Selección de Resúmenes de Menopausia
Enero de 2010
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad
de Chile
Semana del 13 al 19 de Enero 2010
J Clin Endocrinol Metab. 2010 Jan 15. [Epub
ahead of print]
Endothelial Function, But Not Carotid
Intima-Media Thickness, Is Affected Early in Menopause and Is Associated with
Severity of Hot Flushes.
Bechlioulis A, Kalantaridou SN, Naka KK, Chatzikyriakidou A, Calis KA, Makrigiannakis A, Papanikolaou O, Kaponis A, Katsouras C, Georgiou I, Chrousos GP, Michalis LK.
Context: The effect of early menopause on
indices of vascular function has been little studied. Objective: The objective
of the study was to investigate the effect of early menopause on indices of
subclinical atherosclerosis and identify predictors of those indices in early
menopausal women. Design, Setting, and Participants: This was a cross-sectional
study that included 120 early menopausal women (age range 42-55 yr, <3 yr in
menopause) recruited from the menopause outpatient clinic of an academic hospital
and 24 age-matched premenopausal women. Main Outcome Measures: Brachial artery
flow-mediated dilation (FMD) and common carotid intima-media thickness (IMT)
were studied. Estrogen receptor (ER)-alpha (rs2234693 T-->C and rs9340799
A-->G) and ERbeta (rs4986938 A-->G) polymorphisms were studied in
menopausal women. Results: FMD was significantly lower in early menopausal
women compared with controls (5.43 +/- 2.53 vs. 8.74 +/- 3.17%, P < 0.001),
whereas IMT did not differ between groups (P > 0.8). Severity of hot flushes
was the most important independent predictor for FMD (P < 0.001) in
menopausal women. Women with moderate/severe/very severe hot flushes had
impaired FMD in contrast to women with no/mild hot flushes or controls. Women
with no/mild hot flushes did not differ compared with controls. Age and
systolic blood pressure were the main determinants of IMT (both P = 0.004). ER
polymorphisms were not associated with vascular parameters. Conclusions:
Impairment of endothelial function is present in the early menopausal years,
whereas carotid IMT is not affected. Severity of hot flushes is the main
determinant of endothelial dysfunction in early menopausal women. The studied
ER polymorphisms do not offer important information on vascular health in early
menopause.
Menopause. 2010 Jan 8. [Epub
ahead of print]
The impact of smoking on antimüllerian
hormone levels in women aged 38 to 50 years.
Plante BJ, Cooper GS, Baird DD, Steiner AZ.
From the 1Department of Obstetrics and
Gynecology, Warren Alpert Medical School of Brown University, Providence, RI;
2Department of Obstetrics and Gynecology, The University of North Carolina
School of Medicine, Chapel Hill, NC; 3Epidemiology Branch, National Institute
of Environmental Health Sciences, National Institutes of Health, Department of
Health and Human Services, Research Triangle Park, NC; and 4National Center for
Environmental Assessment, US Environmental Protection Agency, Washington, DC.
OBJECTIVE:: Smoking is associated with
increased follicle-stimulating hormone levels and early menopause. Smoking may
directly accelerate ovarian follicular depletion or may act indirectly by
increasing the pituitary production of follicle-stimulating hormone.
Antimüllerian hormone (AMH), produced by ovarian follicles, is a more direct
measure of ovarian reserve. The objective of our study was to determine the
extent to which smoking influences ovarian reserve, as measured by AMH levels.
METHODS:: A community sample of 284 women aged 38 to 50 years completed a
self-administered questionnaire including a detailed smoking history. Serum AMH
levels were measured on day 2, 3, or 4 of the menstrual cycle. The association
between AMH and smoking was analyzed using linear regression, adjusting for age
and body mass index. RESULTS:: Participants aged 38 to 42, 43 to 45, and 46 to
50 years had geometric mean AMH values of 6.7 pM (95% CI, 5.2-8.7 pM), 2.7 pM
(95% CI, 1.9-3.8 pM), and 1.3 pM (95% CI, 1.0-1.7 pM), respectively. Current
smokers, but not past smokers, had 44% lower AMH values than did the reference
group (participants with neither active nor former or passive smoke exposure; P
= 0.04). Passive smoking had no effect on AMH values when compared with the
reference group (P = 0.55). The impact of smoking on AMH values was not dose
dependent based on cigarettes per day (P = 0.08) or pack-years (P = 0.22).
Finally, prenatal exposure to smoking (either maternal or paternal) had no
impact on AMH levels (P = 0.47 and P = 0.89, respectively). CONCLUSIONS::
Active smoking, but not former smoking, is associated with decreased AMH values
in late-reproductive-age and perimenopausal women, suggesting a possible direct
effect of smoking on the depletion of the antral but not primordial follicles.
The direct impact of active smoking on AMH levels in younger women requires
further investigation.
J Clin Endocrinol Metab. 2010 Jan 15. [Epub ahead of print]
Effect of Osteoporosis Treatment on
Mortality: A Meta-Analysis.
Bolland MJ, Grey AB, Gamble GD, Reid IR.
Department of Medicine,
Context: Fragility fractures cause
significant morbidity and mortality. Effective osteoporosis treatment can
reduce fracture incidence, but it is not known whether it reduces mortality.
Objective: The aim of the study was to determine whether effective osteoporosis
treatment reduces mortality. Data Sources: We searched Medline and the Cochrane
Central Register of Trials prior to September 2008, as well as 2000-2008
American Society for Bone and Mineral Research conference abstracts. Study
Selection: Eligible studies were randomized placebo-controlled trials of
approved doses of medications with proven efficacy in preventing both vertebral
and nonvertebral fractures, in which the study duration was longer than 12
months and there were more than 10 deaths. Trials of estrogen and selective
estrogen receptor modulators were specifically excluded. Data Extraction: Data
were extracted from the text of the retrieved articles, published
meta-analyses, or the Food and Drug Administration web site. Data Synthesis:
Eight eligible studies of four agents (risedronate, strontium ranelate,
zoledronic acid, and denosumab) were included in the primary analysis. During
two alendronate studies, the treatment dose changed, and those studies were
only included in secondary analyses. In the primary analysis, treatment was
associated with an 11% reduction in mortality (relative risk, 0.89; 95%
confidence interval, 0.80-0.99; P = 0.036). In the secondary analysis, the
results were similar (relative risk, 0.90; 95% confidence interval, 0.81-1.0; P
= 0.044). Mortality reduction was not related to age or incidence of hip or
nonvertebral fracture, but was greatest in trials conducted in populations with
higher mortality rates. Conclusions: Treatments for osteoporosis with
established vertebral and nonvertebral fracture efficacy reduce mortality in
older, frailer individuals with osteoporosis who are at high risk of fracture.
Maturitas. 2010 Jan 14. [Epub ahead of print]
Bone mineral density and prediction of
non-osteoporotic disease.
Menopause Center, Hôpital Paule de
Viguier, TSA 70034, 330 avenue de Grande-Bretagne, 31059 Toulouse, France;
INSERM U588/I2MR, 31432 Toulouse, France.
It is widely recognized that bone mineral
density (BMD) is one of the best predictors of osteoporotic fractures. Sex
hormone status clearly affects bone either directly or indirectly and a longer
estrogen exposure appears to be a major determinant of postmenopausal BMD.
Accordingly, several studies have led to the hypothesis that BMD might
represent a marker of the accumulated lifetime exposure of estrogen and
therefore be used as a predictor factor of the risk of other postmenopausal
conditions such as breast cancer or cardiovascular diseases (CVD). With regard
to the risk of breast cancer, there is evidence that different surrogate
markers of lifetime exposure to estrogen are associated with an increased risk
for breast cancer. Most of these markers are the opposite of those for the risk
of fracture. Furthermore, several studies have also reported that women with
higher BMD have an increased risk of breast cancer compared to women with lower
BMD. On the other hand, postmenopausal women with osteoporosis are at increased
risk for acute cardiovascular events and mortality independently of age and
cardiovascular risk factors. BMD has been shown to inversely correlate with
surrogate markers of CVD including aortic calcifications and atherosclerosis.
The underlying mechanisms of such a relationship are not fully understood.
Several plausible molecular links are serum lipids, pro-inflammatory cytokines
or the RANK/RANK ligand/osteoprotegerin system. Interestingly, all of these
factors are modulated by estrogens. It could thus be hypothesized that the
intensity of postmenopausal estrogen deficiency could be also the common
pathogenic factor between atherosclerosis and osteoporosis.
Cancer Epidemiol. 2010 Jan 13. [Epub
ahead of print]
Risk factors for breast cancer in women
biopsied for benign breast disease: A nested case-control study.
Kabat GC, Jones JG, Olson N, Negassa A, Duggan C, Ginsberg M, Kandel RA, Glass AG, Rohan TE.
Department of Epidemiology and Population
Health,
Aim: Women with a history of benign breast
disease are at increased risk of subsequent breast cancer. However, few studies
have examined whether established breast cancer risk factors other than
histology are associated with an altered risk of breast cancer in women with
benign breast disease. We used a nested case-control design within a large,
multi-center cohort of women biopsied for benign breast disease (BBD) to
estimate odds ratios for breast cancer in association with exposure to a range
of personal and lifestyle factors. Methods: Cases were women biopsied for BBD
who subsequently developed breast cancer; controls were individually matched to
cases on center and age at diagnosis and were women biopsied for BBD who did
not develop breast cancer in the same follow-up interval as that for the cases.
After excluding women with prevalent breast cancer, 1357 records (661 case
records and 696 records) were available for analysis. We used conditional
logistic regression to obtain crude and multivariable-adjusted estimates of the
association between specific factors and risk of breast cancer. Results: In
multivariable analyses age at first live birth, number of pregnancies, and
postmenopausal status were inversely associated with risk of breast cancer. The
odds ratio for women with age at first birth <25 years and >/=3
pregnancies, relative to nulliparous women, was 0.49, 95% confidence interval
0.13-0.79, and that for postmenopausal women relative to premenopausal women
was 0.60, 95% CI 0.37-0.99. Conclusions: Further study of personal factors
influencing the risk of breast cancer in women with BBD may help to identify
subgroups of the population at increased risk of invasive disease.
J Sex Med. 2010 Jan 14. [Epub
ahead of print]
The Impairment of Sexual Function Is Less
Distressing for Menopausal than for Premenopausal Women.
Berra
M, De
Musso F, Matteucci
C, Perrone
AM, Pelusi
C, Pelusi
G, Meriggiola
MC.
Center for Sexual Health, Department of
Obstetrics and Gynecology,
ABSTRACT Introduction. Menopause requires
psychological and physical adjustments because of the occurring significant
hormonal changes. Sexuality is one of the aspects that undergoes the most
profound modifications. Preliminary data suggest that sometimes women do not
regard sexual changes as problematic and often readjust their life and
relationship according to their new physical status. Aim. The aim of our study
was to evaluate sexual function and the way women feel by comparing healthy
postmenopausal and premenopausal women. Methods. One hundred menopausal (M) and
100 premenopausal (pM) healthy women were asked to complete anonymous
questionnaires to assess sexual function and stress related to sexual activity.
Main Outcome Measures. Female Sexual Function Index (FSFI), Female Sexual
Distress Scale (FSDS) were completed by M and pM women. Results. Medium FSFI
score was 20.5 +/- 9.6 and 26.4 +/- 7.7 (P < 0.0005) and medium FSDS score
was 12.1 +/- 11.7 (95% CI 9.7-14.4) and 11.3 +/- 10.2 (P = 0.917) for M and pM
women, respectively. Twenty-five of the 69 M women and 20 of the 31 pM women
with a pathological score in the FSFI questionnaire scored higher than 15 in
the FSDS (P < 0.0005). The overall prevalence of sexual dysfunction was 20%
and 25% (P = 0.5) in the M and pM women. Conclusions. Our data confirm that
menopause is associated with changes in sexual function that may be compatible
with sexual dysfunction. However, personal distress caused by these changes in
sexual life appears to be lower among menopausal women (36.2%) as compared with
premenopausal women (64.5%). These data suggest that medical treatment for
sexual health in menopause must be highly personalized and carefully
prescribed. Berra M, De Musso F, Matteucci C, Perrone AM, Pelusi C, Pelusi G,
and Meriggiola MC. The impairment of sexual function is less distressing for
menopausal than for premenopausal women.
Am J Epidemiol. 2010 Jan 11. [Epub ahead of print]
Menopausal Hormone Therapy Use and Risk of
Invasive
Delellis Henderson K, Duan L, Sullivan-Halley J, Ma H, Clarke CA, Neuhausen SL, Templeman C, Bernstein L.
Results from epidemiologic studies of
hormone therapy use and colon cancer risk are inconsistent. This question was
investigated in the California Teachers Study (1995-2006) among 56,864
perimenopausal or postmenopausal participants under 80 years of age with no
prior colorectal cancer by using Cox proportional hazards regression. Incident
invasive colon cancer was diagnosed among 442 participants. Baseline-recent
hormone therapy users were at 36% lower risk for colon cancer versus baseline-never
users (baseline-recent users: relative risk (RR) = 0.64, 95% confidence
interval (CI): 0.51, 0.80). Results did not differ by formulation. Estimated
risk was lower among baseline-recent hormone therapy users with increasing
duration between 5 and 15 years of use (RR = 0.49, 95% CI: 0.35, 0.68), but the
trend did not persist in the longest duration group, more than 15 years of use
(RR = 0.69, 95% CI: 0.52, 0.92; P(trend) = 0.60). Long-term recreational
physical activity, obesity, regular use of nonsteroidal antiinflammatory
medications, and daily alcohol intake did not modify these effects;
baseline-recent use was more strongly associated with colon cancer risk among
women with a family history of colorectal cancer (P(heterogeneity) = 0.04).
Baseline-recent hormone therapy use was inversely associated with invasive
colon cancer risk among perimenopausal and postmenopausal women in the
California Teachers Study.
Neuropsychology. 2010
Jan;24(1):68-76.
A cross-sectional study of hormone
treatment and hippocampal volume in postmenopausal women: evidence for a
limited window of opportunity.
Erickson KI, Voss MW, Prakash RS, Chaddock L, Kramer AF.
Department of Psychology,
The influence of hormone treatment on
brain and cognition in postmenopausal women has been a controversial topic.
Contradictory patterns of results have prompted speculation that a critical
period, or limited window of opportunity, exists for hormone treatment to
protect against neurocognitive. In this cross-sectional study of 102
postmenopausal women, we examined whether hippocampal, amygdala, or caudate
nucleus volumes and spatial memory performance were related to the interval
between menopause and the initiation of hormone treatment. Consistent with a
critical period hypothesis, we found that shorter intervals between menopause
and the initiation of hormone treatment were associated with larger hippocampal
volumes compared with longer intervals between menopause and treatment
initiation. Initiation of hormone treatment at the time of menopause was also
associated with larger hippocampal volumes when compared with peers who had
never used hormone treatment. Furthermore, these effects were independent from
potentially confounding factors such as age, years of education, the duration
of hormone treatment, current or past use of hormone therapy, the type of
therapy, and age at menopause. Larger hippocampal volumes in women who
initiated hormone treatment at the time of menopause failed to translate to
improved spatial memory performance. There was no relationship between timing
of hormone initiation, spatial memory performance, and amygdala or caudate
nucleus volume. Our results provide support for a limited window of opportunity
for hormone treatment to influence hippocampal volume, yet the degree to which
these effects translate to improved memory performance is uncertain.
Semana del 6 al 12
de Enero 2010
Menopause. 2010 Jan-Feb;17(1):25-54.
Management of
osteoporosis in postmenopausal women: 2010 position statement of The North
American Menopause Society.
OBJECTIVE:: To update the evidence-based position
statement published by The North American Menopause Society (NAMS) in 2006
regarding the management of osteoporosis in postmenopausal women. METHODS::
Am J Physiol Regul Integr Comp Physiol. 2010 Jan 6. [Epub ahead of print]
Endothelin in
the female vasculature: a role in aging?
Lekontseva ON, Chakrabarti S, Davidge ST.
Cardiovascular diseases are the leading
cause of morbidity and mortality in the world. Aging is associated with an
increased incidence of cardiovascular disease. Premenopausal women are
relatively protected from vascular alterations compared to age-matched men,
likely due to higher levels of the female sex hormones. However, these
vasoprotective effects in women are attenuated after menopause. Thus, the
vascular system in aging women is affected by both the aging process as well as
loss of hormonal protection, positioning women of this age group at a high risk
for cardiovascular diseases such as hypertension, myocardial infarction and
stroke. The endothelin system in general and endothelin-1 (ET-1) in particular
plays an important role in the pathogenesis of vascular dysfunction associated
with aging. Evidence suggests that the female sex steroids can interfere with
the vascular expression and actions of ET-1 via several mechanisms, which may
further contribute to pathological processes in the vasculature of aging women.
In this review, we have summarized hormone-dependent vascular pathways whereby
ET-1 may mediate the deleterious effects of aging in postmenopausal females.
Steroids. 2010 Jan 6. [Epub ahead of print]
Estrogen and
oxidative stress: A novel mechanism that may increase the risk for
cardiovascular disease in women.
White RE, Gerrity R, Barman SA, Han G.
Department of Pharmacology &
Toxicology, Medical
Although early studies demonstrated that
exogenous estrogen lowered a woman's risk of cardiovascular disease, recent
trials indicate that HRT actually increases the risk of coronary heart disease
or stroke. However, there is no clear explanation for this discrepancy. Is
estrogen a helpful or a harmful hormone in terms of cardiovascular function?
This review discusses some recent findings that propose a novel mechanism which
may shed significant light upon this controversy. We propose that nitric oxide
synthase (NOS) expressed within the vascular wall is a target of estrogen
action. Under normal conditions in younger women, the primary product of
estrogen action is NO, which produces a number of beneficial effects on
vascular biology. As a woman ages, however, there is evidence for loss of
important molecules essential for NO production (e.g., tetrahydrobiopterin,
L-arginine). As these molecules are depleted, NOS becomes increasingly
"uncoupled" from NO production, and instead produces superoxide, a
dangerous reactive oxygen species. We propose that a similar uncoupling and
reversal of estrogen response occurs in diabetes. Therefore, we propose that
estrogen is neither "good" nor "bad", but simply stimulates
NOS activity. It is the biochemical environment around NOS that will determine
whether estrogen produces a beneficial (NO) or deleterious (superoxide)
product, and can account for this dual and opposite nature of estrogen
pharmacology. Further, this molecular mechanism is consistent with recent
analyses revealing that HRT produces salutary effects in younger women, but
mainly increases the risk of cardiovascular dysfunction in older postmenopausal
women.
Nutrition. 2010 Jan 4. [Epub ahead of print]
Association of
glycemic load with cardiovascular disease risk factors: The Women's Health
Initiative Observational Study.
Shikany JM, Tinker LF, Neuhouser ML, Ma Y, Patterson RE, Phillips LS, Liu S, Redden DT.
Division of Preventive Medicine,
OBJECTIVE: Associations between dietary
glycemic load (GL) and cardiovascular disease risk factors, including plasma
lipoprotein/lipid levels, blood pressure, and glucose metabolism factors, in
the Women's Health Initiative Observational Study were examined. METHODS: A
random sample of 878 Observational Study participants (postmenopausal women
50-79 y of age) with baseline blood measurements (647 white, 104 black, 127
Hispanic) was included. Dietary GL was estimated from baseline food-frequency
questionnaires, which assessed dietary intake over the previous 3 mo. At the
baseline visit, participants completed demographic and health habit
questionnaires, fasting blood samples were collected, anthropometric
measurements were completed, and blood pressure was assessed. RESULTS: In all
participants combined, GL was inversely associated with high-density
lipoprotein cholesterol (P for trend = 0.004) and positively associated with
log(10)-transformed triacylglycerols (P = 0.008). Although there were no
statistically significant interactions of race/ethnicity with associations
between GL and cardiovascular disease risk factors, stratified results were
suggestive, showing that GL was positively associated with total cholesterol (P
= 0.018) and low-density lipoprotein cholesterol (P = 0.038) in Hispanics. In
white subjects, there was a trend of reduced high-density lipoprotein
cholesterol with higher GL (P = 0.003), whereas GL was positively associated
with log(10)-transformed triacylglycerols (P = 0.015). Associations between GL
and high-density lipoprotein cholesterol and between GL and triacylglycerols
also differed by body mass index, although the interactions were not
statistically significant. CONCLUSION: Among these generally healthy
postmenopausal women, GL was associated with high-density lipoprotein
cholesterol and triacylglycerols. Suggestive effects of race/ethnicity and body
mass index on these associations need to be confirmed in larger studies.
J Bone Miner Metab. 2010 Jan 7. [Epub ahead of print]
First
fractures among postmenopausal women with osteoporosis.
Lilly
After the occurrence of the first
fracture, osteoporosis is no longer a "silent" disease, and the
patient's risk for future fracture is increased several fold. We assessed the
location of first osteoporotic fractures among women with osteoporosis. The
Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a fracture outcomes
study of postmenopausal women with osteoporosis. All subjects received
supplements containing 500 mg elemental calcium and 400-600 IU vitamin D. We
assessed the location of first fractures among women with osteoporosis and no
previous fractures at baseline from the placebo group of this trial after 3
years of follow-up. Prespecified fracture sites included vertebral fractures
and nonvertebral fractures as defined in the MORE study protocol. Among 875
women (mean age, 64.5 +/- 7.4 years) with no prevalent vertebral or nonvertebral
fractures, 9% experienced their first fracture event during the trial.
Fractures of radius and spine each occurred in 3% of patients. Fractures at
other individual sites included ankle (0.6%), metatarsal (0.6%), humerus
(0.5%), rib (0.5%), patella (0.3%), leg (0.2%), hip (0.2%), and clavicle
(0.1%). These data suggest that for postmenopausal women with osteoporosis but
no previous fractures, skeletal care should include a focus on preventing spine
and radius fractures.
Bone. 2010 Jan 2. [Epub ahead of print]
Changes in
Trabecular Microarchitecture in Postmenopausal Women on Bisphosphonate Therapy.
Greenspan SL, Perera S, Recker R, Wagner JM, Greeley P, Gomberg BR, Seaman P, Kleerekoper M.
University of Pittsburgh, Department of
Medicine, Pittsburgh, PA.
PURPOSE: In addition to bone mineral
density (BMD), trabecular microstructure contributes to skeletal strength. Our
goal was to examine changes in trabecular microstructure in women on therapy.
MATERIALS and METHODS: We followed 10 postmenopausal women receiving a
bisphosphonate, risedronate (35 mg once weekly), over 12 months and examined
trabecular microarchitecture with high resolution wrist MR images (hr-MRI). MRI
parameters included bone volume/ total volume (BV/TV), surface density
(representing plates), curve density (representing rods), surface-to-curve
ratio and erosion index (depicting deterioration). We assessed BMD of the
spine, hip and radius and markers of bone turnover. RESULTS: Women had been
receiving bisphosphonate therapy for 43 +/- 9 months (mean +/- SD) prior to the
first MRI. Indices of hr-MRI demonstrated improvement in surface-to-curve ratio
(13.0 %) and a decrease in erosion index (12.1 %) consistent with less
deterioration (both p<0.05). BMD of the spine, hip and radius and markers of
bone turnover remained stable. Parameters of hr-MRI were associated with 1/3
distal radius BMD (correlation coefficient 0.71 to 0.86, p<0.05).
DISCUSSION: We conclude hr-MRI of the radius demonstrates improvements in
trabecular microstructure not appreciated by conventional BMD and provides
additional information on parameters that contribute to structural integrity in
patients on antiresorptive
Wei Sheng Yan Jiu. 2009 Nov;38(6):672-6.
Meta-analysis
of the effects on hormone replacement therapy and oral contraceptives
associated with female lung cancer risk
School of Public Health, Fujian Medical
University, Fuzhou 350004, China. xiaoge8419@163.com
OBJECTIVE: To evaluate the effects of
hormone replacement therapy (HRT) and oral contraceptives (OCs) on lung cancer
risk in women. METHODS: We retrieved studies by systematically searching
Medline and other computerized databases. Pooled odds ratios (OR) were
appropriately derived from fixed-effects or, in the presence of heterogeneity,
random-effects models. RESULTS: Twelve studies were identified including 3
cohort studies and 9 case-control studies. The OR value associated with HRT was
0.88 (95% CI: 0.77-1.01). Subgroup analyses by smoking revealed that the OR
value associated with HRT in smokers' and non-smokers' women were 0.76(95% CI:
0.61-0.95) and 0.78 (95% CI: 0.64-0.95), respectively. There was no statistical
relationship between lung cancer risk and OCs (OR = 0.95; 95% CI: 0.83-1.20).
CONCLUSION: The results suggest a potential decreased risk of female lung
cancer might be associated with HRT. Additional well-designed studies are
warranted to validate these findings
Gynecol Endocrinol. 2010 Jan 5. [Epub ahead of
print]
Gabapentin vs.
low-dose transdermal estradiol for treating post-menopausal women with moderate
to very severe hot flushes.
Aguirre W, Chedraui P, Mendoza J, Ruilova I.
Postmenopausal Health and Female
Endocrinology Unit, Quito, Ecuador.
Background. Gabapentin (GPT), a widely
used drug in neurology, has been proposed as a non-hormonal option for the
management of hot flushes in menopausal women with contraindications for
estrogen therapy. Objective. To compare GPT versus low-dose transdermal
estradiol (E(2)) for treating post-menopausal women with moderate to very
severe hot flushes. Methods. A total of 45 post-menopausal women with moderate
to very severe hot flushes were prospectively and single-blinded randomised to
receive oral GPT 600 mg/night or transdermal 25 mug/day E(2) per week. Hot
flush intensity and frequency were assessed with the Menopause Rating Scale and
a numeric scale respectively at baseline and at 1, 4 and 8 weeks. Side effects
were also assessed. Results. Hot flush intensity and frequency significantly
decreased for both groups at 1, 4 and 8 weeks of treatment as compared to
baseline; however, this decrease was statistically more evident for the E(2)
group. Although the percentage of hot flush intensity and frequency reduction
at the end of the treatment was higher for E2, this was not statistically
significant (68.2% vs. 60.6% for intensity and 70.1% vs. 58.9% for frequency,
respectively, p > 0.05, NS). Encountered side effects included: drowsiness,
dizziness, fatigue (GPT group) and mastodynia, vaginal spotting and a local
allergic reaction (E(2) group). Compliance to treatment was 95.6% (GPT group)
as compared to 90.9% for the E(2) group. Conclusion. Despite statistical
significant differences, from a clinical point of view oral GPT 600 mg was as
effective as low-dose transdermal E(2) in controlling moderate to severe hot
flushes in post-menopausal women, and should be recommended as an alternative
option in those with contraindications to estrogen therapy. More research is
warranted in this regard
Br J Pharmacol. 2009 Dec;158(8):1951-60.
Differential
effects of medroxyprogesterone acetate on thrombosis and atherosclerosis in
mice.
Freudenberger T, Oppermann M, Marzoll A, Heim HK, Mayer P, Kojda G, Weber AA, Schrör K, Fischer JW.
Institut für Pharmakologie,
Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
BACKGROUND AND PURPOSE: The risk for
cardiovascular events including venous and arterial disease and stroke is
elevated after treatment with estrogen and medroxyprogesterone acetate (MPA) in
postmenopausal women. Here, we have investigated the effect of MPA on arterial
thrombosis and atherosclerosis in a murine model of atherosclerosis.
EXPERIMENTAL APPROACH: Apolipoprotein E (ApoE)-/- mice were bilaterally
ovariectomized and treated with placebo, MPA (27.7 microg day(-1)) and MPA +
17-beta-oestradiol (E2; 1.1 microg day(-1)) for 90 days, on a Western-type
diet. Thrombotic response was measured in a photothrombosis model, platelet
activation by fluorescence activated cell sorting (FACS) analysis (CD62P) and
thrombin generation by the endogenous thrombin potential (ETP). Furthermore,
aortic plaque burden and aortic root plaque composition were determined. KEY
RESULTS: MPA and MPA + E2-treated animals showed an aggravated thrombotic
response shown by significantly reduced time to stable occlusion. The
pro-thrombotic effect of MPA was paralleled by increased ETP whereas platelet
activation was not affected. Furthermore, MPA + E2 reduced the number of cells
positive for alpha-smooth muscle actin and increased hyaluronan in the plaque
matrix. Interestingly, total plaque burden was reduced by MPA but unchanged by
MPA + E2. CONCLUSION AND IMPLICATIONS: Long-term treatment with MPA and MPA +
E2 increased arterial thrombosis despite inhibitory effects of MPA on
atherosclerosis in ApoE-deficient mice. Increased thrombin formation, reduced
smooth muscle content and remodelling of non-collagenous plaque matrix may be
involved in the pro-thrombotic effects. Thus, MPA exhibits differential effects
on arterial thrombosis and on atherosclerosis
Semana del 23 de Diciembre de 2009 al 5 de Enero 2010
Menopause. 2009
Dec 29. [Epub ahead of print]
History of hot flashes and
aortic calcification among postmenopausal women.
Thurston RC, Kuller LH, Edmundowicz D, Matthews KA.
From the 1Department of
Psychiatry, School of Medicine, 2Department of Epidemiology, Graduate School of
Public Health, and 3Cardiovascular Institute, School of Medicine, University of
Pittsburgh, Pittsburgh, PA.
OBJECTIVE:: Menopausal hot
flashes are considered largely a quality-of-life issue. However, emerging
research also links hot flashes to cardiovascular risk. In some investigations,
this risk is particularly apparent among women using hormone therapy. The aim
of this study was to determine whether a longer history of reported hot flashes
over the study period was associated with greater aortic and coronary artery
calcification. Interactions with hormone therapy use were examined in an
exploratory fashion. METHODS:: Participants included 302 women participating in
the Healthy Women Study, a longitudinal study of cardiovascular risk during
perimenopause and postmenopause, which was initiated in 1983. Hot flashes
(any/none) were assessed when women were 1, 2, 5, and 8 years postmenopausal.
Electron beam tomography measures of coronary artery calcification and aortic
calcification were completed in 1997-2004. Associations between the number of
visits with report of hot flashes, divided by the number of visits attended,
and aortic or coronary artery calcification (transformed) were examined in
linear regression models. Interactions by hormone therapy use were evaluated.
RESULTS:: Among women using hormone therapy, a longer history of reported hot
flashes was associated with increased aortic calcification, controlling for
traditional cardiovascular risk factors (b = 2.87, SE = 1.21, P < 0.05).
There were no significant associations between history of hot flashes and
coronary artery calcification. CONCLUSIONS:: Among postmenopausal women using
hormone therapy, a longer history of reported hot flashes measured
prospectively was associated with increased aortic calcification, controlling
for traditional cardiovascular risk factors. Hot flashes may signal adverse
cardiovascular changes among certain postmenopausal women.
Maturitas. 2009 Dec 21. [Epub ahead of print]
Risk factors related to the
presence and severity of hot flushes in mid-aged Ecuadorian women.
Chedraui P, Aguirre W, Calle A, Hidalgo L, León-León P, Miranda O, Martínez N, Mendoza M, Narváez J et
al.
Research Group for the
Ecuadorian Climacteric & Menopause Society (SECLIM),
BACKGROUND: Several studies
drawn from the Ecuadorian population have previously reported that more than
half of mid-aged women present hot flushes, which can impair their quality of
life. However up-to-date risk factors for their presence and severity have not
been assessed. OBJECTIVE: To assess hot flush frequency and intensity and
related risk factors among middle-aged Ecuadorian women. METHODS: In this cross-sectional
study, 1154 healthy women aged 40-59 years, visiting healthcare centers of
eight main cities of
Menopause. 2009 Dec 29. [Epub ahead of
print]
Premature menopause is
associated with increased risk of cerebral infarction in Japanese women.
Baba Y, Ishikawa S, Amagi Y, Kayaba K, Gotoh T, Kajii E.
Department of Obstetrics and Gynecology,
OBJECTIVE:: Few epidemiological
studies have examined the relationship between age at menopause and stroke
incidence, and none have done so in Japanese women. Here, we investigated the
relationship between age at menopause and stroke incidence in a large group of
Japanese women. METHODS:: The study participants were 4,790 postmenopausal
women aged 36 to 89 years enrolled in the Jichi Medical School Cohort Study, a
population-based prospective study. Baseline data were obtained by
questionnaire and health checkups between April 1992 and July 1995 in 12 rural
areas in
Genome Med. 2009 Dec 24;1(12):121. [Epub
ahead of print]
Postmenopausal estrogen and
progestin effects on the serum proteome.
Pitteri SJ, Hanash SM, Aragaki A, Amon LM, Chen L, Busald Buson T, Paczesny S, Katayama H, et al.
ABSTRACT: BACKGROUND: Women's
Health Initiative randomized trials of postmenopausal hormone therapy reported
intervention effects on several clinical outcomes, with some important
differences between estrogen alone and estrogen plus progestin. The biological
mechanisms underlying these effects, and these differences, have yet to be
fully elucidated. METHODS: Baseline serum samples were compared to samples
drawn one year later for 50 women assigned to active hormone therapy in both
the estrogen plus progestin and estrogen-alone randomized trials, by applying
an in-depth proteomic discovery platform to serum pools from 10 women per pool.
RESULTS: A total of 378 proteins were quantified in two or more of the 10
pooled serum comparisons, using strict identification criteria. Of these, 169
(44.7%) showed evidence (nominal p<0.05) of change in concentration between
baseline and one year for one or both of estrogen plus progestin and
estrogen-alone. Quantitative changes were highly correlated between the two
hormone therapy preparations. A total of 98 proteins had false discovery rates
<0.05 for change with estrogen plus progestin, compared to 94 for
estrogen-alone. Of these, 84 had false discovery rates <0.05 for both
preparations. The observed changes included multiple proteins relevant to coagulation,
inflammation, immune response, metabolism, cell adhesion, growth factors, and
osteogenesis. There was also evidence of differential changes between the
hormone preparations, with strongest evidence in growth factor and inflammation
pathways. CONCLUSIONS: Serum proteomic analyses yielded a large number of
proteins similarly affected by estrogen plus progestin and by estrogen-alone
and have identified some proteins and pathways that appear to be differentially
affected between the two hormone preparations that may explain their distinct
clinical effects.
Am J Kidney Dis. 2009 Dec 28. [Epub ahead of print]
Kidney Function and Rate of
Bone Loss at the Hip and Spine: The Canadian Multicentre Osteoporosis Study.
Jamal SA, Swan VJ, Brown JP, Hanley DA, Prior JC, Papaioannou A, Langsetmo L, Josse RG; Canadian Multicentre Osteoporosis Study Research Group.
BACKGROUND: The relationship
between kidney function and bone loss is unclear. STUDY DESIGN: A prospective
observational study. SETTING & PARTICIPANTS: 191 men and 444 women aged
>/= 50 years participating in a population-based observational study
designed to determine risk factors for bone loss and fractures. PREDICTORS: The
primary predictor of change in bone mineral density (BMD) was estimated
creatinine clearance (using the Cockcroft-Gault formula) measured at baseline
and stratified by quartiles. Our secondary predictor was estimated glomerular
filtration rate using the Modification of Diet in Renal Disease Study equation,
also stratified by quartiles. OUTCOMES & MEASUREMENTS: Changes in BMD at
the lumbar spine, total hip, and femoral neck during 5 years. RESULTS: Compared
with participants in the first quartile of estimated creatinine clearance
(>101.2 mL/min), those in remaining quartiles were older (quartile 1, 50.0
years; quartile 2 [101.2-83.4 mL/min], 54.7 years; quartile 3 [83.4-68.3
mL/min], 60.5 years; and quartile 4 [<68.3 mL/min], 68.3 years); weighed
less; reported more sedentary hours; were less likely to report excellent, very
good, or good self-reported health; consumed less caffeine; and had lower serum
calcium and phosphate and higher serum parathyroid hormone levels. After
adjusting for age, weight, sex, baseline BMD, and these differences, compared
with those in the first quartile, those in the fourth quartile had decreases in
BMD of 0.08 g/cm(2) (95% CI, 0.04-0.1) at the lumbar spine, 0.08 g/cm(2) (95%
CI, 0.06-0.1) at the femoral neck, and 0.09 g/cm(2) (95% CI, 0.07-0.1) at the
total hip. Bone loss did not increase with worsening kidney function (P for
trend > 0.05). Results were not substantially different using estimated
glomerular filtration rate. LIMITATIONS: Observational study design and
indirect measures of kidney function. CONCLUSIONS: Men and women with impaired
kidney function are at increased risk of bone loss, even with minimal reduction
in kidney function.
PLoS One. 2009 Dec 29;4(12):e8475.
Tissue-specific increases in
11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal
women.
Andersson T, Simonyte K, Andrew R, Strand M, Burén J, Walker BR, Mattsson C, Olsson T.
Division of Medicine, Public
Health and Clinical Medicine,
With age and menopause there is
a shift in adipose distribution from gluteo-femoral to abdominal depots in
women. Associated with this redistribution of fat are increased risks of type 2
diabetes and cardiovascular disease. Glucocorticoids influence body
composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) which
converts inert cortisone to active cortisol is a putative key mediator of
metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may
contribute to postmenopausal central obesity. We hypothesized that
tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the
older, postmenopausal women compared to young, premenopausal women.
Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were
recruited. The participants underwent a urine collection, a subcutaneous
adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the
serum cortisol response after an oral dose of cortisone. Urinary
(5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol)/ tetrahydrocortisone
ratios were higher in postmenopausal women versus premenopausal women in luteal
phase (P<0.05), indicating an increased whole-body 11betaHSD1 activity.
Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat
(P<0.05). Hepatic first pass conversion of oral cortisone to cortisol was
also increased in postmenopausal women versus premenopausal women in follicular
phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion),
suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results
indicate that postmenopausal normal weight women have increased 11betaHSD1
activity in adipose tissue and liver. This may contribute to metabolic
dysfunctions with menopause and ageing in women.
Maturitas. 2009 Dec 24. [Epub ahead of print]
Comparative analysis of the
uterine and mammary gland effects of progesterone and medroxyprogesterone
acetate.
Otto C, Fuchs I, Vonk R, Fritzemeier KH.
TRG Women's Healthcare, Bayer
Schering Pharma AG, Muellerstrasse 178, 13342
OBJECTIVES: In combined hormone
replacement therapy (HRT) progestins are used to inhibit estradiol-activated
uterine epithelial cell proliferation. In comparison to estradiol-only therapy,
combined HRT leads to enhanced proliferation of mammary epithelial cells. In a
quantitative mouse model, we assessed the balance between uterine and undesired
mammary gland effects for two progestins that are widely used in HRT,
progesterone and medroxyprogesterone acetate. STUDY DESIGN: Mice were
ovariectomized and after 14 days they were treated subcutaneously with either
vehicle, estradiol (100ng) or estradiol plus increasing doses of progesterone
or medroxyprogesterone acetate for three weeks. MAIN OUTCOME MEASURES: Measures
for progestogenic mammary gland activity were stimulation of side-branching and
stimulation of epithelial cell proliferation. Progestogenic activity in the
uterus was assessed by measuring inhibition of estradiol-activated uterine
epithelial cell proliferation. ED(50) and ID(50) values for the distinct
readouts were obtained and dissociation factors for uterine versus mammary
gland activity were calculated. RESULTS: MPA demonstrated uterine activity and
mitogenic activity in the mammary gland at the same doses. In contrast,
progesterone showed uterine activity at doses lower than those leading to
significant stimulation of epithelial cell proliferation in the mammary gland.
CONCLUSIONS: Progestins do not behave the same. Use of the natural hormone
progesterone, but not MPA, in combined hormone therapy might offer a safety
window between uterine effects and undesired proliferative activity in the
mammary gland.
Rheumatol Int. 2009 Dec 25. [Epub ahead of
print]
Absolute risk reduction in
osteoporosis: assessing treatment efficacy by number needed to treat.
Med Klinik 4, Klinikum
Leverkusen, Akadem, Lehrkrankenhaus
Postmenopausal osteoporosis is
a chronic condition due to decreased bone mass, leading to reduced bone
strength and increased fracture risk. Currently available pharmacological
treatments include antiresorptive agents (bisphosphonates and raloxifene) and
bone-forming agents (strontium ranelate and two different parathyroid peptides).
Comparison via reduction in relative risk of fracture may produce artificially
high reductions in fracture risk for some agents. Responder analysis based on
absolute risk reduction (ARR, the arithmetic difference between events rates
with and without treatment over a fixed time) and a related parameter, number
needed to treat (NNT, the number of patients needed to treat over a fixed time
to prevent one event) may provide more reliable parameters. We reviewed
placebo-controlled, randomized, double-blind, pivotal phase 3 trials employed
as part of the regulatory process, in order to calculate ARRs and NNTs for
vertebral and hip fracture over 3 years for antiosteoporotic agents currently
available in Europe. The NNT values to prevent one vertebral fracture over 3
years range from 9 for the strontium ranelate to 21 for ibandronate. NNT values
for hip fracture over 3 years range from 48 for strontium ranelate to 91 for
three of the bisphosphonates. Our analysis indicates that the bone-forming
agent strontium ranelate may have the lowest NNT for the prevention of both
vertebral and hip fracture. Responder analysis may enable translation of
clinical trial results into guidance for routine clinical practice by
indicating the amount of effort needed to prevent the same event in comparable
populations with different treatment options.
Bone. 2009 Dec 21. [Epub ahead of print]
Five years treatment with
strontium ranelate reduces vertebral and nonvertebral fractures and increases
the number and quality of remaining life-years in women over 80 years of age.
Seeman E, Boonen S, Borgström F, Vellas B, Aquino JP, Semler J, Benhamou CL, Kaufman JM, Reginster JY.
Austin Health,
INTRODUCTION: Longevity has
resulted in a greater proportion of the population entering a time of life when
increasing bone fragility and falls predispose to fractures, particularly nonvertebral
fractures. Women over 80 years of age constitute 10% of the population but
contribute 30% of all fractures and 60% of all nonvertebral fractures. Despite
this, few studies have examined antifracture efficacy of treatments in this
high-risk group and none has provided evidence for benefits beyond 3 years.
MATERIALS AND METHODS: To determine whether strontium ranelate reduces the risk
of vertebral and nonvertebral fractures during 5 years, we analyzed a subgroup
of 1489 female patients over 80 years of age (mean 83.5+/-3.0 years) with
osteoporosis from the SOTI (spinal osteoporosis therapeutic intervention) and
TROPOS (treatment of peripheral osteoporosis) studies randomized to strontium
ranelate 2 g/d or placebo. All received a supplement of calcium plus vitamin D.
RESULTS: By intention to treat, vertebral fracture risk was reduced by 31%
(relative risk, RR=0.69; 95% confidence interval, CI 0.52-0.92), nonvertebral
fracture risk by 27% (RR=0.73; 95% CI 0.57-0.95), major nonvertebral fracture
risk by 33% (RR=0.67; 95% CI 0.50-0.89) and hip fracture risk by 24% (RR=0.76;
95% CI 0.50-1.15, not significant). Treatment was cost-saving as it decreased
cost and increased QALYs and life-years. DISCUSSION: Strontium ranelate safely
produced a significant reduction in vertebral and nonvertebral fracture risk
during 5 years in postmenopausal women over 80 years of age and was cost
saving.