Date of Award

May 2014

Degree Name

Master of Science (MS)


Exercise Science


Kevin S. Heffernan


Amenorrhea, Arterial Stiffness, Endothelial Function, Estrogen, Exercise, Vascular Remodeling

Subject Categories

Medicine and Health Sciences



Cardiovascular disease (CVD) is a leading cause of death in women. Early stages of subclinical atherosclerosis cause functional changes to the vasculature manifesting as endothelial dysfunction. These early functional changes give way to structural alterations to the vessel wall that can lead to increased arterial stiffness and irreversible vascular remodeling, (i.e. altered lumen diameter and increased intima media wall thickness (IMT)) which can ultimately lead to a cardiac event. Chronic exercise combined with energy deficiency may lead to a lack of menses or amenorrhea in premenopausal women. This state is associated with endothelial dysfunction and is believed to be attributable to hypoestrogenic mechanisms. Whether there are further detrimental structural changes to the artery in exercise-trained amenorrheic women remains unknown. PURPOSE: The primary purpose of this study was to examine indices of endothelial function, arterial stiffness and vascular remodeling in exercise-trained amenorrheic women to gain insight into the extent and severity of subclinical atherosclerotic CVD risk in this population. HYPOTHESES: It was hypothesized that, exercise-trained amenorrheic women would have lower endothelial function, higher arterial stiffness, and unfavorable vascular remodeling (greater femoral IMT and smaller femoral artery diameter) compared with exercise-trained eumenorrheic women and similar levels of endothelial dysfunction, arterial stiffness, and vascular remodeling compared to sedentary eumenorrheic women. METHODS: Forty-three women participated in this study: 10 exercise-trained amenorrheic women (Age 21 ± 3 years, Body Mass Index (BMI) 21.5 ± 2.0 kg/m2), 18 exercise-trained eumenorrheic women (Age 22 ± 3 years, BMI 22.9 ± 2.4 kg/m2), and 15 sedentary eumenorrheic women (Age 23 ± 4 years, BMI 23.9 ± 3.2 kg/m2). Flow mediated dilation (FMD) of the brachial artery was used to measure endothelial function. Carotid-femoral Pulse Wave Velocity (PWV) was used to measure arterial stiffness. Diameters and intima media thickness (IMT) of the superficial femoral artery (SFA) were taken as measures of vascular remodeling, and acquired using ultrasonography. Blood lipids, hematocrit, and hemoglobin were measured using a finger stick. A saliva collection was used to measure estradiol. Air displacement plethysmography was used to measure body fat percentage. Maximal oxygen uptake was used to measure maximal aerobic capacity and a 3-day diet record was administered to measure dietary intake. RESULTS: FMD in exercise-trained amenorrheic women was not significantly different from exercise-trained and sedentary eumenorrheic women (Amenorrheic: 7.15 ± 4.21 mm vs. Exercise-trained Eumenorrheic: 11.10 ± 4.29 mm vs. Sedentary: 0.25 ± 3.86 mm, P = 0.07). There were significant differences between groups in the reactive hyperemia shear rate stimulus (i.e. Area Under the Curve (AUC)), (Amenorrheic: 808 ± 350.1 aU vs. Exercise-trained Eumenorrheic: 862 ± 311.0 aU vs. Sedentary: 1096 ± 311.3 aU, P = 0.05). When FMD was normalized for the shear rate stimulus exercise-trained amenorrheic women had a significantly lower FMD response compared with eumenorrheic women (Amenorrheic: 6.91 ± 1.33mm vs. Exercise-trained Eumenorrheic: 10.97 ± 0.98mm vs. Sedentary: 10.57 ± 1.11mm, P = 0.05). Aortic PWV in the exercise-trained amenorrheic group was not significantly different from the eumenorrheic groups (Amenorrheic: 5.00 ± 1.00 m/s vs. Exercise-trained Eumenorrheic: 4.60 ± 0.50 m/s vs. Sedentary: 5.40 ± 0.80 m/s, P = 0.03). SFA diameters were significantly higher in the exercise-trained groups compared with the sedentary eumenorrheic group (Amenorrheic: 5.70 ± 0.72 mm vs. Exercise-trained Eumenorrheic: 5.68 ± 0.70 mm vs. Sedentary: 5.10 ± 0.63 mm, P = 0.03) while IMT was significantly lower in the exercise-trained amenorrheic women compared with the sedentary eumenorrheic women (Amenorrheic: 0.31 ± 0.03 mm vs. Exercise-trained Eumenorrheic: 0.35 ± 0.06 mm vs. Sedentary: 0.38 ± 0.07 mm, P = 0.01). 17â-Estradiol levels in exercise-trained amenorrheic women were similar to levels in eumenorrheic women (Amenorrheic: 1.66 ± 0.84 pg/ml vs. Exercise-trained Eumenorrheic: 2.22 ± 1.17 pg/ml vs. Sedentary: 2.00 ± 0.81 pg/ml, P = 0.34). Blood lipid and hematological measures, and 3-day dietary record of nutrients, vitamins and minerals were not significantly different between groups (P > 0.05). CONCLUSIONS: Exercise-trained amenorrheic women had endothelial dysfunction, but did not have increased arterial stiffness or adverse vascular remodeling when compared to their eumenorrheic counterparts. This study suggests that vascular dysfunction does not extend beyond the endothelium, as arterial stiffness and vascular remodeling are not affected by the amenorrheic state.


Open Access