Potential Impact of Exercise-Associated Amenorrhea and Subsequent Estrogen Therapy on Cardiovascular Disease Risk Factors in Pre-Menopausal Athletes: A Research Protocol

Abstract

Introduction: Women with exercise-associated amenorrhea (EAA) have impaired pulsatile gonadotropin-releasing hormone (GnRH) release that disrupts sufficient estrogen secretion, causing hypoestrogenism. As there is limited research on the influence of hypoestrogenism on cardiovascular health in pre-menopausal women, the purpose of this study is to assess its effect on the concentrations of estrogen and early cardiovascular diseases (CVD) risk factors – nitric oxide, endothelin-1 (ET-1), and E-selectin – in women with EAA.
Methods: A total of 90 participants between the ages of 18-35 will be selected based on the inclusion criteria of athleticism status (8 hours of structured physical activity/week) and body mass index (BMI) range of 18.5-24.5. Out of the 90 participants, 45 will have EAA and 45 will have regular menstrual status. Exclusion criteria: Smokers, women on contraceptives and those with pre-existing CVD and respiratory health conditions/family history of these conditions. Baseline data of estrogen and CVD risk factor concentrations will be obtained from all 90 participants through bi-weekly blood draws and serum analysis in the first month of the 7-month study. The amenorrheic, athletes (n=45) will receive 0.025 mg of 17-β estradiol transdermally via estrogen patches daily for months 2-7 of the study. Blood will be collected bi-weekly from these amenorrheic, athletes (n=45) during months 2-7 to quantify estrogen and CVD risk factor concentrations during the intervention. Statistical analysis: 2-way ANOVA (analysis of variance) test to compare the levels of E2 and CVD risk factors prior to and following estrogen treatment of amenorrheic, athletic subjects.
Discussion: Although there are many cardiovascular risk factors which can be used as markers to determine the effect of EAA on cardiovascular health, nitric oxide, ET-1, and E-selectin may serve to provide more accurate analysis due to less present confounding factors as other markers. Anticipated results include increased nitric oxide and decreased ET-1 and E-selectin concentrations following estrogen therapy.
Conclusion: Diagnosis and management of menstrual irregularities like EAA is imperative for maintaining good cardiovascular health. Further research to determine whether estrogen therapy can be used as a long-term solution for women with EAA, and whether it should be provided in conjunction with nutritional intervention is recommended.