Original Article The temporal relationship between growth hormone and slow wave sleep is weaker after menopause Nea Kalleinen a,b,⇑ , Arho Virkki c , Olli Polo d , Sari-Leena Himanen e,f , Kerttu Irjala g , Atte Joutsen h , Tarja Porkka-Heiskanen i , Päivi Polo-Kantola a,j a Sleep Research Unit, Department of Physiology, University of Turku, Finland b Department of Cardiology, Satakunta Central Hospital, Finland c Medical Biotechnology, VTT Technical Research Center of Finland, Finland d Department of Pulmonary Diseases, Tampere University Hospital, Finland e Department of Clinical Neurophysiology, Tampere University Hospital, Finland f Department of Physiology, University of Tampere, Finland g Mehiläinen Oy, Turku, Finland h Department of Biomedical Engineering, Tampere University of Technology, Finland i Department of Physiology, University of Helsinki, Finland j Department of Obstetrics and Gynecology, Turku University Central Hospital, Finland article info Article history: Received 11 March 2011 Received in revised form 7 May 2011 Accepted 11 May 2011 Available online 3 December 2011 Keywords: Sleep Menopause Growth hormone Slow wave sleep Hormone therapy Estrogen abstract Objective: To study the temporal association between growth hormone (GH) and slow wave sleep (SWS) in middle-aged women. Methods: Seventeen premenopausal and 18 postmenopausal women were studied using all-night polygraphic sleep recordings and blood sampling at 20-min intervals. The postmenopausal women were re-studied after six months on hormone therapy (HT) according to a randomized, double-blind, placebo- controlled protocol. Results: The total sleep time (premenopausal 361.9 ± 81.5 min, postmenopausal 358 ± 67.7 min) and the percentages of the sleep stages did not differ between pre- and postmenopausal women. In postmeno- pausal women the first GH peak after sleep onset occurred later and with a more variable time interval compared to premenopausal women. The percentage of SWS was highest 40–20 min prior to the first GH peak after sleep onset in both groups with a higher SWS proportion in premenopausal women (p = 0.048), although the total SWS percent for night did not differ. HT did not affect the distribution of SWS in postmenopausal women. Conclusions: The temporal relationship between GH and SWS in premenopausal women is less robust after menopause and is not improved with HT. Ó 2011 Elsevier B.V. All rights reserved. 1. Introduction Most studies show that subjective sleep quality worsens at menopause [1,2], but objective measures of sleep quality do not confirm this [2,3]. In a large longitudinal population-based study (The Wisconsin Sleep Cohort Study) postmenopausal women slept better than premenopausal women according to objectively recorded sleep, but their subjectively reported sleep was worse [2]. Sleep quality is related to female sex hormones since meno- pausal hormone therapy (HT, including both unopposed estrogen and combined estrogen–progestogen) reduces sleep complaints [2,4–7]. However, the mechanisms of action behind the HT effect are not known. Growth hormone (GH) is strongly related to sleep and especially to slow wave sleep (SWS) [8–11]. Repetitive hourly administrations of GH-releasing hormone (GHRH) increase GH as well as non-REM (NREM) sleep with decreased awakenings in men but has the oppo- site, and sleep impairing, effect in women [12]. GH levels [11,13,14] as well as SWS [11,14] decrease with increasing age both in men and women. Women have higher GH levels than men of the same age, but this difference disappears after menopause [13,15]. Compared to men, women show pre-sleep GH surges more often, and addi- tional GH pulses later during the night [16]. We have previously shown that GH is reduced in postmenopause compared to premeno- pause, and that HT reverses this change [17]. Despite higher GH levels and better preserved SWS [18], sleep complaints are more common in women than in men [19,20]. The temporal association between GH and SWS is less known in women because of sparse data, but it is suggested to be weaker than in men [15,21,22]. 1389-9457/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2011.05.010 ⇑ Corresponding author at: Sleep Research Unit, Lemminkäisenkatu 14-18 A, 5th floor, FIN-20520 Turku, Finland. Tel.: +358 2 333 7599; fax: +358 2 241 0057. E-mail address: nea.kalleinen@utu.fi (N. Kalleinen). Sleep Medicine 13 (2012) 96–101 Contents lists available at SciVerse ScienceDirect Sleep Medicine journal homepage: www.elsevier.com/locate/sleep