Impaired vascular function in exercising anovulatory premenopausal women is associated with low bone mineral density

Abstract

In estrogen‐deficient post‐menopausal women, osteoporosis shares a common link with cardiovascular disease risk, including endothelial dysfunction. The current study sought to examine associations between bone mineral density (BMD) and endothelial function in estrogen‐deficient premenopausal women with exercise‐associated menstrual disturbances. Recreationally trained women (24.3 ± 0.8 years; overall mean ± SEM) who were estrogen deficient (amenorrheic or eumenorrheic anovulatory cycles; E2Def; n = 13) or estrogen replete (eumenorrheic ovulatory cycles; E2Rep; n = 14) were studied. Total body and lumbar BMD (L1‐L4) were determined using dual‐energy X‐ray absorptiometry. Serum markers of oxidative stress (oxidized low‐density lipoprotein; OxLDL), energy deficiency (triiodothyronine), and bone turnover (osteocalcin, c‐telopeptide X, P1NP) were assessed. Estrogen exposure was determined by assessing daily urinary estrone‐3‐glucuronide (E1G) across a monitoring period. Calf blood flow (CBF), an index of endothelial function, was measured using strain‐gauge plethysmography. CBF, total body and L1‐L4 BMD, triiodothyronine and E1G were lower (P < 0.05), and c‐telopeptide crosslinks higher (P < 0.05) in E2Def. Osteocalcin and OxLDL did not differ (P > 0.05) between groups. L1‐L4 BMD, osteocalcin, and E1G were the strongest predictors of CBF (R2=0.615, P < 0.001). CBF was the strongest predictor of L1‐L4 BMD (R2=0.478, P < 0.001). L1‐L4 (r = 0.558, P = 0.008) and CBF (r = 0.534, P = 0.004) were independently correlated with E1G. In young recreationally trained premenopausal women with anovulatory menstrual disturbances, low CBF predicts decreased lumbar BMD, suggesting impaired peripheral endothelial function may predict early unfavorable changes in bone metabolism. This finding may be of relevance in the early detection of cardiovascular and bone health decrements in otherwise healthy estrogen‐deficient premenopausal women.

Indexes of aortic wave reflection are not augmented in estrogen‐deficient physically active premenopausal women

“…In response to energy deficiency, ExFHA demonstrate numerous metabolic and hormonal perturbations, including low levels of triiodothyronine (T3) . T3, the physiologically active form of thyroid hormone, is a classic indicator of nutritional status, but it is also known to exert cardiovascular effects.…”

“…In response to energy deficiency, ExFHA demonstrate numerous metabolic and hormonal perturbations, including low levels of triiodothyronine (T3). 9,10,12,13,34 T3, the physiologically active form of thyroid hormone, is a classic indicator of nutritional status, but it is also known to exert cardiovascular effects. Studies report increases in HR and CO and decreases in vascular resistance in response to T3 administration in patients with low T3.…”

Genetic Scores of eNOS, ACE and VEGFA Genes Are Predictive of Endothelial Dysfunction Associated Osteoporosis in Postmenopausal Women

“…It is apparently clear that estrogen deficiency, bone loss and estrogen receptor mediated impaired endothelial function are interconnected, which is endorsed by the finding that even estrogen-deficient premenopausal women have higher chances of endothelial dysfunction induced bone loss [33]. Incremental decrease of BMDs at femoral neck and lumbar spine has been observed to be associated with impaired endothelial function in the present study (Figure 2) suggesting that BMD and endothelial dysfunction are linearly related.…”

Energy availability modulates regional blood flow via estrogen-independent pathways in regularly menstruating young women

“…This may have important health implications for young women. Impaired FBF has been associated with hypertension and increased risk of adverse cardiovascular events (Nishiyasu et al 1992;O'Donnell et al 2019;O'Donnell et al 2014). Long-term LEA can cause chronic estrogen deficiency, with amenorrhea often indicating long-term LEA in active women (Williams et al 2001;Heikura et al 2018).…”