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Polycystic Ovarian Syndrome [keywords]
- The Effect Of Ezetimibe On Androgen Production In Hypercholesterolemic Women With Polycystic Ovary Syndrome. [JOURNAL ARTICLE]
- Cardiovasc Ther 2014 Jul 23.
Statin therapy was found to reduce circulating androgen levels in patients with polycystic ovary syndrome (PCOS). No similar data are available for ezetimibe.The study included 14 women with PCOS and hypercholesterolemia, intolerant to statins or having contraindications to this treatment, who were treated with ezetimibe (10 mg daily). They were compared with 14 matched women with both of these disorders receiving simvastatin (40 mg daily). Plasma lipids, glucose homeostasis markers and serum levels of androgens, sex hormone-binding globulin and gonadotropins were assessed at baseline and after 3 months of treatment.Both simvastatin and ezetimibe decreased plasma levels of total and LDL-cholesterol. Ezetimibe, but not simvastatin, slightly reduced insulin resistance. Simvastatin decreased serum levels of total testosterone (-23%, p<0.001), free testosterone (-32%, p<0.001), androstendione (-20%, p<0.01) and dehydroepiandrosterone sulphate (-17%, p<0.05), as well as tended to reduce the luteinizing hormone/follicle-stimulating hormone ratio (-23%, p=0.095). Ezetimibe only insignificantly reduced serum levels of free testosterone (-14%, p=0.098). There were no differences in the effects of simvastatin on circulating hormone levels between insulin-resistant and insulin-sensitive subjects. In turn, the effect of ezetimibe on free testosterone levels was stronger in insulin-resistant patients.Although ezetimibe and simvastatin are equipotent in lowering lipid levels in hypercholesterolemic patients with coexisting PCOS, simvastatin exhibits a more pronounced effect on circulating androgen levels in this group of patients. This article is protected by copyright. All rights reserved.
- Combined oral contraceptives: health benefits beyond contraception. [Journal Article]
- Panminerva Med 2014 Sep; 56(3):233-44.
It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.
- Leptin in human reproductive disorders. [JOURNAL ARTICLE]
- J Endocrinol 2014 Jul 23.
As a key hormone in energy homeostasis, leptin regulates neuroendocrine function, including reproduction. It has a permissive role in initiating puberty and maintaining the hypothalamic-pituitary-gonadal axis. This is notable in patients with either congenital or acquired leptin deficiency from a state of chronic energy insufficiency. Hypothalamic amenorrhea is the best-studied with clinical trials confirming a causative role of leptin in hypogonadotropic hypogonadism. Implications of leptin deficiency have also emerged in the pathophysiology of hypogonadism in type 1 diabetes. At the other end of the spectrum, hyperleptinemia may play a role in hypogonadism associated with obesity, polycystic ovarian syndrome, and type 2 diabetes. In these conditions of energy excess, mechanisms of reproductive dysfunction include central leptin resistance as well as direct effects at the gonadal level. Thus, reproductive dysfunction due to energy imbalance at both ends can be linked to leptin.
- Anti-Müllerian hormone: correlation with testosterone and oligo- or amenorrhoea in female adolescence in a population-based cohort study. [JOURNAL ARTICLE]
- Hum Reprod 2014 Jul 23.
Can serum anti-Müllerian hormone (AMH) levels measured in female adolescents predict polycystic ovary syndrome (PCOS)-associated features in adolescence and early adulthood?AMH levels associated well with PCOS-associated features (such as testosterone levels and oligoamenorrhoea) in adolescence, but was not an ideal marker to predict PCOS-associated features in early adulthood.Several studies have reported that there is a strong correlation between antral follicle count and serum AMH levels and that women with PCOS/PCO have significantly higher serum AMH levels than women with normal ovaries. Other studies have reported an association between AMH serum levels and hyperandrogenism in adolescence, but none has prospectively assessed AMH as a risk predictor for developing features of PCOS during adulthood.A subset of 400 girls was selected from the prospective population-based Northern Finland Birth Cohort 1986 (n = 4567 at age 16 and n = 4503 at age 26). The population has been followed from 1986 to the present.At age 16, 400 girls (100 from each testosterone quartile: 50 with oligo- or amenorrhoea and 50 with a normal menstrual cycle) were selected at random from the cohort for AMH measurement. Metabolic parameters were also assessed at age 16 in all participants. Postal questionnaires enquired about oligo- or amenorrhoea, hirsutism, contraceptive use and reproductive health at ages 16 and 26.There was a significant correlation between AMH and testosterone at age 16 (r = 0.36, P < 0.001). AMH levels at age 16 were significantly higher among girls with oligo- or amenorrhoea compared with girls with normal menstrual cycles (35.9 pmol/l [95% CI: 33.2;38.6] versus 27.7 pmol/l [95% CI: 25.0;30.4], P < 0.001). AMH at age 16 was higher in girls who developed hirsutism at age 26 compared with the non-hirsute group (31.4 pmol/l [95% CI 27.1;36.5] versus 25.8 pmol/l [95% CI 23.3;28.6], P = 0.036). AMH at age 16 was also higher in women with PCOS at age 26 compared with the non-PCOS subjects (38.1 pmol/l [95% CI 29.1;48.4] versus 30.2 pmol/l [95% CI 27.9;32.4], P = 0.044). The sensitivity and specificity of the AMH (cut-off 22.5 pmol/l) for predicting PCOS at age 26 was 85.7 and 37.5%, respectively. The addition of testosterone did not significantly improve the accuracy of the test. There was no significant correlation between AMH levels and metabolic indices at age 16.AMH is related to oligo- or amenorrhoea in adolescence, but it is not a good marker for metabolic factors. The relatively low rate of participation in the questionnaire at age 26 may also have affected the results. AMH was measured in a subset of the whole cohort. AMH measurement is lacking international standardization and therefore the concentrations and cut-off points are method dependent.Using a high enough cut-off value of AMH to predict which adolescents are likely to develop PCOS in adulthood could help to manage the condition from an early age due to a good sensitivity. However, because of its low specificity, it is not an ideal diagnostic marker, and its routine use in clinical practice cannot, at present, be recommended.The study was funded by a grant from Wellcome Trust (089549/Z/09/Z) to H.L., S.F. and M.-R.J. Study funding was also received from Oulu University Hospital Research Funds, Sigrid Juselius Foundation and the Academy of Finland. None of the authors have any competing interest to declare.
- [Myo-inositol in the treatment of polycystic ovary syndrome.] [JOURNAL ARTICLE]
- Ceska Gynekol 2014; 79(3):242-246.
Objective: Presentation of a comprehensive body of knowledge on the role of insulin sensitizer myo-inositol in the treatment of polycystic ovary syndrome (PCOS).Design: Review article.Setting: Institute for the Care of Mother and Child, Prague.Method: An overview of publishing data.Results and conclusion: Polycystic ovary syndrome is the most common cause of ovarian dysfunction and anovulatory infertility in women. The insulin resistance occurs very frequently as a part of PCOS. This paper reviews the literature documenting the effectiveness of insulin sensitizer myo-inositol in the treatment of ovarian dysfunction, symptoms of hyperandrogenism and wide complex of symptoms of metabolic syndrome. Six randomized controlled trials provides evidence of a positive effect of myo-inositol to normalize ovarian function, improve laboratory and clinical manifestations of hyperandrogenism and insulin resistance. The myo-inositol treatment has been demonstrated as a safe method of PCOS management.Keywords: polycystic ovary syndrome, insulin resistance syndrome, insulin sensitizers, myoinositol, metformin.
- Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome. [Journal Article]
- Eur J Endocrinol 2014 Sep; 171(3):301-9.
Polycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with the syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging.To evaluate the changes in IR and its associations with clinical, biochemical, hormonal, and ultrasound findings in a large cohort of women with PCOS and controls, as they are aging.A cross-sectional study was carried out to evaluate the diverse impacts of aging on IR.An outpatient clinic was chosen for the study.A total of 1345 women with PCOS (Rotterdam criteria) and 302 controls of Caucasian origin and Greek ethnicity comprised the study group.The impact of age on IR, as calculated using homeostasis model assessment of IR (HOMA-IR) index, and several PCOS characteristics were evaluated.In PCOS, age (-0.045±0.008) was negatively, and BMI positively (0.18±0.007) associated with HOMA-IR (R(2)=0.36). When data were stratified with regard to the BMI status, a negative association of age with HOMA-IR was found in lean, normal, and overweight patients (r: -0.266, -0.233, -0.192, P<0.001), which was neutralized in obese patients (r: -0.009, P: NS). Free androgen index and BMI were positively associated with HOMA-IR in all age quartiles. When mean HOMA-IR values were plotted according to BMI subgroups at different age quartiles, a significant gradual decrease in HOMA-IR was observed in normal (P<0.001) and overweight (P: 0.004), but not obese, women (P: 0.202) across age quartiles.Aging increases IR in obese but not in lean and overweight women with PCOS. As BMI and androgens are positively associated with HOMA-IR and androgens decline through time, it appears that if women with PCOS do not become obese they may exhibit a better metabolic profile during their reproductive years.
- Influence of anthropometric measurements on abnormal gonadotropin secretion in women with polycystic ovary syndrome. [Journal Article]
- J Coll Physicians Surg Pak 2014 Jul; 24(7):463-6.
Objective:To evaluate the influence of anthropometric measurements on abnormal gonadotropin secretion in patients with polycystic ovary syndrome (PCOS).
Study Design:Cross-sectional study. Place and Duration of Study: The Institute of Basic Medical Sciences (IBMS), DUHS in collaboration with Gynae/infertility clinics of the Civil Hospital and Lady Dufferin Hospital, Karachi, from October 2010 to February 2011. Methodology: One hundred and sixty three oligomenorrhic PCOS women of reproductive age (18 - 40 years) fulfilling the revised Rotterdam 2003 criteria were studied. The data recorded on a prescribed proforma included current age, age at menarche, menstrual irregularities, presence of hirsuitism, acne, infertility, familial nature, blood pressure, BMI and waisthip ratio. Blood samples for gonadotropin assay were taken randomly on day 6th to 30th of menstrual cycle, in a gel tube. Hormonal assay was performed using chemiluminescent immunoassay. Kruskul Wallis test was used to assess the influence of BMI levels on LH:FSH values.
Results:The mean weight was 66.14 ± 11.02 kg and mean BMI was 27.03 ± 4.42 kg/m2. There was no significant difference in mean LH/FSH ratio (p=.575) among BMI groups. However, there was a positive correlation between BMI and LH:FSH ratio (p=0.04, r=0.155).
Conclusion:There was high frequency of obesity (69%) in women with PCOS. Although no significant difference was found between mean LH:FSH ratio among different BMI groups levels but significant correlation between BMI levels and LH: FSH suggested that there was positive relation between BMI and LH: FSH.
- Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development. [JOURNAL ARTICLE]
- Oncotarget 2014 Jul 16.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. However, the epigenetic mechanism involved in PCOS progression remains largely unknown. Here, combining the DNA methylation profiling together with transcriptome analysis, we showed that (i) there were 7929 differentially methylated CpG sites (β > 0.1, P < 0.05) and 650 differential transcripts (fold change > 1.5, P < 0.005) in PCOS compared to normal ovaries; (ii) 54 genes were identified with methylated levels that were correlated with gene transcription in PCOS; and (iii) there were less hypermethylated sites, but many more hypomethylated sites residing in CpG islands and N_Shore in PCOS. Among these genes, we identified that several significant pathways, including the type I diabetes mellitus pathway, p53 signaling pathway and NOD-like receptor signaling pathway, and some immune and inflammatory diseases may be highly involved in PCOS development. These results suggested that differences in genome-wide DNA methylation and expression patterns exist between PCOS ovaries and normal ovaries; epigenetic mechanisms may in part be responsible for the different gene expression and PCOS phenotype. All of this may improve our understanding of the basic molecular mechanism underlying the development of PCOS.
- Effect of the aqueous extract of Foeniculum vulgare (fennel) on the kidney in experimental PCOS female rats. [Journal Article]
- Avicenna J Phytomed 2014 Mar; 4(2):110-7.
Objective:Foeniculum vulgare seed (F. vulgare) is an herbal plant which is used with phytoestrogene compounds for polycystic ovary syndrome (PCOS) treatment. In this research, renoprotective effect of the aqueous extract of Foeniculum vulgare (AEF) in experimental PCOS female rats is studied. Materials and
Methods:Forty female rats were randomly divided into five groups. The first group served as control, was injected with an equivalent volume (0.2 ml) of normal saline, and received normal diet. Animals in the second group were non poly cystic ovary syndrome (PCOS) rats which were treated with intragastric administration of aqueous extract of F. vulgare (150 mg/kg b.w.). In the third group, the rats were treated with intraperitoneal injection of estradiolvalerate (EV) (4 mg in 0.2 ml of sesame oil). The fourth groups were treated with EV and AEF (150mg/kg bw) with the same route. The fifth groups were treated with EV and AEF (100mg/kg bw). After 4 weeks of study, all of the rats were sacrificed, their kidneys tissues were processed for light microscopy, and some biochemical parameters of serum were measured.
Results:The mean values of blood urea nitrogen in PCOS rats treated with low dose of AEF and EV and non-treated, was significantly (p<0.05) increased compared with non-PCOS and PCOS rats treated with high dose of AEF. Moreover, histopathological changes of kidney samples were comparable in PCOS rats with respect to treated groups with AEF.
Conclusion:Aqueous extract of fennel seed showed the beneficial effect (especially at dose of 150 mg/kg b.w.) on renal function in PCOS rats.
- Pigment epithelium derived factor (PEDF) in the reproductive system. [JOURNAL ARTICLE]
- Reproduction 2014 Jul 21.
The physiological function of the female reproductive organs is hormonally controlled. In each cycle the reproductive organs undergo tissue modifications that are accompanied by formation and destruction of blood vessels. Proper angiogenesis requires an accurate balance between stimulation and inhibition of angiogenesis, maintained by pro- and anti-angiogenic factors. As with many other tissues, vascular endothelial growth factor (VEGF) appears to be one of the major pro-angiogenic factors in the female reproductive organs. Pigment epithelium-derived factor (PEDF) is a non-inhibitory member of the serine protease inhibitors (serpin) superfamily, possessing potent physiologic anti-angiogenic activity that negates VEGF activity. The anti-angiogenic effect of PEDF has been extensively investigated in the eye and in cancer, demonstrating its role in decreasing abnormal neovascularization, mainly by inhibiting the stimulatory activity of several strong pro-angiogenic factors, including VEGF. This review summarizes the function of PEDF in the reproductive system, showing its hormonal regulation and its anti-angiogenic activity. Furthermore, some pathologies of the female reproductive organs, including endometriosis, ovarian hyperstimulation syndrome (OHSS), polycystic ovary syndrome (PCOS), and others, are associated with a faulty angiogenic process; therefore, this review illuminates the role of PEDF in their pathogenesis and treatment. Collectively, we can conclude that although PEDF seems to play an essential role in the physiology and pathophysiology of the reproductive system its full role and mechanism of action still need to be illustrated.