A Narrative Review of the Vascular Consequences of Estrogen Deficiency: A Focus on Female Athletes with Functional Hypothalamic Amenorrhea

Estrogen deficiency is linked with accelerated progression of atherosclerosis. Premenopausal women presenting with ovarian disruption due to functional hypothalamic amenorrhea (FHA) are characterised by estrogen deficiency. One common and reversible form of FHA in association with energy deficiency is exercise-associated amenorrhea (EAA). Despite being young, otherwise healthy and participating in regular exercise training, women with EAA demonstrate paradoxical changes in cardiovascular function, including impaired endothelial function, a known permissive factor for the progression and development of atherosclerosis. Such alterations suggest a profound effect of estrogen deficiency on vascular function. The long-term cardiovascular consequences of impaired vascular function in response to ovarian disruption in women with EAA remain to be determined. However, retrospective studies indicate premature development and progression of coronary artery disease in older premenopausal women reporting a history of hypothalamic ovarian disruption. Importantly, in women with EAA, estrogen therapy and resumption of menses restores endothelial function. In this review we focus on the influence of estrogen deficiency in association with energy deficiency in mediating changes in cardiovascular function in women with EAA, including endothelial function, regional blood flow, arterial stiffness and intima media thickness. The influence of energy deficiency and exercise training are also considered.