goserelin and Insulin-Resistance

Prostate cancer patients at increased risk for relapse after prostatectomy were treated in a neoadjuvant study with androgen deprivation therapy (ADT) in combination with cixutumumab, an inhibitory fully human monoclonal antibody against IGF receptor 1 (IGF-IR).. A clinical trial with prospective collection of serum and tissue was designed to test the potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin components to IGF-IR blockade was also examined.. Eligibility for the trial required the presence of high-risk prostate adenocarcinoma. Treatment consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before prostatectomy. Here we report on an analysis of serum samples from 29 enrolled patients. Changes in IGF and glucose homeostasis pathways were compared to control samples from patients in a concurrent clinical trial of neoadjuvant ADT alone.. Significant increases were seen in GH (P = .001), IGF-I (P < .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone. IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P = .001). No significant changes in blood glucose were evident. Patients with BMIs in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5) levels compared to overweight and obese patients.. Patients with IGF-IR blockade in combination with ADT demonstrated significant changes in IGF and glucose homeostasis pathway factors compared to patients receiving ADT alone. In the patients receiving combination therapy, patients with normal BMI had serum levels of glucose homeostasis components similar to individuals in the ADT-alone cohort, whereas patients with overweight and obese BMIs had serum levels that differed from the ADT cohort.

Topics: Adenocarcinoma; Androgen Antagonists; Anilides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Cohort Studies; Goserelin; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Male; Neoadjuvant Therapy; Nitriles; Obesity; Prostatectomy; Prostatic Neoplasms; Receptor, IGF Type 1; Risk; Secondary Prevention; Somatomedins; Tosyl Compounds; United States

Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine men undergoing ADT for prostate cancer and ten healthy men with normal testosterone levels underwent 12 weeks of endurance training. Primary endpoints were insulin sensitivity (euglycemic-hyperinsulinemic clamps with concomitant glucose-tracer infusion) and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (P<0.0001). The patients and controls demonstrated an increase in peripheral tissue insulin sensitivity of 14 and 11% respectively (P<0.05), with no effect on hepatic insulin sensitivity (P=0.32). Muscle protein content of GLUT4 (SLC2A4) and total AKT (AKT1) was also increased in response to the training (P<0.05 and P<0.01 respectively). Body weight (P<0.0001) and whole-body fat mass (FM) (P<0.01) were reduced, while lean body mass (P=0.99) was unchanged. Additionally, reductions were observed in abdominal (P<0.01), subcutaneous (P<0.05), and visceral (P<0.01) FM amounts. The concentrations of plasma markers of systemic inflammation were unchanged in response to the training. No group × time interactions were observed, except for thigh intermuscular adipose tissue (IMAT) (P=0.01), reflecting a significant reduction in the amount of IMAT in the controls (P<0.05) not observed in the patients (P=0.64). In response to endurance training, ADT-treated prostate cancer patients exhibited improved insulin sensitivity and body composition to a similar degree as eugonadal men.

Topics: Aged; Antineoplastic Agents, Hormonal; Blood Glucose; Body Composition; Cholesterol, HDL; Exercise Therapy; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin Resistance; Male; Middle Aged; Physical Endurance; Prostatic Neoplasms; Testosterone

Thirty-two women with polycystic ovary syndrome (PCOS) were allocated to two antiandrogen treatment regimens; 28 women completed the trial. Twenty women were treated with ethinyloestradiol and cyproterone acetate (EO-CA) cyclically for 6 months and eight women were treated with the gonadotrophin releasing hormone (GnRH) analogue, goserelin for 6 months. Effects on hirsutism, insulin sensitivity (estimated by glucose clamp technique), blood lipids and hormones were measured. Women treated with EO-CA showed a reduction in hirsutism (P <0.05), and decreased serum androgen concentrations (P <0.001) as well as reduced insulin sensitivity (P <0.05). In women treated with goserelin, serum androgen concentrations also decreased (P <0.001), but there was no significant reduction of hirsutism. This group, however, showed an improved insulin sensitivity (P <0.05) despite an unchanged body mass index. Bone mineral density was unaltered in both treatment groups. The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se. In contrast, the reduction in androgen concentrations by goserelin was accompanied by an improved insulin sensitivity.

Topics: Adult; Androgen Antagonists; Androgens; Cyproterone Acetate; Estradiol Congeners; Ethinyl Estradiol; Female; Goserelin; Hirsutism; Humans; Insulin Resistance; Lipids; Polycystic Ovary Syndrome

To investigate acceptability of and preferences for physical activity participation in men receiving androgen-deprivation therapy (ADT) for prostate cancer, to identify influencing clinical and demographic factors, and to determine the percentage meeting national exercise guidelines.. Cross-sectional, descriptive.. Ambulatory care clinic of a large medical center.. 135 men receiving ADT.. A structured interview with a systematic procedure was used to elicit preferences for physical activity.. Exercise preferences and acceptability; evidence-based exercise intervention.. Participants expressed high levels of acceptability of and willingness to participate in aerobic (64% and 79%) and muscle-strengthening (79% and 81%) programs. Preferences were expressed for muscle-strengthening activities performed at home, either alone or in the company of a family member. Flexible, spontaneous, and self-paced programs were preferred. Significant associations were identified for distance, age, obesity, duration of ADT, and meeting American College of Sports Medicine (ACSM) and American Heart Association (AHA) guidelines. Nineteen percent of the study population met the guidelines for weekly physical activity.. High levels of expressed acceptance of and willingness to participate in physical activity programs as well as the small number of participants meeting ACSM and AHA guidelines suggest feasibility of and support the need for the development of exercise programs in this population.. Incorporating patient preferences and evidence-based practice is integral to providing high-quality patient-centered care and is the foundation for appropriate intervention programs. Insight from this study will facilitate the design of programs that better reflect actual preferences of prostate cancer survivors.. ADT-induced changes in body composition are believed to contribute to a reduction in insulin sensitivity and dyslipidemia that contribute to increased cardiovascular risk profile. Exercise has the potential to mitigate the harmful effects of ADT.

Topics: Adenocarcinoma; Aged; Androgens; Antineoplastic Agents, Hormonal; Bone Density; Cross-Sectional Studies; Exercise; Feasibility Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin Resistance; Male; Middle Aged; Muscle Strength; Neoplasms, Hormone-Dependent; Patient Acceptance of Health Care; Patient Preference; Practice Guidelines as Topic; Prostatic Neoplasms; Resistance Training; Socioeconomic Factors

Androgens are suggested to interact with leptin production and with insulin sensitivity in both polycystic ovary syndrome (PCOS) and obesity. The aim of the study was to follow these interactions along with two forms of antiandrogen treatment. Twenty women with PCOS were treated with ethinylestradiol and high dose of cyproteroneacetate (EE-CA) and 8 with the gonadotrophin-releasing hormone (GnRH) analogue goserelin for 6 months. The patients were divided into a low and a high body weight group and compared with a group of overweight women without PCOS. Both treatments resulted in a significant reduction of free testosterone but the concentration of leptin remained unchanged. EECA treatment resulted in deterioration and GnRH in improvement of insulin sensitivity. Serum leptin correlated only with body weight and body fat. It is concluded that leptin levels do not adequately reflect changes in insulin sensitivity or androgen levels after short-term antiandrogen or antigonadotropin treatment.

Topics: Adipose Tissue; Adult; Androgen Antagonists; Apolipoproteins A; Apolipoproteins B; Blood Glucose; Body Composition; Body Constitution; Body Mass Index; Body Weight; C-Peptide; Cyproterone Acetate; Dehydroepiandrosterone Sulfate; Ethinyl Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin; Insulin Resistance; Leptin; Lipoprotein(a); Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Triglycerides