{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T04:56:03Z","timestamp":1758862563023,"version":"3.41.2"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015758","name":"Novo Nordisk Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015758","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Physiological growth hormone is secreted during slow-wave sleep. Traditionally, growth hormone (GH) therapy is given in daily GH injections before sleep. While morning and evening GH injections produce comparable effects on growth and IGF-1 levels, the evening schedule better imitates the physiological diurnal pattern of GH secretion and action. However, the inflexibility of bedtime injection schedules, coupled with the discomfort and psychological distress associated with the injection and local reaction, may cause sleep disturbances in patients, and may significantly burden them and their families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our objective was to evaluate evening vs. morning daily GH injections with respect to sleep-wake pattern, duration, and activity index in children treated with growth hormone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>An open-label, randomized crossover trial of 20 children (11 boys) 5\u201314 years of age with isolated growth hormone deficiency (n=12) and idiopathic short stature (n=8) treated with daily injections of median GH dose 33 (range13-46) mcg\/kg\/d was performed. Each subject received 2 weeks of evening injections and 2 weeks of morning injections. Patients' sleep-wake patterns and activity index were assessed by a 7-day actigraph covering the second week of each treatment schedule.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All subjects slept well, within recommended ranges for sleep parameters, regardless of whether they were receiving morning or evening GH injections. Results were comparable for all measures: total time in bed (min), 526.0 \u00b1 51.8 vs 516.9 \u00b1 57.4 for evening and morning GH injections, respectively; total sleep time (min), 512.4 \u00b1 51.1 vs 504.3 \u00b1 57.7; sleep efficiency (%), 93.6 \u00b1 2.6 vs 94.2 \u00b1 2.3; sleep onset latency (min), 8.9 \u00b1 8.1 vs 7.4 \u00b1 6.8; number of arousals per night, 14.5 \u00b1 5.4 vs 12.5 \u00b1 5.2; and 24-hour activity index, 68.3 \u00b1 4.0 vs 67.0 \u00b1 5.0, respectively. No difference was found between the growth hormone deficient and idiopathic short stature group. No difference was found between boys and girls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Sleep-wake patterns and activity index were not affected by treatment schedules. We recommend that growth hormone injections take place at any regular time according to the family's convenience.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1483199","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T05:12:05Z","timestamp":1739769125000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Morning vs. evening growth hormone injections and their impact on sleep-wake patterns and daytime alertness"],"prefix":"10.3389","volume":"16","author":[{"given":"Aglaya","family":"Levshtein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamad","family":"Sharkia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Shimshi-Barash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tal","family":"Almagor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Albertsson-Wikland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeev","family":"Hochberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giora","family":"Pillar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"German","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4158\/EP.14.2.143","article-title":"Compliance and persistence in pediatric and adult patients receiving growth hormone therapy","volume":"14","author":"Rosenfeld","year":"2008","journal-title":"Endocr Pract"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1159\/000053170","article-title":"Compliance with growth hormone treatment - is it a problem","author":"Hindmarsh","year":"1999","journal-title":"Hormone Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.78.5.8175978","article-title":"Analysis of 24-hour growth hormone profiles in healthy boys and girls of normal stature: relation to puberty","volume":"78","author":"Albertsson-Wikland","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/26.7.902","article-title":"Actigraphy in the assessment of insomnia","volume":"26","author":"Valli\u00e8res","year":"2003","journal-title":"Sleep."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s40271-017-0237-9","article-title":"Understanding treatment burden for children treated for growth hormone deficiency","volume":"10","author":"Brod","year":"2017","journal-title":"patient."},{"key":"B6","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/S1071-9091(96)80028-3","article-title":"The impact of inadequate sleep on children's daytime cognitive function","volume":"3","author":"Dahl","year":"1996","journal-title":"Semin Pediatr neurology."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/00004703-199906000-00005","article-title":"Sleep and behavior problems among preschoolers","volume":"20","author":"Lavigne","year":"1999","journal-title":"J Dev Behav pediatrics: JDBP."},{"key":"B8","article-title":"The pediatric daytime sleepiness scale (PDSS): sleep habits and school outcomes in middle-school children","volume":"26","author":"Drake","year":"2003","journal-title":"Sleep."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2015-0627","article-title":"Systematic review of the relationships between sleep duration and health indicators in school-aged children and youth","volume":"41","author":"Chaput","year":"2016","journal-title":"Appl Physiol Nutr Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpsycho.2013.06.019","article-title":"Sleep deprivation and neurobehavioral functioning in children","volume":"89","author":"Maski","year":"2013","journal-title":"Int J Psychophysiol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsy018","article-title":"Sleep duration and incidence of obesity in infants, children, and adolescents: a systematic review and meta-analysis of prospective studies","volume":"41","author":"Miller","year":"2018","journal-title":"Sleep."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17197315","article-title":"Perceived determinants of children's inadequate sleep health","volume":"17","author":"Belmon","year":"2020","journal-title":"A Concept Mapp Study among Professionals. 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