Is There an Association between Athletic Amenorrhea and Endothelial Cell Dysfunction? ANNE ZENI HOCH 1 , RANIA L. DEMPSEY 2 , GUILLERMO F. CARRERA 3 , CHARLES R. WILSON 3 , ELLEN H. CHEN 4 , VANESSA M. BARNABEI 5 , PAUL R. SANDFORD 6 , TRACEY A. RYAN 8 , and DAVID D. GUTTERMAN 7 1 Sports Medicine Center, Departments of Orthopaedic Surgery/Cardiovascular Center; 2 Family & Community Medicine; 3 Radiology; 4 Cardiovascular Medicine; 5 Patrick & Margaret McMahon Obstetrics & Gynecology; 6 Physical Medicine and Rehabilitation; and 7 Cardiovascular Center, Zablocki Veterans Administration Medical Center, Medical College of Wisconsin, Milwaukee, WI; and 8 Froedtert Memorial Lutheran Hospital, Milwaukee, WI ABSTRACT HOCH, A. Z., R. L. DEMPSEY, G. F. CARRERA, C. R. WILSON, E. H. CHEN, V. M. BARNABEI, P. R. SANDFORD, T. A. RYAN, and D. D. GUTTERMAN. Is There an Association between Athletic Amenorrhea and Endothelial Cell Dysfunction? Med. Sci. Sports Exerc., Vol. 35, No. 3, pp. 377–383, 2003. Purpose: To test the hypothesis that young females with athletic amenorrhea and oligomenorrhea show signs of early cardiovascular disease manifested by decreased endothelium-dependent dilation of the brachial artery. Methods: Ten women with athletic amenorrhea (mean  SE, age 21.9  1.2 yr), 11 with oligomenorrhea (age 20.8  1.1 yr), and 11 age-matched controls (age 20.2  1.1 yr) were studied. Study subjects were amenorrheic an average of 2.3 (range 0.6 –5) yr and oligomenorrheic an average of 6.2 yr. All ran a minimum of 25 miles·wk -1 . They were nonpregnant and free of metabolic disease. Brachial artery flow-mediated dilation (endothelium-dependent) was measured with a noninvasive ultrasound technique in each group. Results: Endothelium-dependent brachial artery dilation was reduced in the amenorrheic group (1.08  0.91%) compared with oligomenorrheic (6.44  1.3%; P  0.05) and eumenorrheic (6.38  1.4%; P  0.05) groups. Conclusion: Athletic amenorrhea is associated with reduced endothelium-dependent dilation of the brachial artery. This may predispose to accelerated development of cardiovascular disease. Key Words: FEMALE ATHLETE TRIAD, WOMEN’S HEALTH, CARDIOVASCULAR DISEASE, FE- MALE ATHLETES I n 1972, Congress passed Title IX, the Educational Amendment Act that ensured that women would have equal opportunities for interscholastic sports participa- tion. Since that time, the number of female athletes has risen dramatically, and today almost 3 million young women compete in American high school sports programs. For women, the benefits of an active lifestyle including running are profound and well known. Women who participate in regular sports programs have been found to have higher self-esteem, a reduction in depression, and better body im- ages (31). The physiological benefits of exercise include increased cardiorespiratory fitness, which leads to decreased cardiovascular disease and obesity (25). Teegarden et al. (32) found that active girls who participate in high school sports had a significantly greater bone mineral density, which may help to prevent osteoporosis in the future. However, as the number of women participating in sports grows, we have also discovered an increasing prevalence of exercise-associated menstrual irregularities (amenorrhea, oligomenorrhea, luteal phase dysfunction, and anovulatory cycles). Athletic amenor- rhea is a component of the Female Athlete Triad, an interre- lated problem of disordered eating, amenorrhea of hypotha- lamic origin, and osteoporosis. Athletic amenorrhea is a complex, multifactorial condition. Extreme exercise, excessive caloric restrictions, physical and emotional stress associated with exercise/competition, percentage of body fat, and genetics all play a role. However, recent studies have pointed toward dietary factors as the key etiologic component in athletic in- duced amenorrhea (26). Although the exact mechanism of athletic amenorrhea is not fully understood, it has been shown to be associated with osteopenia and osteoporosis in several studies (11,12). Ath- letic amenorrhea is known to have a hormonal profile sim- ilar to menopause, characterized by low estrogen levels, which is etiologic in the development of osteoporosis in postmenopausal women. However, the greatest medical consequence of menopause is the associated cardiovascular disease (7). Cardiovascular disease is the number 1 killer of women. Cardiovascular risk increases significantly after menopause, when estrogen levels drop. The earliest sign of Address for correspondence: Anne Zeni Hoch, D.O., Sports Medicine Center, Women’s Sports Medicine Program, Departments of Orthopaedic Surgery/Cardiovascular Center, 9200 West Wisconsin Avenue, Medical College of Wisconsin, Milwaukee, WI 53226; E-mail: azeni@mcw.edu. Submitted for publication March 2002. Accepted for publication November 2002. 0195-9131/03/3503-0377/$3.00/0 MEDICINE & SCIENCE IN SPORTS & EXERCISE ® Copyright © 2003 by the American College of Sports Medicine DOI: 10.1249/01.MSS.0000053661.27992.75 377