that metformin therapy reduces the incidence of cancers (including colorectal cancer, hepatocarcinoma, breast cancer) and cancer-related mortality. Metformin may exert its anti-cancer activity by a direct effect (insulin) and an indirect effect (AMPK and mTOR). Considering all promising clinical information in patients with type 2 diabetes, further clinical trials are currently ongoing with the aim of assessing the role of metformin in oncology, especially as adjuvant in breast cancer therapy.
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Polycystic ovary syndrome (PCOS) is a common metabolic and reproductive disorder in women. An increased cardiovascular risk has to be anticipated in PCOS as it is a metabolically unstable condition. Among cardiovascular risk factors, dyslipidemia is certainly the most persistent and highly prevalent. Predominant observation is an elevation of LDL cholesterol in all PCOS patients. Decreased concentrations of HDL cholesterol are found in obese PCOS from the third decade of life onwards while triglycerides start to rise from the second decade of life. PCOS is associated with oxidative stress, namely increased production of free radicals followed by decreased serum antioxidant levels and antioxidant enzyme activity. Broad range of endocrine and metabolic disturbances like obesity, hyperinsulinemia as well as dyslipidemia might be responsible for PCOS-associated oxidative stress. Therapeutic interventions in PCOS women based on lifestyle modification as well as use of insulin sensitizers did not show significant effect on dyslipidemia. Statins are considered to be a group of promising agents that are safe and effective in improving total cholesterol, LDL cholesterol and triglycerides, and possess antioxidant activity. Supplementation with omega-3 fatty acids, α-lipoic acid and N-acetylcysteine is considered to have an anti-inflammatory and antioxidant effect and to improve dyslipidemia and insulin sensitivity in PCOS women.
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For several decades, metformin has been used as an oral hypoglycaemic agent, where it is the first line of treatment in overweight and obese type 2 diabetic patients. This is because it decreases the hepatic glucose output and acts as an insulin sensitizer by increasing the glucose utilization by muscles and adipocytes. As a result of the improvement in glycaemic control, serum insulin concentrations decline slightly, thus improving hyperinsulinaemia and its signs. In addition, it has been shown that metformin has platelet anti-aggregating and antioxidant effects. These pharmacological properties have allowed metformin to be effective in non-diabetic situations including cutaneous conditions. This is an evidence-based review on the use of metformin in the treatment of skin disorders such as hirsutism, acne, hidradenitis suppurativa, acanthosis nigricans, psoriasis, skin cancer, among others. In addition, cutaneous side-effects such as leukocytoclastic vasculitis, bullous pemphigoid, psoriasiform drug eruption, lichen planus and acute alopecia have been associated with metformin use and are discussed in the article.
Article
Objective: To investigate the effect of undertaking lifestyle interventions during periods of seasonal change on vitamin D status and health outcomes in overweight/obese women with polycystic ovary syndrome (PCOS). Design: Retrospective, unplanned secondary analysis of two cohorts during different seasons. Setting: Outpatient clinical research unit. Patient(s): Fifty overweight/obese women with PCOS. Intervention(s): Twenty-week lifestyle modification program (Clinical Trials registration no.: ACTRN12606000198527); one cohort started in winter and finished in summer, and one started in summer and finished in winter. Main outcome measure(s): 25-Hydroxyvitamin D (25OH-D), weight, waist circumference (WC), body composition, cardiovascular disease (CVD) risk factors, and menstrual cycle length. Result(s): Baseline 25OH-D levels were 27.6 ± 9.0 nmol/L. The winter cohort had lower 25OH-D levels at baseline, which increased over 20 weeks, whereas the summer cohort started with higher levels which decreased. Changes in 25OH-D were inversely correlated with changes in WC and cholesterol when controlling for baseline values, such that increases in 25OH-D were associated with greater reductions in WC and cholesterol. Conclusion(s): Obesity and CVD risk profiles improved in vitamin D-deficient women with PCOS after a 20-week lifestyle intervention during which vitamin D status improved with seasonal change. Clinical trial registration number: ACTRN12606000198527.
Article
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The psychiatric disorders accompanying the clinical symptoms and hormonal abnormalities are important, but underestimated, aspects in PCOS. Obesity, hirsutism, acne, menstrual disturbances and infertility play important roles in lowering the quality of life in women with PCOS. Depression and anxiety are more often observed in patients with PCOS than in healthy women. Some authors consider that there is a relationship between valproic acid treatment of bipolar disease and PCOS. There have been reports that in women with PCOS anorexia nervosa, bulimia nervosa and other unspecified eating disorders are found more often than in the general population. (Endokrynol Pol 2012; 63 (6): 488-491).
Article
Thiazolidinedione (TZD) is one of the therapy options for polycystic ovary syndrome (PCOS) patients; however, the effectiveness of TZD in the treatment of PCOS remains controversial. The aim of this metaanalysis was to clarify the role that TZDs play in the treatment of PCOS. The authors searched the following databases for any date up to June 2012 for randomized controlled trials on PCOS treatment in which interventions for the experimental and control groups were TZDs and placebo, respectively: Medline, Embase, and the Cochrane library. The search strategy identified 173 potential publications, eight of which were included. In the treatment of PCOS, the insulin-lowering effects of TZDs were superior to placebo (95% CI -1.50 to -0.12; P = 0.021), and the lowering of fasting blood glucose was superior to placebo (95% CI -1.06 to -0.05; P = 0.031). There was no difference in reduction of the Ferriman-Gallwey scores or the androgen levels between TZDs and placebo (95% CI -0.57 to 0.10; P = 0.169 and 95% CI -0.64 to 0.09; P = 0.141, respectively). The effects of TZDs on body weight reduction were inferior to placebo (95% CI 0.13 to 0.66; P = 0.003). Significant between-study heterogeneity was detected for several variables assessed. This is the first meta-analysis to evaluate the role that TZDs plays in the treatment of PCOS compared with placebo. The currently available data showed that TZDs can effectively reduce insulin and fasting blood glucose levels in patients with PCOS, but TZDs may not effectively reduce the Ferriman-Gallwey score or androgen levels and may increase body weight.
Article
Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term health risks including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA) are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery post-exercise, compared with age- and BMI-matched controls, suggesting a generalised increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure, and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer-term studies are needed before these treatments can be considered in clinical practice. © 2012 Blackwell Publishing Ltd.
Article
Objective Adverse changes in lipoprotein particle number and size are common with insulin resistance and are associated with increased cardiovascular risk. Comprehensive information regarding lipoprotein particle number and size, and how these parameters relate to body weight, insulin resistance and hyperandrogenemia is lacking in polycystic ovary syndrome (PCOS). We tested the hypothesis that PCOS is associated with atherogenic changes in lipoprotein profile independent of body weight and examined the role of insulin resistance and androgens in these atherogenic changes. Design Case–control study performed at Clinical Research Center a