Selección de Resúmenes de Menopausia

                                                      Semana del 2 al 8 de Septiembre de 2009

                                   Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

 

Climacteric. 2009 Sep 2:1-8. [Epub ahead of print]

Risk of hypoactive sexual desire disorder and associated factors in a cohort of oophorectomized women.

Castelo-Branco C, Palacios S, Combalia J, Ferrer M, Traveria G.

Hospital Clinic, Faculty of Medicine, University of Barcelona.

Background Women with surgical menopause are at high risk of developing hypoactive sexual desire disorder (HSDD), which may cause sexual and emotional discomfort. Aim To determine the prevalence of HSDD and related risk factors in Spanish surgically postmenopausal women. Design Multicenter, cross-sectional study. Material and methods The Brief Profile of Female Sexual Function((c)) (B-PFSF((c))) questionnaire was given to 1136 surgically postmenopausal women between 18 and 81 years old (mean 52.1 +/- 7.1 years) attending gynecological consultations in different urban and rural areas in Spain, covering the country widely. Results From the entire sample, 1083 subjects were finally included. The mean score on the B-PFSF((c)) was 15.9 and a total of 74.4% of the patients presented total scores lower or equal to 20, indicating the risk of presenting with HSDD. The possibility to be at risk of HSDD increased with age from 65.9% in the age group <45 years old to 76.6% in the age group >/=55 years old. Non-users of hormone replacement therapy presented a higher risk of HSDD (odds ratio 2.1; 95% confidence interval 1.3-3.4); the risk was increased as well when the time elapsed since surgical menopause was <5 years (odds ratio 1.8; 95% confidence interval 1.0-3.0). Conclusion Nearly three out of four women who had undergone bilateral oophorectomy were at risk of suffering HSDD; this risk was increased when less than 5 years since surgical menopause had elapsed. The use of hormone replacement therapy was associated with lower HSDD risk.

 

 

Climacteric. 2009 Sep 1:1-11. [Epub ahead of print]

Risk of gynecological cancers in users of estradiol/dydrogesterone or other HRT preparations.

Schneider C, Jick SS, Meier CR.

Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Switzerland.

Objectives Use of postmenopausal hormone replacement therapy (HRT) has been associated with an elevated risk of gynecological cancers. There is evidence that the effect differs with the type of hormone used. Dydrogesterone is pharmacologically very similar to progesterone. Methods We used the UK-based General Practice Research Database (GPRD) to conduct a follow-up study with a nested case-control analysis. We assessed and compared the risk of developing breast, ovarian, endometrial/uterine or cervical cancer in estradiol/dydrogesterone (E/D) users, users of other HRT, or non-users of HRT. Results The breast cancer incidence rates were 2.41 (95% confidence interval (CI) 1.81-3.15), 3.28 (95% CI 3.01-3.55) and 3.16 (95% CI 2.92-3.42) per 1000 person-years for E/D users, users of other HRT or non-users, respectively. In a direct comparison, the breast cancer risk for E/D users was lower than for users of other HRT (odds ratio 0.76, 95% CI 0.56-1.05). The incidence rates of other gynecological cancers were similar or also slightly lower for E/D users than for users of other HRT. Conclusion This study provides evidence that the risk of developing gynecological cancers with E/D use of several months to a few years is similar to the risks of developing gynecological cancer without HRT or use of other HRT.

 

 

Climacteric. 2009 Sep 1:1-10. [Epub ahead of print]

Comparative effects of conventional hormone replacement therapy and tibolone on climacteric symptoms and sexual dysfunction in postmenopausal women.

Ziaei S, Moghasemi M, Faghihzadeh S.

Departments of Obstetrics & Gynecology.

Objective To compare the effects of tibolone with those of conventional hormone replacement therapy on climacteric symptoms and sexual function in postmenopausal women. Materials and methods In a randomized, controlled trial, 140 postmenopausal women were allocated into three groups. Of the subjects included, 47 women received 2.5 mg tibolone + one Cal+D tablet (500 mg calcium and 200 IU vitamin D) daily; 46 women received 0.625 mg conjugated equine estrogen + 2.5 mg medroxyprogesterone (CEE/MPA) + one Cal+D tablet daily; and 47 women received only one Cal+D tablet as the control group. The Greene Climacteric Scale (GCS) questionnaire was used to detect the efficacy of treatment on climacteric symptoms. Rosen's Female Sexual Function Index (FSFI) was used for sexual function evaluation. Sex hormone binding globulin (SHBG), free estradiol index (FEI) and free testosterone index (FTI) were measured before and after treatment. The women were followed up for 6 months Results After treatment, all subscores in the GCS improved in the tibolone and CEE/MPA groups (p < 0.01), except the sexual subscore in the CEE/MPA group, compared with baseline. There were significant differences in the FSFI in the tibolone and CEE/MPA groups in comparison to the control group after treatment. Tibolone, in comparison to CEE/MPA, significantly lowered SHBG levels and increased the FTI and FEI and improved the desire, arousal and orgasm sexual domains of the FSFI (p < 0.001). Conclusion Tibolone may be an alternative to conventional hormone replacement therapy in the treatment of climacteric symptoms and sexual dysfunction in postmenopausal women.

 

 

Arch Womens Ment Health. 2009 Sep 4. [Epub ahead of print]

Association between depressive symptoms and reproductive variables in a group of perimenopausal women attending a menopause clinic in México City.

Flores-Ramos M, Heinze G, Silvestri-Tomassoni R.

Psychiatry and Mental Health Department, Universidad Nacional Autónoma de México (UNAM), Soledad 25-2, Col. Florida, CP 01030, México, D.F, México, flores_ramos@hotmail.com.

The aim of this study was to explore the association between depressive symptoms and some variables related to the reproductive life, such as history of premenstrual dysphoric disorder, antecedent of postpartum depression, previous use of hormonal contraceptives, and current hot flushes, in a group of perimenopausal women attending a menopause clinic. Perimenopausal women, 45 to 55 years old, who had not received hormonal replacement therapy and/or psychotropic medication, were invited to participate in this study. 141 perimenopausal women were included; we obtained their psychiatric and gynecological data, and we evaluated their depressive symptomatology using the CES-D scale. There were a significantly higher number of cases of previous depressive episodes, PMDD and PPD history in depressed patients compared with non-depressed women; current hot flushes prevalence was similar between depressed and non-depressed women. Patients with a PMDD history were more likely to have experienced previous depressive episodes, a PPD history, and high levels of depression. Variables associated with the level of depression were a previous history of PMDD, current hot flushes, and previous depressive episodes. The occurrence of perimenopausal depression is related to a previous history of PMDD, PPD, and depressive episodes; hot flushes only increase the severity of the depressive episode.

 

 

Menopause. 2009 Aug 27. [Epub ahead of print]

Burden associated with chronic sleep maintenance insomnia characterized by nighttime awakenings among women with menopausal symptoms.

Bolge SC, Balkrishnan R, Kannan H, Seal B, Drake CL.

From the 1Consumer Health Sciences, Princeton, NJ; 2Schools of Pharmacy and Public Health, The University of Michigan, Ann Arbor, MI; 3Sanofi-Aventis, Bridgewater, NJ; and 4Henry Ford Hospital Sleep Center and Psychiatry and Behavioral Neurosciences, Wayne State College of Medicine, Detroit, MI.

OBJECTIVE:: The aim of this study was to quantify the burden associated with chronic sleep maintenance insomnia characterized by nighttime awakenings (CINA) among women with menopausal symptoms. METHODS:: Data were obtained from the 2006 US National Health and Wellness Survey, an annual cross-sectional study of US adults 18 years or older. Analyses were limited to female respondents currently experiencing symptoms of menopause. The definition of CINA was experiencing nighttime awakenings at least twice per week for more than 1 month that have moderate to severe impact on daily life and not experiencing difficulty falling asleep. No insomnia was defined as not self-reporting insomnia, sleep difficulties, or sleep symptoms. Outcomes included resource utilization in the past 6 months, Work Productivity and Activity Impairment questionnaire, and Medical Outcomes Study Short-Form Health Survey (SF-8). Linear regression models were developed to assess the independent associations of CINA on outcomes, while adjusting for demographics and comorbidity. RESULTS:: Among women with menopausal symptoms, 141 met the criteria for CINA and 1,305 met the criteria for no insomnia. Adjusting for demographics and comorbidity, those experiencing CINA had 0.1 (P = 0.041) more emergency department visits, 20.8% (P < 0.001) greater activity impairment, and SF-8 physical and mental summary scores that were 4.7 (P < 0.001) and 5.4 (P < 0.001) points, respectively, lower than those of women who are not experiencing insomnia. Among women with menopausal symptoms employed full-time, those experiencing CINA had greater impairment while working (presenteeism; 17.3%, P < 0.001) and overall (16.1%, P < 0.001) than did those who are not experiencing insomnia. CONCLUSIONS:: Among women with menopausal symptoms, CINA in relative isolation was associated with a significant negative impact on healthcare utilization and its associated costs, health-related quality of life, and work productivity.

 

 

Arch Womens Ment Health. 2009 Sep 3. [Epub ahead of print]

Neuroactive steroids after estrogen exposure in depressed postmenopausal women treated with sertraline and asymptomatic postmenopausal women.

Morgan ML, Rapkin AJ, Biggio G, Serra M, Pisu MG, Rasgon N.

Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA, 90095-1740, USA.

Neuroactive steroids (NAS) allopregnanolone (ALLO), Allotetrahydrodeoxycorticosterone (THDOC) and dehydroepiandrosterone (DHEA) are important in the regulation of mood and behavior. Knowledge about these steroids in postmenopausal depression and the effect of estrogen on NAS is lacking. We elected to determine if there were differences in NAS between postmenopausal depressed women and age matched controls. We also investigated the effect of estradiol on NAS in post menopausal depressed women receiving a selective serotonin reuptake inhibitor (SSRI), and in non-depressed postmenopausal controls. As part of a previously published double blind study on estrogen acceleration of antidepressant action, post menopausal women with major depression receiving sertraline and healthy non depressed controls were randomized to transdermal estrogen patch 0.1 mg or placebo. NAS were measured at baseline and after 10 weeks of treatment. Depressed subjects were treated with sertraline 50 mg/day to 100 mg/day for 9 weeks. At the baseline and after treatment ALLO and DHEA were significantly lower in depressed women compared to controls. Although all depressed subjects experienced a positive clinical response, estrogen administration was not associated with changes in NAS in either the depressed or the asymptomatic postmenopausal women. The lower ALLO and DHEA in postmenopausal depressed women suggests that symptoms of depression may be influenced by the synthesis or fluctuation of these NAS. Estradiol exposure did not alter ALLO, DHEA, or THDOC, implying these NAS are unlikely to play a role in any mood changes in post menopausal women given estrogen therapy.

 

 

Osteoporos Int. 2009 Sep 1. [Epub ahead of print]

Impact of supplementation with bicarbonate on lower-extremity muscle performance in older men and women.

Dawson-Hughes B, Castaneda-Sceppa C, Harris SS, Palermo NJ, Cloutier G, Ceglia L, Dallal GE.

Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA, Bess.Dawson-Hughes@Tufts.edu.

This study describes the impact of bicarbonate treatment for 3 months on net acid excretion (NAE), nitrogen excretion, and muscle performance in older men and women. Bicarbonate reduced NAE, and the decrement was associated with a decrease in nitrogen excretion. Treatment also improved muscle power and endurance in the women. INTRODUCTION: Bicarbonate enhances muscle performance during strenuous exercise, but its effect on performance during normal activity in older subjects is unknown. METHODS: In this trial, healthy subjects age 50 and older were randomized to 67.5 mmol of bicarbonate or to no bicarbonate daily for 3 months. Changes in lower-extremity muscle power, endurance, urinary nitrogen, and NAE were compared across treatment groups in the 162 participants included in the analyses. RESULTS: In the men and the women, bicarbonate was well tolerated, and as expected, it significantly decreased NAE. The change in NAE correlated with change in nitrogen excretion in women (r = 0.32, P = 0.002) with a similar trend in men (r = 0.23, P = 0.052). In the women, bicarbonate increased double leg press power at 70% one repetition maximum by 13% (P = 0.003) compared with no bicarbonate and improved other performance measures. Treatment with bicarbonate had no significant effect on muscle performance in the men. CONCLUSIONS: Ingestion of bicarbonate decreased nitrogen excretion and improved muscle performance in healthy postmenopausal women. The bicarbonate-induced decline in NAE was associated with reduced nitrogen excretion in both men and women. These findings suggest that bicarbonate merits further evaluation as a safe, low-cost intervention that may attenuate age-related loss of muscle performance and mass in the elderly.

 

 

Selección de Resúmenes de Menopausia

                                                      Semana del 9 al 15 de Septiembre de 2009

                                   Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

 

Clin Endocrinol (Oxf). 2009 Sep 10. [Epub ahead of print]

Reducing fracture risk with calcium and vitamin D.

Lips P, Bouillon R, van Schoor NM, Vanderschueren D, Verschueren S, Kuchuk N, Milisen K, Boonen S.

Department of Endocrinology and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.

SUMMARY Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, due to different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance. This article tries to define the types of patients, both at risk of osteoporosis and with established disease, who may benefit from calcium and vitamin D supplementation. The importance of adequate compliance in these individuals is also discussed. Calcium and vitamin D therapy has been recommended for older persons, either frail and institutionalized or independent, with key risk factors including decreased bone mineral density, osteoporotic fractures, increased bone remodeling due to secondary hyperparathyroidism and increased propensity to falls. In addition, treatment of osteoporosis with a bisphosphonate was less effective in patients with vitamin D deficiency. Calcium and vitamin D supplementation is a key component of prevention and treatment of osteoporosis unless calcium intake and vitamin D status are optimal. For primary disease prevention, supplementation should be targeted to those with dietary insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been proposed to define vitamin D insufficiency (as opposed to adequate vitamin D status), ranging from 30 to 100 nmol/l. Based on the relationship between serum 25(OH)D, bone mineral density, bone turnover, lower extremity function and falls, we suggest that 50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D insufficiency. Supplementation should therefore generally aim to increase 25(OH)D levels within the 50-75 nmol/l range. This level can be achieved with a dose of 800 IU/day vitamin D, the dose that was used in succesfull fracture prevention studies to date; a randomized clinical trial assessing whether higher vitamin D doses achieve a greater reduction of fracture incidence would be of considerable interest. As calcium balance is not only affected by vitamin D status but also by calcium intake, recommendations for adequate calcium intake should also be met. The findings of community-based clinical trials with vitamin D and calcium supplementation in which compliance was moderate or less have often been negative, whereas studies in institutionalized patients in whom medication administration was supervised ensuring adequate compliance demonstrated significant benefits.

 

 

Menopause. 2009 Sep 9. [Epub ahead of print]

Hyperinsulinemia in nonobese women reporting a moderate weight gain at the beginning of menopause: a useful early measure of susceptibility to insulin resistance.

Lemay A, Turcot L, Déchêne F, Dodin S, Forest JC.

OBJECTIVE:: At menopause, the frequent weight gain excess could be related to insulin resistance. This study evaluated the prevalence of hyperinsulinemia in nonobese women reporting a moderate increase in weight at the beginning of menopause. METHODS:: Women who were postmenopausal for 1 to 5 years and reporting a weight gain of 5 to 15 kg were evaluated for weight, eating habits, physical activity, body circumferences, fasting blood glucose level, insulin level, and lipid profile. An oral glucose tolerance test was performed in subgroups of 21 hyperinsulinemic women and 21 normoinsulinemic women matched for age, weight, height, body mass index, and hysterectomy. RESULTS:: Among 279 postmenopausal women reporting a weight gain of 8.7 +/- 4.4 kg, insulin level was increased in 49 (17.6%) women as compared with normoinsulinemic women (108.53 +/- 31.35 vs 58.96 +/- 14.52 pmol/L, respectively; P < 0.001). Differences were also found for glucose (5.24 +/- 0.37 vs 5.05 +/- 0.42 mmol/L, respectively; P = 0.003), insulin resistance as estimated by homeostasis model assessment HOMA-2-IR (2.01 +/- 0.53 vs 1.10 +/- 0.27, respectively; P < 0.001), weight (72.6 +/- 8.0 vs 69.9 +/- 7.1 kg, respectively; P = 0.023), body mass index (28.3 +/- 2.3 vs 27.2 +/- 2.3 kg/m, respectively; P = 0.003), and waist circumference (89.8 +/- 5.8 vs 86.0 +/- 6.5 cm, respectively; P < 0.001). Triglyceride levels were higher (1.47 +/- 0.66 vs 1.17 +/- 0.61 mmol/L, respectively; P = 0.002) and high-density lipoprotein cholesterol level was lower (1.54 +/- 0.35 vs 1.72 +/- 0.42 mmol/L, respectively; P = 0.007) in the hyperinsulinemic and normoinsulinemic groups. Although insulin levels were higher in 21 hyperinsulinemic women at all times that oral glucose tolerance tests were performed, levels of glucose were also above those of 21 matched normoinsulinemic women at 1 and 2 hours and remained greater than 6.0 mmol/L at 2 hours. CONCLUSIONS:: Because insulin resistance is frequently associated with weight gain in nonobese women at menopause, the measurement of fasting insulin, along with glucose, lipids, and waist circumference, may help to identify those who are at higher risk of developing glucose intolerance, metabolic syndrome, diabetes, and cardiovascular diseases and to implement early preventive measures.

 

 

Ann Rheum Dis. 2009 Sep 9. [Epub ahead of print]

Hormonal replacement therapy may reduce the risk for RA in women with early arthritis who carry HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP: Results from the ESPOIR cohort.

Salliot C, Bombardier C, Saraux A, Combe B, Dougados M.

Rheumatology B, Cochin Hospital, France.

OBJECTIVE: To assess the effect of reproductive factors, especially hormonal replacement therapy (HRT) and its interaction with HLA-DRB1 *01 and/or *04 alleles on the diagnosis of RA and the presence of anti-CCP in women included in the ESPOIR cohort (early arthritis cohort). METHODS: 568 patients were included in the analyses. Analyses were performed using logistic regression. RESULTS: HRT would reduce the risk for RA due to the HLA-DRB1 *01 and/or *04 alleles: from OR=1.88 (95%CI 1.32-2.68, p<0.000) for HLA-DRB1 *01 and/or *04 alleles alone to OR=1.07 (0.51-2.26, p=0.85) in women who carry HLA-DRB1 *01 and/or *04 alleles and who received a HRT. One explanation would be the protective effect of HRT on the presence of anti-CCP (OR=0.43, 95%CI 0.24-0.77, p<0.006). Other reproductive factors such as the number of pregnancies, menopause, and age of the menopause, age of the menarche and a history of pregnancy with poor outcome were not associated with the diagnosis of RA and the presence of anti-CCP. CONCLUSION: HRT may reduce the risk of RA due to HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP.

 

 

Med J Aust. 2009 Sep 7;191(5):263-6.

Is reflexology an effective intervention? A systematic review of randomised controlled trials.

Ernst E.

Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, Exeter, United Kingdom. Edzard.Ernst@pms.ac.uk.

OBJECTIVE: To evaluate the evidence for and against the effectiveness of reflexology for treating any medical condition. DATA SOURCES: Six electronic databases were searched from their inception to February 2009 to identify all relevant randomised controlled trials (RCTs). No language restrictions were applied. STUDY SELECTION AND DATA EXTRACTION: RCTs of reflexology delivered by trained reflexologists to patients with specific medical conditions. Condition studied, study design and controls, primary outcome measures, follow-up, and main results were extracted. DATA SYNTHESIS: 18 RCTs met all the inclusion criteria. The studies examined a range of conditions: anovulation, asthma, back pain, dementia, diabetes, cancer, foot oedema in pregnancy, headache, irritable bowel syndrome, menopause, multiple sclerosis, the postoperative state and premenstrual syndrome. There were > 1 studies for asthma, the postoperative state, cancer palliation and multiple sclerosis. Five RCTs yielded positive results. Methodological quality was evaluated using the Jadad scale. The methodological quality was often poor, and sample sizes were generally low. Most higher-quality trials did not generate positive findings. CONCLUSION: The best evidence available to date does not demonstrate convincingly that reflexology is an effective treatment for any medical condition.

 

 

Maturitas. 2009 Sep 4. [Epub ahead of print]

Premature menopause or early menopause: Long-term health consequences.

Shuster LT, Rhodes DJ, Gostout BS, Grossardt BR, Rocca WA.

Womens Health Clinic, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

OBJECTIVE: To review and summarize current evidence on the health consequences of premature menopause and early menopause. METHODS: We reviewed existing literature and combined graphically some results from the Mayo Clinic Cohort Study of Oophorectomy and Aging. RESULTS: Premature menopause or early menopause may be either spontaneous or induced. Women who experience premature menopause (before age 40 years) or early menopause (between ages 40 and 45 years) experience an increased risk of overall mortality, cardiovascular diseases, neurological diseases, psychiatric diseases, osteoporosis, and other sequelae. The risk of adverse outcomes increases with earlier age at the time of menopause. Some of the adverse outcomes may be prevented by estrogen treatment initiated after the onset of menopause. However, estrogen alone does not prevent all long-term consequences, and other hormonal mechanisms are likely involved. CONCLUSIONS: Regardless of the cause, women who experience hormonal menopause and estrogen deficiency before reaching the median age of natural menopause are at increased risk for morbidity and mortality. Estrogen treatment should be considered for these women, but may not eliminate all of the adverse outcomes.

 

 

J Clin Densitom. 2009 Sep 4. [Epub ahead of print]

25-Hydroxyvitamin D Measurement, 2009: A Review for Clinicians.

Binkley N, Krueger D, Lensmeyer G.

Osteoporosis Clinical Center and Research Program, University of Wisconsin-Madison, Madison, WI, USA.

As clinicians are more widely appreciating the endemic nature of low vitamin D status, measurement of serum 25-hydroxyvitamin D (25(OH)D), the accepted measure of vitamin D status, has increased. Challenges to 25(OH)D measurement include the presence of 2 forms of vitamin D-ergocalciferol and cholecalciferol (vitamin D(2) and vitamin D(3), respectively)- and the hydrophobic nature of vitamin D. The current state of 25(OH)D measurement is reviewed; modest differences between methodologies persist and confound the application of a single cut point (e.g., 30ng/mL/75nmol/L) for the diagnosis of low vitamin D status. The absence of standard calibrators contributes to between-laboratory differences in 25(OH)D measurement. Until there is improved assay standardization and subsequent evidence-based consensus, it seems premature to recommend widespread screening 25(OH)D measurement. Selectively obtaining 25(OH)D measurement in individuals at clinical risk for vitamin D deficiency and/or those most likely to promptly experience benefits from supplementation seems appropriate.

 

 

 

Selección de Resúmenes de Menopausia

                                                      Semana del 16 al 22 de Septiembre de 2009

                                   Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

 

Obesity (Silver Spring). 2009 Sep 17. [Epub ahead of print]

Estrogen Reduces 11beta-Hydroxysteroid Dehydrogenase Type 1 in Liver and Visceral, but Not Subcutaneous, Adipose Tissue in Rats.

Andersson T, Söderström I, Simonyté K, Olsson T.

Department of Public Health and Clinical Medicine, Medicine, Umeå University Hospital, Umeå, Sweden.

Following menopause, body fat is redistributed from peripheral to central depots. This may be linked to the age related decrease in estrogen levels. We hypothesized that estrogen supplementation could counteract this fat redistribution through tissue-specific modulation of glucocorticoid exposure. We measured fat depot masses and the expression and activity of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in fat and liver of ovariectomized female rats treated with or without 17beta-estradiol. 11betaHSD1 converts inert cortisone, or 11-dehydrocorticosterone in rats into active cortisol and corticosterone. Estradiol-treated rats gained less weight and had significantly lower visceral adipose tissue weight than nontreated rats (P < 0.01); subcutaneous adipose weight was unaltered. In addition, 11betaHSD1 activity/expression was downregulated in liver and visceral, but not subcutaneous, fat of estradiol-treated rats (P < 0.001 for both). This downregulation altered the balance of 11betaHSD1 expression and activity between adipose tissue depots, with higher levels in subcutaneous than visceral adipose tissue of estradiol-treated animals (P < 0.05 for both), opposite the pattern in ovariectomized rats not treated with estradiol (P < 0.001 for mRNA expression). Thus, estrogen modulates fat distribution, at least in part, through effects on tissue-specific glucocorticoid metabolism, suggesting that estrogen replacement therapy could influence obesity related morbidity in postmenopausal women.

 

 

Nutr Res. 2009 Aug;29(8):525-530. Links

Low serum 25-hydroxyvitamin D concentrations are associated with greater all-cause mortality in older community-dwelling women.

Semba RD, Houston DK, Ferrucci L, Cappola AR, Sun K, Guralnik JM, Fried LP.

Department of Ophthalmology and the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, MD 21287, USA; Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University, Winston-Salem, NC 27157, USA; Longitudinal Studies Section, National Institute on Aging, Baltimore, MD 21225, USA; Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Epidemiology and Demography Section, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD 20892, USA; Mailman School of Public Health, Columbia University, New York, NY 10032, USA.

Vitamin D deficiency is associated with osteoporosis, poor muscle strength, falls, and fractures. The relationship between serum vitamin D concentrations and mortality in older community-dwelling women has not been well characterized. We hypothesized that women with lower 25-hydroxyvitamin D (25[OH]D) concentrations were at higher risk of mortality. We examined the association between serum 25[OH]D concentrations and all-cause mortality in a prospective, population-based study of 714 community-dwelling women, aged 70 to 79 years, the Women's Health and Aging Studies I and II in Baltimore, Md. The studies were originally designed to evaluate the causes and course of physical disability in older women living in the community. Vital status was determined through follow-up interviews and matching with the National Death Index. During a median of 72 months of follow-up, 100 (14%) of 714 women died. Women in the lowest quartile of 25(OH)D (<15.3 ng/mL or 38.2 nmol/L) were at higher risk of death (hazards ratio, 2.45; 95% confidence interval, 1.12-5.36; P = .02) compared to women in the highest quartile (>27.0 ng/mL or 67.4 nmol/L) of 25(OH)D in a multivariate Cox proportional hazards model adjusting for demographics, season, and conventional risk factors. Older community-dwelling women with low 25(OH)D levels are at an increased risk of death.

 

 

Menopause. 2009 Sep 11. [Epub ahead of print]

Submaximal exercise coronary artery flow increases in postmenopausal women without coronary artery disease after estrogen and atorvastatin.

Puntawangkoon C, Morgan TM, Herrington DM, Hamilton CA, Hundley WG.

From the Departments of 1Internal Medicine, Cardiology Section, 2Public Health Sciences, 3Biomedical Engineering, and 4Radiology, Wake Forest University School of Medicine, Winston-Salem, NC.

OBJECTIVE:: The aim of this study was to determine the effect of statins and hormone therapy on submaximal exercise-induced coronary artery blood flow in postmenopausal women without a history of coronary artery disease. Hormone therapy or statin therapy in early postmenopausal women without coronary artery disease has been shown to enhance arterial endothelial function; we hypothesized that these agents would improve submaximal exercise-induced coronary artery blood flow. METHODS:: Sixty-four postmenopausal women, aged 50 to 65 years without documented coronary artery disease, were randomized in a double-blind, crossover fashion to receive 8 weeks of hormone therapy versus placebo, with or without 80 mg/day of atorvastatin. Before receipt of any therapy and after each treatment period, each woman underwent measures of coronary artery blood flow at rest and stress. RESULTS:: The combination of hormone therapy and atorvastatin increased submaximal exercise-induced coronary artery blood flow (P = 0.04). In the subgroups of women compliant with treatment, resting coronary artery blood flow increased in those receiving hormone therapy (P = 0.03) or statin therapy (P = 0.02). CONCLUSIONS:: In postmenopausal women aged 50 to 65 years without documented coronary artery disease, resting and submaximal exercise-induced coronary artery blood flow improves after receipt of high-dose atorvastatin and conjugated estrogens therapy.

 

 

Urol Int. 2009;83(2):226-9. Epub 2009 Sep 10.

Alendronate reduces the excretion of risk factors for calcium phosphate stone formation in postmenopausal women with osteoporosis.

Yasui T, Itoh Y, Okada A, Hamamoto S, Hirose M, Kobayashi T, Tozawa K, Kohri K.

Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. yasui@med.nagoya-cu.ac.jp

OBJECTIVE: Osteoporosis is associated with the pathogenesis and risk of urolithiasis, which is higher among postmenopausal women (as opposed to premenopausal). Bisphosphonates potently inhibit bone resorption, and are used in the management of bone disease. We investigated the ability of a bisphosphonate to prevent calcium stone formation. METHODS: We studied 12 postmenopausal women (63.8 +/- 7.3 years) who were not receiving osteoporosis therapy, and had stones comprised of calcium phosphate (CaP; n = 3), calcium oxalate (CaOx; n = 3) and CaP + CaOx (n = 6). We measured bone mineral density (BMD), serum and urinary values in 24-hour urine specimens before and 3 months after the oral administration of 5 mg/day of alendronate (ALN). The indexes of the ionic activity product of calcium oxalate, AP(CaOx), and of calcium phosphate, AP(CaP), were estimated using the Tiselius method. RESULTS: ALN significantly reduced the AP(CaP) index (1.53 +/- 1.37 to 0.89 +/- 0.81, p <0.05). Urinary calcium, oxalate, phosphate and the AP(CaOx) index did not significantly change. BMD improved in 11 of the 12 patients. Urinary stones did not develop in any of the patients during the course of the study. CONCLUSION: The results suggested that ALN not only improves BMD and osteoporosis, but also reduces the risk of calcium phosphate stone formation in postmenopausal women.

 

 

J Clin Oncol. 2009 Sep 14. [Epub ahead of print]

Estrogen-Progestagen Menopausal Hormone Therapy and Breast Cancer: Does Delay From Menopause Onset to Treatment Initiation Influence Risks?

Fournier A, Mesrine S, Boutron-Ruault MC, Clavel-Chapelon F.

Institut National de la Santé et de la Recherche Médicale; Université Paris-Sud, Villejuif, France.

PURPOSE: To investigate whether the relation between estrogen-progestagen menopausal hormone therapy (EP-MHT) and breast cancer risk varies according to the delay between menopause onset and treatment initiation. Participants and METHODS: Between 1992 and 2005, 1,726 invasive breast cancers were identified among 53,310 postmenopausal women from the French E3N cohort (mean duration of follow-up, 8.1 years). Hazard ratios (HRs) and CIs were estimated using Cox models, with MHT never users as the reference. RESULTS: Among recent users of EP-MHT, the risk of breast cancer varied according to the timing of treatment initiation. This variation was confined to short durations of use (</= 2 years): the HR was 1.54 (95% CI, 1.28 to 1.86) for short treatments initiated in the 3-year period following menopause onset and 1.00 (95% CI, 0.68 to 1.47) for short treatments initiated later (P = .04 for homogeneity). However, this pattern of risks was not observed in users of EP-MHT containing progesterone, among whom there was no significantly increased risk associated with short duration of use (HR was 0.87 [95% CI, 0.57 to 1.32] for treatments initiated </= 3 years after menopause, and HR was 0.90 [95% CI, 0.45 to 1.81] for treatments initiated later). Longer durations of EP-MHT use were generally associated with increases in breast cancer risk, whatever the gap time. CONCLUSION: Our results suggest that, for some EP-MHT, the timing of treatment initiation transiently modulates the risk of breast cancer and that, when initiated close to menopause, even short durations of use are associated with an increased breast cancer risk. Estrogen + progesterone combinations might be an exception in this regard.

 

 

Fertil Steril. 2009 Sep 10. [Epub ahead of print]

Discontinuation of hormone therapy in the French GAZEL cohort 1990-2006.

Ringa V, Fritel X, Varnoux N, Zins M, Quelen C, Bouyer J.

Institut National d'Etudes Démographiques (INED), Le Kremlin-Bicêtre, France; Institut National de la Santé et de la Recherche Médicale (INSERM), Le Kremlin-Bicêtre, France; University Paris-Sud 11, Faculté de médecine Paris-Sud, Bicêtre Hospital, Le Kremlin-Bicêtre, France.

OBJECTIVE: To analyze changes in hormone therapy (HT) use after the publication of the Women's Health Initiative (WHI) results, in a country (France) where HT is different from that assessed in the WHI. DESIGN: Longitudinal study. SETTING: Women in the GAZEL cohort of employees of the French national power company. PARTICIPANT(S): One thousand six hundred five postmenopausal women ever-users of HT. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Discontinuation of HT. RESULT(S): Rates of discontinuation were higher after 2002: 65% of users who began HT in 1998 were still using it after 5 years. In contrast, >90% of those who began before 1994 were still using it after 5 years. Discontinuation was associated with women's social and medical characteristics and with factors related to side effects and expectations concerning HT. After adjustment for these factors, women were twice as likely to stop HT after publication of the WHI. CONCLUSION(S): Even in France, publication of the WHI has led to a decline in HT use.

 

 

Lancet. 2009 Sep 18. [Epub ahead of print]

Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial.

Chlebowski RT, Schwartz AG, Wakelee H, Anderson GL, Stefanick ML, Manson JE, Rodabough RJ, Chien JW, Wactawski-Wende J, Gass M, Kotchen JM, Johnson KC, O'Sullivan MJ, Ockene JK, Chen C, Hubbell FA; for the Women's Health Initiative Investigators.

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.

BACKGROUND: In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period. METHODS: The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00000611. FINDINGS: After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups. INTERPRETATION: Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer.