Liver function congruence with contraceptive medical profile in women at child-bearing ages
Main Article Content
Keywords
contraceptives, hormones, liver function, hepatotoxicity, reproductive health
Abstract
Hormonal contraceptives are among the most widely used medications worldwide, providing effective and reversible contraception for women. However, their use has been associated with potential side effects, including effects on liver function. This article reviews current evidence on the influences of different hormonal contraceptives agents on liver function in women of childbearing age. A cross-sectional study was conducted on 46 women aged 25-45 years using different contraceptive methods. Serum levels of the liver functional parameters were measured and compared between contraceptive-users versus contraceptive-free group, as well as among different age groups, parity, and contraceptive types. The results showed significantly higher levels of the liver functional parameters in women over 45 years old compared to younger age groups. Contraceptive users also had significantly higher levels of these liver enzymes compared to non-users. Among contraceptive types, combined oral contraceptives were associated with the highest elevations in liver enzymes. The results suggest that prolonged use of hormonal contraceptives, especially combined oral contraceptives, may adversely affect liver function. However, the clinical importance of these elevations needs further investigation. Careful screening and monitoring of liver function is advisable for women on long-term hormonal contraception.
References
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13. Zia A, Callaghan MU, Callaghan JH, Sawni A, Bartlett H, Backos A, et al. Hypercoagulability in adolescent girls on oral contraceptives‐global coagulation profile and estrogen receptor polymorphisms. American journal of hematology. 2015;90(8):725-31. https://doi.org/10.1002/ajh.24064
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18. Mahmood IH, Jaber IM. Effects of hormonal contraceptives on serum glucose, lipid profile and some liver function test. Iraq J Pharm Vol. 2014;14(1).
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20. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. Cmaj. 2005;172(3):367-79. https://doi.org/10.1503/cmaj.1040752
21. Sy FS, Osteria TS, Opiniano V, Gler S. Effect of oral contraceptive on liver function tests of women with schistosomiasis in the Philippines. Contraception. 1986;34(3):283-94. https://doi.org/10.1016/0010-7824(86)90009-0
22. Hargreaves T. Oral contraceptives and liver function. Journal of Clinical Pathology. 1969;1(1):1-0.
23. Teal S, Edelman A. Contraception selection, effectiveness, and adverse effects: a review. Jama. 2021;326(24):2507-18. https://doi.org/10.1001/jama.2021.21392
24. Palacios S, Colli E, Regidor PA. Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime. BMC Women’s Health. 2020;20(1):1-9. https://doi.org/10.1186/s12905-020-01080-9
25. Le Couteur DG, McLean AJ. The aging liver: drug clearance and an oxygen diffusion barrier hypothesis. Clinical pharmacokinetics. 1998;34(5):359-73. https://doi.org/10.2165/00003088-199834050-00003
26. Schmucker DL. Liver function and phase I drug metabolism in the elderly: a paradox. Drugs & aging. 2001;18:837-51. https:// doi.org/10.2165/00002512-200118110-00005
27. Zuñiga-Aguilar E, Ramírez-Fernández O. Fibrosis and hepatic regeneration mechanism. Translational Gastroenterology and Hepatology. 2022;7. https://doi.org/10.21037/tgh.2020.02.21
28. Soma-Pillay P, Nelson-Piercy C, Tolppanen H, Mebazaa A. Physiological changes in pregnancy: review articles. Cardiovascular journal of Africa. 2016;27(2):89-94. https://hdl.handle.net/10520/EJC188686
29. Mégier C, Peoc’h K, Puy V, Cordier AG. Iron metabolism in normal and pathological pregnancies and fetal consequences. Metabolites. 2022;12(2):129. https://doi.org/10.3390/metabo12020129
30. Krier M, Ahmed A. The asymptomatic outpatient with abnormal liver function tests. Clinics in liver disease. 2009;13(2):167-77. https://doi.org/10.1016/j.cld.2009.02.001
31. Schaffner F. The effect of oral contraceptives on the liver. Jama. 1966;198(9):1019-21. https://doi.org/10.1001/ jama.1966.03110220103034
32. Mahmood MD, Merkhan MM. Role of Spironolactone in the Treatment of Female Patterns Hair Loss With Polycystic Ovarian Syndrome. Proceedings of 2nd International Conference on Research in Multidisciplinary Studies: 208-2013.
33. Bonnema RA, McNamara MC, Spencer AL. Contraception choices in women with underlying medical conditions. American family physician. 2010;82(6):621-8.
34. Dhanjal MK. Contraception in women with medical problems. Obstetric medicine. 2008;1(2):78-87. https://doi.org/10.1258/om.2008.080014
35. Sane R, Sinz M. Introduction of drug metabolism and overview of disease effect on drug metabolism. InDrug metabolism in diseases 2017;1-19. Academic Press. https://doi.org/10.1016/B978-0-12-802949-7.00001-8
36. Petitti DB. Combination estrogen–progestin oral contraceptives. New England Journal of Medicine. 2003;349(15):1443-50. https://doi.org/10.1056/NEJMcp030751
37. Dustur S, Wahyuhadi J, Utomo B, Parenrengi MA, Bajamal AH, Dwiningsih SR. Relationship Histopathology Grading of Meningioma with the Use of Medroxyprogesterone Acetate (MPA) as A Hormonal Contraceptive. Pharmacognosy Journal.2022;14(6s). https://doi.org/10.5530/pj.2022.14.193.
38. Yorimoto R, Shoji M, Onda M. Self-efficacy of community pharmacists and associated factors in counselling to support self-medication in Japan: A cross-sectional study. Pharmacy Practice. 2022;20(2):1-7. https://doi.org/10.18549/PharmPract.2022.2.2660
2. Fenton C, Wellington K, Moen MD, Robinson DM. Drospirenone/Ethinylestradiol 3mg/20μg (24/4 Day Regimen) A Review of Its Use in Contraception, Premenstrual Dysphoric Disorder and Moderate Acne Vulgaris. Drugs. 2007;67:1749-65. https://doi.org/10.2165/00003495-200767120-00007
3. Szucs LE, Lowry R, Fasula AM, Pampati S, Copen CE, Hussaini KS, et al. Condom and contraceptive use among sexually active high school students—Youth Risk Behavior Survey, United States, 2019. MMWR supplements. 2020;69(1):11. https://doi.org/10.15585/mmwr.su6901a2
4. Bairagya A, Basu G, Mondal R, Roy SK. Prevalence and reasons behind use of injectable contraceptive among the women of reproductive age group: A cross-sectional survey in rural areas of Nadia District, West Bengal. Journal of Family Medicine and Primary Care. 2021;10(7):2566. https://doi.org/10.4103/jfmpc.jfmpc_2465_20
5. Kapp N. WHO provider brief on hormonal contraception and liver disease. Contraception. 2009;80(4):325-6. https://doi.org/10.1016/j.contraception.2009.01.020
6. Orlenko V, Tronko M, Bolgarskaya S, Yelizarova O. Hormonal and metabolic aspects of diabetes-associated osteoarthritis. Georgian Medical News. 2020 Apr 1(301):98-105.
7. Finco A, Belcaro G, Cesarone MR. Evaluation of oxidative stress after treatment with low estrogen contraceptive either alone or associated with specific antioxidant therapy. Contraception. 2012;85(5):503-8. https://doi.org/10.1016/j. contraception.2011.09.013
8. Kapp N, Curtis K, Nanda K. Progestogen-only contraceptive use among breastfeeding women: a systematic review. Contraception. 2010;82(1):17-37. https://doi.org/10.1016/j.contraception.2010.02.002
9. Phillips SJ, Tepper NK, Kapp N, Nanda K, Temmerman M, Curtis KM. Progestogen-only contraceptive use among breastfeeding women: a systematic review. Contraception. 2016;94(3):226-52. https://doi.org/10.1016/j.contraception.2015.09.010
10. Chane E, Wondifraw H, Hadgu R, Fasil A. 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. Plos one. 2023;18(8):e0289746. https://doi.org/10.1371/journal.pone.0289746
11. Sulaiman EA, Dhiaa S, Merkhan MM. Overview of vitamin D role in polycystic ovarian syndrome. MMSL. 2022;91(1):37-43. https://doi.org/10.31482/mmsl.2021.027
12. Iyomon P, Nwangwa E, Edebiri OE. The effect of steroidal contraceptives on liver enzymes and serum proteins in white albino rats. International Journal of Herbs and Pharmacological Research. 2015;4(4):81-5.
13. Zia A, Callaghan MU, Callaghan JH, Sawni A, Bartlett H, Backos A, et al. Hypercoagulability in adolescent girls on oral contraceptives‐global coagulation profile and estrogen receptor polymorphisms. American journal of hematology. 2015;90(8):725-31. https://doi.org/10.1002/ajh.24064
14. Sammaritano LR. Contraception in women with autoimmune diseases. Handbook of Systemic Autoimmune Diseases. 2005;4:123-40. https://doi.org/10.1016/S1571-5078(05)04011-0
15. Kemmeren JM, Tanis BC, van den Bosch MA, Bollen EL, Helmerhorst FM, van der Graaf Y, et al. Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study: oral contraceptives and the risk of ischemic stroke. Stroke. 2002;33(5):1202-8. https://doi.org/10.1161/01.STR.0000015345.61324.3F.
16. Özcan Ö, den Elzen WP, Hillebrand JJ, den Heijer M, van Loendersloot LL, Fischer J, et al. The effect of hormonal contraceptive therapy on clinical laboratory parameters: a literature review. Clinical Chemistry and Laboratory Medicine (CCLM). 2024;62(1):18-40. https://doi.org/10.1515/cclm-2023-0384
17. Bick AJ, Louw-du Toit R, Skosana SB, Africander D, Hapgood JP. Pharmacokinetics, metabolism and serum concentrations of progestins used in contraception. Pharmacology & therapeutics. 2021;222:107789. https://doi.org/10.1016/j. pharmthera.2020.107789
18. Mahmood IH, Jaber IM. Effects of hormonal contraceptives on serum glucose, lipid profile and some liver function test. Iraq J Pharm Vol. 2014;14(1).
19. Naz F, Jyoti S, Rahul, Akhtar N, Siddique YH. Effect of oral contraceptive pills on the blood serum enzymes and DNA damage
in lymphocytes among users. Indian Journal of Clinical Biochemistry. 2016;31:294-301. https://doi.org/10.1007/s12291-015-0533-x
20. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. Cmaj. 2005;172(3):367-79. https://doi.org/10.1503/cmaj.1040752
21. Sy FS, Osteria TS, Opiniano V, Gler S. Effect of oral contraceptive on liver function tests of women with schistosomiasis in the Philippines. Contraception. 1986;34(3):283-94. https://doi.org/10.1016/0010-7824(86)90009-0
22. Hargreaves T. Oral contraceptives and liver function. Journal of Clinical Pathology. 1969;1(1):1-0.
23. Teal S, Edelman A. Contraception selection, effectiveness, and adverse effects: a review. Jama. 2021;326(24):2507-18. https://doi.org/10.1001/jama.2021.21392
24. Palacios S, Colli E, Regidor PA. Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime. BMC Women’s Health. 2020;20(1):1-9. https://doi.org/10.1186/s12905-020-01080-9
25. Le Couteur DG, McLean AJ. The aging liver: drug clearance and an oxygen diffusion barrier hypothesis. Clinical pharmacokinetics. 1998;34(5):359-73. https://doi.org/10.2165/00003088-199834050-00003
26. Schmucker DL. Liver function and phase I drug metabolism in the elderly: a paradox. Drugs & aging. 2001;18:837-51. https:// doi.org/10.2165/00002512-200118110-00005
27. Zuñiga-Aguilar E, Ramírez-Fernández O. Fibrosis and hepatic regeneration mechanism. Translational Gastroenterology and Hepatology. 2022;7. https://doi.org/10.21037/tgh.2020.02.21
28. Soma-Pillay P, Nelson-Piercy C, Tolppanen H, Mebazaa A. Physiological changes in pregnancy: review articles. Cardiovascular journal of Africa. 2016;27(2):89-94. https://hdl.handle.net/10520/EJC188686
29. Mégier C, Peoc’h K, Puy V, Cordier AG. Iron metabolism in normal and pathological pregnancies and fetal consequences. Metabolites. 2022;12(2):129. https://doi.org/10.3390/metabo12020129
30. Krier M, Ahmed A. The asymptomatic outpatient with abnormal liver function tests. Clinics in liver disease. 2009;13(2):167-77. https://doi.org/10.1016/j.cld.2009.02.001
31. Schaffner F. The effect of oral contraceptives on the liver. Jama. 1966;198(9):1019-21. https://doi.org/10.1001/ jama.1966.03110220103034
32. Mahmood MD, Merkhan MM. Role of Spironolactone in the Treatment of Female Patterns Hair Loss With Polycystic Ovarian Syndrome. Proceedings of 2nd International Conference on Research in Multidisciplinary Studies: 208-2013.
33. Bonnema RA, McNamara MC, Spencer AL. Contraception choices in women with underlying medical conditions. American family physician. 2010;82(6):621-8.
34. Dhanjal MK. Contraception in women with medical problems. Obstetric medicine. 2008;1(2):78-87. https://doi.org/10.1258/om.2008.080014
35. Sane R, Sinz M. Introduction of drug metabolism and overview of disease effect on drug metabolism. InDrug metabolism in diseases 2017;1-19. Academic Press. https://doi.org/10.1016/B978-0-12-802949-7.00001-8
36. Petitti DB. Combination estrogen–progestin oral contraceptives. New England Journal of Medicine. 2003;349(15):1443-50. https://doi.org/10.1056/NEJMcp030751
37. Dustur S, Wahyuhadi J, Utomo B, Parenrengi MA, Bajamal AH, Dwiningsih SR. Relationship Histopathology Grading of Meningioma with the Use of Medroxyprogesterone Acetate (MPA) as A Hormonal Contraceptive. Pharmacognosy Journal.2022;14(6s). https://doi.org/10.5530/pj.2022.14.193.
38. Yorimoto R, Shoji M, Onda M. Self-efficacy of community pharmacists and associated factors in counselling to support self-medication in Japan: A cross-sectional study. Pharmacy Practice. 2022;20(2):1-7. https://doi.org/10.18549/PharmPract.2022.2.2660
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Mar 26, 2025
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Liver function congruence with contraceptive medical profile in women at child-bearing ages. Pharm Pract (Granada) [Internet]. 2025 Mar. 26 [cited 2025 Apr. 21];23(1):1-5. Available from: https://pharmacypractice.org/index.php/pp/article/view/3051
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How to Cite
1.
Liver function congruence with contraceptive medical profile in women at child-bearing ages. Pharm Pract (Granada) [Internet]. 2025 Mar. 26 [cited 2025 Apr. 21];23(1):1-5. Available from: https://pharmacypractice.org/index.php/pp/article/view/3051