0
selected
-
1.
Reduced circulating levels of chemokine CXCL14 in adolescent girls with polycystic ovary syndrome: normalization after insulin sensitization.
García-Beltran, C, Cereijo, R, Quesada-López, T, Malpique, R, López-Bermejo, A, de Zegher, F, Ibáñez, L, Villarroya, F
BMJ open diabetes research & care. 2020;(1)
Abstract
OBJECTIVE CXCL14 (C-X-C motif chemokine ligand-14) is a chemokine released by active brown fat, showing protective effects against insulin resistance in experimental models. Polycystic ovary syndrome (PCOS) in adolescent girls is usually related to hepato-visceral fat excess and insulin resistance, and associates with comorbidities such as type 2 diabetes. Treatment with a low-dose combination of one antiandrogen and antimineralocorticoid drug (spironolactone) and two insulin sensitizers (pioglitazone/metformin) (SPIOMET) is particularly effective in improving these metabolic derangements. Adipose tissue may be involved in the metabolic alterations of PCOS, and it is a likely target of therapeutic action. We investigated the alterations in CXCL14 levels and the effects of drugs composing SPIOMET treatment on CXCL14 in human adipocytes. RESEARCH DESIGN AND METHODS We studied 51 adolescent patients with PCOS and 21 age-matched healthy controls. Thirty-one adolescent patients with PCOS under SPIOMET or oral contraception-based treatment were also studied. For studies in vitro, Simpson Golabi Behmel Syndrome (SGBS) adipose cells were used. Gene expression for CXCL14 and other genes was quantified using quantitative real-time PCR. The levels of CXCL14 and adipokines in serum and cell culture media were determined by ELISA. RESULTS Serum CXCL14 levels are reduced in patients with PCOS. One-year SPIOMET treatment normalized CXCL14 concentrations and improved the metabolic status of patients with PCOS. Pioglitazone induced CXCL14 expression in differentiating human SGBS adipocytes, in parallel with the induction of marker genes of brown adipogenesis. Spironolactone induced CXCL14 expression and release in differentiated human adipocytes. CONCLUSION Insulin sensitization with SPIOMET normalizes the abnormally low levels of CXCL14 in girls with PCOS. This is consistent with the effects of pioglitazone and spironolactone inducing CXCL14 expression and promoting a brown-like phenotype in adipocytes. CXCL14 may be a novel biomarker for PCOS as well as a potential mediator of the beneficial effects of the SPIOMET combination and may hold promise as a therapeutic modulator of the disorder. TRIAL REGISTRATION NUMBERS ISRCTN29234515 and ISCRCTN11062950.
-
2.
Obesity-Related Heart Failure With a Preserved Ejection Fraction: The Mechanistic Rationale for Combining Inhibitors of Aldosterone, Neprilysin, and Sodium-Glucose Cotransporter-2.
Packer, M, Kitzman, DW
JACC. Heart failure. 2018;(8):633-639
Abstract
Obesity-related heart failure with a preserved ejection fraction (HFpEF) is an important phenotype prevalent in the community, especially in people with metabolic disorders (e.g., dyslipidemia, diabetes). These individuals exhibit a marked expansion of plasma volume, but ventricular distensibility is limited, most likely as a result of cardiac microvascular rarefaction acting in concert with myocardial and pericardial fibrosis. Consequently, the increase in plasma volume causes a disproportionate increase in cardiac filling pressures, leading to heart failure, even though systolic ejection is not impaired. The features of this syndrome appear to be related (in part) to the overproduction of adipocyte-derived cell-signaling molecules, including aldosterone and neprilysin. The resulting sodium retention and plasma volume expansion is exacerbated by their mutual actions to promote cardiac and systemic inflammation and fibrosis. Inhibitors of aldosterone, neprilysin, and the sodium-glucose transporter-2 (SGLT2) can ameliorate the plasma volume expansion and pro-inflammatory and profibrotic pathways, potentially opposing the action of diverse adipocytokines. All 3 classes of drugs can reduce the quantity of visceral adipose tissue and ameliorate its abnormal biological properties. This mechanistic framework is supported by the results of large-scale randomized trials with mineralocorticoid receptor antagonists and SGLT2 inhibitors and is being further tested in an ongoing large-scale trial of neprilysin inhibition. The promise of using mineralocorticoid receptor antagonists, neprilysin inhibitors, and SGLT2 inhibitors (alone or in combination) in the management of obesity-related HFpEF suggests that physicians might finally have a phenotype of HFpEF that they can understand and treat.
-
3.
A comparative systematic review of Yasmin (drospirenone pill) versus standard treatment options for symptoms of polycystic ovary syndrome.
Li, J, Ren, J, Sun, W
European journal of obstetrics, gynecology, and reproductive biology. 2017;:13-21
Abstract
OBJECTIVES To systematically review the impact of Yasmin (drospirenone pill) compares with other standard treatments for symptoms of Polycystic Ovary Syndrome (PCOS). STUDY DESIGN The relevant studies of the randomized controlled trials in women with PCOS treated with drospirenone were retrieved and the systematic evaluation was conducted. RESULTS Eighteen articles were included. Compared with drospirenone (DRSP) monotherapy, DRSP plus metformin was better in reducing body mass index (BMI), luteinizing hormone (LH) and low-density lipoprotein cholesterol (LDL-C). Compared with metformin, DRSP was better in modulating serum total testosterone (T), sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH) and free androgen index (FAI), while metformin was more effective in reducing BMI, total cholesterol (TC), LDL-C and Triglyceride (TG). DRSP was superior to cyproterone acetate (CPA) in reducing TC and homeostasis model assessment of insulin resistance (HOMA-IR). DRSP shows better effect in modulating LDL-C and high-density lipoprotein cholesterol (HDL-C) compared with desogestrel (DSG). CONCLUSIONS The available data suggested that DRSP was effective in modulating hormones, insulin and lipid metabolism in women with PCOS. Compared with commonly used drugs for symptoms of PCOS as CPA and DSG, DRSP shows identical or better effect in improving symptoms and protect cardiovascular system. For the PCOS patients with IR, obesity or high LH/FSH ratio, DRSP combines with metformin maybe more effective than use DRSP alone.
-
4.
The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome.
Vieira, CS, Martins, WP, Fernandes, JB, Soares, GM, dos Reis, RM, de Sá, MF, Ferriani, RA
Contraception. 2012;(3):268-75
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with metabolic dysfunction and changes in cardiovascular risk markers, and using oral contraceptives (OCs) may exert a further negative effect on these alterations in patients with PCOS. Thus, the primary objective of this study was to assess the effects on arterial function and structure of an OC containing chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined with spironolactone (OC+SPL), in patients with PCOS. STUDY DESIGN This was a randomized, controlled clinical trial. Fifty women with PCOS between 18 and 35 years of age were randomized by a computer program to use OC or OC+SPL. Brachial artery flow-mediated vasodilation, carotid intima-media thickness and the carotid artery stiffness index were evaluated at baseline and after 6 and 12 months. Serum markers for cardiovascular disease were also analyzed. The intragroup data were analyzed using analysis of variance with Tukey's post hoc test. A multivariate linear regression model was used to analyze the intergroup data. RESULTS At 12 months, the increase in mean total cholesterol levels was greater in the OC+SPL group than in the OC group (27% vs. 13%, respectively; p=.02). The increase in mean sex hormone-binding globulin levels was greater in the OC group than in the OC+SPL group (424% vs. 364%, respectively; p=.01). No statistically significant differences between the groups were found for any of the other variables. CONCLUSION The addition of spironolactone to an OC containing chlormadinone acetate and ethinylestradiol conferred no cardiovascular risk-marker advantages in young women with PCOS.
-
5.
Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors.
Tfayli, H, Ulnach, JW, Lee, S, Sutton-Tyrrell, K, Arslanian, S
The Journal of clinical endocrinology and metabolism. 2011;(5):1311-9
-
-
Free full text
-
Abstract
CONTEXT Adolescents with polycystic ovary syndrome (PCOS) have insulin resistance and higher rates of the metabolic syndrome. OBJECTIVE Our objective was to compare the effects of 6 months treatment with drospirenone/ethinyl estradiol (EE) (3 mg/30 μg) vs. rosiglitazone (4 mg) daily on the hormonal and cardiometabolic profiles of overweight/obese adolescents with PCOS. DESIGN We conducted a randomized, double-blinded, parallel clinical trial in an academic hospital, with n = 46 patients. OUTCOME MEASURES The primary outcome measure was insulin sensitivity, hepatic with [6,6-(2)H(2)]glucose and peripheral with a 3-h hyperinsulinemic-euglycemic clamp. Other outcome measures included plasma androgen profile and response to ACTH stimulation, glucose and insulin response to oral glucose tolerance test, insulin secretion with a 2-h hyperglycemic clamp, fasting lipid profile, inflammatory markers, intima media thickness, aortic pulse wave velocity, body composition by dual-energy x-ray absorptiometry, and abdominal adiposity by computed tomography scan. RESULTS Drospirenone/EE resulted in greater reductions in androgenemia. Neither treatment led to change in weight or body mass index, but rosiglitazone led to a significant decrease in visceral adiposity. Compared with drospirenone/EE, treatment with rosiglitazone improved hepatic and peripheral insulin sensitivity and lowered fasting and stimulated insulin levels during the oral glucose tolerance test. Treatment with drospirenone/EE was associated with elevations in total cholesterol, high-sensitivity C-reactive protein and leptin concentrations, whereas treatment with rosiglitazone led to lower triglycerides and higher adiponectin concentrations. Neither treatment affected intima media thickness or pulse wave velocity. CONCLUSIONS In overweight/obese adolescents with PCOS, 6 months treatment with rosiglitazone was superior to drospirenone/EE in improving the cardiometabolic risk profile, and effective but inferior in attenuating hyperandrogenemia. Additional studies are needed to test insulin sensitizers in the treatment of the reproductive and cardiometabolic aspects of PCOS.
-
6.
Drospirenone for the treatment of hirsute women with polycystic ovary syndrome: a clinical, endocrinological, metabolic pilot study.
Guido, M, Romualdi, D, Giuliani, M, Suriano, R, Selvaggi, L, Apa, R, Lanzone, A
The Journal of clinical endocrinology and metabolism. 2004;(6):2817-23
Abstract
The aim of this study was to investigate the effects of the new estro-progestinic containing the antimineralcorticoid progestogen drospirenone (DRSP) in women with polycystic ovary syndrome (PCOS). Fifteen hirsute PCOS patients were treated with 30 microg ethinyl estradiol plus 3 mg DRSP for 12 cycles. Ultrasonographic pelvic exams, evaluation of hirsutism scores, and hormonal and lipid profile assays were performed at baseline and after three, six, and 12 cycles of treatment. An oral glucose tolerance test and euglycemic hyperinsulinemic clamp were also performed, except at the third cycle. The treatment was well tolerated, and all women attained satisfactory cycle control. Hirsutism significantly improved from the sixth cycle onward. Body weight and fat distribution as well as blood pressure remained stable throughout the treatment. Plasma levels of LH, testosterone, SHBG, and, consequently, the free androgen index significantly fell from the third cycle on. Dehydroepiandrosterone sulfate and 17-hydroxyprogesterone significantly decreased after six cycles. The treatment did not affect glycoinsulinemic homeostasis. A trend toward an increase was seen for total cholesterol, triglycerides, and high- and low-density lipoproteins (HDL and LDL) plasma concentrations, although all parameters remained within the normal range. No modifications in total cholesterol/HDL and HDL/LDL ratios were induced by the therapy. The ethinyl estradiol/DRSP combination seems to be effective in ameliorating clinical and hormonal features of PCOS.