Selección de Resúmenes de Menopausia

Junio de 2010

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

Semanas del 9 al 15 de Junio de 2010

Thromb Haemost. 2010 Jun 10;104(3). [Epub ahead of print]

Risk of recurrent venous thromboembolism after a first oestrogen-associated episode. Data from the REVERSE cohort study.

Le Gal G, Kovacs MJ, Carrier M, Do K, Kahn SR, Wells PS, Anderson DA, Chagnon I, Solymoss S, Crowther M, Righini M, Lacut K, White RH, Vickars L, Rodger M.

Dr. M. Rodger, Division of Hematology, The Ottawa Hospital, General Campus, Ottawa, Ontario, Canada

The use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3-6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged immobilisation. Our objective was to assess the risk of recurrent VTE in women after a first unprovoked episode on oestrogen. The REVERSE study is a cohort study of patients with a first unprovoked VTE treated with anticoagulant treatment for 5-7 months. The risk of recurrent VTE during follow-up was compared between women users and non users of oestrogen at the time of index VTE. Among the 646 patients included, 314 were women, of them 67 were current users of oestrogen at the time of their VTE: 49 were on oral contraceptives and 18 on post-menopausal hormone replacement therapy (HRT). No significant association was found between oestrogen exposure, either oral contraceptives or HRT, and a lower risk of recurrent VTE after adjustment for age, or analysis restricted to women in the same age range as oestrogen contraceptives and HRT users, respectively. The risk of recurrent VTE is low in women after a first otherwise unprovoked oestrogen-associated VTE. However, this risk is not significantly lower than in women whose VTE was not related to oestrogen use.

Menopause. 2010 Jun 6. [Epub ahead of print]

Associations of depression with the transition to menopause.

Freeman EW.

From the Departments of Obstetrics/Gynecology and Psychiatry, University of Pennsylvania, Philadelphia, PA.

OBJECTIVES:: The aims of this study were to identify the risk of depression in the transition to menopause in women with and without a history of depression and to consider that the changing hormonal milieu is one of multiple risk factors for perimenopausal depression. METHOD:: A review of epidemiologic studies of depressed mood in the menopausal transition since the State-of-Science Report of the National Institutes of Health in 2005 was conducted. RESULTS:: Recent longitudinal cohort studies indicate that the likelihood of depressed mood in the menopausal transition is approximately 30% to three times greater compared with that during premenopause. Women with a history of depression are nearly five times more likely to have a diagnosis of major depression in the menopausal transition, whereas women with no history of depression are two to four times more likely to report depressed mood compared with premenopausal women. In some studies, the changing hormonal milieu is significantlyassociated with depressive symptoms in the menopausal transition. Other risk factors for depressed mood in perimenopausal women include poor sleep, hot flashes, stressful or negative life events, employment status, age, and race. CONCLUSIONS:: The findings support the concept that the menopausal transition is a "window of vulnerability" for some women and is framed by the changing hormonal milieu of ovarian aging.

Menopause. 2010 Jun 8. [Epub ahead of print]

Role of androgens in women's sexual dysfunction.

Basson R, Brotto LA, Petkau AJ, Labrie F.

From the 1Department of Psychiatry, Vancouver Hospital, and Departments of 2Obstetrics and Gynaecology, and 3Statistics, University of British Columbia, Vancouver, British Columbia, Canada; and 4Research Center in Molecular Endocrinology, Oncology and Human Genomics, Laval University and Laval University Hospital (CHUL), Quebec, Canada.

OBJECTIVE:: Although suspected, androgen deficit in women with sexual dysfunction has never been established. Given that serum testosterone levels are of limited value, we sought to compare total androgen activity in women with and without hypoactive sexual desire disorder (HSDD). Intracellular production in target tissues is the major source of testosterone in older women and can now be measured. Androgen metabolites, specifically androsterone glucuronide (ADT-G), reflect intracellular and ovarian sources of testosterone. Thus, we predicted significantly lowered levels of metabolites in women with sexual dysfunction. METHODS:: A detailed assessment of the sexual function of women without depression, without serious relationship discord, or receiving medications affecting sexual function included 121 women with HSDD and 124 sexually healthy community controls. Sexual function was assessed using structured interviews, validated questionnaires, and steroid analysis-mass spectrometry levels of ADT-G, testosterone, and precursor hormones. RESULTS:: No group differences in serum levels of testosterone or ADT-G were found. Significantly lower levels of two precursor hormones, dehydroepiandrosterone sulfate and androstene-3beta,17beta-diol, were found in women with sexual dysfunction (P = 0.006 and P = 0.020, respectively). The variability of metabolite and precursor levels was substantial for all women. CONCLUSIONS:: Significantly lower levels of the two precursor steroids dehydroepiandrosterone sulfate and androstene-3beta,17beta-diol but not the major androgen metabolite ADT-G were found in women with HSDD. Although the significance of the former awaits further study, androgen deficiency in women with HSDD was not confirmed. Given the unknown long-term effects of testosterone supplementation, women receiving testosterone therapy should be informed that a deficit of testosterone activity in women with HSDD has not been identified.

Menopause. 2010 Jun 8. [Epub ahead of print]

Desvenlafaxine and escitalopram for the treatment of postmenopausal women with major depressive disorder.

Soares CN, Thase ME, Clayton A, Guico-Pabia CJ, Focht K, Jiang Q, Kornstein SG, Ninan P, Kane CP, Cohen LS.

1McMaster University, Hamilton, Ontario, Canada; 2University of Pennsylvania School of Medicine, Philadelphia, PA; 3University of Virginia, Charlottesville, VA; 4Pfizer Inc., formerly Wyeth Research, Collegeville, PA; 5Virginia Commonwealth University, Richmond, VA; and 6Massachusetts General Hospital, Boston, MA.

OBJECTIVE:: This study assessed the efficacy, safety, and tolerability of the serotonin-norepinephrine reuptake inhibitor desvenlafaxine and the selective serotonin reuptake inhibitor escitalopram for major depressive disorder (MDD) in postmenopausal women. METHODS:: In this randomized, double-blind study, postmenopausal outpatients (aged 40-70 y) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition MDD received flexible-dose desvenlafaxine (100-200 mg/d) or escitalopram (10-20 mg/d) for 8 weeks. Acute-phase responders, that is, women with a 50% or greater reduction from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score, were eligible to continue the same double-blind treatment in the 6-month continuation phase. The primary efficacy outcomes were mean change from baseline in HAM-D17 total score (acute phase), analyzed using a mixed-effects model for repeated measures, and the proportion of women who maintained response (continuation phase), analyzed using logistic regression. RESULTS:: Reductions in HAM-D17 total score at acute-phase endpoint were similar for desvenlafaxine- and escitalopram-treated women (-13.6 vs -14.3, respectively; P = 0.24). No significant difference was observed between groups at continuation-phase endpoint in the proportion of women who maintained response (desvenlafaxine, 82%; escitalopram, 80%; P = 0.70). In both phases, desvenlafaxine and escitalopram were generally safe and well tolerated. CONCLUSIONS:: Among postmenopausal outpatients with MDD, there were no significant differences in the efficacy of desvenlafaxine and escitalopram based on primary efficacy analyses. The results do not support the overall hypothesis that the serotonin-norepinephrine reuptake inhibitor desvenlafaxine has an efficacy advantage for the treatment of MDD in postmenopausal women because, in this particular subgroup, desvenlafaxine failed to prove superiority over escitalopram. Safety and tolerability were comparable.

J Clin Endocrinol Metab. 2010 Jun 9. [Epub ahead of print]

Sex, Menopause, Metabolic Syndrome, and All-Cause and Cause-Specific Mortality--Cohort Analysis from the Third National Health and Nutrition Examination Survey.

Lin JW, Caffrey JL, Chang MH, Lin YS.

Cardiovascular Center and Health Management Center (J.-W.L.), National Taiwan University Hospital, Yun-Lin Branch, Dou-Liou City, Taiwan 640; Department of Medicine (J.-W.L.), College of Medicine, National Taiwan University, Taipei, Taiwan 106; Department of Integrative Physiology and Cardiovascular Research Institute (J.L.C.) and Department of Environmental and Occupational Health (Y.-S.L.), University of North Texas Health Science Center, Fort Worth, Texas 76107; and National Office of Public Health Genomics (M.-H.C.), Centers for Disease Control and Prevention, Atlanta, Georgia 30333.

Objective: This study assessed the mortality risk associated with metabolic syndrome (MetS) for participants from the Third National Health and Nutrition Examination Survey. Design, Setting, and Patients: The study analyzed mortality data from 1364 men and 1321 women aged 40 yr and older based on their MetS status defined by National Cholesterol Education Program Adult Treatment Panel III. Subjects initially using insulin, oral hypoglycemic, antihypertensive, or lipid-lowering medications were excluded. Main Outcome Measures: All-cause, cardiovascular, cardiac, and noncardiovascular mortality were obtained from the Third National Health and Nutrition Examination Survey-linked mortality follow-up file through December 31, 2000. Results: The prevalence of MetS was 33 and 29% for men and women, respectively. In the male subjects, there was no significant association between MetS and mortality. In the women, MetS was an independent risk factor for all-cause mortality [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.29-2.64, P = 0.001], cardiovascular mortality (HR 1.96, 95% CI 1.21-3.17, P = 0.007), cardiac mortality (HR 1.88, 95% CI 1.15-3.09, P = 0.01), and noncardiovascular mortality (HR 1.80, 95% CI 1.13-2.87, P = 0.01). The HR was stronger when postmenopausal women were analyzed separately and became nonsignificant in the premenopausal cohort. The sex-specific HR remained unchanged, regardless of the MetS criteria used or the inclusion of actively treated subjects. Conclusions: MetS poses a significant increase in mortality risk through an observation period as long as 12 yr, primarily in postmenopausal women, that is not apparent in men and premenopausal women. Sex is an important effect modifier of all-cause and cause-specific death.

Osteoporos Int. 2010 Jun 10. [Epub ahead of print]

Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial.

de Villiers TJ, Chines AA, Palacios S, Lips P, Sawicki AZ, Levine AB, Codreanu C, Kelepouris N, Brown JP.

Panorama MediClinic and University of Stellenbosch, Room 118 Parow 7500, Cape Town, South Africa,

Findings from this 5-year phase 3 study of postmenopausal women with osteoporosis showed that bazedoxifene was associated with an overall favorable safety and tolerability profile, with no evidence of endometrial or breast stimulation. Overall, the results at 5 years were consistent with those seen at 3 years. INTRODUCTION: We report safety and tolerability findings from a 5-year randomized, double-blind, phase 3 study of bazedoxifene in postmenopausal women with osteoporosis. METHODS: In the core study, healthy postmenopausal women with osteoporosis (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. During the 2-year study extension, the raloxifene 60-mg treatment arm was discontinued after the 3-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned in a blinded manner to bazedoxifene 20 mg (bazedoxifene 40-/20-mg group) after 4 years. Safety and tolerability data are reported for subjects in the bazedoxifene 20- and 40-/20-mg and placebo groups; efficacy findings are reported elsewhere. RESULTS: A total of 3,146 subjects in the bazedoxifene 20- and 40-mg and placebo groups were enrolled in the extension study (years 4 and 5). Overall, the 5-year incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar among groups. The incidence of hot flushes and leg cramps was higher with bazedoxifene compared with placebo. Venous thromboembolic events, primarily deep vein thrombosis, were more frequently reported in the bazedoxifene groups compared with the placebo group. Reports of cardiac disorders and cerebrovascular events were few and evenly distributed among groups. Bazedoxifene showed a neutral effect on the breast and endometrium. CONCLUSION: Bazedoxifene was associated with an overall favorable safety and tolerability profile in postmenopausal women with osteoporosis over 5 years of therapy, consistent with findings at 3 years.