Semana del 28 de Junio al 4 de Julio de 2006
Dr. Juan Enrique Blümel
Maturitas 2006; 54S:S15
Tibolone and endometrial safety: results from THEBES, a randomized 2-year study comparing tibolone with CEE/MPA
Alec Ferenczy1, D Archer2, J Rymer3, SO Skouby4, W Den Hollander5, F Helmond6
1McGill University and SMBD-Jewish General Hospital, Montreal, Que., Canada; 2CONRAD Clinical Reasearch Center, Norfolk, VA, USA; 3Department of Women's Health, St Thomas' Hospital, London, UK; 4Department of Obstetrics & Gynecology, Frederiksberg Hospital, Copenhagen, Denmark; 5NV Organon, Oss, The Netherlands; 6Organon International, Roseland, NJ, USA
Background and objectives: THEBES was a 2-year, prospective, multicountry, multisite, randomized, double-blind, controlled clinical trial to determine the endometrial response to oral tibolone (1.25 and 2.5 mg/day) versus continuous, combined, daily oral CEE plus MPA (0.625 mg + 2.5 mg/day). Methods: Endometrial lining was assessed at baseline and after 1 and 2 years by transvaginal ultrasound and suction biopsy curettage. Vaginal bleeding patterns were self-recorded in a bleeding episode log. Results: Three thousand two hundred and forty healthy postmenopausal women, mean age 54, were randomized in a 1:1:2 ratio (tibolone 1.25; tibolone 2.5; CEE/MPA). Mean baseline, double wall endometrial thickness was 3.1 mm for the combined tibolone group and 3.0 mm for the CEE/MPA group and 3.6 and 3.4 mm after 2 years treatment. Endometrial histology during 2 years of observation in both tibolone and CEE/MPA intent-to-treat groups is presented in Table 1. During the entire treatment period, 75% of the women in the tibolone group experienced no bleedingor spotting compared to 45% of the women treated with CEE/MPA. Conclusion: This study provides evidence that the endometrial morphology profile in postmenopausal women is similar with tibolone and CEE/MPA.
Kardiol Pol. 2006 Jun;64(6):573-580
Risk factors of atherosclerosis in premenopausal women with a sense of well-being. A pilot study.
Lukaszewicz R, Lukaszewicz M, Ceremuzynski L.
Centrum Medyczne Ksztalcenia Podyplomowego, Oddzial Kardiologii, Szpital Grochowski, Poland
Introduction: Women before menopause are thought to be relatively safe from cardiovascular disease due to the protective effects of oestrogens, although one may question this opinion with regards to women with many typical risk factors. However, because of the shortage of data concerning prevalence of risk factors in young women, it is not known whether this phenomenon is confined to a limited group or affects many women. Aim: The purpose of this study was to determine the prevalence of either typical risk factors of atherosclerosis or emotional disturbances that might increase the probability of coronary artery disease in young women. Methods: The study group involved 62 premenopausal women with a sense of well-being (regular menstruations, activity of serum follicle stimulating hormone < 15 IU/L). Mean age of women was 43.5 years. Total cholesterol, LDL and HDL fractions, triglyceride, lipoprotein (a) and homocysteine concentrations were examined and body mass index was calculated. A psychological examination assessing depression and neuroticism intensity was also performed. Results: Total cholesterol concentration (mean values +/- SD, expressed as mg%, percentage of abnormal results are given in brackets) was 206.3+/-35.8 (67.2), LDL cholesterol 124.3+/-30.2 (55.1), HDL cholesterol HDL 62.5+/-14.8 (6.9), triglyceride 101+/-60.1 (13.8), lipoprotein (a) 18.9+/-17.5 (44.8). Body mass index was 25.2+/-4.1 (41.3). History of smoking was positive in 27.4% and 6.5% of examined women had arterial hypertension. Coexistence of 4 to 5 aforementioned risk factors was noted in 27.4% of studied subjects. Mean homocysteine concentration was 10.7+/-2.1 micromol/L, while 41.3% of subjects had levels above the threshold of 11 micromol/l, commonly considered pathological. Symptoms of depression and neuroticism were seen in 30.5% and 22.5% of women, respectively. Conclusions: This pilot study of young women demonstrated that, in contrary to popular belief, this population is vulnerable to cardiovascular disease due to high prevalence of many risk factors.
J Gen Intern Med. 2006 Jun;21(6):636-41
Correlates of use of antifracture therapy in older women with low bone mineral density.
Ryder KM, Shorr RI, Tylavsky FA, Bush AJ, Bauer DC, Simonsick EM, Strotmeyer ES, Harris TB.
Health ABC Study. The University of Tennessee Health Science Center, Memphis, TN, USA.
BACKGROUND: Guidelines exist for treatment of low bone mineral density (BMD). Little is known about patient characteristics associated with use of treatment. OBJECTIVES: To determine patient-related correlates of medication use following screening dual x-ray absorptiometry (DXA) of older adults. DESIGN: Secondary analysis of a prospective cohort study. SETTING: Pittsburgh, PA and Memphis, TN. PARTICIPANTS: Community-dwelling women between the ages 70 and 79 years enrolled in the Health, Aging, and Body Composition (Health ABC) Study. MEASUREMENTS: Risk factors for fracture and BMD of the hip were assessed at baseline. Patients and their community physicians were supplied the results of the DXA scan. Prescription and over-the-counter medication use was collected at annual exams for 2 years. RESULTS: Of 1,584 women enrolled in Health ABC, 378 had an indication for antifracture therapy and were not receiving such treatment at baseline. By the second annual follow-up examination, prescription antiresorptive medication was reported in 49 (13.0%), whereas 65 (17.2%) received calcium and/or vitamin D supplementation. In adjusted models, the strongest predictor for use of any antifracture medicine was presence of osteoporosis [vs osteopenia, odds ratio (OR), 2.9 (1.7 to 4.7)], white race [OR, 2.6 (1.5 to 4.8)], and receipt of the flu shot [OR, 2.2 (1.3 to 3.8)]. Neither a history of falls nor prior fracture was associated with use of antifracture medications. CONCLUSION: Even when physicians of study participants were provided with DXA scan results, 70% of older high-functioning women with an indication for therapy did not start or remain on an antifracture therapy. Substantial room for improvement exists in fracture prevention following a diagnosis of low BMD-especially among women with a history of falls, prior fractures, and among black women.
Fertil Steril. 2006 Jun 24; [Epub ahead of print]
Tibolone and estradiol plus norethisterone acetate similarly influence endothelium-dependent vasodilatation in healthy postmenopausal women.
Cagnacci A, Renzi A, Cannoletta M, Pirillo D, Arangino S, Volpe A.
Department of Obstetrics, Gynecology and Pediatrics, University Hospital of Modena, Modena, Italy.
In healthy postmenopausal women, E(2) plus norethisterone acetate (1 mg + 0.5 mg) or tibolone (2.5 mg) similarly modify flow-mediated endothelium-dependent vasodilatation. The effect is dependent on baseline vasodilator reserve, with low values being augmented by either treatment.
Hum Reprod Update. 2006 Jun 28; [Epub ahead of print]
Hormones and cardiovascular health in women.
Crosignani PG.
Department of Obstetrics and Gynecology, University of Milano, Via Commenda 12, 20122 Milano, Italy.
Cardiovascular diseases (CVDs) may have their origin before birth: the combination of being small at birth and having an overly rich post-natal diet increases the likelihood of obesity and of acquiring a specific metabolic syndrome in adulthood that carries an increased risk of CVD. The incidence of CVD and mortality is very low in women of reproductive age but rises to a significant level in older women. In this article, we discuss CVD in relation to hormonal contraception, pregnancy and polycystic ovarian syndrome (PCOS) in younger women and menopause in older women. Women with PCOS have a higher risk of diabetes and hypertension, but studies to date have not shown an effect on CVD events. Use of combined hormonal contraception has only small effects on CVD because of the low baseline incidence of myocardial infarction (MI), stroke and venous thromboembolism (VTE) among young women. Women with existing risk factors or existing CVD, however, should consider alternative contraception. In pregnancy, CVD is rare, although, in the West, it now accounts for a significant proportion of maternal mortality as the frequency of obstetrical causes of mortality has substantially declined. The frequency of VTE is 15 per 10 000 during pregnancy and the post-partum period. In older women, menopause causes a slightly higher risk of MI after allowing for age, although there is substantial heterogeneity in the results of studies on menopause and age at menopause and MI. A larger effect might have been expected, because estrogen reduces the risk of developing atherosclerosis in premenopausal women, whereas in post-menopausal women who may have established atherosclerotic disease, estrogen increases the risk of myocardial disease through the effects on plaque stability and clot formation. Recent trial results indicate that hormone treatment in menopause does not favourably affect the risk of MI, stroke or other vascular disease. Thus, prevention of CVD should rely on diet and fitness, low-dose aspirin and treatment of hypertension, hyperglycaemia and hyperlipidaemia.
J Gen Intern Med. 2006 Jun;21(6):630-5
Osteoporosis risk assessment and ethnicity: validation and comparison of 2 clinical risk stratification instruments.
Cass AR, Shepherd AJ, Carlson CA.
The University of Texas Medical Branch, Galveston, TX, USA.
BACKGROUND: Dual energy x-ray absorptiometry (DXA), coupled with early treatment, may reduce morbidity and mortality associated with osteoporosis. Clinical tools to enhance selection of women for DXA screening have not been developed or validated in an ethnically diverse population. OBJECTIVE: To compare the performance of the osteoporosis risk assessment instrument (ORAI) and the simple calculated osteoporosis risk estimation (SCORE) instrument across 3 racial/ethnic groups to identify women who would benefit from DXA scans. DESIGN: Blinded comparison of the instruments in a cross-sectional sample. PARTICIPANTS: Two-hundred twenty-six postmenopausal women were recruited from a university-based family medicine clinic. Women with a prior diagnosis of osteoporosis or those taking bone active medications were excluded. MEASUREMENTS: Participants completed a questionnaire that contained the ORAI and the SCORE questions; 203 completed a DXA scan. RESULTS: The sensitivity and specificity for the ORAI (0.68, [0.49 to 0.88, 95% CI]; 0.66, [0.59 to 0.73, 95% CI]) and the SCORE instrument (0.54, [0.34 to 0.75, 95% CI]; 0.72, [0.65 to 0.78, 95% CI]) differed significantly from previous reports. Overall, the accuracy of the ORAI (66.5%) and SCORE instrument (70.0%) were similar (McNemar's test P value = .37). The accuracy between instruments differed significantly in African-American women (McNemar's test, P value <.001). In African Americans, the SCORE instrument correctly identified more women without osteoporosis, but missed 70% of those with osteoporosis. CONCLUSIONS: The performance of the ORAI and SCORE instrument differed significantly from previous reports. Although both can reduce the use of DXA scans for screening for osteoporosis, lower sensitivities resulted in underrecognition of osteoporosis and may limit their clinical usefulness in an ethnically diverse population.
Maturitas. 2006 Jun 26; [Epub ahead of print
Impact of seafood and fruit consumption on bone mineral density.
Zalloua PA, Hsu YH, Terwedow H, Zang T, Wu D, Tang G, Li Z, Hong X, Azar ST, Wang B, Bouxsein ML, Brain J, Cummings SR, Rosen CJ, Xu X.
Program for Population Genetics, Harvard School of Public Health, Boston, MA, USA; American University of Beirut, Department of Internal Medicine, Beirut, Lebanon.
OBJECTIVES: Over the past decade, dietary choices and nutrition have proven to be major modulators of bone mineral density (BMD) in men and women. We investigated environmental determinants, specifically dietary habits, of BMD by using multiple regression models in a rural Chinese population. METHODS: BMDs were measured at the hip and total body in 5848 men and 6207 women, aged 25-64. Dietary and supplemental intakes were assessed by a simple, one-page questionnaire tailored to collect nutritional information from large rural populations. Another questionnaire was used to collect information on the subjects' age, disease history, smoking, alcohol consumption, physical activity as well as women's menstrual status and reproductive history. Multiple regression models were used to assess the relationships among dietary variables and BMD, after adjusting for age, BMI (body mass index), weight, occupation, smoking status, and alcohol consumption. RESULTS: Increasing seafood consumption was significantly associated with greater BMD in women (p<0.001), especially those consuming more than 250g per week of seafood. One thousand and three hundred and twenty-four men and 1479 women consumed >250g of fruit per week. Higher fruit intake was found to be significantly associated with higher BMD in both sexes (p<0.05). High vegetable consumption, however, did not positively impact BMD. CONCLUSIONS: This study with its large population size has identified preventive measures, as well as some risk factors, involved in bone loss and osteoporosis. Our results highlight the importance of several dietary variables as significant determinants of BMD. It also emphasizes the role of dietary intake in general and shows that specific foods, such as fruits and seafood, can positively impact BMD.
Nucleic Acids Res. 2006 Jun 28;34(11):3279-87. Print 2006
Genes invoked in the ovarian transition to menopause.
Zimon A, Erat A, Von Wald T, Bissell B, Koulova A, Choi CH, Bachvarov D, Reindollar RH, Usheva A.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School Boston, MA 02215, USA.
Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the aging-specific decline in ovarian function are almost completely unknown. To provide the first gene-protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function.
Hum Reprod. 2006 Jun 28; [Epub ahead of print
Differential effects of oral conjugated equine estrogen and transdermal estrogen on atherosclerotic vascular disease risk markers and endothelial function in healthy postmenopausal women.
Ho JY, Chen MJ, Sheu WH, Yi YC, Tsai AC, Guu HF, Ho ES.
Department of Obstetrics and Gynecology, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Taichung, Taiwan.
BACKGROUND: Recent studies have revealed that HRT may increase the risk for atherosclerotic vascular disease (ASVD). METHODS: We investigated the effects of HRT via different administration routes on the markers for ASVD and endothelial function in healthy postmenopausal women. The oral HRT group (n = 18) received conjugated equine estrogen 0.625 mg/day; the transdermal HRT group (n = 18) received 17beta-estradiol (E2) gel 0.6 mg/day for 6 months. The control group (n = 30) had no treatment for 6 months. RESULTS: The C-reactive protein (CRP) rose from 0.129 +/- 0.116 to 0.752 +/- 0.794 mg/dl (P < 0.01) in the oral HRT group but remained unchanged in the transdermal HRT and control groups. The flow-mediated vasodilation (FMD) in the brachial artery was increased significantly by HRT from 6.0% before oral HRT to 14.7% after oral HRT (P < 0.001) and from 5.9% before transdermal HRT to 13.9% after transdermal HRT (P = 0.001). CONCLUSIONS: These data suggest that oral estrogen induces ASVD risk by increasing acute inflammation; however, transdermal estrogen avoids this untoward effect. Additionally, transdermal estrogen exerts a positive effect on endothelial function similar to that of oral estrogen. Therefore, the transdermal route might be favourable in terms of ASVD risks.
J Clin Endocrinol Metab. 2006 Jun 27; Epub ahead of print
Risk of Fracture among Women with Type 2 Diabetes: the Women's Health Initiative Observational Study.
Bonds DE, Larson JC, Schwartz AV, Strotmeyer ES, Robbins J, Rodriguez BL, Johnson KC, Margolis KL.
Departments of Epidemiology and Prevention and Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
Context: Some but not all studies have shown higher rates of fracture in individuals with type 2 diabetes. Objective: To determine the risk of fracture in postmenopausal women with type 2 diabetes and to determine if risk varies by fracture site, ethnicity, and baseline bone density. Design, Setting, and Participants: Women with clinically diagnosed type 2 diabetes at baseline in the Women's Health Initiative Observational Cohort, a prospective study of postmenopausal women (n = 93,676), were compared with women without diagnosed diabetes and risk of fracture overall and at specific sites determined. Main Outcome Measures: All fractures and specific sites separately (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow; lower arm/wrist/hand; spine/tailbone). Bone mineral density in a subset. Results: The overall risk of fracture after 7 yr of follow-up was higher in women with diabetes at baseline after controlling for multiple risk factors including frequency of falls (adjusted RR 1.20, 95% CI 1.11-1.30). In a sub-sample of women with baseline bone mineral density (BMD) scores, women with diabetes had greater hip and spine BMD. The elevated fracture risk was found at multiple sites (hip/pelvis/upper leg; foot; spine/tailbone), among black women (RR 1.33, 95% CI 1.00-1.75), and in women with increased baseline bone density (RR 1.26, 95% CI 0.96-1.66). Conclusion: Women with type 2 diabetes are at increased risk for fractures. This risk is also seen among black and non-Hispanic white women after adjustment for multiple risk factors including frequent falls and increased BMD (in a subset).
Diabetes Care. 2006 Jul;29(7):1573-8
Prospective study of diabetes and risk of hip fracture: the nurses' health study.
Janghorbani M, Feskanich D, Willett WC, Hu F.
School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran. janghorbani@yahoo.com.
OBJECTIVE: The purpose of this study was to determine whether women with type 1 and type 2 diabetes are at higher risk of hip fractures. RESEARCH DESIGN AND METHODS: A total of 109,983 women aged 34-59 years in 1980 were followed through 2002 for the occurrence of hip fracture. At baseline and through biennial follow-up, women were asked about their history and treatment of diabetes and other potential risk factors for hip fracture. RESULTS: During 2.22 million person-years of follow-up, 1,398 women had a hip fracture. Compared with women without diabetes, the age-adjusted relative risk (RRs) of hip fracture was 7.1 (95% CI 4.4-11.4) for women with type 1 diabetes and 1.7 (1.4-2.0) for those with type 2 diabetes. After further adjustment for BMI, smoking, physical activity, menopausal status, daily intake of calcium, vitamin D, protein, and postmenopausal hormone use, the multivariate RR of incident hip fracture in individuals with type 1 diabetes compared with individuals without diabetes was 6.4 (3.9-10.3) and with type 2 diabetes was 2.2 (1.8-2.7). The RRs increased with longer duration of type 2 diabetes (3.1 [2.3-4.0] for >/=12 years compared with no diabetes, P for trend < 0.001) and ever use of insulin. CONCLUSIONS: These data indicate that both type 1 and type 2 diabetes are associated with an increased risk of hip fracture. The results of this study highlight the need for fracture-prevention strategies in women with diabetes.
Int J Gynecol Cancer. 2006 May-Jun;16(3):1348-53
Cholecystectomy and endometrial cancer: a marker of long-term elevated estrogen exposure?
Morimoto LM, Newcomb PA, Hampton JM, Trentham-Dietz A.
Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Excess hormones, both endogenous and exogenous, are implicated in the etiology of endometrial cancer. We considered whether having had gallstones or a cholecystectomy (surgery to remove the gallbladder), which are more common in women who are obese and who use exogenous hormones, might be a marker for high lifetime levels of estrogen. We conducted a population-based study of endometrial cancer cases and community controls in women aged 40-79 years. Participants completed an interviewer-administered questionnaire that elicited exposures prior to diagnosis or reference date, including history of gallstones and cholecystectomy, as well as reproductive history, lifetime body mass, smoking, postmenopausal hormone (PMH) use, and other risk factors. Compared to controls, cholecystectomy was associated with a 50% increased risk of developing endometrial cancer (odds ratio = 1.5 [1.1-2.0]). The relationship appeared to depend upon PMH user status; the association was observed only among never hormone users. Body mass index did not appear to modify this relationship. Having a diagnosis of gallstones was also associated with endometrial cancer, although to a lesser magnitude. Although other etiologic factors may play a role in the relation between cholecystectomy and endometrial cancer, the current analysis suggests that this association is attributable, at least in part, to the sharing of hormonal risk factors.
Int J Gynecol Cancer. 2006 May-Jun;16(3):1069-74
Normal appearing endometrial cells in cervical smears of asymptomatic postmenopausal women have predictive value for significant endometrial pathology.
Siebers AG, Verbeek AL, Massuger LF, Grefte JM, Bulten J.
Departments of Pathology, Epidemiology and Biostatistics, and Gynaecology and Obstetrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
The objective of this study was to determine whether postmenopausal asymptomatic women with normal endometrial cells in their smear are at higher risk for endometrial pathology compared with women without these cells. Histologic follow-up outcome and otherwise cytologic follow-up of 29,144 asymptomatic postmenopausal women was determined. Presence of normal endometrial cells, age, use of hormones, and reported elevated maturation index were assessed. The effect of each variable on outcome as well as the combined effect were evaluated. Prevalence rate of (pre)malignant uterine disease was significantly higher when normal endometrial cells were found in the cervical smear (6.5%) as compared to smears without these cells (0.2%), resulting in a relative risk of 40.2 (95% CI 9.4-172.2). Neither age nor hormone use or elevated maturation index showed significant impact on the outcome. Asymptomatic postmenopausal women with normal endometrial cells in their smear are at significant higher risk for (pre)cancerous endometrial lesion than women without these cells. These cases should be reported to the physician with an explicit comment that normal endometrial cells in a smear of a postmenopausal woman is an abnormal finding, possibly associated with significant endometrial pathology. It raises the question whether further gynecological examination would be more appropriate.
Arch Intern Med. 2006 Jun 26;166(12):1262-8.
Severe hot flashes are associated with chronic insomnia.
Ohayon MM.
Stanford Sleep Epidemiology Research Center, Stanford University School of Medicine, Palo Alto, Calif.
BACKGROUND: Because hot flashes can occur during the night, their presence has been frequently associated with insomnia in women with symptoms of menopause. However, many factors other than hot flashes or menopause can be responsible for insomnia, and several factors associated with insomnia in the general population are also commonly observed in perimenopausal and postmenopausal women who have hot flashes. METHODS: A random sample of 3243 subjects (aged >/=18 years) representative of the California population was interviewed by telephone. Included were 982 women aged 35 to 65 years. Women were divided into 3 groups according to menopausal status: premenopause (57.2%), perimenopause (22.3%), and postmenopause (20.5%). Hot flashes were counted if they were present for at least 3 days per week during the last month and were classified as mild, moderate, or severe according to their effect on daily functioning. Chronic insomnia was defined as global sleep dissatisfaction, difficulty initiating sleep, difficulty maintaining sleep, or nonrestorative sleep, for at least 6 months. Diagnoses of insomnia were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classification. RESULTS: Prevalence of hot flashes was 12.5% in premenopause, 79.0% in perimenopause, and 39.3% in postmenopause. Prevalence of chronic insomnia was reported as 36.5% in premenopause, 56.6% in perimenopause, and 50.7% in postmenopause (P<.001). Prevalence of symptoms of chronic insomnia increased with the severity of hot flashes, reaching more than 80% in perimenopausal women and postmenopausal women who had severe hot flashes. In multivariate analyses, severe hot flashes were significantly associated with symptoms and a diagnosis of chronic insomnia. Poor health, chronic pain, and sleep apnea were other significant factors associated with chronic insomnia. CONCLUSIONS: Severe hot flashes are strongly associated with chronic insomnia in midlife women. The presence of hot flashes should be systematically investigated in women with insomnia. Treating hot flashes could improve sleep quality and minimize the deleterious consequences of chronic insomnia.
Hypertension. 2006 Jun 26; [Epub ahead of print]
Effects of a New Hormone Therapy, Drospirenone and 17-{beta}-Estradiol, in Postmenopausal Women With Hypertension.
White WB, Hanes V, Chauhan V, Pitt B.
Division of Hypertension and Clinical Pharmacology, The Pat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington
Drospirenone (DRSP), a progestin with antialdosterone activity, has been developed for hormone therapy in combination with 17-beta-estradiol (E2) in postmenopausal women. We evaluated the antihypertensive efficacy and safety of various doses of DRSP and E2 and estradiol alone in postmenopausal women with hypertension using ambulatory and clinic blood pressure (BP) monitoring. This was a randomized, double-blind clinical trial of 3 doses of DRSP combined with estradiol, estradiol alone, and placebo in 750 postmenopausal women with stage 1 to 2 hypertension between 45 to 75 years. Ambulatory and clinic BPs, potassium, aldosterone, and lipid measurements and adverse events were evaluated in postmenopausal women with stages 1 to 2 hypertension during 8 weeks of double-blind therapy. DRSP and E2 induced dose-related reductions in the ambulatory and clinic systolic BP with physiological increases in serum aldosterone. Significant decreases in 24-hour systolic pressure were observed at doses of 2 and 3 mg of DRSP combined with estradiol but not by estradiol alone or 1 mg of DRSP with estradiol. There were no significant changes from baseline in potassium in any treatment group. Small, significant reductions in total and low-density lipoprotein cholesterol occurred on all of the active treatments, and serum triglycerides did not change. Adverse event rates were low and similar across treatment groups. In conclusion, these data show that DRSP combined with E2 significantly reduces BP in postmenopausal women with hypertension and did not induce significant increases in serum potassium. These characteristics may lead to a new benefit for this novel hormone therapy in postmenopausal women with hypertension.
Int J Clin Pract. 2006 Jun 23; [Epub ahead of print]
Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study*
Cooper A, Drake J, Brankin E; THE PERSIST INVESTIGATORS.
Bridge Medical Centre, Crawley, UK.
Osteoporosis is a common and debilitating condition associated with significant morbidity and mortality. The efficacy and safety of oral bisphosphonates for the treatment of osteoporosis are well established. However, patient adherence and persistence on treatment are suboptimal. This randomised open-label multi-centre study of 6-months' duration compared persistence on treatment in postmenopausal women with osteoporosis receiving either once-monthly ibandronate plus a patient support programme (PSP), or once-weekly alendronate. To avoid falsely elevated persistence rates often associated with clinical trials, the study was designed to reflect everyday clinical practice in the UK and follow-up visits were limited to be consistent with the primary care setting. Analysis of the primary endpoint showed that persistence was significantly higher in the ibandronate/PSP group compared with the alendronate group (p < 0.0001). The estimated proportion of patients persisting with treatment at 6 months was 56.6% (306/541) and 38.6% (198/513) in the ibandronate/PSP and alendronate groups, respectively. Therefore, compared with alendronate, there was a 47% relative improvement in the proportion of patients persisting with treatment in the ibandronate/PSP group. Secondary endpoint measurements of adherence (e.g. proportion of patients remaining on treatment at study end; proportion of patients discontinuing from the study) were also significantly different in favour of ibandronate plus patient support. In summary, the PERSIST study demonstrated that persistence on treatment was increased in patients receiving once-monthly ibandronate plus patient support compared with once-weekly alendronate. Increased persistence on bisphosphonate treatment is expected to improve patient outcomes and decrease the social and economic burden of osteoporosis.
Eur J Gynaecol Oncol. 2006;27(3):256-61
Proliferative effects of different hormone regimens on mammary glands in ovariectomized rats.
Cirpan T, Iscan O, Terek MC, Ozsener S, Kanit L, Pogun S, Zekioglu O, Yucebilgin S.
Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey.
OBJECTIVE: To compare the proliferative effect of different hormone regimens and estrogen receptor modulation on mammary glands in a rat model of surgical menopause. DESIGN: Experimental animal study. SETTING: University Hospital. INTERVENTION: In a rat model of surgical menopause, 78 adult Sprague Dawley female rats were ovariectomized and treated with estrogen, estrogen combined with continuous or intermittent progesterone or the estrogen receptor modulator raloxifene and their respective vehicle controls. Following intraperitoneal drug administration for 20 days, rats were perfused, mammary glands were removed, tissues were processed for immunohistochemical (Ki-67) and hematoxylin-eosin staining, and investigated under light microscope. MAIN OUTCOME MEASURE: Histopathological examination of mammary glands and Ki-67 positive cells (proliferation index). RESULTS: Histological examination showed dilatation in the duct cysts and vacuolization in the epithelial cells in groups receiving progestin, either intermittent or continuous. Histological findings in the raloxifene group were no different from the control group, and the atrophic terminal ductal lobular unit in adipose tissue rich stroma was similar to postmenopausal breast. In animals with a proliferative response, increased proliferation started and dominated in the terminal ductal lobular unit epithelium. Comparison of Ki-67 proliferation indices between groups revealed that estrogen alone or combined with intermittent progesterone yielded significantly higher Ki-67 indices compared to controls; estrogen combined with continuous progesterone also resulted in increasing the probability of proliferation, but the effect was not as pronounced as the other two groups. Raloxifene treatment, on the other hand, did not cause proliferation. CONCLUSION: Estrogen alone or combined with progesterone may increase the risk of breast cancer by enhancing proliferation in the TDLU; raloxifen does not induce proliferation and may be a safe estrogen receptor modulator regarding its effects on mammary glands during menopause.
Health Qual Life Outcomes. 2006 May 31;4(1):32 [Epub ahead of print]
Quality of life and hormone use: new validation results of MRS scale.
Dinger JC, Zimmermann T, Heinemann LA, Stoehr D.
ABSTRACT: BACKGROUND: The Menopause Rating Scale is a health-related Quality of Life scale developed in the early 1990s and step-by-step validated since then. Recently the MRS scale was validated as outcomes measure for hormone therapy. The suspicion however was expressed that the data were too optimistic due to methodological problems of the study. A new study became available to check how founded this suspicion was. METHOD: An open post-marketing study of 3282 women with pre- and post- treatment data of the self-administered version of the MRS scale was analyzed to evaluate the capacity of the scale to detect hormone treatment related effects with the MRS scale. The main results were then compared with the old study where the interview-based version of the MRS scale was used. RESULTS: The hormone-therapy related improvement of complaints relative to the baseline score was about or less than 30% in total or domain scores, whereas it exceeded 30% improvement in the old study. Similarly, the relative improvement after therapy, stratified by the degree of severity at baseline, was lower in the new than in the old study, but had the same slope. Although we cannot exclude different treatment effects with the study method used, this supports our hypothesis that the individual MRS interviews performed by the physician biased the results towards over-estimation of the treatment effects. This hypothesis is underlined by the degree of concordance of physicians assessment and patients perception of treatment success (MRS results): Sensitivity (correct prediction of the positive assessment by the treating physician) of the MRS and specificity (correct prediction of a negative assessment by the physician) were lower than the results obtained with the interview-based MRS scale in the previous publication. CONCLUSION: The study confirmed evidence for the capacity of the MRS scale to measure treatment effects on quality of life across the full range of severity of complaints before treatment. The difference of the relative improvement after therapy between the old and current study as well as the observed different sensitivity/specificity is - as a matter of probability - more likely to be caused by a bias introduced by the different application of the MRS scale than by a real differences in the efficacy of the therapy. A randomized clinical trial would be needed to test the impact of the latter. The message for future studies is: The MRS scale should be only used as self-administered tool where the suggestive effect of questions raised by health professionals (therapeutic optimism) can be largely excluded.
Menopause. 2006 May 25; [Epub ahead of print]
US women desire greater professional guidance on hormone and alternative therapies for menopause symptom management.
Ma J, Drieling R, Stafford RS.
Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA.
OBJECTIVE:: Women increasingly use alternative therapies for menopause symptom relief. We examined 1) current use and perceptions of hormone and alternative therapies for symptom relief among US women, and 2) healthcare provider involvement in women's decision making. DESIGN:: An online survey was completed by a national sample of 781 US women aged 40 to 60 years (72% survey completion rate) drawn from the Knowledge Networks panel in June 2004. Nationally representative estimates of women's use and perceptions of hormone and alternative therapies were made by accounting for sampling weights and survey design. RESULTS:: Hormone therapy was reported among 263 or 37% of this largely symptomatic sample, of whom 59% had stopped primarily due to concern about its potential risks. Herbal products and soy supplements separately were used among 31% and 13% of symptomatic women, of whom 41% and 67% were current users. Forty-four percent of herb users considered these products helpful with symptom relief. Sampled women generally felt ill informed about proper doses and usage of herbal products. Also, 58% of the sampled women expressed at least some concerns about these products, whereas proven safety was the most important factor when women consider such products. Despite considering healthcare providers the most reliable source of information, sampled women expressed low confidence in their ability to give sufficient information about treatment options for menopause symptoms. CONCLUSIONS:: Alternative therapies have become increasing popular and are quickly approaching hormone therapy in frequency as therapies for symptom relief among menopause-age women in the United States. However, large gaps exist between patient expectations and provider preparedness to guide patient decision making.
Menopause. 2006 May 25; [Epub ahead of print]
Fat mass rather than muscle strength is the major determinant of physical function and disability in postmenopausal women younger than 75 years of age.
Lebrun CE, van der Schouw YT, de Jong FH, Grobbee DE, Lamberts SW.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
OBJECTIVE:: Few studies have investigated the relationships between body composition, functional ability, and age-related disability in postmenopausal women. We investigated the relative role of fat mass, lean mass, and muscle strength in the development of disability in a group of healthy postmenopausal women younger than 75 years. DESIGN:: We performed a cross-sectional study among 396 independently living women aged 56-73 years, randomly selected between 8 and 30 years after menopause. Lean mass and fat mass were assessed by dual-energy x-ray absorptiometry. Muscle strength (grip and leg extensors) was assessed using dynamometry. Functional ability was estimated by Physical Performance Score, physical activity during the preceding year, and impairment in activities of daily living. RESULTS:: Of the participants, 43.7 % were overweight (25 >/= BMI < 30 kg/m), and 17.7% were obese (BM I >/= 30 kg/m). Higher muscle strength was observed with increasing lean body mass, and participants with higher muscle strength scored better in the physical performance score and activities of daily living. Higher fat mass was significantly associated with a lower physical performance score, lower physical activity, and a higher frequency of disability. Increasing fat mass was associated with increasing lean mass and decreasing lean/fat ratio. The increase in lean mass and muscle strength associated with higher fat mass was mainly localized in the legs. CONCLUSIONS:: Our results support the role of fat mass as the primary risk marker for disability, which might later accelerate by the age-related decrease in lean mass and the development of sarcopenia after the age of 75 years.
Menopause. 2006 May 25; [Epub ahead of print]
When is it appropriate to prescribe postmenopausal hormone therapy?
Ettinger B, Barrett-Connor E, Hoq LA, Vader JP, Dubois RW.
University of California, San Francisco, San Francisco, CA; Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland.
OBJECTIVE:: To develop evidence and consensus-based recommendations for the use of hormone therapy (HT) in postmenopausal women. DESIGN:: Using evidence from clinical trials and other publications, a multidisciplinary group of women's health experts developed consensus-based recommendations for HT use in more than 300 clinical scenarios. These panelists utilized the RAND Appropriateness Method and a quantitative scale to rate the appropriateness of treatment options for women with various risk factors and clinical scenarios. RESULTS:: The panel judged it appropriate to prescribe all forms of HT to women with intolerable menopause symptoms and usual (age-expected) risks of cardiovascular disease (CVD), venous thromboembolism (VTE), or stroke. Use of HT was judged not appropriate for the clinical scenarios of bone preservation, cosmetic appearance, current memory loss, loss of libido, or CVD protection. For a woman still using HT after 5 or more years, it was considered appropriate to recommend the options of stopping or lowering the dose even if stopping was previously attempted. In treating intolerable symptoms in the presence of some elevated risk for diseases related to HT, route of administration may affect appropriateness but prior stroke or TIA# risk is a contraindication. CONCLUSIONS:: Standard HT is appropriate for women with intolerable menopausal symptoms in the absence of HT-related risk factors (eg, CVD, stroke, VTE, breast cancer). Panelists judged it appropriate to repeatedly present the option of stopping or reducing the dose. In most cases, presence of risk factors makes standard-dose oral HT not appropriate; however, some women may be candidates for a different dose or route of administration.
Menopause. 2006 May 25; [Epub ahead of print]
Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study.
Haimov-Kochman R, Barak-Glantz E, Arbel R, Leefsma M, Brzezinski A, Milwidsky A, Hochner-Celnikier D.
Department of Obstetrics and Gynecology, Hebrew University Hospital, Jerusalem, Israel.
OBJECTIVE:: To investigate the recurrence and severity of climacteric symptoms after two methods of discontinuation of prolonged hormone therapy. DESIGN:: Postmenopausal women treated with hormone therapy for more than 3years and opting to discontinue therapy were randomly assigned to two treatment groups. Hormone therapy was discontinued either abruptly (group 1) or gradually (group 2). Symptoms in both groups were monitored with the Greene climacteric scale at 1, 3, 6, 9, and 12 months. RESULTS:: Ninety-one women aged 48 to 73 years (mean age 56.8 +/- 4.2 years) participated in the study. The mean therapy duration was 8.8 +/- 3.8 years. No differences were noted between the two groups regarding age at menopause, body mass index, reasons to start therapy, hormone therapy duration, type of regimen, and reasons cited for hormone treatment discontinuation. After cessation of therapy, a similar percentage of patients in each group resumed hormone therapy. Climacteric syndromes, specifically vasomotor dysfunction, were more severe in group 1 than in group 2 during the first 3 months after hormone therapy withdrawal. However, by 6 months vasomotor symptoms were worse in group 2. By 9 to 12 months, no difference was noted between groups. No differences were observed in the percentage of weight gain, vaginal bleeding, and atrophy after discontinuation of therapy by either method. CONCLUSIONS:: Our specific regimen of gradual discontinuation of hormone therapy merely postponed, and neither prevented nor minimized, the reappearance of vasomotor symptoms, mood deterioration, and sexual dysfunction, and the resulting discomfort.
Am J Public Health. 2006 May 30; [Epub ahead of print]
Cessation of Hormone Replacement Therapy After Reports of Adverse Findings From Randomized Controlled Trials: Evidence From a British Birth Cohort.
Mishra G, Kok H, Ecob R, Cooper R, Hardy R, Kuh D.
MRC National National Survey of Health and Developement, University College London.
Objectives. We examined the cessation of hormone replacement therapy (HRT) among British women, by educational level, social class, and cardiovascular risk factors, at the time of publicity about 2 clinical trials of HRT that were halted after adverse findings. Methods. A total of 1387 women aged 57 years reported their monthly HRT use between January 2002 and February 2003. A succession of regression-based time-series models were fitted to detect changes in the proportion of HRT users stratified by education level, social class, hypertension, and obesity. Results. The overall percentage of HRT users declined from 31% in January 2002 to less than 26% by February 2003. Changes in trends of HRT use were first detected in June 2002 (for women with advanced secondary educational qualification or higher) and in July 2002 (for all other groups). The rate of decline was greatest for women with no formal educational qualifications, from the manual social class, or who were hypertensive or obese. Conclusions. These decreases coincided with the announced cessation of a large US clinical trial of HRT. This publicity may have had a differential influence on the immediate decline in HRT use by various groups of British women.
Hum Reprod. 2006 May 26; [Epub ahead of print]
Duration not severity of the climacteric syndrome predicts resumption of hormone therapy after discontinuation: a clinical prospective study.
Haimov-Kochman R, Barak-Glantz E, Ein-Mor E, Arbel R, Brzezinski A, Milwidsky A, Hochner-Celnikier D.
Department of Obstetrics and Gynecology, Hebrew University Hospital, Jerusalem, Israel.
BACKGROUND: Predictive factors of women who are unable to quit prolonged hormonal therapy (HT) are largely unknown. We sought to identify predictors for the resumption of HT after the discontinuation of treatment. METHODS: A cohort prospective study was conducted allocating menopausal women treated with HT for over 3 years. Menopausal symptoms were monitored periodically after HT cessation by the Greene climacteric scale. RESULTS: Eighty-two women participated in the study. Age, the age of menopause, BMI, HT duration, the type of regimen, reasons cited to discontinue HT and the method of discontinuation did not differ between the subjects who successfully discontinued HT and those who failed to quit HT. Only the prevalence of vasomotor symptoms when HT was first prescribed significantly differed between the groups (P = 0.03). Comparable maximal Greene score was recorded in both groups. Over time, the subjects who returned to HT had higher Greene score [Hazard ratio 1.25, confidence interval (CI) 95% (1-1.07)] and significantly higher vasomotor score [Hazard score 1.22, CI 95% (1.02-1.46)]. CONCLUSIONS: The history of hot flashes and the duration of menopausal symptoms upon HT discontinuation predict the resumption of HT. Thus, the return to HT is expected in individuals who are intolerant of prolonged climacteric syndrome.
Maturitas. 2006 May 25; [Epub ahead of print]
Clitoral circulation in postmenopausal women with sexual dysfunction: A pilot randomized study with hormone therapy.
Nappi RE, Ferdeghini F, Sampaolo P, Vaccaro P, De Leonardis C, Albani F, Salonia A, Polatti F.
Research Center for Reproductive Medicine, University of Pavia, Italy; Department of Obstetric and Gynaecology, IRCCS Policlinico "San Matteo", University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy.
OBJECTIVE: The aim of the present pilot, randomized, study was to assess hemodynamic status of clitoral erectile tissues in postmenopausal women reporting female sexual dysfunction (FSD), namely libido and arousal disorders, under hormone therapy (HT). Vaginal health and sexual function were also investigated. STUDY DESIGN: Fifty patients presenting for clinical evaluation of menopausal status and suffering from FSD were randomly assigned to receive tibolone (2.5mg) or 1mg 17beta-estradiol .5mg NETA (EPT) for 6 months. The observational period lasted 7 months during which women underwent to duplex Doppler ultrasonography to obtain clitoral hemodynamic data, were evaluated by using the vaginal health score index (VHIS) and filled in the two-factor Italian McCoy female sexuality questionnaire (MFSQ). RESULTS: Tibolone significantly increased clitoral peak systolic and end diastolic velocity (p<.001 for both), while no significant difference was evident in clitoral circulation of women under EPT at the end of the study. Both tibolone and EPT significantly increased VHIS (p<.001), an effect already evident following 3 months of HT. The atrophic state was significantly improved at 6 months (p<.001) with no significant differences between the two HT regimens. After 3 months, both tibolone and EPT significantly increased the sexuality score (p<.001, for both), but such an effect was significantly more pronounced in FSD women treated with tibolone in comparison with those assuming EPT (p<.002). Between the 3rd and the 6th month, tibolone caused a further significant improvement of sexuality score (p<.001), while women under EPT did not show any significant further change displaying a lower score (p<.001) at the end of the study in comparison with women assuming tibolone. CONCLUSIONS: Clitoral circulation in postmenopausal women reporting FSD is significantly increased under tibolone in comparison with EPT with a better improvement of sexual function, as measured by MFSQ, following 6 months of treatment.
J Obstet Gynaecol. 2006 May;26(4):344-7
Effect of a compound containing isoflavones, primrose oil and vitamin E in two different doses on climacteric symptoms.
Cancelo Hidalgo MJ, Castelo-Branco C, Blumel JE, Lanchares Perez JL, Alvarez De Los Heros JI, For The Isona Study Group.
Hospital Universitario de Guadalajara, Universidad de Alcala de Henares, Madrid.
The object of this study was to evaluate the effect of different doses of a compound containing isoflavones 60 mg, primrose oil 440 mg and vitamin E 10 mg. (IOVE) on menopausal complaints. This was an open, multicentre, randomised, group comparative, efficacy and safety trial. A total of 1,080 postmenopausal women, with climacteric symptoms, were allocated into one of two treatment groups to receive one (Group 1; n = 562) or two IOVE capsules (Group 2; n = 518) per day. The Blatt - Kupperman scale and safety parameters including weight, body mass index, blood pressure and adverse effects were assessed at the first visit before initiating the treatment, and 3 - 6 months thereafter. In addition, cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL) and triglyceride levels were measured at baseline and at the 6th month visit. Finally, at the end of follow-up, the patient's satisfaction was assessed. No differences between groups at the beginning of the study and during the follow-up were observed. A significant reduction in Blatt - Kupperman scores were observed in the two groups. In addition, the reduction of the symptoms was more intense in the first 3 months. Increasing doses of IOVE add no beneficial effects since both studied doses were equally effective in the reduction of climacteric complaints.
Diabetologia. 2006 Jul;49(7):1637-46. Epub 2006 May 3
Apolipoprotein B: a predictor of inflammatory status in postmenopausal overweight and obese women.
Faraj M, Messier L, Bastard JP, Tardif A, Godbout A, Prud'homme D, Rabasa-Lhoret R.
Faculty of Medicine, Department of Nutrition, University of Montreal, 2405 Chemin Cote Ste-Catherine, Montreal, QC, H3T 1A8, Canada, may.faraj@umontreal.ca.
AIMS/HYPOTHESIS: Inflammation is implicated in the development of type 2 diabetes and CHD, but the trigger of inflammation is unclear. Although in vitro and animal studies support a role of elevated levels of atherosclerotic lipoproteins in the activation of inflammation, plasma cholesterol cannot predict inflammatory markers in humans. Moreover, the association between inflammatory markers and other traditional risk factors of diabetes and CHD is unclear. To increase our knowledge of in vivo regulation of inflammation, we examined the association between several traditional risk factors and inflammatory markers. We hypothesised that because apolipoprotein B (ApoB) reflects atherogenic particle number, it is the primary predictor of inflammatory status. SUBJECTS, MATERIALS AND METHODS: We examined the association between several traditional risk factors and plasma high-sensitivity (hs) C-reactive protein (CRP), hsTNF-alpha, soluble TNF receptor 1, IL-6, orosomucoid, haptoglobin and alpha(1)-antitrypsin in 77 non-diabetic overweight and obese postmenopausal women. RESULTS: The inflammatory markers correlated positively with total and abdominal adiposity, blood pressure, 2-h OGTT glucose, insulin resistance, triglyceride, total/HDL cholesterol, ApoB, ApoB:apolipoprotein A1 (ApoA1) ratio and Framingham CHD risk points. They correlated negatively with ApoA1, and total, LDL and HDL cholesterol. ApoB was an independent predictor of the interindividual variation in IL-6, hsCRP, orosomucoid, haptoglobin and alpha(1)-antitrypsin (R (2) range 8-40%); other risk factors were less predictive. Compared with BMI-matched control subjects, women with hyperapobetalipoproteinaemia (hyperapoB) had higher hsTNF-alpha, IL-6, hsCRP and orosomucoid (increase 17-104%). CONCLUSIONS/INTERPRETATION: ApoB is the primary predictor of inflammatory markers in postmenopausal overweight and obese women. Given elevated levels of inflammatory markers in hyperapoB women, we hypothesise that hyperapoB women may have an increased risk of developing both CHD and diabetes.
Adv Ther. 2006 Mar-Apr;23(2):263-73
Effects of combined female sex hormone replacement therapy on body fat percentage and distribution.
Delibasi T, Berker D, Aydin Y, Pinar T, Ozbek M.
Department of Endocrinology and Metabolism, Ankara Numune Hospital, Ankara, Turkey.
The effectiveness of hormone replacement therapy for patients with cardiovascular disease and for postmenopausal women with associated cardiovascular risks is currently under wide investigation. Among the cardiovascular risks are those related to body fat percentage and distribution. The present study undertook to investigate the effects of combined hormone replacement therapy on body fat percentage and distribution in postmenopausal women. Data for the present study were collected via retrospective analyses of 287 healthy postmenopausal women (146 as a study group, 141 as controls). Participants in the study group received 0.625 mg conjugated equine estrogen combined with 2.5 mg medroxyprogesterone acetate per day for 18 months. Body fat percentage and fat distribution were evaluated through the electrical impedance method and measurements of skinfold thickness, respectively. Two indices of centripetal fat distribution were defined: ratio of trunk-to-extremity skinfold thickness (T/E index), and ratio of upper-to-lower body skinfold thickness (U/L index). Investigators found that a daily dose of 0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate taken for 18 months increased body fat percentage by decreasing lean body mass and by affecting upper-to-lower body fat distribution, without producing significant changes in overall weight. A slight decrease in the trunk-to-extremity body fat ratio was noted at 18 months of treatment, but this decrease did not reach statistical significance. Data related to the effects of hormone replacement therapy on body fat percentage and distribution in postmenopausal women are scarce. Additional research is needed to clarify the possible health benefits of hormone replacement therapy.
Gynecol Obstet Fertil. 2006 Jun 6; [Epub ahead of print]
How WHI study influences women doctors' behaviour towards menopause.
Jamin C, Raccah-Tebeka B, Chevallier T, Micheletti MC.
Service de gynecologie-obstetrique, maternite Aline-de-Crepy, Paris, France.
OBJECTIVE: A survey entitled FEMME was conducted during 2002 in order to evaluate among French women doctors their own actual or future menopause perception and this before the WHI publication. The results of this American trial possibly modified the perception of these French women doctors. Therefore the same experts group conducted a new survey, from May to September 2003. The main aim of this survey was to evaluate the possible changes in the medical management of the actual or future menopause of these women, and secondarily to evaluate the changes in their patients' behaviour towards hormone replacement therapy (HRT). POPULATION AND METHODS: Postal auto administered questionnaires were sent to the same 10 000 French women doctors (GP or gynaecologist) whatever their menopausal status or their age. 1365 women doctors (respectively 18,5 or 11% of the gynaecologists or GPs contacted) were volunteers to participate in this survey. Among them, 1120 (84,9%) had already participated in the first part of this survey which took place before the WHI publication. RESULTS: 80% of these women doctors have been informed on WHI results principally by professional press or conferences. 70,9% changed their own actual or future menopause perception as follows. No additional selection of non hormonal treatment have been mentioned in comparison with the first part of the survey. On the other hand for HRT, selections of free estrogen plus progestin associations increased whereas those of fixed combinations decreased: this might be linked to the greater variety of estrogen doses, types of progestin and schedules of treatment (mostly with bleeding) offered by this kind of associations. Finally, duration of HRT is included between three and ten years in most cases. DISCUSSION AND CONCLUSION: Thus, unlike most of their patients, these women's physicians always preferred hormonal treatment for their own actual or future menopause. Only the conditions of these treatments have changed.
Clin Exp Obstet Gynecol. 2006;33(1):59-60
Possible factors affecting the age at menopause among women in the central anatolian region of Turkey.
Hassa H, Tanir HM, Tekin B, Senses T, Oge T, Mutlu FS.
Department of Obstetrics and Gynecology, Faculty of Medicine, Eskisehir, Turkey.
OBJECTIVE: We aimed to investigate the age at menopause and possible related factors in a Turkish population. STUDY DESIGN: In a three-year period, a retrospective analysis of 541 spontaneous menopause cases were evaluated. All postmenopausal women with spontaneous cessation of menses for > or = 12 months and serum FSH levels > 40 IU/l were included in the study. Sociodemographic status, reproductive and medical history, menopausal symptoms, and previous contraceptive and hormonal therapy use were assessed based on an interview using a standardized information system. Age at menarche, parity, menopausal age of mother and sister, history of lactation, physical activity, cigarette smoking, oral contraceptive use and body mass index (BMI) were assessed. RESULTS: Menopausal age of the enrolled cases was positively correlated with mothers and sisters' ages at menopause. Postmenopausal smokers had an earlier age at menopause compared to non-smokers. CONCLUSION: Cigarette smoking results in earlier menopause in the Turkish population. Menopausal ages of mothers and sisters clearly correlated with the age at menopause.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 May;37(3):416-20
Comparative study of effects of hormonal therapies on the healing of fracture in ovariectomized rats and Rats' endometria
Tian Y, Xu KH, Qiao L.
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, China.
OBJECTIVE: To compare the effects of Livial, Progynova and Premarin on osteoporosis associated with femoral fracture in rats, and assess these drugs' influnces on the rats' endometria in order to provide a therapeutic regiment appropriate for postmenopausal osteoporotic fracture. METHODS: Ninety 6-month-old SD female rats were randomly divided into five groups:SHAM, OVX, Livial, Progynova and Premarin. The osteoporotic model was established by ovariectomy except for Sham group. The right femur was broken by operation 8 weeks later. Livial, Progynova,Premarin tablets were given after operation respectively. The rats in five groups were killed at the end of 2, 4, 6, 8 weeks after operation respectively. The study indices included the histological appearance and histomorphometry of bone calluses, osteoblasts, osteoclasts, and endometrium. RESULTS: There were more osteoclasts in OVX group than in other four groups,but no statistically significant differences in number of osteoblasts on the surface of osseous trabecula were seen among the five groups. The biggest area of trabecula was in Livial group while the smallest area was in Progynova group, especially at 4 weeks after operation. The hyperplasia of endometrium measured by morphometry was the same in the Progynova,Premarin groups as in Sham group, whereas it was not found in Livial group at 8 weeks postfracture. CONCLUSION: Estrogen is good for healing of postmenopausal osteoporotic fracture. The possible mechanism relevant to healing is that estrogen inhibits bone absorption, stimulates bone formation, reduces bone turnover and accelerates bone-remodeling. When compared against the treatment with estrogen alone, the treatment with combined sex hormones has better effects on fracture healing. Livial would not bring about endometrium hyperplasia.
J Pediatr Endocrinol Metab. 2006 Apr;19(4):523-8
Efficacy and safety of oral alendronate treatment in children and adolescents with osteoporosis.
Unal E, Abaci A, Bober E, Buyukgebiz A.
Department of Pediatric Endocrinology and Adolescence, Dokuz Eylul University, Izmir, Turkey.
OBJECTIVES: To evaluate the efficacy and safety of oral alendronate on bone mineral density (BMD) in children and adolescents with osteoporosis. METHODS: Oral alendronate was given to 22 patients with an average age of 13.3 +/- 3.9 years (range 4.3-19 years) and BMD z-score < or = -2. Thirteen of them were treated with steroids. Dual-energy X-ray absorptiometry (DEXA) was used to measure lumbar vertebral BMD before and 14 +/- 7.75 months after treatment. Auxological, biochemical (Ca, P, alkaline phosphatase [ALP]) and densitometric parameters before and after treatment were compared for all patients. Responses of the patients taking steroids were compared with those who did not. RESULTS: Post-treatment z-scores of patients were significantly higher than basal values (p < 0.001). Average annual BMD increase with treatment was 32.74 +/- 52.57% (5.17 to 255.42%). Z-score and annual BMD increase in patients taking no steroids were significantly higher than the others (p = 0.020 and p = 0.006, respectively). Post-treatment serum ALP levels were significantly lower than their pretreatment levels (p = 0.007). After 1 year of treatment, osteoporosis completely recovered in six patients (28.6%), improved to osteopenia levels in seven patients (33.3%), continued although the z-score was increased in six patients (28.6%), and worsened in two patients (9.5%). There was no significant difference between the height standard deviation scores (SDS) of patients before and after treatment (p = 0.022). No side effect was observed due to alendronate treatment during the study. CONCLUSION: It is concluded that oral alendronate increases BMD without any side effects in osteoporotic children and adolescents, and it is cheaper and is easier to use than i.v. bisphosphonates.
Osteoporos Int. 2006 Jul;17(7):1008-12. Epub 2006 Apr 27
Bisphosphonates in pregnancy and lactation-associated osteoporosis.
O'sullivan SM, Grey AB, Singh R, Reid IR.
Department of Medicine, University of Auckland, Auckland, New Zealand, s.osullivan@auckland.ac.nz.
INTRODUCTION: Pregnancy and lactation-associated osteoporosis (PLO) is an uncommon condition characterized by the occurrence of fracture(s) during late pregnancy or the puerperium. The aetiology is uncertain, and its management and natural history poorly defined. METHODS: We report a series of 11 women with PLO seen at our institution over the past 20 years, with follow-up ranging from 1 to 19 years. RESULTS: Ten women presented with painful low-trauma vertebral fractures, at a median of 1 month postpartum. In nine cases the fractures were multiple (median: 3, range: 2-5). At least one recognised risk factor for osteoporosis (low body weight, smoking history, family history of osteoporosis/fracture, vitamin D insufficiency) was present in nine patients. Bone density was in the osteoporotic range at the spine (mean T score: -2.8), with less marked reduction at the proximal femur (mean T score: -1.9). Nine patients received bisphosphonate treatment, for a median duration of 24 months. In the five women who received a bisphosphonate within 1 year of presentation, spinal bone density increased by 23% over baseline values after 2 years of treatment (p=0.0014). Of the 5 women who had subsequent pregnancies, one, who had declined bisphosphonate therapy after the initial presentation, sustained a fracture in the postpartum period. Two patients (both of whom were followed for at least 10 years) sustained fractures outside of pregnancy. CONCLUSIONS: PLO is therefore associated with significant morbidity, a high prevalence of recognized risk factors for osteoporosis and a risk of recurrence in subsequent pregnancies. Bisphosphonate therapy administered soon after presentation substantially increases spinal bone density in patients with PLO.
Osteoporos Int. 2006 Jun 7; [Epub ahead of print]
Dietary determinants of post-menopausal bone loss at the lumbar spine: a possible beneficial effect of iron.
Abraham R, Walton J, Russell L, Wolman R, Wardley-Smith B, Green JR, Mitchell A, Reeve J.
Northwick Park Hospital, Harrow, UK.
INTRODUCTION: Previous studies suggesting different effects of diet on post-menopausal bone loss may have given conflicting results because they sometimes failed to exclude confounding conditions or used imprecise methodology. DESIGN: To identify dietary determinants of bone loss from the lumbar spine after menopause in women not taking hormone replacement who developed no evidence of spondylotic or sclerotic degenerative disease, forty-three women were followed with repeated (mean = 12) measurements of bone mineral density (BMD) at L2-4 for 11-14 years. Eleven developed evidence suggestive of degenerative disease and were excluded. Diet was assessed at the beginning of the study and 2.5 years later using 3-day and 7-day periods of weighed intakes. Nutrients estimated were: carbohydrate, fat, protein, fibre, calcium, magnesium, iron, phosphorus, copper, zinc and six vitamins. We tested the ability of diet to predict post-menopausal bone loss using stepwise regression. RESULTS: Each woman's BMD change was described by a single coefficient after log transformation of the BMD data. The best model for BMD loss including dietary factors alone had two significant determinants: daily energy or protein (p=0.0003) intake was adverse, while dietary iron (p=0.002) was predictive of bone maintenance, an effect that persisted if iron was expressed as a ratio to energy intake. Adding body mass index to the model increased the goodness of fit (R (2)adj rose from 0.33 to 0.42) without affecting the statistical significance of the dietary determinants. CONCLUSIONS: Diet may influence bone loss after menopause, with dietary iron (or an associated factor) possibly having a protective effect on bone at the spine.
Br J Cancer. 2006 Jun 6; [Epub ahead of print]
Established breast cancer risk factors by clinically important tumour characteristics.
Garcia-Closas M, Brinton LA, Lissowska J, Chatterjee N, Peplonska B, Anderson WF, Szeszenia-Dabrowska N, Bardin-Mikolajczak A, Zatonski W, Blair A, Kalaylioglu Z, Rymkiewicz G, Mazepa-Sikora D, Kordek R, Lukaszek S, Sherman ME.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, 6120 Executive Blvd. Room 7076, Rockville, MD 20852-7234, USA.
Breast cancer is a morphologically and clinically heterogeneous disease; however, it is less clear how risk factors relate to tumour features. We evaluated risk factors by tumour characteristics (histopathologic type, grade, size, and nodal status) in a population-based case-control of 2386 breast cancers and 2502 controls in Poland. Use of a novel extension of the polytomous logistic regression permitted simultaneous modelling of multiple tumour characteristics. Late age at first full-term birth was associated with increased risk of large (>2 cm) tumours (odds ratios (95% confidence intervals) 1.19 (1.07-1.33) for a 5-year increase in age), but not smaller tumours (P for heterogeneity adjusting for other tumour features (P(het))=0.007). On the other hand, multiparity was associated with reduced risk for small tumours (0.76 (0.68-0.86) per additional birth; P(het)=0.004). Consideration of all tumour characteristics simultaneously revealed that current or recent use of combined hormone replacement therapy was associated with risk of small (2.29 (1.66-3.15)) and grade 1 (3.36 (2.22-5.08)) tumours (P(het)=0.05 for size and 0.0008 for grade 1 vs 3), rather than specific histopathologic types (P(het)=0.63 for ductal vs lobular). Finally, elevated body mass index was associated with larger tumour size among both pre- and postmenopausal women (P(het)=0.05 and 0.0001, respectively). None of these relationships were explained by hormone receptor status of the tumours. In conclusion, these data support distinctive risk factor relationships by tumour characteristics of prognostic relevance. These findings might be useful in developing targeted prevention efforts.
Int J Obes (Lond). 2006 Jun 6; [Epub ahead of print]
Disinhibition, as assessed by the Three-Factor Eating Questionnaire, is inversely related to psychological well-being in postmenopausal women.
Provencher V, Begin C, Piche ME, Bergeron J, Corneau L, Weisnagel SJ, Nadeau A, Lemieux S.
1Institute of Nutraceuticals and Functional Food (INAF) and Department of Food Science and Nutrition, Laval University, Quebec, Canada.
Objective:The main purpose of this cross-sectional study was to verify the hypothesis of a relationship between weight status and psychological well-being, and to examine whether cognitive dietary restraint, disinhibition, susceptibility to hunger and dieting history could be related to psychological well-being.Design and subjects:In a sample of 101 postmenopausal women, we performed anthropometric measurements (weight, height and body mass index (BMI)), and measured psychological well-being (PER Questionnaire). The Three-Factor Eating Questionnaire (TFEQ) and a questionnaire about dieting history (dieters: had already been on a diet; non-dieters: had never been on a diet) were also administrated.Results:A trend for a significant relationship was observed between BMI and psychological well-being (r=-0.17; P=0.08). Significant negative relationships were observed for disinhibition, susceptibility to hunger and all their subscales with psychological well-being (-0.28</=r</=-0.48), whereas no significant differences in psychological well-being were observed between dieters and non-dieters. Finally, women displaying a higher score for habitual susceptibility to disinhibition (which is the subscale of TFEQ that was the most closely related to psychological well-being) had a lower level of psychological well-being, regardless of their weight status.Conclusion:These results show that, as well as being related to weight status, TFEQ-factors are also related to psychological well-being. More specifically, individuals who display higher levels of disinhibition may be at higher risk of having an impaired psychological well-being.Psychological correlates of obesity remain under controversy. As eating behaviors and dieting history have been previously related to obesity status, these dietary variables may contribute to identify overweight and obese individuals who are at higher risk of having an impaired psychological well-being.
Ann Intern Med. 2006 Jun 6;144(11):832-41
Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis.
Nayak S, Olkin I, Liu H, Grabe M, Gould MK, Allen IE, Owens DK, Bravata DM.
VA Palo Alto Health Care System, Palo Alto, California, USA. smitanayak@stanford.edu
BACKGROUND: There is increased interest in quantitative ultrasound for osteoporosis screening because it predicts fracture risk, is portable, and is relatively inexpensive. However, there is no consensus regarding its accuracy for identifying patients with osteoporosis. PURPOSE: To determine the sensitivity and specificity of calcaneal quantitative ultrasound for identifying patients who meet the World Health Organization's diagnostic criteria for osteoporosis. Dual-energy x-ray absorptiometry (DXA) was used as the reference standard. DATA SOURCES: MEDLINE (1966 to October 2005), EMBASE (1993 to May 2004), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (1952 to March 2004), and the Science Citation Index (1945 to April 2004). STUDY SELECTION: English-language articles that evaluated the sensitivity and specificity of calcaneal quantitative ultrasound for identifying adults with DXA T-scores of -2.5 or less at the hip or spine. DATA EXTRACTION: Two authors independently reviewed articles and abstracted data. DATA SYNTHESIS: The authors identified 1908 potentially relevant articles, of which 25 met the inclusion criteria, and calculated the sensitivity and specificity of quantitative ultrasound over a range of thresholds. For the quantitative ultrasound index parameter T-score cutoff threshold of -1, sensitivity was 79% (95% CI, 69% to 86%) and specificity was 58% (CI, 44% to 70%) for identifying individuals with DXA T-scores of -2.5 or less at the hip or spine. For a T-score threshold of 0, sensitivity improved to 93% (CI, 87% to 97%) but specificity decreased to 24% (CI, 10% to 47%). At a pretest probability of 22% (for example, a 65-year-old white woman at average risk), the post-test probability of DXA-determined osteoporosis was 34% (CI, 26% to 41%) after a positive result and 10% (CI, 5% to 12%) after a negative result when using a T-score cutoff threshold of -1. Analysis of other quantitative ultrasound parameters (for example, broadband ultrasound attenuation) revealed similar estimates of accuracy. LIMITATIONS: The relatively small number of included studies limited the authors' ability to evaluate the effects of heterogeneous study characteristics on the diagnostic accuracy of quantitative ultrasound. CONCLUSIONS: The currently available literature suggests that results of calcaneal quantitative ultrasound at commonly used cutoff thresholds do not definitively exclude or confirm DXA-determined osteoporosis. Additional research is needed before use of this test can be recommended in evidence-based screening programs for osteoporosis.
PharmaLive (http://www.pharmalive.com/News/index.cfm?articleid=346228&categoryid=51)
FDA Says Tibolone Not Approvable as a Menopause Treatment in the U.S.
ARNHEM, the Netherlands, June 2, 2006 -The U.S. Food and Drug Administration (FDA) has determined that the New Drug Application (NDA) submitted for tibolone by Akzo Nobel's human healthcare business, Organon, is "not approvable". This response follows an amendment to the NDA which Organon filed with the FDA in December 2005. Organon plans to withdraw the application for tibolone as a treatment for women in the United States with menopausal symptoms. "Although Organon is disappointed with the FDA's response, we will continue to be committed to this proven brand," said Toon Wilderbeek, General Manager of Organon and member of Akzo Nobel's Board of Management responsible for Pharma. "Tibolone is available all over the world in countries outside the U.S. where it has been approved and marketed for nearly 20 years."
Eur J Appl Physiol. 2006 Jun 9; [Epub ahead of print]
Body fat and blood lipids in postmenopausal women are related to resting autonomic nervous system activity.
Kimura T, Matsumoto T, Akiyoshi M, Owa Y, Miyasaka N, Aso T, Moritani T.
Laboratory of Applied Physiology, Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan, t.moritani@neuro.mbox.media.kyoto-u.ac.jp.
The present study investigated the activity of the autonomic nervous system (ANS), a major influence in normal physiological function, and its association with unfavorable postmenopausal states in body composition, lipid and/or glucose metabolism, or cardiovascular profiles. Body composition, blood pressure, and blood profiles of lipid and glucose of 175 postmenopausal women were measured. Resting ANS activity was assessed by heart rate variability (HRV) power spectral analysis. To scrutinize the influence of ANS activity levels on postmenopausal obesity-related factors, we divided the subjects into a low group ( < 220 ms(2)) and a high group ( > 220 ms(2)), based on the total power of HRV. Low-frequency (P < 0.01) and high-frequency power (P < 0.01) were both significantly lower in the low group. No significant difference was found in age, age at menopause, or years after menopause between the two groups. In contrast, body mass index (P < 0.05), percentages of body fat (P < 0.01), and systolic (P < 0.01) and diastolic (P < 0.01) blood pressure were significantly greater in the low group. As to blood lipid profiles, triglycerides (P < 0.05), total cholesterol (P < 0.05), and low-density lipoprotein cholesterol (P < 0.05) were significantly higher in the low group. Our findings indicate that reduced sympatho-vagal activity is associated with higher postmenopausal body fat content, blood pressure, and blood lipid concentrations. This study further implies that such autonomic depression could be a crucial risk factor in undermining the health and, ultimately, the quality of life, of postmenopausal women.
Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):388-94
The Dutch Famine of 1944-1945: a pathophysiological model of long-term consequences of wasting disease.
Kyle UG, Pichard C.
Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland.
PURPOSE OF REVIEW: The tragic circumstances of the Dutch Hunger Winter of 1944-1945 created a unique opportunity to study the relation between exposure to prenatal famine and health in adult life. This review addresses the literature on the effects of maternal malnutrition during the different periods of gestation and childhood on health in adult life. RECENT FINDINGS: Exposure to famine during gestation resulted in increases in impaired glucose tolerance, obesity, coronary heart disease, atherogenic lipid profile, hypertension, microalbuminuria, schizophrenia, antisocial personality and affective disorders. Exposure to famine during childhood resulted in changes in reproductive function, earlier menopause, changes in insulin-like growth factor-I and increases in breast cancer. SUMMARY: Exposure to famine during gestation and childhood has life-long effects on health, and these effects vary depending on the timing of exposure as well as evolution of the recovery period.
Clin J Sport Med. 2006 May;16(3):247-252
Endothelial Function in Post-menopausal Former Elite Athletes.
Hagmar M, Eriksson MJ, Lindholm C, Schenck-Gustafsson K, Hirschberg AL.
Departments of *Obstetrics and Gynecology daggerClinical Physiology double daggerCardiology, Karolinska University Hospital, Stockholm, Sweden.
OBJECTIVE: To characterize endothelial function in postmenopausal former elite athletes in comparison to sedentary controls and to study the influence of hormone replacement therapy (HRT) on endothelial function in these groups of women. DESIGN: Cross-sectional study. SETTING: Research unit at a university hospital. PARTICIPANTS: Twenty postmenopausal former elite but still active endurance female athletes and 19 age-matched sedentary controls. The group of athletes and control subjects were each subdivided into two groups on the basis of utilization or non-utilization of HRT involving estrogen and gestagen. METHODS: Flow-mediated vasodilatation (FMD) was employed as an indicator of endothelial function. Fasting blood samples were analyzed for lipids and body composition determined by dual-energy x-ray absorptiometry. MAIN OUTCOME MEASURES: FMD, blood lipids and body composition. RESULTS: Former elite athletes not utilizing HRT demonstrated the highest FMD of all four subgroups, their values being significantly higher than those of control subjects not utilizing HRT (P<0.05), whereas this difference was not seen between the subgroups of athletes and control subjects using HRT. Serum levels of cholesterol and low-density lipoprotein (LDL) and the percentage of fat mass were significantly lower in the former elite athletes than in the control group (P<0.05 in all cases). However, these variables were not related to FMD. CONCLUSION: This investigation documents enhanced endothelial function in postmenopausal former elite endurance athletes not utilizing HRT, whereas the use of HRT equalizes FMD in former athletes and sedentary control subjects. Our findings suggest that long-term strenuous exercise has beneficial effects on endothelial function in postmenopausal women but that no further improvement can be obtained with HRT.
J Br Menopause Soc. 2006 Jun;12(2):75-80
Hormone replacement therapy: time to move on?
Davey DA.
Department of Obstetrics and Gynaecology, Faculty of Heath Sciences, University of Cape Town, Observatory, South Africa.
The risks and benefits of hormone replacement therapy (HRT) need to be put in perspective. In the analysis of clinical trials, emphasis is often placed on relative risks, statistical significance and 95% confidence intervals, whereas, from a clinical perspective, more may be gained from a consideration of the absolute and attributable risks of therapy. The Council for International Organizations of Medical Sciences recommended that the frequency of adverse events be categorized as 'rare' if less than 1/1000 but more than 1/10,000, and as 'very rare' if less than 1/10,000. In the analyses of the Women's Health Initiative (WHI), the attributable risks were 'appreciable' (i.e. more than 1/1000) only in women aged over 70 years, with the exception of the risks of venous thromboembolism and stroke. The women in the WHI trial do not represent the relatively younger, healthy, postmenopausal women most commonly prescribed HRT, who are probably at much lower risk. Moreover, the WHI trial did not take into account the benefit of relief of menopausal symptoms, which is, for many women, paramount and outweighs the 'rare' long-term risks. Age may be a useful guide to risks and some simple guidelines for management, based on age, are suggested. Many women have been denied or have discontinued HRT because of the fear of risks, which may not have been put in perspective or fully understood. The care of postmenopausal women is not static, and sufficient has now been learned to enable each menopausal woman, with the help of her medical adviser, to come to a balanced and reasonable decision.
J Am Coll Nutr. 2006 Jun;25(3 Suppl):271S-6S
Role of dietary sodium in osteoporosis.
Heaney RP.
Creighton University, 2500 California Plaza, Omaha, Nebraska 68178. rheaney@creighton.edu.
Sodium, in the form of sodium chloride, elevates urinary calcium excretion and, at prevailing calcium intakes, evokes compensatory responses that may lead to increased bone remodeling and bone loss. The calciuria is partly due to salt-induced volume expansion, with an increase in GFR, and partly to competition between sodium and calcium ions in the renal tubule. Potassium intakes in the range of current recommendations actually reduce or prevent sodium chloride-induced calciuria. At calcium intakes at or above currently recommended levels, there appear to be no deleterious effects of prevailing salt intakes on bone or the calcium economy, mainly because adaptive increases in calcium absorption offset the increased urinary loss. Such compensation is likely to be incomplete at low calcium intakes. Limited evidence suggests equivalent bone-sparing effects of either salt restriction or augmented calcium intakes. Given the relative difficulty of the former, and the ancillary benefits of the latter, it would seem that the optimal strategy to protect the skeleton is to ensure adequate calcium and potassium intakes.
Climacteric. 2006 Jun;9(3):204-14
Differential prevalence of quality-of-life categories (domains) in Asian women and changes after therapy with three doses of conjugated estrogens/medroxyprogesterone acetate: the Pan-Asia Menopause (PAM) study.
Limpaphayom KK, Darmasetiawan MS, Hussain RI, Burriss SW, Holinka CF, Ausmanas MK.
Chulalongkorn University, Bangkok, Thailand.
OBJECTIVES: To assess the prevalence of four categories (domains) of menopausal symptoms as markers for quality of life in nine ethnic groups of Asian women. To evaluate changes in quality of life (MENQOL scores) in Asian women following hormone therapy. METHODS: A prospective, randomized, double-blind, multinational clinical trial in 1028 healthy postmenopausal women of nine ethnic groups from 11 Asian countries/regions. Following 2 weeks of baseline observation, the women received one of three conjugated estrogens (CE)/medroxyprogesterone acetate (MPA) doses (in mg) daily for 24 weeks: 0.625/2.5, 0.45/1.5, or 0.3/1.5. At baseline and at the end of weeks 4, 12 and 24 following the start of therapy, the study participants were asked to record, on a menopause-specific quality of life (MENQOL) questionnaire, 29 menopausal symptoms, as experienced during the preceding month. The symptoms were categorized into four domains: vasomotor, psychosocial, physical and sexual. RESULTS: The baseline (pretreatment) symptom scores in each of the four domains varied substantially among the different ethnic groups, ranging from 2.21 to 5.71 in the vasomotor, 2.37-5.96 in the psychosocial, 2.66-5.39 in the physical, and 2.11-6.55 in the sexual domain. Overall, Vietnamese and Pakistani women had the highest baseline scores, i.e. were most afflicted by each set of symptoms in a given domain, and Indonesian, Malay, Taiwanese and Thai women were least afflicted. In the overall population, intervention resulted in statistically significant decreases in the scores of all four domains within 4 weeks of intervention. The beneficial effects were similar in the three dose groups. CONCLUSIONS: The prevalence of four domains of menopausal symptoms, representative of quality of life as recorded on a MENQOL questionnaire, varies considerably among ethnic groups of Asian women. The MENQOL scores in the overall population were significantly lowered in the course of the study, indicating an improvement in quality of life. In the absence of a placebo group, the relative contribution of hormones and placebo in our intervention is unknown.
Climacteric. 2006 Jun;9(3):169-80
Adipose tissue, insulin resistance and low-grade inflammation: implications for atherogenesis and the cardiovascular harm of estrogen plus progestogen therapy.
Tanko LB, Christiansen C.
Center for Clinical and Basic Research, Ballerup, Denmark.
OBJECTIVE: To summarize recent findings providing mechanistic insight into why the relative presence of central to peripheral fat mass is a critical determinant of atherogenesis and why postmenopausal women with android obesity represent a risk population with increased susceptibility to the cardiovascular harm of estrogen plus progestin therapy (EPT). METHODS: Review of own research and related literature in PubMed. RESULTS: In postmenopausal women, android obesity characterized by excessive upper-body combined with relatively poorly developed lower-body fat mass is frequently associated with insulin resistance, low-grade inflammation, and early atherosclerosis. Underlying mechanisms involve disequilibrium between proinflammatory cytokines (high interleukin-6/C-reactive protein) and the anti-inflammatory adipokine (low adiponectin). Recent findings point out that women with abnormal glucose tolerance, a metabolic alteration closely linked to android adiposity, respond with increases in low-grade inflammation and accelerated atherogenesis to EPT that collectively may promote acute complications. We recently pointed out that a progestin could exert a dose-dependent inhibitory effect on circulating adiponectin. Thus, when EPT is prescribed to women with android obesity, further decreases in the protective adiponectin pool may become critical and act as a promoter of thromboembolic complications via its effects on plaque formation and stability. Since android obesity is associated with the highest levels of free estradiol, women with this phenotype might not be trivial candidates for EPT. CONCLUSIONS: The herein summarized findings shed light on important interactions between sex steroids and body fat mass, with functional implications for cardiovascular risk. Since previous trials have not optimized the dose of the progestin for its effect on circulating adiponectin, utmost caution should be exercised in the prescription of available estrogen plus progestin therapies to women with android obesity and/or symptoms of the insulin resistance syndrome.
Addict Behav. 2006 Jun 8; [Epub ahead of print]
Transdermal nicotine for smoking cessation in postmenopausal women.
Oncken C, Cooney J, Feinn R, Lando H, Kranzler HR.
Departments of Medicine and Obstetrics and Gynecology, United States.
This study examined the efficacy of transdermal nicotine in postmenopausal smokers, and whether a history of depression or hormone replacement therapy (HRT) moderated smoking cessation outcomes. Postmenopausal smokers (N=152) received intensive smoking cessation counseling and were randomly assigned to use either a 21-mg nicotine patch for 3 months, with a 1-month taper, or a placebo patch. The primary outcome was biochemically validated 7-day point prevalence smoking abstinence during treatment (i.e., 1, 2, 6, and 12 weeks after the quit date) and 1 year after study medication was discontinued. Subjects who received transdermal nicotine were significantly more likely than placebo-treated subjects to remain abstinent from smoking during treatment, but not at the 1-year follow-up. The majority of subjects (>50%) in both groups accurately identified their treatment assignment. History of depression was associated with a decreased likelihood to abstain from smoking throughout the study. HRT did not moderate smoking outcomes. These data indicate that transdermal nicotine may provide short-term benefits for smoking cessation in postmenopausal women. However, efforts are needed to improve long-term abstinence rates and smoking outcomes among women with a history of depression.
J Obstet Gynaecol Res. 2006 Jun;32(3):305-8
Effects of hormone replacement therapy regimens on mammographic breast density: The role of progestins.
Topal NB, Ayhan S, Topal U, Bilgin T.
Department of Radiology, Faculty of Medicine, Uludag University, Bursa, Turkey.
Aim: To evaluate the effects of different regimens of hormone replacement therapy (HRT) on mammographic breast density. Methods: Mammograms of 113 healthy postmenopausal women who were on different HRT regimens were evaluated retrospectively. All women had a baseline mammography and at least one mammogram after at least 12 months of HRT. Four parenchymal patterns were considered mammographically. Quantification of density changes that occurred on follow-up mammograms was done qualitatively and with reference to densities on baseline mammograms. Results: Sixty women were treated with a continuous estrogen-progestin combination; 16 with a cyclic estrogen-progestin combination and 37 were with estrogen only. Twenty-six women had increased mammographic density after HRT. Mammographic density increase was detected in 23 women (38.3%) of the continuous estrogen-progestin combination group, two women (12.5%) of the cyclic estrogen-progestin combination group and one woman (2.7%) of the estrogen-only group. Mammographic density increase was more common among women in the continuous estrogen-progestin combination group than the other groups and this difference was found to be statistically significant (P < 0.001). Breast density increase was observed in 18 of 30 women (60%) with higher doses of progestin compared to 5 of 30 women (16.7%) with lower dose (P < 0.05). Conclusions: Postmenopausal HRT may increase mammographic breast density. Breast density appears to be mostly affected by higher doses and continuous administration of progestin.
Prescrire Int. 2006 Jun;15(83):107
Tibolone: cancers of the breast and endometrium.
No authors listed
In 2004, the first results of the British Million Women Study, a prospective cohort study that included more than a million women, showed that women using tibolone had nearly 1.5 times the risk of breast cancer as women who never used hormone replacement therapy. The difference was statistically significant. (2) In 2005, after a mean follow-up of 3.4 years, there were 31 cases of endometrial cancer per 10 000 women who used tibolone. This was almost double the level of risk experienced by women who never used hormone replacement therapy. (3) In another British cohort study, based on a general practice database, the risk of endometrial cancer among 4995 women treated with tibolone was almost double that of women who used sequential estrogen-progestin hormone replacement therapy. (4) Tibolone has no proven advantage over estrogen-progestin hormone combinations for treatment of symptoms of menopause, either in terms of efficacy or cancer risks. It is associated with an increased risk of stroke. There is no justification for using tibolone as a treatment for menopausal symptoms.
Gynecol Endocrinol. 2006 Jun;22(6):303-17
The effect of medroxyprogesterone acetate on estrogen-dependent risks and benefits - an attempt to interpret the Women's Health Initiative results.
Kuhl H, Stevenson J.
Department of Obstetrics and Gynecology, J. W. Goethe University, Frankfurt am Main, Germany.
The results of the two arms of the Women's Health Initiative (WHI) study allow a comparative assessment of the contribution of the progestogen component to the changes in risk of cardiovascular disease and cancer during treatment of postmenopausal women with conjugated equine estrogens and medroxyprogesterone acetate (CEE/MPA). However, the high proportion of older and overweight or obese women compromises any conclusions, since we estimate that 50% of the women would have the metabolic syndrome. In overweight postmenopausal women with hyperinsulinemia, the risk of breast cancer is elevated and cannot be increased further by hormone replacement therapy (HRT). Therefore, the non-significant, but consistent reduction in breast cancer risk during treatment with CEE alone might be based on an improvement of hyperinsulinemia. The 24% increase in breast cancer risk in the CEE/MPA group can be regarded as an artifact due to very low numbers of breast cancer diagnoses in the placebo group of women who had received HRT prior to the WHI study. The elevated risk of venous thromboembolism and the transient increase in the risk of coronary heart disease (CHD) during treatment with CEE/MPA but not CEE alone suggests a direct effect of MPA on the vessel wall. MPA has been demonstrated to upregulate the thrombin receptor, the thrombin-induced production of tissue factor and procoagulatory activity in the vessel wall owing to its glucocorticoid activity. In contrast, CEE alone reduced non-significantly the risk of CHD in women aged 50-59 years, suggesting that primary prevention is possible if estrogen replacement therapy is initiated early. As clinical studies on the effect of different progestogens combined with estrogens are scarce, a possible superiority of progestogens other than MPA remains to be proven.
Osteoporos Int. 2006 Jun 24; [Epub ahead of print]
The direct and indirect costs of the chronic management of osteoporosis: a prospective follow-up of 3440 active subjects.
Rabenda V, Manette C, Lemmens R, Mariani AM, Struvay N, Reginster JY.
Department of Public Health, Epidemiology and Health Economics, CHU, Bat. B23, 4000, Liege, Belgium.
INTRODUCTION: The objective of this study was to estimate the direct and indirect costs attributable to osteoporosis (OP) from a societal and a payer's perspective among active subjects living in Belgium and employed in the public workforce. MATERIALS AND METHODS: A cohort of 3440 subjects employed by the Liege City Council was followed for 6 months. The City Council employees were invited to fill a monthly log of the data related to their utilization of health resources (contacts with health professionals, medical examinations, drug use,...) due to OP. Information on work disability (number of days of sick leave) and on informal care (number of days off work incurred by active subjects in helping relatives or friends suffering from OP) was also collected. RESULTS: Of those asked to participate in the study, 1,811 subjects filled in at least one questionnaire. The mean duration of follow-up was 3.46 months. Self-reported prevalence of OP at inclusion was 5.3%. OP subjects were significantly older (52.7+/-6.1 years) than normal subjects (45.5+/-9.8 years) (p<0.05) and included more women (85.3 vs. 55.9%). Direct costs came to <euro>44.6 per OP patient-month: <euro>10.9 was spent on contact with health professionals, <euro>19.0 on medical examinations, <euro>12.1 on drugs and <euro>2.6 on hospitalizations. During this 6-month study, a total of 140 days of sick leave was recorded (mean: 0.4 per OP patient-month). From a payer's perspective, this loss in productivity yielded a mean cost of <euro>34.05 per OP patient-month. A mean number of days off work of 0.018 per active subject-month, attributable to informal care, was recorded. These days of inactivity represented, for the employer, a mean cost of <euro>1.8 per active subject-month. CONCLUSION: The results of this survey of a large sample of active subjects confirm that OP-related expenditures, both for medical care and for loss of productivity, are significant.
Diabetes Metab. 2006 Jun;32(3):251-5
Surrogate indexes vs. euglycaemic-hyperinsulinemic clamp as an indicator of insulin resistance and cardiovascular risk factors in overweight and obese postmenopausal women.
Malita F, Karelis A, St-Pierre D, Garrel D, Bastard J, Tardif A, Prud'homme D, Rabasa-Lhoret R.
Department of Nutrition, Faculty of Medicine, University of Montreal, Montreal, Canada.
BACKGROUND: There is considerable interest in validating the most convenient method to estimate insulin sensitivity in clinical research protocols that could best indicate cardiovascular risk factors. To address this issue we examined the interrelationships of several cardiovascular risk factors with surrogate indexes such as fasting insulin, the homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI) and the revised QUICKI vs the euglycaemic-hyperinsulinemic (EH) clamp in a non-diabetic overweight or obese postmenopausal female population.DESIGN: Cross-sectional study involving 88 obese postmenopausal women (age: 57.5+/-5.0 yrs; body mass index: 32.52+/-4.4 kg/m2; percent body fat: 46.35+/-4.9%).METHODS: Insulin sensitivity was determined by the EH clamp technique as well as by surrogate indexes such as fasting insulin, HOMA, log HOMA, QUICKI and revised QUICKI. Body composition and body fat distribution were measured using dual energy x-ray absorptiometry and computed tomography, respectively.RESULTS: Correlations between insulin resistance indexes (fasting insulin, revised QUICKI, QUICKI, log HOMA, HOMA) vs glucose disposal were similar (range of r's=0.40 to 0.49), suggesting that no index was superior to another with respect to its relationship with the EH clamp. Correlations between the insulin resistance indexes with plasma lipids were comparable among all indexes, however, systolic blood pressure, visceral fat and C-reactive protein were moderately superior with index vs the EH clamp.CONCLUSION: Surrogate measures of insulin resistance, in particular fasting insulin, are simple tools appropriate for epidemiological studies that can be used as substitutes for the EH clamp to estimate glucose disposal and cardiovascular risk factors in overweight and obese postmenopausal women.
Eur J Obstet Gynecol Reprod Biol. 2006 Jun 22; [Epub ahead of print]
Effects of topical estradiol on the facial skin collagen of postmenopausal women under oral hormone therapy: A pilot study.
Patriarca MT, Goldman KZ, Dos Santos JM, Petri V, Simoes RS, Soares JM Jr, Simoes MJ, Baracat EC.
Department of Gynecology, Federal University of Sao Paulo, Sao Paulo, Brazil.
OBJECTIVE: To analyze the dermal collagen of 15 postmenopausal women who had being treated with systemic estrogen replacement before and after using topical a 0.01% estrogen treatment. METHODS: Fifteen patients were included in this clinical trial using the systemic estrogen therapy for at least 1 year (minimum and maximum lengths of therapy were 13 and 40 months, respectively). A facial punch was performed in the preauricular area for collecting samples before and after the 16 weeks of treatment. Blood samples were also collected for estradiol level determination. The morphometric determination of epithelial and dermal thickness as well as dermal collagen were measured using a suitable software. The paired Student's t-test was used for statistical analysis. RESULTS: The epithelial and dermal thickness enhanced after the topic estrogen therapy (P<0.01). The amount of collagen significantly increased after 16 weeks of treatment (P<0.001). The estrogen levels did not significant increase after the topical therapy (P>/=0.05). CONCLUSION: Our data suggested that topical estrogen associated to systemic estrogen therapy seems to increase the expression of skin collagen amount, which may prove to be beneficial for the postmenopausal facial skin.
J Womens Health (Larchmt). 2006 Jun;15(5):584-90
A review of drospirenone for safety and tolerability and effects on endometrial safety and lipid parameters contrasted with medroxy-progesterone acetate, levonorgestrel, and micronized progesterone.
Shulman LP.
Department of Obstetrics and Gynecology, Division of Reproductive Genetics and Graduate Program in Genetic Counseling, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Background: Drospirenone, a novel synthetic progestin, possesses characteristics more like natural progesterone than other synthetic progestins, such as medroxyprogesterone acetate and levonorgestrel. The antiandrogenic and antimineralocorticoid properties of drospirenone may, in the context of menopausal management, provide potential novel benefits in its effect on lipids and blood pressure while reducing the occurrence of water retention, acne vulgaris, and hirsutism. Methods: This review compares safety and tolerability data from clinical trials of drospirenone, medroxyprogesterone acetate, levonorgestrel, and micronized progesterone. Results: Results suggest that drospirenone possesses a generally well-accepted side effect profile and resembles comparator oral progestogens in conferring endometrial protection with no significant effect on weight. One study indicates that drospirenone may have a benign effect on lipid parameters, having been seen to significantly lower total cholesterol and lowdensity lipoprotein levels while maintaining high-density lipoprotein and triglyceride levels. Drospirenone also differs from the other progestogens in lowering blood pressure levels in hypertensive patients while having a mild blood pressure-lowering effect on nonhypertensive patients. Conclusions: Among pharmacological options for menopause management, drospirenone may provide certain advantages over other progestogens in its effect on risk factors for cardiovascular disease and, thus, constitutes a useful addition to the menopausal armamentarium.
Pharmacoepidemiol Drug Saf. 2006 Jun 22; [Epub ahead of print
Changes in pattern of use, clinical characteristics and persistence rate of hormone replacement therapy among postmenopausal women after the WHI publication.
Guay MP, Dragomir A, Pilon D, Moride Y, Perreault S.
Faculty of Pharmacy, University of Montreal, Montreal, Canada.
The WHI was stopped prematurely because of an increased risk of breast cancer, stroke and cardiovascular diseases (CVD) in the hormone replacement therapy (HRT) arm of the trial. Changes in the use of HRT are expected.OBJECTIVE: To assess the impact of the Women's Health Initiative (WHI) publication on the rate of HRT prescription, and the clinical characteristics and persistence rate of new users and its determinants. METHODS: From the RAMQ databases, the total numbers of HRT prescriptions, and of new HRT's users were calculated between 2 January 1998 and 31 May 2003. To assess the clinical characteristics of women, two retrospective cohorts of new HRT's users were constructed before (pre-WHI) and after (post-WHI) the WHI study publication. The persistence rate after 1 year of follow-up was estimated using a Kaplan-Meier analysis. Cox regression models were used to estimate the rate ratio of HRT cessation. RESULTS: The total numbers of HRT users and of new users declined respectively by 28% and 50% in post-WHI. The standard dosage of HRT was significantly less used, while the proportion of women with risk factors of CVD or at very high risk of coronary artery disease (CAD) did not change. The rate of persistence in the pre-WHI cohort was 59% compared to 45% in the post-WHI (p < 0.0001), and women with risk factors of CVD or at very high risk of CAD were less likely to cease their HRT. CONCLUSION: One year after publication, significant changes had already occurred in the trends of use, women's characteristics and estrogen dosage. No change in the proportion of new users with CVD risk factors or at very high risk of CAD was seen.
AJR Am J Roentgenol. 2006 Jul;187(1):73-80
How predictive is breast arterial calcification of cardiovascular disease and risk factors when found at screening mammography?
Kataoka M, Warren R, Luben R, Camus J, Denton E, Sala E, Day N, Khaw KT.
Department of Radiology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
OBJECTIVE: The purpose of this study was to examine the relationship between breast arterial calcification (BAC), commonly found on mammography, and cardiovascular disease and its risk factors. SUBJECTS AND METHODS: The study population, nested within the European Prospective Investigation of Cancer-Norfolk (EPIC-Norfolk) cohort study, consisted of 1,590 women older than 55 years, not taking hormone replacement therapy, and with available screening mammograms. Mammograms were coded by three radiologists for presence or absence of BAC. History of coronary heart disease (CHD), stroke, and diabetes and risk factors for cardiovascular disease (including smoking status, body mass index [BMI], blood pressure, diabetes, and glycosylated hemoglobin [HbA1c]) were independently measured from health examinations in the EPIC study. RESULTS: The prevalence of BAC was 16.0%. Women with BAC were significantly older than those without it. BAC was associated with prevalent CHD, but not stroke. The odds ratio of having CHD was 2.54 (95% confidence interval, 1.03-6.30). The sensitivity and specificity were 32.4% and 85.5%, respectively. Except for smoking, which showed an inverse association, there was no consistent significant association of BAC with cardiovascular disease risk factors including BMI, diabetes, HbA1c, or lipids. CONCLUSION: BAC found on mammograms was associated with prevalent CHD after adjustment for age, but with low sensitivity. BAC may provide additional information toward identifying cardiovascular disease risk among otherwise healthy women.
Gynecol Endocrinol. 2006 Jun;22(6):318-23
Hypoactive sexual desire disorder in postmenopausal women.
Nappi RE, Wawra K, Schmitt S.
Department of Obstetrics and Gynecology, University of Pavia, Pavia, Italy.
Decreases in sex hormone levels with menopause may bring about a number of consequences in women's general health and sexual well-being, especially when levels decline suddenly and prematurely, as in surgical menopause. In addition to the well-established role of estrogens in preserving the biological basis of sexual response, there is emerging evidence that androgens are significant independent determinants affecting sexual desire, activity and satisfaction, as well as mood, energy and other components of women's health. Hypoactive sexual desire disorder (HSDD), a persistent absence of sexual fantasies or thoughts and/or desire for and receptivity to sexual activity that causes personal distress, is experienced by some postmenopausal women. Even though conventional hormone therapy with estrogens or estrogens and progestogens may be effective for vaginal atrophy, increasing vaginal lubrication and reducing dyspareunia, it has not been shown to consistently increase sexual desire or activity and many women with sexual dysfunction remain unresponsive. Several recent, large, phase III studies have shown that the addition of transdermal testosterone to conventional hormone therapy can be helpful in surgically menopausal women presenting with HSDD. After 24 weeks of treatment in these studies, testosterone-treated women experienced significantly greater increases in satisfying sexual activity and sexual desire, and greater decreases in distress, than placebo-treated women. Accurate clinical assessment and individualized management of sexual symptoms are fundamentally important for all menopausal women with HSDD or other sexual problems.
Metabolism. 2006 Jul;55(7):972-9
Effects of raloxifene on lipid and lipoprotein levels in postmenopausal osteoporotic women with and without hypertriglyceridemia.
Dayspring T, Qu Y, Keech C.
North Jersey Institute of Menopausal Lipidology, Wayne, NJ 07470, USA.
This post hoc analysis reports the effects of raloxifene on lipids and lipoproteins in 2659 women with either normal (</=150 mg/dL) or high (>150 mg/dL) triglyceride levels from a substudy of the Multiple Outcomes of Raloxifene Evaluation (MORE) trial. In both triglyceride subgroups, raloxifene significantly improved low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, apolipoprotein A-I, and fibrinogen compared with placebo (P < .05). After raloxifene treatment, women with high triglycerides experienced an equal or more robust reduction in cholesterol, lipoprotein parameters, and ratios of total cholesterol to HDL-C and non-HDL-C to HDL-C than was observed in women with normal triglycerides (P < .05). Mean levels of low-density lipoprotein cholesterol and apolipoprotein B were reduced by 16.5% and 15.8%, respectively, in women with high triglycerides, and by 12.7% and 11.3%, respectively, in women with normal triglycerides. These findings further substantiate that raloxifene improves concentrations of both cholesterol and beta-lipoprotein. The subgroup of women with high triglycerides, who have elevated cardiovascular risk, appear to derive at least equal, if not greater, overall effect on lipid and lipoprotein lowering with raloxifene.
Metabolism. 2006 Jul;55(7):953-9
Estrogen treatment improves arterial distensibility, fibrinolysis, and metabolic profile in postmenopausal women with type 2 diabetes mellitus.
Sztejnsznajd C, da Silva ME, Nussbacher A, Gebara OE, D'Amico EA, Rocha DM, da Rocha TR, Dos Santos RF, Wajngarten M, Fukui RT, Correia MR, Wajchenberg BL, Ursich MJ.
Gynecology Department, Fundacao Pro-Sangue Hemocentro-SP, Sao Paulo, SP, Brazil; InCor of Hospital das Clinicas of the University of Sao Paulo Medical School, Sao Paulo, SP, Brazil.
The effects of isolated estrogen therapy on the hemostatic system and arterial distensibility were determined in postmenopausal females with type 2 diabetes mellitus. This was a prospective nonrandomized study of 19 subjects (age, 56.2 +/- 4.7 years; body mass index, 27.8 +/- 2.4 kg/m(2) [mean +/- SD]). Inclusion was done after 2 months of glycemic and blood pressure control. The study consisted of 4 months of placebo treatment immediately followed by an equal period of oral conjugated equine estrogens (CEE) 0.625 mg/d. Measures included anthropometrics, a metabolic profile (oral glucose tolerance test and fasting glycated hemoglobin, total cholesterol and fractions, and triglyceride levels), and coagulation and fibrinolytic factors at the end of the placebo period and after 4 months of oral CEE. Conjugated equine estrogen therapy decreased plasminogen activator inhibitor 1 (placebo x CEE: 16.33 +/- 9.11 x 13.08 +/- 8.87 UI/mL, P < .03) and increased factor VIII activity (134.11% +/- 46.18% x 145.33% +/- 42.04%, P < .04). An increase in high-density lipoprotein cholesterol levels (placebo x CEE: 42.47 +/- 6.80 x 53.32 +/- 11.89 mg/dL, P < .01), and a decrease in glycated hemoglobin (8.45% +/- 1.30% vs 7.58% +/- 1.06%, P < .02) and in fasting glucose levels (121.51 +/- 21.05 x111.21 +/- 20.74 mg/dL, P = .02) followed CEE therapy. Pulse wave velocity and augmentation index were performed by applanation tonometry and were obtained at the end of the placebo period (placebo), again after an intravenous load of 1.25 mg of CEE (short-term), and after 4 months of oral CEE (long-term). A significant decrease in central (carotid-femoral) pulse wave velocity was seen both after short- and long-term CEE (placebo vs short-term vs long-term: 9.36 +/- 2.58 vs 8.26 +/- 2.20 vs 7.98 +/- 1.90 m/s, respectively [analysis of variance, P < .03]; placebo vs short-term, P < .05; placebo vs long-term, P < .01), whereas augmentation index decreased only after long-term CEE (placebo vs short-term vs long-term: 39.14% +/- 6.94% vs 37.48% +/- 8.67% vs 34.3.3% +/- 8.11% [analysis of variance, P < .05], respectively; placebo vs long-term, P < .05). Long-term administration of CEE leads to an improvement in fibrinolysis and arterial distensibility, associated with an increase of the intrinsic coagulation pathway in postmenopausal women with type 2 diabetes mellitus.
Cancer Causes Control. 2006 Aug;17(6):843-50
Varying levels of family history of breast cancer in relation to mammographic breast density (United States).
Crest AB, Aiello EJ, Anderson ML, Buist DS.
Institute for Public Health Genetics, University of Washington, Seattle, WA, USA.
OBJECTIVE: We examined the relationship between breast cancer family history and mammographic breast density. METHODS: Participants included 35,019 postmenopausal women aged >/=40 years enrolled in a population-based mammography screening program. We collected data on the number and type of 1st and 2nd degree female relatives with a history of breast cancer and their ages at diagnosis. We used the Breast Imaging Reporting and Data Systemtrade mark breast density categories to identify women with fatty (1 = almost entirely fatty or 2 = scattered fibroglandular tissue) and dense (3 = heterogeneously dense or 4 = extremely dense) breasts. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals for dense (N = 18,111) compared to fatty breasts (N = 16,908). RESULTS: The odds of having dense breasts were 17% greater for women with affected 1st degree relatives than women with no family history. The odds increased with more affected 1st degree relatives [>/=3 vs. none (OR = 1.46; 1.05-2.01)] and among women with >/=1 affected 1st degree relative diagnosed <50 years (OR = 1.22; 1.10-1.34). CONCLUSIONS: Having a family history of breast cancer was more strongly associated with mammographic breast density when the affected relatives were more genetically similar. There may be common, yet undiscovered, genetic elements that affect breast cancer and mammographic breast density.
Maturitas 2006; 54S:S15
Tibolone and endometrial safety: results from THEBES, a randomized 2-year study comparing tibolone with CEE/MPA
Alec Ferenczy1, D Archer2, J Rymer3, SO Skouby4, W Den Hollander5, F Helmond6
1McGill University and SMBD-Jewish General Hospital, Montreal, Que., Canada; 2CONRAD Clinical Reasearch Center, Norfolk, VA, USA; 3Department of Women's Health, St Thomas' Hospital, London, UK; 4Department of Obstetrics & Gynecology, Frederiksberg Hospital, Copenhagen, Denmark; 5NV Organon, Oss, The Netherlands; 6Organon International, Roseland, NJ, USA
Background and objectives: THEBES was a 2-year, prospective, multicountry, multisite, randomized, double-blind, controlled clinical trial to determine the endometrial response to oral tibolone (1.25 and 2.5 mg/day) versus continuous, combined, daily oral CEE plus MPA (0.625 mg + 2.5 mg/day). Methods: Endometrial lining was assessed at baseline and after 1 and 2 years by transvaginal ultrasound and suction biopsy curettage. Vaginal bleeding patterns were self-recorded in a bleeding episode log. Results: Three thousand two hundred and forty healthy postmenopausal women, mean age 54, were randomized in a 1:1:2 ratio (tibolone 1.25; tibolone 2.5; CEE/MPA). Mean baseline, double wall endometrial thickness was 3.1 mm for the combined tibolone group and 3.0 mm for the CEE/MPA group and 3.6 and 3.4 mm after 2 years treatment. Endometrial histology during 2 years of observation in both tibolone and CEE/MPA intent-to-treat groups is presented in Table 1. During the entire treatment period, 75% of the women in the tibolone group experienced no bleedingor spotting compared to 45% of the women treated with CEE/MPA. Conclusion: This study provides evidence that the endometrial morphology profile in postmenopausal women is similar with tibolone and CEE/MPA.
Kardiol Pol. 2006 Jun;64(6):573-580
Risk factors of atherosclerosis in premenopausal women with a sense of well-being. A pilot study.
Lukaszewicz R, Lukaszewicz M, Ceremuzynski L.
Centrum Medyczne Ksztalcenia Podyplomowego, Oddzial Kardiologii, Szpital Grochowski, Poland
Introduction: Women before menopause are thought to be relatively safe from cardiovascular disease due to the protective effects of oestrogens, although one may question this opinion with regards to women with many typical risk factors. However, because of the shortage of data concerning prevalence of risk factors in young women, it is not known whether this phenomenon is confined to a limited group or affects many women. Aim: The purpose of this study was to determine the prevalence of either typical risk factors of atherosclerosis or emotional disturbances that might increase the probability of coronary artery disease in young women. Methods: The study group involved 62 premenopausal women with a sense of well-being (regular menstruations, activity of serum follicle stimulating hormone < 15 IU/L). Mean age of women was 43.5 years. Total cholesterol, LDL and HDL fractions, triglyceride, lipoprotein (a) and homocysteine concentrations were examined and body mass index was calculated. A psychological examination assessing depression and neuroticism intensity was also performed. Results: Total cholesterol concentration (mean values +/- SD, expressed as mg%, percentage of abnormal results are given in brackets) was 206.3+/-35.8 (67.2), LDL cholesterol 124.3+/-30.2 (55.1), HDL cholesterol HDL 62.5+/-14.8 (6.9), triglyceride 101+/-60.1 (13.8), lipoprotein (a) 18.9+/-17.5 (44.8). Body mass index was 25.2+/-4.1 (41.3). History of smoking was positive in 27.4% and 6.5% of examined women had arterial hypertension. Coexistence of 4 to 5 aforementioned risk factors was noted in 27.4% of studied subjects. Mean homocysteine concentration was 10.7+/-2.1 micromol/L, while 41.3% of subjects had levels above the threshold of 11 micromol/l, commonly considered pathological. Symptoms of depression and neuroticism were seen in 30.5% and 22.5% of women, respectively. Conclusions: This pilot study of young women demonstrated that, in contrary to popular belief, this population is vulnerable to cardiovascular disease due to high prevalence of many risk factors.
J Gen Intern Med. 2006 Jun;21(6):636-41
Correlates of use of antifracture therapy in older women with low bone mineral density.
Ryder KM, Shorr RI, Tylavsky FA, Bush AJ, Bauer DC, Simonsick EM, Strotmeyer ES, Harris TB.
Health ABC Study. The University of Tennessee Health Science Center, Memphis, TN, USA.
BACKGROUND: Guidelines exist for treatment of low bone mineral density (BMD). Little is known about patient characteristics associated with use of treatment. OBJECTIVES: To determine patient-related correlates of medication use following screening dual x-ray absorptiometry (DXA) of older adults. DESIGN: Secondary analysis of a prospective cohort study. SETTING: Pittsburgh, PA and Memphis, TN. PARTICIPANTS: Community-dwelling women between the ages 70 and 79 years enrolled in the Health, Aging, and Body Composition (Health ABC) Study. MEASUREMENTS: Risk factors for fracture and BMD of the hip were assessed at baseline. Patients and their community physicians were supplied the results of the DXA scan. Prescription and over-the-counter medication use was collected at annual exams for 2 years. RESULTS: Of 1,584 women enrolled in Health ABC, 378 had an indication for antifracture therapy and were not receiving such treatment at baseline. By the second annual follow-up examination, prescription antiresorptive medication was reported in 49 (13.0%), whereas 65 (17.2%) received calcium and/or vitamin D supplementation. In adjusted models, the strongest predictor for use of any antifracture medicine was presence of osteoporosis [vs osteopenia, odds ratio (OR), 2.9 (1.7 to 4.7)], white race [OR, 2.6 (1.5 to 4.8)], and receipt of the flu shot [OR, 2.2 (1.3 to 3.8)]. Neither a history of falls nor prior fracture was associated with use of antifracture medications. CONCLUSION: Even when physicians of study participants were provided with DXA scan results, 70% of older high-functioning women with an indication for therapy did not start or remain on an antifracture therapy. Substantial room for improvement exists in fracture prevention following a diagnosis of low BMD-especially among women with a history of falls, prior fractures, and among black women.
Fertil Steril. 2006 Jun 24; [Epub ahead of print]
Tibolone and estradiol plus norethisterone acetate similarly influence endothelium-dependent vasodilatation in healthy postmenopausal women.
Cagnacci A, Renzi A, Cannoletta M, Pirillo D, Arangino S, Volpe A.
Department of Obstetrics, Gynecology and Pediatrics, University Hospital of Modena, Modena, Italy.
In healthy postmenopausal women, E(2) plus norethisterone acetate (1 mg + 0.5 mg) or tibolone (2.5 mg) similarly modify flow-mediated endothelium-dependent vasodilatation. The effect is dependent on baseline vasodilator reserve, with low values being augmented by either treatment.
Hum Reprod Update. 2006 Jun 28; [Epub ahead of print]
Hormones and cardiovascular health in women.
Crosignani PG.
Department of Obstetrics and Gynecology, University of Milano, Via Commenda 12, 20122 Milano, Italy.
Cardiovascular diseases (CVDs) may have their origin before birth: the combination of being small at birth and having an overly rich post-natal diet increases the likelihood of obesity and of acquiring a specific metabolic syndrome in adulthood that carries an increased risk of CVD. The incidence of CVD and mortality is very low in women of reproductive age but rises to a significant level in older women. In this article, we discuss CVD in relation to hormonal contraception, pregnancy and polycystic ovarian syndrome (PCOS) in younger women and menopause in older women. Women with PCOS have a higher risk of diabetes and hypertension, but studies to date have not shown an effect on CVD events. Use of combined hormonal contraception has only small effects on CVD because of the low baseline incidence of myocardial infarction (MI), stroke and venous thromboembolism (VTE) among young women. Women with existing risk factors or existing CVD, however, should consider alternative contraception. In pregnancy, CVD is rare, although, in the West, it now accounts for a significant proportion of maternal mortality as the frequency of obstetrical causes of mortality has substantially declined. The frequency of VTE is 15 per 10 000 during pregnancy and the post-partum period. In older women, menopause causes a slightly higher risk of MI after allowing for age, although there is substantial heterogeneity in the results of studies on menopause and age at menopause and MI. A larger effect might have been expected, because estrogen reduces the risk of developing atherosclerosis in premenopausal women, whereas in post-menopausal women who may have established atherosclerotic disease, estrogen increases the risk of myocardial disease through the effects on plaque stability and clot formation. Recent trial results indicate that hormone treatment in menopause does not favourably affect the risk of MI, stroke or other vascular disease. Thus, prevention of CVD should rely on diet and fitness, low-dose aspirin and treatment of hypertension, hyperglycaemia and hyperlipidaemia.
Nucleic Acids Res. 2006 Jun 28;34(11):3279-87. Print 2006
Genes invoked in the ovarian transition to menopause.
Zimon A, Erat A, Von Wald T, Bissell B, Koulova A, Choi CH, Bachvarov D, Reindollar RH, Usheva A.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School Boston, MA 02215, USA.
Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the aging-specific decline in ovarian function are almost completely unknown. To provide the first gene-protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function.
Hum Reprod. 2006 Jun 28; [Epub ahead of print
Differential effects of oral conjugated equine estrogen and transdermal estrogen on atherosclerotic vascular disease risk markers and endothelial function in healthy postmenopausal women.
Ho JY, Chen MJ, Sheu WH, Yi YC, Tsai AC, Guu HF, Ho ES.
Department of Obstetrics and Gynecology, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Taichung, Taiwan.
BACKGROUND: Recent studies have revealed that HRT may increase the risk for atherosclerotic vascular disease (ASVD). METHODS: We investigated the effects of HRT via different administration routes on the markers for ASVD and endothelial function in healthy postmenopausal women. The oral HRT group (n = 18) received conjugated equine estrogen 0.625 mg/day; the transdermal HRT group (n = 18) received 17beta-estradiol (E2) gel 0.6 mg/day for 6 months. The control group (n = 30) had no treatment for 6 months. RESULTS: The C-reactive protein (CRP) rose from 0.129 +/- 0.116 to 0.752 +/- 0.794 mg/dl (P < 0.01) in the oral HRT group but remained unchanged in the transdermal HRT and control groups. The flow-mediated vasodilation (FMD) in the brachial artery was increased significantly by HRT from 6.0% before oral HRT to 14.7% after oral HRT (P < 0.001) and from 5.9% before transdermal HRT to 13.9% after transdermal HRT (P = 0.001). CONCLUSIONS: These data suggest that oral estrogen induces ASVD risk by increasing acute inflammation; however, transdermal estrogen avoids this untoward effect. Additionally, transdermal estrogen exerts a positive effect on endothelial function similar to that of oral estrogen. Therefore, the transdermal route might be favourable in terms of ASVD risks.
Int J Gynecol Cancer. 2006 May-Jun;16(3):1069-74
Normal appearing endometrial cells in cervical smears of asymptomatic postmenopausal women have predictive value for significant endometrial pathology.
Siebers AG, Verbeek AL, Massuger LF, Grefte JM, Bulten J.
Departments of Pathology, Epidemiology and Biostatistics, and Gynaecology and Obstetrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
The objective of this study was to determine whether postmenopausal asymptomatic women with normal endometrial cells in their smear are at higher risk for endometrial pathology compared with women without these cells. Histologic follow-up outcome and otherwise cytologic follow-up of 29,144 asymptomatic postmenopausal women was determined. Presence of normal endometrial cells, age, use of hormones, and reported elevated maturation index were assessed. The effect of each variable on outcome as well as the combined effect were evaluated. Prevalence rate of (pre)malignant uterine disease was significantly higher when normal endometrial cells were found in the cervical smear (6.5%) as compared to smears without these cells (0.2%), resulting in a relative risk of 40.2 (95% CI 9.4-172.2). Neither age nor hormone use or elevated maturation index showed significant impact on the outcome. Asymptomatic postmenopausal women with normal endometrial cells in their smear are at significant higher risk for (pre)cancerous endometrial lesion than women without these cells. These cases should be reported to the physician with an explicit comment that normal endometrial cells in a smear of a postmenopausal woman is an abnormal finding, possibly associated with significant endometrial pathology. It raises the question whether further gynecological examination would be more appropriate.
Arch Intern Med. 2006 Jun 26;166(12):1262-8.
Severe hot flashes are associated with chronic insomnia.
Ohayon MM.
Stanford Sleep Epidemiology Research Center, Stanford University School of Medicine, Palo Alto, Calif.
BACKGROUND: Because hot flashes can occur during the night, their presence has been frequently associated with insomnia in women with symptoms of menopause. However, many factors other than hot flashes or menopause can be responsible for insomnia, and several factors associated with insomnia in the general population are also commonly observed in perimenopausal and postmenopausal women who have hot flashes. METHODS: A random sample of 3243 subjects (aged >/=18 years) representative of the California population was interviewed by telephone. Included were 982 women aged 35 to 65 years. Women were divided into 3 groups according to menopausal status: premenopause (57.2%), perimenopause (22.3%), and postmenopause (20.5%). Hot flashes were counted if they were present for at least 3 days per week during the last month and were classified as mild, moderate, or severe according to their effect on daily functioning. Chronic insomnia was defined as global sleep dissatisfaction, difficulty initiating sleep, difficulty maintaining sleep, or nonrestorative sleep, for at least 6 months. Diagnoses of insomnia were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classification. RESULTS: Prevalence of hot flashes was 12.5% in premenopause, 79.0% in perimenopause, and 39.3% in postmenopause. Prevalence of chronic insomnia was reported as 36.5% in premenopause, 56.6% in perimenopause, and 50.7% in postmenopause (P<.001). Prevalence of symptoms of chronic insomnia increased with the severity of hot flashes, reaching more than 80% in perimenopausal women and postmenopausal women who had severe hot flashes. In multivariate analyses, severe hot flashes were significantly associated with symptoms and a diagnosis of chronic insomnia. Poor health, chronic pain, and sleep apnea were other significant factors associated with chronic insomnia. CONCLUSIONS: Severe hot flashes are strongly associated with chronic insomnia in midlife women. The presence of hot flashes should be systematically investigated in women with insomnia. Treating hot flashes could improve sleep quality and minimize the deleterious consequences of chronic insomnia.
Hypertension. 2006 Jun 26; [Epub ahead of print]
Effects of a New Hormone Therapy, Drospirenone and 17-{beta}-Estradiol, in Postmenopausal Women With Hypertension.
White WB, Hanes V, Chauhan V, Pitt B.
Division of Hypertension and Clinical Pharmacology, The Pat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington
Drospirenone (DRSP), a progestin with antialdosterone activity, has been developed for hormone therapy in combination with 17-beta-estradiol (E2) in postmenopausal women. We evaluated the antihypertensive efficacy and safety of various doses of DRSP and E2 and estradiol alone in postmenopausal women with hypertension using ambulatory and clinic blood pressure (BP) monitoring. This was a randomized, double-blind clinical trial of 3 doses of DRSP combined with estradiol, estradiol alone, and placebo in 750 postmenopausal women with stage 1 to 2 hypertension between 45 to 75 years. Ambulatory and clinic BPs, potassium, aldosterone, and lipid measurements and adverse events were evaluated in postmenopausal women with stages 1 to 2 hypertension during 8 weeks of double-blind therapy. DRSP and E2 induced dose-related reductions in the ambulatory and clinic systolic BP with physiological increases in serum aldosterone. Significant decreases in 24-hour systolic pressure were observed at doses of 2 and 3 mg of DRSP combined with estradiol but not by estradiol alone or 1 mg of DRSP with estradiol. There were no significant changes from baseline in potassium in any treatment group. Small, significant reductions in total and low-density lipoprotein cholesterol occurred on all of the active treatments, and serum triglycerides did not change. Adverse event rates were low and similar across treatment groups. In conclusion, these data show that DRSP combined with E2 significantly reduces BP in postmenopausal women with hypertension and did not induce significant increases in serum potassium. These characteristics may lead to a new benefit for this novel hormone therapy in postmenopausal women with hypertension.
Int J Clin Pract. 2006 Jun 23; [Epub ahead of print]
Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study*
Cooper A, Drake J, Brankin E; THE PERSIST INVESTIGATORS.
Bridge Medical Centre, Crawley, UK.
Osteoporosis is a common and debilitating condition associated with significant morbidity and mortality. The efficacy and safety of oral bisphosphonates for the treatment of osteoporosis are well established. However, patient adherence and persistence on treatment are suboptimal. This randomised open-label multi-centre study of 6-months' duration compared persistence on treatment in postmenopausal women with osteoporosis receiving either once-monthly ibandronate plus a patient support programme (PSP), or once-weekly alendronate. To avoid falsely elevated persistence rates often associated with clinical trials, the study was designed to reflect everyday clinical practice in the UK and follow-up visits were limited to be consistent with the primary care setting. Analysis of the primary endpoint showed that persistence was significantly higher in the ibandronate/PSP group compared with the alendronate group (p < 0.0001). The estimated proportion of patients persisting with treatment at 6 months was 56.6% (306/541) and 38.6% (198/513) in the ibandronate/PSP and alendronate groups, respectively. Therefore, compared with alendronate, there was a 47% relative improvement in the proportion of patients persisting with treatment in the ibandronate/PSP group. Secondary endpoint measurements of adherence (e.g. proportion of patients remaining on treatment at study end; proportion of patients discontinuing from the study) were also significantly different in favour of ibandronate plus patient support. In summary, the PERSIST study demonstrated that persistence on treatment was increased in patients receiving once-monthly ibandronate plus patient support compared with once-weekly alendronate. Increased persistence on bisphosphonate treatment is expected to improve patient outcomes and decrease the social and economic burden of osteoporosis.