Serum Markers of Inflammation and Endothelial Function Are Elevated by Hormonal Contraceptive Use but Not by Exercise-Associated Menstrual Disorders in Physically Active Young Women

Overview

Journal J Sports Sci Med

Specialty Orthopedics

Date 2013 Nov 22

PMID 24259996

Citations 5

Authors

Pamela S Hinton

R Scott Rector

James E Peppers

Rebecca D Imhoff

Laura S Hillman

Affiliations

Soon will be listed here.

Abstract

The purpose of the study was to determine the effects of exercise-associated menstrual disorders and hormonal contraceptives (HC) on systemic inflammatory markers and endothelial function in female athletes. Thirty-nine active women (≥5 h of aerobic exercise per wk), aged 18-33 y, participated in this cross-sectional study comparing women with menstrual disorders (MD, n = 10; 0-9 cycles·y(-1)), eumenorrheic women (E, n = 13; 10-13 cycles·y(-1)), and HC users (HC, n = 16; 12 cycles·y(-1)). Fasting serum samples were collected during the early follicular phase (d2-5) for the menstruating women. Tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), C-reactive protein (CRP), soluble vascular adhesion molecule-1 (sVCAM-1), total cholesterol (TC), high- and low density lipoprotein-cholesterol (HDL-C, LDL-C), triglycerides (TG), reproductive hormones, and cortisol were measured in serum. Estradiol, progesterone, and cortisol were not statistically different between MD and E groups; cortisol was significantly greater in the HC versus E group (p = 0.002). TC (p = 0.005), LDL-C (p = 0.03), and CRP (p = 0.05) were increased in the HC versus MD and E groups. TNF-α was significantly higher in the HC (p=0.001) compared with the E group. There were no significant group differences in the concentrations of sVCAM-1 or IL-6. TNF-α and cortisol were positively correlated (r=0.31, p = 0. 058), as were sVCAM-1 and estradiol (r = 0.41, p = 0.010). In conclusion, HC use, but not exercise- associated menstrual disorders, is associated with increased TNFα and LDL-C. Key PointsSerum lipids and markers of inflammation were not altered by exercise-associated oligomenorrhea or amenorrhea.Hormonal contraceptive users had elevated total and LDL cholesterol compared with regularly menstruating non-HC users.C-reactive protein and tumor necrosis factor-α, but not soluble vascular adhesion molecule-1, were increased in hormonal contraceptive users.The long-term effect of these changes on cardiovascular disease is unknown.

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References

Mukherjee T, Nathan L, Dinh H, Reddy S, Chaudhuri G . 17-epiestriol, an estrogen metabolite, is more potent than estradiol in inhibiting vascular cell adhesion molecule 1 (VCAM-1) mRNA expression. J Biol Chem. 2003; 278(14):11746-52. DOI: 10.1074/jbc.M207800200. View

Ainsworth B, Haskell W, Whitt M, Irwin M, Swartz A, Strath S . Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc. 2000; 32(9 Suppl):S498-504. DOI: 10.1097/00005768-200009001-00009. View

Kahl K, Kruse N, Rieckmann P, Schmidt M . Cytokine mRNA expression patterns in the disease course of female adolescents with anorexia nervosa. Psychoneuroendocrinology. 2003; 29(1):13-20. DOI: 10.1016/s0306-4530(02)00131-2. View

Friday K, Drinkwater B, Bruemmer B, Chesnut 3rd C, Chait A . Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol levels in amenorrheic athletes: effects of endogenous hormone status and nutrient intake. J Clin Endocrinol Metab. 1993; 77(6):1605-9. DOI: 10.1210/jcem.77.6.8263148. View

Rickenlund A, Eriksson M, Schenck-Gustafsson K, Linden Hirschberg A . Amenorrhea in female athletes is associated with endothelial dysfunction and unfavorable lipid profile. J Clin Endocrinol Metab. 2004; 90(3):1354-9. DOI: 10.1210/jc.2004-1286. View

ODonnell E, De Souza M . The cardiovascular effects of chronic hypoestrogenism in amenorrhoeic athletes: a critical review. Sports Med. 2004; 34(9):601-27. DOI: 10.2165/00007256-200434090-00004. View

Pigott R, Dillon L, Hemingway I, Gearing A . Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun. 1992; 187(2):584-9. DOI: 10.1016/0006-291x(92)91234-h. View

Taddei S, Virdis A, Ghiadoni L, Mattei P, Sudano I, Bernini G . Menopause is associated with endothelial dysfunction in women. Hypertension. 1996; 28(4):576-82. DOI: 10.1161/01.hyp.28.4.576. View

Gianni W, Ricci A, Gazzaniga P, Brama M, Pietropaolo M, Votano S . Raloxifene modulates interleukin-6 and tumor necrosis factor-alpha synthesis in vivo: results from a pilot clinical study. J Clin Endocrinol Metab. 2004; 89(12):6097-9. DOI: 10.1210/jc.2004-0795. View

10.

Kublickiene K, Svedas E, Landgren B, Crisby M, Nahar N, Nisell H . Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators. J Clin Endocrinol Metab. 2005; 90(11):6113-22. DOI: 10.1210/jc.2005-0419. View

11.

Salem M . Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production. Curr Drug Targets Inflamm Allergy. 2004; 3(1):97-104. DOI: 10.2174/1568010043483944. View

12.

Hoch A, Dempsey R, Carrera G, Wilson C, Chen E, Barnabei V . Is there an association between athletic amenorrhea and endothelial cell dysfunction?. Med Sci Sports Exerc. 2003; 35(3):377-83. DOI: 10.1249/01.MSS.0000053661.27992.75. View

13.

Cybulsky M, Gimbrone Jr M . Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991; 251(4995):788-91. DOI: 10.1126/science.1990440. View

14.

Guazzelli C, Lindsey P, Araujo F, Barbieri M, Petta C, Aldrighi J . Evaluation of lipid profile in adolescents during long-term use of combined oral hormonal contraceptives. Contraception. 2005; 71(2):118-21. DOI: 10.1016/j.contraception.2004.08.002. View

15.

Nathan L, Pervin S, Singh R, Rosenfeld M, Chaudhuri G . Estradiol inhibits leukocyte adhesion and transendothelial migration in rabbits in vivo : possible mechanisms for gender differences in atherosclerosis. Circ Res. 1999; 85(4):377-85. DOI: 10.1161/01.res.85.4.377. View

16.

Silvestri A, Gebara O, Vitale C, Wajngarten M, Leonardo F, Ramires J . Increased levels of C-reactive protein after oral hormone replacement therapy may not be related to an increased inflammatory response. Circulation. 2003; 107(25):3165-9. DOI: 10.1161/01.CIR.0000074208.02226.5E. View

17.

Dreon D, Slavin J, Phinney S . Oral contraceptive use and increased plasma concentration of C-reactive protein. Life Sci. 2003; 73(10):1245-52. DOI: 10.1016/s0024-3205(03)00425-9. View

18.

Souter I, Janzen C, Martinez-Maza O, Breen E, Stanczyk F, Chaudhuri G . Serum levels of soluble vascular cell adhesion molecule-1 are decreased in women receiving oral contraceptives compared with normally menstruating women: implications in atherosclerosis. Fertil Steril. 2005; 83(5):1480-8. DOI: 10.1016/j.fertnstert.2004.11.048. View

19.

Dubey R, Imthurn B, Zacharia L, Jackson E . Hormone replacement therapy and cardiovascular disease: what went wrong and where do we go from here?. Hypertension. 2004; 44(6):789-95. DOI: 10.1161/01.HYP.0000145988.95551.28. View

20.

FRIEDEWALD W, Levy R, Fredrickson D . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18(6):499-502. View