Selección de Resúmenes
de Menopausia
Octubre de
2008
Juan Enrique Blümel. Departamento Medicina
Sur. Universidad de Chile
Semana del 22 al 28 de Octubre 2008
Stroke. 2008 Oct 23. [Epub
ahead of print
Effect of Raloxifene on Stroke and Venous Thromboembolism
According to Subgroups in Postmenopausal Women at Increased Risk of Coronary
Heart Disease.
Mosca L,
Grady D, Barrett-Connor E, Collins P, Wenger N, Abramson BL, Paganini-Hill A,
Geiger MJ, Dowsett
SA, Amewou-Atisso
M, Kornitzer M
From
Columbia University, New York, NY; the University of California, San Francisco,
San Francisco, Calif; the University of California-San
Diego,
BACKGROUND
AND PURPOSE: Raloxifene, a selective estrogen receptor modulator, reduces risk of invasive
breast cancer and osteoporosis, but the effect on risk for stroke and venous thromboembolism in different patient subgroups is not
established. The purpose of this analysis was to evaluate the effect of raloxifene on the incidence of all strokes, stroke deaths,
and venous thromboembolic events according to
participant subgroups. METHODS: This was a secondary end point analysis of an
international, randomized, placebo-controlled clinical trial of 10 101
postmenopausal women with or at increased risk of coronary heart disease
followed a median of 5.6 years. Strokes, venous thromboembolic
events, and deaths were adjudicated by expert centralized committees. Strokes
were categorized as ischemic, hemorrhagic, or undetermined and venous thromboembolic events were subclassified.
RESULTS: The incidences of all strokes did not differ between raloxifene (incidence rate per 100 woman-years=0.95) and
placebo (incidence rate=0.86) treatment groups (P=0.30). In women assigned raloxifene versus placebo, there was a higher incidence of
fatal strokes (incidence rates=0.22 and 0.15, respectively, P=0.0499) and
venous thromboembolic events (incidence rates=0.39
and 0.27, respectively, P=0.02). No significant subgroup interactions were
found except that there was a higher incidence of stroke associated with raloxifene use among current smokers. CONCLUSIONS: In
postmenopausal women at increased risk for coronary events, the incidences of
venous thromboembolism and fatal stroke but not all
strokes were higher in those assigned raloxifene
versus placebo. Raloxifene's effect did not differ
across subgroups, except that the risk of stroke differed by smoking status.
Treatment decisions about raloxifene should be based
on a balance of projected absolute risks and benefits.
Calcif Tissue
Int. 2008 Oct 23. [Epub
ahead of print]
Intramuscular Neridronate in Postmenopausal Women with Low Bone Mineral
Density.
Adami S, Gatti
D, Bertoldo F, Sartori L, Di Munno O,
Filipponi P, Marcocci C, Frediani B, Palummeri E, Fiore CE, Costi D, Rossini M
Rheumatology
Unit, Ospedale di Valeggio, University of Verona, 37067, Valeggio, Verona,
Italy, silvano.adami@univr.it.
Compliance
to osteoporosis treatment with oral bisphosphonates
is very poor. Intermittent intravenous bisphosphonate
is a useful alternative, but this route is not readily available. Neridronate, a nitrogen-containing bisphosphonate
that can be given intramuscularly (IM), was tested in a phase 2 clinical trial
in 188 postmenopausal osteoporotic women randomized to IM treatment with 25 mg neridronate every 2 weeks, neridronate
12.5 or 25 mg every 4 weeks, or placebo. All patients received calcium and
vitamin D supplements. The patients were treated over 12 months with 2-year posttreatment follow-up. After 12-month treatment, all
three doses were associated with significant bone mineral density (BMD)
increases at both the total hip and spine. A significant dose-response
relationship over the three doses was observed for the BMD changes at the total
hip but not at the spine. Bone alkaline phosphatase
decreased significantly by 40-55% in neridronate-treated
patients, with an insignificant dose-response relationship. Serum type I
collagen C-telopeptide decreased by 58-79%, with a
significant dose-response relationship (P < 0.05). Two years after treatment
discontinuation, BMD declined by 1-2% in each dose group, with values still
significantly higher than baseline at both the spine and the total hip. Bone
turnover markers progressively increased after treatment discontinuation, and
on the second year of follow-up the values were significantly higher than pretreatment baseline. The results of this study indicate
that IM neridronate might be of value for patients
intolerant to oral bisphosphonates and unwilling or
unable to undergo intravenous infusion of bisphosphonates.
Metabolism 2008 Nov;57(11):1509-15.
Estrogen
replacement therapy decreases plasma adiponectin but
not resistin in postmenopausal women.
Kunnari A, Santaniemi M, Jokela M, Karjalainen AH, Heikkinen J, Ukkola O, Kesäniemi YA.
Department
of Internal Medicine, Biocenter Oulu, University of
Oulu, Clinical Research Center, Oulu University
Hospital, 90220 Oulu, Finland.
The
effects of estrogen replacement therapy (ERT) to cardiovascular
disease risk are still unclear. Low adiponectin and
high resistin plasma concentrations are reported to
be associated with atherosclerosis. However, it is not known how ERT affects
plasma adiponectin and resistin
concentrations. Seventy-three hysterectomized, nondiabetic, postmenopausal women were randomized in a
double-blind, double-dummy study to receive either peroral
estradiol valerate or transdermal 17beta-estradiol gel for 6 months. Biochemical
measurements were determined from samples taken before and after the therapy. Peroral estradiol valerate therapy decreased adiponectin
concentrations from 13.6 to 11.6 mg/L (P = .008), whereas transdermal
17beta-estradiol gel had no effect (12.7 vs 12.2
mg/L). Neither treatment changed the resistin concentrations
significantly. Plasma concentrations of estradiol and
estrone did not correlate with adiponectin
or resistin concentrations before or after therapy.
The change in adiponectin concentration correlated
significantly with the changes in waist-hip ratio, very low-density lipoprotein
triglycerides, and insulin-like growth factor
J Endocrinol
Invest 2008 Jul;31(7 Suppl):2-6.
Epidemiology of glucocorticoid-induced osteoporosis.
Civitelli R, Ziambaras K.
Division
of Bone and Mineral Diseases, Department of Internal Medicine, Washington University
School of Medicine, Saint Louis MO 63110, USA. rcivitel@im.wustl.edu
Glucocorticoid-induced
osteoporosis is the leading cause of medication-induced osteoporosis. The
incidence of new fractures after one year of glucocorticoid
therapy can be as high as 17%, and observational studies suggest that
fractures, which are often asymptomatic, occur in 30-50% of chronic glucocorticoid-treated patients. Fractures can occur within
3 months of initiation of steroid therapy and with daily doses as low as 2.5 mg
of prednisone, indicating that there is no "safe dose" of glucocorticoid therapy in terms of skeletal safety. Even
inhaled steroids can lead to bone loss, if used for prolonged periods of time.
Importantly in glucocorticoid- treated patients,
fractures tend to occur at bone mineral density levels that usually carry lower
risk in women with post-menopausal osteoporosis, thus implying effects
independent of bone mass. Glucocorticoids seem to
affect skeletal sites that are mostly composed of trabecular
bone, although fractures can occur at cortical sites as well. The combination
of high dose, long duration of treatment, and a continuous pattern of
administration significantly increase the relative risk of fractures. The rapid
and profound bone loss that occurs after initiation of glucocorticoid
therapy has some very practical implications with regards to the site and the
timing of bone mineral density measurements and fracture prevention strategies.
Cochrane Database Syst
Rev. 2008 Oct 8;(4):CD001690
Oestrogens and progestins for preventing and treating postpartum
depression.
Dennis CL,
Ross LE, Herxheimer A
BACKGROUND:
Postpartum depression is a common complication of childbirth, affecting
approximately 13% of women. A hormonal aetiology has long been hypothesised due
to the sudden and substantial fluctuations in concentrations of steroid
hormones associated with pregnancy and the immediate postpartum period. There
is also convincing evidence that oestrogens, progestins,
and related compounds have important central nervous system activity at
physiological concentrations. OBJECTIVES: The primary objective of this review
was to assess the effects of oestrogens and progestins,
including natural progesterone and synthetic progestogens,
compared with placebo or usual antepartum, intrapartum, or postpartum care in the prevention and
treatment of postpartum depression. SEARCH STRATEGY: We searched The Cochrane
Pregnancy and Childbirth Group trials register (June 2004), the Cochrane
Depression Anxiety and Neurosis Group trials register (July 2004), the Cochrane
Central Register of Controlled Trials (July 2004), MEDLINE (1966 to 2004),
EMBASE (1980 to 2004), and CINAHL (1982 to 2004). We scanned secondary
references and contacted experts in the field. SELECTION CRITERIA: All
published and unpublished randomised controlled trials comparing an oestrogen
and progestin intervention with a placebo or usual antepartum,
intrapartum, or postpartum care among pregnant women
or new mothers recruited within the first year postpartum. DATA COLLECTION AND
ANALYSIS: Two review authors participated in the evaluation of methodological
quality, data extraction, and data analysis. Results are presented using
relative risk for categorical data and weighted mean difference for continuous
data. MAIN RESULTS: Two trials, involving 229 women, met the selection
criteria. Norethisterone enanthate,
a synthetic progestogen, administered within 48 hours
of delivery was associated with a significantly higher risk of developing
postpartum depression. Oestrogen therapy was associated with a greater
improvement in depression scores than placebo among women with severe
depression. AUTHORS' CONCLUSIONS: Synthetic progestogens
should be used with significant caution in the postpartum period. The role of
natural progesterone in the prevention and treatment of postpartum depression
has yet to be evaluated in a randomised, placebo-controlled trial. Oestrogen
therapy may be of modest value for the treatment of severe postpartum
depression. Its role in the prevention of recurrent postpartum depression has
not been rigorously evaluated.
Arch Physiol Biochem. 2008 Oct;114(4):211-23
Does obesity play a major role in the
pathogenesis of sleep apnoea and its associated manifestations via
inflammation, visceral adiposity, and insulin resistance?
Vgontzas AN.
Department of Psychiatry, Sleep Research and Treatment Center, Hershey, PA, USA.
Despite the early recognition of the strong
association between obstructive sleep apnoea (OSA) and obesity, and OSA and
cardiovascular problems, sleep apnoea has been treated as a "local
abnormality" of the respiratory track rather than as a "systemic
illness". In 1997, we first reported that the pro-inflammatory cytokines
interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNFalpha)
were elevated in patients with disorders of excessive daytime sleepiness (EDS)
and proposed that these cytokines were mediators of daytime sleepiness. In
subsequent studies, it was shown that IL-6, TNFalpha,
and insulin levels were elevated in sleep apnoea independently of obesity and
that visceral fat was the primary parameter linked with sleep apnoea. Further
studies showed that women with the polycystic ovary syndrome (PCOS) were much
more likely than controls to have sleep-disordered breathing (SDB) and daytime
sleepiness, suggesting a pathogenetic role of insulin
resistance in OSA. Additional accumulated evidence that supports the role of
obesity and the associated metabolic aberrations in the pathogenesis of sleep
apnoea and related symptoms include: obesity without sleep apnoea is associated
with daytime sleepiness; the protective role of gonadal
hormones as suggested by the increased prevalence of sleep apnoea in
post-menopausal women and the significantly reduced risk for OSA in women on
hormonal therapy; partial effects of continuous positive airway pressure (CPAP)
in obese patients with apnoea on hypercytokinemia,
insulin resistance indices, and visceral fat; and that the prevalence of the
metabolic syndrome in the U.S. population from the Third National Health and
Nutrition Examination Survey (1988-1994) parallels the prevalence of
symptomatic sleep apnoea in general random samples. Furthermore, the beneficial
effect of a cytokine antagonist on EDS and apnoea in obese, male apnoeics and that of exercise and weight loss on SDB and
EDS in general random or clinical samples, supports
the hypothesis that cytokines and insulin resistance are mediators of EDS and
sleep apnoea in humans. Finally, our recent finding that in obese, hypothalamic
CRH neuron is hypoactive, provides additional evidence
on the potential central neural mechanisms for depressed ventilation and
consequent development of sleep apnoea in obese individuals. In conclusion,
accumulating evidence provides support to our thesis that obesity via
inflammation, insulin resistance, visceral adiposity, and central neural
mechanisms, e.g. hypofunctioning hypothalamic CRH, play
a major role in the pathogenesis of sleep apnoea, sleepiness, and the
associated cardiovascular co-morb
Semana del 15 al 21 de Octubre 2008
Gynecol Endocrinol. 2008 Aug;24(8):470-4
Impact of diabetes mellitus on the
sexuality of Peruvian postmenopausal.
Mezones-Holguin E, Blümel JE, Huezo M, Vargas R, Castro J, Córdova W, Valenzuela
G, Castelo-Branco C
Faculty
of Human Medicine, National University of Piura, Piura, Peru.
AIM: To evaluate
sexual function among postmenopausal diabetic women. PATIENTS AND METHODS: A
total of 72 postmenopausal women, 36 diabetic, with a stable partner were
included in this study. Sexual functioning was assessed using the Female Sexual
Functioning Index (FSFI) and depression using the Beck Depression Inventory
scale. RESULTS: There was no difference between diabetic and control women
regarding age, years of schooling, number of children, age at menarche, age at
first sexual experience, years postmenopausal or body mass index. Diabetics had
a worse score for depression (11.5 +/- 5.6 vs. 8.9 +/- 4.7, p < 0.03), a
lower frequency of sexual intercourse per month (2.7 +/- 2.8 vs. 4.4 +/- 2.9, p
< 0.01) and a more deteriorated marital relationship (scale of 0-20: 13.4
+/- 2.9 vs. 15.1 +/- 1.9, p < 0.009). Diabetics demonstrated worse scores
globally (19.3 +/- 8.1 vs. 26.8 +/- 4.5, p < 0.0001) and in all domains of
the FSFI: desire (2.6 +/- 1.4 vs. 3.8 +/- 1.1, p < 0.0001), arousal (3.5 +/-
1.9 vs. 4.7 +/- 0.8, p < 0.002), lubrication (3.2 +/- 1.9 vs. 4.5 +/- 1.3, p
< 0.003), orgasm (3.2 +/- 1.8 vs. 4.5 +/- 1.1, p < 0.002), satisfaction
(3.8 +/- 1.3 vs. 4.8 +/- 0.9, p < 0.0005) and pain (3.1 +/- 1.7 vs. 4.6 +/-
1.3, p < 0.0001) (values all mean +/- standard deviation). Considering
sexual dysfunction as a score higher than 26.55, the prevalence of sexual
dysfunction among diabetics was 75.0% vs. 30.6% in the control group (p <
0.001). After adjusting for depression, years of schooling, hysterectomy,
marital relationship and age, diabetes mellitus remained an important risk
factor for sexual dysfunction (odds ratio 6.2, 95% confidence interval
2.0-19.6, p < 0.02). CONCLUSION: Diabetes mellitus affects all areas of
female sexuality and this condition is independent of depression.
Menopause. 2008
Oct 8. [Epub ahead of print
A population-based study of dyspareunia in a cohort of middle-aged Brazilian women.
Valadares
AL, Pinto-Neto
AM, Conde DM, Sousa MH, Osis MJ, Costa-Paiva
L.
From the 1Department of Gynecology and
Obstetrics, Universidade Estadual de Campinas,
Campinas, Brazil; and
2Department of Gynecology and Obstetrics, Universidade
Federal de Goiás, Goiânia, Brazil.
OBJECTIVE:: To investigate the prevalence of dyspareunia
and its associated factors in a cohort of middle-aged women. DESIGN:: A cross-sectional, population-based study was carried out
using an anonymous, self-report questionnaire completed by 200 Brazilian-born
women, 40 to 65 years of age, with 11 years or more of formal education. The
evaluation instrument was based on the Short Personal Experiences
Questionnaire. Sociodemographic, clinical, behavioral, reproductive, and partner-related factors were
assessed. Poisson multiple regression analysis was performed,
and prevalence ratios (PRs) with their 95% CIs were calculated. RESULTS:: The prevalence of dyspareunia
was 39.5%. Multiple analysis showed that dyspareunia
was more common in women who reported nervousness (PR = 1.73, 95% CI:
1.14-2.63) and depression (PR = 1.69, 95% CI: 1.09-2.61). A score of more than
3 for frequency of sexual activity (PR = 0.20, 95% CI: 0.05-0.84) and having
had more than two pregnancies (PR = 0.62, 95% CI: 0.48-0.81) were factors
indicative of a protective effect against dyspareunia.
CONCLUSIONS:: Dyspareunia
was common in this cohort of middle-aged women. Nervousness and depression
increased the likelihood of experiencing dyspareunia.
These findings suggest that psychological symptoms should be taken into
consideration in the management of the middle-aged woman with dyspareunia, and measures should be adopted to minimize the
repercussions of these factors on sexuality.
Atherosclerosis. 2008
Sep 6. [Epub ahead of print
Sex hormone levels and subclinical atherosclerosis in postmenopausal
women: The Multi-Ethnic Study of Atherosclerosis.
Ouyang P, Vaidya D, Dobs A, Golden SH, Szklo M, Heckbert SR, Kopp P, Gapstur SM.
We examined
cross-sectional associations between sex hormones and carotid artery intimal-medial thickness (cIMT)
and coronary artery calcium in women in the Multi-Ethnic Study of
Atherosclerosis. Serum testosterone, estradiol, sex
hormone binding globulin (SHBG), and dehydroepiandrosterone
levels were measured in 1947 postmenopausal women aged 45-84 years (30% White,
14% Chinese-American, 31% Black, and 25% Hispanic) and not on hormone therapy.
Using multiple linear regression we evaluated associations between log(sex hormone) levels and log(cIMT)
adjusted for age, ethnicity, body mass index (BMI) and cardiac risk factors.
Associations between sex hormone levels and the presence and extent of coronary
calcium were evaluated. Total and bioavailable
testosterone were positively associated with common cIMT
independent of age, BMI, hypertension, smoking, HDL-cholesterol,
LDL-cholesterol and insulin sensitivity (p=0.009 and p=0.002, respectively).
SHBG was negatively associated with common cIMT
(p=0.001) but further adjustment for BMI, cardiovascular risk factors, and LDL-
and HDL-cholesterol removed significance. Estradiol
and dehydroepiandrosterone were not associated with
common cIMT. Sex hormones were not associated with
presence of coronary calcium. Among women with measurable coronary calcium,
higher SHBG (p=0.012) and lower bioavailable
testosterone (p=0.007) were associated with greater coronary calcium score. No
heterogeneity by ethnicity was found. In postmenopausal women, testosterone is
independently associated with greater common cIMT.
SHBG is negatively associated and this may be mediated by LDL- and
HDL-cholesterol. In contrast, SHBG and testosterone were associated with extent
of coronary calcium but in the opposite direction compared to carotid intimal-medial thickness. These differences warrant further
evaluation.
J Bone Miner Res. 2008 Oct 10. [Epub
ahead of print]
Activation of Renin-Angiotensin System Induces
Osteoporosis Independently of Hypertension.
Asaba Y, Ito M, Fumoto T, Watanabe K, Fukuhara R, Takeshita S, Nimura Y, Ishida J, Fukamizu A, et al.
Abstract
Hypertension and osteoporosis are two major age-related disorders; however, the
underlying molecular mechanism for this co-morbidity is not known. The renin-angiotensin system (RAS) plays a central role in the
control of blood pressure, and has been an important target of
anti-hypertensive drugs. Using a chimeric RAS model
of transgenic THM (Tsukuba Hypertension Mouse) expressing both the human renin and human angiotensinogen
genes, we have demonstrated in the present study that activation of RAS induces
high turnover osteoporosis with accelerated bone resorption.
Transgenic mice that express only the human renin
gene were normotensive and yet exhibited a low bone
mass, suggesting that osteoporosis occurs independently of the development of
hypertension per se. Ex vivo cultures revealed that angiotensin
II (AngII) acted on osteoblasts,
not directly on osteoclast precursor cells, and
increased osteoclastogenesis-supporting cytokines,
RANKL and VEGF, thereby stimulating the formation of osteoclasts.
Knockdown of AT2 receptor inhibited the AngII
activity, while silencing of the AT1 receptor paradoxically enhanced it,
suggesting a functional interaction between the 2 AngII
receptors on the osteoblastic cell surface. Finally,
treatment of THM mice with an ACE inhibitor, enalapril,
improved osteoporosis as well as hypertension, whereas treatment with losartan, an ARB specific for AT1, resulted in exacerbation
of the low bone mass phenotype. Thus, blocking the synthesis of AngII may be an effective treatment of osteoporosis as well
as hypertension, especially for those afflicted with both conditions.
Panminerva Med. 2008 Sep;50(3):247-54.
Is there a place for postmenopausal hormone therapy use in women with
lupus?
Unit of Endocrinological Gynecology,
The Women Health
Initiative (WHI) randomized trials have reported increase in cardiovascular and
breast cancer risks from the use of post-menopausal hormone therapy (HT). A
striking decrease of HT use has been observed worldwide despite the fact that
other regimens in younger post-menopausal women could be safer. Systemic lupus erythematosis (SLE) is considered as estrogen
sensitive. HT is generally considered as contraindicated in these women who are
especially at risk for cardiovascular diseases and osteoporosis. However,
recent randomized trials have raised the question of a lack of deleterious
effects of estrogen containing oral contraceptives.
In view of the recent knowledge and understanding in the field of menopause the
authors were interested to examine the HT effects in women with SLE by analysis
the published cases control, observational studies and randomized trials. The
randomized trials and large observational studies showed a mild increase risk
in flares and thrombotic events, whereas retrospective studies did not show
increase in these risks but suggesting selection bias. A better profile on the
blood clotting parameters and surrogate markers of the arterial risk can be
obtained by transdermal estrogen
and natural progesterone in non SLE women. Less venous thrombotic events are
observed in women at risk for thrombosis with the transdermal
estradiol administration in a case control study.
However no randomized trial is still available and no epidemiological data are
reassuring on the arterial risk. Prescription of HT has to remain especially
prudent in women with SLE. If a decision of treatment is taken transdermal estradiol and
progesterone or close pregnane derivatives should be
probably most valuable but also used at the minimal dose.
Br J Sports Med. 2008 Oct 16. [Epub
ahead of print
When Will We Treat Physical Activity as a Legitimate Medical Therapy......even
though it does not come in a pill?
Pennington
Biomedical Research Center, United States.
A recent highly
publicized report claimed that an exercise pill as been discovered. (1) A
mystical substance was found to increase endurance in mice without exercise
training. By the way, this is not the first time such an observation has been
made. None the less it was widely reported that this may be the end of the need
to get off the couch and soon all the benefits of exercise will be delivered
via a pill. Sound too good to be true? It likely is,
as mimicking the multiple health benefits of exercise with a pill would be the
equivalent of creating a cancer free cigarette. If exercise could be put in a
pill form, the world as we know it would be radically changed forever with
healthcare and financial implications too large to quantify. We would have a
new powerful therapeutic option for the prevention and treatment of
cardiovascular disease, diabetes, dementia, osteoporosis, depression, old age,
certain types of cancer and many other ailments some of which are not typically
considered "exercise related". (2) In 2007 the Milken Institute,
estimated that the top 7 chronic diseases which include CVD, cancer, diabetes,
mental disorders and lung disease are estimated to cost the US 1.3 billion
dollars annually; with the shift in age of the population this cost is expected
to increase dramatically in coming years. (3) If exercise came in a pill we
could dramatically reduce the prevalence as well as the morbidity and mortality
associated of these conditions creating a much healthier, happier and more
productive world. Many doctors would be out of work and hospitals would have to
be downsized. But creating an exercise pill is no easy task; and as indicated
by the list above, the pill would have to simultaneously benefit numerous
complex physiological systems, not just improve exercise capacity as documented
in the recent report. It is somewhat audacious to suggest that we can mimic the
health benefits of exercise with a pill and while maybe some day in the far
future this may be possible it is not likely anytime soon. However, this topic
is not likely to go away soon as we know of at least 4 other substances that
are currently understudy that claim to increase fitness in animals.
Cardiovasc Diabetol. 2008 Oct 15;7(1):30. [Epub ahead of print
Are the adverse effects of glitazones linked
to induced testosterone deficiency?
Carruthers M, Trinick TR, Jankowska E, Traish AM.
ABSTRACT:
BACKGROUND: Adverse side-effects of the glitazones have
been frequently reported in both clinical and animal studies, especially with rosiglitazone (RGZ) and pioglitazone
(PGZ), including congestive heart failure, osteoporosis, weight gain, oedema
and anaemia. These led to consideration of an evidence-based hypothesis which
would explain these diverse effects, and further suggested novel approaches by
which this hypothesis could be tested. Presentation of hypothesis: The
literature on the clinical, metabolic and endocrine effects of glitazones in relation to the reported actions of
testosterone in diabetes, metabolic syndrome, and cardiovascular disease is
reviewed, and the following unifying hypothesis advanced: "Glitazones induce androgen deficiency in patients with Type
2 Diabetes Mellitus resulting in pathophysiological
changes in multiple tissues and organs which may explain their observed
clinical adverse effects." This also provides further evidence for the lipocentric concept of diabetes and its clinical
implications. Testing of the hypothesis: Clinical studies to investigate the
endocrine profiles, including measurements of TT, DHT, SHBG, FT and estradiol, together with LH and FSH, in both men and women
with T2DM before and after RGZ and PGZ treatment in placebo controlled groups,
are necessary to provide data to substantiate this hypothesis. Also, studies on
T treatment in diabetic men would further establish if the adverse effects of glitazones could be reversed or ameliorated by androgen
therapy. Basic sciences investigations on the inhibition of androgen
biosynthesis by glitazones are also warranted.
IMPLICATIONS OF THE HYPOTHESIS: Glitazones reduce
androgen biosynthesis, increase their binding to SHBG, and attenuate androgen
receptor activation, thus reducing the physiological actions of testosterone,
causing relative and absolute androgen deficiency. This hypothesis explains the
adverse effects of glitazones on the heart and other
organs resulting from reversal of the action of androgens in directing the
maturation of stem cells towards muscle, vascular endothelium, erythroid stem cells and osteoblasts,
and away from adipocyte differentiation. The higher
incidence of side-effects with RGZ than PGZ, may be explained by a detailed
study of the mechanism by which glitazones
down-regulate androgen biosynthesis and action, resulting in a state of
androgen deficiency.
Epidemiology. 2008 Nov;19(6):766-79.
Observational studies analyzed like randomized experiments: an
application to postmenopausal hormone therapy and coronary heart disease.
Hernán MA, Alonso A, Logan R, Grodstein F, Michels KB, Willett WC, Manson JE, Robins JM.
Department
of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
BACKGROUND: The
Women's Health Initiative randomized trial found greater coronary heart disease
(CHD) risk in women assigned to estrogen/progestin
therapy than in those assigned to placebo. Observational studies had previously
suggested reduced CHD risk in hormone users. METHODS: Using data from the
observational Nurses' Health Study, we emulated the design and
intention-to-treat (ITT) analysis of the randomized trial. The observational
study was conceptualized as a sequence of "trials," in which eligible
women were classified as initiators or noninitiators
of estrogen/progestin therapy. RESULTS: The ITT
hazard ratios (HRs) (95% confidence intervals) of CHD for initiators versus noninitiators were 1.42 (0.92-2.20) for the first 2 years,
and 0.96 (0.78-1.18) for the entire follow-up. The ITT HRs were 0.84
(0.61-1.14) in women within 10 years of menopause, and 1.12 (0.84-1.48) in the
others (P value for interaction = 0.08). These ITT estimates are similar to
those from the Women's Health Initiative. Because the ITT approach causes
severe treatment misclassification, we also estimated adherence-adjusted
effects by inverse probability weighting. The HRs were 1.61 (0.97-2.66) for the
first 2 years, and 0.98 (0.66-1.49) for the entire follow-up. The HRs were 0.54
(0.19-1.51) in women within 10 years after menopause, and 1.20 (0.78-1.84) in
others (P value for interaction = 0.01). We also present comparisons between
these estimates and previously reported Nurses' Health Study estimates.
CONCLUSIONS: Our findings suggest that the discrepancies between the Women's
Health Initiative and Nurses' Health Study ITT estimates could be largely
explained by differences in the distribution of time since menopause and length
of follow-up.
Sleep. 2008 Oct 1;31(10):1339-49.
Sex steroid hormone profiles are related to sleep measures from polysomnography and the
Sowers MF, Zheng H, Kravitz HM, Matthews K, Bromberger JT, Gold EB, Owens J, Consens F, Hall M.
Department of
Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA. STUDY OBJECTIVES: To relate
reproductive hormones (and the preceding 7-year rates of their change) to
objectively and subjectively assessed sleep measures, independent of age,
vasomotor symptom frequency, depressive symptoms, and body size. DESIGN: A
cross-sectional sleep substudy nested in the Study of
Women's Health Across the Nation (SWAN), a
longitudinal study of the menopausal transition. SETTING: Community-based.
PARTICIPANTS: 365 Caucasian, African American, and Chinese women. MEASUREMENTS
AND RESULTS: Sleep duration, continuity, and architecture were measured during
two nights of in-home polysomnography (PSG) studies.
Participants completed the Pittsburgh Sleep Quality Index (PSQI) for sleep
quality, sleep diaries for medication, vasomotor symptoms, lifestyle
information and questionnaires for depressive symptoms. Blood collected
annually in the years prior to sleep study was assayed for follicle stimulating
hormone (FSH), estradiol (E2), and total testosterone
(T). More rapid rate of FSH change was significantly associated with higher
delta sleep percent, longer total sleep time (TST), but less favorable self-reported sleep quality (PSQI). Baseline E2
was modestly and negatively associated with sleep quality. Women in the lowest
total testosterone quartile at baseline had more wake time after sleep onset
(WASO) than women in the highest quartile.
Semana del 8 al 14 de Octubre 2008
J Am Coll
Nutr. 2008 Oct;27(5):519-27.
Calcium
supplementation and incident kidney stone risk: a systematic review.
Creighton University, Omaha, NE 68131,
USA. rheaney@creighton.edu
BACKGROUND: A
report of a small increase in kidney stone risk in the calcium treatment arm of
the Women's Health Initiative (WHI) led to a reduction in
Mol
Endocrinol. 2008 Oct 9. [Epub ahead of print
Update
of Estrogen plus Progestin Therapy for Menopausal
Hormone Replacement Implicating Stem Cells in the Increased Breast Cancer Risk.
Department
of Medicine, Division of Endocrinology, University of Colorado at Denver,
Aurora, CO.
This transcript is
based on my "The Year in Hormones & Cancer" lecture at ENDO 08
that reviewed current data surrounding hormone replacement therapy (HRT); the
relationship between systemic estrogen plus progestin
(E+P) treatment and increased breast cancer risk; and explored the hypothesis
that women who "develop" breast cancer while on E+P had occult,
undiagnosed disease before they started therapy. Beginning with recent HRT data
focusing on E+P and its association with breast cancer to set the stage, the
lecture then reviewed our newly published data that progestins
expand breast cancer stem cells. Finally, the issues of occult or undiagnosed
breast cancer in presumably healthy women, and of tumor
dormancy in breast cancer survivors, were brought to bear on the discussion.
Taken together, these apparently disparate themes allowed me to suggest the
idea that systemic progestins have the ability to
reawaken cancers that were presumed to be either nonexistent or cured. To avoid
this potentially devastating outcome while retaining the benefits of E+P, I
advocated the use of local progestin delivery methods, rather than the
currently popular systemic routes.
Maturitas. 2008 Oct 7. [Epub ahead of print
Estrogen therapy influence on periurethral
vessels in postmenopausal incontinent women using Dopplervelocimetry
analysis.
Kobata SA, Girão MJ, Baracat EC, Kajikawa M, Di Bella V Jr, Sartori MG, Jármy-Di Bella
ZI.
UNIFESP - são paulo federal university,
São Paulo, Brazil.
Lack of estrogen affects the urinary tract mainly by diminishing vascular,
muscular and epithelial trophism, resulting in
negative effects on continence in postmenopausal women. Therefore, the use of
estrogens in these patients may revert these
alterations and lead to an expressive improvement of the urinary symptoms. OBJECTIVE:
Study the effect of topical estrogen therapy
(conjugated equine estrogens, estriol or promestriene) in periurethral
vessels detected by Dopplervelocimetric analysis
using, as parameters: the number of vessels, resistance and pulsatility
indexes, as well as the minimum diastolic value. METHODS: Forty-one
postmenopausal women with stress urinary incontinence were randomized into
three groups according to different types of topical estrogen
received during 3 months. Group 1 received conjugated equine estrogens, group 2
received estriol and group 3 received promestriene. Periurethral Dopplervelocimetry analysis was done before estrogen administration and during treatment in all groups.
RESULTS: We observed an increase in the number of the periurethral
vessels in group 1 and group 2, being higher in group 1 than in group 2. The pulsatility index remained unchanged in all three groups.
The resistance index at the periurethral vessels
reduced only at the conjugated estrogen group (group
1). In this same group we noticed an increase in the mean minimal diastolic
value, meaning a better periurethral vascularization. CONCLUSION: Topical conjugated equine
estrogens and estriol were effective in increasing
the number of periurethral vessels in postmenopausal
women with urinary stress incontinence, with the conjugated equine estrogens
being the most effective intervention studied.
J
Laryngol Otol. 2008 Oct 10:1-5.
Impact
of total versus subtotal thyroidectomy on calcium
metabolism and bone mineral density in premenopausal women.
Tunca F, Senyurek YG, Terzioglu T, Tanakol R, Tezelman S.
Department
of General Surgery, Istanbul Medical Faculty, Istanbul University, Turkey.
Objective:This study aimed to compare the impact of
total versus subtotal thyroidectomy on calcium
metabolism and bone mineral density in euthyroid,
premenopausal women.Subjects:The study included 24
premenopausal women who had undergone total (n = 10) or subtotal (n = 14) thyroidectomy and who were receiving nonsuppressive
doses of thyroxine. The median post-operative period
was four years. We determined, in all patients, the following parameters
associated with calcium metabolism: total serum calcium, inorganic phosphate,
intact parathormone, calcitonin
and alkaline phosphatase. The bone mineral density of
the spine and hip were measured using a Hologic QDR
Drugs. 2008;68(15):2131-62.
New Drugs for Type
2 Diabetes Mellitus : What is their Place in Therapy?
Krentz AJ, Patel MB, Bailey CJ.
Department
of Diabetes and Endocrinology, Southampton University Hospitals and University
of Southampton, Southampton, UK.
Oral therapy for
type 2 diabetes mellitus, when used appropriately, can safely assist patients
to achieve glycaemic targets in the short to medium
term. However, the progressive nature of type 2 diabetes usually requires a
combination of two or more oral agents in the longer term, often as a prelude
to insulin therapy. Issues of safety and tolerability, notably weight gain,
often limit the optimal application of anti-diabetic drugs such as sulfonylureas and thiazolidinediones.
Moreover, the impact of different drugs, even within a single class, on the
risk of long-term vascular complications has come under scrutiny. For example,
recent publication of evidence suggesting potential detrimental effects of rosiglitazone on myocardial events generated a heated
debate and led to a reduction in use of this drug. In contrast, current
evidence supports the view that pioglitazone has vasculoprotective properties. Both drugs are contraindicated
in patients who are at risk of heart failure. An additional recently identified
safety concern is an increased risk of fractures, especially in postmenopausal women.Several new drugs with glucose-lowering efficacy that
may offer certain advantages have recently become available. These include (i) injectable glucagon-like
peptide-1 (GLP-1) receptor agonists and oral dipeptidyl
peptidase-4 (DPP-4) inhibitors; (ii) the amylin
analogue pramlintide; and (iii) selective cannabinoid receptor-1 (CB1) antagonists. GLP-1 receptor
agonists, such as exenatide, stimulate
nutrient-induced insulin secretion and reduce inappropriate glucagon secretion
while delaying gastric emptying and reducing appetite. These agents offer a low
risk of hypoglycaemia combined with sustained weight loss. The DPP-4 inhibitors
sitagliptin and vildagliptin
are generally weight neutral, with less marked gastrointestinal adverse effects
than the GLP-1 receptor agonists. Potential benefits of GLP-1 receptor
stimulation on beta cell neogenesis are under
investigation. Pancreatitis has been reported in exenatide-treated
patients. Pramlintide, an injected peptide used in
combination with insulin, can reduce insulin dose and bodyweight. The CB1
receptor antagonist rimonabant promotes weight loss
and has favourable effects on aspects of the metabolic syndrome, including the
hyperglycaemia of type 2 diabetes. However, in 2007 the US FDA declined
approval of rimonabant, requiring more data on
adverse effects, notably depression. The future of dual peroxisome
proliferator-activated receptor-alpha/gamma agonists,
or glitazars, is presently uncertain following
concerns about their safety.In conclusion, several
new classes of drugs have recently become available in some countries that
offer new options for treating type 2 diabetes. Beneficial or neutral effects
on bodyweight are an attractive feature of the new drugs. However, the higher
cost of these agents, coupled with an absence of long-term safety and clinical
outcome data, need to be taken into consideration by clinicians and healthcare
organizations.
Osteoporos Int. 2008 Oct
9. [Epub ahead of print]
The
relation between bisphosphonate use and non-union of
fractures of the humerus in older adults.
Solomon DH, Hochberg
MC, Mogun H, Schneeweiss S.
Division
of Pharmacoepidemiology, Harvard Medical School,
Boston, MA, USA, dsolomon@partners.org.
While
nitrogen-containing bisphosphonates have been shown
to reduce fracture risk in postmenopausal women and men, their safety in the
period after a fracture is unclear. In fully adjusted multivariable regression
models, bisphosphonate use in the post-fracture
period was associated with an increased probability of non-union [odds ratio
(OR) 2.37, 95% confidence interval (CI) 1.13-4.96]. Clinicians might consider
waiting for several months before introduction of a bisphosphonate
after a fracture. INTRODUCTION: While nitrogen-containing bisphosphonates
have been shown to reduce fracture risk in postmenopausal women and men, their
safety in the period after a fracture is unclear. We examined the risk of
non-union associated with post-fracture bisphosphonate
use among a group of older adults who had experienced a humerus
fracture. METHODS: We conducted a nested case-control study among subjects who
had experienced a humerus fracture. From this cohort,
cases of non-union were defined as those with an orthopedic
procedure related to non-union 91-365 days after the initial humerus fracture. Bisphosphonate
exposure was assessed during the 365 days prior to the non-union among cases or
the matched date for controls. Multivariable logistic regression models were
examined to calculate the OR and 95% CI for the association of post-fracture bisphosphonate use with non-union. RESULTS: From the cohort
of 19,731 patients with humerus fractures, 81 (0.4%)
experienced a non-union. Among the 81 cases, 13 (16.0%) were exposed to bisphosphonates post-fracture, while 69 of the 810 controls
(8.5%) were exposed in the post-fracture interval. In fully adjusted
multivariable regression models, bisphosphonate use
in the post-fracture period was associated with an increased
odds of non-union (OR 2.37, 95% CI 1.13-4.96). Albeit limited by small
sample sizes, the increased risk associated with bisphosphonate
use persisted in the subgroup of patients without a history of osteoporosis or
prior fractures (OR 1.91, 95% CI 0.75-4.83). CONCLUSIONS: In this study of
older adults, non-union after a humerus fracture was
rare. Bisphosphonate use after the fracture was
associated with an approximate doubling of the risk of non-union.
Int J Cancer. 2008 Oct 6. [Epub ahead of print]
Plasma
25-hydroxyvitamin D and premenopausal breast cancer risk in a German
case-control study.
Abbas S, Chang-Claude J, Linseisen J.
Division
of Cancer Epidemiology, German Cancer Research Center,
Heidelberg, Germany.
Laboratory and
epidemiological data have linked vitamin D to breast cancer prevention. Beside
dietary intake, endogenous production of vitamin D substantially contributes to
a subject's vitamin D status. Most studies, however, have assessed dietary
intake only. Although differential effects of vitamin D on premenopausal and
postmenopausal breast cancer have been discussed, this is the first study to
investigate the association of plasma 25-hydroxyvitamin D [25(OH)D], as
indicator of the overall vitamin D status, with breast cancer risk with
restriction to premenopausal women only. We used data of a population-based
case-control study comprising 289 cases and 595 matched controls. Information
on sociodemographic and breast cancer risk factors
was collected by questionnaire and plasma 25(OH)D was
measured by enzyme immunoassay. Odds ratios (ORs) and 95% confidence intervals
(CIs) were calculated using conditional logistic regression. We observed a
significant inverse association between breast cancer risk and plasma 25(OH)D concentrations. Compared with the lowest category (<30
nmol/L), the ORs (95% CI) for the upper categories
(30-45, 45-60, >/=60 nmol/L) were 0.68
(0.43-1.07), 0.59 (0.37-0.94) and 0.45 (0.29-0.70), respectively (p(trend) = 0.0006). The association was shown to be
nonlinear (p(nonlinearity) = 0.06) in fractional
polynomial analysis with a stronger effect in women at low plasma 25(OH)D
levels, providing some evidence of a threshold effect (at circa 50 nmol/L). The association was stronger in progesterone
receptor negative tumors, with suggestive evidence of
effect heterogeneity (p(heterogeneity) = 0.05,
case-only model). Our findings support a protective effect of vitamin D for
premenopausal breast cancer.
Acta Reumatol Port. 2008
Jul-Sep;33(3):314-328.
Performance of
decision algorithms for the identification of low bone mineral density in portuguese postmenopausal women.
Machado P, Silva JA.
Servico de
Reumatologia dos Hospitais da Universidade de Coimbra Coimbra
Portugal.
Objectives Although several algorithms have been proposed to select
postmenopausal women PMW for dual-energy x-ray absorptiometry
DEXA measurements information on their utility in clinical practice is scarce.
Our aim was to assess the utility and the economic repercussion of the use of
five of these algorithms in Portuguese postmenopausal women. Methods We
included 588 PMW and selected five simple algorithms ORAI ABONE Body Weight
Criterion (BWC) OSTA and a modified version of OSTA OST . Sensitivities
specificities predictive values areas under the receiver operating
characteristic curve AUROC and economic estimates were computed. Results
Sensitivities ranged between 71.2 -80.8 and AUROC between 0.611-0.674. In PMW
aged > 65 years the use of any of the algorithms would cause extra costs or
a residual saving. In PMW aged > 55 and <65Y considering total savings
ABONE had the best performance but considering savings per preventable fracture
ORAI assumed the lead followed by BWC. In the age group > 40 and < 55Y
the most profitable option considering total savings would be not doing DEXA to
anyone considering savings per preventable fracture BWC figures as the most
useful. Conclusions This study provides evidence for the validity of all the
selected tools as useful algorithms to select PMW for DEXA. On the basis of our
results and considering the importance of simplicity in the applicability of an
algorithm we would suggest the following strategy in Portuguese PMW 1 Aged >
65Y perform DEXA irrespective of other risk factors. 2 Aged <65Y perform DEXA if body weight < 70Kg.
Semana del 1 al 7 de Octubre 2008
Vasc Health Risk Manag. 2008;4(3):515-24
Relaxin as a natural agent
for vascular health.
Department
of Anatomy, Histology and Forensic Medicine, Sect. Histology, University of Florence Italy.
Hypertension, atherothrombosis, myocardial infarction, stroke, peripheral
vascular disease, and renal failure are the main manifestations of
cardiovascular disease (CVD), the leading cause of death and disability in
developed countries. Continuing insight into the pathophysiology
of CVD can allow identification of effective therapeutic strategies to reduce
the occurrence of death and/or severe disabilities. In this context, a healthy
endothelium is deemed crucial to proper functioning and maintenance of
anatomical integrity of the vascular system in many organs. Of note,
epidemiologic studies indicate that the incidence of CVD in women is very low
until menopause and increases sharply thereafter. The loss of protection
against CVD in post-menopausal women has been chiefly attributed to ovarian
steroid deficiency. However, besides steroids, the ovary also produces the
peptide hormone relaxin (RLX), which provides potent vasoactive effects which render it the most likely
candidate as the elusive physiological shield against CVD in fertile women. In
particular, RLX has a specific relaxant effect on peripheral and coronary
vasculature, exerted by the stimulation of endogenous nitric oxide (NO) generation
by cells of the vascular wall, and can induce angiogenesis. Moreover, RLX
inhibits the activation of inflammatory leukocytes and platelets, which play a
key role in CVD. Experimental studies performed in vascular and blood cell in
vitro and in animal models of vascular dysfunction, as well as pioneer clinical
observations, have provided evidence that RLX can prevent and/or improve CVD,
thus offering background to clinical trials aimed at exploring the broad
therapeutic potential of human recombinant RLX as a new cardiovascular drug.
Osteoporos Int. 2008 Oct 2. [Epub ahead of print
DXA-based
hip structural analysis of once-weekly bisphosphonate-treated
postmenopausal women with low bone mass.
Bonnick SL, Beck TJ, Cosman F, Hochberg
MC, Wang H, de Papp AE.
Clinical
Research Center of North Texas, Denton, TX, 76210,
USA, sbonnickcrcnt@verizon.net.
DXA-based hip
structural analysis from 947 individuals completing two large osteoporosis
clinical trials was pooled and analyzed. Treatment with once-weekly (OW) ALN or
OW RIS resulted in significant improvements from baseline in geometric parameters
at all three HSA ROIs. Improvements were generally greater with OW ALN than OW
RIS. INTRODUCTION: BMD can be altered by changes in distribution and quantity
of bone and changes in mineralization. These effects cannot be distinguished
with conventional measurements of BMD. Currently, tissue composition is
evaluated only by invasive means. Structural geometry of the proximal femur,
however, can be measured in vivo by several methods, including dual energy
X-ray absorptiometry (DXA) using specialized hip structure
analysis (HSA) software. METHODS: DXA-based HSA was obtained and analyzed in a
subset of 947 subjects participating in the Fosamax Actonel Comparison Trials. Data were pooled to evaluate
treatment effects on the structural geometry of the proximal femur by
once-weekly alendronate (ALN) 70 mg and risedronate (RIS) 35 mg in postmenopausal women with low
bone mass. RESULTS: Both ALN and RIS treatment over 2 years resulted in
improvements in HSA-derived geometry at all three HSA regions of interest (ROI).
The largest treatment effects were seen at the intertrochanteric
ROI. Consistently greater treatment effects were seen with ALN compared with
RIS at all three HSA-ROIs. CONCLUSIONS: HSA offers insight into the potential
mechanisms of fracture risk reduction from pharmacologic intervention. In the
current study, treatment with once-weekly bisphosphonates
resulted in significant improvements in hip geometric parameters.
Cancer Epidemiol
Biomarkers Prev. 2008 Sep 30. [Epub
ahead of print]
Conjugated Equine
Estrogens and Colorectal Cancer Incidence and Survival: The Women's Health
Initiative Randomized Clinical Trial.
Ritenbaugh C, Stanford
JL, Wu L, Shikany JM, Schoen RE, Stefanick ML, Taylor V, Garland C, et
al.
For the Women's Health Initiative Investigators.
BACKGROUND: In
separate Women's Health Initiative randomized trials, combined hormone therapy
with estrogen plus progestin reduced colorectal
cancer incidence but estrogen alone in women with
hysterectomy did not. We now analyze features of the colorectal cancers that
developed and examine the survival of women following colorectal cancer
diagnosis in the latter trial.Participants and
METHODS: 10,739 postmenopausal women who were 50 to 79 years of age and had
undergone hysterectomy were randomized to conjugated
equine estrogens (0.625 mg/d) or matching placebo. Colorectal cancer incidence
was a component of the monitoring global index of the study but was not a
primary study endpoint. Colorectal cancers were verified by central medical
record and pathology report review. Bowel exam frequency was not protocol
defined, but information on their use was collected.RESULTS:
After a median 7.1 years, there were 58 invasive colorectal cancers in the
hormone group and
BMC Cancer. 2008 Sep 30;8(1):279. [Epub ahead of print
The effect
of menopause and hysterectomy on systemic vascular endothelial growth factor in
women undergoing surgery for breast cancer.
Lowery AJ, Sweeney KJ, Molloy AP, Hennessy E, Curran C, Kerin MJ.
ABSTRACT:
BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine produced physiologically by the uterus.
Pathological secretion by tumours promotes growth and metastasis. High
circulating VEGF levels potentially have a deleterious effect on breast cancer
by promoting disease progression. The aims of this study were to investigate
circulating VEGF levels in breast cancer patients and assess the effect of
menopause or hysterectomy on systemic VEGF. METHODS: Patients undergoing
primary surgery for breast cancer and controls matched for age, menopausal and
hysterectomy status were prospectively recruited. Serum VEGF, FSH, LH, Estrogen and Progesterone and platelet levels were
measured. Serum VEGF was corrected for platelet load (sVEGFp)
to provide a biologically relevant measurement of circulating VEGF. SVEGFp levels were analysed with respect to tumour
characteristics, menopausal status and hysterectomy status. RESULTS: Two
hundred women were included in the study; 89 breast cancer patients and 111
controls. SVEGFp levels were significantly higher in
breast cancer patients compared to controls (p=0.0001), but were not associated
with clinico-pathological tumor
characteristics. Systemic VEGF levels reduced significantly in the breast
cancer patients following tumor excision (p=0.018).
The highest systemic VEGF levels were observed in postmenopausal breast cancer
patients. Postmenopausal women who had had a previous hysterectomy had
significantly higher VEGF levels than those with an intact postmenopausal
uterus (p=0.001). CONCLUSION: This study identifies an intact postmenopausal
uterus as a potential means of reducing circulating levels of VEGF which could
confer a protective effect against breast cancer metastatic potential.
BMC Cancer. 2008 Sep 30;8(1):278. Epub ahead of print
Weight, height,
body mass index and risk of breast cancer in postmenopausal women: a
case-control study.
Montazeri A, Sadighi J, Farzadi F, Maftoon F, Vahdaninia M, Ansari M, Sajadian A, Ebrahimi M, et al
BACKGROUND: Many
women in
J Cell Biochem. 2008
Sep 26. [Epub ahead of print]
Leptin signaling in breast cancer: An overview.
Cirillo D, Rachiglio AM, la Montagna R, Giordano A, Normanno N.
Protein Chemistry Laboratory, Centro
di Ricerche Oncologiche di Mercogliano, Mercogliano (AV), Italy.
The adipocyte-derived peptide leptin
acts through binding to specific membrane receptors, of which six isoforms (obRa-f) have been
identified up to now. Binding of leptin to its
receptor induces activation of different signaling
pathways, including the JAK/STAT, MAPK, IRS1, and SOCS3 signaling
pathways. Since the circulating levels of leptin are
elevated in obese individuals, and excess body weight has been shown to
increase breast cancer risk in postmenopausal women, several studies addressed
the role of leptin in breast cancer. Expression of leptin and its receptors has been demonstrated to occur in
breast cancer cell lines and in human primary breast carcinoma. Leptin is able to induce the growth of breast cancer cells
through activation of the Jak/STAT3, ERK1/2, and/or PI3K pathways, and can mediate
angiogenesis by inducing the expression of vascular endothelial growth factor
(VEGF). In addition, leptin induces transactivation of ErbB-2, and interacts in triple negative
breast cancer cells with insulin like growth factor-1 (IGF-1) to transactivate the epidermal growth factor receptor (EGFR),
thus promoting invasion and migration. Leptin can
also affect the growth of estrogen receptor
(ER)-positive breast cancer cells, by stimulating aromatase
expression and thereby increasing estrogen levels
through the aromatization of androgens, and by inducing MAPK-dependent
activation of ER. Taken together, these findings suggest that the leptin system might play an important role in breast cancer
pathogenesis and progression, and that it might represent a novel target for
therapeutic intervention in breast cancer.
Menopause. 2008
Sep 26. [Epub ahead of print]
Effect
of one-week treatment with vaginal estrogen
preparations on serum estrogen levels in
postmenopausal women.
Labrie F, Cusan L, Gomez JL, Côté I, Bérubé R, Bélanger P, Martel C, Labrie C.
Oncology
and Molecular Endocrinology Research Center, Laval
University Hospital Research Center (CRCHUL) and
Laval University, Quebec, Canada.
OBJECTIVE:
Approximately 50% of postmenopausal women suffer from vaginal atrophy, and a
large proportion of them choose intravaginal estrogen preparations administered for local action to
avoid systemic exposure to estrogens and its associated risk of breast and
uterine cancer. The primary objective of this study was the evaluation of the
systematic bioavailability of estradiol and estrone and the pharmacokinetics of two of the most
frequently used intravaginal estrogen
preparations, namely Vagifem and Premarin
cream. DESIGN: While immunobased assays could not
previously provide accurate measurement of serum estrogen
concentrations in postmenopausal women, we have used validated mass
spectrometry assays to measure the pharmacokinetics of serum estradiol and estrone during the
24 hours following the seventh daily application of 25 microg
estradiol (Vagifem) and
J Bone Joint Surg Am. 2008 Oct;90(10):2142-8
Low
incidence of anti-osteoporosis treatment after hip fracture.
Rabenda V, Vanoverloop J, Fabri V, Mertens R, Sumkay F, Vannecke C, Deswaef A, Verpooten GA, Reginster JY.
Department
of Public Health, Epidemiology and Health Economics, Liège,
Belgium.
BACKGROUND:
Following hip fracture, pharmacologic treatment can reduce the rate of
subsequent fragility fractures. The objective of the present study was to
assess the proportion of patients who are managed with bisphosphonates
or selective estrogen-receptor modulators after hip
fracture and to evaluate, among those managed with alendronate,
the twelve-month compliance and persistence with treatment. METHODS: Data were
gathered from health insurance companies and were collected by AIM (Agence Intermutualiste) for the
Belgian National Social Security Institute (INAMI). We selected all
postmenopausal women who had been hospitalized for a hip fracture between April
2001 and June 2004 and had not been previously managed with bisphosphonates.
Patients who had received alendronate treatment after
the hip fracture were categorized according to their formulation use during the
follow-up study (daily, weekly, daily followed by weekly, or weekly followed by
weekly). Compliance at twelve months was quantified with use of the medication
possession ratio (i.e., the number of days of alendronate
supplied during the first year of treatment, divided by 365). Persistence with
prescribed treatment was calculated as the number of days from the initial
prescription to a lapse of more than five weeks after completion of the
previous prescription refill. The cumulative treatment persistence rate was
determined with use of Kaplan-Meier survival curves. RESULTS: A total of 23,146
patients who had sustained a hip fracture were identified. Of these patients,
6% received treatment during the study period: 4.6% received alendronate, 0.7% received risedronate,
and 0.7% received raloxifene. Bisphosphonate
treatment was dispensed to 2.6% and 3.6% of the patients within six months and
one year after the occurrence of the hip fracture, respectively. Among women
who received alendronate daily (n = 124) or weekly (n
= 182) and were followed for at least one year after the hip fracture, the twelve-month
mean medication possession ratio was 67% (65.9% in the daily group and 67.7% in
the weekly group). The analysis of persistence with treatment included a total
of 726 patients (
Clin Cancer Res. 2008 Oct 1;14(19):6336-42
Prevention
of Anastrozole-Induced Bone Loss with Monthly Oral Ibandronate during Adjuvant Aromatase
Inhibitor Therapy for Breast Cancer.
Lester JE, Dodwell D, Purohit OP, Gutcher SA, Ellis SP, Thorpe R, Horsman JM, Brown JE, et al
Academic
Unit of Clinical Oncology, University of Sheffield, Sheffield, United Kingdom.
PURPOSE: The aromatase inhibitor anastrozole
is a highly effective well-tolerated treatment for postmenopausal
endocrine-responsive breast cancer. However, its use is associated with
accelerated bone loss and an increase in fracture risk. The ARIBON trial is a
double-blind, randomized, placebo-controlled study designed to evaluate the
impact of bisphosphonate treatment on bone mineral
density (BMD) in women taking anastrozole.
EXPERIMENTAL DESIGN: BMD was assessed in 131 postmenopausal, surgically treated
women with early breast cancer at two