Study of Pharmacodynamics of LIK066 in Overweight and Obese Women With Polycystic Ovary Syndrome...
Polycystic Ovary SyndromeThe purpose of the study was to evaluate whether LIK066 can be developed for the treatment of polycystic ovary syndrome (PCOS) in overweight and obese women.
Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone...
Polycystic Ovary SyndromeHyperandrogenismMany, but not all, girls with high levels of the male hormone testosterone go on to develop polycystic ovary syndrome (PCOS) as adults. Women with PCOS often have irregular menstrual periods, excess facial and body hair, and weight gain. PCOS is also a leading cause of difficulty becoming pregnant. The investigators do not understand why some girls with high hormones develop PCOS and others do not. In a previous study by our group, some girls with high levels of male hormones had abnormalities in the secretion of another hormone, called luteinizing hormone (LH), that are often seen in women with PCOS. However, another group had normal LH secretion. The girls with the abnormal LH secretion had higher levels of another hormone, called insulin, than the girls with normal LH secretion. The investigators will test whether metformin, an insulin-sensitizing agent, changes the effects of high male hormone levels in adolescent girls, specifically by looking at their LH secretion response following metformin treatment.
Sex Steroids, Sleep, and Metabolic Dysfunction in Women
Polycystic Ovary Syndrome (PCOS)Obstructive Sleep Apnea1 moreIncreased plasma triglyceride concentration is a common feature of the metabolic abnormalities associated with obesity and a major risk factor for cardiovascular disease. Obesity is a major risk factor for two conditions that appear to be increasing in prevalence in women: the polycystic ovary syndrome (PCOS) and sleep disordered breathing. PCOS affects 5-8% of women. Sleep disordered breathing affects up to 10% of women. Obstructive sleep apnea (OSA) is the most common cause for sleep disordered breathing and particularly prevalent in obese women with PCOS (~50%). Both PCOS and OSA augment the increase in plasma triglyceride (TG) concentration associated with obesity, and the effects of PCOS and OSA on plasma TG concentration appear to be additive. The mechanisms responsible for the adverse effects on plasma TG metabolism are not known. The primary goal of this project, therefore, is to determine the mechanisms responsible for the increase in plasma TG concentration in obese women with PCOS and OSA. It is our general hypothesis that alterations in the hormonal milieu that are characteristic of these two conditions are, at least in part, responsible for the increase in plasma TG concentration in obese women with the conditions. Furthermore, we hypothesize that the hormonal aberrations characteristic of the two conditions are particularly harmful to obese, compared with lean, women. The effects of PCOS on skeletal muscle protein metabolism are also not known. However, sex hormones are thought to be important regulators of muscle protein turnover suggesting that muscle protein metabolism is likely to be affected by PCOS. We will examine this by determining the effect of individual sex hormones on muscle protein metabolism and hypothesize that testosterone administration will stimulate muscle protein metabolism while estrogen and progesterone administration will inhibit muscle protein metabolism.
Incretin Effect in PCOS Women
Polycystic Ovary SyndromeThis study investigates the incretin effect in women with polycystic ovary syndrome (PCOS) before and after removal of their insulin resistance by metformin. The investigators' hypothesis is that insulin resistant women with PCOS have a reduced incretin effect and elevated glucagon responses as measured by a 75-g oral glucose tolerance test and isoglycemic i.v. glucose infusion. The investigators hypothesise that both can be improved when their insulin resistance is removed.
Effect of Vitamin D on Hormonal, Metabolic and Cardiovascular Risk Factors in Patients With Polycystic...
Polycystic Ovary SyndromeThis is a double blind randomised placebo-controlled study involving women with polycystic ovary syndrome (PCOS). The patients will be randomised either to Vitamin D 3200 IU or placebo for three months. The main hypothesis of this study is "Vitamin D improves hormonal, metabolic and cardiovascular risk markers in women with PCOS".
Potential Impact of Polycystic Ovarian Syndrome on Protein Modifications and Accumulation
Polycystic Ovarian Syndrome (PCOS)Insulin Resistance2 moreA goal of this study is to use a novel methodology to determine whether insulin resistance in women with polycystic ovary syndrome (PCOS) is related to the accumulation of proteins with modifications. This could lead to future research to determine if these modifications interfere with their proper function. Additionally, the investigators will determine how protein quality is affected by exercise training. Aerobic exercise enhances the endogenous oxidant buffering systems which may minimize oxidative damage to proteins. The investigators propose that aerobic exercise minimizes the accrual of modified proteins by increasing the synthesis of new proteins, but also by increasing the degradation and removal of old and damaged proteins. Based on our previous studies the investigators observed that insulin affects plasma protein synthesis and aerobic exercise improves insulin sensitivity not only in muscle but also in liver. The investigators therefore propose that aerobic exercise and related increase in insulin sensitivity (and decline in insulin levels) will reduce accumulation of old and modified skeletal muscle and plasma proteins leading to improved function.
The Effect of Dipeptidyl Peptidase 4 Inhibition on Growth Hormone Secretion in Women With Polycystic...
Polycystic Ovary SyndromeAdults with abdominal obesity are at high risk for cardiovascular disease and also exhibit diminished growth hormone (GH) secretion; the latter further contributes to the development of visceral adiposity, impaired fibrinolysis and inflammation.Growth hormone releasing hormone (GHRH), the primary stimulus for endogenous GH secretion, is a substrate of dipeptidyl peptidase 4 (DPP4); inhibition of DPP4 with the currently available anti-diabetic therapy, sitagliptin, may therefore increase GH secretion by decreasing the degradation of GHRH. The proposed research will test the hypothesis that chronic sitagliptin therapy will enhance GH secretion and vascular function while improving glucose tolerance in patients with impaired GH secretion who are at risk for the development of diabetes mellitus and cardiovascular disease, specifically obese women with polycystic ovary syndrome.
Liver and Fat Regulation in Overweight Adolescent Girls
Hepatic SteatosisPolycystic Ovarian Syndrome1 moreWomen with polycystic ovarian syndrome (PCOS) have increased rates of hepatic steatosis compared to weight similar women with regular menses. It is unclear if this is related to high testosterone or insulin resistance. The investigators will assess hepatic glucose release, rates of lipolysis and hepatic de novo lipogenesis in the fasted and postprandial state to determine if alterations in the processes contribute to hepatic steatosis. Participants will be overweight, sedentary girls with or without PCOS. Those with PCOS will either be medication naive, or must be taking metformin or combined oral contraceptives (COCPs) for a period of at least 6 months prior to study procedures.
Clinical, Metabolic and Endocrine Effects of the Treatment With Drospirenone and Ethinyl Estradiol...
PCOSPolycystic Ovary SyndromePolycystic ovary syndrome (PCOS) is a heterogeneous syndrome with a variety of metabolic and endocrine abnormalities and clinical symptoms. The primary defect in PCOS consists of an abnormal androgen synthesis and secretion, particularly by ovarian theca cells. Insulin resistance and obesity may act as triggers, explaining the frequent association of PCOS with these metabolic conditions. Hyperinsulinaemia, which results from insulin resistance, stimulates both ovarian and adrenal androgen secretion and suppresses sex hormone-binding globulin synthesis from the liver. It results in an increase in free, biologically active androgens which are related to clinical signs such as hirsutism, acne, seborrhea, and alopecia. Combined oral contraceptive (COC) therapy is a common treatment for PCOS and it was widely used in this group of patients providing clinical improvement in the areas of excessive hair growth, unpredictable menses, acne, and weight gain. More recent studies outlined a deficiency in myo-inositol in women with PCOS and insulin-resistance. Myo-inositol is a precursor for many inositol-containing compounds and it plays critical and diverse roles in signal transduction, membrane biogenesis, vesicle trafficking, and chromatin remodeling. It is a precursor in the synthesis of phosphatidylinositol polyphosphates (PIPs) that are a source of several second messengers. It has been reported that the administration of myo-inositol reduces serum insulin, decreases serum testosterone and enhances ovulation. Due to the different beneficial actions, the aim of the present study is to evaluate the clinical, metabolic and endocrine effects of treatment with COC (drospirenone and ethinyl estradiol)alone or in combination with myo-inositol, in young women with PCOS and insulin resistance.
A Comparison of Letrozole and Clomifene Citrate
Polycystic Ovarian SyndromeSubfertilityPolycystic ovary syndrome (PCOS) is one of the most common endocrinopathies, affecting 5% to 10% of women of reproductive age. Women with PCOS suffer from anovulatory infertility. Following lifestyle modification with weight reduction in obese PCOS women, clomifene citrate (CC) is considered the first line treatment for ovulation induction (OI) in these women. 75-80% of women will ovulate after CC administration. However, there is a discrepancy between the ovulation rate and pregnancy rate, which was reported to be 22% per each ovulating cycles after CC. Other alternatives, including gonadotropin injections and laparoscopic ovarian drilling, carried different disadvantages, such as costly treatment and risks of ovarian hyperstimulation syndrome and multiple pregnancy rate in gonadotrophin therapy and surgical risks and risk of ovarian failure in surgical treatment. The use of aromatase inhibitor, letrozole (LTZ), in reproductive medicine started in 2001. After this publication, there have been many groups of investigators studying the use of LTZ either in OI or ovarian stimulation in IVF cycles. A large multicentre randomized trial reported a significantly higher ovulation rate and live-birth rate comparing LTZ with CC. In majority of the publications, the multiple pregnancy rate was lower in LTZ group than in CC group. This can be attributed to the higher chance of monofollicular development after LTZ compared with CC. However, there is no information comparing the hormonal profile and follicular development after letrozole and CC. Mild ovarian stimulation using LTZ or CC in conjunction with intrauterine insemination is commonly offered to ovulatory women with unexplained infertility, minimal endometriosis or mild factor to improve the pregnancy rate. There is again no information comparing the hormonal profile and follicular development after letrozole and CC in ovulatory women. The aim of this study is to compare the hormonal profile after the use of LTZ and CC in anovulatory PCOS women and ovulatory women with unexplained subfertility. The hypothesis is that the FSH risk after LTZ is shorter than that of CC.