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Polycystic Ovarian Syndrome [keywords]
- What Is New in Polycystic Ovary Syndrome?: Best Articles From the Past Year. [JOURNAL ARTICLE]
- Obstet Gynecol 2014 Sep; 124(3):630-632.
This month, we focus on current research in polycystic ovary syndrome. Dr. Hansen discusses six recent publications, and each is concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts.
- MicroRNAs Related to Polycystic Ovary Syndrome (PCOS). [REVIEW]
- Genes (Basel) 2014; 5(3):684-708.
Polycystic ovary syndrome (PCOS) is the most common, though heterogeneous, endocrine aberration in women of reproductive age, with high prevalence and socioeconomic costs. The syndrome is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism, as well as being associated with infertility, insulin resistance, chronic low-grade inflammation and an increased life time risk of type 2 diabetes. MicroRNAs (miRNAs) are small, non-coding RNAs that are able to regulate gene expression at the post-transcriptional level. Altered miRNA levels have been associated with diabetes, insulin resistance, inflammation and various cancers. Studies have shown that circulating miRNAs are present in whole blood, serum, plasma and the follicular fluid of PCOS patients and that they might serve as potential biomarkers and a new approach for the diagnosis of PCOS. In this review, recent work on miRNAs with respect to PCOS will be summarized. Our understanding of miRNAs, particularly in relation to PCOS, is currently at a very early stage, and additional studies will yield important insight into the molecular mechanisms behind this complex and heterogenic syndrome.
- Conditional Knockout of the Androgen Receptor in Gonadotropes Reveals Crucial Roles for Androgen in Gonadotropin Synthesis and Surge in Female Mice. [JOURNAL ARTICLE]
- Mol Endocrinol 2014 Aug 26.:me20141154.
Polycystic ovary syndrome is the major cause of infertility in reproductive aged women. PCOS is associated with high circulating levels of androgens and impaired metabolic function. The goal of this study is to understand how androgen signaling via the androgen receptor (AR) impacts reproductive function. We knock out the AR gene specifically in pituitary gonadotropes (PitARKO) to explore the role of androgen on the development of reproductive function in female mice. There was no difference in the age of puberty between control and PitARKO littermates which was assessed by the ages of vaginal opening and first estrus. Cyclicity and fertility were also studied and there was no significant difference between control and PitARKO mice. We observed a significant decrease in basal FSH serum and mRNA levels with no corresponding change in LH serum and mRNA levels. While the numbers of litters born to control and PitARKO females were the same, the litter size was significantly smaller for PitARKO mice. LH and FSH response to ovariectomy was altered with reduced LH/FSH hormone and mRNA level in PitARKO females. This reduction may be due to reduced expression of activin A/B and GnRHR. Preovulatory surge levels of LH and FSH were dramatically lower in PitARKO mice. The number of corpora lutea was decreased while the number of antral follicles was similar between control and PitARKO mice. Overall the pituitary androgen receptor contributes to the elaboration of the LH surge and normal reproductive function by regulating LH/FSH expression and secretion.
- Micronized estradiol and progesterone therapy in primary, preinvasive endometrial cancer (1A/G1) in young women with polycystic ovarian syndrome. [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2014 Aug 26.:jc20141693.
Introduction: This repot presents original, combined mode of treatment of preinvasive endometrial cancer (IA/G1) in young women with polycystic ovarian syndrome. Objectives: The assessment of treatment with natural female sexual hormones in combination with antidiabetic, antioxidative, antidopaminergic and antiserotonin therapy on the concentrations of hormones and serotonin in blood serum in young women with polycystic ovary syndrome and preinvasive endometrial cancer. Design: This study was performed within 12 months. Setting: The study was conducted in the Department of Menopause and Andropause of the Pomeranian Medical University in Szczecin, Poland. Participants and study design: Participants were 57 young PCOS women with concomitant preinvasive endometrial cancer (1AG1). These women were 18-29 years old. They were treated with modified transdermal hormonal replacement therapy (MHRT). Moreover in permanent combined treatment Metformax 850 mg/day, Bromcriptine mesylate 2,5mg/day, Melatonin 5mg/day were applied. Interventions: Interventions in the study included blood sampling and D&C. Main outcome measures: The concentrations of gonadotropins, estrogens (E1, E2), progesterone, total/free testosterone, prolactin in basic conditions and after metoclopramide stimulating test, dehydroepiandrosterone sulphate (DHEA-S), serotonin in blood serum were measured. Results: A significant increase in the concentrations of gonadotropins, estrogens, progesterone was found. Moreover the concentrations of androgens, prolactin and serotonin were significantly decreased. Conclusion: Micronized estradiol and progesterone in primary, preinvasive endometrial cancer (IA/G1) in young women, with polycystic ovarian syndrome with concomitant antidiabetic, antioxidative, antidopaminergic and antiserotonin therapy, favorably influenced on the concentrations of female sexual hormones, lipid metabolism and caused the restoration of normal endometrium.
- Long term complications of polycystic ovary syndrome (PCOS). [JOURNAL ARTICLE]
- Ann Endocrinol (Paris) 2014 Aug 22.
Polycystic ovary syndrome (PCOS) is a frequent endocrine disease affecting 10 to 15% of women. Menstrual disorders, hyperandrogenism and ultrasonographic aspect of ovaries are typical of the disease and are established diagnostic criteria. But PCOS has also long term complications frequently forgotten and underestimated. During pregnancy, gestational diabetes and gestational hypertensive disorders can occur. At an older age, metabolic disease such as glucose intolerance, type 2 diabetes or dyslipidaemia are frequently described. Women with PCOS have increased classical cardiovascular risks and increased subclinical cardio-vascular disease without proven increase of cardiovascular morbidity and mortality. Finally, endometrial cancer seems to be more frequent in women with PCOS. Therefore, PCOS have numerous long-term health risks and a life-long follow-up is necessary for these women "at-risk" to detect and prevent complications as soon as possible.
- [In vitro oocyte maturation for female fertility preservation.] [JOURNAL ARTICLE]
- Gynecol Obstet Fertil 2014 Aug 18.
Recovering immature oocytes from unstimulated ovaries, followed by in vitro maturation (IVM) was initially proposed to avoid the risks and side effects of exogenous gonadotropin administration. Therefore, during the past decades, IVM was mainly offered to patients with polycystic ovary syndrome at high risk of ovarian hyperstimulation syndrome. However, the development of fertility preservation has recently opened new perspectives in the field of IVM. The present review reports the possible indications of IVM, in the strategy of female fertility preservation.
- Gestational diabetes mellitus risk factors in women with polycystic ovary syndrome (PCOS). [JOURNAL ARTICLE]
- Eur J Obstet Gynecol Reprod Biol 2014 Aug 7.:195-199.
To compare the incidence of gestational diabetes mellitus (GDM) in Iranian infertile women with polycystic ovary syndrome (PCOS) and women without PCOS after pregnancies resulting from either assisted reproductive technology (ART) or spontaneous as well as to determine the risk factors of GDM in PCOS women.In a cross-sectional study, we evaluated medical records of 234 spontaneous pregnant women without PCOS in Akbarabadi Women's Hospital affiliated to Tehran University of Medical Science, Tehran, Iran, along with 234 pregnant women with PCOS and 234 pregnant non-PCOS women with ART conception who were treated at Royan institute, Tehran, Iran, at the same period of time, 2012 to February 2013. Exclusion criteria were as following: maternal age ≥40, family history of diabetes in first-degree relatives, pre-pregnancy diabetes and history of gestational diabetes, history of stillbirth, recurrent miscarriage, birth weight baby ≥4kg (macrosomia), parity >4, Cushing's syndrome, congenital adrenal hyperplasia and overt hypothyroidism. The GDM diagnosis was according to American Diabetes Association (ADA) criteria. Incidence and the risk factors for GDM were evaluated.The incidence rates of GDM were 44.4%, 29.9% and 7.3% for PCOS ART, non-PCOS ART and non-PCOS spontaneous pregnant women, respectively. Multivariable logistic regression was used for determining risk factors of GDM in PCOS women with adjusted odds ratios for age, parity and hypothyroidism, the results revealed the most important and significant predictors for development of GDM in PCOS women as follow: menstrual irregularity (OR=4.2; 95% CI=1.7-10.6), serum triglycerides level ≥150mg/dL (OR=1.9; 95% CI=1.07-3.6) and pregestational metformin use (OR=0.4; 95% CI=0.2-0.7).Pregnant Iranian women with a history of infertility and PCOS are at increased risk for developing GDM. It is recommendable to perform screening test for GDM in PCOS women with ART treatment, irregular menses and high serum triglycerides level in the early stage of pregnancy. Pregestational use of metformin can be effective in reducing the occurrence of GDM.
- Intraindividual right-left comparison of sonographic features in polycystic ovary syndrome (PCOS) diagnosis. [JOURNAL ARTICLE]
- Eur J Obstet Gynecol Reprod Biol 2014 Aug 4.:124-129.
Sonographic features of polycystic ovaries consist of elevated antral follicle count or ovarian volume of at least one ovary. The aim of this prospective cross-sectional study was to estimate intraindividual differences in sonographic measurements between the both ovaries of PCOS patients and controls and clinical consequences.Both ovaries of 85 PCOS patients and 48 controls were scanned transvaginally and agreement of sonographic measurements was analyzed using the Bland-Altman method. Concordance correlation coefficients (CCC) were computed.Mean differences between right and left ovaries were 0.24 (95% confidence interval [95% CI]: -0.32-0.80) follicles for AFC and 1.14 (95% CI: 0.34-1.92)ml for OV in the whole study population, 0.14 (95% CI: -0.68-0.96) follicles for AFC and 1.48 (95% CI: 0.39-2.58)ml for OV in PCOS patients, 0.42 (95% CI: -0.19-1.02) follicles for AFC and 0.53 (95% CI: -0.50-1.56)ml for OV in controls. Rather wide limits of agreement and low CCCs (<0.7 for all estimates) indicated poor agreement between the ovaries for both sonographic measurements. Width between lower and upper limits of agreement was higher for PCOS patients than for controls. 23.5% of the PCOS patients showed polycystic ovarian morphology (PCOM) only in one ovary, resulting in 9.4% potentially missed PCOS diagnosis according to the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.Substantial differences in antral follicle count and ovarian volume between the right and left ovary were observed. In approximately 10% of the PCOS patients in our study only the examination of both ovaries has led to a reliable diagnosis of PCOS. In clinical practice it is recommended to scan both ovaries for a reliable diagnosis of abnormal sonographic findings in PCOM and PCOS diagnosis.
- Genome-wide identification of aberrantly methylated promoters in ovarian tissue of prenatally androgenized rats. [JOURNAL ARTICLE]
- Fertil Steril 2014 Aug 20.
To identify aberrantly methylated candidate genes that are involved in the development of polycystic ovary syndrome (PCOS).Animal model.University-affiliated laboratory.Sprague-Dawley rats.The prenatally androgenized (PNA) rat model was established. Pregnant rats were treated with daily SC injections of T propionate during late gestation, and their female offspring were studied as adults.Serum glucose and hormone levels, ovary morphology and cell apoptosis, genome-wide CpG methylation, and expression of caspase-3 protein were measured.In the PNA group, the levels of serum glucose, 17-hydroxyprogesterone, and T were significantly higher when compared with the control group. Ovarian morphology showed increased atretic follicles and cystic follicles. Using the MeDIP-chip approach, we identified 528 genes that were hypermethylated in PNA ovaries. Gene ontology analyses revealed that these genes are involved in a variety of reproductive development and biological processes. The methylation enrichments of Bcl2l1 and Scr5a1 observed in the PNA group by MeDIP-quantitative polymerase chain reaction assay were significantly higher than those obtained from the control group. Furthermore, the mRNA level of the Bcl2l1 gene was significantly decreased in the PNA group. The percentage of caspase-3-positive cells in the PNA group was obviously higher compared with the control group, by terminal deoxynucleotidyl transferase dUTP nick end labeling detection as well.DNA methylation alteration may be an important factor affecting the genes involved in the pathophysiological processes that result in the phenotype of PCOS.
- Atypical Polycystic Ovary Syndrome - A Genetic Analysis. [JOURNAL ARTICLE]
- Exp Clin Endocrinol Diabetes 2014 Aug 22.
Background/aims: Although polycystic ovary syndrome (PCOS) is a common endocrinopathy the pathogenesis is not entirely understood. Typically, high androgen levels are associated with increased virilization. We report 2 rare groups of patients with either unexpectedly high testosterone levels despite low virilization as well as patients with low testosterone levels despite high grade of virilization. One possibility for the atypical PCOS may be based on an altered androgen receptor (AR) signaling. Methods: 6 patients and when available the parents were included in this study. Alterations of the metaphase chromosomes by GTG staining, the length of both the trinucleotide CAG- and GGC-repeats of the androgen receptor (AR) gene was determined by PCR, further the entire AR gene was sequenced and analyzed. Results: The GTG banding revealed no chromosomal alterations and the range of CAG- and GGC-repeat lengths are within the normal range. Interestingly, by sequencing of the entire AR gene few genetic mutations were identified. Conclusion: The detected mutations do not alter the AR protein sequence but they change the codon usage towards less frequent codons that potentially may alter AR protein levels and androgen signaling. In addition to this, we postulate also other causes for manifestation of atypical PCOS, which may include AR-coregulators or epigenetic alterations. To our knowledge this is the first report of combining chromosomal analysis of PCOS patients with full sequencing of the human AR gene and linking codon usage to PCOS.