Body composition and energy balance: lack of effect of short-term hormone replacement in postmenopausal women.

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.

Effects of short-term hormone replacement on serum leptin levels in postmenopausal women.

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.

Disappearance of endogenous luteinizing hormone is prolonged in postmenopausal women.

Pituitary secretion of LH is increased after menopause, but it is not known whether changes in LH clearance also contribute to elevated serum levels. To determine whether the disappearance of endogenous LH is decreased in postmenopausal women (PMW), compared with normal cycling women, GnRH receptor blockade was used to inhibit endogenous secretion of LH and the glycoprotein free alpha-subunit (FAS), and the decline of serum levels was monitored. The NAL-GLU GnRH antagonist ([Ac-D-2Nal1,D-4ClPhe2, D-3Pal3,Arg5,D-4-p-methoxybenzoyl-2-aminobutyric acid6,D-Ala10]GnRH) was administered s.c., at doses of 5, 15, 50, and 150 microg/kg, to 15 euthyroid PMW in 21 studies. Blood was sampled every 10 min, for 4 h before and 8 h after a single sc injection of the GnRH antagonist, followed by hourly samples, ending at 20 h after injection. Results of the maximally suppressive doses (50 and 150 microg/kg) were compared with those of 24 normal cycling women in the early follicular phase and late follicular phase or early luteal phase, and 8 women at the midcycle surge (MCS), who also received these doses of the GnRH antagonist. The best fit curve describing the decay of hormone serum levels after maximal GnRH receptor blockade was determined by nonlinear regression analysis. The elimination of both LH and FAS, after GnRH receptor blockade, exhibited apparent first-order kinetics characterized by a single exponential phase. No differences were seen in percent suppression or half-lives (t1/2) of LH or FAS, between the 50- and 150-microg/kg antagonist doses, in any of the subject populations; and percent suppression of LH was similar across all groups. The t1/2 of LH was prolonged in PMW (139 +/- 35 min, mean +/- est. SD), in comparison with both the MCS (78 +/- 20 min; P < 0.0005) and other cycle stages (57 +/- 28 min; P < 0.0001). However, the disappearance of FAS was not different in PMW, compared with MCS or other cycle stages (t1/2 = 51 +/- 26, 41 +/- 12, and 41 +/- 19 min, respectively). Our conclusions were: 1) Disappearance of endogenous LH after GnRH receptor blockade is significantly prolonged in PMW, compared with the MCS or other cycle stages; 2) The disappearance of FAS is not altered in PMW, suggesting that differences in the disappearance of LH relate to LH microheterogeneity rather than systemic factors.