leuprolide and Metabolic-Syndrome

In a mouse model, degarelix generated the least metabolic consequences via low follicle-stimulating hormone (FSH) levels compared with orchiectomy and leuprolide after 4 months of androgen deprivation therapy (ADT). Here, we comparatively investigated the influence of ADT with degarelix or leuprolide on the development of metabolic syndrome in patients with prostate cancer (PCa).. Patients with hormone-naive PCa were recruited. Eligible patients were randomized (1:1) to monthly degarelix or monthly leuprolide for 6 months. Key trial variables were monitored monthly. The primary endpoint was changes in fasting blood sugar (FBS). Secondary endpoints were changes in body weight, abdominal circumference, lipid profiles, and hemoglobin A1c (HbA1c) and FSH levels. Computed tomography was performed to measure subcutaneous and visceral fat areas before and after 6 months of ADT. Data were analyzed using the χ. From the 100 patients registered, 85 completed the trial (degarelix: 40 patients; leuprolide: 45 patients). Mean increases in FBS did not differ between the two arms. Similarly, there were no differences between the arms in mean increases in body weight, abdominal circumference, lipid profiles, HbA1c, or subcutaneous and visceral fat areas. Follicle-stimulating hormone levels were significantly lower in the degarelix arm than in the leuprolide arm (p < 0.05).. Lipid and glucose metabolism did not differ significantly between the arms, while FSH levels were significantly lower in the degarelix arm.

Topics: Aged; Aged, 80 and over; Anilides; Antineoplastic Combined Chemotherapy Protocols; Humans; Leuprolide; Male; Metabolic Syndrome; Middle Aged; Nitriles; Oligopeptides; Prospective Studies; Prostatic Neoplasms; Tosyl Compounds

Unlike in other mouse models of atherogenesis, it has recently been suggested that orchiectomy plays a role in accelerating atherosclerosis and inhibiting the progression of cardiovascular disease in the ApoE. Male ApoE. Castration was achieved for all three modes of ADT. However, degarelix-treated mice gained significantly less weight, had lower serum leptin levels and systolic blood pressure compared to orchiectomy and leuprolide-treated mice. ADT improved dysglycemia and atherosclerotic burden. GnRH-antagonist significantly improved survival compared to GnRH-agonist but not compared to orchiectomy.. Further characterization of the ApoE

Topics: Androgen Antagonists; Animals; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Disease Models, Animal; Hyperglycemia; Insulin; Leuprolide; Male; Metabolic Syndrome; Mice; Mice, Knockout, ApoE; Oligopeptides; Orchiectomy; Protective Factors

Inducing testosterone deficiency, as the standard treatment of prostate cancer, may cause metabolic disorders including insulin resistance, dyslipidemia, central obesity, cardiovascular diseases, and type 2 diabetes. This study measured responses to testosterone deficiency in high-carbohydrate, high-fat (H) diet-fed rats. We then tested whether eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) ethyl esters (Omacor) reversed these metabolic changes. Male Wistar rats (8⁻9 weeks old) were divided into eight groups with four groups fed corn starch and four groups fed H diet. For each diet, one group received diet only; one group was orchidectomized; one group was given leuprolide (gonadotrophin-releasing hormone agonist, 2 mg/kg every 4th week); and the last group was treated with leuprolide and their diet was supplemented with 3% Omacor for the last eight weeks. The protocol was for 16 weeks. Leuprolide worsened metabolic syndrome symptoms and cardiovascular function, and orchidectomy produced greater responses. In H fed leuprolide-treated rats, Omacor decreased systolic blood pressure and left ventricular diastolic stiffness, reduced infiltration of inflammatory cells and collagen deposition in the heart, and reduced lipid accumulation and inflammatory cell infiltration without improving liver damage. These results suggest that Omacor has potential to attenuate metabolic complications in prostate cancer patients with induced testosterone deprivation.

Topics: Animals; Antineoplastic Agents, Hormonal; Blood Pressure; Diet, Carbohydrate Loading; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Humans; Leuprolide; Liver; Male; Metabolic Syndrome; Prostatic Neoplasms; Rats; Rats, Wistar; Testosterone

Observational studies relate androgen deprivation therapy (ADT) to metabolic syndrome (MS) and cardiovascular disease, an association potentially subject to uncontrollable confounding factors, especially diet and genetic/metabolic risk factors. In the absence of prospective randomized clinical trials, causality remains unproven. We comparatively investigated the effects of different ADT modalities on the development of MS and atherosclerosis in a mouse model.. Low-density lipoprotein receptor knockout mice underwent orchiectomy plus vehicle (2.5% mannitol), sham surgery plus vehicle (control), sham surgery plus gonadotropin-releasing hormone (GnRH) antagonist (degarelix), or sham surgery plus GnRH agonist (leuprolide) (n = 9-13/group) and were followed for 4 months. Visceral fat accumulation, lean body mass, adipocyte size, fasting blood glucose, glucose tolerance, serum levels of leptin, follicle-stimulating hormone, luteinizing hormone, and testosterone, along with atherosclerotic plaque size and characteristics were measured.. All 3 modes of ADT decreased circulating testosterone levels in mice, although leuprolide treatment reached nadir levels of testosterone later. Orchiectomized and leuprolide-treated mice gained significantly more visceral fat compared with degarelix-treated mice. Improved glucose tolerance tests were recorded in degarelix-treated mice. The aortic atherosclerotic plaque area in leuprolide-treated and orchiectomized mice was larger than in control mice (P<0.005 and P = 0.002, respectively), but it was not significantly different from control in degarelix-treated mice. The necrotic core area in degarelix-treated mice was smaller compared with leuprolide-treated and orchiectomized mice (P = 0.011 and P = 0.002, respectively).. Our results suggest that ADT induced MS and atherosclerosis in a preclinical mouse model to a mode-specific extent. GnRH antagonist generated the least atherosclerosis and characteristics of MS compared with orchiectomy and GnRH agonist.

Topics: Adipose Tissue; Adiposity; Androgen Antagonists; Animals; Antineoplastic Agents, Hormonal; Atherosclerosis; Disease Models, Animal; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Metabolic Syndrome; Mice; Mice, Knockout; Oligopeptides; Orchiectomy; Random Allocation; Receptors, LDL

In men with prostate cancer, gonadotropin-releasing hormone (GnRH) agonists increase fat mass, decrease insulin sensitivity, and increase triglycerides, features that are shared with metabolic syndrome. To the authors' knowledge, however, less is known regarding the effects of GnRH agonists on other attributes of the metabolic syndrome.. In an open-label prospective study, 26 men with recurrent or locally advanced prostate cancer were treated with leuprolide for 12 months. Outcomes included changes in blood pressure, body composition, lipids, adipocytokines, and C-reactive protein.. The mean weight, body mass index, and waist circumference increased significantly from baseline to Month 12 (P < .001 for each comparison). Fat mass increased by 11.2% +/- 1.5% (P < .001) and the percentage lean body mass decreased by 3.6% +/- 0.5% (P < .001). The total abdominal fat area increased by 16.5% +/- 2.6% (P < .001), with the accumulation of subcutaneous fat accounting for 94% of the observed increase. The waist-to-hip ratio and blood pressure did not change significantly. Serum high-density lipoprotein (HDL) cholesterol concentrations increased significantly (P = .002). Serum adiponectin levels increased by 36.4 +/- 5.9% from baseline to Month 3 and remained significantly elevated through Month 12 (P < .001). Resistin and C-reactive protein levels did not change significantly.. The term metabolic syndrome does not appear to adequately describe the effects of GnRH agonists in men with prostate cancer. In contrast to the metabolic syndrome, GnRH agonists increase subcutaneous fat mass, HDL cholesterol, and adiponectin, and do not alter the waist-to-hip ratio, blood pressure, or C-reactive protein level.

Topics: Adiponectin; Aged; Antineoplastic Agents, Hormonal; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Gonadotropin-Releasing Hormone; Humans; Insulin Resistance; Leuprolide; Lipids; Male; Metabolic Syndrome; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Syndrome

Topics: Adiponectin; Adipose Tissue; Antineoplastic Agents, Hormonal; Body Mass Index; Body Weight; Cholesterol, HDL; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Metabolic Syndrome; Prostatic Neoplasms