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Polycystic Ovarian Syndrome [keywords]
- Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome. [JOURNAL ARTICLE]
- J Assist Reprod Genet 2014 Aug 30.
Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) play crucial roles in follicular development and oocyte maturation. This study aimed to investigate and compare the expression of these proteins in ovarian tissues of women with and without polycystic ovary syndrome (PCOS).Ovarian tissues from 28 patients with PCOS and 26 normal ovulatory women were collected, and the expression of GDF9 and BMP15 in oocytes and granulosa cells was evaluated via immunohistochemical staining.GDF9 and BMP15 were first expressed in primordial follicles at very low levels, and their expression increased gradually with follicular development, reaching the highest levels in Graafian follicles. However, less GDF9 and BMP15 expression was observed in primordial, primary, and secondary follicles in ovarian tissues of PCOS patients compared with levels in the control tissues (P < 0.05). In Graafian follicles, GDF9 and BMP15 expression reached comparable levels in the PCOS and control groups (P > 0.05).The expression of GDF9 and BMP15 in ovarian tissues varies among the developmental stages in both oocytes and granulosa cells in human ovarian tissues. The expression of these proteins is reduced and delayed in the early follicular stage in PCOS ovarian tissues, and these differences in expression may be associated with aberrant follicular development in patients with PCOS.
- Expression of anti-Müllerian hormone in letrozole rat model of polycystic ovary syndrome. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2014 Aug 29.:1-5.
Abstract Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age with anti-müllerian hormone (AMH) two to three times higher, but the mechanism of increased AMH, excessive follicles and follicle stagnation in PCOS still needs further research. Methods: Female Sprague-Dawley rats were treated with a gavage of 1.0 mg/kg of letrozole carboxymethylcellulose solution once daily for 21 consecutive days. Serum steroid concentrations, ovarian morphology, ovarian expression of AMH and AMH-RII protein were determined and their relationships were studied. Results: According to the morphology and endocrinology, the letrozole model group was a successful PCOS model. Serum AMH and ovarian local expression of AMH and AMH-RII were both increased in letrozole model group. The elevated AMH had a positive correlation with T, growing follicle count and a negative correlation with body weight. Conclusions: The letrozole model group is a good animal model for the study of AMH in PCOS patients with obesity or insulin resistance. The increased serum AMH level in PCOS is the consequence of the androgen-induced excess of small antral follicles. These results lead to the hypothesis that reducing AMH may become a therapeutic target of PCOS, which is worth further research.
- [Correlation analysis between polycystic ovary syndrome susceptibility genes and metabolic phenotypes.] [JOURNAL ARTICLE]
- Zhonghua Fu Chan Ke Za Zhi 2014 Jun; 49(6):441-445.
To investigate the relationship between polycystic ovary syndrome (PCOS) susceptibility single nucleotide polymorphisms (SNP) and metabolic phenotypes in glucose and lipid metabolism and explore the pathophysiological mechanism of the susceptibility genes.Three of PCOS susceptibility locus 2p16.3 (rs13405728 of LHCGR gene), 2p21 (rs13429458, rs12478601 of THADA gene) and 9q33.3 (rs2479106, rs10818854 of DENNDIA gene) were selected and the metabolic phenotypes were compared between different genotypes of SNP in PCOS patients (using dominant model).Low-density lipoprotein cholesterol was significantly increased in CC genotype group than in TC + TT groups at rs12478601 of THADA gene [(2.5 ± 0.8), (2.4 ± 0.8) mmol/L; P = 0.01]. Serum insulin level of 2 hours after 75 g glucose intake was significantly higher in GG+AG groups than that of AA group at rs2479106 of DENND1A gene[(71 ± 65), (64 ± 50) mU/L; P = 0.05 ], and the prevalence of type II diabetes in first-degree relatives of patients were also increased [9.9% (66/666), 6.9% (52/751); P < 0.05]. No association was found between metabolic phenotypes and genotypes of rs13429458, rs10818854, and rs13405728.Genetic factors probably have effect on the metabolic characteristics of PCOS. THADA gene is related to lipid metabolism, while DENND1A gene may be involved in insulin metabolism in patients with PCOS.
- How long should we continue clomiphene citrate in anovulatory women? [JOURNAL ARTICLE]
- Hum Reprod 2014 Aug 27.
What is the effectiveness of continued treatment with clomiphene citrate (CC) in women with World Health Organization (WHO) type II anovulation who have had at least six ovulatory cycles with CC but did not conceive?When women continued CC after six treatment cycles, the cumulative incidence rate of the ongoing pregnancy rate was 54% (95% CI 37-78%) for cycles 7-12.If women with WHO type II anovulation fail to conceive with CC within six ovulatory cycles, guidelines advise switching to gonadotrophins, which have a high risk of multiple gestation and are expensive. It is however not clear what success rate could be achieved by continued treatment with CC.We performed a retrospective cohort study of women with WHO II anovulation who visited the fertility clinics of five hospitals in the Netherlands between 1994 and 2010. We included women treated with CC who had had at least six ovulatory cycles without successful conception (n = 114) after which CC was continued using dosages varying from 50 to 150 mg per day for 5 days.Follow-up was a total of 12 treatment cycles. Primary outcome was the cumulative incidence rate of an ongoing pregnancy at the end of treatment.We recruited 114 women that had ovulated on CC for at least six cycles but had not conceived. Of these 114 women, 35 (31%) had an ongoing pregnancy resulting in a cumulative incidence rate of an ongoing pregnancy of 54% after 7-12 treatment cycles with CC.Limitations of our study are its retrospective approach.Randomized trials comparing continued treatment with CC with the relatively established second line treatment with gonadotrophins are justified. In the meantime, we suggest to only begin this less convenient and more expensive treatment for women who do not conceive after 12 ovulatory cycles with CC.None.Not applicable.
- 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.