Selección de
Resúmenes de Menopausia
Octubre de 2009
Juan Enrique Blümel.
Departamento Medicina Sur. Universidad
de Chile
Semana
del 28 de Octubre al 3 de Noviembre de 2009
Circulation. 2009 Oct 26. [Epub
ahead of print]
Anthropometry,
Body Fat, and Venous Thromboembolism. A Danish Follow-Up Study.
Severinsen MT, Kristensen SR, Johnsen SP, Dethlefsen C, Tjřnneland A, Overvad K.
Department of Clinical Epidemiology,
Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark; and Institute
of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
BACKGROUND:
-Obesity, measured as body mass index, is associated with venous
thromboembolism (VTE). Body mass index is a marker of excess weight and
correlates well with body fat content in adults; however, it fails to consider
the distribution of body fat. We assessed the association between
anthropometric variables and VTE. Methods and Results-From 1993 to 1997, 27 178
men and 29 876 women 50 to 64 years of age were recruited into a Danish
prospective study (Diet, Cancer, and Health). During 10 years of follow-up, the
outcome of VTE events was identified in the Danish National Patient Registry
and verified by review of medical records. Body weight, body mass index, waist
circumference, hip circumference, and total body fat were measured at baseline.
We used Cox proportional hazard models to assess the association between
anthropometry and VTE. Age was used as a time axis, with further adjustment for
smoking, physical activity, height, hypertension, diabetes mellitus,
cholesterol, and, among women, use of hormone replacement therapy. We verified
641 incident VTE events and found monotonic dose-response relationships between
VTE and all anthropometric measurements in both sexes. In mutually adjusted
analyses of waist and hip circumference, we found that hip circumference was
positively associated with VTE in women but not in men, whereas waist
circumference was positively associated with VTE in men but not in women.
Conclusions-All measurements of obesity are predictors of the risk for VTE.
Positive associations were found between VTE and body weight, body mass index,
waist circumference, hip circumference, and total body fat mass.
Pharmacotherapy. 2009
Nov;29(11):1357-74.
Use of
antidepressants for management of hot flashes.
Department of Pharmacy Practice, Harrison
School of Pharmacy, Auburn University, Auburn, Alabama, USA. dgc0001@auburn.edu
A
growing body of evidence suggests that antidepressant therapies, particularly
selective serotonin reuptake inhibitors and venlafaxine, are effective in the
management of hot flash symptoms. Several of these agents have the support of
the American College of Obstetricians and Gynecologists and the North American
Menopause Society. To review the literature on antidepressants for the
treatment of hot flashes in women, we searched the PubMed, International
Pharmaceutical Abstracts, and MEDLINE databases from inception through May
2009. All publication types that included human participants and that were
published in English were eligible for review. These articles, relevant
abstracts, and additional references were used to collect pertinent data.
Although initial small pilot trials were conducted solely in breast cancer
survivors, additional studies have been conducted both in breast cancer
survivors and in relatively healthy menopausal women. Data on the benefits with
many of these agents are conflicting. Venlafaxine and paroxetine have been
studied more extensively than any of the other antidepressants and are more
consistent in effectively reducing the frequency and severity of hot flashes,
based on these study results. Desvenlafaxine, sertraline, fluoxetine, and
citalopram should be considered second- or third-line options if patients fail
therapy with or cannot tolerate venlafaxine or paroxetine, based on the current
published data. Duloxetine, escitalopram, fluvoxamine, and mirtazapine should
be reserved as last-line therapy until more rigorous studies are conducted
assessing their use in the management of hot flashes.
Am J Med. 2009 Nov;122(11):1016-1022.e1.
Bayesian
meta-analysis of hormone therapy and mortality in younger postmenopausal women.
Salpeter SR, Cheng J, Thabane L, Buckley NS, Salpeter EE.
BACKGROUND:
There is uncertainty over the risks and benefits of hormone therapy. We
performed a Bayesian meta-analysis to evaluate the effect of hormone therapy on
total mortality in younger postmenopausal women. This analysis synthesizes
evidence from different sources, taking into account varying views on the
issue. METHODS: A comprehensive search from 1966 through January 2008
identified randomized controlled trials of at least 6 month's duration that
evaluated hormone therapy in women with mean age <60 years and reported at
least one death, and prospective observational cohort studies that evaluated
the relative risk of mortality associated with hormone therapy after adjustment
for confounding variables. RESULTS: The results were synthesized using a
hierarchical random-effects Bayesian meta-analysis. The pooled results from 19
randomized trials, with 16,000 women (mean age 55 years) followed for 83,000
patient-years, showed a mortality relative risk of 0.73 (95% credible interval
0.52-0.96). When data from 8 observational studies were added to the analysis,
the resultant relative risk was 0.72 (credible interval 0.62-0.82). The
posterior probability that hormone therapy reduces total mortality in younger
women is almost 1. CONCLUSIONS: The synthesis of data using Bayesian
meta-analysis indicates a reduction in mortality in younger postmenopausal
women taking hormone therapy compared with no treatment. This finding should be
interpreted taking into account the potential benefits and harms of hormone
therapy.
Osteoporos Int. 2009 Oct 30. [Epub
ahead of print]
Immune
changes in post-menopausal osteoporosis: the Immunos study.
Breuil V, Ticchioni M, Testa J, Roux CH, Ferrari P, Breittmayer JP, Albert-Sabonnadičre
C, Durant J, De Perreti F, Bernard A, Euller-Ziegler L, Carle GF.
Service de Rhumatologie, CHU de Nice, Hôpital
l'Archet, Route Saint Antoine de Ginestičre,Nice, France.
The
phenotypic and functional characteristics of immune cells of osteoporotic women
compared to healthy controls similar for age and estrogen level showed for the
first time significant changes in several B lymphocytes populations in
postmenopausal osteoporosis, related to bone mineral density (BMD) and
fractures, and a significant lower basal secretion of interferon-gamma
(IFN-gamma) by CD4(+). INTRODUCTION: To investigate the interactions between
bone and immune system, we studied the phenotypic and functional
characteristics of immune cells of 26 postmenopausal women with osteoporotic
(OP) fractures compared to 24 healthy controls. METHODS: We analyzed surface
markers of peripheral B, CD4(+) and CD8(+) lymphocytes and cytokine secretion
in supernatants of these cells cultured with or without stimulation. Body
composition was assessed by dual energy X-ray absorptiometry. RESULTS: The two
groups were similar for age and estrogen level. OP women had a significantly
lower body mass index, fat mass, and lean mass. The number of CD19(+),
CD19(+)/CD27(+), CD19(+)/CD27(+)/CD5(-)/CD38(+) and CD19(+)/CD27(+)/RANK(+),
CD4(+)/CD27(+)/CD45RA(-)/RANK(+), and CD4(+)/CD27(+)/CD45RA(-)/CD28(+) was
lower in OP women and positively correlated to BMD. In OP women, under basal
conditions, CD4(+) secreted less IFN-gamma and B lymphocytes more granulocyte
macrophage colony-stimulating factor (GM-CSF). GM-CSF was positively correlated
to fracture rate and negatively to BMD. CONCLUSIONS: Our results suggest that,
regardless of age and estrogen status, postmenopausal OP is associated with
immune changes, highlighting a possible role of IFN-gamma in the
pathophysiology of OP and reporting, for the first time, changes in several B
lymphocyte populations. These alterations may reflect the frailty observed
after fracture, providing new insight into the mechanisms of morbidity and
mortality associated with OP fractures.
Womens Health (Lond Engl). 2009 Nov;5(6):637-47.
Long-term
prevention with hormone-replacement therapy after the menopause: which women
should be targeted?
Alexandersen P, Karsdal MA, Christiansen C.
Center for Clinical & Basic Research
a/s, Ballerup Byvej 222, DK-2750 Ballerup, Denmark. peter.alexandersen@ccbr.com
For
decades, hormone-replacement therapy (HRT) was considered safe and was the
first choice in prevention of postmenopausal osteoporosis induced by estrogen
deficiency. Numerous experimental and epidemiological studies further supported
a protective effect of exogenous female sex hormones on atherogenesis and
coronary heart disease (CHD) in women after the menopause. However, the fact
that these promising results were not translated into lower incidences of CHD
events in hormone-treated women compared with placebo in subsequent, large,
randomized studies of healthy subjects as well as women with known CHD raised a
very intense debate concerning the safety of HRT in terms of cardiovascular
risk. A critical mass of data points toward a protective influence of HRT on
cardiovascular disease end points in early postmenopausal women, but increased
harm in elderly women, especially those with abdominal adiposity or metabolic
syndrome. Once the quasi-hysterical reaction to the largest of the randomized
studies (the Women's Health Initiative) has abated, a future strategy should be
to concentrate on identifying those relatively few individuals who are not
suitable for HRT, as HRT still remains the most thoroughly investigated
pharmacological prevention strategy of osteoporosis.
J Clin Endocrinol Metab. 2009 Oct 26. [Epub
ahead of print]
Effect
of Transdermal Teriparatide Administration on Bone Mineral Density in
Postmenopausal Women.
Cosman F, Lane NE, Bolognese MA, Zanchetta JR, Garcia-Hernandez PA, Sees K, Matriano JA, Gaumer K, Daddona PE.
Context:
Treatment of osteoporosis with an anabolic agent, teriparatide [human PTH 1-34
(TPTD)], is effective in reducing incident fractures, but patient resistance to
daily sc injections has limited its use. A novel transdermal patch, providing a
rapid, pulse delivery of TPTD, may provide a desirable alternative. Objective:
The aim of the study was to determine the safety and efficacy of a novel
transdermal TPTD patch compared to placebo patch and sc TPTD 20-mug injection
in postmenopausal women with osteoporosis. Design: Our study consisted of
6-month, randomized, placebo-controlled, positive control, multidose daily
administration. Patients: We enrolled 165 postmenopausal women (mean age, 64
yr) with osteoporosis. Interventions: A TPTD patch with a 20-, 30-, or 40-mug
dose or a placebo patch was self-administered daily for 30-min wear time, or 20
mug of TPTD was injected daily. Outcomes: The primary efficacy measure was mean
percentage change in lumbar spine bone mineral density (BMD) from baseline at 6
months. Results: TPTD delivered by transdermal patch significantly increased
lumbar spine BMD vs. placebo patch in a dose-dependent manner at 6 months (P
< 0.001). TPTD 40-mug patch increased total hip BMD compared to both placebo
patch and TPTD injection (P < 0.05). Bone turnover markers (procollagen type
I N-terminal propeptide and C-terminal cross-linked telopeptide of type I
collagen) increased from baseline in a dose-dependent manner in all treatment
groups and were all significantly different from placebo patch (P < 0.001).
All treatments were well tolerated, and no prolonged hypercalcemia was
observed. Conclusion: Transdermal patch delivery of TPTD in postmenopausal
women with osteoporosis for 6 months is safe and effective in increasing lumbar
spine and total hip BMD.
Osteoporos Int. 2009 Oct 27. [Epub
ahead of print]
Use of
bisphosphonates and raloxifene and risk of deep venous thromboembolism and
pulmonary embolism.
Vestergaard P, Schwartz K, Pinholt EM, Rejnmark L, Mosekilde L.
Department
of Endocrinology and Metabolism C, Aarhus University Hospital, Tage Hansens
Gade 2, 8000, Arhus C, Denmark, p-vest@post4.tele.dk.
Prior
studies have associated raloxifene and strontium ranelate with deep venous
thromboembolism and pulmonary embolism. In a cohort study, we observed an
increased risk also with the bisphosphonates. However, the increase was present
already before the start of bisphosphonates pointing at an effect of the
underlying condition. INTRODUCTION: We seek to study the association between
use of drugs against osteoporosis and risk of deep venous thromboembolism (DVT)
and pulmonary embolism (PE). METHODS: Nationwide register-based cohort study
from Denmark with all users of bisphosphonates and other drugs against
osteoporosis between 1996 and 2006 (n = 103,562) as cases and three age- and
gender-matched controls from the general population (n = 310,683). RESULTS:
Before start of a drug against osteoporosis, an increased risk of DVT/PE was
present in the crude analysis for alendronate, etidronate, and risedronate.
However, upon adjustment, this increase in risk disappeared. Before start of
raloxifene, a decreased risk of DVT/PE was present (odds ratio (OR) = 0.53, 95%
confidence interval (CI), 0.39-0.71). After start of a drug, alendronate (HR =
1.20, 95% CI, 1.00-1.43), clodronate (HR = 4.06, 95% CI, 1.47-11.2), and
etidronate (HR = 1-37, 95% CI, 1.23-1.51) were all associated with an increased
risk of DVT/PE, while raloxifene was only borderline, significantly associated
with risk of DVT/PE (HR = 1.64, 95% CI, 0.97-2.77). No dose-reponse
relationship was present except for alendronate, where the risk was inversely
associated with dose, i.e., the risk of DVT/PE decreased with increasing
average daily dose. The HR for DVT/PE was higher with clodronate and etidronate
than with alendronate. Alendronate and raloxifene carried the same risk for
DVT/PE. CONCLUSION: Bisphosphonates seem associated with an increased risk of
DVT/PE. However, the association does not seem to be causal.
Semana del 21 al
27 de Octubre de 2009
Clin Interv
Aging. 2009;4:357-65. Epub
2009 Oct 12.
Gastrointestinal tolerability with
ibandronate after previous weekly bisphosphonate treatment.
Derman R, Kohles JD, Babbitt A.
Department
of Obstetrics and Gynecology, Christiana Hospital, Newark, DE, USA.
Data
from two open-label trials (PRIOR and CURRENT) of women with postmenopausal
osteoporosis or osteopenia were evaluated to assess whether monthly oral and
quarterly intravenous (IV) ibandronate dosing improved self-reported
gastrointestinal (GI) tolerability for patients who had previously experienced
GI irritation with bisphosphonate (BP) use. In PRIOR, women who had
discontinued daily or weekly BP treatment due to GI intolerance received
monthly oral or quarterly IV ibandronate for 12 months. The CURRENT subanalysis
included women receiving weekly BP treatment who switched to monthly oral
ibandronate for six months. GI symptom severity and frequency were assessed
using the Osteoporosis Patient Satisfaction Questionnaire. In PRIOR, mean GI
tolerability scores increased significantly at month 1 from screening for both
treatment groups (oral: 79.3 versus 54.1; IV: 84.4 versus 51.0; p < 0.001
for both). Most patients reported improvement in GI symptom severity and
frequency from baseline at all post-screening assessments (>90% at Month
10). In the CURRENT subanalysis >60% of patients reported improvements in
heartburn or acid reflux and >70% indicated improvement in other stomach upset
at month 6. Postmenopausal women with GI irritability with daily or weekly BPs
experienced improvement in symptoms with extended dosing monthly or quarterly
ibandronate compared with baseline.
J Clin
Endocrinol Metab. 2009 Oct 22. [Epub ahead of print]
Effects of Conjugated Equine Estrogens on
Cognition and Affect in Postmenopausal Women with Prior Hysterectomy.
Resnick SM, Espeland MA, An Y, Maki PM, Coker LH, Jackson R, Stefanick ML, Wallace R,
Rapp SR.
Context:
Different menopausal hormone therapies may have varied effects on specific
cognitive functions. We previously reported that conjugated equine estrogens
(CEE) with medroxyprogesterone acetate had a negative impact on verbal memory
but tended to impact figural memory positively over time in older
postmenopausal women. Objective: The objective of the study was to determine
the effects of unopposed CEE on changes in domain-specific cognitive function
and affect in older postmenopausal women with prior hysterectomy. Design: This
was a randomized, double blind, placebo-controlled clinical trial. Setting: The
study was conducted at 14 of 40 Women's Health Initiative (WHI) clinical
centers. Participants: Participants were 886 postmenopausal women with prior
hysterectomy, aged 65 yr and older (mean 74 yr), free of probable dementia, and
enrolled in the WHI and WHI Memory Study (WHIMS) CEE-Alone trial for a mean of
3 yr and followed up for a mean of 2.70 yr. Intervention: Intervention was
0.625 mg of CEE daily or placebo. Main Outcome Measures: Annual rates of change
in specific cognitive functions and affect, adjusted for time since
randomization, were measured. Results: Compared with placebo, unopposed CEE was
associated with lower spatial rotational ability (P < 0.01) at initial
assessment (after 3 yr of treatment), a difference that diminished over 2.7 yr
of continued treatment. CEE did not significantly influence change in other
cognitive functions and affect. Conclusions: CEE did not improve cognitive
functioning in postmenopausal women with prior hysterectomy. CEE was associated
with lower spatial rotational performance after an average of 3 yr of treatment.
Overall, CEE does not appear to have enduring effects on rates of
domain-specific cognitive change in older postmenopausal women.
J Clin
Endocrinol Metab. 2009 Oct 22. [Epub ahead of print]
The Effect of Transdermal Testosterone on
Mammographic Density in Postmenopausal Women Not Receiving Systemic Estrogen
Therapy.
Davis SR, Hirschberg AL, Wagner LK, Lodhi I,
von Schoultz B.
Procter &
Gamble Pharmaceuticals (L.K.W., I.L.), Mason, Ohio 45040.
Context:
Greater mammographic density is associated with increased breast cancer risk
and reduced diagnostic mammographic sensitivity and may be seen with
estrogen/progestin therapy (EPT). The effects of testosterone therapy on
mammographic density in postmenopausal women not on EPT are not known.
Objective: Our objective was to compare effects of two doses of the
testosterone transdermal patch (TTP) with placebo in postmenopausal women
without concomitant EPT on mammographic density over 52 wk. Design: We
conducted a randomized, double-blind, placebo-controlled, parallel-group,
multinational trial. Patients: Patients included 279 postmenopausal women
participating in a testosterone and sexual function study with paired mammograms
for baseline and 52 wk/exit. Interventions: Patients were randomized to
placebo, TTP 150 mug/d, or TTP 300 mug/d, stratified by menopause type (natural
or surgical). Main Outcome Measures: Change from baseline to wk
Gend Med. 2009
Sep;6(3):433-43.
Relationship between serum progesterone concentrations
and cardiovascular disease, diabetes, and mortality in elderly Swedish men and
women: An 8-Year prospective study.
Nilsson SE, Fransson E, Brismar K.
Background:
The use of synthetic progesterone-like substances in hormone replacement
therapy and birth control pills has been associated with increases in
cardiovascular morbidity and the prevalence of diabetes. Objectives: The
primary aims of this study were to investigate whether physiologic
concentrations of progesterone might also be associated with cardiovascular
disease and diabetes, and to explore potential gender differences in these
associations in elderly Swedish men and women. Methods: This prospective,
longitudinal study was performed in a Swedish population-based sample of
opposite-sex twins aged between 71 and 80 years who were not receiving sex
hormone therapy. Serum concentrations of progesterone, estradiol, C-reactive
protein (CRP), and urea were measured at baseline (1996) and at 8-year
follow-up (2004), and serum concentrations of cystatin and insulin were
measured only at follow-up. The outcomes of interest were cardiovascular
morbidity (myocardial infarction, angina pectoris, peripheral arterial disease,
stroke, congestive heart failure [CHF], cardiac arrhythmia, hypertension, and
thromboembolism), diabetes, and mortality throughout the observation period.
Results: At baseline, the study sample included 230 men and 195 women (mean [SD]
age, 74.6 [2.6] years). At follow-up, 132 men and 145 women (mean age, 82.4
[2.5] years) met the inclusion criteria, of whom 128 men and 112 women did so
at both baseline and follow-up. Serum progesterone concentrations, which did
not differ significantly from reported concentrations for the age group, were
significantly associated with mortality across the observation period (P <
0.001). At follow-up, higher serum progesterone was significantly associated
with the occurrence of CHF (P < 0.01); this association remained robust
after adjustment for CRP, cystatin, and insulin levels. Conclusion: In these
elderly Swedish men and women, increased physiologic concentrations of
progesterone were found to be associated with an increased prevalence of CHF,
independent of inflammatory factors, markers of renal function, and insulin
metabolism.
Climacteric. 2009 Oct 22. [Epub
ahead of print]
Comparative effects of continuous combined
hormone therapy and tibolone on body composition in postmenopausal women.
Ziaei S, Moaya M, Faghihzadeh S.
Departments
of Obstetrics & Gynecology.
ObjectiveTo
compare the effects of tibolone with those of continuous combined hormone
replacement therapy (HT) on body composition in postmenopausal women.
MethodsOne hundred and fifty postmenopausal women were enrolled in a
randomized, controlled trial to compare the effects of tibolone with continuous
combined HT on body composition. Patients were randomly allocated into three
groups and followed for 9 months. Of the subjects included, 50 women received
2.5 mg tibolone plus one Cal+D tablet (500 mg calcium and 200 IU vitamin D)
daily, 50 women received 0.625 mg conjugated equine estrogen and 2.5 mg
medroxyprogesterone acetate (CEE/MPA) plus one Cal+D tablet daily, and the rest
(50 women) received only one Cal+D tablet and served as a control group. Body
composition was evaluated with measurements of body mass index (BMI), weight,
waist-to-hip ratio (WHR), fat mass and fat-free mass (FFM) before and after the
intervention. Measurements of body fat mass percentage, fat mass, body fat-free
mass percentage and fat-free mass (FFM) were assessed by measurement of skin-fold
thickness. Results Tibolone significantly increased weight, BMI and FFM and
decreased WHR after the treatment in comparison with baseline (p < 0.05).
However, only weight and BMI increased significantly in the CEE/MPA group after
the treatment (p < 0.05). There were significant increases in weight, BMI
and fat mass in the control group after 9 months. In the comparison of the
parameters after the treatment between the three groups, tibolone significantly
increased FFM compared with the control and CEE/MPA groups (p < 0.01).
Conclusions The effect of tibolone on body composition is favorable and
therefore tibolone may be regarded as an alternative to continuous combined
hormone therapy in postmenopausal women.
J Clin
Endocrinol Metab. 2009 Oct 21. [Epub ahead of
print]
Higher Serum Testosterone Concentration in
Older Women is Associated with Insulin Resistance, Metabolic Syndrome, and
Cardiovascular Disease.
Patel SM, Ratcliffe SJ, Reilly MP, Weinstein R, Bhasin S,
Blackman MR, Cauley JA, et al.
Context:
Early postmenopausal women with higher testosterone (T) levels have increased insulin
resistance (IR) and cardiovascular risk factors, but whether this translates
into increased cardiovascular disease later in life is unknown. Objective: The
objective of the study was to determine whether higher T levels are associated
with IR, the metabolic syndrome (MetSyn), and coronary heart disease (CHD) in
elderly women. Design: Total T and free T by equilibrium dialysis were measured
using ultrasensitive assays in 344 women aged 65-98 yr enrolled in the
Cardiovascular Health Study. Cross-sectional analyses were performed to examine
the associations between total and free T and IR, MetSyn, and CHD. Results:
There was a stepwise increase in the homeostasis model assessment of insulin
resistance with increasing total (P = 0.0.003) and free T (P = 0.02) level and
a corresponding decrease in Quantitative Insulin Sensitivity Check Index (P
< 0.001 and P = 0.002, respectively). In adjusted models, higher levels of
both total and free T were strongly associated with abdominal obesity and high
fasting glucose, the two MetSyn components most strongly linked to IR. After
adjustment, women in the top quartile of total T levels had a 3-fold greater
odds of MetSyn (odds ratio 3.15, 95% confidence interval 1.57-6.35) than those
in the bottom quartile and a 3-fold greater odds of CHD (odds ratio 2.95, 95%
confidence interval 1.2-7.3) than those in second quartile, whereas free T was
not significantly associated with MetSyn or CHD. Conclusions: Higher levels of
T are associated with IR, MetSyn, and CHD in elderly women. Whether T is a
marker or mediator of cardiovascular disease in this population merits further
investigation.
J Vasc
Surg. 2009 Oct 16. [Epub ahead of print]
Aggressive lipid-lowering is more effective
than moderate lipid-lowering treatment in carotid plaque stabilization.
Kadoglou NP, Sailer N, Moumtzouoglou A, Kapelouzou A, Gerasimidis T, Liapis CD.
Department
of Vascular Surgery, University of Athens, Thessaloniki, Greece and Athens,
Greece.
OBJECTIVE:
Atherosclerotic plaque stabilization is a promising strategy to prevent
cerebrovascular events in patients with carotid atherosclerosis. Vascular
calcification inhibitors, known osteopontin (OPN) and osteoprotegerin (OPG), have
emerged as novel cardiovascular biomarkers. This open-label, prospective study
aimed to examine whether aggressive lipid-lowering therapy with atorvastatin is
more effective than moderate lipid-lowering in increasing carotid plaque
echogenicity, assessed by Gray-Scale Median (GSM) score and suppressing serum
OPN and OPG levels in patients with moderate carotid stenosis. METHODS: One
hundred forty patients (64 males, 76 females), aged 50 to 75 years, with
carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial
[NASCET]: 30%-60% for symptomatic and 30%-70% for asymptomatic), but without
indications for surgical intervention, were enrolled. Patients with coronary
heart disease, renal failure, hypothyroidism, osteoporosis, and ongoing use of
statins were excluded. Patients were randomly assigned to: Group A (N = 70):
Moderate lipid-lowering therapy with low-dose of atorvastatin (10 mg-20 mg) to
target LDL-C <100 mg/dL. Group B (N = 70): Aggressive lipid-lowering therapy
with high-dose of atorvastatin (80 mg) to target LDL-C <70 mg/dL. Blood
pressure, lipid and glycemic indexes, hsCRP, serum OPN, and OPG were measured
at baseline and after 12 months as well as the GSM score. Independent samples t
test, paired samples t test, Pearson correlation, and multiple regression
analysis were used (P < .05). RESULTS: There were no significant differences
between groups at baseline. Three patients in group A experienced either
cerebrovascular or cardiac ischemic attacks, while two patients in group B underwent
coronary angioplasty during follow-up. Group B showed a more pronounced
improvement in total cholesterol and LDL-cholesterol compared with group A (P
< .05). Moreover, atorvastatin treatment suppressed serum hsCRP, OPN, and
OPG levels from baseline in both groups (P < .001). Notably, aggressive
treatment decreased OPN (P = .012) and OPG (P = .025) levels to a greater
degree compared with moderate treatment. Similarly, GSM score was remarkably
increased in both groups, but that augmentation was greater in group B (from
66.39 +/- 23.66 to 100.4 +/- 25.31) than in group A (from 64.4 +/- 23.62 to
85.39 +/- 20.21) (P = .024). No change in the degree of carotid stenosis was
noted in both treatment arms. Importantly, the aforementioned reduction in OPN
(r = -0.517, P = .024) and OPG (r = -0.312, P = .008) levels was inversely
associated with GSM score changes in univariate and standard multiple
regression analysis (R(2) = 0.411, P = .021). CONCLUSIONS: Among patients with
moderate carotid stenosis, an aggressive atorvastatin regimen enhanced carotid
plaque echogenicity and reduced serum OPN and OPG levels to a greater extent
than respective moderate atorvastatin therapy. Most importantly, those
atorvastatin-induced effects were associated with OPN and OPG suppression in a
dose-dependent manner.
Cancer
Causes Control. 2009 Oct 21. [Epub ahead of print]
Screening mammography intervals among
postmenopausal hormone therapy users and nonusers.
Onega T, Mackenzie T, Weiss J, Goodrich M,
Titus-Ernstoff L.
Department
of Community and Family Medicine, Dartmouth Medical School, Hanover, NH, USA.
BACKGROUND:
The recent decline in
Cancer
Epidemiol Biomarkers Prev. 2009 Oct 20. [Epub ahead of
print]
Colorectal Cancer Incidence and
Postmenopausal Hormone Use by Type, Recency, and Duration in Cancer Prevention
Study II.
Hildebrand JS, Jacobs EJ, Campbell PT, McCullough ML, Teras LR,
Thun MJ, Gapstur SM.
Department
of Epidemiology, American Cancer Society, Atlanta, Georgia.
The
Women's Health Initiative randomized trials showed a reduction in colorectal
cancer risk with the use of estrogen plus progesterone (E + P), but not with
estrogen alone (E-only), after intervention periods <7 years. Using data
from the Cancer Prevention Study II Nutrition Cohort, we examined associations
of colorectal cancer risk with E-only and E + P, including analyses by recency
and duration of hormone use. During 13.2 years of follow-up, 776 cases of
invasive colorectal cancer occurred among 67,412 postmenopausal women
participants. Cox proportional hazards models were used to estimate multivariate-adjusted
relative risks (RR) and 95% confidence intervals (95% CI) of colorectal cancer
for current and former hormone users according to hormone type and duration of
use. Relative to women who never used postmenopausal hormones, current, but not
former, use of E-only was associated with a reduced risk of colorectal cancer
(RR 0.76; 95% CI, 0.59-0.97). Among current E-only users, duration of use was
inversely and linearly associated with risk (P(trend) = 0.01). Use of E-only
for <5 years was not associated with reduced risk, whereas use for >/=20
years was associated with a 45% reduction in risk (RR, 0.55; 95% CI,
0.36-0.86). There were no statistically significant associations between E + P
and colorectal cancer risk. Our results suggest a strong inverse association of
long-term use of E-only with colorectal cancer risk, underscoring the
importance of collecting data on duration of hormone use in epidemiologic
studies of postmenopausal hormones and risk of disease.
Semana del 14 al
20 de Octubre de 2009
Arterioscler Thromb Vasc Biol. 2009 Oct 15. [Epub
ahead of print]
Postmenopausal Hormone
Therapy and Risk of Idiopathic Venous Thromboembolism. Results From the E3N
Cohort Study.
Canonico M, Fournier A, Carcaillon L, Olié V, Plu-Bureau G, Oger E, Mesrine S, Boutron-Ruault MC, Clavel-Chapelon F, Scarabin PY.
Inserm Unit
780, Cardiovascular Epidemiology Section, Cedex, France; University Paris-South
11, Cedex, France; Inserm ERI20/University Paris-South 11, Villejuif, France;
University Paris Descartes, Paris, France; and Centre Régional de
PharmacoVigilance, Service de Pharmacologie, CHU de Rennes, France.
OBJECTIVE:
Oral estrogen therapy increases venous thromboembolism risk among
postmenopausal women. Although recent data showed transdermal estrogens may be
safe with respect to thrombotic risk, the impact of the route of estrogen
administration and concomitant progestogens is not fully established. METHODS
AND RESULTS: We used data from the E3N French prospective cohort of women born
between 1925 and 1950 and biennially followed by questionnaires from 1990.
Study population consisted of 80 308 postmenopausal women (average follow-up:
10.1 years) including 549 documented idiopathic first venous thromboembolism.
Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox
proportional models. Compared to never-users, past-users of hormone therapy had
no increased thrombotic risk (HR=1.1; 95% CI: 0.8 to 1.5). Oral not transdermal
estrogens were associated with increased thrombotic risk (HR=1.7; 95% CI: 1.1
to 2.8 and HR=1.1; 95% CI: 0.8 to 1.8; homogeneity: P=0.01). The thrombotic
risk significantly differed by concomitant progestogens type (homogeneity:
P<0.01): there was no significant association with progesterone, pregnanes,
and nortestosterones (HR=0.9; 95% CI: 0.6 to 1.5, HR=1.3; 95% CI: 0.9 to 2.0
and HR=1.4; 95% CI: 0.7 to 2.4). However, norpregnanes were associated with
increased thrombotic risk (HR=1.8; 95% CI: 1.2 to 2.7). CONCLUSIONS: In this
large study, we found that route of estrogen administration and concomitant
progestogens type are 2 important determinants of thrombotic risk among
postmenopausal women using hormone therapy. Transdermal estrogens alone or
combined with progesterone might be safe with respect to thrombotic risk.
Eur J Nutr. 2009 Oct
13. [Epub ahead of print]
Alcohol
consumption and the risk of coronary heart disease in postmenopausal women with
diabetes: Women's Health Initiative Observational Study.
Rajpathak SN, Freiberg MS, Wang C, Wylie-Rosett J, Wildman RP, Rohan TE, Robinson JG, Liu S, Wassertheil-Smoller S.
Department
of Epidemiology and Population Health, Albert Einstein College of Medicine,
Bronx, NY, 10461, USA, swapnil.rajpathak@einstein.yu.edu.
BACKGROUND:
Although several observational studies have consistently reported an inverse
association between moderate alcohol consumption and risk of coronary heart
disease (CHD), it is yet not well established if this association also exists
among people with type 2 diabetes. The aim of this study is to evaluate the
association between the frequency and quantity of alcohol intake and the risk
of developing CHD among postmenopausal women with diabetes. METHODS: We
conducted a prospective cohort study, which included 3,198 women with
self-reported diabetes and without any history of cardiovascular disease at
baseline, in the Women's Health Initiative Observational Study. Alcohol intake
was assessed by a semiquantitative food frequency questionnaire. The primary
outcome of this study was CHD, which was validated by medical record review.
Cox proportional hazards regression was used to estimate the hazard ratio (HR)
for the association of alcohol intake and risk of incident CHD while adjusting
for several potential confounders. RESULTS: During the 22,546 person-years of
follow-up, there were 336 incident cases of CHD. Both frequency and quantity of
alcohol intake were inversely associated with the risk of developing CHD.
Compared to nondrinkers, the multivariable HRs across categories of frequency
of alcohol consumption (</=0.5, 0.5-2 and >/=2 drinks/week) were 0.89
(95% confidence intervals [CI]: 0.63, 1.26), 0.84 (95% CI: 0.56, 1.25) and 0.65
(95% CI: 0.43, 0.99), respectively (p for trend: 0.04). This association did
not appear to differ based on the type of the alcoholic beverage consumed.
CONCLUSIONS: Moderate alcohol consumption of postmenopausal women with type 2
diabetes may have a benefit on CHD similar to that seen in postmenopausal
nondiabetic women. The potential risks of alcohol on noncardiac outcomes may
need consideration when recommending alcohol to women with diabetes.
Am J Epidemiol. 2009 Oct
14. [Epub ahead of print]
Postmenopausal
Breast Cancer Risk and Dietary Patterns in the E3N-EPIC Prospective Cohort
Study.
Cottet V, Touvier M, Fournier A, Touillaud MS, Lafay L, Clavel-Chapelon F, Boutron-Ruault MC.
Drs.
Vanessa Cottet and Mathilde Touvier contributed equally to this article, and
their names are given in alphabetical order.
Since
evidence relating diet to breast cancer risk is not sufficiently consistent to
elaborate preventive proposals, the authors examined the association between
dietary patterns and breast cancer risk in a large French cohort study. The
analyses included 2,381 postmenopausal invasive breast cancer cases diagnosed
during a median 9.7-year follow-up period (1993-2005) among 65,374 women from
the E3N-EPIC cohort. Scores for dietary patterns were obtained by factor
analysis, and breast cancer hazard ratios were estimated by Cox proportional
hazards regression for the highest quartile of dietary pattern score versus the
lowest. Two dietary patterns were identified: "alcohol/Western"
(essentially meat products, French fries, appetizers, rice/pasta, potatoes,
pulses, pizza/pies, canned fish, eggs, alcoholic beverages, cakes, mayonnaise,
and butter/cream) and "healthy/Mediterranean" (essentially
vegetables, fruits, seafood, olive oil, and sunflower oil). The first pattern
was positively associated with breast cancer risk (hazard ratio = 1.20, 95%
confidence interval (CI): 1.03, 1.38; P = 0.007 for linear trend), especially
when tumors were estrogen receptor-positive/progesterone receptor-positive. The
"healthy/Mediterranean" pattern was negatively associated with breast
cancer risk (hazard ratio = 0.85, 95% CI: 0.75, 0.95; P = 0.003 for linear
trend), especially when tumors were estrogen receptor-positive/progesterone
receptor-negative. Adherence to a diet comprising mostly fruits, vegetables,
fish, and olive/sunflower oil, along with avoidance of Western-type foods, may
contribute to a substantial reduction in postmenopausal breast cancer risk.
Arch Intern Med. 2009 Oct
12;169(18):1684-91
New-onset
breast tenderness after initiation of estrogen plus progestin therapy and
breast cancer risk.
Crandall CJ, Aragaki AK, Chlebowski RT, McTiernan A, Anderson G, Hendrix SL, Cochrane BB, Kuller LH, Cauley JA.
Department
of Medicine, David Geffen School of Medicine at University of California, UCLA
Medicine/GIM, Los Angeles, CA 90024, USA. ccrandall@mednet.ucla.edu
BACKGROUND:
Estrogen plus progestin therapy increases breast cancer incidence and breast
tenderness. Whether breast tenderness during estrogen plus progestin therapy is
associated with breast cancer risk is uncertain. METHODS: We analyzed data from
the Women's Health Initiative Estrogen + Progestin Trial, which randomized
postmenopausal women with an intact uterus to receive daily conjugated equine
estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg (n = 8506), or
placebo (n = 8102). At baseline and annually, participants underwent
mammography and clinical breast examination. Self-reported breast tenderness
was assessed at baseline and at 12 months. The incidence of invasive breast
cancer was confirmed by medical record review (mean follow-up of 5.6 years).
RESULTS: Of women without baseline breast tenderness (n = 14,538), significantly
more assigned to receive conjugated equine estrogens plus medroxyprogesterone
vs placebo experienced new-onset breast tenderness after 12 months (36.1% vs
11.8%, P < .001). Of women in the conjugated equine estrogens plus
medroxyprogesterone group, breast cancer risk was significantly higher in those
with new-onset breast tenderness compared with those without (hazard ratio,
1.48; 95% confidence interval, 1.08-2.03; P = .02). In the placebo group,
breast cancer risk was not significantly associated with new-onset breast
tenderness (P = .97). CONCLUSIONS: New-onset breast tenderness during
conjugated equine estrogens plus medroxyprogesterone therapy was associated
with increased breast cancer risk. The sensitivity and specificity of the
association between breast tenderness and breast cancer were similar in
magnitude to those of the Gail model.
J Bone Miner Res. 2009 Oct
12. [Epub
ahead of print]
Obesity and
Fractures in Postmenopausal Women.
Premaor MO, Pilbrow L, Tonkin C, Parker R, Compston J.
Abstract
Low BMI is a recognized risk factor for fragility fracture whilst obesity is
widely believed to be protective. As part of a clinical audit of guidance from
the National Institute of Health and Clinical Excellence (NICE) we have
documented the prevalence of obesity and morbid obesity in postmenopausal women
aged < 75 years presenting to our Fracture Liaison Service (FLS). Between
January 2006 and December 2007 1005 postmenopausal women aged < 75 years
with a low trauma fracture were seen in the FLS. 805 of these women (80%)
underwent assessment of bone mineral density (BMD) by dual energy X-ray
absorptiometry (DXA) and values for body mass index (BMI were available in 799.
The prevalence of obesity (BMI 30-34.9 kg/m(2)) and morbid obesity (BMI >/=
35 kg/m(2)) in this cohort was 19.3% and 8.4% respectively. 59.1% of obese and
73.1% of morbidly obese women had normal BMD, and only 11.7% and 4.5%
respectively had osteoporosis (p<0.0001). Multiple regression analysis
revealed significant negative associations between hip T-score and age
(p<0.0001), and significant positive associations with BMI (p<0.0001) and
previous fracture (p=0.001). Our results demonstrate a surprisingly high
prevalence of obesity in postmenopausal women presenting to a FLS with low
trauma fracture. The majority of these women had normal BMD as measured by DXA.
Our findings have important public health implications in view of the rapidly
rising increase in obesity in many populations and emphasise the need for
further studies to establish the pathogenesis of fractures in obese individuals
and to determine appropriate preventive strategies.
Cochrane Database Syst Rev. 2009 Oct
7;(4):CD001405.
Oestrogen
therapy for urinary incontinence in post-menopausal women.
Cody JD, Richardson K, Moehrer B, Hextall A, Glazener CM.
Cochrane
Incontinence Review Group, University of Aberdeen, 1st Floor, Health Sciences
Building, Foresterhill, Aberdeen, UK, AB25 2ZD.
BACKGROUND:
It is possible that oestrogen deficiency may be an aetiological factor in the
development of urinary incontinence in women. OBJECTIVES: To assess the effects
of local and systemic oestrogens used for the treatment of urinary
incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group
Specialised Register of trials (2 April 2009) and the reference lists of
relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised
controlled trials that included oestrogens in at least one arm, in women with
symptomatic or urodynamic diagnoses of stress, urgency or mixed urinary
incontinence or other urinary symptoms post-menopause. DATA COLLECTION AND
ANALYSIS: Trials were evaluated for methodological quality and appropriateness
for inclusion by the review authors. Data were extracted by at least two authors
and cross checked. Subgroup analyses were performed grouping participants under
local or systemic administration. Where appropriate, meta-analysis was
undertaken. MAIN RESULTS: Thirty- three trials were identified which included
19,313 (1,262 involved in trials of local administration) incontinent women of
whom 9417 received oestrogen therapy. Sample sizes ranged from 16 to 16,117.
The trials used varying combinations of type of oestrogen, dose, duration of
treatment and length of follow up. Outcome data were not reported consistently
and were available for only a minority of outcomes.Systemic administration (of
oral oestrogens) resulted in worse incontinence than on placebo (RR 1.32, 95%
CI 1.17 to 1.48). This result is heavily weighted by a subgroup of women from
the Hendrix trial, which had large numbers of participants and a longer follow
up of one year; all the women had had a hysterectomy and the treatment used was
conjugated equine oestrogen. The result for women with an intact uterus where
oestrogen and progestogen combined were used also showed a statistically
significant worsening of incontinence (RR 1.11, 95% CI 1.04 to 1.18).There was
some evidence that oestrogens used locally (for example vaginal creams or
tablets) may improve incontinence (RR 0.74, 95% CI 0.64 to 0.86). Overall,
there were around one to two fewer voids in 24 hours and nocturnal voids
amongst women treated with local oestrogen, and there was less frequency and
urgency. No serious adverse events were reported although some women
experienced vaginal spotting, breast tenderness or nausea.Women who were
continent and received systemic oestrogen replacement, with or without
progestogens, for reasons other than urinary incontinence were more likely to
report the development of new urinary incontinence in one large study.The data
were too few to address questions about oestrogens compared with or in
combination with other treatments, different types of oestrogen or different
modes of delivery. AUTHORS' CONCLUSIONS: Local oestrogen treatment for
incontinence may improve or cure it, but there was little evidence from the
trials on the period after oestrogen treatment had finished and none about
long-term effects. However, systemic hormone replacement therapy, using
conjugated equine oestrogen, may make incontinence worse. There were too few
data to reliably address other aspects of oestrogen therapy, such as oestrogen
type and dose, and no direct evidence on route of administration. The risk of
endometrial and breast cancer after long-term use suggests that oestrogen
treatment should be for limited periods, especially in those women with an
intact uterus.
Semana
del 7 al 13 de Octubre de 2009
Maturitas. 2009 Oct 6. [Epub ahead of print]
Effects
of sleep disturbance on the quality of life of Turkish menopausal women: A
population-based study.
OBJECTIVES: The purpose of this study was
to investigate sleep disturbances among menopausal women: their prevalence,
risk factors for them and the quality of life of women who have them. DESIGN: A
population-based sample of 887 Turkish women aged 45-59 years and living in
Malatya was recruited in this cross-sectional descriptive study. The women were
administered the Interview Form, which covers sociodemographic, health and
lifestyle variables, as well as the Women's Health Initiative Insomnia Rating
Scale, the Menopause Specific Quality of Life Questionnaire and the Beck
Depression Inventory. RESULTS: The prevalence of sleep disturbance in this
sample of menopausal women was 54%. Logistic regression models revealed that
the risk of sleep disturbance was 2.4 times higher in the perimenopausal than
in the premenopausal period, 1.7 times higher among those who received hormone
therapy than among those who did not, 1.5 times higher among those with a
physical disease than among those without, and 3.9 times higher among those
with depression than among those without; an increase of one year in age was
associated with a 5% increase in the prevalence of sleep disturbance. Average
scores on the vasomotor, psychosocial, physical and sexual sub-scales of the
Menopause Specific Quality of Life Questionnaire were significantly higher for
women with sleep disturbance than for those without (P<0.001). CONCLUSIONS:
The prevalence of sleep disturbance was found to be high among menopausal
women. Initiatives aimed at reducing sleep disturbance should be added to
menopausal care programmes in order to improve the quality of life of
menopausal women.
Vascul
Pharmacol. 2009 Oct
5. [Epub ahead of print]
Alendronate
affects calcium dynamics in cardiomyocytes in vitro.
Kemeny-Suss N, Kasneci A, Rivas D, Afilalo J, Komarova SV, Chalifour LE, Duque G.
Faculty
of Dentistry, McGill University, Montreal, Quebec, Canada, H3A 2B2.
Therapy with bisphosphonates, including
alendronate (ALN), is considered a safe and effective treatment for
osteoporosis. However, recent studies have reported an unexpected increase in
serious atrial fibrillation (AF) in patients treated with bisphosphonates. The
mechanism that explains this side effect remains unknown. Since AF is
associated with an altered sarcoendoplasmic reticulum calcium load, we studied
how ALN affects cardiomyocyte calcium homeostasis and protein isoprenylation in
vitro. Acute and long-term (48h) treatment of atrial and ventricular
cardiomyocytes with ALN (10(-8)-10(-6)M) was performed. Changes in calcium
dynamics were determined by both fluorescence measurement of cytosolic free Ca(2+)
concentration and western blot analysis of calcium-regulating proteins.
Finally, effect of ALN on protein farnesylation was also identified. In both
atrial and ventricular cardiomyocytes, ALN treatment delayed and diminished
calcium responses to caffeine. Only in atrial cells, long-term exposure to ALN
induced transitory calcium oscillations acutely, and led to development of
oscillatory component in calcium responses to caffeine. Changes in calcium
dynamics were accompanied by changes in expression of proteins controlling
sarcoendoplasmic reticulum calcium. In contrast, ALN minimally affected protein
isoprenylation in these cells. In summary, treatment of atrial cardiomyocytes
with ALN induced abnormalities in calcium dynamics consistent with induction of
a self-stimulatory, pacemaker-like behavior, which may contribute to
development of cardiac side effects associated with these drugs.
N Engl J
Med. 2009 Oct
8;361(15):1459-65.
Osteoporosis
associated with neutralizing autoantibodies against osteoprotegerin.
Riches PL, McRorie E, Fraser WD, Determann C, van't Hof R, Ralston SH.
Rheumatic
Diseases Unit, Institute of Genetics and Molecular Medicine, University of
Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
Autoantibodies against osteoprotegerin,
which block the inhibitory effect of osteoprotegerin on signaling by the
receptor activator of nuclear factor (NF)-kappaB (RANK), were identified in a
man with celiac disease who presented with severe osteoporosis and high bone
turnover. The osteoporosis did not respond to the treatment of his celiac
disease but was completely reversed by bisphosphonate therapy. Autoantibodies
against osteoprotegerin were detected in three additional patients with celiac
disease. Such autoantibodies may be associated with the development of
high-turnover osteoporosis, but whether autoantibodies against osteoprotegerin
commonly contribute to the pathogenesis of osteoporosis in patients with celiac
disease remains to be determined.
Am J
Physiol Regul Integr Comp Physiol. 2009 Oct
7. [Epub ahead of print]
Estrogen
replacement restores flow-induced vasodilation in coronary arterioles of aged
and ovariectomized rats.
Leblanc AJ, Reyes R, Kang LS, Dailey RA, Stallone JN, Moningka NC, Muller-Delp JM.
The risk for cardiovascular disease (CVD) increases
with advancing age; however, the age at which CVD risk increases significantly
is delayed by more than a decade in women compared to men. This
cardioprotection, which women experience until menopause, is presumably due to
the presence of ovarian hormones, in particular estrogen. The purpose of this
study was to determine how age and ovarian hormones affect flow-induced
vasodilation in the coronary resistance vasculature. Coronary arterioles were
isolated from young (6 mos), middle-aged (14 mos), and old (24 mos) intact,
ovariectomized (OVX) and ovariectomized + estrogen replaced (OVE) female
Fischer-344 rats to assess flow-induced vasodilation. Advancing age impaired
flow-induced dilation of coronary arterioles (Young: 50 +/- 4 vs. Old: 34 +/-
6; % relaxation). Ovariectomy reduced flow-induced dilation in arterioles from
young females and estrogen replacement restored vasodilation to flow. In aged
females, flow-induced vasodilation of arterioles was unaltered by OVX; however,
estrogen-replacement improved flow-induced dilation by ~ 160%. The contribution
of NO to flow-induced dilation, assessed by nitric oxide synthase (NOS)
inhibition with L-NAME, declined with age. L-NAME did not alter flow-induced
vasodilation in arterioles from OVX rats, regardless of age. In contrast,
L-NAME reduced flow-induced vasodilation of arterioles from estrogen-replaced
rats at all ages. These findings indicate that the age-induced decline of
flow-induced, NO-mediated dilation in coronary arterioles of female rats is related,
in part, to a loss of ovarian estrogen and estrogen supplementation can improve
flow-induced dilation, even at an advanced age.
J Clin
Endocrinol Metab. 2009 Oct
6. [Epub ahead of print]
Influence
of Age and Obesity on Serum Estradiol, Estrone, and Sex Hormone Binding
Globulin Concentrations following Oral Estrogen Administration in
Postmenopausal Women.
Karim R, Mack WJ, Hodis HN, Roy S, Stanczyk FZ.
Department
of Pediatrics (R.K.), Department of Preventive Medicine (R.K., W.J.M., H.N.H),
Atherosclerosis Research Unit (R.K., W.J.M., H.N.H), Department of Medicine
(H.N.H.), and Department of Obstetrics and Gynecology (S.R., F.Z.S.),
University of Southern California, Los Angeles, California 90033.
Objective: Hormone therapy (HT) increases
the risk of venous thrombosis and stroke. Risk of venous thrombosis and stroke
is higher in older, overweight, and obese women using HT. However, the impact
of age and obesity on estrogen concentrations among HT users is not well
defined. Method: We measured serum levels of estrone, total and free estradiol,
and SHBG in 180 postmenopausal women participating in the Estrogen in the
Prevention of Atherosclerosis Trial (EPAT), 91 receiving estradiol therapy (ET)
and 89 taking placebo, every 6 months over 2 yr. Mean on-trial levels of
estrogens and SHBG were compared across age, body mass index (BMI), and waist
to hip ratio categories among ET users and placebo separately. Results: Among
the ET users, total (P = 0.01) and free estradiol (P = 0.002) were
significantly directly associated with BMI adjusted for age. SHBG was inversely
related to waist to hip ratio adjusted for age (P = 0.005). Age was not
associated with any of the estrogen or SHBG concentrations in ET or placebo
groups. BMI was positively associated with estrone concentrations among older
but not younger ET users (P for interaction = 0.03). Conclusion: Overweight and
obese women using ET attain greater concentrations of estrogen compared to women
with normal BMI, whereas ET users with abdominal obesity attain lower SHBG
levels. Obese older women using ET have the highest concentration of estrone.
It may be useful to consider age and obesity when prescribing HT to minimize
the risk of venous thrombosis or stroke in postmenopausal women. Further
research regarding relationships among circulating hormone levels and risk for
these conditions is required to substantiate this conclusion.
Climacteric
2009; 12: 445 - 453
Risk of
cardiovascular outcomes in users of estradiol/dydrogesterone or other HRT
preparations
C.
Schneider; S. S. Jick; C. R. Meier
Background. Use of postmenopausal hormone replacement
therapy (HRT) used to be promoted to reduce the risk of ischemic cardiovascular
diseases, a concept which has been challenged by results of the large Women's
Health Initiative trial in users of estrogen and progestin. It is postulated
that the type of progestin used in HRT affects the cardiovascular risk. Methods We used the UK-based General
Practice Research Database to conduct a follow-up study with a nested
case-control analysis. We assessed and compared the risk of developing
myocardial infarction, thrombotic stroke or venous thromboembolism in
estradiol/dydrogesterone users, users of other HRT, or non-users of HRT. Results The incidence rates of
myocardial infarction, thrombotic stroke and venous thromboembolism in
estradiol/dydrogesterone users were 0.40 (95% confidence interval (CI)
0.18-0.76), 0.27 (95% CI 0.10-0.58) and 0.31 (95% CI 0.13-0.64) per 1000
person-years, respectively. As compared to non-users of HRT, the adjusted
relative risk estimates (odds ratios) in the nested case-control analysis for
estradiol/dydrogesterone users or users of other HRT were 1.06 (95% CI
0.48-2.36) and 1.12 (95% CI 0.84-1.51) for myocardial infarction, 0.50 (95% CI
0.21-1.22) and 1.18 (95% CI 0.94-1.48) for thrombotic stroke, and 0.84 (95% CI
0.37-1.92) and 1.42 (95% CI 1.10-1.82) for venous thromboembolism,
respectively. Conclusion The
study provides evidence that estradiol/dydrogesterone use of several months to
a few years is not associated with a higher risk of cardiovascular events than
use of other HRT.
J Sex Med. 2009
Oct;6(10):2690-2697.
The
Relationship between Self-Reported Sexual Satisfaction and General Well-Being
in Women.
Davison SL, Bell RJ, Lachina M, Holden SL, Davis SR.
Women's Health Program,
Department of Medicine, Central and Eastern Clinical School, Monash University,
Alfred Hospital, Prahran, Vic., Australia;
Introduction. The extent to which
low sexual function or sexual dissatisfaction in women impacts on well-being
remains uncertain, yet this is a critical issue in the controversy as to the
benefits of pharmacotherapy for women seeking treatment for female sexual
dysfunction. Aim. To explore the relationship between well-being and
self-perceived satisfaction with sexual function in women and to determine if
there is an independent effect of menopausal status or age. Design. A
community-based cross-sectional study. Patients. A total of 421 women, aged 18
to 65 years were recruited from the community. Women were required to
self-identify at study outset as being either satisfied or dissatisfied with
their sexual life and be premenopausal or postmenopausal. Main Outcome
Measures. Scores from the Psychological General Well-Being Index (PGWB), the
Beck Depression Index (BDI) and a daily diary of sexual function. Results. A
group of 349 women were included in the analysis. Total PGWB and domain scores
of positive well-being and vitality were lower in dissatisfied women compared
to satisfied women. PGWB total and domain scores of depressed mood, positive
well-being and vitality were higher in older women. Menopause did not have an
independent effect on well-being. Conclusions. Women who self-identify as
having sexual dissatisfaction have lower psychological general well-being.
These findings reinforce the importance of addressing sexual health and
well-being in women as an essential component of their health care.
Semana del 30 de Septiembre al 6 de Octubre de 2009
Obesity
(Silver Spring). 2009 Oct
1. [Epub ahead of print]
Metabolic Syndrome and Changes in Body Fat
From a Low-fat Diet and/or Exercise Randomized Controlled Trial.
Camhi SM, Stefanick ML, Katzmarzyk PT, Young DR.
Population Science, Pennington Biomedical
Research Center, Baton Rouge, Louisiana, USA.
It is difficult to identify the successful
component(s) related to changes in metabolic syndrome (MetS) from lifestyle
interventions: the weight loss, the behavior change, or the combination. The
purpose of this study is to determine the effects of a weight-stable randomized
controlled trial of low-fat diet and exercise, alone and in combination, on
MetS. Men (n = 179) and postmenopausal women (n = 149) with elevated
low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein
cholesterol (HDL-C) were randomized into a 1-year, weight-stable trial with
four treatment groups: control (C), diet (D), exercise (E), or diet plus
exercise (D+E). MetS was defined using a continuous score. Changes in MetS
score (DeltaMetS) were compared between groups using analysis of covariance, stratified
by gender and using two models, with and without baseline and change in percent
body fat (DeltaBF) as a covariate. In men, DeltaMetS was higher for D vs. C (P
= 0.04), D+E vs. C (P = 0.0002), and D+E vs. E (P = 0.02). For women, DeltaMetS
was greater for D vs. C (P = 0.045), E vs. C (P = 0.02), and D+E vs. C (P =
0.004). After adjusting for DeltaBF, all differences between groups were
attenuated and no longer significant. DeltaMetS were associated with DeltaBF
for both men (P < 0.0001) and women (P = 0.004). After adjustment for
DeltaBF, low-fat diet alone and in combination with exercise had no effect on
MetS. The key component for MetS from low-fat diet and/or increased physical
activity appears to be body fat loss.
J Bone
Joint Surg Am. 2009
Oct;91(10):2376-80.
Patients with wrist fractures are less
likely to be evaluated and managed for osteoporosis.
Gong HS, Oh WS, Chung MS, Oh JH, Lee YH, Baek GH.
Department of Orthopaedic Surgery, Seoul
National University Bundang Hospital, Seoul National University College of
Medicine, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, South
Korea.
BACKGROUND: Although osteoporosis is being
evaluated and treated increasingly in elderly patients with fragility
fractures, some studies have suggested that physicians may be missing important
opportunities, especially in patients with nonvertebral fractures. The purpose
of the present study was to determine whether specialists responsible for
treating fractures at various locations have different propensities for
evaluating and treating osteoporosis after a fracture in female patients over
the age of fifty years. METHODS: A retrospective nationwide cohort study was
performed with use of data collected during 2007 by the Korean Health Insurance
Review Agency, which covers 97% of the population. The incidences of fractures
around the hip, spine, and wrist in female patients more than fifty years of
age and the frequencies of bone density scans for osteoporosis and the use of
medications for its treatment were analyzed and compared. RESULTS: The database
identified 31,540 hip fractures, 58,291 spine fractures, and 61,234 wrist
fractures in female patients who were more than fifty years of age in
BMC
Cancer. 2009 Oct
1;9(1):349. [Epub ahead of print]
Intensity and timing of physical activity
in relation to postmenopausal breast cancer risk: the prospective NIH-AARP Diet
and Health Study.
Peters TM, Moore SC, Gierach GL, Wareham NJ, Ekelund U, Hollenbeck AR, Schatzkin A, Leitzmann MF.
ABSTRACT: BACKGROUND: Despite strong
evidence of an inverse association of physical activity with postmenopausal
breast cancer risk, whether a certain intensity or time of life of physical
activity is most effective for lowering breast cancer risk is not known.
METHODS: In 118,899 postmenopausal women in the prospective NIH-AARP Diet and
Health Study, we examined the relations of light and moderate-to-vigorous
intensity physical activity during four periods of life
("historical": ages 15-18, 19-29, 35-39 years; "recent":
past 10 years) to postmenopausal breast cancer risk. Physical activity was
assessed by self-report at baseline, and 4287 incident breast cancers were
identified over 6.6 years of follow-up. RESULTS: In age-adjusted and
multivariate Cox regression models, >7 hours/week of moderate-to-vigorous
activity during the past 10 years was associated with 16% reduced risk of
postmenopausal breast cancer (RR:0.84; 95%CI:0.76,0.93) compared with
inactivity. The association remained statistically significant after adjustment
for BMI (RR:0.87; 95%CI:0.78,0.96). Neither moderate-to-vigorous intensity
activity during other periods of life nor light intensity activity during any
period of life was related to breast cancer risk, and associations did not vary
by tumor characteristics. CONCLUSIONS: A high level of recent, but not
historical, physical activity of moderate-to-vigorous intensity is associated
with reduced postmenopausal breast cancer risk. More precise recall of recent
physical activity than activity in the distant past is one possible explanation
for our findings.
Calcif
Tissue Int. 2009 Oct
1. [Epub ahead of print]
Minimum Required Vitamin D Level for
Optimal Increase in Bone Mineral Density with Alendronate Treatment in
Osteoporotic Women.
Ishijima M, Sakamoto Y, Yamanaka M, Tokita A, Kitahara K, Kaneko H, Kurosawa H.
Department of Orthopaedics, Juntendo
University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo.
Vitamin D insufficiency and deficiency are
common in the elderly. Most previous studies using alendronate have used
vitamin D supplementation regardless of individual vitamin D status. However,
the minimum required vitamin D levels for the efficacy of alendronate treatment
of osteoporosis remain unclear. Fifty-two postmenopausal women, diagnosed with
osteoporosis, were enrolled in this prospective study, in which they took 5 mg
of alendronate daily for 6 months without any supplements. Associations between
baseline factors and their changes during the treatment and the change in the
lumbar spine bone mineral density (LS-BMD) were examined. The most appropriate
cut-off level of 25-hydroxyvitamin D (25[OH]D) for the optimal increase in
LS-BMD with alendronate was determined using the Akaike information criterion
statistical criterion. Overall, alendronate treatment significantly increased
LS-BMD by 4.7%. The basal serum 25(OH)D and change in urinary NTX were
significantly associated with the increase in LS-BMD. The increase in LS-BMD
between the two groups was not different when comparing those with baseline
25(OH)D above vs. below 30 ng/ml. However, 25(OH)D of 25 ng/ml was determined
to be the minimum required vitamin D level for an adequate effect of
alendronate. Vitamin D status may affect the increase in LS-BMD with
alendronate treatment in individuals being treated for osteoporosis, and a
25(OH)D level >25 ng/ml appears to be required for an optimal LS-BMD
response.
Hum
Reprod Update. 2009 Sep
30. [Epub ahead of print]
Should the ovaries be removed or retained
at the time of hysterectomy for benign disease?
Hickey M, Ambekar M, Hammond I.
School of Women's and Infants' Health,
University of Western Australia, King Edward Memorial Hospital, 374 Bagot Road,
Subiaco, WA 6008, Australia.
BACKGROUND Bilateral oophorectomy is
commonly performed at the time of hysterectomy for benign disease. Indications
for oophorectomy vary, but in most cases relatively little high-quality
information is available to inform the surgeon or patient regarding the
relative risks and benefits of ovarian conservation or removal. This review
will address the common clinical situations when oophorectomy may be performed
and will evaluate the evidence for risk and benefit in each of these
circumstances. The aim of this review is to bring together the evidence
regarding oophorectomy in pre- and post-menopausal women and to highlight the
areas needing further study. METHODS We searched the published literature for
studies related to outcomes following surgical menopause, risk-reducing surgery
for ovarian cancer, surgical treatment for endometriosis, bilateral
oophorectomy for benign disease and treatment for premenstrual
syndrome/premenstrual dysphoric disorder. RESULTS Rates of oophorectomy at the
time of hysterectomy for benign disease appear to be increasing. There is good
evidence to support bilateral salpingoophorectomy (BSO) as a risk-reducing
surgery for women at high risk of ovarian cancer, but relatively little evidence
to support oophorectomy or BSO in other circumstances. There is growing
evidence from observational studies that surgical menopause may impact
negatively on future cardiovascular, psychosexual, cognitive and mental health.
CONCLUSION Clinicians and patients should fully consider the relative risks and
benefits of oophorectomy on an individual basis prior to surgery.
Hypertension. 2009 Sep 28. [Epub ahead of print]
Effect of Cardiorespiratory Fitness on
Vascular Regulation and Oxidative Stress in Postmenopausal Women.
Pialoux V, Brown AD, Leigh R, Friedenreich CM, Poulin MJ.
Departments of Physiology and
Pharmacology, Medicine, and Clinical Neurosciences, Hotchkiss Brain Institute,
and Libin Cardiovascular Institute of Alberta, Faculty of Medicine, and Faculty
of Kinesiology, University of Calgary, Calgary, Alberta, Canada; Alberta Health
Services, Calgary, Alberta, Canada.
Increasing evidence exists suggesting an
important role for oxidative stress in the pathogenesis and progression of
hypertension in women via a decrease of NO production after menopause. Regular
physical training has been shown to upregulate antioxidant enzymatic systems,
which may slow down the usual increase of oxidative stress in postmenopausal
women. The aims of this study were to determine the impact of fitness status on
enzymatic antioxidant efficiency, oxidative stress, and NO production and to
determine the associations among oxidative stress, enzymatic antioxidant and NO
production, mean arterial blood pressure (MABP), and cerebrovascular
conductance (CVC) in postmenopausal women (n=40; 50 to 90 years old). Physical
fitness, physical activity, resting MABP, and CVC were measured. End product of
NO, lipid peroxidation (malondialdehyde and 8-iso-prostaglandin F2alpha), DNA
oxidation (8-hydroxy-2'-deoxyguanosine), protein nitration (nitrotyrosine),
antioxidant glutathione peroxidase, and catalase activities were measured in
plasma. We identified significant negative associations between oxidative
stress and indices of physical fitness (malondialdehyde: r=-0.33, P<0.05;
8-iso-prostaglandin F2alpha: r=-0.39, P<0.05; 8-hydroxy-2'-deoxyguanosine:
r=-0.35, P<0.05) and physical activity (malondialdehyde: r=-0.30, P<0.05;
8-iso-prostaglandin F2alpha: r=-0.41, P<0.01; 8-hydroxy-2'-deoxyguanosine:
r=-0.39, P<0.05). Conversely, glutathione peroxidase was positively
correlated with fitness level (r=0.55; P<0.01). Finally, MABP and CVC were
significantly associated with 8-hydroxy-2'-deoxyguanosine (MABP: r=0.36,
P<0.05; CVC: r=-0.36, P<0.05), nitrotyrosine (MABP: r=0.39, P<0.05;
CVC: r=-0.32, P<0.05), and the end product of NO (MABP: r=-0.57, P<0.01;
CVC: r=0.44, P<0.01). These findings demonstrate that, after menopause,
fitness level and regular physical activity mediate against oxidative stress by
maintaining antioxidant enzyme efficiency. Furthermore, these results suggest
that oxidative stress and NO production modulate MABP and CVC.
J
Psychiatr Res. 2009 Sep
24. [Epub ahead of print]
Suicide attempts among women during low
estradiol/low progesterone states.
Baca-Garcia E, Diaz-Sastre C, Ceverino A, Perez-Rodriguez MM, Navarro-Jimenez R, et
al.
Department of Psychiatry at the New York
State Psychiatric Institute and Columbia University, NY, USA; Department of
Psychiatry, Fundacion Jimenez Diaz Hospital, Autonoma University of Madrid,
Spain; Centro de Investigación Biomédica en Red en el área de Salud Mental
(CIBERSAM), Madrid, Spain.
The relationship between the menstrual
cycle and risk for suicidal behaviors is not clear. The aim of this study is to
determine whether perimenstrual phases in fertile women are associated with
acute risk for suicide attempt and explore whether risk is elevated during low
estradiol/low progesterone states. Women (N=431) recruited within 24h of a
suicide attempt were assessed for psychopathology, suicidal behavior and LH,
FSH, estradiol and progesterone blood levels. Among fertile women (N=281/431),
suicide attempts were more likely to occur during menses (26%, 72/281 observed
vs. 15%, 43/281 expected attempts; p<0.001). Compared to women whose
attempts occurred during other phases, women who attempted suicide during low
estradiol/low progesterone states (menstrual phase, amenorrhea and menopause)
reported severe suicide intent, a measure that may be predictive of eventual
suicide death. Suicide attempts among women are more likely when estrogen and
progesterone levels are low and attempts made under these conditions are
associated with greater severity. Low gonadal hormone levels may constitute a
key factor in the neurobiological basis of suicidal behavior among women,
suggesting a novel, testable hypothesis regarding the underpinnings of suicidal
acts.
Maturitas. 2009 Sep 23. [Epub ahead of print]
When, why and for whom there is a
relationship between physical activity and menopause symptoms.
McAndrew LM, Napolitano MA, Albrecht A, Farrell NC, Marcus BH, Whiteley JA.
Dept. of Veterans Affairs NJ Healthcare
System, War Related Illness and
OBJECTIVES: The relationship between
enhanced physical activity and decreased menopause symptoms is equivocal. In
this study we sought to better understand this relationship by examining the
association of physical activity to different symptom domains and by examining
mediating and moderating variables. STUDY DESIGN: Women participating in a
randomized control trial on physical activity were given a menopause symptom
measure (MENQOL) at follow-up. Of the 280 women participating, 113 (mean
age=52) reported having symptoms they attributed to menopause. Regression
analyses were run to examine if change in physical activity predicted fewer
symptoms. Exercise self-efficacy was examined as a mediator and depressive
symptoms as a moderator. RESULTS: An increase in physical activity from
baseline was found to be related to reporting fewer total menopause symptoms
(beta=-0.22, p=.02). When the total menopause symptoms score was examined by
domain, increased physical activity was found to be related to reporting fewer
general symptoms attributed to menopause (psychosocial (beta=-0.18, p=.05) and
physical (beta=-0.23, p=.01)), but had no effect on specific symptoms of
menopause (vasomotor and sexual). Exercise self-efficacy was found to mediate
the relationship between increased physical activity and total, physical and
psychosocial menopause symptoms. Finally, for individuals with high depressive
symptoms, those who increased physical activity the most reported fewer sexual
symptoms of menopause. CONCLUSION: This study suggests that physical activity
participation is associated with lower general symptom reporting as opposed to
specifically impacting menopause symptoms. Further, exercise self-efficacy
mediates the relationship between physical activity and general menopause
symptoms, suggesting a psychological pathway.
Hear Res. 2009 Sep 22. [Epub ahead of print]
The menopause triggers hearing decline in
healthy women.
Hederstierna C, Hultcrantz M, Collins A, Rosenhall U.
Division of Otorhinolaryngology and
Hearing, Karolinska Institute, Stockholm, Sweden.
BACKGROUND: Epidemiological studies have
shown that women have better high-frequency thresholds than men in virtually
all age groups, and that age-related hearing decline starts after