The effect of vitamin D receptor BsmI genotype on the response to osteoporosis treatment in postmenopausal women: a pilot study.

AIM: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The frequency of early, spontaneous miscarriage associated with the leu33pro polymorphism of Glycoprotein IIIa: a pilot study.

BACKGROUND: Inherited thrombophilia is associated with both poor obstetrical outcomes and increased cardiovascular risk later in life. In fact, a personal history of spontaneous miscarriage is reported to increase the risk of subsequent ischaemic heart disease. AIMS: This pilot study aims to evaluate the association between genetic polymorphism-related increased risk of arterial thrombosis and the history of spontaneous miscarriage early in pregnancy, among healthy postmenopausal women. METHODS: The following polymorphisms were assessed in 84 healthy post-menopausal women: Glycoprotein IIIa leu33pro, Apolipoprotein E2/E3/E4, Methylenetetrahydrofolate reductase, Apolipoprotein B arg3500gln, Paraoxonase 1 gln182arg, Plasminogen activator inhibitor 1 4G/5G, Cholesterol-7(α) -hydroxylase and Cholesterol ester transfer protein (ΤaqIB) B1/B2. The association between the polymorphisms and history of spontaneous pregnancy loss was evaluated. RESULTS: The frequency of the PL(A2) allele of glycoprotein IIIa was significantly higher in women who experienced spontaneous miscarriage when compared with controls (P = 0.033). Glycoprotein IIIa leu33pro polymorphism correlated positively with the frequency of spontaneous miscarriage (P = 0.027). Among women reporting miscarriage, 55.6% were heterozygous compared with 44.4% who were wild type. We found no significant association between any of the other polymorphisms and spontaneous pregnancy loss. CONCLUSIONS: Our findings indicate that Glycoprotein IIIa leu33pro polymorphism is associated with early, spontaneous miscarriage. The causative role of this polymorphism as a risk factor of pregnancy loss needs further investigation by prospective studies.

Estrogen plus progestin treatment: effect of different progestin components on serum markers of apoptosis in healthy postmenopausal women.

One hundred healthy postmenopausal women were randomly assigned to receive 17ß-E2 1 mg/drospirenone 2 mg or 17ß-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.

Endometriosis and other benign and malignant müllerian lesions in pelvic and extrapelvic organs.

OBJECTIVE: To conduct a retrospective study on case reports found in literature across the world on benign müllerian lesions of the urogenital tract and on cases of malignant transformation from müllerian duct remnants in order to better understand these rare anatomopathologic entities and to avoid overdiagnosis and overtreatment. STUDY DESIGN: We reviewed a number of case reports on benign and malignant müllerian lesions and compared the developments associated with endometriosis, endosalpingiosis and endocervicosis. RESULTS: Our sampling of case reports confirm the suggestion that both malignant neoplasms and benign müllerian lesions can arise in foci of endometriosis in both pelvic and extrapelvic sites. CONCLUSION: The development of malignant tumors is a well-known complication of endometriosis and endosalpingiosis, but data about endocervicosis are unclear.

Prolactin and preclinical atherosclerosis in menopausal women with cardiovascular risk factors.

Hyperprolactinemia has been associated with endothelial dysfunction and an adverse cardiovascular risk profile, possibly as a result of the vasoconstrictive properties of prolactin. In this cross-sectional study, we examined the hypothesis that prolactin contributes to the increased cardiovascular risk occurring in early menopause by studying apparently healthy women without hyperprolactinemia. Prolactin serum levels were measured by immunoassay in 76 women aged 54.4+/-4.9 years in menopause for 4.9+/-2.8 years, and possible correlations with traditional cardiovascular risk factors and surrogate markers of preclinical atherosclerosis, arterial stiffening, and endothelial and microcirculatory function were examined. Positive correlations between prolactin serum levels and arterial blood pressure, but no other traditional risk factors, were found. Prolactin also correlated with central aortic systolic (r=0.337; P=0.002) and diastolic (r=0.272; P=0.012) blood pressures and pulse wave velocity (r=0.264; P=0.02), a marker of aortic stiffness, but not with endothelial or microcirculatory function or carotid intima-media thickness. By multivariate regression analysis, prolactin levels determined, independent of traditional risk factors, both blood pressures and aortic stiffness. Notably, prolactin correlated with European Society of Cardiology HeartScore (r=0.364; P=0.002), a composite index that predicts 10-year cardiovascular mortality. Prolactin levels >8.0 ng/mL had 100% sensitivity to predict a high peripheral blood pressure. Prolactin may play a role in accelerated arteriosclerosis in early menopause by affecting central/peripheral blood pressure and arterial stiffness. In contrast, no correlation was observed with other risk factors or surrogate markers of atherosclerosis. Prospective studies to assess whether prolactin is an additional hormone increasing cardiovascular risk are warranted.

The role of the oxidative-stress in the endometriosis-related infertility.

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 women's reproductive capacity. The association between endometriosis and infertility is described in several studies and still remains debated.

Measurable serum markers of oxidative stress response in women with endometriosis.

OBJECTIVE: To evaluate the hypothesis of increased systemic oxidative stress in patients with endometriosis. SETTING: Tertiary care university hospital. DESIGN: Cross-sectional study. PATIENT(S): Sixty-six women of reproductive age undergoing laparoscopy. INTERVENTION(S): All women were investigated for endometriotic foci during laparoscopy. Forty-five women had laparoscopically and histologically confirmed endometriosis, and 21 women did not have endometriosis. MAIN OUTCOME MEASURE(S): Four markers of oxidative stress were assessed in the serum of each patient: heat shock protein 70 (HSP70), HSP70b', thioredoxin (TRX), and ischemia-modified albumin (IMA). RESULT(S): Mean serum HSP 70b' level was higher in patients with endometriosis compared with controls (0.178 ng/mL, SD 0.103, and 0.135 ng/mL, SD 0.014, respectively). The disease stage did not affect HSP70b' levels. Heat shock protein 70, IMA, and TRX levels did not differ between patients with endometriosis and controls. Women with a history of arterial hypertension had higher mean IMA levels compared with women with normal blood pressure independently of the presence of endometriosis (106.7 [SD 25.4] U/mL and 85.0 [SD 11.5] U/mL, respectively). CONCLUSION(S): Endometriosis is associated with increased systemic oxidative stress. The implication of increased systemic oxidative stress in disease progression or the association with other oxidative stress-related pathologic conditions needs to be addressed in further studies.

Apolipoprotein E and paraoxonase 1 polymorphisms are associated with lower serum thyroid hormones in postmenopausal women.

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-alpha hydroxylase A204C and cholesterol ester transfer protein B1/B2. RESULTS: A statistically significant correlation was found between Apolipoprotein E and paraoxonase 1 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.

Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women.

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 alpha-hydroxylase A-204C, and cholesterol ester transfer protein (TaqIB) B1/B2. Hormonal assays included FSH, LH, 17-beta-estradiol, testosterone, sex hormone-binding globulin (SHBG), DHEA sulfate, Delta-4-androstenedione (Delta4A), 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.

Apoptosis in atherosclerosis: a mini-review.

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.

CYP A-204C polymorphism is associated with subclinical atherosclerosis in postmenopausal women.

OBJECTIVE: To assess the association of common polymorphisms involved in lipoprotein oxidation, platelet activation, and cholesterol and homocysteine metabolism with subclinical atherosclerosis and indices of endothelial function and arterial elasticity in healthy postmenopausal women. DESIGN: The study investigated 84 healthy postmenopausal women recruited from the Menopause Clinic of the 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital. The following polymorphisms were genotyped: apolipoprotein B 3500, apolipoprotein E (E2/E3/E4), cholesterol 7 alpha-hydroxylase A-204C (CYP A-204C), cholesterol ester transfer protein B1/B2, glycoprotein IIIa leu33pro, integrin beta 3 PLA1/PLA2, plasminogen activator inhibitor 1 4G/5G, paraoxonase 1 gln192 arg, and methylenetetrahydrofolate reductase ala222val. Ultrasound examination aimed to assess the presence of atherosclerotic plaque and to measure intima-media thickness in the carotid and femoral arteries and to estimate the augmentation index, brachial flow-mediated dilatation, and radial and femoral pulse-wave velocity. RESULTS: The cholesterol 7 alpha-hydroxylase A-204C polymorphism was positively associated with the presence of atherosclerotic plaque (P = 0.004) and carotid and femoral intima-media thickness (P = 0.047 and P = 0.025, respectively). CONCLUSIONS: The CYP A-204C polymorphism was positively associated with subclinical atherosclerosis in healthy postmenopausal women. It remains to be clarified whether the presence of these polymorphisms may be valuable in assessing the inherent risk among postmenopausal women.

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.

Thoracic endometriosis syndrome.

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.

E-cadherin expression in cervical epithelial cells of postmenopausal women: association with hormone therapy, tibolone, and raloxifene.

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.

Pathogenesis of endometriosis: the role of defective 'immunosurveillance'.

OBJECTIVE: To analyse the aetiopathogenesis and the role of defective 'immunosurveillance' in endometriosis. METHOD: Review of studies on the pathogenesis of endometriosis, focusing particularly on novel molecules which express adhesive or proteolytic properties. Hypotheses addressing the role of oxidative stress in endometriosis were also reviewed. RESULTS: Endometriosis is a multifactorial disease associated with a general inflammatory response aiming to clear the peritoneal cavity from the ectopic endometriotic cells and tissue. Modern theories suggest that this inflammatory response creates an environment that may promote implantation and proliferation due to defective 'immunosurveillance'. CONCLUSION: The modern interpretation of the theory of reflux menstruation holds that women destined to develop endometriosis have a deficient immune system, which cannot defend against regurgitated endometrial cells. New findings on genetics, immune modulation, and secreted products of endometriotic lesions of affected women have given insight into the pathogenesis of this disorder and may serve as the background for new treatments of endometriosis-associated pain and infertility.

Ovarian endometriosis associated with ovarian cancer and endometrial-endocervical polyps.

AIM: To determine the prevalence of ovarian cancer and endometrial polyps in women with moderate and severe ovarian endometriosis. METHODS: A retrospective analysis of 667 cases of moderate and severe endometriosis laparoscopically and histologically confirmed during the period 1997-2004. RESULTS: One hundred and ninety-three (29%) of cases were American Fertility Society (AFS) stage III (moderate endometriosis) and 473 (71%) were AFS stage IV (severe endometriosis). Ovarian cancer was diagnosed in 13 cases (2.0%), while an endometrial or endocervical polyp was identified in 35 cases (5.3%). The incidence of endometrial polyps in the group with moderate endometriosis tended to be higher (15/193, 7.8%) than in the group with severe endometriosis (20/473, 4.2%), and the same results were obtained in the ovarian cancer group (moderate: 6/193, 3.1%; severe: 7/473, 1.5%). However, neither of the two differences was statistically significant. CONCLUSIONS: Ovarian endometriosis may be associated with an increased incidence of both ovarian cancer and endometrial polyps. Careful evaluation for coexistent pathology should be undertaken in women with symptomatic endometriosis.

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.

Quality of life and psychological symptoms in Greek postmenopausal women: association with hormone therapy.

Quality of life (QoL) in menopause is influenced by many parameters, including vasomotor symptoms, psychological status and culture. The aim of the present study was to examine the association of hormone therapy (HT) with QoL and psychological symptoms in Greek postmenopausal women. The study assessed 216 postmenopausal women (mean age 54.5 years) attending a university menopause clinic in Greece. Fifty-three were users of HT and 163 were not. QoL was evaluated by the Utian Quality of Life Scale (UQOL) and psychological symptoms were assessed by the Symptom Checklist-90-R (SCL-90-R). Women on HT were younger and more educated than women not using HT. Adjusting the analysis for the women's characteristics, HT users had better total UQOL scores than non-users (p < 0.05). Marital status and education had independent effects on QoL, with married and more educated women scoring higher (p < 0.05). Assessment of psychological symptomatology, after adjustment for sociodemographic variables across the different dimensions, revealed that HT users had better SCL-90-R scores than non-users for obsessionality, interpersonal sensitivity and for the general index (p < 0.05). Concluding, even though the impact of sociodemographic and lifestyle variables must be factored into the assessment of QoL, HT use is independently related to an improvement in the total score and in most domains of QoL, and has a significant positive effect on many aspects of psychological well-being in Greek postmenopausal women.

Association between serum tumor necrosis factor-alpha and corticotropin-releasing hormone levels in women with preterm labor.

AIM: To evaluate the association of serum corticotropin-releasing hormone (CRH) and tumor necrosis factor-alpha (TNF-alpha) in preterm labor. METHODS: Forty-nine primigravidas with a singleton viable pregnancy between 28 and 34 weeks of gestation were studied. They were divided into two groups. Group A consisted of 30 pregnant women (mean gestational age: 30.6 week) who presented with preterm labor and group B consisted of 19 pregnant women (mean gestational age: 29.8 week) with normal pregnancies. RESULTS: Women of group A had significantly higher serum CRH levels compared to those of group B (P < 0.01). Similarly, serum TNF-alpha levels were significantly higher in women of group A when compared to women of group B (7.8 +/- 3.72 pg/mL and 5.1 +/- 3.72 pg/mL, respectively). Furthermore, a positive correlation was found between serum CRH and TNF-alpha levels in both groups, which was stronger in women of group A. CONCLUSIONS: Our findings suggest that the increased levels of TNF-alpha and CRH found in pregnant women presenting with preterm labor may be involved in the pathophysiological mechanism of the latter. Furthermore, a positive interaction may exist between TNF-alpha and placental CRH, which may lead to enhanced production of the second and, therefore, facilitate the onset of labor.

Differential effect of hormone therapy and tibolone on lipids, lipoproteins, and the atherogenic index of plasma.

The aim of our study was to assess the effect of various regimens and doses of hormone therapy and tibolone on the Atherogenic Index of Plasma (AIP). A total of 519 postmenopausal women attending our menopause clinic were studied in a prospective design. Women with climacteric symptoms were randomly assigned to receive 1 of the following regimens: tibolone 2.5 mg, conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA), 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA), or 17beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (low E2/NETA). Serum parameters were assessed at baseline and after 6 months and included total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoprotein A1 and apolipoprotein B. The AIP was assessed as the log (triglycerides [mmol/L]/HDL-C [mmol/L]). CEE/MPA treatment associated with lower mean LDL-C but higher mean triglyceride levels (-15.5 mg/dL +/- 3.6, P = 0.0001; 12.6 mg/dL +/- 4.8, P = 0.01). Furthermore, CEE/MPA treatment resulted in higher AIP levels (0.073 +/- 0.021, P = 0.001). On the contrary, both E2/NETA regimens and tibolone associated with lower mean triglyceride and HDL-C levels (E2/NETA, triglycerides: -9.8 mg/dL +/- 5.0, P = 0.049; HDL-C: -4.9 mg/dL +/- 1.8, P = 0.01, low E2/NETA triglycerides: -12.5 mg/dL +/- 4.1, P = 0.003; HDL-C: -4.7 mg/dL +/- 1.3, P = 0.001; tibolone, triglycerides: -21.9 mg/dL +/- 2.7, P = 0.0001; HDL-C: -12.7 mg/dL +/- 1.1, P = 0.0001). None of the 3 regimens had any effect on AIP. The effect of a particular regimen of hormone therapy on the lipid-lipoprotein profile differs depending on the parameter assessed. The use of unified markers such as AIP will be helpful in evaluating the overall effect of lipid-lipoprotein modulation on the cardiovascular system. In fact, the concurrent assessment of the therapy effect on both LDL-C and AIP may be more dependable in evaluating the cardiovascular impact of a given regimen.