October 31st, 2008
Mark O. Goodarzi, MD, PhD, Michelle R. Jones, BSc, Yii-Der I. Chen, PhD and Ricardo Azziz, MD, MBA, MPH
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine (M.O.G., M.R.J.), Department of Obstetrics and Gynecology (M.O.G., Y-D.I.C., R.A.), and Medical Genetics Institute (M.O.G., Y-D.I.C.), Cedars-Sinai Medical Center, Los Angeles, California 90048; and Departments of Medicine (M.O.G., Y-D.I.C., R.A.) and Obstetrics and Gynecology (R.A.), the David Geffen School of Medicine at UCLA, Los Angeles, California 90095
Diabetes Care
ABSTRACT
Objective: Insulin resistance has been reported in up to 70% of women with polycystic ovary syndrome (PCOS). Physiologic and genetic data currently implicate post-insulin receptor signaling defects in substrates such as GSK3β . The AKT2 gene was chosen as a candidate for PCOS because its product affects glucose metabolism and mitogenic signaling, interacts with GSK3β, and mediates cell survival in the ovary.
Research Design and Methods: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. 287 White women with PCOS and 187 White controls were genotyped for 4 SNPs in AKT2. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Single nucleotide polymorphisms (SNPs) and haplotypes were tested for association with PCOS risk and phenotypic markers of PCOS.
Results: Minor allele carriers of SNPs rs3730051 and rs8100018 had increased odds of PCOS (OR=2.2, p=0.004 and OR=2.4, p=0.001, respectively). The haplotype T-G-C-T was significantly associated with PCOS (OR=2.0, p=0.01). Carriers of the risk haplotypes for both AKT2 and GSK3B had a further increased odds of PCOS (OR=3.1, p=0.005).
Conclusions: These data suggest that polymorphisms in two components of the insulin signaling pathway, AKT2 and GSK3B, are associated with PCOS. Presence of multiple lesions in a single pathway may confer increased risk.
http://care.diabetesjournals.org/cgi/content/short/dc08-0532v1?rss=1
October 30th, 2008
Sathyapalan T, Kilpatrick ES, Coady AM, Atkin SL
Department of Diabetes and Endocrinology, University of Hull, Hull, UK; Department of Clinical Biochemistry, Hull Royal Infirmary, Hull, UK; Department of Obstetric Ultrasound, Hull & East Yorkshire Women’s & Children’s Hospital, Hull, UK.
Source J Clin Endocrinol Metab 2008 Oct 21.
Abstract Context: Polycystic ovary syndrome (PCOS) is associated with increased risk of cardiovascular morbidity whereas statins are proven to reduce cardiovascular mortality and morbidity through lipid lowering and perhaps through their pleotrophic effects. Statins can also reduce testosterone in vitro by inhibiting ovarian theca-interstitial cell proliferation, steroidogenesis and reducing inflammation in vivo.
Objective: To assess the effect of atorvastatin on inflammatory markers, insulin resistance and biochemical hyperandrogenemia in patients with PCOS.
Design: Randomised, double blind placebo controlled study.
Setting: Tertiary care setting in United Kingdom.
Patients: Forty medication naïve patients with PCOS and biochemical hyperandrogenaemia.
Methods: Patients were randomised to either atorvastatin 20mg daily or placebo.
Main outcome measures: The primary end point of the study was a change in the inflammatory marker hsCRP. The secondary end points were a change in insulin resistance and total testosterone.
Results: After 12 weeks of atorvastatin there was a significant reduction (mean+/-SEM) in total cholesterol (4.6+/-0.2 vs. 3.4+/-0.2 mmol/L,p<0.01), LDL cholesterol (2.9+/-0.2vs.1.8+/-0.2 mmol/L,p<0.01), triglycerides (1.34+/-0.08vs.1.08+/-0.13mmol/L,p<0.01), hsCRP (4.9+/-1.4vs.3.4+/-1.1mg/Lp=0.04), free androgen index (13.4+/-0.6vs.8.7+/-0.4 p<0.01), testosterone[4.1+/-0.2vs.2.9+/-0.1 nmol/Lp<0.01) and insulin resistance as measured by HOMA-IR(3.3+/-0.4vs.2.7+/-0.4). There was a significant increase in SHBG (31.1+/-1.0vs.35.3+/-1.2 nmol/L,p<0.01). There was a positive correlation between the reduction in HOMA-IR in the atorvastatin group with the reduction in triglycerides and the reduction of FAI. There was a significant deterioration of HOMA-IR in the placebo group (3.0+/-0.4vs.3.8+/-0.5).
Conclusions: This study suggests that atorvastatin is effective in reducing inflammation, biochemical hyperandrogenemia and metabolic parameters in patients with polycystic ovary syndrome after a 12 week period.
PubMed ID 18940877
October 28th, 2008
S. Pourabolghasema, S. Najmib, M.A. Aramic
Department of Obstetrics and Gynecology, Tabriz University (Medical Sciences), Taleghani Hospital,
Consultant Neurologist, Tabriz University (Medical Sciences), Razi Hospital, Tabriz,
Consultant Neurologist, Neurology Clinic, Milad General Hospital, Tehran, Iran
Eur Neurol 2009;61:42-45 (DOI: 10.1159/000165349)
Abstract
Background: To evaluate the role of some sex hormones in migraine headaches, the aim of this study was to assess the prevalence and characteristics of headache, especially migraine, in patients with polycystic ovary syndrome (PCO) compared with women without this disease. Methods: One hundred and thirty-three women with PCO and 107 controls were interviewed by 2 neurologists experienced in headache diagnosis. The headache disorders were classified according to the International Headache Society criteria. The statistical significance was determined using the chi2 test, and a p value of <0.05 was considered significant. Results: Forty-five women (33.8%) of the 133 cases without PCO complained of headache. Of the PCO patients, 48 women (44.9%) suffered from headache. The prevalence of headache was not significantly higher among women with PCO (p = 0.85). The same results were found for migraine headache (p = 0.13). Conclusion: Migraine is not more frequent in women with PCO. It was concluded that male sex hormones and especially testosterone do not play an important role in the exacerbation of migraine headache.
Copyright © 2008 S. Karger AG, Basel
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=165349&Ausgabe=241146&ProduktNr=223840
October 25th, 2008
The first week I had horrible gas pains. The second week it was diarrhea. By the third week when the vomiting began I knew I could not take Metformin, also known as glucophage, anymore. According to my gynecologist, Metformin would regulate my missing periods, clear up my acne, and decrease the hair growing in places that I did not want it to. Instead, all I got was a steady stream of horrible reactions that left me weak, tearful and depressed.
I had heard my doctor’s warning of possible side effects but, really, who listens to those? If there was a wonder drug that was going to help me I was determined to take it; so determined that when my adverse symptoms started I ignored them. But by the third week, when things got worse, I began to feel betrayed. I was angry at the internet articles, angry at the blogs, angry at my neighbor who had taken Metformin and been fine, angry at my doctor. It seemed that there was no cure for me, no easy road to regular periods or losing weight or nice skin.
When I first learned about Metformin on the internet, all the news seemed very positive. It was the wonder drug for all women trying to get pregnant or for those of us trying to combat the symptoms caused by Polycystic Ovarian Syndrome (PCOS). Women who had never had a regular menstrual cycle suddenly were regular as rain. Women who had been trying to have a baby for years suddenly were having twins. How I wished that were me… but sadly it was not.
As it happens, I had another neighbor who suffered from some of the same symptoms of PCOS that I did. While out in our yards one day she asked me how things were going with the Metformin and was not surprised when I broke down in tears telling her how horrible I felt. She too had suffered from adverse reactions to the drug and understood my frustrations. She suggested that I try a more natural solution that would help give me a total body and mind makeover. The treatment she used was called the Insulite 5 Element System which combines diet, exercise, vitamins, addiction/cravings awareness and support components to help reverse Insulin Resistance. Insulin Resistance — the root cause of PCOS — causes the body to improperly utilize insulin making it unable to convert glucose to energy and causing hormonal imbalance.
Today, I am feeling healthier than ever. I understand that in order to combat PCOS I need to eat a low carbohydrate diet, take multiple supplements and exercise regularly. I have learned that when I do not do these things I start to feel sluggish and my body slips back into its old bad habits of growing unwanted facial hair and gaining weight at warp speed. Despite the work it takes, I can tell you that I am a much happier person when following the Insulite PCOS System. It sure beats taking Metformin and suffering from its debilitating side effects.
www.pcos.insulitelabs.com
