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Our understanding of the mechanisms by which sleep deteriorates with age almost exclusively stems from comparisons of young and elderly subjects. The present study investigated the different effects of a 25-h sleep deprivation on the recovery sleep initiated in the morning (when circadian sleep propensity decreases) of young (20-39 y) and middle-aged subjects (40-60 y). Middle-aged subjects showed a steeper increase in the duration of wakefulness during daytime recovery sleep than the young subjects. Slow-wave sleep (SWS) and EEG slow-wave activity (SWA: spectral power between 0.5-4.5 Hz) were potentiated in both groups following sleep deprivation. However, the rebound of SWS and SWA was significantly less pronounced in the middle-aged than in the young. This reduction in homeostatic recuperative drive in middle-aged subjects might account for the decrease in their ability to maintain sleep when they have to recuperate at an abnormal circadian phase. These results helps to understand the increase in complaints related to shift work and jet lag in the middle years of life.

Postmenopausal women (PMW) commonly believe that hormone replacement (HR) leads to weight gain, and fear of weight gain and/or an actual increase in weight is one of the principle reasons evoked for the discontinuation of HR. However, the potential effects of physiologic HR on body composition have yet to be separated from the effects of lifestyle or aging. Therefore, we examined the effect of short-term hormone replacement and age on alterations in weight, body composition, and energy balance. A prospective study of 28 healthy PMW aged 45 to 55 years (younger PMW, studies completed n = 18) and 70 to 80 years (older PMW, studies completed n = 15) was conducted. The last menstrual period was more than 12 months previously. The women had a body mass index (BMI) less than 30 kg/m(2) and were taking no medication. Subjects were studied at baseline, after 1 month of transdermal estrogen (Estraderm, 50 microg/day) administration (E2), followed by a further month of transdermal estrogen with progesterone (100 mg per vagina twice daily) for the final 7 days (E2 + P). Anthropometric measurements and energy assessments were performed at each visit. Physiologic HR was achieved in each subject, and there was no difference between levels achieved in older and younger women. Resting energy expenditure and activity level were positively correlated with fat-free mass (P <.0001), while energy intake was not. Resting energy expenditure was lower in older compared with younger PMW when adjusted for fat-free mass (P <.005). Energy intake was also lower in the older PMW when corrected for fat-free mass (P <.0001); as was activity level (P <.05). There was no effect of hormonal treatment on any of the parameters measured. Changes in weight from baseline for E2 (0.37 +/- 0.25 and 0.61 +/- 0.27 kg in younger and older) and E2 + P (0.11 +/- 0.38 and 0.28 +/- 0.31 kg) were not statistically significant. In addition, there was no difference in BMI, fat mass, fat-free mass, total body water, or waist-to-hip ratio (WHR) between groups or with hormonal treatment. In conclusion, short-term transdermal HR is not associated with significant changes in weight or other anthropometric measures in younger or older PMW. These studies confirm the decrease in energy expenditure that occurs with aging, but indicates that there is no effect of HR on resting energy expenditure., (Copyright 2001 by W.B. Saunders Company)

Unlabelled: Increasing evidence suggests that aging is associated with dynamic changes in the hypothalamic and pituitary components of the reproductive axis that are independent of changes in gonadal hormone secretion. This study was designed to determine the effect of age on GnRH pulse frequency in women in the absence of gonadal feedback using gonadotropin free alpha-subunit (FAS) and LH as neuroendocrine markers of endogenous GnRH secretion. All studies were performed in healthy, euthyroid postmenopausal women (PMW) during daytime hours. The impact of sampling interval and duration on assessment of pulse frequency in PMW was first examined in 10 women with a mean age of 61.6 +/- 8 yr (mean +/- SD), in whom blood was sampled every 5 min for 12 h. Each 5-min series was then reduced to simulate a 10-min series and then a 15-min series for pulse analysis, and the effect of 8 h compared with 12 h of sampling was determined. To define the changes in the frequency and amplitude of pulsatile hormone secretion with aging, 11 younger (45-55 yr) and 11 older (70-80 yr) PMW were then studied over 8 h at a 5-min sampling interval. In the initial series, the mean interpulse intervals (IPIs) for FAS were 53.8 +/- 3.6, 69.2 +/- 3.9, and 87.6 +/- 7.3 min at sampling intervals of 5, 10, and 15 min, respectively (P < 0.0005). The LH IPI also increased progressively with sampling intervals of 5, 10, and 15 min (54.4 +/- 2.5, 70.4 +/- 2.3, and 91.1 +/- 4.4 min; P < 0.0001). At the 5-min sampling interval, the calculated number of pulses/24 h was not different between a 12-h series compared with an 8-h series for either FAS or LH. In the second series of studies, the older PMW had lower gonadotropin levels (LH, 86.5 +/- 8.8 vs. 51.3 +/- 7.7 IU/L, P < 0.01; FSH, 171.6 +/- 16.9 vs. 108.2 +/- 10.5 IU/L, P < 0.005; FAS, 1021.5 +/- 147.4 vs. 425.6 +/- 89.6 ng/L, P < 0.005, in younger and older PMW, respectively) despite no differences in estrone or estradiol levels. The older PMW also demonstrated a slower FAS pulse frequency compared with their younger counterparts, as reflected in an increased FAS IPI (52.6 +/- 3.1 and 70.6 +/- 5.9 min; P < 0.002). The difference in IPIs between younger and older PMW was not statistically significant for LH (65.4 +/- 5.6 and 71.8 +/- 6.6 min for younger and older PMW, respectively). FAS pulse amplitude was decreased in older PMW compared with younger PMW (431.7 +/- 66.2 vs. 224.6 +/- 81.9 ng/L; P < 0.01), whereas the decrease in LH pulse amplitude with age was of borderline statistical significance (23.2 +/- 3.1 vs. 15.9 +/- 2.1 IU/L; P = 0.09)., In Conclusion: 1) the use of a 5-min sampling interval and measurement of FAS as the primary marker of GnRH pulse generator activity indicate that GnRH pulse frequency in younger PMW is faster than previously reported, but not increased over that seen in the late follicular phase and midcycle surge in women with intact ovarian function; and 2) the marked decrease in FAS pulse frequency with age provides evidence of age-related changes in the hypothalamic component of the reproductive axis that are independent of changes in gonadal function.

Objective: Leptin is a hormone which is secreted by adipocytes and appears to influence the reproductive axis. Previous studies have demonstrated higher leptin levels in relation to body fat mass in women compared to men, higher levels in normally cycling compared to postmenopausal women, and a decrease in leptin levels with increased age. The purpose of this study was to determine whether oestrogen replacement with or without progesterone increases serum leptin levels in postmenopausal women, independently of changes in body fat, and to determine if ageing affects leptin levels at baseline or in response to hormone replacement., Patients: Twenty-one healthy postmenopausal women on no hormone replacement were studied at baseline, after 1 month of oestrogen (E2: estraderm 50 microg/day) and after a further month of oestrogen and 7 days of progesterone (P: progesterone 100 mg per vagina bid) designed to achieve physiological hormone levels. Subjects included 11 younger (45-55 years) and 10 older (70-80 years) postmenopausal women., Results: The relationship between leptin and the absolute fat mass (% body fat x weight [kg]) at baseline was not different between the younger and older postmenopausal women. The adequacy of physiological hormone replacement was confirmed in all subjects. Despite the absence of an effect of hormone replacement on weight, body mass index (BMI), % and absolute fat mass (bioimpedance) or waist-hip ratio, there was an increase in serum leptin levels with hormone replacement (15.4 +/- 1.7, 17.6 +/- 1.7, and 18.1 +/- 1.6 microg/l; mean +/- SEM at baseline, with E2, and with E2 + P, respectively; P < 0.001 vs. baseline) for the group as a whole. An increase in leptin with hormonal treatment was seen in both the younger (15.1 +/- 2.1, 18.1 +/- 2.4, and 18.5 +/- 1.9 microg/l; P < 0.01) and the older (15.7 +/- 2.8, 17.0 +/- 2.5, 17.7 +/- 2.8 microg/l; P = 0.06) postmenopausal women., Conclusions: (1) Short-term physiological oestrogen replacement increases serum leptin levels in postmenopausal women independently of changes in fat mass; and (2) physiological progesterone replacement does not influence leptin levels in postmenopausal women.

The goals of this study were to determine whether women with idiopathic hypogonadotropic hypogonadism (IHH) respond to pulsatile GnRH replacement therapy with exaggerated glycoprotein free alpha-subunit (FAS) levels, as reported in GnRH-deficient men, and to determine whether this pattern is unique to congenital GnRH deficiency or is also characteristic of patients with hypogonadotropic hypogonadism caused by other factors. GnRH was administered i.v. at a physiologic frequency and dose (75-100 ng/kg.bolus) to women with IHH (n = 11; n = 6 with anosmia); acquired GnRH deficiency secondary to treatment for cranial tumors (AHH; n = 7); and secondary hypothalamic amenorrhea (HA; n = 8). Results were compared with 24 normal cycling women. Gonadotropins, sex steroids, and FAS levels were measured in samples drawn daily across induced or normal menstrual cycles in patients or normal women, respectively. Samples were drawn at the same time of day and were collected 45 min after a GnRH bolus in patients. All women ovulated in response to pulsatile GnRH. There were no differences in the patterns of LH or gonadal steroid secretion between any of the patient groups (IHH, AHH, and HA). The patterns of LH and FSH secretion in the induced patient cycles were not different from normal women, with the exception of lower midcycle FSH levels in IHH women (P < 0.002). However, the daily dynamic secretion of FAS was exaggerated in IHH (compared with AHH, HA, and normal) women (P < 0.002). The increase in FAS levels in IHH was dependent on cycle stage, with the greatest difference observed during the early (P < 0.005) and midfollicular phase (P < 0.05) and the early luteal phase (P < 0.05). There was no difference in FAS between groups during the late follicular phase, at the midcycle, or in the midluteal and late luteal phase. This exaggerated FAS response to GnRH replacement in IHH was demonstrated in repeat cycles in two patients. Conclusions are: 1) Women with IHH respond to pulsatile GnRH replacement with an exaggerated secretion of FAS, which seems to be modified by gonadal factors; 2) this exaggerated FAS response, which is similar to that seen in GnRH-deficient men, is unique to congenital GnRH deficiency, and it is not observed in patients with acquired or secondary hypogonadotropic hypogonadism, suggesting that IHH patients may be missing a factor, in addition to GnRH, which normally restrains FAS secretion; and 3) the FAS response may prove to be a useful marker to distinguish constitutional delay of puberty from congenital GnRH deficiency.