Influence of exogenous melatonin on catecholamine levels in postmenopausal women prior and during oestradiol replacement

OBJECTIVE: In young individuals melatonin administration reduces circulating norepinephrine. Some effects of melatonin are reduced in elderly women and are modulated by gonadal steroids. Accordingly, the influence of melatonin on catecholamine levels was investigated in postmenopausal women without and with oestradiol replacement. DESIGN: Prior to and after 2 months of transdermal oestradiol (50 microg/day), women were studied on two consecutive days, on which they received placebo or 1 mg of melatonin orally in a randomised and double-blind fashion. PATIENTS: Fourteen healthy postmenopausal women. MEASUREMENTS: Resting levels of epinephrine and norepinephrine and their responses to both a cold stimulus, performed by placing a hand in a basin of water and ice for 2 minutes, and to 10 minutes of upright position (upright test). RESULTS: Prior to oestradiol, melatonin did not modify baseline or stimulated catecholamine levels. In contrast, during oestradiol, melatonin tended to reduce, although not significantly, baseline norepinephrine levels (P = 0.053), and significantly reduced peak values (P = 0.0061) and integrated norepinephrine response (P = 0.0076) to the cold stimulus. Responses of norepinephrine to the upright test were not modified, while those of epinephrine were increased (P = 0.042). During, but not prior to oestradiol replacement, modifications induced by melatonin (melatonin day-placebo day) in the norepinephrine response to the cold (r2 = 0. 457; P = 0.0079) and the upright (r2 = 0.747; P = 0.0001) tests were linearly and inversely related to the responses of the placebo day. CONCLUSIONS: Melatonin does not modulate adrenergic activity in postmenopausal women without hormone replacement therapy. Oestradiol replacement restores the capability of melatonin to modulate adrenergic activity, particularly the norepinephrine response to stimuli.     

Relation of folates, vitamin B12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A five-year longitudinal evaluation

Elevation of homocysteine is associated with an increased risk for bone fractures. Whether the risk is due to homocysteine or to the reduced levels of cofactors necessary for its metabolisation, such as folates or vitamin B12, is not completely clear. In this study we wanted to determine whether in postmenopausal women, levels of folates, homocysteine or vitamin B12 are predictive of the rate of vertebral bone mineral density (BMD) change. The study was conducted at the centre for the menopause of our university hospital. Between September 2001 and March 2002, 161 healthy postmenopausal women volunteered for a cross-sectional evaluation of BMD and levels of serum folates, homocysteine and vitamin B12. Women were recalled for a second evaluation of vertebral BMD after about 5 years. Women having used anti-resorptive therapies for more than 1 year were excluded. The analysis was possible in 117 postmenopausal women. The annual rate of vertebral BMD change was independently related to levels of folates (coefficient of regression (CR): 2.040; 95%CI: 0.483, 3.596; p=0.011), and initial BMD values (CR: -0.060; 95%CI: -0.117, -0.003; p=0.040). No significant relation was found between the change of vertebral BMD and homocysteine or vitamin B12. BMD values at the first (r=0.225; p=0.016) and the second (r=0.206; p=0.027) evaluation were related to levels of folates, but not of homocysteine or of vitamin B12. These data suggest an important role for folates deficiency in the vertebral BMD decline of postmenopausal women.     

The relation of season of birth to severity of menopausal symptoms

OBJECTIVE: Season of birth influences the rate of several psychiatric disorders. In this study, we investigated whether climacteric symptoms and, in particular, psychological and somatic symptoms of postmenopausal women were influenced by their season of birth. DESIGN: This retrospective multicenter study was performed on 2,541 women in natural menopause, free of hormone therapy. The score of the Greene Climacteric Scale and of its vasomotor, psychological (anxiety and depression), and somatization subscales were stratified by season of a woman's birth. Data were controlled for possible confounders, such as age, years since menopause, body mass index, education occupation, smoking habits, and season of evaluation. RESULTS: The Greene Climacteric Scale appeared to be associated with the season of birth, with the lowest scores being observed in women born in autumn and the highest scores in women born in spring (+2.11; 95% CI, 0.67-3.56; P = 0.01), and summer (+2.22; CI, 0.82-3.63; P = 0.01). Lowest scores in autumn and highest scores in spring were also observed for psychological symptoms subscaled as anxiety and depression (+1.43; CI, 0.54-2.32; P = 0.01) and somatic symptoms (+0.59; CI, 0.15-1.04; P = 0.01). CONCLUSIONS: In this study, we found a relationship between season of birth and some menopause-associated symptoms. Further study is needed to confirm these relationships and examine possible mechanisms.     

Administration of raloxifene does not influence 24-hour ambulatory blood pressure of postmenopausal women with osteopenia: a double-blind placebo-controlled study

OBJECTIVE: Because estrogens may decrease 24-hour blood pressure of postmenopausal women, we tested the effect of the selective estrogen receptor modulator raloxifene on ambulatory blood pressure. STUDY DESIGN: Postmenopausal women with osteopenia who were otherwise healthy were assigned randomly in a double blind-fashion to receive placebo (n = 16 women) or raloxifene (60 mg/d, n = 16 women). Before and after 4 months, the blood pressure of each woman was monitored every 30 minutes for 41 hours with the use of an ambulatory device. RESULTS: Similar to the placebo outcome, the raloxifene administration did not modify 24-hour daytime (7 AM -11 PM) and nighttime (11 PM -7 AM) blood pressure and heart rate values. Day-night differences and the 24-hour rhythmic variation of mean blood pressure, which was evaluated by cosinor analysis, were also not affected by placebo or by raloxifene. CONCLUSION: Raloxifene does not influence 24-hour blood pressure of postmenopausal women. These data are reassuring for the cardiovascular safety of the long-term raloxifene administration.     

Seasonal onset of the menopause

OBJECTIVES: A seasonal rhythm of reproduction is evident in humans. Herein it was investigated whether also the cessation of woman's fertile life follows a seasonal rhythm. METHODS: A retrospective study was performed on 2436 women in postmenopause for more than 12 months, in our menopause centres. Time of menopause was stratified for month and season. The variation was compared to the seasonal rhythm of 14,310 conceptions. RESULTS: The onset of menopause was more frequent (p<0.0001) in winter (32.5%) than in spring (20.8%), autumn (20.3%) and summer (26.2%), in which a minor peak was also observed (p<0.0001 vs. spring and autumn). The two peaks were temporally coincident with the transitions between the high to low and low to high rate of conceptions. CONCLUSIONS: The present data show that in women, like reproduction also the onset of menopause shows a seasonal modulation.     

Influence of transdermal estradiol in the regulation of leptin levels of postmenopausal women: a double-blind, placebo-controlled study.

OBJECTIVE: To investigate whether the administration of transdermal estradiol is capable of modifying circulating levels of leptin. DESIGN: Forty postmenopausal women randomly received in a double-blind fashion, a transdermal patch containing either placebo or estradiol (50 microg/day). After 2 months of treatment, they were switched to the alternate treatment for another 2 months. Leptin levels were measured at the end of the placebo and estradiol administration. In a subset of 28 women an evaluation of body composition via bioelectrical impedance and an oral glucose tolerance test (OGTT; 75 g) were also performed at the end of the placebo and estradiol administration. Glucose, insulin, and leptin levels were measured in all OGTT samples. RESULTS: Leptin levels were related directly to body mass index (BMI), fat mass, and insulin, and inversely related to lean mass. In comparison to placebo, transdermal estradiol increased estradiol (from 77.8 +/- 8.4 pmol/l to 183.1 +/- 20.9 pmol/l; p < 0.0001) but did not significantly modify leptin (19.1 +/- 2.4 microg/l vs. 18.6 +/- 2 microg/l) or BMI. Estradiol did not modify fat mass or lean mass, significantly increased intracellular water (31.1 +/- 0.7% vs. 37.2 +/- 2.3%, p < 0.05), and decreased extracellular water (40.5 +/- 0.7% vs. 36.3 +/- 1.7%; p < 0.04). Leptin did not increase during OGTT, but a significant decrease, linearly related to BMI ( r = 0.519; p = 0.0189), was observed at the end of the test. CONCLUSIONS: Low doses of transdermal estradiol exert no influence on fasting leptin levels or BMI. The possibility that different doses of estradiol exert a more pronounced effect on circulating leptin needs to be addressed in comparative studies.     

Season of birth influences the timing of menopause

BACKGROUND: Seasons may influence prenatal growth and future fertility. This study investigated whether season and month of birth influenced the timing of menopause in a group of women attending three Italian menopause clinics. METHODS and RESULTS: Age at menopause of 2822 post-menopausal women (>12 months of amenorrhoea) was stratified by month and season of birth. Mean age at menopause was 49.42 years (SEM: 0.78 years). Menopause occurred earlier for women born in the spring (age 49.04+/-0.15 years) than in the autumn (49.97+/-0.14 years). The earliest menopause was found in women born in March (48.9+/-0.25 years) and the latest in women born in October (50.3+/-0.25 years). The effect of season of birth on age at menopause remained even when considering factors that in our analysis were capable of significantly interfering with the timing of menopause, such as age at menarche, body mass index, smoking habit, level of education and type of job. CONCLUSIONS: Taking into consideration the retrospective design of the study, and a possible recall bias, the present data seem to suggest that environmental factors linked to seasons are capable of interfering with the timing of a woman's ovarian exhaustion by an action exerted in the prenatal period.     

Biometrical threshold of biparietal diameter for certain fetal sex assignment by ultrasound.

OBJECTIVES: The aim of this study was to establish the biometric threshold of biparietal diameter (BPD), assumed to be an independent variable of gestational age, at which 100% accuracy in the assessment of fetal sex by ultrasonography is achievable. METHODS: Transvaginal and/or transabdominal sonography was used for detecting the 'sagittal sign' as a marker of fetal sex in 385 fetuses with BPD between 18 and 29 mm. The results of ultrasound examination were compared with sex at birth or with karyotype obtained from amniotic fluid cells or chorionic villus sampling. RESULTS: Fetal sex assignment was feasible in 337 of 385 cases (87.5%). Of the 312 fetuses with known fetal sex outcome, 164 were males and 148 were females. An accuracy rate of 100% was achieved when a BPD of > or = 23 mm was obtained. CONCLUSION: This study provides important information about the earliest stage of fetal development, expressed in terms of BPD, at which a diagnosis of fetal sex can be made with 100% accuracy.     

Effects of progestins on estrogen-induced increase in C-reactive protein in postmenopausal women

Background: C-reactive protein (CRP) represents an independent risk factor for coronary disease and stroke. Because oral estrogens increase CRP levels, with inflammatory and thrombotic consequences, we determined whether the co-administration of a progestin might modify the estrogenic effect on CRP. Methods: In a non-randomized, non-blinded study, we measured C-reactive protein serum concentrations with high-sensitivity technique (hs-CRP) in 163 healthy postmenopausal women divided into groups as follow: 52 not taking hormones (referent group), and 111 taking hormone replacement therapy (HRT) (42 of whom treated with unopposed estrogen, and 69 with an estrogen/progestin combination). Results: Compared with non-users of hormones, median CRP levels were 66% (95% confidence interval: from 44 to 89%) higher and 112% (95% confidence interval: from 89 to 168%) higher among women using a combined estrogen/progestin regimen and, respectively, among women taking unopposed estrogen [1.54 mg/L in the referent group; 2.56 mg/L in the estrogen/progestin group (P=0.032), and 3.27 mg/L in the unopposed estrogen group (P=0.004)]. Furthermore, there was no difference in CRP distributions between women taking different types of progestins. Conclusion: concurrent progestin administration may attenuate estrogen’s pro-inflammatory effects, independently on the type of used progestin.