KADAR 2,3-DINOR-6-KETO-PROSTAGLANDIN-F1 DALAM URIN WANITA PASCAMENOPAUSE ALAMI DAN PRAMENOPAUSE YANG MINUM ASPIRIN 100 MG

Authors

  • Zita Arieselia Departemen Farmakologi dan Terapi, Fakultas Kedokteran UNIKA Atma Jaya
  • Arini Setiawati Departemen Farmakologi dan Terapi Fakultas Kedokteran Universitas Indonesia
  • Rianto Setiabudy Departemen Farmakologi dan Terapi, Fakultas Kedokteran UNIKA Atma Jaya
  • Ali Baziad Fakultas Kedokteran Universitas Indonesia

Keywords:

2,3-dinor-6-keto-prostaglandin-F1a, low dose aspirin, postmenopausal women, thromboxane/prostacyclin ratio

Abstract

Background: The prevalence of cardiovascular diseases in women increases sharply after menopause. In postmenopausal women, thromboxane production increases while prostacyclin production decreases. Low dose aspirin (75- 150 mg) has long been known as an antiplatelet aggregator. Aspirin reduces the production of both thromboxane (potent thrombocyte aggregator and vasoconstrictor) and prostacyclin (anti thrombocyte aggregator and potent vasodilator).
Methods: The present study was an open-label clinical trial with 2 parallel groups. One group consisted of 15 premenopausal women (age > 40 years) while the other group 15 postmenopausal women (for 3 - 5 years). Twenty-four hours urine was collected from each subject before and after aspirin 100 mg daily for 7 days. The concentration of prostacyclin was measured as its metabolite (2,3-dinor-6-keto-prostaglandin-F1) in urine using EIA (Enzyme Immunoassay). Thromboxane as its urinary metabolites (11-dehidrotromboksan-B2) was also measured in these same urine samples in the previous study.
Results: Previous study showed that aspirin significantly reduced thromboxane in both groups, with significantly larger percentage reduction in postmenopausal women compared to premenopausal women. Results of the present study showed that aspirin reduced prostacyclin significantly in both premenopausal women (mean difference = 78.44 ng/g creatinine; p = 0.001) and postmenopausal women (mean difference = 35.71 ng/g creatinine; p <0.001), but the percentage reduction between the groups was not significantly different (46,26% vs. 40,94%; p = 0,574). The decrease in thromboxane and prostacyclin should be compared (as the decrease in the ratio of 11-dehidrotromboksan-B2 / 2,3-dinor-6-keto-prostaglandin-F1) to assess aspirin efficacy as an antithrombotic. Calculation of the ratio of 11-dehidro-tromboksanB2 / 2,3-dinor-6-keto-prostaglandin-F1 before aspirin consumption was much higher in postmenopausal women compared to that in premenopausal women (4.09 vs. 1.13; p = 0.001). The decrease in 11-dehidro-tromboksan-B2 / 2,3- dinor-6-keto-prostaglandin-F1? ratio by aspirin was found much larger in postmenopausal women compared to that in premenopausal women (1.91 vs.0.17; p = 0.022).
Conclusions: It was concluded that aspirin reduced prostacyclin significantly in each group with nonsignificant percentage reduction between groups, but reduced the 11-dehidro-tromboksan-B2/2,3-dinor-6-keto-prostaglandin-F1? ratio much larger in post-menopausal women compared to that in premenopausal women.

Downloads

Download data is not yet available.

References

Rosenfield LE. Women and heart disease. In: Zaret BL, Moser M, Cohen LS, Morrow W, editors. Yale University School of Medicine Heart Book. Connecticut: Reed Business Information; 1992. p. 237- 43.

Wilson PWF, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97: 1837-47.

Jendryczko A, Tomala J. An imbalance between the excretion of thromboxane and prostacyclin metabolites in women after the menopause. Zentralbl Gynakol.1993; 115(4): 163-66.

Antithrombotic Trialists' Collabora-tion. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ.2002; 324: 71-86.

Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. New Engl J Med.2005; 352 (13):1293-304.

Fischer S, Bernutz C, Meier H, Weber PC. Formation of prostacyclin and thromboxane in man as measured by the main urinary metabolites. PubMed. 1986;876(2): 194-9.

Farker K, Schweer H, Vollandt R, Massr N, Nagel U, Seyberth HW, et al. Measurements of urinary prostaglandins in young ovulatory women during the menstrual cycle ang in postmenopausal women. Science Direct. 1997; 54(3): 655-64.

Sellers M, Xu F, Stallone. Selective estrogen receptor agonists enhance blood pressure, thromboxane and prostacyclin in aortic coarctation-induced hypertensive female rats. Federation of American Societies for Experimental Biology Journal. 2008; 22: 14.

Egan KM, Lawson JA, Fries S, Koller B, Rader DJ, Smyth EM, et al. COX-2 derived prostacyclin confers atheroprotection on female mice. The American Association for the Advancement of Science. 2004; 306 (5703): 1954-7.

Calkin AC, Sudhir K, Honisett S, Williams MRI, Dawood T, Komesaroff PA. Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2. The Journal of Clinical Endocrinology & Metabolism. 2002; 87(11): 5072-5.

Eikelboom JW, Hirsh J, Weitz JI, Johnston M, Qilong Y, Yusuf S. Aspirin resistant thrombosane biosynthesis and the risk of myocardial infarction, strike, cardiovascular death in patients at high risk for cardiovascular events. Circulation. 2002: 1650-5.

Kataoka M, Nagaya N, Satoh T, Itoh T, Murakami S, Iwase T, et al. A long-acting prostacyclin agonist with thromboxane inhibitory activity for pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine. 2005; 172: 1575-80.

Pedersen AK. Dose-related kinetics of aspirin: presystemic acetylation of platelet cyclooxygenase. New Engl J Med. 1984; 311(19): 1206-11.

Walsh SW. Low-dose aspirin: treatment for the imbalance of increased thromboxane and decreased prostacyclin in preeclampsia. Am J Perinatol. 1989;6(2): 124-32.

Al-Meshari A, Aleem MA. Story of low-dose aspirin: its potential use in obstetrics by way of influencing thromboxane and prostacyclin. Annals of Saudi Medicine. 1995; 15(2): 103-6.

Published

2024-07-12

How to Cite

1.
Arieselia Z, Setiawati A, Setiabudy R, Baziad A. KADAR 2,3-DINOR-6-KETO-PROSTAGLANDIN-F1 DALAM URIN WANITA PASCAMENOPAUSE ALAMI DAN PRAMENOPAUSE YANG MINUM ASPIRIN 100 MG. DJM [Internet]. 2024 Jul. 12 [cited 2024 Nov. 27];10(2). Available from: https://ejournal.atmajaya.ac.id/index.php/damianus/article/view/5698
Abstract views: 13 | PDF downloads: 12

Most read articles by the same author(s)