orlistat and Hyperandrogenism

Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles.

Topics: Adipokines; Bariatric Surgery; Combined Modality Therapy; Comorbidity; Diet, Reducing; Exercise Therapy; Female; Glucagon-Like Peptide 1; Gonadal Steroid Hormones; Humans; Hyperandrogenism; Inflammation; Insulin Resistance; Lactones; Life Style; Metformin; Models, Biological; Motivation; Obesity; Obesity, Abdominal; Orlistat; Polycystic Ovary Syndrome; Prevalence; Sympathetic Nervous System; Weight Loss

The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum anti-Müllerian hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

Topics: Adult; Anti-Mullerian Hormone; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Exercise; Female; Humans; Hyperandrogenism; Insulin Resistance; Lactones; Luteinizing Hormone; Obesity; Orlistat; Overweight; Polycystic Ovary Syndrome; Testosterone; Up-Regulation; Weight Loss; Young Adult

Mean insulin resistance (IR) is greater and it is also more variable in overweight women with polycystic ovarian syndrome (PCOS) compared to weight matched controls. Whilst treatment will reduce the mean IR, it is not known if the IR variability is also reduced.. To compare the change in IR and its variability before and after treatment with insulin sensitization through metformin and pioglitazone, compared to that induced by weight loss with orlistat.. Randomized, open labelled parallel study.. Endocrinology outpatient clinic at a referral centre.. Thirty obese PCOS patients [BMI 36.0 +/- 1.2 kg/m(2) (mean +/- SEM)] participated in the study.. The change in biological variability (BV) was assessed by measuring IR (homeostasis model assessment method) at 4-day intervals on 10 consecutive occasions before and 12 weeks after randomization to metformin, pioglitazone or orlistat.. The primary end point of the study was a change in BV of IR.. Treatment with pioglitazone, orlistat and metformin reduced the overall IR by 41.0 +/- 4.1%, 19.7 +/- 6.4% and 16.1 +/- 6.8% (P = 0.005, P = 0.013, P = 0.17, respectively) and IR variability by 28.5 +/- 18.0%, 41.8 +/- 11.6% and 23.7 +/- 17.0 (P = 0.20, P = 0.015 and P = 0.28, respectively). Free androgen index reduced significantly with all treatments.. Only orlistat reduced both IR and its variability significantly, though all three drugs were effective in reducing hyperandrogenism within the 12-week period of the study.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Female; Humans; Hyperandrogenism; Hypoglycemic Agents; Insulin; Insulin Resistance; Lactones; Metformin; Orlistat; Pioglitazone; Polycystic Ovary Syndrome; Thiazolidinediones; Treatment Outcome

To assess the effects of weight loss on serum adipokine levels in polycystic ovary syndrome (PCOS).. We determined serum leptin, adiponectin, resistin, and visfatin levels in 60 overweight/obese women with PCOS and 48 BMI-matched female volunteers. Measurements were repeated after 24 weeks of treatment with orlistat 120 mg 3 times per day along with an energy-restricted diet.. At baseline, serum visfatin concentration was higher in patients with PCOS than in controls (p = 0.036); serum levels of leptin, adiponectin, and resistin did not differ between the two groups. After 24 weeks, a significant reduction in BMI and waist circumference was observed in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). Also serum leptin levels decreased in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). The reduction in serum leptin levels did not differ between groups. Serum adiponectin, resistin, and visfatin levels did not change in either group.. Leptin, adiponectin, and resistin do not appear to play major pathogenetic roles in overweight/obese patients with PCOS. In contrast, visfatin emerges as a potentially important mediator of the endocrine abnormalities of these patients. However, serum visfatin levels are not substantially affected by weight loss.

Topics: Adipokines; Adiponectin; Adult; Anti-Obesity Agents; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hyperandrogenism; Insulin Resistance; Lactones; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Orlistat; Polycystic Ovary Syndrome; Resistin; Waist Circumference; Weight Loss; Young Adult