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      Effects of Second and Third Generation Oral Contraceptives on Lipid and Carbohydrate Metabolism in Overweight and Obese Women: A Randomized Triple-Blind Controlled Trial

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          Abstract

          Background

          Combined oral contraceptives (COCs) have not been shown to have major effects on lipid and carbohydrate metabolism in normal-weight women. However, we have limited information about the effects on women at high risk for cardiovascular disease and diabetes due to being overweight and obese.

          Objectives

          To evaluate the effects of second and third generation contraceptive pills on lipid and carbohydrate metabolism in overweight and obese women.

          Patients and Methods

          This triple-blind controlled trial was performed on 137 healthy women aged 18 - 40 years with a body mass index of 25-34.9 (kg/m 2) who were referred to health centers in Tabriz, Iran from 2014 to 2015. The women were randomly divided into groups who were to take 30 mcg ethinyl estradiol/150 mcg levonorgestrel (EE/LGN) (n = 69) or 30 mcg ethinyl estradiol/150 mcg desogestrel (EE/DSG) (n = 68) with an allocation ratio of 1: 1 for three cycles. As primary outcomes, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting plasma glucose (FPG) were assessed; total cholesterol (TC), triglycerides (TG), and 2-hour plasma glucose in the 75-g oral glucose tolerance test (2-hour 75-g OGTT) were assessed as secondary outcomes.

          Results

          The differences in lipid and carbohydrate parameters were not significant between the two groups, except for HDL-C (Adjusted MD (CI95%) = 7.00 (2.98 to 11.02)). HDL-C decreased with EE/LGN (P = 0.016) and increased with EE/DSG (P = 0.004). LDL-C and TC increased in both groups, whereas TG increased only with EE/DSG (P < 0.05). Compared with the baseline, FPG levels did not differ significantly in both groups, but EE/DSG increased 2-hour 75-g OGTT (P = 0.010).

          Conclusions

          We observed no significant differences between the two groups in lipid and carbohydrate metabolism, except for HDL-C. Considering the importance of overweight and obese women’s health, studies with longer follow-up periods are recommended in this respect.

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          Most cited references20

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          Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus.

          Abdominal obesity contributes to insulin resistance, a metabolic abnormality linked to the development of type 2 diabetes mellitus and cardiovascular disease (CVD). Insulin resistance generally precedes the development of type 2 diabetes. Currently, an estimated 10 million US adults have diabetes and another 25 million have impaired glucose tolerance (IGT), an intermediate step between insulin resistance and diabetes. The pathophysiologic mechanisms known to increase CVD risk in individuals with insulin resistance include formation of advanced glycation end products, hypertension, proinflammatory and prothrombotic states, and dyslipidemia (i.e., low levels of high-density lipoprotein cholesterol, increased levels of triglycerides, small, dense low-density lipoprotein cholesterol particles, apoplipoprotein B, and inflammation). The increased flux of free fatty acids from adipose tissue to the liver promotes dyslipidemia. Insulin resistance and impaired glucose tolerance are associated with increased CVD risk. Individuals with coexisting metabolic syndrome and diabetes have the highest prevalence rates of CVD. The Nurses' Health Study showed that CVD risk was elevated even before the development of diabetes compared with women who never developed diabetes. Lifestyle modification is recommended as the first-line treatment for obesity and its metabolic sequelae. Pharmacotherapy may be useful in patients for whom nonpharmacologic approaches alone are ineffective or insufficient. Primary care physicians play a critical role in the early identification and treatment of patients at increased risk for the development of type 2 diabetes and CVD because of their obesity and associated complications.
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            Characteristics and metabolic effects of estrogen and progestins contained in oral contraceptive pills.

            Estrogen and progestins have been used by millions of women as effective combined oral contraceptives. Oral contraceptives (OCs) modify surrogate markers such as lipoproteins, insulin response to glucose, and coagulation factors, that have been associated with cardiovascular and venous risk. Ethinyl-Estradiol (EE) exerts a stronger effect that natural estradiol (E2) on hepatic metabolism. New progestins with high specificity have been designed to avoid interaction with other receptors and prevent androgenic, estrogenic or glucocorticoid related side-effects. The risks and benefits of new progestins used in contraception depend upon their molecular structure, the type and dose of associated estrogen, and the delivery route. The lower impact of E2-based combinations on metabolic surrogate markers may result in an improved safety profile, but only clinical outcomes are relevant to assess the risk. Large surveillance studies are warranted to confirm this hypothesis. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Metabolic effects of contraceptive steroids.

              Estrogen and progestins have been used by millions of women as effective combined contraceptives. The safety of hormonal contraceptives has been documented by years of follow-up and serious adverse events that may be related to their use are rare in the young population exposed to these agents. The balance between the benefits and the risks of contraceptive steroids is generally positive in particular when comparing to the risks of pregnancy and especially in women with risk factors. The metabolic changes induced by the synthetic steroids used in contraception, such as lipoprotein changes, insulin response to glucose, and coagulation factors have been considered as potential markers of cardiovascular and venous risk. Observations of these effects have led to modifications of the composition of hormonal contraceptive in order to minimize these changes and hence potentially decrease the risks. The synthetic estrogen Ethinyl-Estradiol (EE) exerts a stronger effect that natural estradiol (E2) on hepatic metabolism including estrogen-dependent markers such as liver proteins. This stronger hepatic impact of EE has been related to its 17α-ethinyl group which prevents the inactivation of the molecule and results in a more pronounced hepatic effect of EE as compared to estradiol. Due to its strong activity, administering EE via a non-oral route does not prevent its impact on liver proteins. In order to circumvent the metabolic changes induced by EE, newer products using more natural compounds such as estradiol (E2) and estradiol valerate (E2V) have been introduced. The synthetic progestins used for contraception are structurally related either to testosterone (T) (estranes and gonanes) or to progesterone (pregnanes and 19-norpregnanes). Several new progestins have been designed to bind more specifically to the progesterone receptor and to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor interactions. Dienogest (DNG), and drospirenone (DRSP) and the 19-norpregnanes including Nestorone® (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG) have been combined with estrogen either EE or E2 or estradiol valerate (E2V). Risks and benefits of the newer progestins used in contraception depend upon the type of molecular structure, the type and dose of estrogen associated in a combination and the route of administration. The lower metabolic impact of estradiol-based combinations may result in an improved safety profile, but large surveillance studies are warranted to confirm this plausible hypothesis. So far, the contraindications and warnings for use of current COCs also apply to the estradiol-based COCs.
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                Author and article information

                Journal
                Iran Red Crescent Med J
                Iran Red Crescent Med J
                10.5812/ircmj
                Kowsar
                Iranian Red Crescent Medical Journal
                Kowsar
                2074-1804
                2074-1812
                19 June 2016
                September 2016
                : 18
                : 9
                : e36982
                Affiliations
                [1 ]Department of Midwifery, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, IR Iran
                [2 ]Department of Midwifery, Nursing and Midwifery Faculty, Tabriz Health Services Management Research Centre, Tabriz University of Medical Sciences, Tabriz, IR Iran
                Author notes
                [* ]Corresponding Author: Samira Pourzeinali-Beilankouh, Department of Midwifery, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, IR Iran. Tel: +98-4134474467, Fax: +98-4134796969, E-mail: Pourzeinalisyahoo.com, Pb.samira@ 123456gmail.com
                Article
                10.5812/ircmj.36982
                5253509
                e6cde5dd-6a83-4f56-bf15-8c2eee5f29b1
                Copyright © 2016, Iranian Red Crescent Medical Journal

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

                History
                : 08 February 2016
                : 28 March 2016
                : 23 April 2016
                Categories
                Research Article

                Medicine
                levonorgestrel,desogestrel,overweight,obesity,lipid metabolism,carbohydrate metabolism
                Medicine
                levonorgestrel, desogestrel, overweight, obesity, lipid metabolism, carbohydrate metabolism

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