Serum leptin levels and body composition in postmenopausal women: effects of hormone therapy.

OBJECTIVE: To confirm the effect of postmenopausal hypoestrogenism and hormone therapy (HT) on body composition and serum leptin levels. DESIGN: Prospective, longitudinal study evaluating body composition (body mass index, and total and percent fat mass and lean mass measured at the arms, legs and trunk) with dual-energy x-ray absorptiometry and serum leptin levels by radioimmunoassay in 44 healthy postmenopausal women randomized to receive either no treatment (n = 22) or transdermal 17beta-estradiol (50 microg/day) in continuous regimen and nomegestrol (5 mg/day for 12 days/month) in a sequential regimen (n = 22). RESULTS: One year after the beginning of the study, in untreated women, total and trunk fat mass and percent fat were significantly increased, whereas trunk lean mass was significantly decreased. On the contrary, women treated with HT did not show any significant difference in body composition parameters. In untreated women, serum leptin levels were significantly increased at the end of the study in comparison with baseline values. Serum leptin levels at the other times evaluated were not significantly different from baseline values. In women treated with HT, serum leptin levels did not show significant changes throughout the study. CONCLUSIONS: Untreated postmenopausal women show an increase in total and percent fat mass and a centralization of fat distribution. Serum leptin levels parallel this increase, resulting in significantly higher levels 1 year after the study. Women treated with HT are protected against these changes. This may represent a protective mechanism against cardiovascular diseases.

Estrogen and raloxifene modulate leptin and its receptor in hypothalamus and adipose tissue from ovariectomized rats.

Obesity, from declining estrogen levels after menopause, increases the risk of heart disease, diabetes, and hypertension. Ovariectomy (OVX) in rats is a good model of estrogen insufficiency. The ensuing mild obesity is useful to study how hypoestrogenism alters adiposity. This study examines the hypothesis that in ovariectomized (OVX) rats modification of estrogen levels or treatment with a selective estrogen receptor modulator, raloxifene (RAL), alters leptinemia and modulates leptin receptor (Ob-R) abundance in hypothalamus and white adipose tissue, similar to the modification of adipose status induced by hypoestrogenism. Mid- and long-term studies (7 and 22 wk) were conducted to monitor the change in leptinemia in rats after estrogen loss by OVX and after estrogen replacement by 17beta-estradiol (OVX+E(2)) or RAL treatment (OVX+RAL). Leptin was significantly higher in OVX rats vs. controls, in a time-dependent manner. This effect was reversed by both E(2) and RAL treatment at 7 wk (P < 0.05) and 22 wk (P < 0.001). Moreover, E(2) or RAL treatment reversed the OVX-induced increases in food intake, body weight, and fat mass content; the modifications of serum parameters were examined to evaluate the different lipid profiles. We also evaluated Ob-R expression in hypothalamus and adipose tissue by Western blot analysis. The expression of the long functional isoform (Ob-Rb) increased at 7 wk only in adipose tissue and decreased at 22 wk in OVX rats in both tissues; these effects were reversed by E(2) or RAL treatment. We provide evidence that central and peripheral Ob-Rb expression is related to modification of estrogen levels.

Effects of bilateral ovariectomy and postoperative hormonal replacement therapy with 17beta-estradiol or raloxifene on serum leptin levels.

OBJECTIVE: To verify the effects of hypoestrogenism and replacement therapy on body mass index (BMI) and leptin in ovariectomized women. DESIGN: We conducted a longitudinal study on 56 women undergoing abdominal bilateral ovariectomy divided into three groups: 19 untreated controls, 18 scheduled to receive 17beta-estradiol, and 19 on raloxifene starting 15 days after surgery. Height, weight, and BMI were recorded on the day of surgery, 5 and 15 days later, and then after 6 months. Leptin and estradiol concentrations were determined by radioimmunoassay on the day of surgery, days 1, 5, and 15, and 6 months after. RESULTS: Leptin levels rose significantly on the day after surgery [median (range): 18.2 (9.8-25.0), 12.5 (9.1-20.9), and 20.5 (12.9-24.5); P< 0.01 v basal] and returned to values similar to baseline on day 5 in all groups. Six months later, controls showed significantly higher leptin levels in comparison with both treated women and basal values [median (range): 19.7 (10.4-22.8), 11.0 (7.6-16.9), and 13.5 (9.1-14.8) ng/ml; P< 0.01). Estradiol levels decreased in all groups, reaching statistical significance 5 days after surgery ( P< 0.01 v basal). A significant rise was observed 6 months after surgery in women treated with estrogens ( P< 0.01). Six months after surgery, BMI increased in untreated controls in comparison with treated women and baseline, although not significantly. CONCLUSIONS: The absence of modifications in leptin on days 5 and 15 after ovariectomy suggests that, in humans, estrogens may not exert an important effect on leptin secretion. After 6 months, replacement therapy maintained leptin levels and BMI was unmodified, whereas untreated controls showed a significant increase in leptin and a trend toward higher BMI, suggesting that replacement therapy may prevent changes in fat distribution and in leptin levels.

Menstrual status and serum leptin levels in anorectic and in menstruating women with low body mass indexes.

OBJECTIVE: To evaluate serum leptin levels in anorectic women, menstruating women with low body mass indexes (BMI) and normally menstruating women with normal BMI. DESIGN: Prospective study. SETTING: University clinics. PATIENT(S): Fourteen amenorrheic patients with anorexia nervosa (group A), 11 menstruating women with a BMI <18 kg/m(2) (group B), and 20 normal controls. MAIN OUTCOME MEASURE(S): Determination of BMI, caloric intake, total fat mass, ovarian volume, and serum leptin, insulin-like growth factor I, FSH, LH, E(2), PRL, and TSH levels. INTERVENTION(S): None. RESULT(S): Mean BMI and fat mass were similar in groups A and B and significantly higher in controls. Mean caloric intake was significantly lower in group A than in group B and controls. Median serum leptin levels were significantly lower in group A than in group B and controls, and significantly lower in group B than in controls. Median serum insulin-like growth factor I levels were significantly lower in group A than in group B and controls. Binary segmentation analysis of groups A and B showed that LH was the most relevant variable in differentiating the two groups, followed by leptin. CONCLUSION(S): A threshold of leptin levels exist above which, even in the presence of low body mass indexes, the menstrual function is preserved.