With the noticeable exception of gonadotrophins secretion in post-menopausal women, most modifications of pituitary secretion observed in aging are associated with alterations of circadian rhythmicity, which is centrally generated by a pacemaker located in the suprachiasmatic nuclei of the hypothalamus, and of sleep, another centrally controlled process. In animals and humans, these nuclei present a number of agerelated morphological and neurochemical alterations (1). While circadian rhythmicity persists in healthy elderly subjects, many 24-h rhythms are dampened and/or advanced in old age. The tendency for earlier sleep onset, a more fragmented and more shallow sleep period and earlier morning awakenings is representative of these alterations (2). Several hormonal rhythms that are modulated by the circadian clock have been shown to be of lower amplitude and/or phase advanced, including those of cortisol, melatonin and thyroidstimulating hormone (TSH) (3). In addition, several studies also suggest a shortening of the endogenous circadian period (3–5).
Georges Copinschi and Eve Van Cauter
Anne Caufriez, Jacqueline Golstein, Ali Tadjerouni, Daniele Bosson, Francis Cantraine, Claude Robyn, and Georges Copinschi
Abstract. Among 28 menstruating women tested once randomly during the cycle, somatomedin-C (Sm-C) values were lower in the 10 women in normal follicular phase than in the 10 women in normal luteal phase or the 8 women with hyperandrogenism. Among these 28 subjects, Sm-C showed a positive correlation with testosterone and a positive correlation of borderline significance with oestradiol. A positive correlation was also evidenced between Sm-C and In progesterone among the 20 women of this group who were not hyperandrogenic. In 5 other normal women investigated daily throughout an entire menstrual cycle, Sm-C concentrations were higher during days +4 to +9 of this cycle (luteal phase) than during days −3 to −8 (follicular phase). In another group of 21 healthy women, Sm-C values were increased during medroxyprogesterone acetate (150 mg trimestrially) treatment. In 7 normal men, Sm-C decreased during ethinyl-oestradiol (1 mg daily for 5 days) administration. These findings suggest that circulating Sm-C levels are modulated by variations of sex steroids which occur during the menstrual cycle as well as by pharmacological doses of oestrogens and progestagens.
Lisa L Morselli, Arlet Nedeltcheva, Rachel Leproult, Karine Spiegel, Enio Martino, Jean-Jacques Legros, Roy E Weiss, Jean Mockel, Eve Van Cauter, and Georges Copinschi
We previously reported that adult patients with GH deficiency (GHD) due to a confirmed or likely pituitary defect, compared with healthy controls individually matched for age, gender, and BMI, have more slow-wave sleep (SWS) and higher delta activity (a marker of SWS intensity). Here, we examined the impact of recombinant human GH (rhGH) therapy, compared with placebo, on objective sleep quality in a subset of patients from the same cohort.
Single-blind, randomized, crossover design study.
Fourteen patients with untreated GHD of confirmed or likely pituitary origin, aged 22–74 years, participated in the study. Patients with associated hormonal deficiencies were on appropriate replacement therapy. Polygraphic sleep recordings, with bedtimes individually tailored to habitual sleep times, were performed after 4 months on rhGH or placebo.
Valid data were obtained in 13 patients. At the end of the rhGH treatment period, patients had a shorter sleep period time than at the end of the placebo period (479±11 vs 431±19 min respectively; P=0.005), primarily due to an earlier wake-up time, and a decrease in the intensity of SWS (delta activity) (559±125 vs 794±219 μV2 respectively; P=0.048).
Four months of rhGH replacement therapy partly reversed sleep disturbances previously observed in untreated patients. The decrease in delta activity associated with rhGH treatment adds further evidence to the hypothesis that the excess of high-intensity SWS observed in untreated pituitary GHD patients is likely to result from overactivity of the hypothalamic GHRH system due to the lack of negative feedback inhibition by GH.