Liraglutide in polycystic ovary syndrome: a randomized trial, investigating effects on thrombogenic potential.
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ABSTRACT:
SUBMITTER: Nylander M
PROVIDER: S-EPMC5424770 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
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Liraglutide in polycystic ovary syndrome: a randomized trial, investigating effects on thrombogenic potential.
Nylander Malin M Frøssing Signe S Kistorp Caroline C Faber Jens J Skouby Sven O SO
Endocrine connections 20170124 2
Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on markers of VTE and CVD risk, in PCOS. In a double-blind, placebo-controlled, randomized trial, 72 overweight and/or insulin-resistant women with PCOS were randomized, in a 2:1 ratio, to liraglutide or placebo 1.8 mg/day. Endpoints included between-group difference in change (baseline to follo ...[more]
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Project description:Liraglutide (LIRA) treatment is associated with the dose-dependent reduction of weight. Higher doses are more effective than lower doses, although higher doses are also more poorly tolerated. Metformin may enhance the weight-lowering potential of LIRA via the stimulatory modulation of incretin in addition to its direct beneficial effects in PCOS. The aim of the present study was to evaluate whether metformin as an adjunct to low-dose LIRA affects body weight with increased efficacy compared with low-dose LIRA alone in obese patients with PCOS. In a 12-week study, 44 obese women with PCOS were randomly offered either combined treatment (COMBO) with 1,000 mg metformin twice a day and 1.2 mg LIRA once a day, or treatment with 1.2 mg LIRA alone. The primary outcome of treatment was an alteration in the levels of obesity. A total of 43 patients [aged 30.3±4.4 years; body mass index (BMI) 37.2±4.5 kg/m2; mean ± standard deviation] completed the study. The subjects treated with COMBO lost on average 6.2±2.4 kg compared with a 3.8±3.5 kg weight loss in the patients treated with LIRA alone (P=0.024). The BMI decreased by 2.2±0.8 kg/m2 in patients treated with COMBO and by 1.4±1.2 kg/m2 in patients treated with LIRA alone (P=0.024). A clinically significant ?5% weight reduction was achieved in 59.1% of patients treated with COMBO and 42.9% of patients treated with LIRA alone. Reductions in glucose levels following oral glucose tolerance testing, as well as in androstenedione levels in the COMBO group were significantly greater compared with those in the LIRA group. The side effects were mild and transient in the two treatment groups. A combination of metformin and low-dose LIRA was more effective than low-dose LIRA alone in reducing body weight in obese patients with PCOS.
| S-EPMC4812364 | biostudies-literature
Project description:BackgroundAt present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear.MethodsRNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation.ResultsIn the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation.ConclusionsThe present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS.Trial registrationNot applicable.
| S-EPMC11302332 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a heterogenous endocrine disorder with typical symptoms of oligomenorrhoea, hyperandrogenism, hirsutism, obesity, insulin resistance and increased risk of type 2 diabetes mellitus. Extensive evidence indicates that PCOS is a genetic disease and numerous biochemical pathways have been linked with its pathogenesis. A number of genes from these pathways have been investigated, which include those involved with steroid hormone biosynthesis and metabolism, action of gonadotropin and gonadal hormones, folliculogenesis, obesity and energy regulation, insulin secretion and action and many others. In this review, we summarize the historical and recent findings in genetic polymorphisms of PCOS from the relevant publications and outline some genetic polymorphisms that are potentially associated with the risk of PCOS. This information could uncover candidate genes associating with PCOS, which will be valuable for the development of novel diagnostic and treatment platforms for PCOS patients.
| S-EPMC5937197 | biostudies-literature
Project description:Acupuncture has been demonstrated to improve menstrual frequency and to decrease circulating testosterone in women with polycystic ovary syndrome (PCOS). Our aim was to investigate whether acupuncture affects ovulation frequency and to understand the underlying mechanisms of any such effect by analyzing LH and sex steroid secretion in women with PCOS. This prospective, randomized, controlled clinical trial was conducted between June 2009 and September 2010. Thirty-two women with PCOS were randomized to receive either acupuncture with manual and low-frequency electrical stimulation or to meetings with a physical therapist twice a week for 10-13 wk. Main outcome measures were changes in LH secretion patterns from baseline to after 10-13 wk of treatment and ovulation frequency during the treatment period. Secondary outcomes were changes in the secretion of sex steroids, anti-Müllerian hormone, inhibin B, and serum cortisol. Ovulation frequency during treatment was higher in the acupuncture group than in the control group. After 10-13 wk of intervention, circulating levels of estrone, estrone sulfate, estradiol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, free testosterone, dihydrotestosterone, androsterone glucuronide, androstane-3?,17?-diol-3-glucuronide, and androstane-3?,17?-diol-17-glucuronide decreased within the acupuncture group and were significantly lower than in the control group for all of these except androstenedione. We conclude that repeated acupuncture treatments resulted in higher ovulation frequency in lean/overweight women with PCOS and were more effective than just meeting with the therapist. Ovarian and adrenal sex steroid serum levels were reduced with no effect on LH secretion.
| S-EPMC4116535 | biostudies-literature
Project description:Lifestyle modification is recommended in women with polycystic ovary syndrome (PCOS) prior to conception but there are few randomized trials to support its implementation or benefit.This study aimed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS.This was a randomized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS, age 18-40 y and body mass index 27-42 kg/m(2).Women were randomly assigned to receive either 16 weeks of 1) continuous oral contraceptive pills (OCPs) (ethinyl estradiol 20 mcg/1 mg norethindrone acetate) ("OCP"); 2) lifestyle modification consisting of caloric restriction with meal replacements, weight loss medication (either sibutramine, or orlistat), and increased physical activity to promote a 7% weight loss ("Lifestyle"); or 3) combined treatment with both OCP and lifestyle modification ("Combined"). After preconception intervention, women underwent standardized ovulation induction with clomiphene citrate and timed intercourse for four cycles. Pregnancies were followed with trimester visits until delivery.Weight, ovulation, and live birth were measured.We consented 216 and randomly assigned 149 women (Lifestyle: n = 50; OCP: n = 49; Combined: n = 50). We achieved significant weight loss with both Lifestyle (mean weight loss, -6.2%; 95% confidence interval (CI), -7.4--5.0; and Combined (mean weight loss, -6.4%; 95% CI, -7.6--5.2) compared with baseline and OCP (both P < .001). There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP (odds ratio [OR, 2.47; 95% CI, 1.42-4.27) whereas no change in metabolic syndrome was detected in the Lifestyle (OR, 1.18; 95% CI, 0.63-2.19) or Combined (OR, 0.72; 95% CI, 0.44-1.17) groups. Cumulative ovulation rates were superior after weight loss: OCP, 46%; Lifestyle, 60%; and Combined, 67% (P < .05). Live birth rates were OCP, 12%; Lifestyle, 26%; and Combined, 24% (P = .13).A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and, compared with oral contraceptive pretreatment, leads to higher ovulation rates.
| S-EPMC4702450 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and hyperandrogenism; it is also associated with increased cardiovascular risks such as adverse lipid profile and endothelial dysfunction. Metformin and, more recently, statins have been shown to improve endocrine and metabolic aspects of PCOS.The aim of the study was to compare effects of simvastatin and metformin on PCOS.In a prospective trial, women with PCOS (n = 136) were randomized to simvastatin (S), metformin (M), or simvastatin plus metformin (SM) groups. Evaluations were performed at baseline and after 3 months.The study was conducted at an academic medical center.The change of serum total testosterone was measured.The study was completed by 113 subjects. Total testosterone decreased significantly and comparably in all groups: by 17.1, 13.6, and 15.1%, respectively, in the S, M, and SM groups. Significant decreases were also observed in all groups with respect to body mass index, C-reactive protein, and soluble vascular cell adhesion molecule-1. DHEAS declined significantly only in the S group. None of the treatments were associated with significant changes in LH or FSH. Total cholesterol and low-density lipoprotein cholesterol significantly declined only in S and SM groups.Simvastatin treatment was superior to metformin alone, whereas a combination of simvastatin and metformin was not significantly superior to simvastatin alone.
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Project description:The aim of this study was to investigate the effects of yoga exercises on anthropometric parameter and clinical sign of PCOS among women undergoing infertility treatment. This clinical trial study was performed on 61 women with PCOS who have undergone infertility treatment at Sarem Hospital in Tehran, Iran. The patients were first selecting based on purposeful and then randomly assigning to the intervention and control groups. In the intervention group, yoga exercises were performed for 6 weeks and the patients in the control group only received routine care. Anthropometric parameters and clinical signs were performed and recorded. After the intervention, here was a significant reduction in hirsutism, abdominal circumference, and hip circumference scores in the intervention group compared to the control group (P < 0.05). Given the effects of yoga exercises on the improvement of hirsutism, abdominal circumference, and hip circumference, it is suggested to use yoga as a treatment strategy in women with PCOS.
| S-EPMC8213483 | biostudies-literature
Project description:ObjectiveTo summarize baseline characteristics from a large multicenter infertility clinical trial.DesignCross-sectional baseline data from a double-blind randomized trial of two treatment regimens (letrozole vs. clomiphene).SettingAcademic Health Centers throughout the United States.Patient(s)Seven hundred fifty women with polycystic ovary syndrome (PCOS) and their male partners took part in the study.Intervention(s)None.Main outcome measure(s)Historic, biometric, biochemical, and questionnaire parameters.Result(s)Females averaged 30 years and were obese (body mass index [BMI] 35) with ∼20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). Most of the women had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH-to-FSH ratio (∼2), and antimüllerian hormone levels (8.0 ng/mL). In addition, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH-to-FSH levels, antimüllerian hormone levels, and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Men were obese (BMI 30) and had normal mean semen parameters.Conclusion(s)The treatment groups were well matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators.Clinical trial registration numberNCT00719186.
| S-EPMC3899700 | biostudies-literature
Project description:ContextPolycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder characterized by hyperandrogenism, is the leading cause of anovulatory infertility.ObjectiveThis proof-of-concept study evaluated clinical efficacy and safety of the neurokinin 3 (NK3) receptor antagonist fezolinetant in PCOS.MethodsThis was a phase 2a, randomized, double-blind, placebo-controlled, multicenter study (EudraCT 2014-004409-34). The study was conducted at 5 European clinical centers. Women with PCOS participated in the study. Interventions included fezolinetant 60 or 180 mg/day or placebo for 12 weeks. The primary efficacy end point was change in total testosterone. Gonadotropins, ovarian hormones, safety and tolerability were also assessed.ResultsSeventy-three women were randomly assigned, and 64 participants completed the study. Adjusted mean (SE) changes in total testosterone from baseline to week 12 for fezolinetant 180 and 60 mg/day were -0.80 (0.13) and -0.39 (0.12) nmol/L vs -0.05 (0.10) nmol/L with placebo (P < .001 and P < .05, respectively). Adjusted mean (SE) changes from baseline in luteinizing hormone (LH) for fezolinetant 180 and 60 mg/d were -10.17 (1.28) and -8.21 (1.18) vs -3.16 (1.04) IU/L with placebo (P < .001 and P = .002); corresponding changes in follicle-stimulating hormone (FSH) were -1.46 (0.32) and -0.92 (0.30) vs -0.57 (0.26) IU/L (P = .03 and P = .38), underpinning a dose-dependent decrease in the LH-to-FSH ratio vs placebo (P < .001). Circulating levels of progesterone and estradiol did not change significantly vs placebo (P > .10). Fezolinetant was well tolerated.ConclusionFezolinetant had a sustained effect to suppress hyperandrogenism and reduce the LH-to-FSH ratio in women with PCOS.
| S-EPMC8372662 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by androgen excess and ovarian dysfunction and presents with increased cardiometabolic risk factors such as obesity, insulin resistance, and elevated blood pressure (BP). We previously reported that administration of dihydrotestosterone (DHT) to female rats elicits cardiometabolic derangements similar to those found in women with PCOS. In this study, we tested the hypothesis that the DHT-mediated cardiometabolic derangements observed in PCOS are long lasting despite DHT withdrawal. Four-week-old female Sprague Dawley rats were treated with DHT (7.5 mg/90 days) or placebo for 6 months. DHT was discontinued (ex-DHT), and rats were followed for 6 additional months. After 6 months of DHT withdrawal, food intake, body weight, fat and lean mass, fasting plasma insulin, leptin, and adiponectin were elevated in ex-DHT rats. BP remained significantly elevated, and enalapril, an angiotensin-converting enzyme (ACE) inhibitor, normalized BP in ex-DHT rats. Expression of components of the intrarenal renin-angiotensin system was increased in ex-DHT rats. The cardiometabolic features found in ex-DHT rats were associated with lower plasma androgen levels but increased expression of renal and adipose tissue androgen receptors. In summary, androgen-induced cardiometabolic effects persisted after DHT withdrawal in a PCOS experimental model. Activation of intrarenal renin-angiotensin system plays a major role in the androgen-mediated increase in BP in ex-DHT. Upregulation of the renal and adipose tissue androgen receptor may explain the long-lasting effects of androgens. In clinical scenarios characterized by hyperandrogenemia in women, prompt normalization of androgen levels may be necessary to prevent their long-lasting cardiometabolic effects.
| S-EPMC6065488 | biostudies-literature