Malin Nylander

Effect of Liraglutide on Ectopic Fat in Polycystic Ovary Syndrome: A Randomized Clinical Trial

Women with polycystic ovary syndrome (PCOS) were treated with the GLP‐1 receptor agonist liraglutide to investigate the effect on liver fat content, visceral adipose tissue (VAT) and the prevalence of nonalcoholic fatty liver disease (NAFLD). In a double‐blind, placebo‐controlled, randomized clinical trial 72 women with PCOS, with a BMIu2009>u200925u2009kg/m2 and/or insulin resistance, were treated with liraglutide or received placebo 1.8u2009mg/d (2:1) for 26u2009weeks. Liver fat content was assessed by 1 HMR spectroscopy, VAT by MRI, body composition by DXA, and glucose metabolism by oral glucose tolerance test. Compared with placebo, liraglutide treatment reduced body weight by 5.2u2009kg (5.6%), liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two‐thirds (all Pu2009<u2009.01). Sex‐hormone‐binding‐globulin (SHBG) levels increased by 19% (Pu2009=u2009.03), and free testosterone decreased by 19% (Pu2009=u2009.054). HbA1c, fasting glucose and leptin were reduced (all: Pu2009<u2009.05), whereas measures of insulin resistance, adiponectin and glucagon did not change. In conclusion, 26u2009weeks of liraglutide treatment in PCOS resulted in significant reductions in liver fat content, VAT and the prevalence of NAFLD.

The LIPT-Study: On Risk Markers of Vascular Thrombosis in Polycystic Ovary Syndrome. A Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Liraglutide

Overweight and insulin resistance (IR) are central pathogenic features of the Polycystic Ovary Syndrome (PCOS), and weight loss is the main treatment option. PCOS is also associated with signs of a chronic inflammation, activation of the coagulation system, defect endothelial function and increased arterial stiffness, all regarded as risk factors or markers for the development of cardiovascular disease. These factors are not taken into account in the definition of the syndrome, which is based on the 3 Rotterdam criteria. An uncertainty of the clinical risk of cardiovascular disease (CVD) in these relatively young women has led to many studies on surrogate markers of CVD in PCOS, including the search for new markers with additional information of the arteriosclerotic burden in PCOS. GLP-1 analogues, originally developed for the treatment of diabetes, induce weight loss also in non-diabetic people. We therefore questioned whether treatment with the GLP-1 analogue Liraglutide to women with PCOS in doses used for diabetes could induce weight loss and improve IR and through this action, or independently, improve markers of vascular thrombosis in women with PCOS. Thus, 70 overweight and/or insulin resistant PCOS women were planned treated for 26 weeks in a placebo controlled randomized trial with the following effect parameters to be evaluated: Changes in Thrombin generation time, Adrenomedullin, Atrial natriuretic peptide, body fat composition (DEXA), liver fat content (MRI), BMI, IR, sex hormones and ovarian morphology. The protocol and the background for the study are brought in this report.

Quantification of visceral adipose tissue in polycystic ovary syndrome: dual-energy X-ray absorptiometry versus magnetic resonance imaging:

Background Polycystic ovary syndrome (PCOS) is associated with frequent overweight and abdominal obesity. Quantifying visceral adipose tissue (VAT) in PCOS patients can be a tool to assess metabolic risk and monitor effects of treatment. The latest dual-energy X-ray absorptiometry (DXA) technology can measure VAT and subcutaneous adipose tissue (SAT) in a clinical setting. Purpose To compare DXA-measurements of VAT and SAT with the gold standard MRI in women with PCOS. Material and Methods A cross-sectional study of 67 overweight women with PCOS was performed. Measurements of VAT and SAT were performed by DXA in a 5-cm thick transverse slice at the L4/L5 level and by MRI in a 1-cm thick transverse slice at the L3 level. Results Mean (SD) DXA-VAT was 81 (34) cm3, DXA-SAT was 498 (118) cm3, MRI-VAT was 117 (48) cm3, and MRI-SAT was 408 (122) cm3. MRI and DXA measures of VAT (ru2009=u20090.82, Pu2009<u20090.001) and SAT (ru2009=u20090.92, Pu2009<u20090.001) correlated closely, and DXA-VAT was stronger correlated with MRI-VAT than BMI (ru2009=u20090.62, Pu2009<u20090.001) and waist circumference (ru2009=u20090.60, Pu2009<u20090.001). DXA-VAT coefficient of variance was 6.7% and inter correlation coefficient was 0.98. Bland–Altman analyses showed DXA to slightly underestimate VAT and SAT measurements compared with MRI. Conclusion DXA and MRI measurements of VAT and SAT correlated closely despite different size of region of interest, and DXA-VAT was superior to waist circumference and BMI in estimating MRI-VAT. DXA showed high reproducibility making it is suitable for repeated measurements in the same individual over time.

Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome: a randomized clinical trial

Polycystic ovary syndrome (PCOS) encompasses an ovarian and a metabolic dysfunction. Glucagon-like peptide-1 (GLP-1) analogues facilitate weight loss and ameliorate metabolic dysfunction in overweight women with PCOS, but their effect on ovarian dysfunction is scarcely reported. In a double-blind, randomized trial, 72 women with PCOS were allocated to intervention with the GLP-1 analogue liraglutide or placebo (1.8u2009mg/day), in a 2:1 ratio. At baseline and 26-week follow-up, bleeding pattern, levels of AMH, sex hormones and gonadotrophins were assessed and ovarian morphology evaluated. Liraglutide caused 5.2u2009kg (95% CI 3.0 to 7.5, P < 0.0001) weight loss compared with placebo. Bleeding ratio improved with liraglutide: 0.28 (95% CI 0.20 to 0.36, P < 0.001); placebo: 0.14 (95% CI 0.02 to 0.26, P < 0.05); between-group difference: 0.14 (95% CI 0.03 to 0.24, P < 0.05). In the liraglutide group, SHBG increased by 7.4u2009nmol/L (95% CI 4.1 to 10.7) and free testosterone decreased by 0.005u2009nmol/L (95% CI -0.009 to -0.001). Ovarian volume decreased by -1.6u2009ml (95% CI -3.3 to 0.1) with liraglutide versus placebo. Nausea and constipation were more prevalent in the liraglutide group. Liraglutide improved markers of ovarian function in overweight women with PCOS, and might be a possible intervention.

Ovarian morphology in polycystic ovary syndrome: estimates from 2D and 3D ultrasound and magnetic resonance imaging and their correlation to anti-Müllerian hormone:

Background Due to improved ultrasound scanners, new three-dimensional (3D) modalities, and novel Anti-Müllerian hormone (AMH)-assays, the ultrasound criteria for polycystic ovarian morphology are under debate and the appropriate thresholds are often requested. Purpose To quantify the differences in estimates of ovarian volume and antral follicle count (AFC) from two-dimensional (2D) and 3D transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). Material and Methods A cross-sectional study on 66 overweight women with polycystic ovary syndrome (PCOS) according to Rotterdam criteria. Ovarian volume and AFC were estimated from MRI, 2D TVUS, and 3D TVUS, and serum AMH levels were assessed. Bland–Altman statistics were used for comparison. Results Participants had a median age of 29 years (age range, 19–44 years) with a mean BMI of 32.7u2009kg/m2 (SD 4.5). Ovarian volume from 2D TVUS was 1.48u2009mL (95% confidence interval [CI], 0.94–2.03; Pu2009<u20090.001) and 1.25u2009mL (95% CI, 0.62–1.87; Pu2009<u20090.001) smaller than from 3D TVUS and MRI, respectively. AFC from 2D TVUS was 18% (95% CI, 13–23; Pu2009<u20090.005) and 16% (95% CI, 6–25; Pu2009<u20090.005) smaller than estimates from 3D TVUS and MRI, respectively. Correlations between AMH and AFC from 2D TVUS, 3D TVUS, and MRI were 0.67, 0.78, and 0.70, respectively (Pu2009<u20090.001 for all). Conclusion In an overweight PCOS population, 2D TVUS underestimated ovarian volume and AFC as compared with 3D TVUS and MRI. Serum AMH correlated best with AFC from 3D TVUS, followed by MRI and 2D TVUS. The advantage of 3D TVUS might be of minor clinical importance when diagnosing PCOS, but useful when the actual AFC are of interest, e.g. in fertility counseling and research.

The Integumentary System

The skin is a large organ covering the exterior of the human body. It consists of two distinct layers: an epithelial barrier, the epidermis, and a strong and elastic layer of connective tissue, the dermis. The skin is attached to underlying structures by the subcutaneous tissue, which contains various amounts of adipose tissue. Associated with the skin are “epidermal derivatives”: hair follicles, nails, and sweat and sebaceous glands.

The Digestive System II: The Associated Organs

The salivary glands, the liver, the gallbladder, and the pancreas constitute the accessory organs of the digestive system. These organs have exocrine secretion that chemical breakdown ingested food to facilitate digestion. Furthermore, the liver and pancreas have multiple other functions essential for homeostasis, e.g., the endocrine function of the pancreas that regulates blood glucoses’ level and the detoxification function of the liver.

The Respiratory System

The respiratory system consists of conductive airways, paired lungs, and a ventilation mechanism. The respiration mechanism, an exchange of gases between inhaled air and the blood of the pulmonary capillaries, takes place in the alveoli. Apart from gas exchange, the respiratory system also filters and temperates inhaled air and contributes to production of speech (larynx), to sense of smell (nasal cavities), and to maintenance of the pH homeostasis (bicarbonate buffer system of the blood).

The Urinary System

The paired kidneys, the urine bladder, and the urethra constitute the urinary system. The kidneys remove waste products from the body, conserve water, and reabsorb electrolytes and metabolic substances. Furthermore, they are essential for maintenance of the pH homeostasis, the blood pressure, and the volume and composition of the extracellular fluid. The urine is transported from the kidneys to the urinary bladder via the paired ureters, and after storage in the urinary bladder, the urine is discharged via the urethra.

The Male Reproductive System

The male reproductive system consists of external reproductive organs, penis and scrotum, and internal reproductive organs: testes, a duct system, and accessory glands. The adult, paired testes produce both male sex hormones (androgens) and sperm cells (spermatogenesis). Androgens, primarily testosterone, are necessary for development and maintenance of male behavioral and physical manifestations and for spermatogenesis.