Thyroid function and autoimmunity are associated with the risk of vertebral fractures in postmenopausal women.

Overt or subclinical thyroid dysfunction may affect the risk of fragility fractures. The aim of the present study was to assess the association of thyroid function and autoimmunity with vertebral fractures (VF) in a large sample of Greek postmenopausal women. This cross-sectional study recruited 335 euthyroid postmenopausal women, aged 35-79 years. Euthyroidism was verified by serum thyroid-stimulating hormone (TSH) within the laboratory reference range (0.4-4.5 µIU/mL). VFs were diagnosed by lumbar spine lateral radiographs, according to quantitative procedures. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, as well as levels of anti-thyroglobulin (anti-TG) and thyroid peroxidase antibodies (anti-TPO) were compared according to the presence of VFs. Multivariate logistic regression showed that the presence of VFs was predicted independently by ln-TSH levels (OR = 0.290, p = 0.037) and positive anti-TG antibodies (OR = 3.308, p = 0.026) in models adjusted for age, menopausal age, and ln-HOMA-IR. Stepwise logistic regression analysis showed that the presence of VFs was predicted by menopausal age (OR = 1.120, p = 0.001), ln-TSH (OR = 0.312, p = 0.052), and thyroid autoimmunity (anti-TG and anti-TPO positive: OR = 6.637, p = 0.007) in a model that also included age and ln-HOMA-IR. Women with lower circulating TSH had higher risk of having a VF, independently of age, menopausal age, and insulin resistance. The presence of positive anti-TG/anti-TPO antibodies also indicated an elevated risk of fracture. Levels of thyroid hormones had no apparent effect on the risk of fracture. Further studies are necessary to establish the significance of our findings.

Stress urinary incontinence and endogenous sex steroids in postmenopausal women.

AIMS: Urinary incontinence in general is a major cause of quality of life impairment, morbidity and hospitalization. Its onset is strongly linked to the menopause. Our study aimed to elucidate the possible relationship between endogenous circulating estrogens and the onset and development of stress urinary incontinence (SUI). METHODS: One hundred and thirty eight peri- and postmenopausal women with SUI were matched 1:1 with continent women based on age and BMI. Morning fasting blood samples were drawn from all subjects for assessment of estradiol (E2), FSH, LH, Testosterone, Δ4-Androstendione (Δ4Α), DHEAS, prolactin, SBHG as well as a biochemical profile (glucose, insulin, triglycerides, cholesterol, HDL, LDL, ApoA1, ApoB). Hormone and biochemical parameters were compared between continent and incontinent women. RESULTS: Incontinent women had significantly lower serum estradiol levels compared to those in the control group (17.30 ± 8.16 vs. 24.22 ± 8.99, P < 0.001). Furthermore, the same association was observed for serum Δ4Α (146.07 ± 52.63 vs. 159.99 ± 42.62, P = 0.017). These associations remained significant after controlling for age, menopausal age, BMI, and number of deliveries. CONCLUSIONS: These results may indicate that within the postmenopausal range, endogenous sex hormones may be associated with the presence of SUI in women not on menopausal hormone therapy. Neurourol. Urodynam. 36:121-125, 2017. © 2015 Wiley Periodicals, Inc.

Association of sex hormones and glucose metabolism with the severity of multiple sclerosis.

PURPOSE/AIM OF THE STUDY: We evaluated possible associations between the severity of multiple sclerosis (MS) and levels of sex hormones as well as biochemical parameters in a sample of ambulatory patients. MATERIAL AND METHODS: This cross-sectional study recruited 133 adults (52 men, 66 premenopausal and 15 postmenopausal women), with relapsing-remitting MS. Fasting venous blood samples were drawn for biochemical and hormonal evaluation. These parameters were tested for possible associations with MS severity, assessed using the Expanded Disability Status Scale (EDSS)-scores. RESULTS: Follicle-stimulating hormone correlated with mean EDSS scores (r = -0.369, p = 0.038) in the premenopausal subgroup. However, this association became non-significant in the age-adjusted multivariate analysis (p = 0.141; power = 67%, type α error 0.10). Free androgen exhibited a borderline negative effect on EDSS-scores in the subgroup of men (r = -0.367, p = 0.093), which was lost after adjusting for age and duration of disease (p = 0.192; statistical power = 93%, type α error 0.05). Levels of estradiol tended to affect disability status of postmenopausal women (normal-mild vs. severe impairment: 23.33 ± 11.73pg/mL vs. 14.74 ± 6.30pg/mL, p = 0.095). Levels of sex hormones or indices of glycemic metabolism did not differ between patients presenting with EDSS scores higher or lower than the median value. CONCLUSION: Sex hormones and indices of glucose metabolism exhibited only a middle effect on EDSS scoring, which was not independent from the presence of confounders like age and duration of MS. The present study highlights the need for additional research, in order to elucidate the role of sex hormones and insulin resistance in the course of MS.

The Acute Effect of the Antioxidant Drug U-74389G on Red Blood Cell Distribution Width Levels During Hypoxia Reoxygenation Injury in Rats.

UNLABELLED: The AIM of this experimental study was to evaluate the effect of the antioxidant drug "U-74389G" in a rat model of hypoxia reoxygenation (HR) using the previously established protocol. Effects of treatment were evaluated by mean red blood cell distribution width (RDW) levels. MATERIALS AND METHODS: 40 rats of a mean weight of 231.875 g were employed in the study. RDW levels were determined at 60 min (groups A and C) and at 120 min (groups B and D) after starting the reoxygenation. Groups A and B received no drugs, whereas rats from groups C and D were administered with U-74389G. RESULTS: demonstrated that U-74389G administration significantly decreased the RDW levels by 4.96% + 2.27% (p = 0.0175). Reoxygenation time non-significantly decreased the RDW levels by 0.27% + 2.41% (p = 0.8889). Together, U-74389G administration and reoxygenation time non-significantly decreased the RDW levels by 2.54% + 1.39% (p = 0.0679). CONCLUSIONS: U-74389G administration particulary in concert without reperfusion declines the RDW levels even within the short - time context of 1.5 hours reperfusion.

Antioxidant 21-aminosteroid "U-74389G" ameliorates the short-time effect of hypoxia-reoxygenation on the platelet count in rats.

AIM: The aim of this experimental study was to examine the effect of the antioxidant drug "U-74389G", on rat model and particularly in a hypoxia-reoxygenation protocol. The beneficial effect or non-effectiveness of that molecule were studied hematologically using blood mean platelet count. Results were that U-74389G administration interacted or not with reoxygenation time decreased the platelet count by 6.12% ± 3.58% (p = 0.0857) and 12.83% ± 5.79% (p = 0.0303) respectively. CONCLUSIONS: U-74389G administration interacted or not with reoxygenation time decreases the platelet count within short-term time of 2 hours by different significance levels.

Vitamin D receptor Bsm1 polymorphism, calcium metabolism and bone mineral density in patients with multiple sclerosis: a pilot study.

Vitamin D receptor's (VDR) genotypes have been associated both with the development of bone disease and the pathogenesis of multiple sclerosis (MS). We aimed to evaluate the association between the presence of Bsm1 restriction fragment length polymorphism of VDR and bone loss in ambulatory patients with MS. This cross-sectional study included 82 adult patients with relapsing-remitting MS. Fasting blood samples were obtained for biochemical-hormonal assessment and genotyping. Bone mineral density (BMD) was assessed at the lumbar spine (LS) and the femoral neck (FN), using dual energy X-ray absorptiometry. Possible associations between VDR's genotypes and BMD levels as well as biochemical and hormonal indices were evaluated. Among premenopausal women and men, carriers of the B allele exhibited higher BMD and Z score at the FN and a trend toward higher BMD at the LS, compared to patients with the bb genotype, after adjusting for age, BMI, sex, EDSS scoring, interferon administration, duration of MS and total steroids intake. Among postmenopausal women, the presence of the B allele was not associated with BMD or T score at any site, whereas carriers of the B allele exhibited higher levels of calcium (p value 0.008, univariate). No other significant differences were exhibited between levels of electrolytes, parathormone, 25-hydroxyvitamin D3 and the genotype of VDR, in any of the groups. VDR's Bsm1 polymorphism is associated with a mild effect on BMD in younger patients with MS. Larger studies are necessary to corroborate these findings.

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.

Maternal serum resistin concentrations in gestational diabetes mellitus and normal pregnancies.

AIM: To investigate changes in maternal serum resistin levels during pregnancy and postpartum and clarify their relationship to insulin resistance. METHODS: Thirty normal pregnant women were compared to 30 women diagnosed with gestational diabetes mellitus (GDM). Serum resistin levels were collected at the time of glucose challenge test (26-28 weeks), at 38 gestational weeks and at the third postpartum day and measured with enzyme immunoassay. Correlation of resistin to the homeostatic model assessment-insulin resistance (HOMA-IR) was performed. RESULTS: Maternal serum resistin levels at 38 weeks were significantly higher in pregnant women with GDM compared to the control group (0.28 vs 0.21 ng/mL, P = 0.02) and the same was true for the immediate puerperium (0.25 vs 0.19 ng/mL, P = 0.03). A significant increase in resistin levels was observed in GDM women from 26-28 weeks to 38 weeks (0.21 vs 0.28 ng/mL, P = 0.02), but not in controls. A decrease in serum resistin levels was noted in both the GDM and control groups, at 38 weeks and the immediate postpartum period, but this decrease did not reach statistical significance in either of the two groups. Resistin levels were positively correlated to HOMA-IR at 26-28 weeks of gestation (r = +0.253, P = 0.05). CONCLUSION: GDM is associated with increased resistin serum levels in term pregnancy as well as postpartum. Resistin is positively correlated to HOMA-IR at 26-28 weeks of gestation. A reduction in maternal resistin after delivery indicates a significant placental or fetal contribution in the production of resistin.

Circulating leptin and ghrelin are differentially influenced by estrogen/progestin therapy and raloxifene.

BACKGROUND: Leptin and ghrelin are increasingly being recognized as cardiotropic hormones, promoting or inhibiting the atherosclerotic process, respectively. Apoptosis may be one pathway through which the actions of these hormones are mediated. Sex hormones are reported to influence the secretion and action of ghrelin and leptin. OBJECTIVE: To evaluate (1) the association of circulating ghrelin and leptin with selected markers of receptor-mediated apoptosis and (2) the effect of estrogen monotherapy, low dose estrogen-progestin therapy, tibolone and raloxifene on serum ghrelin and leptin in healthy postmenopausal women. METHODS: Eighty eight postmenopausal women aged 44-62 years were randomly allocated to daily (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5 mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum markers of apoptosis sFas, Fas-ligand (Fas-L) and caspase-1 were measured at baseline. Serum leptin and ghrelin were measured at baseline and at 3 months. RESULTS: Body Mass Index (BMI) and estradiol levels correlated positively, while FSH correlated negatively with serum leptin (BMI: r=0.646, p=0.005, estradiol: r=0.432, p=0.001, FSH: r=-0.401, p=0.002). Insulin levels associated positively with circulating leptin (r=0.394, p=0.011) and negatively with circulating ghrelin (r=-0.401, p=0.009). Serum leptin decreased significantly in E2/NETA group (baseline: 2.882+/-0.76 ng/ml, 3 months: 2.687+/-0.66 ng/ml, p=0.043), while it increased significantly in the raloxifene group (baseline: 2.671+/-0.54 ng/ml, 3 months: 2.839+/-0.47 ng/ml). Ghrelin levels decreased significantly only in the raloxifene group (baseline: 1634+/-592 pg/ml, 3 months: 1408+/-534 pg/ml). CONCLUSION: Apoptosis may be a pathway through which leptin exerts a pro-atherogenic effect. Low dose HT may act cardioprotectively by decreasing leptin levels in healthy recently menopaused women.

Circulating chemoattractants RANTES, negatively related to endogenous androgens, and MCP-1 are differentially suppressed by hormone therapy and raloxifene.

BACKGROUND: The cardinal role of chronic inflammation in the development of atherosclerosis is increasingly being recognized. Estrogens may prevent the evolution of atherosclerosis by suppressing immune response. Furthermore, the conflicting reports on the cardiovascular effects of hormone therapy between observational and clinical trials have triggered interest on the effect of alternative therapies on the cardiovascular system. OBJECTIVE: The aim of this study was to assess the effect of estrogen, estrogen-progestin, tibolone and raloxifene therapy on circulating markers of chemotaxis in healthy postmenopausal women. METHODS: Eighty-eight postmenopausal women aged 44-62 years were randomly allocated to daily: (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured at baseline and at 3 months. RESULTS: Endogenous testosterone and free androgen index (FAI) correlated negatively, while SHBG correlated positively with serum RANTES (testosterone: r=-0.27, p=0.033; FAI: r=-0.43, p=0.004: SHBG: r=0.34, p=0.026). Serum MCP-1 decreased significantly in the CEE group (baseline 125.3+/-51 pg/ml, 3 months 84.5+/-36.1 pg/ml, p=0.043), while no difference was detected between baseline and post-treatment levels in the other groups. Furthermore, a significant decrease in serum RANTES was observed at the end of 3 months only in the E2/NETA and the raloxifene group (E2/NETA baseline 8690.6+/-3880.0 pg/ml, 3 months 6894.0+/-1720.0 pg/ml, p=0.007; raloxifene baseline 9042.4+/-3765.6 pg/ml, 3 months 6718.1+/-2366.2 pg/ml, p=0.011). CONCLUSION: Endogenous androgens may suppress chemotactic response. Postmenopausal hormone therapy and raloxifene may inhibit the expression of chemoattractant molecules and thus attenuate inflammation. The relevance of these findings in terms of clinically established caridoprotection remains to be clarified.

Comparison of the Acute Hematopoietic Capacities of Erythropoietin and U-74389G Concerning Hematocrit Levels.

AIM: This study compared the hematopoietic capacities of erythropoietin (Epo) and antioxidant drug U-74389G, based on 2 preliminary studies. The provided results on hematocrit levels augmentation were co-evaluated in a hypoxia reoxygenation protocol of an animal model. MATERIALS AND METHODS: Hematocrit levels were evaluated at the 60th reoxygenation min (for groups A, C and E) and at the 120th reoxygenation min (for groups B, D and F) in 60 rats. Groups A and B received no drugs, rats from groups C and D were administered with Epo; whereas rats from groups E and F were administered with U-74389G. RESULTS: The first preliminary study of Epo non-significantly increased the hematocrit levels by 0.24%+1.38% (p-value=0.8586). The second preliminary study of U-74389G significantly raised the hematocrit levels by 3.16%+1.33% (p-value=0.0196). These 2 studies were co-evaluated since they came from the same experimental setting. The outcome of the co-evaluation was that U-74389G has approximately 12.66-fold higher hematopoietic potency than Epo (p-value=0.0000). CONCLUSION: The anti-oxidant capacities of U-74389G provide satisfactory acute hematopoietic properties; presenting approximately 12.66-fold hematocrit level rise than epo (p-value=0.0000).

A 5-year study on the effect of hormone therapy, tibolone and raloxifene on vaginal bleeding and endometrial thickness.

OBJECTIVES: To study the effect of standard and low-dose estrogen-progestin therapy (EPT), tibolone and raloxifene on the incidence of vaginal spotting/bleeding and endometrial thickness over a 5-year period. METHODS: Seven hundred eighty-six postmenopausal women were studied in an open prospective design. Vaginal spotting/bleeding and endometrial thickness as assessed by transvaginal ultrasonography was compared between six categories of women over a 5-year period: three categories in women on continuous combined estrogen-progestin therapy, one category under tibolone, one category under raloxifene and one under no treatment. More specifically, women received tibolone 2.5 mg (N = 204), raloxifene HCl 60 mg (N = 137), conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg (N = 122), 17beta-estradiol 2mg/norethisterone acetate 1mg (N = 58), 17beta-estradiol 1mg/norethisterone acetate 0.5mg (N = 76) or no therapy (controls, N = 189). Women with suspected endometrial pathology were referred for hysteroscopy. RESULTS: Bleeding/spotting incidence was highest among standard dose EPT users (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg: 40.1%, 17beta-estradiol 2mg/norethisterone acetate 1mg: 44.8%, p < 0.001 compared to controls). Low-dose EPT associated with lower incidence of spotting/bleeding (34.1%). The incidence under tibolone and raloxifene was 22.5% and 2.9%, respectively, while 3.2% of women not receiving therapy reported vaginal spotting/bleeding. Mean endometrial thickness was not significantly affected in any of the groups studied. The drop-out rate due to spotting/bleeding was higher in the two higher dose EPT regimens. After logistic regression analysis, age at baseline was the only significant predictor of subsequent spotting/bleeding (b = -0.25, S.E. = 0.09, p = 0.006), while menopausal age and pre-treatment serum FSH had marginal significance. CONCLUSIONS: EPT, tibolone and raloxifene do not appear to associate with significant changes in endometrial thickness in the majority of cases. The low-dose EPT regimen associated with a decreased incidence of unscheduled spotting/bleeding compared to the standard dose regimens. Tibolone expressed a favorable endometrial profile, as seen in its effect on unscheduled spotting/bleeding and mean endometrial thickness. Raloxifene associated with the lowest incidence in S/B and the lowest drop-out rate.s.

The Effect of the Antioxidant Drug "U-74389G" on Creatinine Levels during Ischemia Reperfusion Injury in Rats.

OBJECTIVE: The aim of this experimental study was to examine the effect of the antioxidant drug "U-74389G" on a rat model using an ischemia reperfusion protocol. The effect of U-74389G was studied biochemically by measuring mean blood creatinine levels. MATERIALS AND METHODS: Forty rats were used in the study. Creatinine levels were measured at 60 min of reperfusion (groups A and C) or at 120 min of reperfusion (groups B and D), where groups A and B were controls and groups C and D received U-74389G administration. RESULTS: U-74389G administration significantly decreased the predicted creatinine levels by 21.02 ± 5.06% (p = 0.0001). Reperfusion time non-significantly increased the predicted creatinine levels by 4.20 ± 6.12% (p = 0.4103). However, U-74389G administration and reperfusion time together produced a significant combined effect in decreasing the predicted creatinine levels by 11.69 ± 3.16% (p = 0.0005). CONCLUSION: Independent of reperfusion time, U-74389G administration significantly decreased the creatinine levels in an ischemic rat model. This study demonstrates that short-term U-74389G administration improves renal function by increasing creatinine excretion.

Effect of gonadal steroid receptors alterations on the pathophysiology of pelvic organ prolapse and urinary incontinence.

BACKGROUND: The aim of this study was to investigate the contribution of the gonadal steroid receptors expression to the pathophysiological pathways of pelvic organ prolapse (POP) and urodynamic stress urinary incontinence (USUI) after menopause. METHODS: This was a prospective closely-matched controlled clinicopathological study. Immunohistochemistry for estrogen receptor isoform α (ER-α) and ß (ER-ß), as well as for progesterone receptor (PR), was performed on formaline-fixed and paraffin-embedded sections of specimens coming from the pubocervical fascia of postmenopausal women who were allocated into three groups: patients with synchronous POP and USUI (Group A), patients diagnosed with only POP (Group B), and patients without POP or USUI who underwent gynecological surgery for another benign indication (control group, Group C). RESULTS: There was no statistically significant difference among the three groups for age, parity, body mass index, or smoking. The expression of ER-α receptors was found significantly reduced among samples of Group B when compared with control group. Statistically significant reduction not only for ER-α, but for ER-ß, as well, was noticed among samples of Group A, compared to the other two groups. No remarkable differences concerning the density of PR receptors were observed among the three groups. CONCLUSIONS: Alterations of ER-α in the pubocervical fascia and around the urethra in postmenopausal women may play an important role in the pathophysiology of POP. In addition, the risk for developing USUI among POP patients seems to be strongly associated with the reduction of both estrogen receptors (ER-α and ER-ß) expression.

Determinants of Secondary Hyperparathyroidism in Bariatric Patients after Roux-en-Y Gastric Bypass or Sleeve Gastrectomy: A Pilot Study.

Objective. Nutritional deficiencies are common after bariatric surgery. We aimed to assess the prevalence and possible predictors of secondary hyperparathyroidism (SHPT) in bariatric patients. Methods. A total of 95 patients who had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were assessed after a median of 3 years after surgery. Anthropometric/demographic and weight-loss parameters were compared according to the presence of SHPT, independently for men/premenopausal women and postmenopausal women. Results. SHPT was highly prevalent (men/premenopausal women, 52.1%; postmenopausal women, 31.9%). Among men/premenopausal women, multivariate analysis indicated that SHPT was predicted by (a) 25-hydroxyvitamin D levels (Exp(B) = 0.869, P-value = 0.037), independently of age, sex, smoking; (b) calcium (Exp(B) = 0.159, P-value = 0.033) and smoking, independently of age and sex; (c) magnesium (Exp(B) = 0.026, P-value = 0.046) and smoking, independently of age and sex. Among postmenopausal women, SHPT was predicted by menopausal age independently of age, smoking, and levels of 25-hydroxyvitamin D or calcium. The development of SHPT was not associated with the type of surgery. Conclusions. RYGB and SG exhibited similar effects regarding the regulation of the hypothalamus-pituitary-parathyroid axis after surgery. Vitamin D status and menopausal age appear to determine SHPT on the long term. SHPT should be sought and vigorously treated with calcium and vitamin D supplementation.

Vertebral fracture prevalence among Greek healthy middle-aged postmenopausal women: association with demographics, anthropometric parameters, and bone mineral density.

BACKGROUND CONTEXT: The prevalence of skeletal fractures shows a marked geographic variability; however, data regarding the Greek population remain limited. PURPOSE: To evaluate the frequency of asymptomatic vertebral fractures (VFs), and potential risk factors, in a large sample of Greek postmenopausal women. STUDY DESIGN: A cross-sectional study at the University Menopause Clinic. PATIENT SAMPLE: Four hundred fifty-four postmenopausal women aged 35 to 80 years, with an average menopausal age of 9.2±7.1 years. OUTCOME MEASURES: They included medical history, anthropometric and biochemical parameters, bone mineral density (BMD) at lumbar spine (LS) and femoral neck (FN), and LS lateral radiographs. METHODS: Lumbar spine lateral radiographs were evaluated according to quantitative procedures, aiming to identify VFs. Anthropometric and biochemical parameters and values of BMD were compared according to the presence of VFs. RESULTS: A total of 37 (8.15%) women had at least one VF. Lumbar spine and FN-osteoporosis was identified in up to 23.1% and 40.9% subjects with prevalent VFs, respectively. The prevalence of VFs was largely associated with age, with women aged 60 years or more presenting an up to fourfold risk compared with younger women. Moreover, the presence of VFs was associated with higher menopausal age, advanced age at menarche, a history of early menopause, and prolonged lactation. Lower LS-BMD and, especially, FN-BMD were negatively associated with VF prevalence (prevalent VF vs. no VF: LS-BMD, 0.89±0.16 g/cm(2) vs. 0.98±0.16 g/cm(2), p=.010; FN-BMD, 0.72±0.10 g/cm(2) vs. 0.81±0.12 g/cm(2), p=.008). CONCLUSIONS: Asymptomatic VFs are common among Greek healthy middle-aged postmenopausal women. More than 50% subjects with prevalent VFs present with normal BMD or osteopenia. Age and bone density classification at the FN presented the strongest association with the prevalence of VFs.

The effect of hormone therapy and raloxifene on serum matrix metalloproteinase-2 and -9 in postmenopausal women.

OBJECTIVE: The aim of the study was to investigate the effect of continuous-combined hormone therapy and raloxifene on the total and active forms of serum matrix metalloproteinase (MMP) -2 and -9. DESIGN: The study was double-blinded, with a placebo run-in period of 28 to 50 days. Twenty-eight women received either 17beta-estradiol 2 mg + norethisterone acetate 1 mg (E2/NETA) or raloxifene HCL 60 mg for a period of 6 months. Total and active forms of MMP-2 and -9 were estimated at baseline and at month 6. RESULTS: Total MMP-2 increased significantly in both E2/NETA and raloxifene groups (raloxifene baseline: 278.1 +/- 18.1 ng/mL; 6 months: 303.1 +/- 29.9 ng/mL, P = 0.008) (E2/NETA baseline: 281.9 +/- 27.5 ng/mL; 6 months: 298.8 +/- 12.7 ng/mL, P = 0.025). Similarly, both treatments increased the active MMP-2 fraction, although only the raloxifene-associated increase acquired significance (raloxifene baseline: 24.9 +/- 8.6 ng/mL; 6 months: 31.6 +/- 15.3 ng/mL, P = 0.045) (E2/NETA baseline: 21.7 +/- 5.7 ng/mL; 6 months: 27.4 +/- 5.8 ng/mL, P = 0.128). Total as well as active fractions of MMP-9 were not significantly affected by either treatment. CONCLUSIONS: Both E2/NETA and raloxifene increased the total and active MMP-2 serum levels. MMP-9 was not significantly affected by either regimen. Larger, long-term clinical trials are needed to elucidate the effect of HT and raloxifene on MMPs and the possible clinical implications for cardiovascular health.

Effect of hormone therapy and raloxifene on serum VE-cadherin in postmenopausal women.

OBJECTIVE: To investigate the effect of continuous combined hormone therapy and raloxifene on serum VE-cadherin. DESIGN: The study was double blinded, with a placebo run-in period of 28-50 days. SETTING: University menopause clinic. PATIENT(S): Twenty-eight healthy postmenopausal women devoid of climacteric complaints. INTERVENTION(S): Subjects were randomized to 17beta-estradiol (2 mg) + norethisterone acetate (1 mg; E(2)-NETA) or raloxifene hCL (60 mg) for a period of 6 months. MAIN OUTCOME MEASURE(S): Serum VE-cadherin, which was estimated at baseline and at month 6. RESULT(S): Serum VE-cadherin decreased significantly in both E(2)-NETA and raloxifene groups (raloxifene baseline +/- SD: 1.17 +/- 0.44 ng/mL, 6 months: 0.82 +/- 0.29 ng/mL; E(2)-NETA baseline: 1.19 +/- 0.47 ng/mL, 6 months: 0.92 +/- 0.49 ng/mL). Percentage changes from baseline were -21.7 +/- 24.3 for E(2)-NETA and -26.0 +/- 20.6 for raloxifene. CONCLUSION(S): The effect of E(2)-NETA and raloxifene suggests that these drugs may preserve interendothelial junction integrity and control vascular permeability. Although this effect may influence the progress of the atheromatous lesion, its clinical impact on coronary artery disease (CAD) remains uncertain.

Effect of hormone replacement therapy and tibolone on serum leptin levels in postmenopausal women.

OBJECTIVE: To evaluate the effect of estrogen replacement therapy (ERT), continuous combined hormone replacement therapy (HRT) and tibolone on serum leptin levels in healthy postmenopausal women. METHODS: Eighty-four healthy postmenopausal women aged 43-63 years were studied prospectively. Hysterectomized women (n = 16) received conjugated equine estrogens (CEE) 0.625 mg. Women with an intact uterus were randomly allocated either to CEE+medroxyprogesterone acetate (CEE/MPA) 5 mg or tibolone 2.5 mg. Serum leptin levels were assessed at baseline and after 6 months of treatment. RESULTS: The three groups did not differ with respect to age, body mass index (BMI) or baseline serum leptin levels. Overweight women (BMI > 25 kg/m2) had higher baseline leptin levels (27.0 +/- 11.4 ng/ml) compared to their lean counterparts (BMI < or = 25 kg/m2; leptin: 16.5 +/- 8.1 ng/ml, P = 0.0001). Neither CEE nor CEE/MPA had any effect on serum leptin levels at the end of 6 months either in overweight or in lean women (overweight: CEE baseline 34.4 +/- 13.3 ng/ml, 6 months 36.9 +/- 15.8, P = 0.89, CEE/MPA baseline 22.4 +/- 9.8 ng/ml, 6 months 26.8 +/- 8.7 ng/ml, P = 0.1; lean: CEE baseline 12.6 +/- 4.4 ng/ml, 6 months 13.2 +/- 5.8 ng/ml, P = 0.36, CEE/MPA baseline 17.2 +/- 10.6 ng/ml, 6 months 18.8 +/- 8.8 ng/ml, P = 0.31). Similarly serum leptin remained unchanged at the end of the study in both lean and overweight women on tibolone (overweight: baseline 22.9 +/- 8.1 ng/ml, 6 months 18.5 +/- 12 ng/ml, P = 0.37; lean: baseline 13.2 +/- 5.6 ng/ml, 6 months 17.3 +/- 8.4 ng/ml). CONCLUSION: BMI is a strong determinant of serum leptin levels in healthy postmenopausal women. Neither ERT/HRT nor tibolone exert any effect on serum leptin after 6 months in lean or overweight postmenopausal women. Further studies are required to verify the exact role of estrogen and tibolone on leptin production and function in postmenopausal women.

Effect of hormone replacement therapy and tibolone on serum total homocysteine levels in postmenopausal women.

OBJECTIVE: To assess the effect of continuous combined hormone replacement therapy (HRT) or tibolone on serum total homocysteine (tHcy) levels in postmenopausal women. STUDY DESIGN: Ninety-five postmenopausal women aged 41-68 years were included in the study. Seventy-three women with climacteric complaints, osteopenia or osteoporosis received either conjugated equine estrogens 0.625 mg combined with medroxyprogesterone acetate 5 mg (CEE/MPA, n=31) or tibolone 2.5 mg (n=42). Twenty-two healthy women, matched for chronological and menopausal age, served as controls. Serum tHcy levels were assessed at baseline, 6, 12 and 18 months. RESULTS: No difference was recorded between groups regarding demographic characteristics or mean baseline serum tHcy. Serum tHcy levels decreased significantly in the CEE/MPA compared to baseline (change at 18 months: -3.9%, P<0.05). The magnitude of the decrease was higher in the subgroup of women with baseline tHcy levels above the median (change at 18 months: -15.0%, P<0.01). No change in tHcy levels was detected in the tibolone group throughout the study period, either in the whole group (change at 18 months: 1.9%, NS) or in the subgroup with baseline tHcy levels above the median (change at 18 months: -3.23%, NS). CONCLUSION: Continuous CEE/MPA reduces tHcy especially in women with high pretreatment tHcy levels. Tibolone has no effect on serum tHcy levels at least during the first 18 months of therapy. Larger studies with longer follow-up are required to confirm these results.