Selección de Resúmenes de Menopausia
Semana del 3 al 9 de Junio de
2009
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad de
Chile
Horm Metab Res. 2009 Jun
4. [Epub ahead of print]
Adipocytokines, Sex Hormones, and Cardiovascular Risk
Factors in Postmenopausal Women: Factor Analysis of the Rancho Bernardo Study.
Krentz AJ, Mühlen DV, Barrett-Connor E.
1Division
of Epidemiology, Department of Family & Preventive Medicine, University of
California, San Diego, La Jolla, California, USA.
Steroid
sex hormones modulate the expression of adipocytokines
implicated in the pathogenesis of athero-thrombotic
cardiovascular disease. We used exploratory factor analysis to search for
latent associations between circulating sex steroid hormones, adipocytokines, and cardiovascular risk factors in a
well-characterized cohort of postmenopausal women. Among participants in the
Rancho Bernardo community study we identified 515 Caucasian women with a mean
age of 74+/-8 years and mean body mass index of 24.2+/-3.7 kg/m (2). All had
intact ovaries and none was using estrogen therapy.
We constructed models aiming for structural clarity and high loading of
variables on individual factors. Total adiponectin
loaded with major lipid subfractions (low-density
lipoprotein cholesterol, high-density lipoprotein cholesterol, and fasting
triglycerides) and with sex hormone-binding globulin. Leptin
loaded with central obesity (waist circumference) and fasting insulin levels.
Neither adipocytokine loaded with total or bioavailable testosterone or with estradiol
or dehydroepiandrosterone sulfate.
Sex hormones consistently loaded together on a separate factor; this
co-segregation was not influenced by body mass index. Exclusion of women with
diabetes did not alter these observations. In conclusion, we identified
evidence of latent associations between adipocytokines
and a range of cardiovascular risk factors in postmenopausal women. Our results
suggest that cardiovascular risk in older women may be modulated through a
hitherto unrecognized association between adiponectin,
lipid subfractions, and sex
hormone bioavailability.
Gynecol Endocrinol. 2009 Jun 2:1-4. [Epub ahead of
print]
Hormone replacement therapy and successful pregnancy
in a patient with premature ovarian failure.
Dragojevic-Dikic S, Rakic S, Nikolic B, Popovac S.
Gynecology -
Obstetrics Clinic 'Narodni front',
Premature
ovarian failure (POF), premature ovarian insufficiency, premature menopause or hypergonadotropic hypogonadism, a
serious life-changing condition that affects young women, remains an enigma and
the researcher's challenge. In the present article we described a case of
singleton pregnancy in a 33-year-old patient, presenting with POF and treated
with hormone replacement therapy. Twenty months later this therapy led to
maturation of one follicle, recruitment and fertilisation of the residual oocyte and spontaneous pregnancy ensued. A normal infant
was delivered by cesarean section.
J Sex Med. 2009 Jun
1. [Epub ahead of print]
Prevalence and Impact of Vaginal Symptoms among
Postmenopausal Women.
ABSTRACT Introduction. Vulvovaginal atrophy (VVA) is reported by
one-quarter to one-half of postmenopausal women. Aim.
We evaluated the prevalence, inconvenience of, and issues surrounding hormone
use for VVA symptoms in women who were current, past, and never users of
menopausal hormone therapy (MHT), along with the relationship of sexual
activity to VVA symptoms. Methods. An online survey
was sent to 3,471 women >/=45 years old participating in a panel of
approximately 43,000
Breast Cancer Res Treat. 2009 Jun 3. [Epub ahead of print]
The efficacy of sertraline
for controlling hot flashes in women with or at high risk of developing breast
cancer.
Wu MF, Hilsenbeck SG, Tham YL, Kramer R, Elledge RM, Chang JC, Friedman LC.
Dan L.
Duncan Cancer Center, Baylor College of Medicine, One
Baylor Plaza BCM 600, Houston, TX, 77030, USA, mengfenw@bcm.edu.
The aim
of the study is to evaluate the efficacy of sertraline
for controlling hot flashes in women with or at high risk of breast cancer.
This was a randomized, double-blind, placebo-controlled study. All participants
were asked to complete hot flash diaries. Participants reporting weekly hot flash
scores >15 during baseline week underwent a 1-week single-blind placebo
run-in. Those reporting hot flash score reductions >50% following placebo
run-in were excluded. The remaining women received an assigned treatment for 4
weeks. Both groups' demographic and clinical characteristics were similar with
a greater decline, but not statistically significant, in hot flash frequencies
and scores in the sertraline-treated group compared
with the placebo (P = 0.13 and P = 0.15, respectively). Emotional well-being
improved significantly in the sertraline group (P =
0.041). The study failed to demonstrate effectiveness of sertraline
in attenuating hot flashes in women with or at high risk of developing breast
cancer who were not recommended to take hormone replacement therapy.
J Alzheimers Dis. 2009 May;17(1):151-9.
Does
vitamin d reduce the risk of dementia?
Sunlight,
Nutrition, and Health Research Center (SUNARC), P.O.
Box 641603, San Francisco, CA 94164-1603, USA.
The
understanding of the role of vitamin D in maintaining optimal health has
advanced sharply in the past two decades. There is mounting evidence for
beneficial roles for vitamin D in reducing the risk of bone diseases and
fractures, many types of cancer, bacterial and viral infections, autoimmune
diseases, and cardiovascular diseases. Recently, several reports have also been
published regarding the role of vitamin D in neuroprotection.
This article develops the hypothesis that vitamin D can reduce the risk of
developing dementia, presenting the evidence from observational and laboratory
studies. The observational evidence includes that low serum 25-hydroxyvitamin D
[25(OH)D] has been associated with increased risk for cardiovascular diseases,
diabetes mellitus, depression, dental caries, osteoporosis, and periodontal
disease, all of which are either considered risk factors for dementia or have
preceded incidence of dementia. The laboratory evidence includes several
findings on the role of vitamin D in neuroprotection
and reducing inflammation. Although this evidence is supportive, there do not
appear to be observational studies of incidence of dementia with respect to prediagnostic serum 25(OH)D or
vitamin D supplementation. Such studies now
appear to be warranted.
Ann Intern Med. 2009 Jun
2;150(11):752-65.
Short-term
hormone therapy suspension and mammography recall: a randomized trial.
Buist DS, Anderson ML, Reed SD, Aiello Bowles EJ, Fitzgibbons ED, Gandara JC, Seger D, Newton KM.
Group
Health Center for Health Studies, University of
Washington, and Group Health Permanente, 125 16th Avenue East, Seattle, WA
98112, USA. buist.d@ghc.org
BACKGROUND:
Without population-based evidence, some clinicians recommend short-term
suspension of hormone therapy to improve the performance of mammography.
Hormone therapy increases breast density, and abnormal screening mammograms are
more common among women with denser breasts and among women using hormone
therapy. OBJECTIVE: To test whether 1 to 2 months of hormone therapy suspension
before screening mammography decreases additional mammographic imaging (recall)
in women age 45 to 80 years. DESIGN: 3-group randomized, controlled trial.
SETTING: Integrated health plan in western
Maturitas. 2009 May
30. [Epub ahead of print]
The role
of testosterone in the management of hypoactive sexual desire disorder in
postmenopausal women.
The
At
least 16 million women over the age of 50 currently experience low sexual
desire, with approximately 4 million women exhibiting hypoactive sexual desire
disorder (HSDD). Although early research established that testosterone therapy
improves sexual desire in postmenopausal women, safer and more efficacious
administration routes were explored. Large randomized, double-blinded
placebo-controlled studies demonstrate that transdermal
testosterone improves sexual function and activity in postmenopausal women with
HSDD. Large multi-center Phase III trials further
confirm the positive effects of the testosterone patch in the treatment of
HSDD. More recent studies are exploring the utility of testosterone gels. Based
upon data from two recent clinical relevance studies, physicians can be
reassured that postmenopausal women with HSDD report a meaningful benefit with
testosterone therapy, and further, women will only continue therapy if they
experience a meaningful benefit. Although most trials combined testosterone
with estrogen/progesterone therapy, the recent
APHRODITE trial examined testosterone alone, showing increased sexual desire
with mild adverse events. Concerns regarding the long-term safety profile of transdermal testosterone must be addressed before the FDA
will approve a testosterone product for women. Although some fear an increased
risk of breast cancer with exogenous testosterone administration, recent
studies support the idea that androgens can play a role in suppressing the
proliferative effects of estrogen and progesterone.
Long-term safety data is now being collected and analyzed and Phase III trials
focusing on long-term risks are underway. In the meantime, transdermal
testosterone appears to be a safe and effective therapy for postmenopausal
women with HSDD [Swanson S, DeRogatis L, Snabes M, Simes S, Zborowski J. Treatment of HSDD in surgically menopausal
women: a newly initiated Phase III, randomized, double-blind,
placebo-controlled, multi-center study of the safety
and efficacy of LibiGel.
Selección de Resúmenes
de Menopausia
Semana del 10 al 16 de Junio de
2009
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad de Chile
Osteoporos Int. 2009 Jun 11. [Epub ahead of print]
FRAX(R) assessment of osteoporotic fracture probability in
Lippuner K, Johansson
H, Kanis JA, Rizzoli R.
Osteoporosis
Policlinic, Inselspital,
A Swiss-specific
FRAX(R) model was developed. Patient profiles at increased probability of
fracture beyond currently accepted reimbursement thresholds for bone mineral
density (BMD) measurement by dual X-ray absorptiometry
(DXA), and osteoporosis treatment were identified. INTRODUCTION: This study
aimed to determine which constellations of clinical risk factors, alone, or combined
with BMD measurement by DXA, contribute to improved identification of Swiss
patients with increased probability of fracture. METHODS: The 10-year
probability of hip and any major osteoporotic fracture was computed for both
sexes, based on Swiss epidemiological data, integrating fracture risk and death
hazard, in relation to validated clinical risk factors, with and without BMD
values. RESULTS: Fracture probability increased with age, lower body mass index
(BMI), decreasing BMD T-score, and all clinical risk factors used alone or
combined. Several constellations of risk factor profiles were identified,
indicating identical or higher absolute fracture probability than risk factors
currently accepted for DXA reimbursement in
Am J Clin Nutr. 2009 Jun 10. [Epub ahead of
print]
Meta-analysis of the effects of flaxseed interventions on blood lipids.
Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X.
BACKGROUND:
Several clinical trials have investigated the effects of flaxseed and
flaxseed-derived products (flaxseed oil or lignans)
on blood lipids; however, the findings have been inconsistent. OBJECTIVE: We
aimed to identify and quantify the effectiveness of flaxseed and its
derivatives on blood lipid profiles. DESIGN: A comprehensive literature search
was performed on the basis of English reports of randomized controlled trials
of flaxseed or its derivatives on lipid profiles in adults, which were
published from January 1990 to October 2008. Attempts also were made to access
unpublished data. Study quality was assessed by using the Jadad
score, and a meta-analysis was conducted. RESULTS: Twenty-eight studies were
included. Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L (95% CI: -0.20, 0.00 mmol/L)
and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), respectively; significant reductions were observed
with whole flaxseed (-0.21 and -0.16 mmol/L,
respectively) and lignan (-0.28 and -0.16 mmol/L, respectively) supplements but not with flaxseed
oil. The cholesterol-lowering effects were more apparent in females
(particularly postmenopausal women), individuals with high initial cholesterol
concentrations, and studies with higher Jadad scores.
No significant changes were found in the concentrations of HDL cholesterol and
triglycerides. CONCLUSIONS: Flaxseed significantly reduced circulating total
and LDL-cholesterol concentrations, but the changes were dependent on the type
of intervention, sex, and initial lipid profiles of the subjects. Further
studies are needed to determine the efficiency of flaxseed on lipid profiles in
men and premenopausal women and to explore its potential benefits on other cardiometabolic risk factors and prevention of
cardiovascular disease.
Eur J Contracept
Reprod Health Care. 2009 Jun 5:1-10. [Epub
ahead of print]
Twenty or thirty microgram ethinyloestradiol
in an oral contraceptive: Does it make a difference in the mind and the daily
practice of gynaecologists and general practitioners?
Bitzer J, Frey B, von Schonau M, Sabler N, Tschudin S.
Department of
Obstetrics and Gynaecology, University Women's Hospital
Objectives
Currently, evidence-based guidelines concerning the use of oral contraceptives
(OCs) containing either 20 or 30 mug ethinyloestradiol (EE) and the same progestogen,
are lacking. We wanted to identify whether Swiss gynaecologists and general
practitioners (GPs) have specific criteria on which they base their prescribing
habit. Methods Two questionnaires were submitted to 158 physicians. The first
one contained a list of possible criteria relevant for decision making and a
description of specific clinical situations. The second one concerned actual
patients who received either a 20 mug (Yasminelle(R))
or a 30 mug (Yasmin(R)) OC containing the same progestogen drospirenone. Results
The most relevant criteria for decision making (in hierarchical order) were
family history of venous thromboembolic disease
(VTE), headache, smoking, age beyond 35, stability of the menstrual cycle,
breast tenderness, body mass index, irregular bleeding and acne. The 20 mug
dosage was preferred for women older than 35, those smoking more than 15
cigarettes per day, those with a family history of VTE, and those complaining
of breast tenderness or headache. The 30 mug dosage was preferred for patients
with a history of irregular bleeding, a family history of osteoporosis,
expected poor compliance and acne. Conclusion Swiss gynaecologists and GPs do
not preferentially prescribe the lowest possible dosage of EE. They use
indirect markers they consider relevant for differential prescribing. For some
markers, there is inconsistency, indicating that preferences for 20 mug and 30
mug preparations may be influenced by other factors.
Menopause. 2009 Jun 6. [Epub ahead of print]
Serum 25-hydroxyvitamin D is related to indicators of overall physical
fitness in healthy postmenopausal women.
Stewart JW, Alekel DL, Ritland LM, Van Loan M, Gertz E, Genschel U.
From the
1Department of Food Science and Human Nutrition, Iowa State University, Ames,
IA; 2United States Department of Agriculture/Agricultural Research Service,
Western Human Nutrition Research Center, University
of California, Davis, CA; and 3Department of Statistics, Iowa State University,
Ames, IA.
OBJECTIVE::
Inadequate vitamin D status is related to increased adiposity, risk of falls,
and muscle weakness, particularly in older people. We hypothesized that serum
25-hydroxyvitamin D [25(OH)D] is related to physical fitness indices (androidal fat, whole body lean mass, balance, strength) in
healthy postmenopausal women. METHODS:: Covariates for fitness indices included
age or years since menopause, weight, 25(OH)D, energy expenditure, and calcium
intake. Overall and regional (androidal fat mass =
waist + hip fat) body composition was assessed (N = 242) via dual-energy x-ray absorptiometry. RESULTS:: Regression analyses revealed that
71% of variability (P </= 0.0001) in androidal fat
mass was accounted for by weight (53.0%, P </= 0.0001), white blood cell
(WBC) count (2.0%, P </= 0.0001), supplemental calcium (1.7%, P = 0.0004),
years since menopause (1.1%, P = 0.0034), 25(OH)D (1.0%, P = 0.0051), and
vegetable servings (0.6%, P = 0.027); 64% of variability (P </= 0.0001) in
lean mass was accounted for by weight (63.1.%, P </= 0.0001), WBC count
(1.4%, P = 0.0038), and 25(OH)D (1.0%, P = 0.013); 12% of variability (P </=
0.0001) in balance (right + left leg) was accounted for by age (3.8%, P =
0.0019), 25(OH)D (2.0%, P = 0.025), and WBC count (1.8%, P = 0.032); 14% of
variability (P </= 0.0001) in handgrip strength (right + left) was accounted
for by weight (9.3%, P </= 0.0001), 25(OH)D (2.4%, P = 0.013), WBC count
(2.1%, P = 0.019), and age (1.6%, P = 0.044); and 22% of variability (P </=
0.0001) in torso strength was accounted for by site (15.0%, P </= 0.0001)
and weight (4.6%, P = 0.0003). CONCLUSIONS:: Serum 25(OH)D was the common
contributor to physical fitness indices (androidal fat
mass, lean mass, balance, handgrip strength) in healthy postmenopausal women.
Ann Pharmacother. 2009 Jun 9. [Epub ahead of print]
Assessing the Clinical Efficacy of Sildenafil
for the Treatment of Female Sexual Dysfunction(July/August).
Brown DA, Kyle JA, Ferrill MJ.
OBJECTIVE: To
review the clinical data regarding the efficacy and safety of sildenafil for the treatment of female sexual dysfunction
(FSD). DATA SOURCES: A MEDLINE search from 1950 to February 2009 was conducted
using the key words sildenafil and female sexual
dysfunction. Human studies and publication in English were used as primary
limits. A combination of several publication-type limits was used to locate the
clinical trials (eg, clinical trial, controlled
clinical trial, randomized clinical trial). A bibliographic search was also
performed of all located articles. STUDY SELECTION AND DATA EXTRACTION:
Clinical trials involving sildenafil treatment of
premenopausal and postmenopausal women with FSD and women with FSD due to
concomitant medications and/or disease states were reviewed. DATA SYNTHESIS: An
increasing number of clinical trials have been published regarding the
treatment of FSD with sildenafil. Eight studies
demonstrated a possible benefit from treatment for FSD in patients receiving sildenafil, regardless of dose, while 4 trials did not show
any significant differences with treatment. It appears that sildenafil
might be beneficial for women with FSD caused by diseases such as multiple
sclerosis, type 1 diabetes, spinal cord injury, and use of antidepressant
medications. CONCLUSIONS: Although data suggest a possible role of sildenafil for the treatment of FSD, the information should
be interpreted cautiously, as many of the studies included small sample sizes,
used inappropriate statistical tests, and used nonvalidated
assessment tools. A better FSD classification system and consistent use of
validated assessment tools might help alleviate differences among clinical
trials and provide a more cohesive foundation for assessing the safety and
efficacy of sildenafil for the treatment of FSD.
Cancer Res. 2009 Jun 9. [Epub ahead of print]
Subcellular Localization of Cyclic AMP-Responsive
Element Binding Protein-Regulated Transcription Coactivator
2 Provides a Link between Obesity and Breast Cancer in Postmenopausal Women.
Brown KA, McInnes KJ, Hunger NI, Oakhill JS, Steinberg
GR, Simpson ER.
Prince Henry's
Institute, Monash Medical Centre; Departments of
Physiology and Biochemistry and Molecular Biology, Monash
University, Clayton, Melbourne, Victoria, Australia and St. Vincent's Institute
and Department of Medicine, University of Melbourne, Fitzroy, Victoria,
Australia.
Epidemiologic evidence
supports a correlation between obesity and breast cancer in women.
AMP-activated protein kinase plays an important role
in energy homeostasis and inhibits the actions of cyclic AMP-responsive element
binding protein-regulated transcription coactivator 2
(CRTC2). In postmenopausal women, the cyclic AMP-responsive element binding
protein-dependent regulation of aromatase is a
determinant of breast tumor formation through local
production of estrogens. The present work aimed to examine the effect of adipokines on aromatase
expression and identify additional mechanisms by which prostaglandin E2 causes
increased aromatase expression in human breast
adipose stromal cells. Treatment of human adipose stromal cells with forskolin and phorbol 12-myristate 13-acetate (PMA), to mimic
prostaglandin E2, resulted in nuclear translocation of CRTC2. Aromatase promoter II (PII) activity assays showed that
CRTC2 in addition to forskolin/PMA treatment
significantly increased PII-induced activity. CRTC2 binding to PII was examined
by chromatin immunoprecipitation, and forskolin/PMA treatment was associated with increased
binding to PII. Treatment of human adipose stromal
cells with leptin significantly up-regulated aromatase expression associated with nuclear translocation of
CRTC2 and increased binding of CRTC2 to PII. Adiponectin
treatment significantly decreased forskolin/PMA-stimulated
aromatase expression, consistent with the decreased
nuclear translocation of CRTC2 and the decreased binding of CRTC2 to PII. The
expression and activity of the AMP-activated protein kinase
LKB1 was examined and found to be significantly decreased following either forskolin/PMA or leptin
treatment. In contrast, adiponectin significantly
increased LKB1 expression and activity. In conclusion, the regulation of aromatase by CRTC2, in response to the altered hormonal
milieu associated with menopause and obesity, provides a critical link between
obesity and breast cancer.
Menopause. 2009 Jun 3. [Epub ahead of print]
The effects of bazedoxifene on mammographic
breast density in postmenopausal women with osteoporosis.
Harvey JA, Holm MK, Ranganath R, Guse PA, Trott EA, Helzner E.
From the
1Department of Radiology, University of Virginia, Charlottesville, VA; 2Innovis
Health, Dakota Clinic, Ltd, Fargo, ND; and 3Wyeth Research, Collegeville, PA.
OBJECTIVE:: This
study aimed to assess quantitative changes in mammographic breast density after
24 months of therapy with bazedoxifene compared with raloxifene or placebo in postmenopausal women with
osteoporosis. METHODS:: This was a retrospective, ancillary study of a subset
of women enrolled in a multicenter, double-blind, randomized, placebo- and
active-controlled phase 3 trial evaluating bazedoxifene
for the treatment of postmenopausal osteoporosis. Participants were randomly
assigned to receive bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo once daily for 3 years. To be
eligible for breast density evaluation, participants had to be 62 years or
younger and completed 24 months of treatment, with mammograms at baseline and
24 months. Original mammogram pairs (left craniocaudal
views) for each participant were digitized and analyzed by a radiologist.
Breast density was measured using interactive thresholding
to segment the mammogram, and percent density was determined using a validated
software program. RESULTS:: Mammogram pairs were obtained from 444
participants. Baseline and demographic characteristics were similar among
groups (mean age, 58.7 y). After 24 months, the mean percent changes in breast
density from baseline were low (bazedoxifene 20 mg,
-1.2%; bazedoxifene 40 mg, -0.4%; raloxifene
60 mg, -0.5%; placebo, -0.2%) and not significantly different among groups.
CONCLUSIONS:: Treatment with bazedoxifene for 2 years
did not affect age-related changes in breast density in this population of
postmenopausal women with osteoporosis. The changes in breast density with bazedoxifene 20 or 40 mg were similar to those with raloxifene 60 mg or placebo.
Nutr Metab Cardiovasc Dis. 2009 Jun 4. [Epub ahead of
print]
Comparison between several insulin sensitivity indices and metabolic
risk factors in overweight and obese postmenopausal women: A MONET study.
Malita FM, Messier V, Lavoie JM, Bastard JP, Rabasa-Lhoret R, Karelis AD.
Department of
Nutrition,
BACKGROUND AND
AIMS: The purpose of this study was to compare the relationship of several
insulin sensitivity indices with cardiometabolic risk
factors in overweight and obese postmenopausal women. METHODS AND RESULTS: This
was a cross-sectional study involving 137 overweight and obese postmenopausal
women (age: 57.7+/-4.8 yrs; body mass index: 32.4+/-4.6kg/m(2); body fat:
38.6+/-9.2kg). Insulin sensitivity was determined by the euglycaemic-hyperinsulinemic
(EH) clamp technique as well as by oral glucose tolerance test (OGTT) derived
indices (Stumvoll, Matsuda and SI(is)) and fasting
surrogate indices (HOMA, QUICKI). Cardiometabolic
risk factors included: body composition and visceral fat that were measured
using dual energy X-ray absorptiometry and computed
tomography, respectively. Peak oxygen consumption, lower body muscle strength
(using weight training equipment), physical activity energy expenditure (doubly
labeled water), plasma lipids and C-reactive protein
were also measured. Correlations of insulin sensitivity indices with metabolic
risk factors showed some similarities, however, a wide range of variations were
also observed. Furthermore, our results showed that visceral fat was the
primary predictor for surrogate and OGTT indices, explaining 15-28% of the
variance and the triglycerides/HDL-C ratio was the primary predictor for the EH
clamp indices, explaining 15-17% of the variance. CONCLUSION: The present study
indicates that the different methods of measuring and/or expressing insulin
sensitivity display variations for associations with cardiometabolic
risk factors. Therefore, interpretations of relationships between insulin
sensitivity indices and cardiometabolic risk factors
should take into account the method used to estimate and express insulin
sensitivity.
Selección de Resúmenes
de Menopausia
Semana
del 17 al 23 de Junio de 2009
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad de Chile
Horm Metab
Res. 2009 Jun 17. [Epub ahead of print]
Efficacy and Safety
of Denosumab in Postmenopausal Women with Osteopenia or Osteoporosis: A Systematic Review and a
Meta-analysis.
Anastasilakis AD, Toulis KA, Goulis DG, Polyzos SA, Delaroudis S, Giomisi A, Terpos E.
1Department of
Endocrinology, 424 Military Hospital,
Receptor activator
of nuclear factor-kappaB ligand
(RANKL) is a cytokine essential for osteoclast
differentiation, activation, and survival. Denosumab,
a human monoclonal antibody against RANKL, constitutes a promising antiresorptive agent for osteoporosis. We searched MEDLINE,
EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and other
trial registries through January 2009. We selected randomized controlled trials
(RCTs) of denosumab in
women with low bone mass that described the changes on bone markers and bone
mineral density (BMD) as well as the adverse events including fracture risk. We
analyzed data from nine RCTs involving 10 329
participants. Although denosumab universally
decreased bone markers and increased lumbar and hip BMD, the efficacy
evaluation based on percentage (%) mean change from the baseline was not
possible due to missing data. Denosumab was not
associated with a significant reduction in fracture risk [OR (95% CI) 0.74
(0.33 to 1.64), p=0.45]. Increased risk of serious adverse events [OR (95% CI)
1.83 (1.10 to 3.04), p=0.02] and serious infections [OR (95% CI) 4.45 (1.15 to
17.14), p=0.03] were evident. In conclusion, although effective as an antiresorptive agent, denosumab
has not yet proved its efficacy on fracture risk reduction while increased
infection risk questions its safety.
Semin Reprod Med. 2009
Jul;27(4):338-45. Epub 2009 Jun 15.
Autonomic
regulation of blood pressure in menopause.
Department of
Internal Medicine, Hypertension Division, University of Texas Southwestern Medical Center,
Dallas, TX 75390-8586, USA. wanpen.vongpatanasin@utsouthwestern.edu
A large body of
evidence indicates a major influence of sex hormones, particularly estrogen, on autonomic regulation of blood pressure (BP).
The sympathetic nervous system is now widely recognized as a major regulator of
BP homeostasis and contributor to pathogenesis of hypertension in humans.
Menopause is accompanied by an accelerated age-related rise in sympathetic
nerve activity (SNA). Mechanisms underlying sympathetic activation in menopause
are unknown but may be related to impaired central modulation of baroreflex function or direct inhibitory influence of estrogen on SNA. Menopause is also accompanied by enhanced
alpha-adrenergic peripheral vasoconstriction both at rest and during exercise.
In ovariectomized rats, reduced nitric oxide release
from the skeletal muscle caused by estrogen
deficiency contributes to augmented sympathetic vasoconstriction during muscle
contraction. The alteration in central autonomic regulation coupled with
enhanced vascular adrenergic sensitivity may be responsible for elevation in
resting BP and exaggerated pressor responses to
exercise and mental stress in postmenopausal women.
Adv Exp Med Biol. 2009;646:31-9.
Developmental
origins of osteoporosis: the role of maternal nutrition.
Cooper C,
Harvey N, Cole Z, Hanson M, Dennison E.
MRC Epidemiology
Resource Centre and Centre for Developmental Origins of Health and Adult
Disease, University of Southampton, Southampton General Hospital, Southampton,
SO16 6YD, cc@mrc.soton.ac.uk.
Osteoporosis is a
major cause of morbidity and mortality through its association with age-related
fractures. Although most effort in fracture prevention has been directed at
retarding the rate of age-related bone loss, and reducing the frequency and
severity of trauma among elderly people, evidence is growing that peak bone
mass is an important contributor to bone strength during later life. The normal
patterns of skeletal growth have been well characterised in cross-sectional and
longitudinal studies. It has been confirmed that boys have higher bone mineral
content, but not volumetric bone density, than girls. Furthermore, there is a
dissociation between the peak velocities for height gain and bone mineral
accrual in both genders. Puberty is the period during which volumetric density
appears to increase in both axial and appendicular
sites. Many factors influence the accumulation of bone mineral during childhood
and adolescence, including heredity, gender, diet, physical activity, endocrine
status, and sporadic risk factors such as cigarette smoking. In addition to
these modifiable factors during childhood, evidence has also accrued that
fracture risk might be programmed during intrauterine life. Epidemiological
studies have demonstrated a relationship between birthweight,
weight in infancy, and adult bone mass. This appears to be mediated through
modulation of the set-point for basal activity of pituitary-dependent endocrine
systems such as the hypothalamic-pituitary-adrenal (HPA) and growth
hormone/insulin-like growth factor-1 (GH/IGF-1) axes. Maternal smoking, diet
(particularly vitamin D deficiency) and physical activity also appear to
modulate bone mineral acquisition during intrauterine life; furthermore, both
low birth size and poor childhood growth, are directly linked to the later risk
of hip fracture. The optimisation of maternal nutrition and intrauterine growth
should also be included within preventive strategies against osteoporotic
fracture, albeit for future generations.
Acta Cytol. 2009
May-Jun;53(3):277-82.
Value of cervical
cytology in diagnosing endometrial carcinoma in women with postmenopausal
bleeding.
van Doom HC, Opmeer BC, Kooi GS, Ewing-Graham PC, Kruitwagen RF, Mol BW.
Department of Gynecological Oncology,
OBJECTIVE: To
assess the accuracy of the cervical smear in the diagnosis of endometrial
cancer in women with postmenopausal bleeding, with an emphasis on the
diagnostic relevance of normal endometrial cells. STUDY DESIGN: Women presenting
with abnormal postmenopausal bleeding, not using hormone replacement therapy,
were included prospectively. Cervical cytology was coded according to both the Papanicolaou (Pap) classification and the Dutch coding
system (CISOE-A), which classifies endometrial and other cell types separately.
For both classification systems, likelihood ratios (LR) for the presence of
(pre) malignancy of the endometrium were calculated.
RESULTS: We included 543 women with postmenopausal bleeding. A (pre) cancerous
endometrial lesion was present in 64 women (11.7%). A Pap III increased the
probability of (pre) malignancy (LR 3.5), whereas Pap IV and Pap V virtually
proved the presence of carcinoma. The CISOE-A classification showed similar
results. The presence of normal endometrial cells did not increase the
probability of endometrial (pre) malignancy. CONCLUSION: Adding the results of
the cervical smear to endometrial thickness could detect incidental endometrial
cancers that are missed by transvaginal sonography (< 5 mm). In women with postmenopausal
bleeding the presence of normal endometrial cells is not predictive of
endometrial cancer.
Cancer. 2009 Jun
12. [Epub ahead of print]
Hormone replacement
therapy and survival in lung cancer in postmenopausal women in a rural
population.
Huang B,
Carloss H, Wyatt SW, Riley E.
BACKGROUND::
Hormone replacement therapy (HRT) may play a role in the development of lung
cancer and subsequent survival. Results from studies exploring these issues are
inconsistent. A retrospective study in a rural population was conducted to
determine whether a history of HRT use is associated with survival of
postmenopausal women with lung cancer. METHODS:: A retrospective medical chart
review of 648 postmenopausal women, diagnosed with a first primary lung cancer
between1995 and 2005, was conducted in a regional hospital in
Ther Clin
Risk Manag. 2009
Apr;5(2):169-75. Epub 2009 May 4.
Treatment of
osteoporosis with annual iv zoledronic acid: effects
on hip fracture.
INSERM U831, Université de Lyon, Division of Rheumatology, Hôpital E Herriot, Hospices Civils
de Lyon, Lyon, France.
BACKGROUND:
Several treatments for postmenopausal osteoporosis have been available in the
past decade, but adherence to these treatments has been judged inadequate. The
prevention of hip fracture by these medications is still modest. METHODS: A
literature search was performed for treatment with zoledronic
acid for the prevention of hip fracture. RESULTS: In the The
Health Outcomes and Reduced Incidence with Zoledronic
Acid Once Yearly (HORIZON) Pivotal Fracture Trial, involving 7765
postmenopausal women with low bone mineral density or with prevalent vertebral
fracture, women taking zoledronic acid had a 41%
relative risk reduction for hip fracture, at 3 years, compared to placebo. In
the HORIZON Recurrent Fracture Trial, 2127 patients (76% were women) were
randomized to receive either zoledronic acid or
placebo after sustaining a first hip fracture. A reduction of 30% in the second
hip fracture risk was observed, but it did not reach statistical significance. Zoledronic acid was generally safe in these trials,
although a slightly increased rate of severe atrial
fibrillations was observed in the HORIZON Prevention Fracture Trial, but not in
the HORIZON Recurrent Fracture Trial. CONCLUSION: Yearly zoledronic
acid reduces the risk of hip fracture, both in postmenopausal osteoporotic women with and without prevalent vertebral
fracture and in men and women with a recent first hip fracture.
Curr Oncol. 2009 May;16(3):21-5
Hormone replacement
therapy and outcomes for women with non-small-cell lung cancer: can an
association be confirmed?
BACKGROUND: A
recent report suggested that women who had been taking hormone replacement
therapy (hrt) experienced significantly decreased
survival after a lung cancer diagnosis. Given the large cohort of women who
have received hrt, it is important to try to confirm
that association. METHODS: We reviewed female patients diagnosed with lung
cancer at our institution between January 1999 and December 2003 for age at
diagnosis, disease stage, treatment, smoking history, hrt,
performance status, weight loss, age at menopause, and overall survival.
Patients were excluded if they had small-cell lung cancer or an unknown primary
cancer, or if they had had previous or synchronous non-lung, non-skin cancers.
Statistical analysis used the chi-square test for categorical variables and the
Kaplan-Meier method and Cox regression model for univariate
and multivariate analyses of overall survival. RESULTS: Of 397 eligible
patients, most (68%) were stage iii or iv. The group included very few
never-smokers (5%). The proportion of patients with experience of prior or
current hrt was 29%, and no effect on overall
survival was observed. Median survival was 13 months in the non-hrt group and 14 months in the hrt
group. Significant factors predicting for overall survival included performance
status, stage, and weight loss. CONCLUSIONS: Stage, performance status, and
weight loss are the most powerful predictors of survival for women with
non-small-cell lung cancer. As compared with non-hrt
users, patients with prior hrt use.