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Despite the fact that irritability is frequently the main presenting complaint of perimenopausal and postmenopausal women, studies specifically researching irritability in this population are scant. One hundred sixty three (163) peri- and postmenopausal women non-HT users, attending a menopause clinic, were included in this cross-sectional study. The investigation focused on whether the occurrence of inward and outward irritability in menopause is associated with various menopausal parameters, such as vasomotor symptoms, insomnia, menopausal status, hormone levels, and with the presence of chronic disease. Furthermore, we examined the possible association of inward and outward irritability with measures of anxiety and depression. Outward and inward irritability of peri- and postmenopausal women seem to be related to chronic disease, a factor that may be partially influenced by the older age of menopausal women. Outwardly directed irritability is found to be related to FSH and LH levels, independently of specific menopausal symptoms, such as vasomotor symptoms or insomnia. Outward irritability was found to be positively correlated with depressive symptomatology, whereas inward irritability correlated with both anxiety and higher depressive symptomatology.

The purpose of our study was to investigate the possible effect of BsmI vitamin D receptor (VDR's) polymorphism on changes in bone mineral density (BMD) and bone turnover markers in postmenopausal women receiving different treatments. This pilot study included 42 postmenopausal women with elevated fracture risk, randomized into 1-year treatment with weekly oral alendronate or daily subcutaneous teriparatide. Both groups received daily supplements of 1000 mg calcium and 800 IU vitamin D. Blood samples were obtained for biochemical evaluation and genotyping. BMD at the lumbar spine and femoral neck were assessed with dual energy X-ray absorptiometry. Baseline, follow-up BMD and markers of bone turnover were assessed according to the BsmI genotype. BMD at the lumbar spine increased in patients carrying at least one b allele, while it decreased in patients with the BB genotype (P = 0.041). Whereas no gene-treatment interaction was observed in teriparatide-receiving patients, women with the BB genotype receiving alendronate resulted in negative BMD (-0.056 ± 0.032 g/m(2) ) and T-score (-0.295 ± 0.190) gradient, compared to carriers of the b allele (BMD: +0.020 ± 0.017 g/m(2) , P = 0.054; T-score: +0.217 ± 0.100, P = 0.030). No effect of genotype was apparent with respect to gradients of biochemical bone markers. These preliminary results indicate that alendronate has a differential effect on BMD, depending on the VDR genotype. Carriers of the b allele may be more responsive to treatment compared to patients with the BB genotype. The interaction of VDR's BsmI polymorphism with the efficacy of the anti-osteoporotic treatment needs further investigation by larger prospective studies. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

One hundred healthy postmenopausal women were randomly assigned to receive 17β-E2 1 mg/drospirenone 2 mg or 17β-E2 1 mg/norethisterone acetate 0.5 mg for 6 months, and circulating soluble Fas, soluble Fas ligand, and cytochrome c were measured at baseline and at 6 months in 87 women who completed the study. Although cytochrome c levels were undetectable, circulating soluble Fas/soluble Fas ligand ratio decreased in both groups, suggesting a decrease in ligand-mediated apoptosis. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc.

Background/Aim: The role of neutrophils and platelets in atherothrombotic disease is well established. The aim of our study was to investigate the effect of HT and tibolone on the soluble markers of neutrophil and platelet activation, “a disentigrin and metalloproteinase domain” (ADAM-8) and CD40 ligand (CD40L) respectively, in healthy post-menopausal women. Subjects and methods: One hundred and six healthy post-menopausal women were randomly allocated to: estradiol plus drospirenone (E-2/DSP), E-2 hemihydrate 1 mg plus norethisterone acetate (E-2/NETA) 0.5 mg, and tibolone 2.5 mg. Serum ADAM-8 and CD40L were measured at baseline and at 6 months. Results: Baseline values of ADAM-8 and CD40L were similar between groups. No significant correlation was revealed between ADAM-8 or CD40L and parameters related to cardiovascular risk factors in each group. No significant changes were observed between baseline values and values at 6 months (E-2/DSP group: ADAM-8: 267.4 +/- 71.3 pg/ml vs 270.7 +/- 42.8 pg/ml, p=0.86, CD40L: 6.43 +/- 3.13 vs 6.79 +/- 2.70 ng/ml, p=0.67), (E-2/NETA group: ADAM-8: 308.3 +/- 64.3 vs 294.7 +/- 57.7 pg/ml, p=0.40, CD40L: 9.68 +/- 2.81 vs 8.59 +/- 5.13 ng/ml, p=0.51), (tibolone group: ADAM-8: 307.5 +/- 87.5 vs 289 +/- 48.1 pg/ml, p=0.48, CD40L: 9.46 +/- 4.30 vs 9.26 +/- 4.60 ng/ml, p=0.99). Conclusions: Our study has not revealed an association between estrogen plus progestin treatment or tibolone on serum ADAM-8 and CD40L levels in healthy post-menopausal women. Larger prospective studies are needed to further investigate the effect of low-dose HT or tibolone on serum markers of neutrophil and platelet activation. (J. Endocrinol. Invest. 33: 720-724, 2010) (C) 2010, Editrice Kurtis

Objective Autoimmune thyroiditis and overt or subclinical hypothyroidism have been associated with increased prevalence of cardiovascular disease (CVD). Design Cross-sectional investigation of the association between gene polymorphisms related to CVD with thyroid function and autoimmunity. Patients In total 84 healthy postmenopausal women aged 49-69 years. Measurements FT3, FT4, anti-TPO and anti-TG were assessed in the sera of participants. The following polymorphisms were assessed from peripheral lymphocyte DNA: Apolipoprotein E E2/E3/E4, paraoxonase 1 A/B, Glycoprotein IIIa leu33pro, MTHFR ala222val, ApoBarg3500gln, plasminogen activator inhibitor 1 4G/5G, cholesterol 7-α hydroxylase A204C and cholesterol ester transfer protein B1/B2. Results A statistically significant correlation was found between Apolipoprotein E and paraoxonase1 polymorphisms and serum thyroid hormones: carriers of the E2 or E4 allele of the ApoE gene had lower levels of FT4 (P = 0·0005) than women with the E3/E3 genotype. Carriers of the B allele of paraoxonase 1 gene had lower levels of FT3 compared to women with the wild-type genotype (P = 0·047). A statistically significant positive association (P = 0·049) was also observed between anti-TG antibodies and the presence of the E2 allele of the Apolipoprotein E gene. Conclusions Polymorphisms of apolipoprotein E and paraoxonase 1 are associated with different levels of thyroid hormone and anti-Tg antibody levels in the study population in this pilot study. The mechanism underlying this association remains to be elucidated. © 2009 Blackwell Publishing Ltd.

Objectives To evaluate the effect on breast density of two low-dose hormone therapy regimens identical in their estrogen component but different in the progestin. Methods A total of 81 non-hysterectomized postmenopausal women were allocated either to 17β-estradiol 1 mg and norethisterone acetate 0.5 mg E2NETA, n 43 or to 17β-estradiol 1 mg and drospirenone 2 mg E2DRSP, n 38. Treatment was continuous and lasted 12 months. The main outcomes were the changes in breast density according to the Wolfe classification between baseline and 12-month mammograms. Results Involution of the fibroglandular tissue was not seen in either of the treatment groups. Under E2NETA, breast density increased in seven women 16.3. In contrast, only three women 7.9 exhibited a density increase under E2DRSP. Conclusions Although hormone therapy appears to suspend breast involution, it does not increase breast density in the majority of treated women. Progestins differing in pharmacological properties may have a variable impact on breast density. © 2009 International Menopause Society.

Endometriosis is a common gynecological disorder of the reproductive age characterised by pelvic pain, dysmenorrhea and infertility. Classic theories have failed to propose a precise pathogenetic mechanism. Recent studies have investigated the role of the immune system and oxidative stress in the development of endometriosis as well as the identification of biomarkers for a non-invasive diagnosis of the disease. At endometriotic sites, inflammatory cells including eosinophils, neutrophils and macrophages generate reactive oxygen species that contribute to the development of oxidative stress in the peritoneal cavity. Oxidative stress further augments immune response in affected sites. The oxidants exacerbate the development of endometriosis by inducing chemoattractants and endometrial cell growth-promoting activity. The oxidative proinflammatory state of the peritoneal fluid is an important mediator of endometriosis. Many studies investigate the correlation of endometriosis and oxidative stress but the results are discrepant. Furthermore, oxidative stress has been implicated in unexplained infertility and has been associated with some of its causative factors. Oxidative stress influences womens reproductive capacity. The association between endometriosis and infertility is described in several studies and still remains debated.

Objective: To assess the association of genetic polymorphisms related to cardiovascular disease (CVD) risk with anthropometric parameters and indices of androgenicity in healthy postmenopausal women. Design: Cross-sectional study in a University Menopause Clinic. Methods: The following polymorphisms were assessed in 84 healthy postmenopausal women: glycoprotein IIIa Leu33Pro, apolipoprotein E2/E3/ E4, methylenetetrahydrofolate reductase (MTHFR) Ala222Val, apolipoprotein B Arg3500Gln, paraoxonase 1 Gln192Arg, plasminogen activator inhibitor 1 4G/5G, cholesterol-7 α-hydroxylase A-204C, and cholesterol ester transfer protein (TaqIB) B1/B2. Hormonal assays included FSH, LH, 17-β-estradiol, testosterone, sex hormone-binding globulin (SHBG), DHEA sulfate, Δ-4-androstenedione (Δ4A), free androgen index (FAI), free estrogen index (FEI), and homocysteine (Hcy). The anthropometric components were body mass index (BMI) and waist-to-hip ratio (WHR). Results: MTHFR Ala222Val polymorphism was positively associated with testosterone, FAI, and FEI (P=0.001, P=0.0004, and P=0.014 respectively) and negatively with SHBG (P=0.047). Furthermore, women bearing this polymorphism had higher BMI and WHR compared with women with the wild-type variant (P=0.027 and P=0.044 respectively). Conclusions: MTHFR Ala222Val polymorphism is associated with increased androgenicity and elevated BMI and WHR in healthy postmenopausal women. The significance of this association with respect to the CVD risk of postmenopausal women remains to be elucidated in future studies. © 2008 European Society of Endocrinology.

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity and is usually confined to the pelvis. Thoracic endometriosis syndrome (TES) is a rare disorder characterized by the presence of functioning endometrial tissue in the pleura, the lung parenchyma and the airways. TES may present with hemoptysis, due to the shedding of endometrial tissue in the bronchial tree, or spontaneous pneumothorax or hemothorax if the endometrial tissue is localized peripherally. Patients are of reproductive age, often nulliparous, with long-standing symptoms. The crucial issue for establishing the diagnosis is the cyclicity of the symptoms which occur along with the menstrual cycle. TES is virtually a diagnosis of exclusion, established on clinical grounds, since neither CT nor endoscopy are specific for TES. Treatment consists of gonadotropin-releasing hormone analogues, aiming to suppress the hypophyseal-gonadal axis, so as to ensure a regression of the endometrial implants. If medical treatment fails, surgical resection of the endometriomas is suggested, although relapse rate may be high. Copyright © 2007 S. Karger AG.

This study assesses the possible associations between postmenopausal therapy (hormone therapy, raloxifene, and tibolone) and E-cadherin expression in normal cervical Papanicolaou smears (squamous, glandular, and metaplastic cells). E-cadherin immunostaining was less intense in metaplastic cells of women on tibolone, whereas hormone therapy and raloxifene were not associated with altered E-cadherin expression. © 2008 American Society for Reproductive Medicine.

Apoptosis in atherosclerotic lesions is triggered by inflammatory processes, both via cell-cell contact and by cytokines and oxidized lipids. The role of apoptosis in atherogenesis is dual, depending on the stage of the plaque: In early stages, apoptotic death of smooth muscle - and inflammatory cells, such as lymphocytes and macrophages, may delay atherosclerotic process. However, once the plaque is formed, apoptosis may lead to plaque rupture and thrombosis. © 2008 Bentham Science Publishers Ltd.

Objectives Hormone therapy increases the risk of venous thromboembolism, possibly through a negative effect on coagulation inhibitors. The aim of the study was to assess the effect of conjugated equine estrogens alone or in combination with medroxyprogesterone acetate, low-dose 17/3-estradiol combined with norethisterone acetate and tibolone on inhibitors of coagulation. Methods Two hundred and sixteen postmenopausal women received orally either conjugated equine estrogens 0.625 mg (CEE, n = 24) or tibolone 2.5 mg (n = 24) or CEE + medroxyprogesterone acetate 5 mg (CEE/MPA, n = 34) or 17 beta-estradiol I mg + norethisterone acetate 0.5 mg (E2/NETA, n = 66) or no therapy (control, n=68) for 12 months. Plasma antithrombin, protein C and total protein S were measured at baseline and at 12 months. Results CEE, CEE/MPA and E2/NETA treatment were associated with a significant decrease in antithrombin levels (CEE: baseline 235.6 47.6 mg/1, follow-up 221.3 +/- 48.3mg/l, p=0.0001; CEE/MPA: baseline 251.1 +/- 38.6mg/l, followup 225.0 +/- 42.6mg/l, p=0.009; E2/NETA: baseline 257.1 +/- 59.4mg/l, followup 227.1 +/- 50.4mg/l, p=0.007; tibolone: baseline 252.6 +/- 62.4mg/l, follow-up 261.9 +/- 59.1 mg/l, p = 0.39). Protein C decreased significantly in the CEE ‘and CEE/ MPA groups (CEE: baseline 3.64 +/- 1.17 mg/l, follow-up 2.48 +/- 1.47 mg/l, p = 0.004; CEE/MPA: baseline 3.24 +/- 1.23mg/l, follow-up 2.61 +/- 1.38mg/l, p=0.001; E2/NETA: baseline 3.24 +/- 1.10 mg/l, follow-up, 3.15 +/- 1.11 mg/l, p 0.08; tibolone: baseline 3.26 +/- 1.25 mg/l, follow-up 3.09 +/- 1.32 mg/l, p = 0.37). Protein S decreased significantly only in the CEE/MPA group (CEE: baseline 19.4 +/- 2.76 mg/l, followup 18.0 +/- 2.45 mg/l, p = 0.56; CEE/MPA: baseline 18.4 +/- 3.42 mg/l, follow-up 14.5 +/- 3.43 mg/l, p = 0.005; E2/NETA: baseline 19.0 +/- 3.11 mg/l, follow-up 19.5 +/- 3.43 mg/l, p = 0.18; tibolone: baseline 18.5 +/- 3.09 mg/l, follow-up 18.0 +/- 4.09 mg/l, p = 0.32). Conclusions Estrogen and estrogen-progestin therapy are associated with a reductionin coagulation inhibitors, the extent of which depends on the regimen administered.Tibolone appears to have no effect on inhibitors of coagulation.

Objectives: The aim was to investigate patient compliance with different osteoporosis medications commonly prescribed in clinical practice, to determine risk factors associated with discontinuation and to evaluate quality of changes. Research design and methods: We conducted a 1-year observational study of patients of age >= 60 years in a clinical setting at 917 sites in 10 European countries (Germany, Greece, UK, Netherlands, Romania, Norway, Finland, Estonia), Lebanon and South Africa. data, concomitant diseases, the reasons for intervention, educational, socio-economical and disease knowledge were captured at Self-reported compliance, discontinuation data health status were collected. Main outcome measures: Out of 5198 patients, 3490 (67.1%) patients received 60 daily raloxifene (RAL), 452 (8.7%) 10 mg daily alendronate (AQD), 769 (14.8%) 70 mg once weekly alendronate (AQW) and 487 (9.4%) 5 mg daily risedronate (RIS). Among patients completing the study (4231, 81%), the percentage of patients with high compliance was 80% (RAL), 79% (AOD), 65% (AQM and 76% (RIS). The discontinuation due to side effects was highest on AQW (7.0%), followed by AQD (6.4%), RAL (3.8%) and RIS (3.4%). The discontinuation-rate was higher for patients with a history of surgical menopause, increased age, lack of knowledge about medical prevention of osteoporosis and thin frame as a reason for intervention. The EQ-5D weighted index showed the highest improvement for RIS (0.13), followed by RAL (0.11), ADD (0.08) and AQW (0,07). Conclusions: Data from this non-interventional observational study indicate moderate overall compliance and discontinuation rate with the prescribed osteoporosis medications.

The aim of this study was to assess the association of endogenous sex steroids with bone mineral density (BMD) in healthy postmenopausal women not on hormone therapy. A total of 884 postmenopausal women aged 42-71 years were studied in a cross-sectional design. Parameters assessed were follicle-stimulating hormone, luteinizing hormone, estradiol, total testosterone, sex hormone-binding globulin, free estrogen index (FEI), free androgen index (FAI), Δ4-androstendione (Δ4A), dehydroepiandrosterone sulfate (DHEAS), bone alkaline posphatase, and bone mineral density at the lumbar spine (L-BMD) and femoral neck (N-BMD). Estradiol and FEI associated positively with both L-BMD and N-BMD (r = 0.21-0.47, P < 0.01). These associations remained significant after adjustment for age, years since menopause, and body mass index. FAI correlated positively with both L-BMD and N-BMD (r = 0.18 and 0.33, respectively; P < 0.01). At the multivariate analysis, however, FAI remained the significant determinant only for N-BMD. Δ4A associated positively with N-BMD (r = 0.27, P = 0.001), whereas DHEAS showed no association with BMD at either site. Thus, endogenous steroids are significant determinants of postmenopausal BMD. Endogenous estradiol may be more important for lumbar spine BMD, whereas endogenous androgens are associated mainly with femoral neck BMD. © Springer-Verlag Tokyo 2006.

Objectives: To evaluate and compare the effect of different than classical hormone therapy medications, such as raloxifene and tibolone, on the uterine arteries and endometrium of postmenopausal women using transvaginal ultrasonography. Methods: The prospective study included 62 healthy, postmenopausal women recruited from the Menopausal Clinic of the 2nd Department of Obstetrics and Gynecology of the University of Athens. Subjects were randomly allocated to receive raloxifene HCl in a daily dose of 60 mg orally (Group A-31 women) or tibolone in a daily dose of 2.5 mg orally (Group B-31 women). The study period was 6 months and all subjects were assessed using transvaginal ultrasonography before treatment initiation as well as after 3 and 6 months for evaluation of the endometrial thickness and the pulsatility (PI) and resistance (RI) indices at the level of the uterine arteries. Results: No significant differences in RI, PI and endometrial thickness were observed in the raloxifene group during the 6-month treatment. In the tibolone group, PI and RI values decreased linearly from baseline to the end of the study, whereas the endometrial thickness was significantly increased during the first 3 months remaining unaltered thereafter. Comparisons between the two study groups revealed significant percent change of values in the pre-treatment to month-3 period and no difference with regard to pre-treatment, month-3 and month-6 absolute values. Conclusion: Raloxifene and tibolone exert dissimilar effects on uterine blood supply parameters and endometrial thickness. © 2005 Elsevier Ireland Ltd. All rights reserved.

The evaluation of fetal well-being by Doppler velocimetry in cases of intrauterine growth restriction (IUGR) is of great importance as it is very useful in detecting those IUGR fetuses that are at high risk because of hypoxemia. Several Doppler studies initially on fetal arteries and recently on the fetal venous system provide valuable information for the clinicians concerning the optimal time to deliver. Doppler sonography in combination with the other biophysical methods such as cardiotocogram and biophysical profile score should be used in everyday practice for the monitoring and appropriate management of the growth-restricted fetuses. The purpose of this review is to describe the current approaches in Doppler assessment of IUGR fetal circulation. © 2006 New York Academy of Sciences.

Bisphosphonates belong to a class of compounds similar to pyrophosphate. In these compounds the oxygen atom of the pyrophosphate is replaced by a carbon atom resulting in a P-C-P bond. They exert a potent inhibitory effect on osteoclasts and are therefore potent antiresorptive agents. They reduce bone turnover, increase bone mineral density, and decrease fracture risk both at the lumbar spine and the hip. Bisphosphonates have a high affinity for bone surfaces, where they accumulate, mainly at sites of bone remodeling. Due to their selectivity in action, they are usually not associated with systemic side effects. Their main unwanted effect is upper gastrointestinal irritation. Alendronate and risedronate are the two most widely used compounds in the treatment of postmenopausal osteoporosis. They are administered orally either daily or once weekly. Ibandronate is a highly potent newer third-generation bisphosphonate administered once monthly with similar efficacy with respect to bone mineral density and fracture risk. Zoledronate, another potent third-generation bisphosphonate, currently approved for the treatment of malignancy-associated hypercalcemia, is currently undergoing phase III trials for the treatment of postmenopausal osteoporosis as an intravenous (i.v.) infusion once annually. © 2006 New York Academy of Sciences.

Objective: To assess the association between endogenous sex hormones and risk factors for atherosclerosis in healthy postmenopausal women. Design: Cross-sectional study in a university menopause clinic. Methods: Serum sex hormones and lipid-lipoprotein profile, arterial pressure, homocysteine and insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA-111), were assessed in 598 healthy postmenopausal women not on hormone therapy. Results: Compared with women in the lowest testosterone quartile (Q), women in the highest testosterone quartile had higher total cholesterol (Q1: 225.2±41.3 vs Q4: 246.2±38.4 mg/dl, P

Menopause-related oestrogen deficiency increases the risk of cardiovascular disease (CVD). The presence of abdominal obesity, dyslipidemia, hypertension, fasting hyperglycaemia or impaired glucose tolerance further aggravates the CVD risk imposed by menopause. A detailed personal history should be recorded, covering PCOS, gestational diabetes mellitus, alcohol intake and smoking, as well as a family history of cardiovascular disease. Screening of the a-symptomatic post-menopausal woman should include fasting lipid profile, plasma glucose and liver, renal and thyroid function tests. Serum low-density lipoprotein cholesterol (LDL-c) > 130 mg/dL is associated with an increased risk of CVD. Levels of triglycerides (TG) ≥ 150 mg/dL and high-density lipoprotein cholesterol (HDL-c) ≤ 50 mg/dL coupled with an increase in small dense LDL and very low-density lipoprotein (VLDL) particles constitute the atherogenic dyslipidemia, which characterizes the metabolic syndrome. In women with previous VTE episodes, screening for thrombophilia is advisable, as well as an estimation of baseline homocysteine and C-reactive protein (CRP). Non-pharmacological intervention should be targeted towards smoking cessation, a low-salt, low-fat, high-fibre diet and increased physical activity. © 2005 Elsevier Ireland Ltd. All rights reserved.

Objective: To assess endogenous androgen and insulin resistance status in postmenopausal women receiving continuous combined hormone therapy (HT), tibolone, raloxifene or no therapy. Methods: A total of 427 postmenopausal women aged 42-71 years were studied in a cross-sectional design. Among them 84 were taking HT (46 women conjugated equine estrogens 0.625 mg; medroxyprogesterone acetate, 5 mg, CEE/MPA; and 38 women 17 beta-estradiol 2 mg: norethisterone acetate 1 mg, E2/NETA); 83 were taking tibolone 2.5 mg; 50 were taking raloxifene HCl 60 mg: and 210 women were not receiving any therapy. Main outcome measures were FSH, LH estradiol, total testosterone, SHBG, free androgen index (FAI), Delta(4)-Androstendione (Delta(4)-A), Dehydroepiandrosterone sulphate (DHEAS) and HOMA insulin resistance index (HOMA-IR). Results: In women not on hormone therapy smoking and older age was associated with lower DHEAS levels. FAI values increased linearly with increasing BMI. Age and BMI were positive determinants of HOMA-IR, while no association was identified between endogenous sex steroids and insulin resistance. CEE/MPA therapy was associated with higher SHBG, lower FAI and lower HOMA-IR values compared to women not on therapy (age and BMI-adjusted SHBG: CEE/MPA 148.8 nmol/l, controls 58.7 nmol/l, p < 0.01 age-adjusted FAI: CEE/MPA 0.8, controls 3.2,p < 0.05; age-adjusted HOMA-IR: CEE/MPA 1.3, controls 2.6, p < 0.05). On the contrary, E2/NETA treatment had no effect on these parameters. Women on tibolone had lower SHBG. higher FAI and similar HOMA-IR values compared to controls (age and BMI-adjusted SHBG: 24.1 nmol/l, p < 0.01; FAI: 6.0. p < 0.05: HOMA-IR: 2.3, p = NS). Raloxifene users did not exhibit any difference with respect to sex steroids and HOMA-IR levels. Conclusions: CEE/MPA users had lower free testosterone and improved insulin sensitivity. Tibolone on the other hand associated with higher free testosterone, while raloxifene did not relate to any of these parameters. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

During menopause women tend to gain body fat. The increase in adiposity seems to be a consequence of the decline in endogenous estrogens and the reduced energy expenditure. The role of post-menopausal hormone replacement therapy (pHT) in modulating visceral obesity is controversial. Some studies have shown that pHT has no effect on body weight while in other studies pHT increased body weight. Leptin is an adipocyte-derived hormone and its levels reflect the amount of adipose tissue. Obesity is associated with elevated serum leptin levels. The effect of pHT on leptin levels is also controversial. In some studies pHT increased leptin levels while other studies have not confirmed this increasing effect. The major problem encountered during administration of hormone therapy seems to be the timing of pHT initiation which is a strong confounder on the effect of pHT on leptin levels in postmenopausal women.

The aim of the study was to assess the effect of continuous hormone therapy (HT) for 1 yr on pulse wave analysis and central aortic pressure in healthy postmenopausal women. Sixty-five healthy postmenopausal women were randomly allocated to receive either conjugated equine estrogens 0.625 ring plus medroxyprogesterone acetate 5 mg (CEE/MPA, Premelle 5, Wyeth - Ayerst Lab, Philadelphia, PA, no.=32) or no therapy (no.=33). Treatment was continuous, and the study period lasted 12 months. Central aortic pressure, augmentation and augmentation index (AI) were determined non-invasively using applanation tonometry. All measurements were performed at baseline and at the end of the study by the same person. Ns differences were found between baseline values and values at the end of the study in either the control or the CEE/MPA group in central systolic aortic pressure (107.0 +/- 13.1 vs 107.6 +/- 11.3 mmHg, p=0.80, and 110.8 +/- 10.8 vs 112.3 +/- 11.4 mmHg, p=0.23, respectively), augmentation (112.6 +/- 4.2 vs 11.9 +/- 4.8 mmHg, p=0.45 and 11.7 +/- 3.7 vs 12.6 +/- 4.2 mmHg, p=0.34, respectively), and percentage of AI (36.8 +/- 9.3 vs 36.3 +/- 10.3, p=0.81 and 34.1 +/- 8.9 vs 34.9 +/- 9.8, p=0.72, respectively). The results of this preliminary report suggest that HT for 1 yr does not have any significant effect on central aortic pressure and wave reflection in healthy postmenopausal women. (c) 2005, Editrice Kurtis.

Objective: To evaluate the effect of continuous combined hormone therapy (HT), tibolone and raloxifene on circulating vascular endothelial growth factor (VEGF) in postmenopausal women. Design: One-year prospective intervention study. Methods: One hundred and forty-six postmenopausal women with a mean age of 51.8+/-1-4.1. (S.D.) years received 0.62 5 mg conjugated equine estrogen (CEE) plus 5 mg medroxyprogesterone acetate (MPA) (CEE/MPA, n = 34), 2.5 mg tibolone (n = 3 7), 60 mg raloxifene (n = 40) or no active treatment (control group. n = 35). Plasma VEGF was estimated at baseline and at 6 and 12 months. Results: In both the CEE/MPA-treated and the tibolone-treated groups plasma VEGF increased significantly at month 6 and remained elevated at month 12 (CEE/MPA baseline: 268.1 +/- 187.8 pg/ml, month 6: 320.0 +/- 175.3 pg/ml, month 12: 321.1 +/- 181.8 pg/ml, P = 0.01: tibolone baseline: 240.6 +/- 165.8 pg/ml, month 6: 271.4 +/- 172.7 pg/ml, month 12: 274.8 +/- 183.1 pg/ml, P = 0.03). These changes were significantly different from the respective changes in the control group after adjusting for T-score in bone densitometry (CEE/MPA: P = 0.02, tibolone: P = 0.04). The effect of HT or tibolone on plasma VEGF was mainly evident in women with low baseline VEGF levels (< 243.2 pg/ml, median for whole sample). On the contrary, VEGF levels in the raloxifene-treated or the control group did not change throughout the study. Conclusion: Both continuous combined HT and tibolone increased circulating VEGF in postmenopausal women. while raloxifene had no effect. Further research is needed to clarify the clinical relevance of these findings with respect to cardiovascular risk 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. (C) 2004 by American Society for Reproductive Medicine.

The aim of this study was to assess lipid and apolipoprotein levels in postmenopausal women taking various regimens of replacement therapy or no therapy. Seven hundred forty-eight postmenopausal women followed in the Menopause Clinic of the, 2(nd) Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, were studied in a cross-sectional design. Women were either non-users of replacement therapy (no.=511) or users of one of the following regimens: conjugated equine estrogen 0.625 mg (CEE, no.=34), CEE 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA, no.=60), 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E-2/NETA, no.=44), tibolone 2.5 mg (no.=84), raloxifene HCl 60 mg (no.=51). Total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein A(1) (ApoA(1)) and apolipoprotein B (ApoB) levels were assessed. Women were grouped according to replacement regimen and mean levels of lipid and apolipoproteins were compared between groups. Women in the raloxifene group were older and longer menopaused. After adjustment for age and duration of menopause; TG levels were significantly lower in the tibolone and E-2/NETA groups (75 and 89.9 mg/dl, respectively) compared to non-users. TC was lower in all therapy groups, but the difference acquired significance only in the E-2/NETA (207.8 mg/dl), compared to non-users (231.5 mg/dl). LDLC levels were significantly lower in the CEE (133.8 mg/dl), CEE/MPA (130.4 mg/dl) and raloxifene group (129.9 mg/dl) compared to non-users (151.9 mg/dl). There was no difference in HDL-C levels between users and non-users (58.9 mg/dl) except for the tibolone group where HDL-C was significantly lower (48.6 mg/dl). ApoA(1) levels were significantly higher in the CEE/MPA group (194.4 mg/dl) and significantly lower in the tibolone group (141.6 mg/dl) compared to non-users (170.4 mg/dl). No difference was detected between groups concerning ApoB levels. In conclusion, tibolone therapy is associated with lower TG levels as well as lower HDL and ApoA(1) levels. ERT, continuous combined estrogen-progestin therapy (HRT) and raloxifene are associated with lower LDL-C levels. Among continuous combined HRT users, CEE/MPA is associated with higher ApoA(1) levels, while E-2/NETA with lower TG levels. Large prospective randomized studies are required to validate these results.

The aim of this study was to evaluate factors that influence leptin levels in postmenopausal women. One hundred and forty-four postmenopausal women were evaluated cross-sectionally. In every woman a complete medical history was obtained, body mass index (BMI) was recorded and morning fasting blood was obtained for the determination of serum leptin, follicle stimulating hormone (FSH), estradiol, testosterone, Delta(4)androstendione, dehydroepiandrosterone sulphate (DHEAS) and insulin. In univariate analysis, age, BMI and insulin were positively correlated with serum leptin, while DHEAS showed a negative association with leptin concentrations (age r=0.21, p=0.005, BMI r=0.41, p=0.0001, insulin r=0.20, p=0.008, DHEAS r=-0.28, p=0.0001). In stepwise multivariate regression analysis serum leptin could be best predicted from BMI, serum insulin and serum DHEAS [leptin= (1.41 * BMI) (0.01 * DHEAS) + (3.26 * insulin) -26.3; model r(2)=0.24, p=0.001]. In conclusion, BMI and serum insulin have a positive while serum DHEAS has a negative impact on serum leptin. Neither endogenous estradiol, nor endogenous testosterone are associated with leptin levels. Further studies are needed to elucidate the role of leptin in determining body weight and composition in postmenopausal women. (C) 2003, Editrice Kurtis.

This randomized double-blind study was conducted to investigate the effects of 17beta-estradiol plus norethisterone acetate, and raloxifene, on nitric oxide (NO), prostacyclin (PGI(2)) and endothelin-1 (ET-1) serum levels in postmenopausal women. Treatment was initiated after a 28-50 day placebo period. Fourteen women were treated daily with 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E-2 + NETA), and 14 with raloxifene HCl 60 mg for a period of 6 months. Serum NO, PGI(2) and ET-1 levels were estimated at baseline, after placebo, and at months 3 and 6. E-2 + NETA decreased NO levels significantly, while raloxifene did not cause any appreciable change. Both regimens decreased PGI(2) levels and ET-1 levels significantly. Finally, E-2 + NETA and raloxifene increased the NO/ET-1 ratio by 61.4% and 81.1 %, respectively. In conclusion, both regimens may exert a cardio-protective effect by decreasing ET-1 levels and increasing the NO/ET-1 ratio. In contrast, both regimens had a negative influence on PGI(2) levels.

Objectives: To assess total homocysteine (tHcy) and folate levels in postmenopausal women and investigate whether age, menopause duration, kind of menopause and tobacco use had an effect on these levels. Methods: Total homocysteine and folate levels were measured in fasting blood samples of 200 postmenopausal women with normal thyroid and renal function tests. Patients were not receiving vitamins or hormone replacement therapy. Results: Total homocysteine levels increased significantly after 60 years while folate levels showed a decrease trend after 65 years. Menopause duration had no effect on folate levels and increased significantly tHcy levels after > 180 months duration. The kind of menopause did not influence tHcy and folate levels. Tobacco use reduced significantly folate levels. Conclusions: Age seems to be the principal factor influencing tHcy levels. We believe that decreased folate levels also reflect an age-associated inadequate dietary intake. Tobacco use did not alter tHcy levels; however, we found smoking to lower folate levels. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Recurrent spontaneous miscarriage (RSM) is a multifactorial problem. Auto- and alloimmune parameters have been implicated. Antithyroid antibodies (ATA) were tested in a group of women with RSM. The presence of antipaternal antibodies (APCA) was evaluated as an index of alloimmune contribution. Thirty euthyroid women with RSM (three or more consecutive miscarriages) aged 25-37 years were compared with 15 matched controls. Thyroid peroxidase (TPO) and thyroglobulin antibodies were tested with a chemiluminescence immunoassay and APCA were tested with a cross-match reaction. Results were compared using the chi-squared test. There was a higher frequency of ATA in women with RSM compared to controls (37% versus 13%, p < 0.05). Twenty of the women (67%) with RSM were tested negative for APCA, indicating an alloimmune contribution to their infertility. In this subgroup of women, the frequency of ATA continued to be higher than controls (40% versus 13%, p < 0.05). In conclusion, women with RSM, independent of APCA status, have a higher frequency of ATA. This may represent an additional marker for impaired regulation of the maternal immune system.