Evaluation of Cardiovascular Disease Risk Factors in Adult Female Rats Exposed to Combined Oral Contraceptive Pills

Enebrayi, Nelson Onitsha *

Department of Medical Laboratory Science, Faculty of Basic Sciences, College of Health Science, Niger Delta University, Wilberforce Island, Amassoma, Bayelsa State, Nigeria.

Okutu, Jackson Borobuebi

Department of Medical Laboratory Science, Faculty of Basic Sciences, College of Health Science, Niger Delta University, Wilberforce Island, Amassoma, Bayelsa State, Nigeria.

Hope Charlotte

Department of Pharmacology, Bayelsa Medical University, Bayelsa State, Nigeria.

Ugochukwu, Chioma Promise

Department of Medical Laboratory Sciences, College of Health Sciences, Nnamdi Azikiwe University, Nnewi, Anambra State, Nigeria.

Egoro, Emmanuel Tonbra

Department of Medical Laboratory Science, Faculty of Basic Sciences, College of Health Science, Niger Delta University, Wilberforce Island, Amassoma, Bayelsa State, Nigeria.

*Author to whom correspondence should be addressed.


Background: Prolonged daily intake of oral contraceptive pills may result in cardiotoxicity. However, there are conflicting reports on the effects of combined oral contraceptive pills on cardiovascular disease risk factors.

Aim: This study investigated the cardiotoxicity effect of combined oral contraceptive pills in female albino rats, by the estimation of serum cardiovascular diseases risk factors.

Methods: Twenty-four rats were randomly allotted into three groups of eight rat each. Group A (saline water and feed treated; n=8) which served as control group, Group B (0.6 mg/kg body weight of combined oral contraceptive pills treated for 48 days; n=8) and group C (0.6 mg/kg body weight of combined oral contraceptive pills treated for 60 days; n=8). After the required weeks of treatment, the animals were sacrificed and blood and heart tissue samples were collected for biochemical and histological analysis using standard procedures.

Results: The result showed significant increased body weight gain after the treatment with combined oral contraceptive pills. There was an elevation in serum C-reactive protein, and reduction in Nitric Oxide levels in the combined oral contraceptive pills treated rats. Total cholesterol, low density lipoprotein, triglyceride, cardiac troponin-1, lactate dehydrogenase, creatine kinase-MB and malondialdehyde levels were increased in the combined oral contraceptive pills treated rats compared with control group. Histological result as revealed by the photomicrographs showed degeneration of transverse muscles, vascular congestion and vascular necrosis.

Conclusion: The study has confirmed that combined oral contraceptive pills causes an alteration in cardiovascular disease risk factors and cytoarchitecture of the heart. Thus, can induces ischemic heart disease.

Keywords: Cardiovascular disease, combined oral contraceptive pills, hyperlipidemia, C-reactive protein

How to Cite

Onitsha , E. N., Borobuebi , O. J., Charlotte, H., Promise , U. C., & Tonbra , E. E. (2023). Evaluation of Cardiovascular Disease Risk Factors in Adult Female Rats Exposed to Combined Oral Contraceptive Pills. Asian Journal of Medical Principles and Clinical Practice, 6(2), 266–277. Retrieved from https://journalajmpcp.com/index.php/AJMPCP/article/view/187


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George GS, Onitsha EN. “Micronutrient alterations in hormonal contraceptive use. International Journal of Current Research. 2017; 9, (01), 45432-45434

Naz FS, Jyoti N, Akhtar MA, Siddique YH. Lipid Profile of Women Using Oral Contraceptive Pills. Pakistan Journal of Biological Sciences. 2012; 15(19), 947-950.

Akshara S, Rohitash J. Adverse effect of combined oral contraceptive pills. Asian. Journal of Pharmaceutical and Clinical Research. 2017;10(1):17-21.

Shulman LP. The state of hormonal contraception today: benefits and risks of hormonal contraceptives: combined estrogen and progestin contraceptives. American Journal of Obstetrics Gynecology. 2011; 205(4), 9-13.

Hyejin P, Kisok K. Trends and Factors Associated with Oral Contraceptive Use among Korean Women Healthcare (Basel). 2021; 9(10): 1386. DOI: 10.3390/healthcare9101386

Allen RH, Cwiak CA, Kaunitz AM. Contraception in women over 40 years of age. Canadian Medical Association Journal. 2013;185(7):565-573.

Dragoman MV, Tepper NK, Fu R, Curtis KM, Chou R, Gaffield ME. A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception. Int J Gynaecol Obstet. 2018;141(3):287-294.


Mendis S, Puska P, Norrving B. Global Atlas on Cardiovascular Disease Prevention and Control. World Health Organization in collaboration with the World Heart Federation and the World Stroke Organization. 2011;3–18.

World Health Organization. Global Atlas on Cardiovascular Disease Prevention and Control. Mendis S, Puska P, Norrving B editors. World Health Organization (in collaboration with the World Heart Federation and World Stroke Organization), Geneva; 2011.

George AA, Sheila S, Robert AN, Bernice A, Daniel A, Albert GB. Effect of hormonal contraceptives on lipid profile and the risk indices for cardiovascular disease in a Ghanaian community. International Journal of Women Health. 2014; 6, 597–603.

Ezeiruaku FC, Onitsha EN. The Risk of Developing Heart Diseases Increases withthe Duration of the Diabetic Disease Illness among the Patients with Type 2 Diabetes Mellitus in Yenagoa Bayelsa State, Nigeria. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS). 2020;19(5):21-28.

Paradis G, Chiolero A. The cardiovascular and chronic Disease Epidemic in low- and middle-income countries. A Global Health challenges. JAM Coll Cardiol. 2011; 57 (17): 1775-1777.

Hassarajani S, Souza TD, Mengi SA, Chattopadhayay 2007. Efficacy study of the bioactive fraction (F-3) of Acorus calamus in hyperlipidemia. Indian J Pharmacol. 2007;39:196-200

Hogan MC, Foreman KJ, Naghavi M. Maternal mortality for 181 countries, 1980–2008: a systematic analysis of progress towards Millennium Development Goal 5. The Lancet. 2010; 375:1609‐1623.

Katarzyna K, Milena Ś, Anna B, Mariola Ś, and Halina M. Influence of oral contraceptives on lipid profile and paraoxonase and commonly hepatic enzymes activities. J Clin Lab Anal. 2018; 32(1): e22194.

DOI: 10.1002/jcla.22194

Zahra M, Ali D, Hossein F, Moslem K, Seyed HH, Masoud D. The impacts of pill contraceptive low-dose on plasma levels of nitricoxide, homocysteine, and and lipid profiles in the exposed vs. non exposed women: as thrisk factor for cardiovascular diseases. Contraception and Reproductive Medicine. 2020;5:7.


Dilshad HD, Rabia I, Safila N, Ghulam S. Effect of hormonal contraceptives on serum lipids: A prospective study. Pakistan Journal of Pharmaceutical Sciences, 2016; 29(4):1379-1382

Ridker MP, Libby P. Novel Atherosclerotic Risk Factor; High-Sensitivity C-reactive protein. In: Libby P, Bonow RO, Mann DL, Zipes DP. editors. Braunwald’s Heart Disease. A Textbook of Cardiovascular Medicine: Philadelphia: 2008;1012–1017.

Cozlea DL, Farcas DM, Nagy A. The impact of C reactive protein on global cardiovascular risk on patients with coronary artery disease. Current Health Science Journal. 2013; 39(4):225–231.

Amit KT, Umesh CJ. Debarshi Journal International journal of Scientific Research. 2021;10(5): 2277 – 8179.

DOI : 10.36106/ijsr

Petto J, Pereira LS, Santos ACN, Giesta BA, Melo TA, Ladeia AMT. Subclinical inflammation in women taking oral contraceptives. Rev Bras Cardiol. 2013;26(6):465-471

Alan CNS, Jefferson P, Francisco TOO, Diego PD, Ana MT. C-Reactive Protein in Oral Contraceptive Users: Related Factors and Cardiovascular Risk. International Journal of Cardiovascular Sciences. 2016;29(4):320-32.

DOI: 10.5935/2359-4802.20160051

Fallah S, Nouroozi V, Seifi M, Samadikuchaksaraei A, Aghdashi, EM. Influence of Oral Contraceptive pills on homocysteine and nitric oxide levels: As risk factors for cardiovascular disease. Journal Clinical Laboratory Analysis. 2012; 26(2):120-123.

Cherney D Z, Scholey JW, Cattran DC, Kang AK, Zimpelmann J, Kennedy C, Lai V, Burns KD, Miller JA. The Effect of Oral Contraceptives on the Nitric Oxide System and Renal Function. American Journal of Physiology and Renal Physiology. 2007;1-9.

Toryila JE, Amadi K, Odeh SO, Adelaiye AB, Egesie UG, Achie N. Dynamics of Combined Oral Contraceptive: A Study of Some Haematological Parameters in Female Wistar Rats. OSR Journal of Pharmacy, 2014; 4(9):15-19.

Makler MT, Hinrichs DJ Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia. Am J Trop Med Hyg. 1993;48(2):205-10.

DOI: 10.4269/ajtmh.1993.48.205

Passing H, Bablok, W. A new biometrical procedure for Testing different Analytical Methods. Journal of Clinical Biochemistry. 1983; 21:709-720.

Onitsha EN and Okutu JB. Influence of Vitamin E and Selenium on Reproductive Hormones and Lipid Peroxidation Levels in Lead-induced Toxicity in Female Wistar Rats. IOSR Journal of Environmental Science, Toxicology and Food Technology (IOSR-JESTFT), 2021;15(2):01-09.

Babuin L, Jaffe AS. Troponin: The biomarker of choice for the detection of cardiac injury, CMAJ. 2005; 173(10): 1191–1202. DOI: 10.1503/cmaj.050141

Ochei JK, Kolhatkar A. Medical Laboratory Science Theory and Practice. London. 2005; 399 – 406.

Edelman AB, Cherala G, Stanczyk FZ. Metabolism and pharmacokinetics of contraceptive steroids in obese women: a review. Contraception. 2011;82:314–323.

Ekhator CN, Osifo UC. The Effect of Oral Contraceptive Pills (OCP) On Body Weight: A Call for Further Studies. International Journal of Basic, Applied and Innovative Research. 2012;1(4): 155 – 160.

Asma D, Brown C, Pearlstein TB. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstetrics Gynecology. 2015;106(3):492-501.

Farnaz F, Ellstrom AA, Milsom I. The long-term influence of combined oral contraceptives on body weight. Human Reproduction. 2011; 26 (7):1917–24.

Krivak TC, Kristin KZ. Venous Thromboembolism in Obstetrics and Gynecology; Obstet Gynecol., 2007; 109(3):761-77. DOI:10.1097/01.AOG.0000255819.10187.70.

Cauci S, Di Santolo M, Culhane JF, Stel G, Patel G, Gonano F, Guaschino S. Effects of third- generation oral contraceptives on high-122 sensitivity C-reactive protein and Homocysteine in young women. Obstetrics Gynecology. 2008;111:857-864.

Gabriele P, Natasha I, Mariapaola C, Giovanni P, Federica M, Vincenzo A, Francesco S, Domenica A, Alessandra B. "Oxidative Stress: Harms and Benefits for Human Health", Oxidative Medicine and Cellular Longevity. 2017;13:201-202.

Kim K, Park H. Effect of oral contraceptive use on lipid profile in Korean women aged 35–55 years. Contraception. 2012;86(5):500-505.

Xi-Ying W, Fen Z, Chi Z, Liang-Rong Z, Jian Y. Biomarkers for Acute Myocardial Infarction and Heart Failure. Biomed Res Int., 2020; 2020: 2018035. DOI: 10.1155/2020/2018035

Zakharova MY, Meyer RM, Brandy KR, Datta YH, Joseph MS, Schreiner PJ. Risk factors for heart attack, stroke, and venous thrombosis associated with hormonal contraceptive use. Clinical and Applied Thrombosis/Hemostasis. 2011;17(4):323‐331.

Tchaikovski SN, Rosing J. Mechanisms of estrogen induced venous thromboembolism. Thrombosis Research. 2010;126(1):5‐11.

Borissoff JI, Spronk HM, Cate H. The haemostatic system as a modulator of atherosclerosis. New England Journal of Medicine, 2011; 364(18):1746‐1760.

Mallick AK, Ahsan M, Das B, Saxena S, Samanta S, Kukreja S. Study of lipid profile during late reproductive phase, perimenopause and postmenopause in North Indian Women. International Journal of Medical Research and Review. 2015; 3(1):46-50.

Rad M, Kluft C, De Kam ML, Meijer P, Cohen AF, Grubb GS, Constantine GD, Burggraaf J. Metabolic profile of a continuous versus a cyclic low-dose combined oral contraceptive after one year of use. The European Journal of Contraception & Reproductive Health Care. 2011;16(2): 85–94.

De-Groote D, d'Hauterive SP, Pintiaux A, Balteau B, Gerday C, Claesen J. Foidart JM. Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18–35 years old. Contraception. 2009;80(2):187-193.

Pincemail J, Vanbelle S, Gaspard U, Collette G, Haleng J, Cheramy-Bien JP, Charlier C, Chapelle JP, Giet D, Alpert A, Limet R, Defraigne JO. Effect of different contraceptive methods on the oxidative stress status in women aged 40-48 years from the ELAN study in the province of Liege. Belgium. Human Reproduction. 2007;22:2335-2343.

Al-Kushi AG, El-Boshy ME, ElSawy NA, Omar, OAS, Header EA. Pathological Comparative Studies on Aqueous and Ethanolic Extracts of Zingiber officinale on Antioxidants and Hypolipidemic Effects in Rats. Life Science Journal. 2013; 10(2):2393 – 2403.

Massart A, Portier H, Rosado F, Toumi H, Filaire E. Lipid peroxidation in judoists using oral contraceptives. International Journal of Sports Medicine. 2012;33(10):781-788.

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):503–508.