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      Effects of oral contraceptives on metabolic parameters in adult premenopausal women: a meta-analysis

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          Abstract

          Objective

          To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis.

          Patients and methods

          Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, BMI, insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random-effects model. We performed subgroup analyses by study duration (<12 months vs ≥12 months) and polycystic ovary syndrome (PCOS) status.

          Results

          Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel ( P < 0.001) to 35.1 mg/dL for chlormadinone ( P < 0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, P < 0.001) and drospirenone (+7.4 mg/dL, P < 0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL ( P < 0.001). Levonorgestrel (+6.8 mg/dL, P < 0.001) and norgestimate (+11.5 mg/dL, P = 0.003) increased LDLc, while dienogest decreased it (–7.7 mg/dL, P = 0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration.

          Conclusion

          Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.

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          Most cited references91

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            Sex-Specific Differences in Lipid and Glucose Metabolism

            Energy metabolism in humans is tuned to distinct sex-specific functions that potentially reflect the unique requirements in females for gestation and lactation, whereas male metabolism may represent a default state. These differences are the consequence of the action of sex chromosomes and sex-specific hormones, including estrogens and progesterone in females and androgens in males. In humans, sex-specific specialization is associated with distinct body-fat distribution and energy substrate-utilization patterns; i.e., females store more lipids and have higher whole-body insulin sensitivity than males, while males tend to oxidize more lipids than females. These patterns are influenced by the menstrual phase in females, and by nutritional status and exercise intensity in both sexes. This minireview focuses on sex-specific mechanisms in lipid and glucose metabolism and their regulation by sex hormones, with a primary emphasis on studies in humans and the most relevant pre-clinical model of human physiology, non-human primates.
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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.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                October 2020
                10 September 2020
                : 9
                : 10
                : 978-998
                Affiliations
                [1 ]School of Medicine , Universidad de los Andes, Bogotá, Colombia
                [2 ]Department of Health Research Methods , Evidence, and Impact, McMaster University, Ontario, Canada
                [3 ]School of Medicine , Universidad de los Andes, and Fundación Santa Fe de Bogotá, Section of Endocrinology, Bogotá, Colombia
                Author notes
                Correspondence should be addressed to C O Mendivil: carlosolimpo@ 123456gmail.com
                Article
                EC-20-0423
                10.1530/EC-20-0423
                7576645
                33048062
                0db8dff2-e822-4901-9846-b60c23c4c53e
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 28 August 2020
                : 10 September 2020
                Categories
                Research

                oral contraceptive,lipids,lipoproteins,insulin resistance metabolism

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