PubMed Research Feed

Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 2-year randomized, double-blind, placebo-controlled study.

Menopause. 2008 Nov 20;

Authors: D'Anna R, Cannata ML, Marini H, Atteritano M, Cancellieri F, Corrado F, Triolo O, Rizzo P, Russo S, Gaudio A, Frisina N, Bitto A, Polito F, Minutoli L, Altavilla D, Adamo EB, Squadrito F

OBJECTIVE:: To evaluate in a 24-month, prospective, randomized, double-blind, placebo-controlled study whether pure administration of the phytoestrogen genistein (54 mg/d) might reduce the number and severity of hot flushes in postmenopausal women, with no adverse effect on the endometrium and vagina. DESIGN:: A total of 389 participants met the parent study criteria and were randomly assigned to receive the phytoestrogen genistein (n = 198) or placebo (n = 191). About 40% of participants in both groups did not experience hot flushes, and the evaluation was performed in a subgroup of 236 participants (genistein, n = 119; placebo, n = 117). Reductions from the baseline in the frequency and severity of hot flushes were the principal criteria of efficacy. Endometrial thickness was evaluated by ultrasonography. The maturation value was also used to determine hormonal action on the vaginal cells. RESULTS:: There were no significant differences in vasomotor symptoms between groups at the baseline (4.4 +/- 0.33 hot flushes per day in the genistein group and 4.2 +/- 0.35 hot flushes per day in the control group). After 12 months of genistein therapy, there was a significant reduction (-56.4%) in the mean number of hot flushes, with a significant difference compared with the control group. After 24 months, there was no further decrease in the number of hot flushes in both groups. No significant difference was found in mean endometrial thickness and the maturation value score between the two groups, either at the baseline or after 24 months. CONCLUSIONS:: The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on the endometrium and vagina, but after the first year, there was no further improvement in the decrease in hot flushes.

PMID: 19034051 [PubMed - as supplied by publisher]

Is age at menopause increasing across Europe? Results on age at menopause and determinants from two population-based studies.

Menopause. 2008 Nov 20;

Authors: Dratva J, Gómez Real F, Schindler C, Ackermann-Liebrich U, Gerbase MW, Probst-Hensch NM, Svanes C, Omenaas ER, Neukirch F, Wjst M, Morabia A, Jarvis D, Leynaert B, Zemp E

OBJECTIVE:: To investigate the variability and determinants of menopause age in two European cohort studies, the European Respiratory Health Survey and the Swiss Air Pollution and Lung Disease in Adults Cohort. DESIGN:: Age at menopause was estimated in 5,288 women, aged 30 to 60 years, randomly selected in nine European countries between 1998 and 2002. Determinants of natural and surgically induced menopause were investigated by Cox regression and heterogeneity by meta-analysis. Follicle-stimulating hormone and luteinizing hormone levels were assessed in a subsample. RESULTS:: A quarter of the women were postmenopausal by age 50.8 years. Median age of natural menopause was 54 years. Hormone levels were within expected ranges for premenopausal and postmenopausal women. Surgically induced menopause was highly prevalent (22%-47%), associated with earlier timing of menopause. Determinants of earlier menopause were current smoking (hazard ratio [HR], 1.59; 95% CI, 1.27-1.98), body mass index greater than 30 kg/m (HR, 1.32; 95%, CI, 1.02-1.70), and low physical activity (HR, 1.37; 95%, CI, 1.12-1.67). The determinant for later menopause was multiparity (HR, 0.74; 95% CI, 0.62-0.89). Predictors were similar for naturally and surgically induced menopause. Oral contraceptive use yielded heterogeneous effects on timing of menopause. Later birth was associated with later menopause (HR, 0.934; 95% CI, 0.91-0.96). This evidence of a secular trend is heterogeneous across countries. CONCLUSIONS:: Age at menopause varies across Europe, shifting toward higher ages. This secular trend seems paradoxical because several adult determinants, that is, overweight, smoking, sedentarity, and nulliparity, associated with early menopause are on the rise in Europe. The heterogeneity of the secular trend suggests additional country-specific factors not included in the study, such as improved childhood nutrition and health, that have an influence on reproductive aging.

PMID: 19034049 [PubMed - as supplied by publisher]

Effect of oral estrogen on substrate utilization in postmenopausal women.

Fertil Steril. 2008 Oct;90(4):1275-8

Authors: Lwin R, Darnell B, Oster R, Lawrence J, Foster J, Azziz R, Gower BA

We tested the hypothesis that a 2-month intervention with unopposed oral conjugated equine estrogens (0.625 mg/d) would decrease lipid oxidation, as assessed by 24-hour, whole-room, indirect calorimetry in 14 postmenopausal women. Estrogen (E) treatment was associated with declines in both 24-hour and postprandial lipid oxidation and an increase in fat mass (mean [+/-SD] 2-month difference 1.1 +/- 1.0 kg; mean 6-month difference 1.8 +/- 2.2 kg), suggesting that, on an acute basis, oral E may increase adiposity by limiting lipid oxidation.

PMID: 18001731 [PubMed - indexed for MEDLINE]

Relaxin as a natural agent for vascular health.

Vasc Health Risk Manag. 2008;4(3):515-24

Authors: Bani D

Hypertension, atherothrombosis, myocardial infarction, stroke, peripheral vascular disease, and renal failure are the main manifestations of cardiovascular disease (CVD), the leading cause of death and disability in developed countries. Continuing insight into the pathophysiology of CVD can allow identification of effective therapeutic strategies to reduce the occurrence of death and/or severe disabilities. In this context, a healthy endothelium is deemed crucial to proper functioning and maintenance of anatomical integrity of the vascular system in many organs. Of note, epidemiologic studies indicate that the incidence of CVD in women is very low until menopause and increases sharply thereafter. The loss of protection against CVD in post-menopausal women has been chiefly attributed to ovarian steroid deficiency. However, besides steroids, the ovary also produces the peptide hormone relaxin (RLX), which provides potent vasoactive effects which render it the most likely candidate as the elusive physiological shield against CVD in fertile women. In particular, RLX has a specific relaxant effect on peripheral and coronary vasculature, exerted by the stimulation of endogenous nitric oxide (NO) generation by cells of the vascular wall, and can induce angiogenesis. Moreover, RLX inhibits the activation of inflammatory leukocytes and platelets, which play a key role in CVD. Experimental studies performed in vascular and blood cell in vitro and in animal models of vascular dysfunction, as well as pioneer clinical observations, have provided evidence that RLX can prevent and/or improve CVD, thus offering background to clinical trials aimed at exploring the broad therapeutic potential of human recombinant RLX as a new cardiovascular drug.

PMID: 18827902 [PubMed - indexed for MEDLINE]

Sodium and bone health: impact of moderately high and low salt intakes on calcium metabolism in postmenopausal women.

J Bone Miner Res. 2008 Sep;23(9):1477-85

Authors: Teucher B, Dainty JR, Spinks CA, Majsak-Newman G, Berry DJ, Hoogewerff JA, Foxall RJ, Jakobsen J, Cashman KD, Flynn A, Fairweather-Tait SJ

High salt intake is a well-recognized risk factor for osteoporosis because it induces calciuria, but the effects of salt on calcium metabolism and the potential impact on bone health in postmenopausal women have not been fully characterized. This study investigated adaptive mechanisms in response to changes in salt and calcium intake in postmenopausal women. Eleven women completed a randomized cross-over trial consisting of four successive 5-wk periods of controlled dietary intervention, each separated by a minimum 4-wk washout. Moderately low and high calcium (518 versus 1284 mg) and salt (3.9 versus 11.2 g) diets, reflecting lower and upper intakes in postmenopausal women consuming a Western-style diet, were provided. Stable isotope labeling techniques were used to measure calcium absorption and excretion, compartmental modeling was undertaken to estimate bone calcium balance, and biomarkers of bone formation and resorption were measured in blood and urine. Moderately high salt intake (11.2 g/d) elicited a significant increase in urinary calcium excretion (p = 0.0008) and significantly affected bone calcium balance with the high calcium diet (p = 0.024). Efficiency of calcium absorption was higher after a period of moderately low calcium intake (p < 0.05) but was unaffected by salt intake. Salt was responsible for a significant change in bone calcium balance, from positive to negative, when consumed as part of a high calcium diet, but with a low calcium intake, the bone calcium balance was negative on both high and low salt diets.

PMID: 18410231 [PubMed - indexed for MEDLINE]

[Hypertension in women]

Arch Cardiol Mex. 2008 Apr-Jun;78 Suppl 2:S2-98-103

Authors: Lomelí C, Rosas M, Mendoza-González C, Lorenzo JA, Pastelín G, Méndez A, Ferez SM, Attie F

The cardiovascular disease is a crucial cause of morbidity and mortality in the woman mainly when they arrive at menopause. The pathophysiology and neurohormonal mechanisms widely vary with respect to the man. This finding has given the support to think that the estrogens may be playing a protector role in cardiovascular disease. However, the associated risk factors like obesity, diabetes, dislipidemia, smoking and sedentary life are increasing in an exponential form. In Mexico the population age distribution establishes that 60% of the women with hypertension are aged < 54 years old. This is reason why as factor of independent cardiovascular risk is commonest. Nevertheless, after the menopause cardiovascular mortality is greater in the woman than in the man. In this review, the importance of the new pathophysiological mechanisms and the clinical-therapeutic approach are analyzed, making emphasis in the importance of the change in the life style and also in the nutritional aspects. In Mexico the woman still have a unique role in the nutritional culture.

PMID: 18938690 [PubMed - in process]

[Clinical guidelines for detection, prevention, diagnosis and treatment of systemic arterial hypertension in Mexico (2008)]

Arch Cardiol Mex. 2008 Apr-Jun;78 Suppl 2:S2-5-57

Authors: Rosas M, Pastelín G, Vargas-Alarcón G, Martínez-Reding J, Lomelí C, Mendoza-González C, Lorenzo JA, Méndez A, Franco M, Sánchez-Lozada LG, Verdejo J, Sánchez N, Ruiz R, Férez-Santander SM, Attie F,

The multidisciplinary Institutional Committee of experts in Systemic Arterial Hypertension from the National Institute of Cardiology "Ignacio Chávez" presents its update (2008) of "Guidelines and Recommendations" for the early detection, control, treatment and prevention of Hypertension. The boarding tries to be simple and realistic for all that physicians whom have to face the hypertensive population in their clinical practice. The information is based in the most recent scientific evidence. These guides are principally directed to hypertensive population of emergent countries like Mexico. It is emphasized preventive health measures, the importance of the no pharmacological actions, such as good nutrition, exercise and changes in life style, (which ideally it must begin from very early ages). "We suggest that the changes in the style of life must be vigorous, continuous and systematized, with a real reinforcing by part of all the organisms related to the health education for all population (federal and private social organisms). It is the most important way to confront and prevent this pandemic of chronic diseases". In this new edition the authors amplifies the information and importance on the matter. The preventive cardiology must contribute in multidisciplinary entailment. Based mainly on national data and the international scientific publications, we developed our own system of classification and risk stratification for the carrying people with hypertension, Called HTM (Arterial Hypertension in Mexico) index. Its principal of purpose this index is to keep in mind that the current approach of hypertension must be always multidisciplinary. The institutional committee of experts reviewed with rigorous methodology under the principles of the evidence-based medicine, both, national and international medical literature, with the purpose of adapting the concepts and guidelines for a better control and treatment of hypertension in Mexico. This work group recognizes that hypertension is not an isolated disease; therefore its approach must be in the context of the prevalence and interaction with other cardiovascular risk factors such as obesity, diabetes, dislipidemia and smoking among others. The urgent necessity is emphasized to approach in a concatenated form the diverse cardiovascular risk factors, since independently of which they share common pathophysiological mechanisms, its suitable identification and control will affect without any doubt the natural history of the other concatenated risk factor. By all means that to greater participation of factors, greater it will be the global cardiovascular risk but never, however, the specific weight is due to avoid that each one has on the global cardiovascular risk. In this Second edition we try to amplify and give systematic forms for the clinical approach for the suspicion of secondary hypertension and we emphasizes that hypertension in the woman with or without menopause should be careful analyzed, and special recommendations are given for the hypertension in pregnancy. Also we have approached some aspects related to the hypertensive emergencies and other special situations. In this second version some recommendations are presented for boarding hypertension in children and adolescents.

PMID: 18928127 [PubMed - in process]

The Gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status.

Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1339-43

Authors: Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, Chang-Claude J

Vitamin D pathway gene polymorphisms may influence breast cancer risk by altering potential anticarcinogenic effects of vitamin D. The association between polymorphisms in the vitamin D binding protein (Gc) and postmenopausal breast cancer risk, with additional focus on the influence of serum 25-hydroxyvitamin D [25(OH)D], the biomarker for vitamin D status in humans, has not been examined thus far. We assessed the combined effects of two known functional polymorphisms in the Gc gene (rs4588 and rs7041), composing the phenotypic alleles Gc1s, Gc1f (combined: Gc1), and Gc2, on postmenopausal breast cancer risk and potential effect modification by 25(OH)D status in a population-based case-control study including 1,402 cases and 2,608 matched controls. Odds ratios (OR) for breast cancer risk adjusted for potential confounders were calculated for Gc genotypes. ANOVA was used to compare geometric means of serum 25(OH)D across Gc genotypes. Serum 25(OH)D concentrations in the control group significantly differed by Gc genotype, being lowest in Gc2 allele carriers. The geometric means of 25(OH)D were 53.0, 47.8, and 40.4 nmol/L for Gc1-1, Gc2-1, and Gc2-2 genotypes, respectively (P(trend) < 0.0001). Gc2-2 genotype was associated with a significantly decreased risk of postmenopausal breast cancer with an odds ratio (95% confidence interval) of 0.72 (0.54-0.96), compared with homozygote Gc1s allele carriers. No interaction between 25(OH)D status and Gc genotype was observed, nor did the association change considerably after adjustment for 25(OH)D status. Our results provide evidence for a serum 25(OH)D-independent effect of Gc2 allele carrier status in postmenopausal breast cancer.

PMID: 18559548 [PubMed - indexed for MEDLINE]

Dietary intakes of selected nutrients and food groups and risk of cervical cancer.

Nutr Cancer. 2008 May-Jun;60(3):331-41

Authors: Ghosh C, Baker JA, Moysich KB, Rivera R, Brasure JR, McCann SE

We investigated the relationships between intakes of selected dietary nutrients and food groups and risk of cervical cancer in a hospital-based, case-control study including 239 cases diagnosed with squamous cell carcinoma of the cervix and 979 hospital patients with nonneoplastic diagnoses who completed a self-administered questionnaire between 1982 and 1998 at Roswell Park Cancer Institute. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusting for age, education, smoking status, use of oral contraceptives, barrier contraceptives and spermicides, family history of cervical cancer, year questionnaire completed, and energy intake. Significant reductions in risk of approximately 40-60% were observed for women in the highest vs. lowest tertiles of dietary fiber (OR=0.59, 95% CI=0.37-0.94), vitamin C (OR=0.52, 95% CI=0.33-0.80), vitamin E (OR=0.44, 95% CI=0.27-0.72), vitamin A (OR=0.47, 95% CI=0.30-0.73), alpha-carotene (OR=0.41, 95% CI=0.27-0.63), beta-carotene (OR=0.44, 95% CI=0.29-0.68), lutein (OR=0.51, 95% CI=0.33-0.79), folate (OR=0.55, 95% CI=0.34-0.88), and total fruit and vegetable intake (OR=0.52, 95% CI=0.34-0.77). Our findings suggest that a diet rich in plant-based nutrients may be important in reducing the risk of cervical cancer.

PMID: 18444167 [PubMed - indexed for MEDLINE]

Evolution and Predictors of Change in Total Bone Mineral Density Over Time in HIV-Infected Men and Women in the Nutrition for Healthy Living Study.

J Acquir Immune Defic Syndr. 2008 Oct 3;

Authors: Jacobson DL, Spiegelman D, Knox TK, Wilson IB

BACKGROUND:: Osteopenia is common in the era of effective antiretroviral therapy (ART), yet the etiology is unclear. We evaluated the association of host factors, disease severity, and ART to changes in total body bone mineral density (total BMD) over time in HIV-infected men (n = 283) and women (n = 96). METHODS:: Total BMD was measured annually by whole-body dual-energy absorptiometry (DXA), and medical, dietary, and behavioral history was collected. The median time from first to last DXA was 2.5 years (range 0.9-6.8 years). Using a repeated measures regression model, we identified variables independently associated with percent change in total BMD between consecutive DXA exams (n = 799 intervals), adjusted for age, race, sex, menopause, and smoking. We estimated percent change in total BMD over an average interval (1 year) standardized for representative levels of each determinant in males, premenopausal women, and postmenopausal women. RESULTS:: Median baseline age, CD4, and viral load were 42 years, 364 cells per cubic millimeter, and 2.7 log10 copies per milliliter, respectively. The estimated change in total BMD for those not on ART was -0.37% per year [95% confidence interval (CI) -0.76 to -0.02] for men, -0.08% per year (95% CI -0.49 to 0.33) for premenopausal women, and -1.07% per year (95% CI -1.86 to -0.28) for postmenopausal women. Greater loss of total BMD was associated with lower albumin, lower body mass index, prednisone/hydrocortisone use, tenofovir use, and longer duration of didanosine. Strength training and long duration of d4T and saquinavir prevented or mitigated bone loss. For those on ART for 3 years (not including the above agents), the rate of loss was -0.57% per year (95% CI -1.00 to -0.14) for men, -0.28% (95% CI -0.71 to 0.15) for premenopausal women, and -1.27% (95% CI -2.07 to -0.47) for postmenopausal women. Postmenopausal women had greater loss than premenopausal women and men. CONCLUSIONS:: Low body weight, low albumin, catabolic steroid use, and menopause may accelerate bone loss, and strength training may be protective. Tenofovir and didanosine may also have a deleterious effect on BMD.

PMID: 18845956 [PubMed - as supplied by publisher]

Coffee consumption and risk of endometrial cancer: a prospective study in Japan.

Int J Cancer. 2008 Nov 15;123(10):2406-10

Authors: Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Kurahashi N, Yamaji T, Tsugane S,

Coffee has been proposed to decrease the circulating insulin and estrogen levels, which are related to the development of endometrial cancer. However, few studies have prospectively assessed the association between coffee consumption and endometrial cancer. We conducted a population-based prospective cohort study in 53,724 Japanese women aged 40-69 years with no history of cancer at baseline in 1990-1994. We used Cox proportional hazards regression analysis to estimate the hazard ratio (HR) and 95% confidence interval (CI) of endometrial cancer incidence in relation to coffee consumption. All reported p values are 2-tailed. During the 15-year follow-up period, we documented 117 cases of endometrial cancer. Coffee consumption was significantly associated with a decreased risk of endometrial cancer. After adjustment for age, study area, body mass index, menopausal status, age at menopause for postmenopausal women, parity, use of exogenous female hormones, smoking status and by consumption of green vegetables, beef, pork and green tea, the multivariate HRs (95% CI) of endometrial cancer in women who drank coffee </=2 days/week, 3-4 days/week, 1-2 cups/day and >/=3 cups/day were 1.00, 0.97 (0.56-1.68), 0.61 (0.39-0.97) and 0.38 (0.16-0.91), respectively (p for trend = 0.007). In contrast, green tea consumption was not significantly associated with a reduced risk of endometrial cancer (p for trend = 0.22). The inverse association between coffee consumption and risk of endometrial cancer was consistently observed in subgroup analyses stratified by potential confounders. Coffee consumption may be associated with a decreased risk of endometrial cancer.

PMID: 18711700 [PubMed - indexed for MEDLINE]

New concepts on risk factors of HPV and novel screening strategies for cervical cancer precursors.

Eur J Gynaecol Oncol. 2008;29(3):205-21

Authors: Syrjänen K

During the past several years, this author has been engaged in coordinating two major multicentre trials testing optional screening tools for cervical cancer (CC) in low-resource settings both in East Europe and in Latin America. These international trials include the NIS (New Independent States of the former Soviet Union) cohort (n = 3,187 women) and the LAMS (Latin American Screening) study (n = 12,114 women). In both studies, a sizeable cohort of women (887 and 1,011, respectively) have been prospectively followed-up to assess the natural history of high-risk human papillomavirus (HR-HPV) infections and the role of implicated risk factors as potential predictors of disease outcome (acquisition, persistence and clearance). In this communication some of the key observations recently reported from the NIS and LAMS studies will be discussed, with special emphasis on i) risk factors that are still controversial (i.e., oral contraception; OC, and smoking) or not previously studied (drug addiction), on ii) reproductive factors as potential cofactors of HPV infections in cervical carcinogenesis (i.e., age at menarche, menopause), and finally on iii) the performance of different screening strategies among young and older women. Although closely related to these topics, a detailed discussion on the dynamics of HPV infections (acquisition, persistence, clearance) and their predictive factors falls outside the scope of this communication, because they have been extensively discussed in a series of original reports and in a recent review of the author in this journal. The NIS cohort failed to establish OC as a risk factor of CC. In all future studies, the strong confounding effects from the lifestyle behavioural factors must be taken into account, while interpreting the data on OCs as potential risk factors of CC. Similarly, it now seems that the increased risk (if any) of CC among smokers seems to be attributed to the increased acquisition of HR-HPV infections, of which the smoking status is an independent predictor in a multivariate model. The same seems to apply to drug addiction as a risk factor of CC as well. The recent LAMS data show that drug abuse itself is not a risk factor of i) contracting HR-HPV infection or ii) developing high-grade CIN. Instead, drug abuse seems to be closely associated with several of the indicators of risky sexual behaviour, which predisposes the women to oncogenic HPV infections and thus indirectly contributes to the development of CIN2+ lesions. Data from the NIS cohort clearly implicate that menarche age is not associated with increased risk of HR-HPV infection, or development of high-grade CIN, feasibly explained by the fact that menarche age does not have any effect on the outcome of CIN lesions or HR-HPV infections in a longitudinal setting. Another special group are postmenopausal women, recently shown to have a second peak of HR-HPV prevalence in many populations. The NIS cohort data suggest that among women who fail to eradicate their HR-HPV infection by menopause, there is i) a transition from multiple infections to single-type infections, and ii) selection of an integrated viral clone has already taken place, driving the process towards an aggressively progressing cervical disease. Finally, these special features of HR-HPV infections among younger and older women lead us to consider, whether different screening strategies are needed for younger and older women. Consonant with other recent reports, data from the LAMS study show that conventional Pap and HC2, but not LBC and VIA, perform significantly differently among younger and older women. However, the choice of an optimal screening test for young and older women depends on whether the highest positive predictive value (PPV) (Pap test) or the best balance between sensitivity and specificity (SE/SP) (HC2) is used as the selection criteria. Both the NIS cohort and LAMS study have significantly contributed to solving several of the open issues in the natural history of HR-HPV infections, including their risk factors, covariates necessary in cervical carcinogenesis as well as in sorting out the optional screening strategies in low-resource settings and for women in different age groups. In the long run, it is most likely that the cost-effectiveness will be the decisive factor for which screening tests will be selected. Needless to reiterate that screening for cervical cancer precursors will be mandatory until the foreseeable future, even in this emerging era of prophylactic HPV vaccination.

PMID: 18592782 [PubMed - indexed for MEDLINE]

Benefit of herbal alternatives for menopausal dysphoric disorder (MDD) without adverse side effects.

Menopause. 2008 May-Jun;15(3):576-7; author reply 577

Authors: Niederhofer H

PMID: 18467957 [PubMed - indexed for MEDLINE]

Effects of phytoestrogens derived from red clover on atherogenic adhesion molecules in human endothelial cells.

Menopause. 2008 May-Jun;15(3):542-50

Authors: Simoncini T, Garibaldi S, Fu XD, Pisaneschi S, Begliuomini S, Baldacci C, Lenzi E, Goglia L, Giretti MS, Genazzani AR

OBJECTIVE: In the search for safer approaches to address menopausal symptoms, the administration of plant-derived estrogens has gained popularity. Recent evidence suggests that these compounds may act neutrally or even beneficially on surrogate cardiovascular risk markers in postmenopausal women. However, little is known of the effects of phytoestrogens on vascular cells. DESIGN: Endothelial expression of leukocyte adhesion molecules plays a critical role in the development of atherosclerosis and in plaque destabilization, and estrogen reduces the expression of these proatherogenic molecules. We studied the regulation of the expression of intercellular adhesion molecule-1 (ICAM-1) and of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells by phytoestrogens contained in red clover extracts. Moreover, we characterized the mechanistic basis for these actions. RESULTS: Red clover extracts, particularly genistein and daidzein, inhibit the endothelial expression of ICAM-1 and VCAM-1 induced by bacterial lipopolysaccharide. The addition of red clover extracts to reproductive life or menopausal concentrations of 17beta-estradiol results in an additive decrease in expression of endothelial adhesion molecules. The reduction of ICAM-1 and VCAM-1 expression in the presence of red clover extracts is paralleled by a cytoplasmic stabilization of the proinflammatory transcription factor nuclear factor-kappaB. CONCLUSIONS: Red clover extracts act as anti-inflammatory and antiatherogenic agents on human endothelial cells by reducing the expression of the leukocyte adhesion molecules ICAM-1 and VCAM-1. On the basis of these results, red clover extracts may induce beneficial actions on human vessels.

PMID: 18467954 [PubMed - indexed for MEDLINE]

Fructus ligustri lucidi extract improves calcium balance and modulates the calciotropic hormone level and vitamin D-dependent gene expression in aged ovariectomized rats.

Menopause. 2008 May-Jun;15(3):558-65

Authors: Zhang Y, Dong XL, Leung PC, Che CT, Wong MS

OBJECTIVE: Fructus ligustri lucidi (FLL) is a widely used herb in China that is classically included in antiaging formulas for the treatment of age-related symptoms. Our laboratory previously showed that FLL could regulate calcium balance in young ovariectomized (OVX) rats. In the present study, we aimed to determine whether FLL could regulate calcium balance in aged OVX rats and to study the potential mechanisms that mediate its action in vivo. DESIGN: Aged OVX rats were orally administered an ethanol extract of FLL and its vehicle and fed with diets containing different levels of calcium [low calcium diet (LCD), 0.1% Ca; medium calcium diet (MCD), 0.6% Ca; and high calcium diet (HCD), 1.2% Ca] for 12 weeks. RESULTS: Significant reductions in urinary and fecal calcium excretion were found in the FLL-treated animals, resulting in a significant induction of calcium retention in rats fed with the MCD and HCD. FLL treatment significantly increased the serum 1,25-dihydroxyvitamin D3 level and slightly decreased the serum parathyroid hormone level in OVX rats fed with the MCD and HCD. When OVX rats were challenged by LCD, the inductions of serum parathyroid hormone and 1,25-dihydroxyvitamin D3 were decreased by FLL administration. FLL treatment significantly up-regulated duodenal vitamin D receptor and calcium transport protein 1 mRNA expression in rats fed with the HCD. FLL treatment reduced the expression of renal vitamin D receptor and 25-hydroxyvitamin D-24-hydroxylase mRNA in OVX rats fed with the LCD and MCD. CONCLUSIONS: Twelve weeks of FLL treatment could reduce calcium loss, modulate the parathyroid hormone-vitamin D axis, and increase vitamin D-dependent calcium transport in aged OVX rats, suggesting that FLL might be useful as an alternative medicine for improving calcium balance in postmenopausal women.

PMID: 18327153 [PubMed - indexed for MEDLINE]

Effects and safety of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women.

Menopause. 2008 May-Jun;15(3):530-5

Authors: Manonai J, Chittacharoen A, Udomsubpayakul U, Theppisai H, Theppisai U

OBJECTIVE: To evaluate the effect of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women and to evaluate the safety of Pueraria mirifica on endometrium; breast tissue; and hematologic, hepatic, and renal systems. DESIGN: This was a randomized, double-blind, placebo-controlled study in a university hospital of healthy postmenopausal women aged 45 to 60 years old. Women were enrolled voluntarily and randomly received 20, 30, or 50 mg Pueraria mirifica in capsules or identical placebo once daily for 24 weeks. Outcome measures were lipid profiles, bone-specific alkaline phosphatase level, endometrial thickness, endometrial histology, breast ultrasonography, complete blood count, liver function test, and renal function test. RESULTS: After 24 weeks of treatment, 71 women were evaluated. Of the 71 women, 51 randomly received varying doses of Pueraria mirifica and 20 received placebo. Pueraria mirifica and placebo significantly increased triglyceride levels by 15% from baseline levels (P<0.05). The Pueraria mirifica group showed a significant decrease in bone-specific alkaline phosphatase levels after 24 weeks of treatment compared with the placebo group; from 0.22+/-0.18 U/L to 0.13+/-0.01 U/L in the Pueraria mirifica group and from 0.20+/-0.10 U/L to 0.20+/-0.14 U/L in the placebo group. Endometrial thickness did not change after treatment in both groups (P>0.05). No endometrial proliferation or hyperplasia was reported after 24 weeks of treatment in both groups. There were no significant differences in adverse effects on breast tissue, complete blood count, and liver and renal function tests between the Pueraria mirifica and placebo groups in this study. CONCLUSION: Pueraria mirifica at a dose of 20, 30, and 50 mg/d for a 24-week period demonstrated an estrogen-like effect on bone turnover rate. Pueraria mirifica did not demonstrate an estrogen-like effect on endometrial thickness and endometrial histology. Mild adverse effects occurred after Pueraria mirifica and placebo treatment.

PMID: 18202589 [PubMed - indexed for MEDLINE]

The effect of ovariectomy combined with hindlimb unloading and reloading on the long bones of mature Sprague-Dawley rats.

Menopause. 2008 May-Jun;15(3):494-502

Authors: Tou JC, Foley A, Yuan YV, Arnaud S, Wade CE, Brown M

OBJECTIVE: To determine the effect of loss of ovarian function and mechanical loading (ie, inactivity) alone or in combination on bone mass and strength. DESIGN: Mature (aged 6 mo) rats were ovariectomized to induce loss of ovarian function and bone. Hindlimb unloading (HLU) was used to determine the effect of mechanical unloading and reloading on bone mass and strength. Bone mass of the femur and tibia was determined using dual-energy x-ray absorptiometry. Femoral and tibial bone strength was determined by a three-point bending test and by a torsion test. RESULTS: Ovariectomy (OVX) alone decreased total bone mineral density (BMD) in the femur (-5.5%, P=0.03) and tibia (-7.3%, P=0.01) compared with that for sham-operated animals. HLU alone for 4 weeks had no significant effect on bone. Together OVX/HLU accentuated BMD loss in the femur (-10.5%, P<0.01) compared with that for sham-operated animals. The femur was more sensitive than the tibia to the combination of OVX/HLU, indicated by the reduction (-5.3%, P<0.05) of total BMD below that achieved by OVX alone. Torsion tests showed that OVX/HLU but not OVX or HLU alone reduced bone strength. There was a correlation between lower femoral total BMD (r2=0.65, P<0.001) and reduced torque strength. Bone loss did not continue during the 2 weeks of reloading. CONCLUSIONS: OVX accompanied by mechanical unloading results in more rapid and severe bone loss than either OVX or unloading alone and therefore is associated with a greater likelihood of osteoporosis.

PMID: 18030174 [PubMed - indexed for MEDLINE]

The association between vascular function-related genes and age at natural menopause.

Menopause. 2008 May-Jun;15(3):511-6

Authors: van Disseldorp J, Broekmans FJ, Peeters PH, Fauser BC, van der Schouw YT

OBJECTIVE: In this study we attempted to confirm recent findings suggesting that age at natural menopause might be affected by single nucleotide polymorphisms in certain cardiovascular risk factor genes, such as genes encoding for blood clotting factors II, V, and VII and the apolipoprotein E2 gene. Such validation might increase support for the theory that ovarian aging is partly due to aging of the vascular supply to the ovary. DESIGN: We used a random sample of 742 naturally postmenopausal women from a large population-based cross-sectional study. Data on age at natural menopause, smoking, body mass index, reproductive history, and other health factors were collected through questionnaires. We studied the association between single nucleotide polymorphisms in the genes encoding for coagulation factors II, V, and VII and the apolipoprotein E2 gene and age at natural menopause using linear regression analysis. We corrected for oral contraceptive use, parity, current smoking, and body mass index. RESULTS: Only the heterozygous deletion/insertion mutation in clotting factor VII was significantly associated with an increase of menopausal age of 0.81 year (95% CI: 0.12-1.50 y). The homozygous variant, however, was not. The single nucleotide polymorphisms in the other genes studied were not significantly associated with age at natural menopause. Adjustment for various lifestyle factors did not change the associations between single nucleotide polymorphisms and age at menopause. CONCLUSIONS: Earlier findings relating specific point mutations in cardiovascular risk factor genes with age of natural menopause could not be confirmed in the present study.

PMID: 18030173 [PubMed - indexed for MEDLINE]

Effects of menstrual cycle on gene transfection through mouse vagina for DNA vaccine.

Int J Pharm. 2008 Aug 6;360(1-2):164-70

Authors: Kanazawa T, Takashima Y, Hirayama S, Okada H

Human immunodeficiency virus (HIV) infections mainly occur through the vaginal and rectal mucosal membranes. In the present study, to develop a DNA vaginal vaccine against viral and bacterial infections, the effects of the menstrual cycle on DNA transfection through the vaginal mucosa in female mice and transfection enhancement by electroporation, a chelating agent, cell-penetrating peptides (CPP) and nuclear localizing signals (NLS) were investigated. The transfection efficiencies of a marker plasmid DNA (pDNA), pCMV-Luc, on the vaginal mucosal membrane in mice at the stages of metestrus and diestrus were significantly higher than those at the stages of proestrus and estrus. The gene expression was markedly enhanced by electroporation and by pretreatment with the chelating agent. The highest level of expression was obtained by 2h pretreatment with 5% citric acid solution combined with electroporation with 15 pulses at 250 V/cm for 5 milliseconds (ms). Furthermore, a synergistic promoting effect on pDNA transfection was obtained by co-administration of CPP, the Tat peptide analog, and NLS, the NF-kappaB analog. These results indicate that effective DNA vaccination administered through the vaginal tract is possible by selecting the menstrual stage and overcoming the mucosal barrier using a combination of methods that promotes uptake.

PMID: 18573624 [PubMed - indexed for MEDLINE]

The frequency of ovulation from the affected ovary decreases following laparoscopic cystectomy in infertile women with unilateral endometrioma during a natural cycle.

J Assist Reprod Genet. 2008 Jun;25(6):239-44

Authors: Horikawa T, Nakagawa K, Ohgi S, Kojima R, Nakashima A, Ito M, Takahashi Y, Saito H

PURPOSE: To evaluate the cystectomy-induced damage on the follicular growth and ovulation of an affected ovary during natural cycles. METHODS: Twenty-eight infertile patients with unilateral ovarian endometriomas who underwent laparoscopic cystectomy were retrospectively evaluated. The ovulation rate of an affected ovary during natural cycles was compared before and after cystectomy in each patient, and it was also determined if ovulation from the affected ovaries resulted in pregnancy. RESULTS: After surgery, the ovulation rate was significantly lower than that before cystectomy (16.9 +/- 4.5% vs. 34.4 +/- 6.6%, P = 0.013). After surgery, 14 pregnancies were achieved without IVF treatment, and only 2 of them (14.3%) were achieved from an operated-side ovary. However, the pregnancy rate per ovulatory cycle of the operated-side ovary was not different from that of the intact ovary (8.8% vs. 5.8%, P = 0.750). CONCLUSIONS: Laparoscopic cystectomy is an invasive treatment in that it reduces the frequency of ovulation; however the pregnancy rate per ovulation did not deteriorate.

PMID: 18563551 [PubMed - indexed for MEDLINE]