Its prevalence is markedly higher in recreationally and competitively exercising women and women with physically demanding jobs (≈1% to 44%) than in sedentary women (≈2% to 5%).2,3 Hypothalamic-pituitary-ovarian suppression in physically active women with FHA (ExFHA) has been related causally to energy deficiency (ie, caloric deficit) in association with high energy expenditure and insufficient energy intake (ie, low caloric intake).
4Circulating estradiol concentrations in women with ExFHA are chronically low and resemble those observed in postmenopausal women and in men. 5,6 In postmenopausal women, estrogen deficiency is associated with increases in blood pressure (BP) and a marked acceleration in the development and progression of atherosclerosis.7 Cardiovascular consequences of premenopausal hypoestrogenemia in ExFHA women are not yet known, but disruption of the menstrual cycle during the reproductive years is also associated with the premature development and progression of coronary artery disease. 8,9 However, in contrast to postmenopausal women, ExFHA women have lower resting systolic blood pressure (SBP) and heart rate (HR) than age-and fitness-matched estrogen-replete physically active women.10,11 The presence of low arterial BP, despite hypoestrogenemia, suggests that estrogen deficiency may have different consequences for BP regulation in premenopausal and postmenopausal women.The sympathetic nervous system and the renin-angiotensinaldosterone system (RAAS) are cornerstones of BP regulation. Estrogen modulates both. In estrogen-deficient Abstract-Our prior observations in normotensive postmenopausal women stimulated the hypotheses that compared with eumenorrheic women, active hypoestrogenic premenopausal women with functional hypothalamic amenorrhea would demonstrate attenuated reflex renin-angiotensin-aldosterone system responses to an orthostatic challenge, whereas to defend blood pressure reflex increases in muscle, sympathetic nerve activity would be augmented. To test these hypotheses, we assessed, in recreationally active women, 12 with amenorrhea (ExFHA; aged 25±1 years; body mass index 20.7±0.7 kg/m 2 ; mean±SEM) and 17 with eumenorrhea (ExOv; 24±1 years; 20.9±0.5 kg/m 2 ), blood pressure, heart rate, plasma renin, angiotensin II, aldosterone, and muscle sympathetic nerve activity at supine rest and during graded lower body negative pressure (−10, −20, and −40 mm Hg). At baseline, heart rate and systolic blood pressure were lower (P<0.05) in ExFHA (47±2 beats/min and 94±2 mm Hg) compared with ExOv (56±2 beats/min and 105±2 mm Hg), but muscle sympathetic nerve activity and renin-angiotensin-aldosterone system constituents were similar (P>0.05). In response to graded lower body negative pressure, heart rate increased (P<0.05) and systolic blood pressure decreased (P<0.05) in both groups, but these remained consistently lower in ExFHA (P<0.05). Lower body negative pressure elicited increases (P<0.05) in renin, angiotensin II, and aldosterone in ExOv, but not in ExFHA (P>0.05). Muscle sympatheti...