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Nutritional status changes fracture risk in hypothalamic amenorrhea
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Adolescent girls and young women with hypothalamic amenorrhea have differing fracture risks depending on whether the condition was brought on by anorexia nervosa or athletic oligo-amenorrhea, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
Anorexia nervosa and athletic amenorrhea represent conditions of functional hypothalamic amenorrhea, a common cause of secondary amenorrhea associated with weight loss, excessive exercise or stress, Madhusmita Misra, MD, MPH, the Fritz Bradley Talbot and Nathan Bill Talbot professor of pediatrics at Harvard Medical School and division chief of pediatric endocrinology at Massachusetts General Hospital, and colleagues wrote in the study background.
“Although we have known for many years that low-weight eating disorders, such as anorexia nervosa, are high-risk conditions for impaired bone metabolism and fractures, this study indicates deleterious effects of oligo-amenorrhea on bone in even normal-weight athletes engaged in weight-bearing activity,” Misra told Endocrine Today. “The study findings suggest that one may need to consider therapeutic interventions even before heavily exercising young women meet current criteria for osteoporosis.”
Misra and colleagues analyzed data from 426 women and girls aged 14 to 22 years, including 231 with anorexia nervosa (31.6% were not amenorrheic), 94 with athletic oligo-amenorrhea and 101 normal-weight, eumenorrheic controls. Enrolled athletes engaged in weight-bearing exercise for at least 4 hours per week or completed at least 20 miles of running per week for at least 6 months in the preceding year; athletic oligo-amenorrhea was defined as lack of a menstrual period for at least 3 months within the preceding 6 months, or absence of menses at age 15 years. Participants with anorexia were screened for anorexia studies being conducted at Massachusetts General Hospital between 2002 and 2016. Eumenorrheic controls had BMI between the 10th and 90th percentiles for age and at least nine menstrual cycles in the preceding year. Participants self-reported fracture history and underwent DXA measurements for assessment of areal bone mineral density of the whole body, lumbar spine and total hip, with areal BMD z scores calculated for age, sex and race. Volumetric BMD, bone geometry and structure were assessed at the distal radius and tibia via high-resolution peripheral quantitative CT for a subset of participants.
Researchers found that participants with anorexia had lower whole body and hip areal BMD scores vs. those with athletic oligo-amenorrhea and controls, whereas there were no differences between participants with athletic oligo-amenorrhea and controls (P < .0001 for all comparisons). Participants with anorexia and athletic oligo-amenorrhea had lower spine areal BMD z scores vs. controls (P < .01). Differences persisted after researchers controlled for age, race and height z scores, apart from an attenuation in the difference between participants with athletic oligo-amenorrhea and controls for spine areal BMD z scores, according to the researchers.
At the distal radius, researchers observed lower total and trabecular volumetric BMD, cortical area and thickness and estimated strength for participants with anorexia vs. controls, persisting after adjustment for age, race and height z scores. However, after adjusting for BMI z scores, any between-group differences were lost, according to the researchers.
At the tibia, participants with anorexia had lower measurements for total and trabecular volumetric BMD, percent cortical area and thickness and percent trabecular area and number vs. those with athletic oligo-amenorrhea and controls (P .05 for all comparisons). Participants with athletic oligo-amenorrhea had lower cortical volumetric BMD vs. controls (P = .002), despite greater cortical perimeter (P = .046); however, these groups did not differ for other bone parameters, according to the researchers. Differences among groups were no longer significant after controlling for BMI z scores.
Researchers also observed that overall fracture prevalence was similar in participants with anorexia (38.2%; P = .008) and athletic oligo-amenorrhea (42.6%; P = .005) vs. controls (22.4%). Those with athletic oligo-amenorrhea were more likely to experience stress fractures (25%; P < .0001) vs. participants with anorexia (5%; P < .0001) and controls (1.2%). In contrast, more participants with anorexia were likely to experience non-stress fractures (35.7%; P = .005) vs. those with athletic oligo-amenorrhea (20%; P = .01) or controls (21.2%).
“Young athletes should be counseled to optimize caloric intake to avoid inadvertent undereating, and any disordered eating behavior should be addressed early to prevent occurrence of oligo-amenorrhea,” Misra said. “Anorexia nervosa, of course, has significant deleterious effects on bone density, structure and strength estimates, and should similarly be diagnosed and treated early during the disease to avoid long-lasting effects on bone health.”
As Endocrine Today previously reported, the Endocrine Society released a clinical practice guideline in March, stating that women with functional hypothalamic amenorrhea should receive multidisciplinary treatment, including medical, dietary and mental health support to avoid potential chronic health complications ranging from infertility to osteoporosis.
“While data are becoming available for bone outcomes in adolescents and young adult women with functional hypothalamic amenorrhea, data remain sparse for over-exercising adolescent and young adult men with or without eating disorders,” Misra said. “More studies are necessary to address this knowledge gap.” – by Regina Schaffer
For more information:
Madhusmita Misra, MD, MPH, can be reached at Massachusetts General Hospital for Children, 175 Cambridge St., Fifth Floor, Boston, MA 02114; email: mmisra@mgh.harvard.edu.
Disclosures: The authors report no relevant financial disclosures.
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