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This study aimed to evaluate the influence of hormone replacement therapy (HRT), the estradiol concentration and body mass index (BMI, kg/m(2)) on the serum leptin concentration in postmenopausal women.352 healthy postmenopausal women (mean age, 60.9 +/- 8.5 years) participated in this comparative study. 71 (30%) women (mean age 55.9 +/- 8.3 years) had taken HRT, while 281 (70%) women (mean age, 59.1 +/- 10.6 years) had not. Baseline characteristics -age, weight, height, BMI (greater than or = 25 or25), follicle stimulating hormone, estradiol, and leptin values-were compared in the two groups. In a second analysis to evaluate the influence of HRT, estradiol concentrations, and BMI on leptin concentrations, these data were analysed in women allocated to one of four groups: (a) postmenopausal women not on HRT with a BMI25 (n = 130); (b) postmenopausal women not on HRT with a BMI greater than or = 25 (n = 151); (c) postmenopausal women on HRT with a BMI25 (n = 48); and (d) postmenopausal women on HRT with a BMI greater than or = 25 (n = 23). Leptin concentrations were subsequently analysed in relation to BMI and age and BMI and estradiol concentrations to determine any independent effect of these variables.The women taking HRT had a significantly lower mean age, weight, BMI and follicle stimulating hormone concentration than those who were not taking HRT. Furthermore, they had a higher mean height and serum estradiol value, but a significantly lower serum leptin concentration. After controlling for BMI, neither the use of HRT nor the estradiol concentration was found to be related to the leptin value (group (a) versus (c) and group (b) versus (d)), but there were significant differences in leptin concentrations between HRT users with BMI greater than or = 25 and BMI25 and between women not taking HRT with BMI greater than or = 25 and BMI25 (groups (a) versus (b) and (c) versus (d)). Furthermore, women with a BMI greater than or = 25 had significantly higher leptin concentrations than women with a BMI25, irrespective of the HRT use.Leptin concentrations are significantly higher in obese postmenopausal women than in their non-obese counterparts. Serum leptin concentrations are not influenced by HRT use or estradiol concentrations. Further studies are needed to elucidate the role of HRT and estrogen on serum leptin concentrations.

This study was undertaken to evaluate the impact of hormone replacement therapy on results of quantitative ultrasonometry of the heel.A total of 2006 healthy perimenopausal women (mean age, 52.2 (10.3 years) were recruited in 5 German centers: 611 women (30%) had received hormone replacement therapy and 1395 (70%) had not. About 90% of the hormone replacement therapy users were current users, and the rest had stopped6 months before the study. Speed of sound, broadband ultrasonographic attenuation, and the stiffness index were compared among the following groups: all users and nonusers of hormone replacement therapy, hormone replacement therapy users and nonuser control subjects matched for age and body mass index, and hormone replacement therapy users grouped in relation to the duration of hormone replacement therapy use and age and control subjects matched for body mass index.Women who were using hormone replacement therapy had significantly higher values (P.001) than did nonusers for all ultrasonographic variables, even after we controlled for age and body mass index. Women who had used hormone replacement therapy for3 years had significantly higher values (P.001) than did matched control subjects for all variables. Differences increased with the duration of hormone replacement therapy use.Quantitative ultrasonometric measurement at the heel differentiates hormone replacement therapy users from nonusers, reflects duration of hormone replacement therapy use, and could be useful in both clinical trials and patient management.

Objectives: To compare a composite ultrasonometry variable, the stiffness index (SI), with its two component variables of speed of sound (SOS) and broadband ultrasound attenuation (BUA), in identifying post-menopausal women with low bone mineral density (BMD) and/or osteoporotic fracture. Methods: A cross sectional sample of 1217 women (mean (S.D.) age 53.9 (9.7) years) was studied. Risk factors for osteoporosis were assessed by detailed questionnaire and women with diseases, or those taking treatments known to affect bone metabolism were excluded. Women were allocated to one of four groups: pre-menopausal women (n=476), healthy post-menopausal women (n=583), post-menopausal women with low BMD (n=101), and post-menopausal women with osteoporotic fracture (n=57). An Achilles ultrasonometer was used to perform quantitative ultrasonometry (QUS) at the os calcis. The SI, calculated mathematically from SOS and BUA, was computed. Results: Analysis of receiver operating curves (ROC) between healthy post-menopausal women and post-menopausal women with low BMD but no fracture, showed that the area under the curve (AUC) for SI was significantly greater than that for BUA (P

Under the protection of ascorbic acid a 2-hydroxyestrone bovine serum albumin conjugate was prepared containing intact 2-hydroxyestrone as determined by gas chromatographymass spectrometry. Using this antigen highly specific antibodies were raised in rabbits. Cross-reactivity for 2-hydroxyestradiol and 2-hydroxyestriol was 26 and 4.5%, respectively. An assay procedure of 2-hydroxyestrone in human plasma is described. Using special precautions the assay allows the determination of 2-hydroxyestrone in plasma samples of women (50–95 pg/ml), pregnant women (105–220 pg/ml), men (45–65 pg/ml) and children (20–40 pg/ml).

Short-term (0.5-4 h) treatment of rat pituitary cells in culture with estradiol (E2) results in a significant decrease of Gonadotropin-Releasing Hormone (GnRH) induced LH-release. We studied whether changes in the concentrations of GnRH-receptors (GnRH-R) might account for this phenomenon: pituitary cells from adult female rats were incubated for 4 or 24 h in the presence or absence of 10(-9) M E2. Then saturation curves of D-Ala6-des-Gly10-GnRH ethylamide binding were obtained. In addition, binding studies were carried out in cultures incubated for 0.5, 1, 2 or 4 h with or without 10(-9) M E2 using a near saturating concentration of GnRH-analog. No changes of GnRH-R affinity occurred (4 h experiments: Ka in vehicle treated cells: 0.94 +/- 0.2 x 10(9) M-1, Ka in E2 treated cells: 1.06 +/- 0.3 x 10(9) M-1; 24 h experiments: Ka vehicle: 0.95 +/- 0.2 x 10(9) M-1, Ka E2: 0.82 +/- 0.3 x 10(9) M-1). The GnRH-R concentrations, however, were significantly reduced (44 +/- 3%; P less than 0.001) by 4 h E2 treatment and increased (by 68 +/- 8%; P less than 0.01) by 24 h of E2 treatment. The GnRH induced LH-release in aliquots of the same cell preparations was significantly reduced after 4 h and markedly increased after 24 h of E2 treatment. The experiments on the time-course of the reduction of D-Ala6-GnRH-binding by E2 treatment showed that the number of GnRH-R was significantly decreased (24 +/- 1%; P less than 0.05) already after 0.5 h of exposure to the estrogen. This is also the time period after which the negative E2-effect on GnRH-induced LH-release becomes significant. These data provide first evidence that the short-term negative E2-effect on GnRH induced LH-release by rat pituitary cells in culture could be mediated via a reduction of available GnRH-R.

Portions of pregnancy and midcycle urines were submitted to hot acid hydrolysis, extracted with benzene/ethyl acetate and the extracts washed with ascorbic acid buffer. From the remaining organic phase the catecholestrogens were removed with borate buffer and further purified on Sephadex LH-20 columns. After derivatisation 4-hydroxyestrone was separated from the isomeric 2-hydroxyestrone peak were identical with that of authentic 4-hydroxyestrone. After treatment of the extracts with sodium borohydride 4-hydroxyestradiol-17 beta was identified by GC-MS. By the addition of trace amounts of tritiated 4-hydroxyestrone a recovery of 40% was calculated. On the basis of this recovery and the peak heights of the gas chromatograms an excretion of 4 microgram (midcycle) and 40 microgram (pregnancy) of 4-hydroxyestrone/24 h was estimated.

The effects of RU 486 on the modulation of LH release by progesterone were investigated in cultured anterior pituitary cells from ovariectomized adult female rats. The inhibitory effect of progesterone on LH secretion was demonstrable in estrogen-treated pituitary cells, in which addition of 10(-6) M progesterone to cells cultured in the presence of 10(-9) M estradiol for 52 h reduced the LH response to GnRH (10(-11) to 10(-7) M). When RU 486 was superimposed upon such combined treatment with estradiol and progesterone, the suppressive effect of progesterone on GnRH-induced LH release was completely abolished. The converse (facilitatory) effect of progesterone on LH secretion was observed in pituitary cells pretreated with 10(-9) M estradiol for 48 h and then with 10(-6) M progesterone for 4 h. When RU 486 was added together with progesterone during the 4 h treatment period, the facilitatory effect of progesterone was blocked and LH release fell to below the corresponding control value. The direct effect of RU 486 on LH secretion in the absence of exogenous progesterone was evaluated in cells cultured in the absence or presence of 10(-9) M estradiol and then treated for 4 to 24 h with increasing concentrations of RU 486 (10(-12) to 10(-5) M) and stimulated with GnRH (10(-9) M) during the last 3 h of incubation. In estrogen-deficient cultures, 4 h exposure to RU 486 concentrations of 10(-6) M and above decreased the LH response to GnRH by up to 50%. In cultures pretreated with 10(-9) M estradiol, GnRH-stimulated LH responses was inhibited by much lower RU 486 concentrations, of 10(-9) M and above. After 24 h of incubation the effects of RU 486 were similar in control and estradiol-pretreated pituitary cell cultures. Thus, RU 486 alone has a significant inhibitory effect on LH secretion that is enhanced in the presence of estrogen. The antiprogestin is also a potent antagonist of both the inhibitory and the facilitatory actions of progesterone upon pituitary gonadotropin release in vitro.

As a first step to investigate whether gonadotropin releasing hormone (GnRH) analogs might be able to modulate directly the proliferation of human epithelial ovarian carcinomata, we checked if binding sites for GnRH are present in these malignancies. Specific binding of [ 125 I][d-Ala 6 -des Gly 10 ]-GnRH-ethylamide (GnRH agonist=GnRH-A) could be demonstrated in plasma membranes from 32 out of 40 ovarian carcinomata tested. This binding was dependent on temperature, time and plasma membrane concentration. Mathematical analysis of the binding data showed that the interaction of GnRH-A with the binding sites was consistent with a single class of low affinity, high capacity binding sites (K a = 1.42 ± 0.14 × 10 5 M −1 ; range: 0.3 – 3.8 × 10 5 M −1 ; R=209 ± 69 × 10 −12 M/mg membrane protein; range 16–400 × 10 −12 M/mg MP; x ¯ S.E., n = 32). Native GnRH and the GnRH antagonist [d-p-Glu 1 ,d-Phe 2 ,d-Trp 3,6 ]-GnRH had K a values comparable to those of the GnRH-A used. [ 125 I]GnRH-A binding could not be displaced by oxytocin, thyrotropin releasing hormone and corticotropin releasing factor in concentrations up to 10 −4 M . Somatostatin cross-reacted with binding sites from some carcinomata, while it did not displace GnRH-A binding in membranes from others. Though the functional role of this specific binding site for GnRH in human epithelial ovarian carcinomata is still obscure, it might be part of an autocrine regulatory system and provide a possible point of attack for therapeutic approaches using GnRH analogs in this malignancy.