Cognitive function in association with sex hormones in postmenopausal women

Several studies have suggested gender differences in cognitive function, but data on the association between sex hormones and cognitive function are contradictory. The aim of our randomized double-blind study was to explore the possible relations between cognitive function and serum levels of sex hormones, oxytocin and insulin-like growth factor-I (IGF-I) in postmenopausal women. Two-hundred healthy postmenopausal women were randomly assigned to receive estrogen, testosterone or placebo treatment for 1 month. The associations of spatial ability, verbal fluency and verbal memory with serum levels of estradiol, testosterone, estradiol/testosterone ratio, androstanediol, oxytocin and IGF-I were analyzed. Spatial ability showed a negative correlation with serum estradiol, estradiol/testosterone ratio, oxytocin levels and a positive association with androstanediol levels. Verbal fluency displayed a negative relationship with serum levels of testosterone, IGF-I and a positive with estradiol/testosterone ratio. Verbal memory displayed a positive correlation to androstanediol. Data suggest that not only absolute levels of sex hormones but also the balance between estrogen and testosterone and their metabolites may be important for cognitive function in women.     

Serum lipid levels and bone mineral density in Greek postmenopausal women

Contradictory results have been reported regarding a relationship between serum lipid levels and bone mineral density. The purpose of this study was to further investigate a possible relationship between those parameters in Greek postmenopausal women. A total of 591 patients followed at a tertiary hospital were examined for seven different lipid factors in relation to dual-emission X-ray absorptiometry measurements at the lumbar spine. Lipoprotein-a was the only lipid measurement that univariately showed an almost significant trend of association with bone mass category (analysis of variance [ANOVA] p value 0.062 for Ln(Lipoprotein-a)). In multiple regression, it was noted that a non-significant negative trend of association of high density lipoprotein (HDL) cholesterol and Apolipoprotein AI with lumbar T-score (p value 0.058 and 0.075, respectively). In age subgroup analysis, Lipoprotein-a and Ln(Lipoprotein-a) presented a negative correlation with lumbar T-score for women with age ≥ 53 years (p value 0.043 and 0.070, respectively), while a negative correlation of HDL and Apolipoprotein AI levels with lumbar T-score remained in women with age < 53 years (p value 0.039 and 0.052, respectively). The findings do not support a strong relationship between lipid levels and bone mass measurements.     

Association between metabolic syndrome and serum leptin levels in postmenopausal women

Menopausal status is associated with weight gain, increased central fat mass, abnormal lipid metabolism, insulin resistance and susceptibility to metabolic syndrome (MetS). Leptin is synthesised and secreted by adipocytes. Serum leptin levels are highly correlated with fat mass. We determined the association between MetS and serum leptin levels in 153 postmenopausal women. The difference in serum leptin level between MetS and non-MetS groups showed a statistical significance after adjusting for body mass index (BMI; 19.9 ± 9.5 vs 12.1 ± 5.9 ng/ml, p = 0.013). The indicator of abdominal obesity, waist-to-hip ratio (WHR) and visceral fat area (VFA), had a positive correlation with serum leptin level in non-obese subjects after adjusting for BMI (p = 0.017, p < 0.001, respectively). Of the components of MetS, abdominal obesity and the number of MetS components had a positive correlation with serum leptin level (p < 0.05, p < 0.001, respectively).     

Reference intervals for serum sex steroids and gonadotropins in regularly menstruating women.

Reference intervals for novel fluoro-immunoassays for serum luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P) were established in 40 healthy regularly menstruating women. Serum samples for sex steroids, including testosterone (T), androstenedione (A) and dehydroepiandrosterone sulphate (DHEAS), as well as sex hormone binding globulin (SHBG) and gonadotropins, were collected in the early follicular and mid-luteal phases of the menstrual cycle. The need for the timing of androgen and gonadotropin samples was also determinated. Serum E2 and P were measured by radio-immuno- and time-resolved fluoro-immunoassays. Various assay methods correlated closely, but the reference intervals varied considerably from one method to another. In the early follicular phase the LH/FSH ratio only ranged between 0.2 and 1.7 (mean +/- S.D.; 0.8 +/- 0.3); the variation was greater (from 0.3 to 3.5) in the luteal phase, when the mean was also significantly higher (1.5 +/- 0.9, p = 0.0001). Similarly the mean values of T and SHBG were higher in the luteal phase, while the other androgen concentrations and calculated androgen indexes were equal, compared with the follicular phase values. Thus the timing of hormone determinations is warranted in the investigation of the gonadotropin and androgen status in normally menstruating women. Moreover, the upper limit of the LH/FSH ratio examined with new, sensitive methods is lower than that previously stated. The use of an intra-uterine contraceptive device (IUD) had no effect on hormone levels.     

Behaviour of some steroids in postmenopausal women with coelomic ovarian tumors

In order to study the hormonal pattern in ten postmenopausal women with coelomic ovarian tumors we measured Estrone, Androstenedione, DHEA-S and Testosterone plasmatic levels before and after surgery. Estrone and Androstenedione plasmatic levels were significantly higher in patients with coelomic ovarian tumors than in the control group and they showed a rapid and constant decrease after surgery. Nevertheless we didn't find any ovarian histological picture to explain the hormonal increase.     

The effect of risedronate treatment on serum osteoprotegerin and bone marker levels in postmenopausal women with osteoporosis

Background.?To evaluate the effect of risedronate treatment on osteoprotegerin (OPG), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin (OC), and deoxypyridinoline (DPD).

Methods.?Eighty postmenopausal osteoporotic patients were randomized into two groups. In first group, patients received 35?mg of risedronate once a week and calcium with vitamin D per day. In second group, patients received only calcium with vitamin D per day. Bone turnover markers were measured at baseline, 1st, 3rd and 6th month.

Results.?OPG levels were significantly reduced at 1st and 6th month of treatment in both groups, but no statistically significant difference was detected between groups. In the group treated with risedronate, difference in CTX level was observed at 3rd month of treatment, while a difference in DPD and OC levels were observed at 6th month of treatment. The baseline OPG levels correlated with age, menopause duration, and CTX levels. There was no correlation between OPG levels and the levels of the other markers during treatment.

Conclusion.?The present study showed that using risedronate in treatment of postmenopausal osteoporosis causes no specific changes in OPG levels; therefore, in contrast to some of the studies in the literature OPG may not be useful marker in monitoring of bisphosphonate.     

The effect of estrogen deficiency, estrogen and estro-progestagene therapy on total plasma homocysteine and serum lipid peroxide levels in postmenopausal women

OBJECTIVES: Elevated plasma homocysteine (Hcy) concentration is a risk factor for atherosclerosis and venous thrombosis. DESIGN: an observational study. MATERIALS AND METHODS: 120 healthy women were recruited and divided in two subgroups--postmenopausal women (M-80 women) and premenopausal women (40 women) with normal menstruation as control group. 26 women with surgical menopause were treated with percutaneous estrogen therapy and remaining 54 women were treated with estro-progestagen replacement therapy. Measurements of FSH and estradiol was made using radioimmunoassay. HCY was assessed using enzymatic conversion method. RESULTS: Concentrations of Hcy and lipid peroxides (LPO) in postmenopausal study group were higher than in the premenopausal. Treatment with estradiol (E2) alone or in combination with medroxyprogesterone acetate decreased LPO and Hcy concentrations to levels observed in premenopausal group. CONCLUSIONS: Our results suggest that estrogens have a profound influence on Hcy and LPO levels. Reduction in Hcy levels after treatment lowers the production of free radicals and thus contributes to lipid peroxidation decrease and LPO levels reduction after therapy. A practical conclusion may be proposed: in postmenopausal women with elevated Hcy levels who require hormonal replacement therapy, Hcy level control is indicated in order to administer such a therapy, which decreases Hcy concentrations.     

Nitric oxide and pro-inflammatory cytokine serum levels in postmenopausal women with the metabolic syndrome

Background: The metabolic syndrome (METS) increases after the menopause which may enhance cardiovascular risk in part explained by a pro-inflammatory state. Objective: Measure nitric oxide (NO), tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) serum levels in postmenopausal women with and without the METS (Adult Treatment Panel III criteria). Methods: Analyte levels were compared among those with and without the syndrome and each of its diagnostic components. Rho Spearman coefficients were also calculated to determine correlations between analyte levels and various numeric variables. Results: Median age of all studied women (n = 88) was 54.4 years, 62.5% had abdominal obesity, 14.8% hyperglycemia, 59.1% high triglycerides (TG) and 44.3% hypertension. Women with the METS (n = 44) displayed higher body mass index values and higher rates of abdominal obesity, hyperglycemia, hypertriglyceridemia, hypertension and low HDL-C levels. Median NO and IL-6 levels were significantly higher in women with the METS as compared to controls (p < 0.05). Independent of presenting the METS, analytes were higher in those displaying abdominal obesity (IL-6), hypertension (IL-6 and TNF-α) and more METS diagnostic criteria and abnormal HDL-C, TG and glucose levels (NO). Both cytokines positively correlated with the number of METS criteria, age and time since menopause, IL-6 positively with waist circumference and TNF-α positively with blood pressure levels. NO levels inversely correlated with HDL-C values and positively with the number of METS criteria, glucose, and TG levels; correlation with the latter being the highest (r² = 0.65, p = 0.0001). Conclusion: Postmenopausal women with the METS displayed higher IL-6 and NO levels, with significant correlations found between studied analytes and some of the components of the syndrome.     

Effects of gestrinone on serum lipid and lipoprotein levels in women with endometriosis

Gestrinone (G) was given to 12 females with endometriosis in weekly doses of 5 or 10mg for 4 to 6 months, and the change in serum lipids and lipoproteins was analysed. G decreased total cholesterol by 20% (p less than 0.05), triglycerides by 36% (p less than 0.05), phospholipids by 28% (p less than 0.01) and lipid peroxides by 34% (p less than 0.05), among which reductions in them were statistically significant when compared with the pretreatment levels. Levels of high density lipoproteins (HDL) also fell: HDL-cholesterol by 41% (p less than 0.01), HDL-triglycerides by 49% (p less than 0.05) and HDL-phospholipids by 38% (p less than 0.01) which were significant. Concurrently apolipoproteins (Apo) and lecithin-cholesterol acyltransferase activity (LCAT) decreased: Apo A-I by 31% (p less than 0.01), Apo A-II by 13% (p less than 0.05) and LCAT by 53% (p less than 0.05), which were significant. In contrast, there were few changes in the levels of low density lipoproteins (LDL) and Apo B. There was also little effect on very low density lipoproteins (VLDL) except VLDL-triglycerides which decreased by 52% (p less than 0.05). Meanwhile free fatty acids increased by 61% (p less than 0.05). Therefore, the atherogenic index defined as the ratio of LDL-cholesterol to HDL-cholesterol rose as much as 92% (p less than 0.01) of the initial value in 24 weeks of medication. When these results were examined with respect to the 5 and 10mg administration group, dose-dependent effects were observed, but these were not marked.(ABSTRACT TRUNCATED AT 250 WORDS)     

Raloxifene increases serum leptin levels in postmenopausal women: a prospective study

OBJECTIVE: The purpose of this study was to investigate the effect of raloxifene on leptin and insulin-like growth factor-I levels and their relation with the biochemical markers of bone metabolism in postmenopausal women. STUDY DESIGN: Sixty-four women were given 60 mg/d raloxifene for 6 months. Serum leptin, insulin-like growth factor-I, alkaline phosphatase, calcium, osteocalcin, and collagen type I cross-link C-telopeptide levels were measured before and after the treatment. The patients were grouped as obese (body mass index, > or =25 kg/m2) or non-obese (body mass index, <25 kg/m2). RESULTS: The mean basal leptin level was significantly higher (P < .001), and the mean cross-link C-telopeptide level was significantly lower (P = .001) in obese patients. Raloxifene therapy increased leptin levels (P < .001) and decreased insulin-like growth factor-I, alkaline phosphatase, and cross-link C-telopeptide levels significantly (P < .001). There was a strong negative correlation between leptin and cross-link C-telopeptide (r = -0.703; P < .001). Insulin-like growth factor-I was not correlated with any parameter. CONCLUSION: Raloxifene increases serum leptin levels while decreasing bone resorption in postmenopausal women.     

Effects of estrogen dose and smoking on lipid and lipoprotein levels in postmenopausal women

The joint effects of conjugated estrogen use, age, body mass index, and smoking on plasma lipid and lipoprotein levels were assessed in 585 women who used oral estrogen and 1093 women who did not who participated in the Walnut Creek Contraceptive Drug Study. Whether administered daily or cyclically, conjugated estrogen was associated with reductions in low-density lipoprotein cholesterol levels and increases in high-density lipoprotein cholesterol and triglyceride levels. The adjusted mean low-density lipoprotein cholesterol concentration was 132 mg/dl for women who used conjugated estrogen in a dose ≥ 1.25 mg/day; the adjusted corresponding mean concentration was 147 mg/dl for postmenopausal women who did not use estrogen. A dose-response pattern was demonstrated between conjugated estrogen and low- and high-density lipoprotein cholesterol levels. A maximum low-density lipoprotein cholesterol level reduction was reached at a dose of 1.25 mg, suggesting a saturation phenomenon. Stepwise dose-response increases in high-density lipoprotein cholesterol levels were also found with estrogen therapy, with a maximum increase of 8 to 10 mg/dl observed with the 1.25 mg dose. Estrogen-related rises in low-density lipoprotein cholesterol levels and decreases in high-density lipoprotein cholesterol levels were offset by 2 to 3 mg/dl in women who smoked. It may be concluded, therefore, that among postmenopausal women, low-risk lipoprotein profiles as assessed by low- and high-density lipoprotein cholesterol levels are found in nonsmokers whose postmenopausal hormone therapy includes the equivalent of a conjugated estrogen dose of 1.25 mg.     

Fetal sex dependent hormone levels in early pregnant women with elevated maternal serum alpha-fetoprotein

Maternal serum and amniotic hormone levels have been investigated in two groups of women in pregnancy weeks 18-21. One group (B) was composed of women with high alpha-fetoprotein levels in serum without fetal abnormality, and a matched control group (A) with normal alpha-fetoprotein levels in serum. Amongst group B women were four pregnancy complications: two spontaneous abortions, one premature delivery, and one cesarean section due to fetal asphyxia. Group B women were significantly different from group A women. Thus, higher maternal serum levels of total estriol (P = 0.030), testosterone (P = 0.016), and alpha-fetoprotein (P = 0.018) were noted in the presence of male fetuses; and higher hPL (P = 0.004), FSH (P = 0.037), and alpha-fetoprotein (P = 0.002) concentrations in women carrying female fetuses, who were accompanied by lower total estriol concentrations (P = 0.045). Differences between groups B and A in terms of amniotic fluid analyses were only related to female fetal sex. Thus, group B showed higher hPL (P = 0.028), testosterone (P = 0.020), and FSH (P = 0.006) levels, and lower alpha-fetoprotein (P = 0.013) concentrations. It is concluded that elevated maternal serum levels of alpha-fetoprotein are accompanied in female fetuses by an endocrine milieu different from that of matched controls. This difference may put the conceptus at a disadvantage, but the majority of the girls were born on time without signs of small-for-date.     

Relationship between serum testosterone and sex hormone binding globulin in menstruating and postmenopausal women

The relationship between total testosterone (T), sex hormone binding globulin (SHBG) and calculated non-SHBG-bound testosterone (NST) was studied in randomly collected blood samples from healthy menstruating (n = 61) and postmenopausal (n = 65) women. In 12 of the menstruating women, blood samples were also collected more frequently during the menstrual cycle. Total T and SHBG were positively correlated in menstruating women in random samples as well as during different phases of the menstrual cycle, but not in postmenopausal women. Upper and lower limits of NST were independent of SHBG in menstruating but not in postmenopausal women. The data are at variance with the common concept about SHBG regulation and suggest a kind of compensatory mechanism in order to maintain a constant androgen homeostasis in menstruating but not in postmenopausal women. Consequently, supranormal total T or subnormal SHBG values do not necessarily indicate hyperandrogenicity in normally menstruating women.     

Effect of cyclic estrone sulfate treatment on lipid profiles of postmenopausal women with elevated cholesterol levels

The effects of two doses of cyclic unopposed estrone sulfate therapy on the lipid profiles of 153 healthy postmenopausal women with baseline total cholesterol levels above 219 mg/dL were compared in a multicenter, double-blind, placebo-controlled study. Patients were assigned randomly to one of three treatment groups: estrone sulfate 0.625 mg (N = 59) or 1.25 mg (N = 43), or placebo (N = 51). The median baseline total cholesterol levels of the three treatment groups were 262, 269, and 262 mg/dL, respectively. Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and the HDL/LDL ratio were assessed after 6, 9, and 12 months of treatment. There was a significant monotonic dose-response relationship of estrone sulfate in raising HDL levels, lowering LDL levels, and raising the HDL/LDL ratio at all intervals measured. These results indicate that estrone sulfate is effective in creating a beneficial change in the lipid profile of postmenopausal women with elevated baseline total cholesterol.     

Short-term effects of hormone therapy on serum C-reactive protein levels in postmenopausal women

Objectives: The aim of this study was to investigate the effects of tibolone and conjugated equine estrogens (CEEs) plus medroxyprogesterone acetate (MPA) (CEE + MPA) on levels of serum C-reactive protein (CRP), an independent risk factor for cardiovascular disorders, in postmenopausal women. Study design: In this prospective randomized study, we randomly assigned 58 healthy postmenopausal women to CEE (0.625 mg/day) plus MPA (2.5 mg/day) (CEE + MPA) or tibolone (2.5 mg/day). The serum levels of CRP at 3 months after starting treatment were compared with baseline values for both therapies. Results: After 3 months of treatment the median CRP levels increased by 29% in the CEE + MPA group and by 5% in the tibolone group. But, these changes did not have statistical significance (P=0.15, P=0.06, respectively). Conclusions: Our findings show that neither tibolone nor CEE + MPA caused significant changes in serum CRP levels in postmenopausal women. The potential impact of hormone therapy on serum CRP levels should be investigated in ongoing clinical trials.     

Effects of estrone sulfate alone or with medroxyprogesterone acetate on serum lipoprotein levels in postmenopausal women

OBJECTIVE: To determine the effects of estrone sulfate alone or with different doses of medroxyprogesterone acetate on serum lipid and lipoprotein levels. METHODS: A multicenter, double-masked, randomized trial for 1 year involved 682 postmenopausal women, aged 53.8 +/- 0.2 years (mean +/- standard deviation) with intact uteri. Subjects received fixed daily doses of 0.625 mg of estrone sulfate and one of the following regimens: placebo; 2.5 mg daily of medroxyprogesterone acetate; 5 mg daily of medroxyprogesterone acetate; or 10 mg of medroxyprogesterone acetate for the first 12 days of each 28-day cycle. Fasting lipid and lipoprotein levels were measured at baseline and weeks 12, 16, 24, 30, 36, and 52 of treatment. Absolute mean changes from baseline were determined by paired t test, and treatment effects were determined by analysis of variance. RESULTS: Total cholesterol levels decreased significantly (P <.05) from baseline in all study groups; however, reduction was significantly greater (P <.001) in the 2.5-, 5-, and 10-mg groups (-13.3%, -15.2%, and -14.1%) than in the placebo group (-4.9%). Low-density lipoprotein cholesterol levels decreased significantly and equally in all groups (-10.1% to -12.3%). High-density lipoprotein cholesterol levels increased by 3.2% with unopposed estrogen (P <.05) and did not change from baseline with combined therapy. Triglyceride and very low-density lipoprotein cholesterol levels increased by 13.4% and 2.7%, respectively, in the placebo group, did not change in the 2.5-mg group, decreased by 10.2% and 2.0% and by 11.4% and 2.2% in the 5- and 10-mg groups, respectively (P <.05). CONCLUSION: Estrone sulfate at the daily dose of 0.625 mg alone or with medroxyprogesterone acetate significantly improved lipoprotein levels. Combined therapy with medroxyprogesterone acetate and estrone sulfate was associated with statistically significantly greater reduction in total cholesterol and statistically significantly less increase in triglyceride levels than unopposed estrone sulfate therapy.     

The effect of treatment with oestradiol and oestriol on fasting serum cholesterol and triglyceride levels in postmenopausal women.

The effect of natural oestrogens on serum cholesterol and serum triglyceride levels was studied in a controlled double-blind clinical trial. No statistically significant changes were found in the blood lipids when comparing the patients treated with oestradiol, 2 mg, and oestriol, 1 mg, and those given placebo.     

Urinary profile of endogenous steroids in postmenopausal women with stress urinary incontinence.

OBJECTIVE: To predict the role of estrogen in prevention of and therapy for stress urinary incontinence by comparing the urinary levels of estrogens and androgens and, to indirectly evaluate metabolism of estrogens and androgens by comparing the concentration ratios of precursor metabolites with those in controls (normal subjects). STUDY DESIGN: Urine samples collected for 24 hours were obtained from postmenopausal women with stress urinary incontinence (n = 20) and from age-matched, postmenopausal, normal female subjects (n = 14). The urinary levels of 20 estrogens and 25 androgens were analyzed by gas chromatography/mass spectrometry. RESULTS: The urinary levels of androgens were significantly higher in patients with stress urinary incontinence than normal subjects, and the urinary levels of estrogens were somewhat higher in patients than normal subjects. However, there were no significant differences between the groups, nor were there significant differences in the metabolism of estrogens and androgens between two groups. CONCLUSION: The urinary levels of endogenous steroids were rather higher in patients with stress urinary incontinence than in normal subjects, so it appears that estrogen should not play a significant role in prevention of and therapy for stress urinary incontinence.     

Tibolone versus four estrogen replacement therapy protocols and plasma lipid levels in postmenopausal women.

OBJECTIVES: To compare tibolone therapy with four different estrogen replacement therapy protocols, with regard to the effects on plasma lipid profiles. METHODS: The plasma lipid levels of 178 postmenopausal women in five different therapy groups were compared with each other as well as their baseline levels with 6-month intervals during 2-year follow-up. Student's t-test, paired t-test and Pearson correlation analysis were utilized for statistical analysis. RESULTS: HDL cholesterol levels increased significantly from baseline in groups using oral estrogen (P<0.05) but a slight non-significant decrease was seen in tibolone therapy (P>0.05). LDL cholesterol levels significantly decreased at the end of the second year in oral estrogen and tibolone users (P<0.05). Triglyceride levels increased non-significantly with estrogen therapy (P>0.05), whilst decreased significantly in the tibolone group (P<0.05). CONCLUSION: Tibolone may be a good alternative to estrogen replacement therapy in postmenopausal women, as it has beneficial effects on LDL cholesterol and triglyceride levels, which play important role in atherosclerosis.