Energy Deficiency Suppresses Bone Turnover in Exercising Women With Menstrual Disturbances.

CONTEXT: In exercising women, energy deficiency can disrupt the balance of bone formation and resorption, resulting in bone loss and an altered rate of bone turnover, which may influence future bone mineral density and fracture risk. OBJECTIVE: To assess the effects of energy status and estrogen status on bone turnover. DESIGN: Cross-sectional. SETTING: The Women's Health and Exercise Laboratory at Pennsylvania State University. PARTICIPANTS: Exercising women (n = 109) operationally defined as energy deficient or replete based on total triiodothyronine concentration and as estrogen deficient or replete based on menstrual cycle history and reproductive hormone metabolites. MAIN OUTCOME MEASURES: Bone formation index [procollagen type I N-terminal propeptide (P1NP) concentration corrected for average P1NP concentration in healthy reference group, i.e., [P1NP]i/median [P1NP]ref], bone resorption index [serum C-terminal telopeptide (sCTx) concentration corrected for average sCTx concentration in healthy reference group, i.e., [sCTx]i/median [sCTx]ref], bone balance (ratio of bone formation index to bone resorption index to indicate which process predominates), and bone turnover rate (collective magnitude of bone formation index and bone resorption index to indicate overall amount of bone turnover). RESULTS: The combination of energy and estrogen deficiency resulted in less bone formation and a lower rate of bone turnover compared with women who were estrogen deficient but energy replete. Regardless of estrogen status, energy deficiency was associated with decreased bone resorption as well. No main effects of estrogen status were observed. CONCLUSIONS: The results highlight the critical role that adequate energy plays in the regulation of bone turnover, especially bone formation, in exercising women with menstrual disturbances.

Iron status at opposite ends of the menstrual function spectrum.

OBJECTIVES: Although exercising women are at high risk of poor iron status, it is unknown how non-pathological, physiological menstrual function affects iron status. As such, this study investigates the association between menstrual function and iron status in exercising women with amenorrhea and exercising women with ovulatory, eumenorrheic menstrual cycles. DESIGN: Cross-sectional analysis of iron depletion prevalence, iron status indices, exercise parameters, and diet composition. METHODS: Women aged 18-35 years performing at least 2 h per week of aerobic exercise were recruited. Women with amenorrhea (AMEN) were defined by the absence of menses for at least 90 days or less than 6 menses in the past 12 months (n = 82). Women with ovulatory, eumenorrheic menstrual cycles (OvEU) were defined by the presence of ovulatory cycles of 26-35 days in length for the past 6 months (n = 109). Group differences in serum ferritin (Ft), soluble transferrin receptor (sTfR), total body iron (TBI), hemoglobin (Hb), hematocrit (Hct), iron depletion prevalence (Ft <15 µg/L), peak oxygen consumption (VO2peak), exercise minutes per week, and diet logs were assessed. RESULTS: The prevalence of iron depletion was greater in OvEU when compared to AMEN (26% vs. 15%, p = 0.04). No significant differences were observed between AMEN and OvEU in Ft (30.2 ± 2.2 vs. 24.9 ± 2.6 µg/L; p = 0.62), sTfR (5.2 ± 1.4 vs. 4.9 ± 1.5 mg/L; p = 0.95), TBI (5.3 ± 2.7 vs. 4.8 ± 3.7 mg/kg; p = 0.42), Hb (13.2 ± 0.4 vs. 13.4 ± 0.6 g/dL; p = 0.80), Hct (39.5 ± 0.8% vs. 39.8 ± 4.1%; p = 0.93), or exercise parameters. AMEN consumed more vitamin C than OvEU (269 ± 180 vs. 129 ± 141 mg/day, p < 0.001), but all other dietary factors were similar between AMEN and OvEU. CONCLUSION: Exercising women with ovulatory, eumenorrheic cycles are at a greater risk of iron depletion than exercising, amenorrheic women. Thus, menstrual function must be considered when screening for poor iron status in exercising women.

Food Versus Pharmacy: Assessment of Nutritional and Pharmacological Strategies to Improve Bone Health in Energy-Deficient Exercising Women.

PURPOSE OF REVIEW: The review aims to summarize our current knowledge surrounding treatment strategies aimed at recovery of bone mass in energy-deficient women suffering from the Female Athlete Triad. RECENT FINDINGS: The independent and interactive contributions of energy status versus estrogen status on bone density, geometry, and strength have recently been reported, highlighting the importance of addressing both energy and estrogen in treatment strategies for bone health. This is supported by reports that have identified energy-related features (low body weight and BMI) and estrogen-related features (late age of menarche, oligo/amenorrhea) to be significant risk factors for low bone mineral density and bone stress injury in female athletes and exercising women. Nutritional therapy is the recommended first line of treatment to recover bone mass in energy-deficient female athletes and exercising women. If nutritional therapy fails after 12 months or if fractures or significant worsening in BMD occurs, pharmacological therapy may be considered in the form of transdermal estradiol with cyclic oral progestin (not COC).

A summary of the influence of exogenous estrogen administration across the lifespan on the GH/IGF-1 axis and implications for bone health.

Bone growth, development, and remodeling are modulated by numerous circulating hormones. Throughout the lifespan, the extent to which each of the hormones impacts bone differs. Understanding the independent and combined impact of these hormones on controlling bone remodeling allows for the development of more informed decision making regarding pharmacology, specifically the use of hormonal medication, at all ages. Endocrine control of bone health in women is largely dictated by the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and the hypothalamic-pituitary-ovarian (HPO) axis. Growth hormone, secreted from the pituitary gland, stimulates cells in almost every tissue to secrete IGF-1, although the majority of circulating IGF-1 is produced hepatically. Indeed, systemic IGF-1 concentrations have been found to be correlated with bone mineral density (BMD) in both pre- and post-menopausal women and is often used as a marker of bone formation. Sex steroids produced by the ovaries, namely estradiol, mediate bone resorption through binding to estrogen receptors on osteoclasts and osteoblasts. Specifically, by increasing osteoclast apoptosis and decreasing osteoblast apoptosis, adequate estrogen levels prevent excessive bone resorption, which helps to explain the rapid decline in bone mass that occurs with the menopausal decrease in estrogen production. Though there are documented correlations between endogenous estrogen concentrations and GH/IGF-1 dynamics, this relationship changes across the lifespan as sex-steroid dynamics fluctuate and, possibly, as tissue responsiveness to GH stimulation decreases. Aside from the known role of endogenous sex steroids on bone health, the impact of exogenous estrogen administration is of interest, as exogenous formulations further modulate GH and IGF-1 production. However, the effect and extent of GH and IGF-1 modulation seems to be largely dependent on age at administration and route of administration. Specifically, premenopausal women using combined oral contraceptive therapy (COC), post-menopausal women taking oral hormone therapy (HT), and both pre- and post-menopausal women using a transdermal form of estrogen therapy (COC or HT) demonstrate disparate GH/IGF-1 responses to exogenous estrogen. This review serves to summarize what is currently known regarding the influence of exogenous estrogen administration across the lifespan on the GH/IGF-1 axis and implications for bone health.