Selección de Resúmenes
de Menopausia
Agosto de 2008
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad de Chile
Semana del 20 al 26 de Agosto 2008
Obesity (Silver Spring). 2008 Jul 17. [Epub ahead of print]
Weight Regain and Health-related Quality of
Life in Postmenopausal Women.
Yankura DJ, Conroy MB, Hess R, Pettee KK, Kuller LH, Kriska AM.
1School of Medicine,
Weight
loss improves health-related quality of life (HRQoL).
However, regain after loss is common; little is known about the impact of
weight regain on HRQoL in postmenopausal women. Woman
on the Move through Activity and Nutrition (WOMAN) is a randomized lifestyle
intervention trial of diet, physical activity, and weight loss in 508
postmenopausal women aged 52-62 years. This analysis focused on the women who
lost >/=5 lb during the initial phase of the study, baseline to 6 months (n
= 248). This cohort was divided into three groups based on subsequent weight
change between 6 and 18 months: weight loss (WL; >/=5 lb loss), weight
stable (WS; <+/-5 lb change), and weight regain (WR; >/=5 lb gain). HRQoL was measured at baseline, 6, and 18 months using the
Short Form-36. Of the 248 women studied, 51 (21%) continued to lose weight
after initial weight loss, while 127 (51%) maintained a stable weight, and 70
(28%) regained weight. Between baseline and 6 months, women in WR group had
decreased mental health and social-functioning scores, while the WL and WS
groups improved in these subscales. Between baseline and 18 months, energy improved
most significantly in those with continued weight loss (P = 0.0003). Weight
loss was correlated with a small to moderate improvement in perceived general
health and energy, which was reversed by weight gain. Further study is needed
to investigate the impact of a decline in mental health and social functioning
on future weight regain.
Ann
Intern Med. 2008 Aug 19;149(4):242-50
Serum 25-hydroxyvitamin D concentrations
and risk for hip fractures.
Cauley JA, Lacroix AZ, Wu L, Horwitz M, Danielson ME, Bauer DC, Lee JS, Jackson RD et al
BACKGROUND:
The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D]
concentration and hip fractures is unclear. OBJECTIVE: To see whether low serum
25(OH) vitamin D concentrations are associated with hip fractures in
community-dwelling women. DESIGN: Nested case-control study. SETTING: 40
clinical centers in the
Hypertens Res. 2008 Jun;31(6):1191-7
Relationship
between Carotid Atherosclerosis and Lumbar Spine Bone Mineral Density in
Postmenopausal Women.
Sumino H, Ichikawa S, Kasama S, Takahashi T, Sakamoto H, Kumakura H, Takayama Y, et al
Department of Nursing, Faculty of Nursing,
Osteoporosis
and increased carotid intima-media thickness (IMT)
have been associated with atherosclerosis. We investigated the correlation
between carotid IMT and lumbar spine bone mineral density (BMD) in
postmenopausal women. We studied the carotid IMT in 175 postmenopausal women,
including 43 women (control) with normal spinal BMD, 73 women with osteopenia, and 59 women with osteoporosis. Carotid IMT was
assessed by ultrasonography. BMD at the lumbar spine
(lumbar 2 to 4 vertebrae) was measured by dual-energy X-ray absorptiometry.
Age, years since menopause, and carotid IMT were
significantly greater in the osteoporosis group than in the control (all
p<0.01) and osteopenia groups (all p<0.01).
Estradiol was significantly lower in the osteoporosis
group than in the control group (p<0.05). BMD was significantly lower in the
osteoporosis group than in the osteopenia or control
group (both p<0.01) and in the osteopenia group
than in the control group (p<0.01). After adjusting for age, years since
menopause, and estradiol, women with osteoporosis had
significantly greater carotid IMT than controls (p<0.05). The univariate linear regression analysis revealed that carotid
IMT was significantly positively correlated with age, years since menopause,
and low-density lipoprotein (LDL) cholesterol (all p<0.05) and was
significantly negatively correlated with estradiol
and BMD (all p<0.05), but showed no significant association with other
clinical variables. In multivariate regression analysis, the carotid IMT was
significantly positively correlated with LDL cholesterol (p<0.01) and
negatively correlated with BMD (p<0.01), but not with other variables.
Carotid atherosclerosis might be associated with lumbar spine bone mass in
postmenopausal women, suggesting that postmenopausal women with osteoporosis
may have more advanced carotid atherosclerosis than those with a normal bone
mass.
BMJ. 2008 Aug 21;337:a1190. doi:
10.1136/bmj.a1190.
Health related quality of life after
combined hormone replacement therapy: randomised
controlled trial.
Welton AJ, Vickers MR, Kim J, Ford D, Lawton BA, Maclennan AH, Meredith SK, et
al.
MRC General Practice Research Framework, Stephenson House,
OBJECTIVE:
To assess the effect of combined hormone replacement therapy (HRT) on health
related quality of life. DESIGN: Randomised placebo
controlled double blind trial. SETTING: General practices in
J Bone
Miner Res. 2008 Aug 20. [Epub
ahead of print
Mechanical Stimulation of Mesenchymal Stem Cell Proliferation and Differentiation
Promotes Osteogenesis While Preventing Dietary
Induced Obesity.
Luu Y, Capilla E, Rosen C, Gilsanz V, Pessin J, Judex S, Rubin CT.
Abstract
Mesenchymal stem cells (MSCs) are defined by their
ability to self-renew and differentiate into the cells which form mesodermal tissues such as bone and fat. Low magnitude
mechanical signals (LMMS) have been shown to be anabolic to bone, and recently
reported to suppress the development of fat in normal animals fed a regular
diet. Using male C57BL/6J mice, the ability of LMMS (0.2 g, 90 Hz signal
applied for 15 mins/day, 5 day/wk) to simultaneously
promote bone formation and prevent diet induced obesity was correlated to
mechanical influences on the molecular environment of the bone marrow, as
indicated by the population dynamics and lineage commitment of MSCs. Six weeks
of LMMS increased the overall marrow-based stem cell population by 37% and the
number of MSCs by 46%. Concomitant with the increase in stem cell number, the
differentiation potential of MSCs in the bone marrow was biased towards osteoblastic and against adipogenic
differentiation, as reflected by up-regulation of the transcription factor
Runx2 by 72% and down-regulation of PPARgamma by 27%.
The phenotypic impact of LMMS on MSC lineage determination was evident at 14w,
where visceral adipose tissue formation was suppressed by 28%, while trabecular bone volume fraction in the tibia was increased
by 11%. Translating this to the clinic, a one year trial in young women
(15-20y; n=48) with osteopenia showed that LMMS
increased trabecular bone in the spine and kept
visceral fat at baseline levels, while control subjects showed no change in
bone density yet an increase in visceral fat. Mechanical modulation of stem
cell proliferation and differentiation indicates a unique therapeutic target to
aid in tissue regeneration and repair, and may represent the basis of a
non-pharmacologic strategy to simultaneously prevent obesity and osteoporosis.
Menopause
Int. 2008 Sep;14(3):123-8
Depression during menopausal transition: a review
of treatment strategies and pathophysiological
correlates.
MD
FRCPC, Director, Women's Health Concerns Clinic (WHCC), Department of
Psychiatry and Behavioural Neurosciences, McMaster
University, James Street South, FB 638, Hamilton, Canada.
It has
long been recognized that women are at a higher risk than men to develop
depression and that such risk is particularly associated with reproductive
cycle events. Recent long-term, prospective studies have demonstrated that the
transition to menopause is associated with higher risk for new onset and
recurrent depression. A number of biological and environmental factors are
independent predictors for depression in this population, including the
presence of hot flushes, sleep disturbance, history of severe premenstrual
syndrome or postpartum blues, ethnicity, history of stressful life events, past
history of depression, body mass index, socioeconomic status and the use of
hormones and antidepressants. Accumulated evidence suggests that ovarian
hormones modulate serotonin and noradrenaline
neurotransmission, a process that may be associated with underlying pathophysiological processes involved in the emergence of
depressive symptoms during periods of hormonal fluctuation in biologically
predisposed subpopulations. Transdermal estradiol and serotonergic and
noradrenergic antidepressants are efficacious in the treatment of depression
and vasomotor symptoms in symptomatic, midlife women. The identification of
individuals whom might be at a higher risk for depression during menopausal
transition could guide preventive strategies for this population.
Menopause
Int. 2008 Sep;14(3):111-6
Prophylactic oophorectomy in premenopausal women and long-term health.
Shuster LT, Gostout BS, Grossardt BR, Rocca WA.
MD, FACP, Women's Health Clinic, Mayo Clinic,
OBJECTIVE:
To review the data on long-term outcomes in women who underwent prophylactic
bilateral oophorectomy, a common surgical procedure
that has more than doubled in frequency since the 1960s. STUDY DESIGN:
Literature review of the published data on the consequences of prophylactic
bilateral oophorectomy. Special emphasis was given to
the Mayo Clinic Cohort Study of Oophorectomy and
Aging. Main outcome measures Overall mortality, cardiovascular disease,
cognitive impairment and dementia, parkinsonism,
osteoporosis, psychological wellbeing and sexual function. RESULTS: There is a
growing body of evidence suggesting that the premature loss of ovarian function
caused by bilateral oophorectomy performed before
natural menopause is associated with several negative outcomes. In particular,
studies have revealed an increased risk of premature death, cardiovascular
disease, cognitive impairment or dementia, parkinsonism,
osteoporosis and bone fractures, decline in psychological wellbeing and decline
in sexual function. The effects involve different organs (e.g. heart, bone, or
brain), and different functions within organs (e.g. cognitive, motor, or
emotional brain functions). Estrogen treatment may prevent some but not all of
these negative outcomes. CONCLUSION: The potential adverse effects of
prophylactic bilateral oophorectomy on heart health,
neurological health, bone health and quality of life should be carefully
weighed against its potential benefits for cancer risk reduction in women at
average risk of ovarian cancer.
Int J Cancer. 2008 Aug
18. [Epub ahead of
print
Coffee consumption and risk of endometrial
cancer: A prospective study in
Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Kurahashi N, et al.
Epidemiology and Prevention Division,
Coffee
has been proposed to decrease the circulating insulin and estrogen levels,
which are related to the development of endometrial cancer. However, few
studies have prospectively assessed the association between coffee consumption
and endometrial cancer. We conducted a population-based prospective cohort
study in 53,724 Japanese women aged 40-69 years with no history of cancer at
baseline in 1990-1994. We used Cox proportional hazards regression analysis to
estimate the hazard ratio (HR) and 95% confidence interval (CI) of endometrial
cancer incidence in relation to coffee consumption. All reported p values are
2-tailed. During the 15-year follow-up period, we documented 117 cases of
endometrial cancer. Coffee consumption was significantly associated with a
decreased risk of endometrial cancer. After adjustment for age, study area,
body mass index, menopausal status, age at menopause for postmenopausal women,
parity, use of exogenous female hormones, smoking status and by consumption of
green vegetables, beef, pork and green tea, the multivariate HRs (95% CI) of
endometrial cancer in women who drank coffee </=2 days/week, 3-4 days/week,
1-2 cups/day and >/=3 cups/day were 1.00, 0.97 (0.56-1.68), 0.61 (0.39-0.97)
and 0.38 (0.16-0.91), respectively (p for trend = 0.007). In contrast, green
tea consumption was not significantly associated with a reduced risk of
endometrial cancer (p for trend = 0.22). The inverse association between coffee
consumption and risk of endometrial cancer was consistently observed in
subgroup analyses stratified by potential confounders. Coffee consumption may
be associated with a decreased risk of endometrial cancer.
Menopause. 2008 Jul-Aug;15(4 Pt 1):706-13.
The sexuality of middle-aged women with a
sexual partner: a population-based study.
Valadares AL, Pinto-Neto AM, Conde DM, Osis MJ, Sousa MH, Costa-Paiva L.
Department of Gynecology and Obstetrics, Universidade
Estadual de Campinas,
OBJECTIVE:
To evaluate the factors associated with the sexuality of middle-aged women with
sexual partners. DESIGN: A cross-sectional, population-based study was carried
out using an anonymous, self-response questionnaire
completed by Brazilian-born women 40 to 65 years old with 11 years or more of
formal education who had a sexual partner. Of the 378 women who agreed to
participate in the study, 219 answered all the questions used for calculation
of the sexuality score and reported having a sexual partner. The instrument was
based on the Short Personal Experiences Questionnaire. Seven components were
analyzed: satisfaction in sexual activities, orgasm, intensity of desire,
self-classification of sexual life, and frequency of arousal, sexual activity,
and sexual fantasies. Sociodemographic, clinical,
behavioral, reproductive, and partner-related factors were evaluated. Poisson
multiple regression analysis was performed, and
prevalence ratios (PRs) with their 95% CIs were estimated. RESULTS: The median
sexuality score was 9 (range, 2.45-13.77). The prevalence of below-median
scores was higher in women who lived with their sexual partner (PR = 2.07; 95%
CI: 1.17-3.69), who were in the menopausal transition or were postmenopausal
(PR = 1.69; 95% CI: 1.08-2.65), and who were hypertensive (PR = 1.65; 95% CI:
1.19-2.30). Sexual activities involving penetration (PR = 0.48; 95% CI:
0.31-0.73) and a score of 6 for satisfaction with partner as a lover (PR =
0.34; 95% CI: 0.20-0.60) were indicative of a protective effect against poor
sexuality. CONCLUSIONS: In this cohort, the sexuality of women in midlife was
negatively associated with the factors of living with a sexual partner, being
in the menopausal transition or postmenopausal, and being hypertensive.
Therefore, greater attention should be paid to identifying these factors, and
measures should be adopted to minimize their repercussions on the sexuality of
middle-aged women.
Semana del 13 al 19 de Agosto 2008
N Engl
J Med. 2008 Aug 14;359(7):697-708.
The Effects of Tibolone
in Older Postmenopausal Women.
Cummings
SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos
V, Verweij P, Mol-Arts M, Kloosterboer L, Mosca L, Christiansen
C, Bilezikian J, Kerzberg EM, Johnson S, Zanchetta J, Grobbee DE, Seifert W, Eastell R; the LIFT
Trial Investigators.
BACKGROUND: Tibolone has estrogenic, progestogenic,
and androgenic effects. Although tibolone prevents
bone loss, its effects on fractures, breast cancer, and cardiovascular disease
are uncertain. METHODS: In this randomized study, we assigned 4538 women, who
were between the ages of 60 and 85 years and had a bone mineral density T score
of -2.5 or less at the hip or spine or a T score of -2.0 or less and radiologic
evidence of a vertebral fracture, to receive once-daily tibolone
(at a dose of 1.25 mg) or placebo. Annual spine radiographs were used to assess
for vertebral fracture. Rates of cardiovascular events and breast cancer were
adjudicated by expert panels. RESULTS: During a median of 34 months of
treatment, the tibolone group, as compared with the
placebo group, had a decreased risk of vertebral fracture, with 70 cases versus
126 cases per 1000 person-years (relative hazard, 0.55; 95% confidence interval
[CI], 0.41 to 0.74; P<0.001), and a decreased risk of nonvertebral
fracture, with 122 cases versus 166 cases per 1000 person-years (relative
hazard, 0.74; 95% CI, 0.58 to 0.93; P=0.01). The tibolone
group also had a decreased risk of invasive breast cancer (relative hazard,
0.32; 95% CI, 0.13 to 0.80; P=0.02) and colon cancer (relative hazard, 0.31;
95% CI, 0.10 to 0.96; P=0.04). However, the tibolone
group had an increased risk of stroke (relative hazard, 2.19; 95% CI, 1.14 to
4.23; P=0.02), for which the study was stopped in February 2006 at the
recommendation of the data and safety monitoring board. There were no
significant differences in the risk of either coronary heart disease or venous thromboembolism between the two groups. CONCLUSIONS: Tibolone reduced the risk of fracture and breast cancer and
possibly colon cancer but increased the risk of stroke in older women with
osteoporosis.
Menopause. 2009
Aug 1. [Epub ahead of print]
A personal perspective on fracture risk
assessment tools.
From the
The World Health
Organization and the Foundation for Osteoporosis Research and Education have
each recently posted fracture risk assessment tools on Web sites. To be most
useful, these tools need to provide risk data in a form that is easily used by
clinicians as they discuss treatment options with their patients. This article
critiques these two tools and offers clinicians
suggestions for key elements that should be included in fracture risk reports.
Reports based on risk assessment tools need to provide data in a meaningful
form that patients can easily grasp. Much more than risk numbers are needed,
and, ideally, fracture risk tools should be integrated into bone densitometry
reporting or placed into comprehensive, user-friendly, decision aids.
Cancer Treat Rev. 2008;34 Suppl 1:S3-18. Epub 2008 Jun 2.
Guidance for the management of breast cancer treatment-induced bone
loss: a consensus position statement from a UK Expert Group.
Reid DM, Doughty J, Eastell R, Heys SD, Howell A, McCloskey
EV, Powles T, Selby P, Coleman RE.
Department
of Rheumatology,
In postmenopausal
women, the use of aromatase inhibitors increases bone
turnover and induces bone loss at sites rich in trabecular
bone at an average rate of 1-3% per year leading to an increase in fracture
incidence compared to that seen during tamoxifen use.
The bone loss is much more marked in young women with treatment-induced ovarian
suppression followed by aromatase inhibitor therapy
(average 7-8% per annum). Pre-treatment with tamoxifen
for 2-5 years may reduce the clinical significance of the adverse bone effects
associated with aromatase inhibitors, particularly if
this leads to a shortening in the duration of exposure to an aromatase inhibitor. However, skeletal status should still
be assessed at the commencement of aromatase
inhibitor therapy. The rate of bone loss in women who experience a premature
menopause before the age of 45 or are receiving ovarian suppression therapy is
accelerated by the concomitant use of aromatase
inhibitors. These patients are considered to be at high risk of clinically
important bone loss and should have a baseline dual energy X-ray absorptiometry (DXA) assessment of bone mineral density
(BMD). Randomised clinical trials in postmenopausal women indicate that bisphosphonates prevent the bone loss and accelerated bone
turnover associated with aromatase inhibitor therapy
and are a promising strategy for the prevention and treatment of osteoporosis
in this setting. Treatment initiation recommendations are based on a
combination of risk factors for osteoporotic fracture and BMD levels. Bisphosphonates, along with a healthy lifestyle and
adequate intake of calcium and vitamin D are the treatments of choice to
prevent bone loss. Due to the rate of bone loss associated with breast cancer
treatments, and uncertainties about the interaction between aromatase
inhibitor use and BMD for fracture risk, the threshold for intervention has
been set at a higher level than that generally recommended for postmenopausal
osteoporosis. Management recommendations have been summarised in two
algorithms, one for women experiencing a premature menopause and the other for
postmenopausal women requiring adjuvant aromatase
inhibitor therapy.
Eur J Obstet
Gynecol Reprod Biol. 2008 Aug 11. [Epub
ahead of print]
Randomized, double-blind,
placebo-controlled study of oral lactobacilli to improve the vaginal flora of
postmenopausal women.
Petricevic L, Unger FM, Viernstein H, Kiss H.
Department of
Obstetrics and Gynaecology, Medical University of Vienna, Waehringer
Guertel 18-20, A-1090 Vienna, Austria.
OBJECTIVE: The
purpose of this randomized, double-blind, placebo-controlled study was to
evaluate the influence of the orally administered probiotic
strains Lactobacillus rhamnosus GR-1 and
Lactobacillus reuteri RC-14 on the quality of the
vaginal flora in postmenopausal women. STUDY DESIGN: Postmenopausal women with
Nugent scores between 4 and 6 in initial vaginal swab,
were randomized into two groups. Women in the intervention group received probiotic capsules containing 2.5x10(9)CFU (colony forming
units) each of lyophilized L. rhamnosus GR-1 and L. reuteri RC-14 and women in the control group received an
oral placebo once daily, in both groups for 14 days. Final vaginal swabs were
taken 1 day after the last administration of the medication. The primary
efficacy variable was a change in the Nugent score between baseline and the end
of the study of at least two grades in each individual patient. RESULTS:
Seventy two women were recruited in the study, 35 assigned to the intervention
group and 37 to the control group. Twenty-one of the 35 subjects (60%) in the
intervention group and 6 of the 37 subjects (16%) in the control group showed a
reduction in the Nugent score by at least two grades. The difference in the
number of patients with improvement was highly significant (p=0.0001). The
median difference in Nugent scores between baseline and the end of the study
was 3 in the intervention group and 0 in the control group (p=0.0001).
CONCLUSION: Our results provide evidence for an alternative modality to restore
the normal vaginal flora using specific probiotic
strains administered orally.
Menopause. 2008 Jul-Aug;15(4 Suppl):810-5.
Chemoprevention in postmenopausal women.
Department of
Medicine, Division of Hematology/Oncology, University
of Pittsburgh School of Medicine, Pittsburgh, PA, USA. rastogip@upmc.edu
Several large,
prospective trials have evaluated tamoxifen compared
with placebo for breast cancer risk reduction in women at increased risk of
breast cancer. Combined results from these trials demonstrate that tamoxifen at 20 mg/d reduced the incidence of breast cancer
by 38%. The risk of developing breast cancer is the primary determinant of net
benefit, with greater benefits accrued to women with the highest risk of breast
cancer. Age and the presence of risk factors for increased toxicity also have
an effect on the net benefit associated with tamoxifen.
The greatest clinical benefit from tamoxifen is
evident for younger women who are at lower risk of thromboembolic
complications and uterine cancer, women without a uterus, and women with breast
biopsy results indicative of atypical hyperplasia or lobular carcinoma in situ.
Raloxifene has also been shown to reduce the risk of
invasive breast cancer in women with osteoporosis and is as effective as tamoxifen for reducing the risk of invasive breast cancer
in postmenopausal women at increased risk of breast cancer. In high-risk
younger, postmenopausal women, raloxifene seems to
offer a net benefit when comparing the reduction of risk of breast cancer and
prevention of fractures with the risk of stroke, venous thromboembolic
events, uterine events, and symptomatic side effects. Raloxifene
offers an acceptable option for breast cancer risk reduction in postmenopausal
women.
Menopause. 2008 Jul-Aug;15(4 Suppl):804-9.
Risks and benefits
of therapy with menopausal hormones versus selective estrogen-receptor
modulators in peri- and postmenopausal women at
increased breast cancer risk.
Center for Outcomes
Research and Evaluation,
Decision making
about menopausal therapies is complex because of the number of clinical factors
that must be considered. Menopausal hormone therapy can relieve the vasomotor
symptoms of menopause, but the most common preparation, combination estrogen and progesterone, increases the risk of breast
cancer. Both tamoxifen and raloxifene
can reduce the risk of developing invasive breast cancer, but the adverse
effects of these drugs differ substantially. Risk models have been built to
identify women at high risk for developing breast cancer, but their application
in clinical practice has been develop disappointingly low. We propose an
approach for identifying and managing menopausal women at high risk for breast
cancer that can be readily implemented in clinical practice. The first step is
to identify women at sufficiently high risk for breast cancer to merit
treatment. For women aged 45 or older, the presence of one or more first-degree
relatives with breast cancer and one or more previous breast biopsies will
identify those whose 5-year risk is 2% or higher. For women 55 years or older,
the presence of either one of these risk factors is sufficient. Any woman with
a family history of breast cancer should be assessed as to whether she is
likely to carry a BRCA mutation and referred for genetic counseling
and possible genetic testing. Decisions about treatment options should be based
on the presence or absence of bothersome vasomotor symptoms, an intact uterus,
and risk factors for cardiovascular disease. A simple algorithm is presented to
streamline identification and management of menopausal women at high risk for
breast cancer.
Menopause. 2008 Jul-Aug;15(4 Suppl):782-9.
Epidemiology, genetics, and risk evaluation of postmenopausal women at
risk of breast cancer.
Department of
Medicine, Division of Hematology/Oncology, University
of Pittsburgh School of Medicine, Pittsburgh, PA, USA. vvogel@magee.edu
Breast cancer risk
factors have been studied for the past three decades, and the single most
important risk factor is age. Hormonally linked adult reproductive and
anthropometric risk factors contribute to the etiology
of postmenopausal breast cancer. The risk of breast cancer increases among
women older than 50 years of age who have benign breast disease, especially
those with atypical ductal or lobular hyperplasia.
Lobular carcinoma in situ increases risk significantly, as do a family history
of breast cancer in first-degree relatives and the presence of BRCA1 or BRCA2
mutations. Diet, exercise, and environmental factors play a very small role in
overall risk. Mammographic breast density increases relative risk fivefold
among women with the highest density, and breast cancer risk is two to three
times greater in women with elevated serum levels of estradiol
or testosterone. Multivariate risk models allow determination of composite
relative risks and cumulative lifetime risk, although improved models for
African American women are required. For postmenopausal women, newer risk
models are being developed and validated that include age, breast density, race,
ethnicity, family history of breast cancer, a previous breast biopsy, body mass
index, age at onset of natural menopause, hormone therapy, and previous
false-positive mammography. A simpler model that includes only age, breast
cancer in first-degree relatives, and previous breast biopsy performs well for estrogen receptor-positive breast cancer in postmenopausal
women. As many as 10 million women in the
Arch Gynecol
Obstet. 2008 Aug 9. [Epub ahead of print]
Evaluation of the sexual function and quality of life in raloxifene treated postmenopausal women.
Biri A, Korucuoglu U, Ilhan MN, Ciftci B, Bozkurt N, Guner H.
Department
of Obstetrics and Gynecology,
OBJECTIVE: To
evaluate the net effect of raloxifene on overall quality
of life and sexual function in postmenopausal women. METHODS: The study was
performed in the Gynecology and Obstetrics outpatient
clinic of Gazi University Faculty of Medicine between
January 2002 and February 2005. Fifty postmenopausal women, in whom raloxifene was indicated for prevention and treatment of
osteoporosis, were considered the study group. Fifty postmenopausal women who
were not osteoporotic were enrolled as the control group. Participants
completed a questionnaire composed of several parts (GRISS, BDI and ISI), at
the beginning and end of the 12-month treatment period. RESULTS: Two groups
were similar to each other with respect to total GRISS scores at the beginning
and at the end of the study (P = 0.929 and P = 0.508; respectively). Raloxifene was associated with a significant improvement
from baseline in the total scores of BDI (P = 0.0001), whereas this improvement
was not significantly different from the control group (P = 0.216). With regard
to ISI scores, there were no differences between groups in total scores. Raloxifene use did not seem to affect subscores
of ISI either. CONCLUSIONS: This study failed to prove any deleterious effect
of raloxifene on quality of life and sexual
functions.
Am J Clin Nutr. 2008 Aug;88(2):513S-519S.
Summary of evidence-based review on vitamin
D efficacy and safety in relation to bone health.
Cranney A, Weiler HA, O'Donnell
S, Puil L.
Clinical
Epidemiology Program, Ottawa Health Research Institute,
The objective of
this evidence review was to synthesize the literature on the effectiveness and
safety of nutritional and ultraviolet radiation sources of vitamin D with
respect to bone health outcomes at all stages of life. The goals were to
identify knowledge gaps for the research community and to highlight areas that
required further research. We completed an extensive literature search of
multiple databases and a multilevel selection process with synthesis of results
from 167 included studies. We included a variety of outcomes (eg, falls, bone mineral density, fractures, and adverse
events). This report provides an overview of the methods and a summary of the
key findings. In addition, we discuss areas where the evidence is inconclusive,
as well as methodologic issues that we encountered.
We found inconsistent evidence of an association between serum 25-hydroxyvitamin
D [25(OH)D] concentration and bone mineral content in
infants and fair evidence of an association with bone mineral content or
density in older children and older adults. The evidence of an association
between serum 25(OH)D concentration and some clinical
outcomes (fractures, performance measures) in postmenopausal women and older
men was inconsistent, and the evidence of an association with falls was fair.
We found good evidence of a positive effect of consuming vitamin D-fortified
foods on 25(OH)D concentrations. The evidence for a
benefit of vitamin D on falls and fractures varied. We found fair evidence that
adults tolerated vitamin D at doses above current dietary reference intake
levels, but we had no data on the association between long-term harms and
higher doses of vitamin D.
Cancer
Causes Control. 2008 Aug 14. [Epub ahead of print]
Coffee and caffeine intake and the risk of ovarian cancer: the
Lueth NA, Anderson
KE, Harnack LJ, Fulkerson
JA, Robien K.
Division of
Epidemiology and Community Health, School of Public Health, University of
Minnesota, Minneapolis, MN, USA.
Laboratory data
suggest that caffeine or some components of coffee may cause DNA mutations and
inhibit tumor suppressor mechanisms, leading to neoplastic growth. However, coffee consumption has not been
clearly implicated in the etiology of human
postmenopausal ovarian cancer. This study evaluated the relationship of coffee
and caffeine intake with risk of epithelial ovarian cancer in a prospective
cohort study of 29,060 postmenopausal women. The participants completed a
mailed questionnaire that assessed diet and health history and were followed
for ovarian cancer incidence from 1986 to 2004. Age-adjusted and
multivariate-adjusted hazard ratios were calculated for four exposure
variables: caffeinated coffee, decaffeinated coffee,
total coffee, and total caffeine to assess whether or not coffee or caffeine
influences the risk of ovarian cancer. An increased risk was observed in the
multivariate model for women who reported drinking five or more cups/day of
caffeinated coffee compared to women who reported drinking none (HR = 1.81, 95%
CI: 1.10-2.95). Decaffeinated coffee, total coffee, and caffeine were not
statistically significantly associated with ovarian cancer incidence. Our
results suggest that a component of coffee other than caffeine, or in
combination with caffeine, may be associated with increased risk of ovarian
cancer in postmenopausal women who drink five or more cups of coffee a day.
Menopause. 2008
Jul 25. [Epub ahead of print]
Trend in incidence
of osteoporosis-related fractures among 40- to 69-year-old women: analysis of a
large insurance claims database, 2000-2005.
Islam S, Liu Q, Chines A, Helzner E.
From
Wyeth Pharmaceuticals,
OBJECTIVE:: To determine the trend in incidence of fractures among perimenopausal and postmenopausal women during the periods
immediately before and after publication of the Women's Health Initiative and
Heart and Estrogen/Progestin Replacement Study (HERS)
II data. DESIGN:: This was an ecological study using a
claims database for multiple healthcare plans. The cohort of women aged 40 to
69 years was included. Diagnostic codes for fractures likely to be osteoporosis
related and prescriptions for hormone therapy and other bone-modifying
medications were identified. Annual incidence rates and trends in incidence
over time for fractures and prescriptions were determined for the period 2000
through 2005. RESULTS:: Enrollment
among women aged 40 to 69 years increased from 919,389 in 2000 to 2,872,372 in
2005. A total of 43,017 new fractures were identified. There was a significant
increasing trend in age-adjusted rates of radius and ulna, vertebra, ribs, hip,
pelvis, multiple, and pathologic fractures during the period from 2003 through
2005 (P < 0.03). The incidence of each fracture type was significantly
greater during 2004 to 2005 than 2000 to 2001 (P < 0.04). The use of estrogen, estrogen plus
progestin, and other hormones declined over the period from 2000 to 2003,
whereas the use of other bone-modifying drugs increased from 2003 through 2005.
CONCLUSIONS:: The incidence of fractures among perimenopausal and postmenopausal women increased
significantly in the 3 years after publication of Women's Health Initiative and
Heart and Estrogen/Progestin Replacement Study II
results. This trend followed a decline in the use of hormone therapy,
concurrent with an increase in the use of other bone-modifying agents.
Endocrinology. 2008
Aug 14. [Epub ahead of print]
The
Pairing of a Selective Estrogen Receptor Modulator, Bazedoxifene, With Conjugated Estrogens as a New Paradigm
for the Treatment of Menopausal Symptoms and Osteoporosis Prevention.
Kharode Y, Bodine PV, Miller CP, Lyttle CR, Komm BS.
Wyeth
Research, WHMSB,
The menopausal transition
is associated with decreased ovarian function and concomitant decline in estrogen production, which may result in physiologic
effects such as hot flashes, reduced bone mass, and altered lipid profile. It
is well established that these unfavorable changes
are effectively offset with estrogen therapy (ET) or,
in women with a uterus, estrogens in combination with a progestin (hormone
therapy [HT]). Selective estrogen receptor modulators
(SERMs), which exhibit both estrogen receptor (ER)
agonist and antagonist activities depending on the target tissue, have been
regarded as offering the potential to provide the benefits of ET and HT with an
improved safety and tolerability profile. To date, no SERM alone has
demonstrated an ideal benefit-risk profile for menopausal therapy. The tissue
selective estrogen complex (TSEC), or the pairing of
a SERM with estrogens, may provide an optimal blend of ER agonist and
antagonist activities. We evaluated the physiologic profile of this novel
therapeutic paradigm by using various in vivo models to assess uterine,
vasomotor, lipid, and skeletal responses to a TSEC partnering bazedoxifene with conjugated estrogens (CE). Bazedoxifene 3.0 mg/kg effectively antagonized CE-induced
uterine stimulation without reversing the positive effects of CE on vasomotor
instability. When paired with CE, bazedoxifene 3.0
mg/kg reduced total cholesterol levels by up to 20% compared with CE alone and
significantly increased total bone density relative to control. These
preclinical findings showed that the appropriate dose combination of bazedoxifene/CE exhibits positive vasomotor, lipid, and
skeletal responses with minimal uterine stimulation.
Semana del 30 de Julio al 5 de Agosto 2008
Arch Intern Med. 2008 Jul 28;168(14):1568-75
Menopause and the metabolic
syndrome: the Study of Women's Health Across the
Nation.
Janssen I, Powell LH, Crawford S, Lasley B, Sutton-Tyrrell K.
Department of Preventive Medicine,
BACKGROUND: Cross-sectional studies suggest that prevalence of the
metabolic syndrome (MetS) increases from premenopause to postmenopause in
women, independent of age. Little is known about why. We hypothesized that the
incidence of the MetS increases with progression
through menopause and that this increase is explained by the progressive androgenicity of the hormonal milieu. METHODS: This
longitudinal, 9-year study of 949 participants in the Study of Women's Health Across the Nation investigates the natural history of the
menopausal transition. Participants of 5 ethnicities at 7 geographic sites were
recruited when they were premenopausal or early perimenopausal
and were eligible for this study if they (1) reached menopause during the
study; (2) had never taken hormone therapy, and (3) did not have diabetes
mellitus or the MetS at baseline. The primary outcome
was the presence of MetS using National Cholesterol
Education Program Adult Treatment Panel III criteria. Secondary outcomes were
the components of the MetS. RESULTS: By the final
menstrual period, 13.7% of the women had new-onset MetS.
Longitudinal analyses, centered at the final menstrual period, were adjusted
for age at menopause, ethnicity, study site, marital status, education, body
mass index, smoking, and aging. Odds of developing the MetS
per year in perimenopause were 1.45 (95% confidence
interval, 1.35-1.56); after menopause, 1.24 (95% confidence interval,
1.18-1.30). These odds were significantly different (P < .001). An increase
in bioavailable testosterone or a decrease in sex
hormone-binding globulin levels increased the odds. CONCLUSIONS: As
testosterone progressively dominates the hormonal milieu during the menopausal
transition, the prevalence of MetS increases,
independent of aging and other important covariates. This may be a pathway by
which cardiovascular disease increases during menopause.
Breast Cancer Res Treat. 2008 Aug 1. [Epub
ahead of print
Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer
patients: a double-blind, randomized cross-over study.
Buijs C, Mom CH, Willemse PH, Marike Boezen H, Maurer JM, Wymenga AN, de Jong RS, et al.
Department of Medical Oncology,
Purpose Breast cancer patients with treatment-induced menopause
experience frequent and severe hot flashes (HF). We compared venlafaxine and clonidine for the
treatment of HF with regard to side effects, efficacy, quality of life and
sexual functioning. Methods In a double-blind, cross-over study, 60 breast
cancer patients experiencing HF were randomized to 8 weeks venlafaxine
followed by 2 weeks wash-out, and 8 weeks clonidine
or vice versa. HF frequency and severity, side effects, quality of life and
sexuality were assessed. Results Thirty patients started with venlafaxine and 30 with clonidine.
Premature discontinuation for toxicity occurred in 14/59 during venlafaxine and 5/53 during clonidine
(P = .038). Venlafaxine induced more side effects.
Median reduction in HF score was 49% for venlafaxine
and 55% for clonidine (ns). Conclusion Venlafaxine and clonidine are
equally, but moderately effective in HF reduction. Side effects are the main
reason for drug discontinuation, occurring more often with venlafaxine.
Arch Intern Med. 2008 Jul 28;168(14):1500-11
Low-fat dietary pattern and risk of treated diabetes
mellitus in postmenopausal women: the Women's Health Initiative randomized
controlled dietary modification trial.
Tinker LF, Bonds DE, Margolis KL, Manson JE, Howard BV, Larson J, et al; Women's Health Initiative.
Women's Health Initiative,
BACKGROUND: Decreased fat intake with weight loss and increased exercise
may reduce the risk of diabetes mellitus in persons with impaired glucose
tolerance. This study was undertaken to assess the effects of a low-fat dietary
pattern on incidence of treated diabetes among generally healthy postmenopausal
women. METHODS: A randomized controlled trial was conducted at 40
Cancer. 2008 Jul 29. [Epub
ahead of print
Hip bone density predicts breast cancer risk
independently of Gail score: results From the Women's Health Initiative.
Chen Z, Arendell L, Aickin M, Cauley J, Lewis CE, Chlebowski R.
Epidemiology and Biostatistics,
BACKGROUND.: The Gail model has been commonly used to estimate a woman's risk of
breast cancer within a certain time period. High bone mineral density (BMD) is
also a significant risk factor for breast cancer, but it appears to play no
role in the Gail model. The objective of the current study was to investigate
whether hip BMD predicts postmenopausal breast cancer risk independently of the
Gail score. METHODS.: In this prospective study, 9941
postmenopausal women who had a baseline hip BMD and Gail score from the Women's
Health Initiative were included in the analysis. Their average age was 63.0 +/-
7.4 years at baseline. RESULTS.: After an average of
8.43 years of follow-up, 327 incident breast cancer cases were reported and
adjudicated. In a multivariate Cox proportional hazards model, the hazards
ratios (95% confidence interval [95% CI]) for incident breast cancer were 1.35
(95% CI, 1.05-1.73) for high Gail score (>/=1.67%) and 1.25 (95% CI,
1.11-1.40) for each unit of increase in the total hip BMD T-score. Restricting
the analysis to women with both BMD and a Gail score above the median, a sharp
increase in incident breast cancer for women with the highest BMD and Gail
scores was found (P < .05). CONCLUSIONS.: The
contribution of BMD to the prediction of incident postmenopausal breast cancer
across the entire population was found to be independent of the Gail score.
However, among women with both high BMD and a high Gail score, there appears to
be an interaction between these 2 factors. These findings suggest that BMD and
Gail score may be used together to better quantify the risk of breast cancer.
J Bone Miner Res. 2008 Jul 29. [Epub
ahead of print
Hormone Therapy Improves Femur Geometry Among
Ethnically Diverse Postmenopausal Participants in the Women's Health Initiative
Hormone Intervention Trials.
Chen Z, Beck T, Cauley JA, Lewis CE, Lacroix A, Bassford T, Wu G, Sherrill D, Going S.
Abstract Loss of bone strength underlies osteoporotic fragility
fractures. We hypothesized that hormone interventions significantly improve the
structural geometry of proximal femur cross-sections. Study participants were
from the Women's Health Initiative hormone intervention trials: either the
conjugated equine estrogen only (N(placebo) = 447,
N(CEE) =422) trial or the estrogen plus progestin (N(placebo) = 441, N(E+P) =
503) trial, who were 50-79 years old at baseline and were followed up to 6
years. Bone density scans by dual-energy x-ray absorptiometry
(DXA) were conducted at baseline, year1, year 3, and year 6. Femur geometry was
derived from hip DXA scans using the hip structural analysis (HSA) method.
Mixed effect models with the intent-to-treat analysis approach were used. There
were no significant differences in treatment effects between the E-alone and
the E+P trial, so the analyses were conducted with participants combined from
both trials. Treatment benefits (p<0.05) on femur geometry were observed as
early as one year after the intervention. From baseline to year 6, section
modulus (a measure of maximum bending stress) was preserved and buckling ratio
(an index of cortical instability under compression) was reduced by hormone
interventions (p<0.05); the differences in the percent changes from baseline
to year 6 between women on hormone intervention vs. women on placebo were 2.3%
to 3.6% for section modulus and - 5.3% to - 4.3 % for buckling ratio. Hormone
interventions led to favorable changes in femur geometry, which may help
explain the reduced fracture risk observed in hormone interventions.
J Bone Miner Res. 2008 Jul 29. [Epub ahead of print
Efficacy of Bazedoxifene in Reducing New Vertebral Fracture Risk in
Postmenopausal Women With Osteoporosis: Results From a
3-Year, Randomized, Placebo- and Active-Controlled Clinical Trial*
Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ, et al
In this 3-year, randomized, double-blind, placebo- and active-controlled
study, healthy postmenopausal women with osteoporosis (aged 55-85 years) were
treated with bazedoxifene 20 or 40 mg/day, raloxifene 60 mg/day, or placebo. The primary endpoint was
incidence of new vertebral fractures after 36 months; secondary endpoints
included nonvertebral fractures, bone mineral density
(BMD), and bone turnover markers. Among 6,847 subjects in the intent-to-treat
population, the incidence of new vertebral fractures was significantly lower
(P<0.05) with bazedoxifene 20 mg (2.3%), bazedoxifene 40 mg (2.5%), and raloxifene
60 mg (2.3%) compared with placebo (4.1%), with relative risk reductions of
42%, 37%, and 42%, respectively. The treatment effect was similar among
subjects with or without prevalent vertebral fracture (P=0.89 for treatment by
baseline fracture status interaction). The incidence of nonvertebral
fractures with bazedoxifene or raloxifene
was not significantly different from placebo. In a post-hoc analysis of a
subgroup of women at higher fracture risk (femoral neck T-score </=-3.0
and/or >/=1 moderate or severe vertebral fracture or multiple mild vertebral
fractures; n=1,772), bazedoxifene 20 mg showed a 50%
and 44% reduction in nonvertebral fracture risk
relative to placebo (P=0.02) and raloxifene 60 mg
(P=0.05), respectively. Bazedoxifene significantly
improved BMD and reduced bone marker levels (P<0.001 vs
placebo). The incidence of vasodilatation, leg cramps, and venous thromboembolic events was higher with bazedoxifene
or raloxifene compared with placebo. In conclusion, bazedoxifene significantly reduced the risk of new
vertebral fracture in postmenopausal women with osteoporosis and decreased the
risk of nonvertebral fracture in subjects at higher
fracture risk.
Menopause. 2008 Jul 24. [Epub
ahead of print
A long-term user of
cosmetic cream containing estrogen developed breast cancer and endometrial
hyperplasia.
Komori S, Ito Y, Nakamura Y, Aoki M, Takashi T, Kinuta T, Tanaka H, Koyama K.
From the Department of Obstetrics and Gynecology,
A 93-year-old woman was referred to our clinic for abnormal genital
bleeding. It was found that she had endometrial hyperplasia and breast cancer.
Her uterus was as large as that of a normal adult menstruating woman. She
indicated that she had been applying cosmetic cream containing a low
concentration of ethynylestradiol to her face and
body three times a day for 75 years. It is possible that this long-term use of
the ethynylestradiol-containing cream is related to
the development of breast cancer and endometrial hyperplasia.
Biol Psychiatry. 2008 Jul 25. [Epub ahead of print
Elevated
Neuroimmune Biomarkers in Sweat Patches and Plasma of
Premenopausal Women with Major Depressive Disorder in Remission: The POWER
Study.
Cizza G, Marques AH, Eskandari F, Christie IC, Torvik S, Silverman MN, Phillips TM, Sternberg EM.
Clinical Endocrinology Branch, National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH),
BACKGROUND: Major depressive disorder (MDD) is inconsistently associated
with elevations in proinflammatory cytokines and neuropeptides. We used a skin sweat patch, recently
validated in healthy control subjects, and recycling immunoaffinity
chromatography to measure neuroimmune biomarkers in
patients with MDD mostly in remission. METHODS: We collected blood at
Open Clin Cancer J. 2008 Jan 18;2:1-6.
Metabolic
profile of breast cancer in a population of women in southern
Lopez-Saez JB, Martinez-Rubio JA, Alvarez MM, Carrera
CG, Dominguez Villar M, et al.
Departamento de Medicina, Facultad de Medicina, Universidad de Cádiz,
Cádiz, Spain.
Background: There are indications that mortality in breast cancer is
related with dietary factors, but no study has been large enough to characterise reliably how, this risk is influenced. To
establish a logistic regression equation that would predict breast cancer from
factors in the endocrinological and metabolic
profile, we studied endocrinological and metabolic
risk factors that are modified by the diet, in a population of women with
breast cancer in southern Spain.Patients and Methods:
We carried out a simple a case-control study comparing 204 women with breast
cancer (96 premenopausal and 108 postmenopausal women) and 250 healthy control
subjects. The predictive variables were basal glycaemia,
insulin, glycosylated haemoglobin
(HbA1c), C-peptide, insulin-like growth factor-I (IGF-I), total cholesterol,
triglycerides, high density lipoprotein-c (HDL-C), low density lipoprotein-c
(LDL-C), selenium and Quetelet index (BMI).Results:
The metabolic profile differed between pre- and postmenopausal patients, and
metabolic alterations were greater in postmenopausal than in premenopausal
women. The differences between healthy subjects and breast cancer patients were
clearly significant.Conclusions: Our findings have
several potential practical applications in the early detection of breast cancer,
especially in premenopausal women; in primary prevention; and in the
development of a mathematical model of breast carcinogenesis.
J Clin Endocrinol Metab. 2008 Jul 29. [Epub ahead of print
Correlates
of low testosterone and symptomatic androgen deficiency in a population-based
sample.
Hall SA, Esche GR, Araujo AB, Travison TG, Clark RV, Williams RE, McKinlay JB.
New England Research Institutes,
Risk factors for low testosterone and symptomatic androgen deficiency
(AD) may be modifiable. Objective: To examine demographic, anthropometric, and
medical correlates of low testosterone and symptomatic AD. Design: Data were
used from the Boston Area Community Health Survey, an epidemiologic study
conducted from 2002-2005. Setting: Community-based random sample of racially
and ethnically diverse men. Patients or other Participants: Data were available
for 1,822 men. Interventions: N/A Main outcome measures: Multivariate logistic
regression was used to estimate odds ratios (ORs) and 95% confidence intervals
(CIs) for associations of covariates with 1) low testosterone and 2)
symptomatic AD. The operational definition of \'low testosterone' was serum
total testosterone <300 ng/dl and free
testosterone <5 ng/dl; symptomatic AD was defined
as the additional presence of symptoms: any of low libido, erectile
dysfunction, or osteoporosis; or 2 or more of sleep disturbance, depressed
mood, lethargy, or diminished physical performance. Results: Factors associated
with low testosterone included age (OR=1.36, 95% CI: 1.11, 1.66, per decade);
low per-capita income (</=$6,000 per household member vs. >$30,000)
(OR=2.86, 95% CI: 1.39, 5.87); and waist circumference (per 10-cm increase)
(OR=1.75, 95% CI: 1.45, 2.12). Only age (OR=1.36, 95% CI: 1.04, 1.77), waist
circumference (OR=1.88, 95% CI: 1.44, 2.47) and health status (OR=0.21, 95% CI:
0.05, 0.92, excellent vs. fair/poor) were associated with our construct of
symptomatic AD. Of all variables, waist circumference was the most important
contributor in both models. Conclusions: Waist circumference is a potentially
modifiable risk factor for low testosterone and symptomatic AD. Manifestation
of symptoms may be a consequence of generally poor health status.