The effects of transdermal estradiol on the response to mental stress in postmenopausal women: a randomized trial.

PURPOSE: Estrogens inhibit adrenomedullary catecholamine release and catecholamine-mediated responses to stress. We examined whether estrogen supplementation reduces the sympathoadrenal response to mental stress in postmenopausal women. MATERIALS AND METHODS: We compared the effects of 3-week treatment with transdermal 17-beta-estradiol and placebo in 10 postmenopausal women using a randomized, blinded, crossover design. We measured plasma catecholamine levels and the cardiovascular and metabolic responses to a 15-minute stress with mental arithmetic. Treatments were compared using repeated measures analysis of variance. RESULTS: During placebo treatment, mean (+/- SD) epinephrine levels reached a peak of 431 +/- 135 pmol/liter after 15 minutes of stress; the epinephrine response was blunted during estradiol treatment, with a peak of 357 +/- 77 pmol/liter (P <0.05). Estradiol also blunted the diastolic blood pressure response to stress (baseline levels of 78 +/- 15 mm Hg vs peak of 90 +/- 6 mm Hg during placebo; baseline of 80 +/- 8 mm Hg vs peak of 84 +/- 6 mm Hg during estradiol; P <0.05). Estradiol treatment also blunted the decrease in the standard deviation of the mean of the electrocardiographic RR intervals and the increase in the ratio between the low-frequency and high-frequency bandwidths. CONCLUSION: We observed a moderate, although significant, reduction in markers of the stress response to mental arithmetic in postmenopausal women treated with transdermal 17-beta-estradiol.

Determinants of age at menopause in Italy: results from a large cross-sectional study. ICARUS Study Group. Italian Climacteric Research Group Study.

OBJECTIVE: To identify the determinants of age at menopause in an Italian population, using data from the Italian Climacteric Research Group Study (ICARUS). METHODS: ICARUS is a prospective study of the effect of menopause on women's health that has been running in menopause clinics throughout Italy since 1995. A total of 4300 women with spontaneous menopause, aged 55 years or more and observed for the first time at the participating centres are included in the present analysis. RESULTS: The mean age at menopause in the total population was 50.9 years. After taking into account potential covariates, the women reported smoking, had a slightly lower mean age at menopause than non smokers 50.4 versus 50.9 years; P = 0.01. The mean age at menopause in nulliparae was 50.0 years, and, respectively 50.4, 50.6, 50.9, 51.2 and 50.9 years in those reporting 1, 2, 3, 4 and 5 or more births (P < 0.01). A low body mass index and an early age at menarche were associated with early menopause in the crude analysis, but these associations disappeared after taking into account the confounding factors. CONCLUSIONS: This study offers an estimate of the mean age at menopause of women attending menopause clinics in Italy, on the basis of the data obtained from a large sample. It also indicates that smoking and nulliparity are associated with early menopause.

Oestrogens prevent the increase of human serum soluble interleukin-6 receptor induced by ovariectomy in vivo and decrease its release in human osteoblastic cells in vitro.

OBJECTIVE: Interleukin-6 (IL-6) seems to be a key mediator of the increased bone loss that follows loss of ovarian function. Based on this and on evidence that oestrogen deficiency may also increase cell sensitivity to IL-6, we studied the effects of ovariectomy and of oestrogen replacement therapy on the serum levels of IL-6 and of soluble IL-6 receptor (sIL-6R) in vivo. DESIGN AND PATIENTS: Thirty-seven fertile women undergoing surgery for benign uterine diseases were divided into 3 groups and monitored for 12 months: hysterectomized women (n = 9), ovariectomized untreated women (n = 12) and ovariectomized women starting treatment with transdermal estradiol (E2, 50 microg/d) 1 month after surgery (n = 16). RESULTS: Hysterectomy alone caused no significant changes of sIL6R whereas serum levels of sIL-6R rose progressively after ovariectomy (mean +/- SEM: 31 +/- 9% and 38 +/- 7% over baseline, at 6 and 12 months, respectively; P < 0.01). Oestrogen replacement therapy prevented the increase of sIL6R over a 1-year period. A similar pattern was also found for serum IL-6 but the changes did not reach statistical significance. In ovariectomized (OVX) women there were significant correlations between serum sIL-6R levels and FSH (r = 0.59; P < 0. 01), oestradiol (r = - 0.43; P < 0.01), testosterone (r = - 0.41; P < 0.05), osteocalcin (r = 0.42; P < 0.05) and bone alkaline phosphatase (r = 0.44; P < 0.05). To examine whether oestrogen directly regulates sIL-6R secretion by bone cells, we studied in vitro the basal and phorbol ester (PMA) stimulated release of sIL-6R in a human osteoblastic cell-line (MG-63) and in a tumour-derived osteoclastic cell line (GCT-51). Osteoblastic (but not osteoclastic) cells spontaneously produced considerable amounts of sIL-6R and the protein kinase-C activator PMA (10-8 M) increased the release of sIL-6R by osteoblasts more than 3-fold. More strikingly, 17beta E2 (but not 17alpha) significantly inhibited both the spontaneous- and PMA-induced release of sIL-6R by osteoblastic cells (P < 0.05). CONCLUSIONS: These results indicate that oestrogen loss causes alterations of the IL-6 system, and that sIL-6R is under the direct inhibitory control of oestrogens both in vivo and in vitro.

Sociodemographic and clinical factors associated with HRT use in women attending menopause clinics in Italy.

OBJECTIVE: The aim of this analysis is to find any association between the use of hormone replacement therapy (HRT) and sociodemographic and clinical factors among women attending 54 menopause clinics in Italy. METHODS: The analysis includes data relating to 17,851 women who attended one of 54 menopause clinics in Italy for general gynecological evaluations and counselling between 1995 and 1997. The characteristics of women reporting ever HRT use were compared with those of never users. The odds ratios (ORs) of HRT use were computed in relation to selected reference categories, together with their 95% confidence intervals (CIs). RESULTS: Of the 17,851 women interviewed, 8539 reported ever HRT use. The mean age of the never and ever HRT users was 52.8 years and 53.7 years, respectively. Higher education was associated with an increased frequency of HRT use: in comparison with women reporting no or primary-/middle-school education, the OR of HRT use of women reporting a high-school diploma or university degree was 1.3 (95% CI 1.1-1.6). HRT use tended to be less frequently reported with increasing body mass index (BMI): in comparison with women whose BMI was < 23.4 kg/m2, the OR of HRT use in those with a BMI of 23.4-26.1 kg/m2 and > or = 26.2 kg/m2 was 0.8 (95% CI 0.8-0.9) and 0.6 (95% CI 0.5-0.7), respectively. Among the postmenopausal women, those who had undergone surgical menopause had an OR of HRT use of 1.3 (95% CI 1.2-1.4). A history of breast cancer was associated with a lower frequency of HRT use (OR 0.3, 95% CI 0.2-0.4). Likewise, a history of thromboembolic disease (OR 0.5, 95% CI 0.4-0.7) or myocardial infarction (OR 0.7, 95% CI 0.6-0.9) was associated with a lower frequency of HRT use. CONCLUSIONS: In our study population, the variable most closely related to HRT use was education/social class, thus underlining the impact of information campaigns on HRT and women's health. Among the medical determinants, our analysis indicates that a history of myocardial infarction, thromboembolic disease or breast cancer is associated with less frequent use of HRT.