Estrogen and peptide YY are associated with bone mineral density in premenopausal exercising women J.L. Scheid, R.J. Toombs, G. Ducher, J.C. Gibbs, N.I. Williams, M.J. De Souza ⁎ Women's Health and Exercise Laboratory, Department of Kinesiology, Penn State University, University Park, PA, USA abstract article info Article history: Received 8 October 2010 Revised 11 March 2011 Accepted 14 April 2011 Available online 28 April 2011 Edited by: Toshio Matsumoto Keywords: Estrogen Peptide YY Exercise Bone mineral density Women Background: In women with anorexia nervosa, elevated fasting peptide YY (PYY) is associated with decreased bone mineral density (BMD). Prior research from our lab has demonstrated that fasting total PYY concentrations are elevated in exercising women with amenorrhea compared to ovulatory exercising women. Purpose: The purpose of this study was to assess the association between fasting total PYY, average monthly estrogen exposure and BMD in non-obese premenopausal exercising women. Methods: Daily urine samples were collected and assessed for metabolites of estrone 1-glucuronide (E1G) and pregnandiol glucuronide (PdG) for at least one menstrual cycle if ovulatory or a 28-day monitoring period if amenorrheic. Fasting serum samples were pooled over the measurement period and analyzed for total PYY and leptin. BMD and body composition were assessed by dual-energy X-ray absorptiometry. Multiple regression analyses were performed to determine whether measures of body composition, estrogen status, exercise minutes, leptin and PYY explained a significant amount of the variance in BMD at multiple sites. Results: Premenopausal exercising women aged 23.8 ± 0.9 years with a mean BMI of 21.2 ± 0.4 kg/m 2 exercised 346 ± 48 min/week and had a peak oxygen uptake of 49.1 ± 1.8 mL/kg/min. Thirty-nine percent (17/44) of the women had amenorrhea. Fasting total PYY concentrations were negatively associated with total body BMD (p = 0.033) and total hip BMD (p = 0.043). Mean E1G concentrations were positively associated with total body BMD (p = 0.033) and lumbar spine (L2–L4) BMD (p = 0.047). The proportion of variance in lumbar spine (L2–L4) BMD explained by body weight and E1G cycle mean was 16.4% (R 2 = 0.204, p = 0.012). The proportion of variance in hip BMD explained by PYY cycle mean was 8.6% (R 2 = 0.109, p = 0.033). The proportion of variance in total body BMD explained by body weight and E1G cycle mean was 21.9% (R 2 = 0.257, p = 0.003). Conclusion: PYY, mean E1G and body weight are associated with BMD in premenopausal exercising women. Thus, elevated PYY and suppressed estrogen concentrations are associated with, and could be directly contributing to, low BMD in exercising women with amenorrhea, despite regular physical activity. © 2011 Elsevier Inc. All rights reserved. Introduction Exercise-related menstrual disturbances are often observed in women who participate in physical activity ranging from the recrea- tional to the competitive level, and from exercise of moderate to strenuous intensity [1,2]. Amenorrhea represents the most extreme presentation of menstrual irregularity and is described as “functional hypothalamic amenorrhea” (FHA) since the disruption occurs at the level of the hypothalamus, concomitant with an energy deficiency, leading to chronically suppressed reproductive function and reduced circulating estrogen concentrations [3,4]. Alterations in metabolic and endocrine homeostasis indicative of an energy deficiency in exercising women with FHA include suppressed resting energy expenditure (REE) [5–7], reduced concentrations of total triiodothyronine (TT 3 ) [5,6,8] insulin-like growth factor-1 (IGF-1) [9], and insulin [7], and elevated concentrations of growth hormone (GH) [10], ghrelin [8,11,12], and cortisol [2,9,13]. The metabolic and endocrine alterations demonstrated in exercising women with FHA are likely contributing to low bone mineral density (BMD) and consequently, leading to musculoskeletal consequences such as stress fractures and pathological bone loss [14]. In our laboratory, we have reported elevated peptide YY (PYY) concentrations in exercising women with FHA secondary to an energy deficit [15]. Peptide YY is a gastrointestinal peptide secreted from the endocrine L cells of the ileum of the intestine and appears to be involved with appetite suppression, satiety, and energy homeostasis [19–22]. PYY acts centrally to inhibit neuropeptide Y (NPY) and activate the pro- opiomelanocortin (POMC) neurons in the arcuate nucleus resulting in a reduction in food intake [19]. Interestingly, while exercising women and adolescent athletes with FHA demonstrate elevations in fasting PYY concentrations [15,23], women with a more severe energy deficiency, i.e. women and adolescent girls with anorexia nervosa, also demon- strate elevated fasting PYY concentrations [16–18]. These findings Bone 49 (2011) 194–201 ⁎ Corresponding author at: Department of Kinesiology, Penn State University, University Park, PA 16802, USA. Fax: +1 814 865 4602. E-mail address: mjd34@psu.edu (M.J. De Souza). 8756-3282/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.bone.2011.04.011 Contents lists available at ScienceDirect Bone journal homepage: www.elsevier.com/locate/bone