Long-term estrogen deficiency lowers regional blood flow, resting systolic blood pressure, and heart rate in exercising premenopausal women

Abstract

The cardiovascular consequences of hypoestrogenism in premenopausal women are unclear. Accordingly, the influence of menstrual status and endogenous estrogen (E2) exposure on blood pressure (BP), heart rate (HR), and calf blood flow in young (18 -35 yr) regularly exercising premenopausal women with exercise-associated menstrual aberrations was investigated. Across consecutive menstrual cycles, daily urinary ovarian steroid levels were analyzed, and the area under the curve was calculated to determine menstrual status and E2 exposure. BP, HR, blood flow, vascular conductance, and resistance were measured at baseline and following ischemic calf exercise. Exercising subjects consisted of 14 ovulatory (ExOv), 10 short-term (anovulatory and Յ100 days amenorrhea; ST-E 2 Def), and 8 long-term (Ͼ100 days amenorrhea; LT-E2 Def) E2-deficient women. Nine sedentary ovulatory subjects (SedOv) were also studied. All groups were similar in age (24.8 Ϯ 0.7 yr), height (164.8 Ϯ 1.3 cm), weight (57.9 Ϯ 0.9 kg), and body mass index (21.3 Ϯ 0.3 kg/m 2 ). E2-deficient groups had lower (P Ͻ 0.002) E2 exposure compared with ovulatory groups. Resting systolic BP, HR, blood flow, and vascular conductance were lower (P Ͻ 0.05) and vascular resistance higher (P Ͻ 0.05) in LT-E2 Def compared with both ovulatory groups. Peak ischemic blood flow, vascular conductance, and HR were also lower (P Ͻ 0.05) and vascular resistance higher (P Ͻ 0.05) in LT-E2 Def compared with all other groups. Our findings show that exercising women with longterm E2 deficiency have impaired regional blood flow and lower systolic BP and HR compared with exercising and sedentary ovulatory women. These cardiovascular alterations represent markers of altered vascular function and autonomic regulation of which the long-term effects remain unknown.exercise-associated amenorrhea; menstrual aberrations; vascular resistance EXERCISE-ASSOCIATED AMENORRHEA (EAA) is the most severe of menstrual disturbances (10, 11). The etiology of EAA is linked to chronic energy deficiency that is communicated as inhibitory signals to the reproductive axis (11). Chronic suppression of ovarian steroids in postmenopausal women is associated with an increased risk of premature chronic diseases, including cardiovascular disease (9). Little is known of the short-and long-term cardiovascular consequences of hypoestrogenism in otherwise healthy premenopausal exercising women.Preliminary data suggest that women with EAA may develop a proatherogenic phenotype, including increases in total cholesterol, low density lipoprotein (LDL)-cholesterol, and apolipoprotein (apo)B, with concurrent decreases in apoAI and the apoAI-to-apoB ratio (24, 38), increased susceptibility of LDL-cholesterol to peroxidation (2), and impaired brachial artery endothelium-dependent flow-mediated vasodilation (38,45,46). Alarmingly, the severity of endothelial dysfunction in EAA (38,45,46) is similar to that previously observed in postmenopausal women (6) and coronary artery diseased patients (7). Reversibility of endothelial d...

Discordant Orthostatic Reflex Renin–Angiotensin and Sympathoneural Responses in Premenopausal Exercising-Hypoestrogenic Women

“…10,11 Similar hemodynamic changes have been documented in older sedentary hypoestrogenic postmenopausal women. 36,37 We now report for the first time that compared with estrogen replete women, hypoestrogenic ExFHA women demonstrate (i) lower HR and BP during orthostatic stress as well as at rest; (ii) a shift toward sympathetic control of BP regulation during LBNP; and (iii) uncoupling of reflex sympathoneural and RAAS responses to this hypotensive stimulus.…”

“…31 Thus, it is plausible that low triiodothyronine, as observed in ExFHA women in the current and in previous 10,11 studies, may also contribute to this low renin state. Considering the similarity of body mass index in our 2 groups and the clinical absence of edema, intravascular volume expansion is an unlikely RAAS-suppressive mechanism.…”

“…The present study adds to a body of literature describing altered cardiovascular function in exercise-trained women with FHA, including impaired conduit 11,35 and resistance 10,11 vessel function and increased regional vascular resistance. 10,11 Similar hemodynamic changes have been documented in older sedentary hypoestrogenic postmenopausal women.…”

“…Exercising status was defined as >2 hours/week of structured exercise for >6 months and a peak aerobic capacity of ≥40 mL/kg/min. 10 In eumenorrheic women, ovulatory status was confirmed in the menstrual cycle before testing by using a commercial urinary ovulation hormone kit (Clearblue Easy; Unipath Diagnostics, Waltham, MA).…”

“…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.…”