{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:13:29Z","timestamp":1781565209372,"version":"3.54.5"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Hormonal contraceptives are artificial preparations that contain artificial progestins and Ethinylestradiol; these preparations are utilized by women of reproductive age to prevent pregnancy. Roughly a billion women in the world use some form of contraceptive worldwide. Despite the utility of these preparations, they are linked with several adverse effects, including disturbances of liver functionality and integrity. However, previous studies conducted to assess the association between hormonal contraceptive utilization and liver function tests reported conflicting results, and the effects remained a matter of concern.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The study enrolled a total of 264 participants, who were allocated into two groups. One group of hormonal contraceptive users who use the medication for a minimum of six months: Depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), Norplant, and Implant users and another age-matched non-user control group in a ratio of 1:1. A semi-structured questionnaire was used to collect socio-demographic, behavioral, and clinical data. Five ml serum blood sample was collected for liver function test analysis on a Beckman Coulter Clinical Chemistry analyzer (DXC 700 AU). Independent t-test was used to compare liver function tests of hormonal contraceptive users and non-user controls, whereas ANOVA followed by a Bonferroni post hoc test was used for intra- (between classes of contraceptives) and inter-group (between each class of contraceptives and controls) comparisons and to identify factors associated.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Hormonal contraceptive users were observed to have a statistically significant higher mean value of liver enzymes assessed compared to non-user control groups: aspartate aminotransferase (AST) (47.07\u00b114.79 versus 25.92\u00b17.37; p &lt;0.001), alanine aminotransferase (ALT) (35.83\u00b113.76 versus 16.56 \u00b1 5.03; p &lt;0.001), alkaline phosphatase (ALP) (63.34\u00b114.74 versus 45.41\u00b114.34, p &lt;0.001) and for \u03b3-glutamyl transferase (GGT) (47.37\u00b124.32 versus 19.45 \u00b1 6.86 p &lt;0.001). Similarly, the mean value of total and direct bilirubin (mg\/dL) among HC users showed a statistically significant elevation (0.68 \u00b1 0.22 against 0.32 \u00b1 0.13, p &lt;0.001) for total bilirubin and (0.14 \u00b1 0.06 against 0.06 \u00b1 0.03, p &lt;0.001) for direct bilirubin respectively. However, no statistically significant result was observed in the mean values of total protein and albumin. For total protein (6.7 \u00b1 0.89 versus 6.5 \u00b1 1.15, p 0.07) and for albumin (5.4 \u00b1 0.92 versus 5.3 \u00b1 1.08; p 0.30). The current study also indicates the level of hepatic function test alteration is related to the type of hormonal contraceptives, duration of usage, and level of adherence to a specific class of contraceptives.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion and recommendation<\/jats:title>\n<jats:p>Hormonal contraceptive use was observed to affect hepatic function. Based on this finding, we strongly recommend to closely monitor liver function tests in women using hormonal contraceptives.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0289746","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T17:46:51Z","timestamp":1692294411000},"page":"e0289746","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Assessment of liver function tests of women taking hormonal contraceptives at University of Gondar comprehensive specialized hospital and Family Guidance Association of Gondar (FGAE), 2022; a comparative cross-sectional study"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6570-3781","authenticated-orcid":true,"given":"Elias","family":"Chane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habtamu","family":"Wondifraw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2040-6838","authenticated-orcid":true,"given":"Rishan","family":"Hadgu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7677-4454","authenticated-orcid":true,"given":"Alebachew","family":"Fasil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"issue":"1","key":"pone.0289746.ref001","article-title":"Clinical relevance in present day hormonal contraception","volume":"37","author":"P-A Regidor","year":"2019","journal-title":"Hormone molecular biology and clinical investigation"},{"issue":"2829","key":"pone.0289746.ref002","first-page":"495","article-title":"Hormonal contraception\u2014what kind, when, and for whom?","volume":"108","author":"I Wiegratz","year":"2011","journal-title":"Deutsches \u00c4rzteblatt International"},{"issue":"10","key":"pone.0289746.ref003","doi-asserted-by":"crossref","first-page":"e022338","DOI":"10.1136\/bmjopen-2018-022338","article-title":"Dyslipidaemias in women using hormonal contraceptives: a cross sectional study in Mulago Hospital Family Planning Clinic, Kampala","volume":"8","author":"R Bakesiima","year":"2018","journal-title":"Uganda. BMJ open"},{"key":"pone.0289746.ref004","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/aogs.12771","article-title":"Physiology, production and action of progesterone","volume":"94","author":"S Taraborrelli","year":"2015","journal-title":"Acta obstetricia et gynecologica Scandinavica"},{"issue":"1","key":"pone.0289746.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jcp.s1-3.1.1","article-title":"Oral contraceptives and liver function","volume":"1","author":"T Hargreaves","year":"1969","journal-title":"Journal of Clinical Pathology"},{"issue":"3","key":"pone.0289746.ref006","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/13625187.2018.1455087","article-title":"Subclinical cardiovascular disease parameters after one year in new users of depot medroxyprogesterone acetate compared to copper-IUD","volume":"23","author":"K Cursino","year":"2018","journal-title":"The European journal of contraception & reproductive health care: the official journal of the European Society of Contraception"},{"issue":"3","key":"pone.0289746.ref007","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s12291-015-0533-x","article-title":"Effect of oral contraceptive pills on the blood serum enzymes and dna damage in lymphocytes among users","volume":"31","author":"F Naz","year":"2016","journal-title":"Indian Journal of Clinical Biochemistry"},{"issue":"2","key":"pone.0289746.ref008","doi-asserted-by":"crossref","DOI":"10.4314\/ijbcs.v5i2.72161","article-title":"The influence of age on lipid profile among women taking hormonal contraceptives","volume":"5","author":"CU Okeke","year":"2011","journal-title":"International Journal of Biological and Chemical Sciences"},{"issue":"1","key":"pone.0289746.ref009","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/13625189809167479","article-title":"Sex hormonal preparations and the liver","volume":"3","author":"S Dourakis","year":"1998","journal-title":"The European Journal of Contraception & Reproductive Health Care"},{"issue":"5","key":"pone.0289746.ref010","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/ajcn\/49.5.845","article-title":"Oral contraceptives: effect of long-term use on liver vitamin A storage assessed by the relative dose response test","volume":"49","author":"K Amatayakul","year":"1989","journal-title":"The American journal of clinical nutrition"},{"issue":"5","key":"pone.0289746.ref011","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1159\/000197290","article-title":"Oral contraceptives and the liver","volume":"7","author":"JM Metreau","year":"1972","journal-title":"Digestion"},{"issue":"4","key":"pone.0289746.ref012","first-page":"81","article-title":"The effect of steroidal contraceptives on liver enzymes and serum proteins in white albino rats","volume":"4","author":"P Iyomon","year":"2015","journal-title":"International Journal of Herbs and Pharmacological Research"},{"issue":"6","key":"pone.0289746.ref013","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/00005792-196645060-00010","article-title":"ESTROGEN PHARMACOLOGY: IV. Studies on the Structural Basis for Estrogen-Induced Impairment of Liver Function","volume":"45","author":"T Gallagher","year":"1966","journal-title":"Medicine"},{"key":"pone.0289746.ref014","article-title":"Progestin","author":"M Edwards","year":"2021","journal-title":"StatPearls"},{"issue":"3","key":"pone.0289746.ref015","first-page":"315","article-title":"Pharmacodynamics of combined estrogen-progestin oral contraceptives: 1","volume":"10","author":"C Bastianelli","year":"2017","journal-title":"Effects on metabolism. Expert review of clinical pharmacology"},{"issue":"11","key":"pone.0289746.ref016","doi-asserted-by":"crossref","first-page":"912","DOI":"10.3109\/09513590.2015.1062860","article-title":"Effects of a combined oral contraceptive containing 20 mcg of ethinylestradiol and 3 mg of drospirenone on the blood pressure, renin-angiotensin-aldosterone system, insulin resistance, and androgenic profile of healthy young women","volume":"31","author":"CRG Giribela","year":"2015","journal-title":"Gynecological Endocrinology"},{"issue":"1","key":"pone.0289746.ref017","doi-asserted-by":"crossref","first-page":"e22194","DOI":"10.1002\/jcla.22194","article-title":"Influence of oral contraceptives on lipid profile and paraoxonase and commonly hepatic enzymes activities","volume":"32","author":"K Kowalska","year":"2018","journal-title":"Journal of clinical laboratory analysis"},{"issue":"5","key":"pone.0289746.ref018","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.contraception.2011.09.013","article-title":"Evaluation of oxidative stress after treatment with low estrogen contraceptive either alone or associated with specific antioxidant therapy","volume":"85","author":"A Finco","year":"2012","journal-title":"Contraception"},{"issue":"6","key":"pone.0289746.ref019","doi-asserted-by":"crossref","first-page":"R221","DOI":"10.1530\/EJE-14-0527","article-title":"Mechanisms in endocrinology: epidemiology of hormonal contraceptives-related venous thromboembolism","volume":"171","author":"J Hugon-Rodin","year":"2014","journal-title":"European journal of endocrinology"},{"key":"pone.0289746.ref020","article-title":"UN: World Fertility and Family Planning 2020: Highlights","year":"2020","journal-title":"United Nations, Department of Economic and Social Affairs, Population"},{"key":"pone.0289746.ref021","article-title":"Contraceptive Use by Method","author":"U Nations","year":"2019","journal-title":"United Nations, Department of Economic and Social Affairs New York"},{"issue":"3","key":"pone.0289746.ref022","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.contraception.2012.08.029","article-title":"Trends in contraceptive use","volume":"87","author":"JE Darroch","year":"2013","journal-title":"Contraception"},{"key":"pone.0289746.ref023","article-title":"How family planning supply and the service environment affect contraceptive use: findings from four East African countries","author":"W Wang","year":"2012","journal-title":"International Health and Development, ICF International"},{"issue":"1","key":"pone.0289746.ref024","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40834-021-00162-9","article-title":"Contraceptive prevalence rate and associated factors among reproductive age women in four emerging regions of Ethiopia: a mixed method study","volume":"6","author":"D Bekele","year":"2021","journal-title":"Contraception and Reproductive Medicine"},{"key":"pone.0289746.ref025","volume-title":"Ethiopia mini demographic and health survey 2019: key indicators","author":"I EPHIEE","year":"2019"},{"issue":"2","key":"pone.0289746.ref026","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11154-011-9182-4","article-title":"Metabolic effects of contraceptive steroids","volume":"12","author":"R Sitruk-Ware","year":"2011","journal-title":"Reviews in endocrine and metabolic disorders"},{"issue":"3","key":"pone.0289746.ref027","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3126\/kumj.v18i3.49228","article-title":"Hormonal Contraceptives Use and Their Adverse Effects: A Cross-Sectional Study among the Women Visiting Tertiary Care Center","volume":"71","author":"S Shakya Shrestha","year":"2020","journal-title":"Kathmandu Univ Med J"},{"issue":"5","key":"pone.0289746.ref028","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1177\/2042098614548857","article-title":"Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks","volume":"5","author":"J Brynhildsen","year":"2014","journal-title":"Therapeutic advances in drug safety"},{"key":"pone.0289746.ref029","first-page":"2","article-title":"STUDIES ON SOME PLASMA BIOCHEMICAL PARAMETERS IN SHORT AND LONG TERM USERS OF ORAL CONTRACEPTIVES CONTAINING LOWER DOSES OF ESTROGEN AND PROGESTIN COMPOSITION IN LAGOS, NIGERIA","volume":"1","author":"ET Egoro","year":"2018","journal-title":"health"},{"issue":"2","key":"pone.0289746.ref030","first-page":"5355","article-title":"Activities of some liver enzymes in serum of woman receiving oral contraceptives, injection and Cu-IUD","volume":"14","author":"SA Rahim","year":"2020","journal-title":"EurAsian Journal of BioSciences"},{"key":"pone.0289746.ref031","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.mri.2019.04.010","article-title":"Hepatic complications of oral contraceptive pills and estrogen on MRI: Controversies and update-Adenoma and beyond","volume":"60","author":"J Ponnatapura","year":"2019","journal-title":"Magnetic resonance imaging"},{"issue":"1","key":"pone.0289746.ref032","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MEG.0000000000000233","article-title":"A systematic review of the prevalence of mildly abnormal liver function tests and associated health outcomes","volume":"27","author":"S Radcke","year":"2015","journal-title":"European journal of gastroenterology & hepatology"},{"key":"pone.0289746.ref033","article-title":"Liver function tests","author":"V Lala","year":"2020","journal-title":"StatPearls"},{"key":"pone.0289746.ref034","author":"S Erkabu","year":"2021","journal-title":"Journal of Spleen And Liver Research"},{"issue":"25","key":"pone.0289746.ref035","first-page":"6","article-title":"The impact of the 2003 heat wave on mortality and hospital admissions in England","volume":"2005","author":"H Johnson","journal-title":"Health statistics quarterly"},{"issue":"2","key":"pone.0289746.ref036","first-page":"75","article-title":"Current views on liver diseases in Ethiopia","volume":"15","author":"E Tsega","year":"1977","journal-title":"Ethiopian medical journal"},{"key":"pone.0289746.ref037","first-page":"59","article-title":"Effect of hormonal contraceptives on selected biochemical indices of liver function in women receiving oral and injectable contraceptives in Isolo, Lagos State, Nigeria","volume":"2","author":"Esther. N Adejumo","year":"2017","journal-title":"Journal of Public & Allied Health Sciences"},{"key":"pone.0289746.ref038","doi-asserted-by":"crossref","first-page":"e00148","DOI":"10.1016\/j.plabm.2019.e00148","article-title":"Evaluation of the Beckman Coulter DxC 700 AU chemistry analyzer","volume":"18","author":"V Bush","year":"2020","journal-title":"Practical laboratory medicine"},{"issue":"172","key":"pone.0289746.ref039","article-title":"The effects of norethisterone on blood pressure, serum glucose concentrations, AST, ALT, and alkaline phosphatase Activities","volume":"2","author":"IH Mahmood","year":"2011","journal-title":"The Medical Journal of Tikrit University"},{"issue":"2","key":"pone.0289746.ref040","first-page":"62","article-title":"Activities of some liver enzymes in serum of humans receiving DMPA and CUPID contraceptives","volume":"1","author":"I Onyesom","year":"2013","journal-title":"SchJAppMedSci"},{"issue":"3","key":"pone.0289746.ref041","first-page":"223","article-title":"Acute intermittent porphyria and oral contraception. Case report","volume":"77","author":"J Bianketti","year":"2006","journal-title":"Ginekologia polska"},{"issue":"2","key":"pone.0289746.ref042","first-page":"52","article-title":"Effects of duration of use of hormonal contraceptives on liver function","volume":"3","author":"J Ebele","year":"2009","journal-title":"Research Journal of Medical Sciences"},{"issue":"3","key":"pone.0289746.ref043","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/oxfordjournals.aje.a114267","article-title":": EFFECT OF ESTROGEN\/PROGESTIN POTENCY ON CLINICAL CHEMISTRY MEASURES THE LIPID RESEARCH CLINICS PROGRAM PREVALENCE STUDY","volume":"123","author":"KNOPP WALDEN CE","year":"1986","journal-title":"American journal of epidemiology"},{"issue":"2","key":"pone.0289746.ref044","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.nwh.2019.01.008","article-title":"A New Year-Long Combination Hormonal Contraceptive","volume":"23","author":"KK Blakely","year":"2019","journal-title":"Nursing for women\u2019s health"},{"issue":"1","key":"pone.0289746.ref045","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.contraception.2005.06.065","article-title":"Effects of a subdermal levonorgestrel contraceptive implant (Norplant) on serum cholesterol, triglycerides, ALT and AST in Iranian women","volume":"73","author":"M Taheri","year":"2006","journal-title":"Contraception"},{"issue":"02","key":"pone.0289746.ref046","doi-asserted-by":"crossref","first-page":"046","DOI":"10.30574\/wjbphs.2022.9.2.0037","article-title":"Assessment on the effect of selected oral contraceptives on the liver functionality and integrity","volume":"9","author":"T Odinga","year":"2022","journal-title":"World Journal of Biology Pharmacy and Health Sciences"},{"issue":"34","key":"pone.0289746.ref047","article-title":"EVALUATIVE STUDY FOR THE BIOCHEMICAL & PHYSIOLOICAL EFEECTS OF ORAL CONTRACEPTION IN IRAQI WOMEN","volume":"5","author":"HM SHACKER","year":"2008","journal-title":"Medical Journal of Babylon"},{"issue":"4","key":"pone.0289746.ref048","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1210\/jcem-61-4-595","article-title":"Effects of a short course of estrogen on mineral metabolism in postmenopausal women","volume":"61","author":"JL Stock","year":"1985","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"pone.0289746.ref049","author":"F Schiele","year":"1998","journal-title":"Biological effects of eleven combined oral contraceptives on serum triglycerides\u03b3-glutamyltransferase, alkaline phosphatase, bilirubin and other biochemical variables"},{"issue":"9","key":"pone.0289746.ref050","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.3390\/10091145","article-title":"Oxidative stress, lipid profile and liver functions in average Egyptian long term depo medroxy progesterone acetate (DMPA) users","volume":"10","author":"L Faddah","year":"2005","journal-title":"Molecules"},{"issue":"5","key":"pone.0289746.ref051","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jogoh.2019.02.006","article-title":"Update on the contraceptive contraindications","volume":"48","author":"D Serfaty","year":"2019","journal-title":"Journal of Gynecology Obstetrics and Human Reproduction"},{"issue":"1","key":"pone.0289746.ref052","article-title":"Status of Liver Enzymes in Women on Hormonal Contraceptives in Maiduguri","volume":"5","author":"Y Mamza","year":"2020","journal-title":"Sokoto Journal of Medical Laboratory Science"},{"issue":"5","key":"pone.0289746.ref053","first-page":"1465","article-title":"Estrogen replacement therapy continuously combined with four different dosages of dydrogesterone: effect on calcium and lipid metabolism","volume":"79","author":"G Voetberg","year":"1994","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"issue":"1","key":"pone.0289746.ref054","doi-asserted-by":"crossref","first-page":"91","DOI":"10.5455\/2319-2003.ijbcp20130118","article-title":"Oral contraceptives induced hepatotoxicity","volume":"2","author":"BA Srikanth","year":"2013","journal-title":"International Journal of Basic & Clinical Pharmacology"},{"issue":"1","key":"pone.0289746.ref055","first-page":"19","article-title":"The effect of chronic estrogen application on bile and gallstone composition in women with cholelithiasis","volume":"41","author":"D Sieron","year":"2016","journal-title":"Minerva endocrinologica"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0289746","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T17:47:31Z","timestamp":1692294451000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0289746"}},"subtitle":[],"editor":[{"given":"Enoch","family":"Aninagyei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,8,17]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0289746","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,17]]}}}