Selección de Resúmenes de Menopausia
Junio de 2007
Curr Drug Metab. 2007 Jun;8(5):519-25.
Calcium metabolism and oxidative stress in bone fractures: role of
antioxidants.
Department of Clinical
Biochemistry, Faculty of Medicine,
Calcium ion is an essential
structural component of the skeleton. There is growing evidence for the
importance of nutrition in the maintenance of bones and joints health.
Nutritional imbalance combined with endocrine abnormalities may be involved in
osteoporosis. For example, essential fatty acids and their metabolites were
reported to have beneficial action in osteoporosis. The mechanism by which
fatty acids prevent osteoporosis may involve inhibition of pro-inflammatory
cytokines, which are known to have a major role in osteoporosis through
induction of oxidative stress which had adverse effects on the skeleton. Other
risk factors for osteoporosis, such as smoking, hypertension and diabetes
mellitus are also associated with increased oxidative stress and free radicals
levels. When bone fracture occurs, a remarkable yield of free radicals is
generated by the damaged tissues. However, controlled production of free
radicals by normally functioning osteoclasts could accelerate destruction of
calcified tissues and assist bone remodeling. Enhanced osteoclastic activity
observed in bone disorders may have been responsible for increased production
of reactive oxygen species [ROS] in the form of superoxide, which is evident by
increased levels of serum malondialdehyde [MDA] levels. One of the most
damaging effects of ROS is lipid peroxidation, the end product of which is MDA
which also served as a measure of osteoclastic activity. Inhibition of the
antioxidant enzymes activities, such as superoxide dismutase and glutathione
peroxidase, was found to increase superoxide production by the osteoclasts
which represented by increased levels of MDA. Therefore, oxidative stress is an
important mediator of bone loss since deficiency of antioxidant vitamins has
been found to be more common in the elderly osteoporotic patients. It is
concluded from this review that increased free radical production overwhelms
the natural antioxidants defense mechanisms, subjecting individuals to
hyperoxidant stress and thus leading to osteoporosis. In addition,
administration of antioxidants might protect bones from osteoporosis and also
might help in the acceleration of healing of fractured bones.
Ann Intern Med. 2007 Jun
19;146(12):839-47.
Effects of the phytoestrogen genistein on bone metabolism in osteopenic
postmenopausal women: a randomized trial.
Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, Gaudio A, Mazzaferro S, Frisina A, Frisina N, Lubrano C, Bonaiuto M, D'Anna R, Cannata ML, Corrado F, Adamo EB, Wilson S, Squadrito F.
Azienda Ospedaliera Universitaria Policlinico G.
Martino, University of Messina, Messina, Italy.
BACKGROUND: Observational
studies and small trials of short duration suggest that the isoflavone
phytoestrogen genistein reduces bone loss, but the evidence is not definitive.
OBJECTIVE: To assess the effects of genistein on bone metabolism in osteopenic
postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled
trial. SETTING: 3 university medical centers in
Hepatol Res. 2007 Jun 15; [Epub ahead of print]
Clinical significance of fatty liver associated with metabolic syndrome.
Kogiso T, Moriyoshi Y, Nagahara H.
Department of General
Medicine,
Aim: Metabolic syndrome (MS)
has been recognized as a high-risk disorder that leads to life-threatening
diseases, such as coronary vascular disease. The aim of the present study was
to investigate the association of fatty liver (FL) with MS in order to
establish an effective treatment for FL. Methods: One thousand two hundred and
fifty-four individuals (694 males, 560 females) who visited the Department of
General Medicine, International Medical Center of Japan for a human dry dock
annual check-up from 2000 to 2004 were analyzed. Results: FL was diagnosed in
41.5% of the males and 10.7% of the females, with the prevalence rate
increasing in postmenopausal females over 55 years old. High body mass index
and waist circumference were observed in those with FL, whereas body mass index
reduction was strongly correlated with a decrease in alanine aminotransferase
level (R = 0.6,P < 0.01). MS complications were more common in subjects with
FL and the most common initial events of MS were shown to be obesity,
hyperlipidemia and FL, followed by glucose intolerance and hypertension.
Subjects with FL showed a higher level of high-sensitivity C-reactive protein
(hs-CRP) (normal: FL = 0.38: 0.73 mg/L, P < 0.05), which was strongly correlated
with serum markers that indicated lipid and glucose metabolism in females with
FL (R = 0.61-0.77, P < 0.05). Conclusions: FL could be a part of or, at
least, a predictor of MS. Further, bodyweight reduction is an effective
treatment for FL.
Gend Med. 2006 Dec;3(4):254-69.
Estrogen replacement in menopausal women: recent and current prospective
studies, the WHI and the KEEPS.
Kronos Longevity Research
Institute, 2390 E. Camelback,
In the wake of the Women's
Health Initiative (WHI) trials, many questions have yet to be resolved
regarding the use of hormone replacement therapy (HRT) in postmenopausal women,
primarily whether HRT's cardioprotective effects outweigh a possible increase
in breast cancer risk. Several factors, including differences in HRT regimens,
the duration of follow-up, and study participants' ages, may have contributed
to the widely different conclusions of the WHI trials in comparison to the
observational studies. A woman's risk of dying from heart disease is roughly 10
times greater than her risk of dying from breast cancer. Soon after menopause,
the rate of heart disease accelerates rapidly, whereas the rate of breast
cancer increases slowly. Estrogens have been found to reduce coronary heart
disease and to have favorable effects on lipid profiles. The risks of adverse
health effects must be balanced against the benefits associated with HRT
Further research into the timing of estrogen replacement treatment may be
crucial to the prevention of cardiovascular disease.
Pharmacol Ther. 2007 May 13; [Epub ahead of print]
Regulation of cardiac ion channels via non-genomic action of sex steroid
hormones: Implication for the gender difference in cardiac arrhythmias.
Department of
Bio-informational Pharmacology, Tokyo Medical and
Long QT syndrome (LQTS) is a
disorder associated with prolonged electrocardiographic QT intervals and the
development of ventricular arrhythmias. LQTS occurs as a congenital form in an
autosomal-dominant or an autosomal-recessive manner, and as an acquired form
occurred in various cardiac disorders and induced by drug side actions.
Accumulating clinical information indicates the presence of gender difference
in LQTS. Rate-corrected QT interval (QT(c) interval) is longer in females than in
males, and female gender itself is an independent risk factor for development
of arrhythmias in both congenital and acquired forms of LQTS. Gender
differences in QT(c) interval and arrhythmic event in LQTS are not observed
before puberty, while they become suddenly notable upon the onset of puberty.
In females, QT(c) interval and risk of arrhythmic events in LQTS patients
fluctuates during the menstrual cycle, and is affected by hormone replacement
therapy. These clinical data suggest a critical role of sex steroid hormones on
QT(c) interval and gender difference in LQTS risk. Sex steroid hormones have
been traditionally considered as transactivation factors regulating the
expression of target genes. However, accumulating evidences indicate the
presence of novel non-transcriptional mechanisms of signal transduction through
steroid hormone receptors. Sex steroid hormones rapidly regulate cardiac ion
channel activity without transcription processes, which involves nitric oxides
produced via the PI3-kinase/Akt/eNOS signaling cascade. In addition to
transcriptional regulation, non-transcriptional regulation of cardiac ion
channels is in part responsible for the gender difference in LQTS risk and its
fluctuation during the menstrual cycle in females.
Blood Coagul Fibrinolysis. 2007
Jul;18(5):455-460.
Hormone therapy and raloxifene reduce the coagulation inhibitor
potential.
Andresen MS, Eilertsen AL, Abildgaard U, Sandset PM.
Haematological Research
Laboratory, Department of Medicine,
The coagulation inhibitor
potential (CIP) assay may detect major thrombophilia at a sensitivity of 100%
and a specificity of 70-80%. Subnormal CIP might be associated with increased
risk of thrombosis. This study compared the effect on CIP in plasma samples from
postmenopausal women treated with four different regimens. Fibrin aggregation
in plasma was monitored after activation with tissue factor. The effect of
potentiated inhibition of coagulation was measured. Plasma samples from 202
healthy women randomly assigned to receive treatment for 12 weeks with
conventional-dose or low-dose hormone therapy, raloxifene or tibolone were
examined. Major thrombophilias were excluded. Compared with baseline, the
median level in CIP was reduced by 64% in the conventional-dose group, by 38%
in the low-dose group and by 31% in the raloxifene group, whereas for those
treated with tibolone the median CIP increased by 9%. The median changes in CIP
were significant for both hormone therapy groups (P < 0.0001) and for the
raloxifene group (P = 0.003), but not for the tibolone group (P = 0.653). The
12 women with heterozygous factor V Leiden mutation had a significantly reduced
median CIP level (P < 0.0001) at baseline. Hormone therapy and raloxifene,
associated with venous thromboembolism, reduce the CIP. Tibolone does not
reduce the CIP.
Nota
Clin Exp Pharmacol Physiol. 2007
Jul;34(7):672-6.
Sex hormones and the cardiovascular system: effects on arterial function
in women.
The Jean Hailes Foundation for
Women's Health, Monash Institute for Health Services Research and Diabetes
Unit, Southern Health,
1. It has long been
hypothesized that oestrogen may be cardioprotective. This hypothesis is
supported by diverse and comprehensive mechanistic studies in animals and
humans. Consistently, in observational studies, oestrogen use in
post-menopausal women significantly reduced cardiovascular disease.
Contrastingly, large interventional trials focusing on chronic disease
prevention in older post-menopausal women have suggested neutral (oestrogen
alone) or adverse (combined oestrogen/progestin preparations) cardiovascular
effects. 2. The negative initial interpretation and extrapolation of the early
randomized, controlled interventional trials, primarily the Women's Health
Initiative, has recently been theoretically reconciled with the positive
mechanistic and observational studies. As a new interventional literature
emerges, it has been suggested that if oestrogen is used from menopause onwards
it is likely to be protective, but if instituted after endothelial damage has
occurred in an oestrogen-deficient post-menopausal state, the beneficial vessel
wall effects are not observed and the procoagulant effects result in overall
increased cardiovascular risk. 3. The present article reviews the literature on
arterial function and oestrogen use in the setting of the early endothelial
protection theory. This theory is generally supported by the data on oestrogen
effects on arterial function. In general, in studies of premenopausal women the
effects of oestrogen were positive, with similar benefits noted if oestrogen
was used early after menopause. However, where hormone therapy was commenced
some years after menopause, the beneficial effects on arterial function were
not observed. In clinical practice, hormone therapy is primarily used at
menopause for the treatment of menopausal symptoms. The data on arterial
function reviewed herein, along with emerging interventional human studies,
suggest that the cardiovascular effects of this practice are not adverse.
Maturitas. 2007 Jun 17; [Epub ahead of print]
Neurovascular and hemodynamic responses to hyperinsulinemia in healthy
postmenopausal women.
Cardoso CG, Sakai D, Pinto LG, Labes E, de Gusmăo JL, Abrahăo SB, Tinucci T, Mion D, Fonseca AM, Forjaz CL.
Acute hyperinsulinemia
produces sympathetic activation, vasodilation, and cardiovascular changes in
healthy young men. Postmenopausal period is accompanied by sympathetic,
vascular and cardiovascular changes. Nevertheless, the effects of acute insulin
infusion were not known in postmenopausal women. To study this aspect, 26
postmenopausal healthy women were submitted to an euglycemic hyperinsulinemic
clamp performed during 120min. Heart rate (HR: ECG), blood pressure (BP:
oscillometric method), forearm blood flow (FBF: plethysmography), plasma
norepinephrine (NE), plasma epinephrine (EP), and cardiovascular autonomic
modulation (spectral analysis of R-R interval and BP variabilities) were
measured before and during the clamp. Glycemia was kept similar to baseline
during the clamp (84.6+/-1.2mg/dl versus 87.1+/-1.6mg/dl), while plasma insulin
increased significantly to a level of 89.3+/-5.6muU/ml. Insulin infusion
significantly increased plasma NE (+45+/-17pg/ml), EP (+20+/-9pg/ml), and low
to high frequency ratio of R-R interval variability (LH/HF: 1.2+/-0.4), but did
not change low frequency component of BP variability. FBF
(+0.7+/-0.2mlmin(-1)100ml(-1)) was also significantly enhanced by
hyperinsulinemia. HR and systolic BP increased with insulin infusion (+4+/-1
bat/min and +6+/-2mmHg, respectively, P<0.05), while diastolic BP did not
change. In conclusion, in healthy postmenopausal women, acute hyperinsulinemia
produces sympathetic activation, and vasodilation, which results in HR and
systolic BP enhancements, with no change in diastolic BP. This pattern of
response is similar to the one usually observed in healthy young men.
Menopause. 2007 Jun 14; [Epub ahead of print]
Expression of calcitonin gene-related peptide, adrenomedullin, and
receptor modifying proteins in human adipose tissue and alteration in their
expression with menopause status.
Gupta P, Harte AL, da Silva NF, Khan H, Barnett AH, Kumar S, Sturdee DW, McTernan PG.
Women's Unit, Solihull
Hospital and University of Birmingham, Heart of England NHS Foundation Trust,
Lode Lane Solihull, West Midlands, UK; 2Unit for Diabetes and Metabolism,
Warwick Medical School Research Wing, Clinical Sciences Building, UHCW Trust,
Clifford Bridge Road, Walsgrave, Coventry, UK; and 3Department of Medicine,
University of Birmingham and Heart of England NHS Foundation Trust, Birmingham,
UK.
OBJECTIVE:: Calcitonin
gene-related peptide (CGRP) is a vasoactive, proinflammatory neuropeptide
implicated in the pathogenesis of cardiovascular disease. Elevated CGRP levels
during hot flushes and pregnancy suggest that reproductive hormones may
influence CGRP secretion. CGRP and the related protein adrenomedullin (ADM) may
function through adipose tissue-mediated effects, since adipose tissue is an
important site of cytokine production and the main site for estrogen production
after menopause. This study examined mRNA and protein expression of CGRP, ADM,
and the receptor activity-modifying proteins and the effects of menopausal
status in human adipose tissue. DESIGN:: Protein/mRNA levels were determined in
adipose tissue biopsy samples collected from premenopausal (n = 22:
follicle-stimulating hormone, <20 IU/L; estradiol [mean +/- SEM], 434.5 +/-
87.81 pmol/L) and postmenopausal (n = 25: follicle-stimulating hormone, >20
IU/L; estradiol, 43.4 +/- 6.95 pmol/L) women. RESULTS:: Our studies determined
that CGRP, ADM, and receptor activity-modifying proteins were expressed in
abdominal fat, adipocytes, and preadipocytes. CGRP and ADM mRNA levels were increased
in abdominal subcutaneous fat in postmenopausal women compared with
premenopausal women (betaCGRP: premenopause Delta cycle threshold [Ct], 31.07
+/- 0.28 vs postmenopause DeltaCt, 30.35 +/- 0.17, P = 0.035; ADM: premenopause
subcutaneous fat DeltaCt, 12.41 +/- 0.2 vs postmenopause subcutaneous fat
DeltaCt, 11.55 +/- 0.14, P < 0.001) with CGRP differentially expressed in
subcutaneous and omental depots. CGRP protein expression was higher in
postmenopausal women (P < 0.05) in both fat depots. CONCLUSIONS:: Our
findings suggest that adipose tissue represents an important site for CGRP and
ADM production and that menopause status alters their expression in abdominal
fat. This offers a potential mechanism to explain the role of CGRP in
menopausal vasomotor symptoms and the increased risk of cardiovascular disease
in postmenopausal women.
Cancer. 2007 Jun 19; [Epub ahead of print]
Exogenous hormone use and meningioma risk: what do we tell our patients?
Claus EB, Black PM, Bondy ML, Calvocoressi L, Schildkraut JM, Wiemels JL, Wrensch M.
Epidemiology and Public
Health,
The decision to commence or
continue use of hormone replacement therapy or oral contraceptives in women
presumed or known to be diagnosed with intracranial meningioma is a common
clinical question in neurosurgery. A review of the English-language literature
was undertaken to examine the association between the use of exogenous hormones
and meningioma risk. Seven publications were identified, 6 of which met
criteria for inclusion. No randomized clinical trial data were available,
hence, results were collected from 2 population-based case-control studies, 2
hospital-based case-control studies, 1 nested case-control study drawn from a
large national cohort, and 1 retrospective cohort study. At present, there is
no statistical evidence of an increased risk of meningioma among users of oral
contraceptives. Although not definitive, available data suggest an association
between the use of hormone replacement therapy and increased meningioma risk.
Further evaluation of exogenous hormone use in women with meningioma is needed
with particular attention to stratification by hormone (ie, estrogen and/or
progesterone) composition, duration of and age at use as well as tumor receptor
subtype.
Drugs Aging. 2007;24(6):453-66.
Drospirenone, a new progestogen, for postmenopausal women with
hypertension.
Mallareddy M, Hanes V, White WB.
Division of Hypertension and
Clinical Pharmacology, Pat and Jim Calhoun Cardiology Center, University of
Connecticut School of Medicine, Farmington, Connecticut, USA.
The prevalence of hypertension
increases in women after the menopause. Associated with the rise in
postmenopausal blood pressure (BP) are increased salt sensitivity and imbalance
between the renin-angiotensin-aldosterone system and nitric oxide pathways that
lead to sodium and water retention. Drospirenone is the first synthetic
progestogen with antialdosterone activity similar to natural progesterone.
Drospirenone counteracts the salt- and water-retaining effects of estrogen and
causes natriuresis, which leads to a reduction in BP. In preclinical studies as
well as early efficacy studies (for menopausal symptoms), drospirenone
exhibited antihypertensive and natriuretic effects. Subsequent clinical trials
in postmenopausal women proved that drospirenone with 17beta-estradiol has a
significant BP-lowering effect in untreated hypertension and has additive
effects when coadministered with ACE inhibitors, angiotensin II type 1 receptor
antagonists and thiazide diuretics. The lowest effective dose of drospirenone
for reduction in BP is 2mg, a dose that is also protective of the uterus in
women treated with estrogen therapy. Additionally, clinical trials have shown
that drospirenone up to 3 mg/day has an acceptable safety profile with no
clinically significant elevations in plasma potassium in patients with
concomitant NSAID use, diabetes mellitus or mild to moderate renal
insufficiency. In addition to effectively relieving menopausal symptoms and
lowering BP, drospirenone reduces bodyweight and lipoprotein concentrations.
Thus, drospirenone is a unique progestogen that confers the additional benefit
of BP reduction, an effect that could lead to potential benefit with respect to
some cardiovascular risk concerns in women taking hormone therapy.
BMC Musculoskelet Disord. 2007 Jun 28;8(1):55 [Epub
ahead of print]
Risk of falling in patients with a recent fracture.
van Helden S, Wyers CE, Dagnelie PC, van Dongen MC, Willems G, Brink PR, Geusens PP.
ABSTRACT:
BACKGROUND: Patients with a history of a fracture have an increased risk for
future fractures, even in short term. The aim of this study was to assess the
number of patients with falls and to identify fall risk factors that predict
the risk of falling in the first three months after a clinical fracture.
METHODS: Prospective observational study with 3 months of follow-up in a large
European academic and regional hospital. In 277 consenting women and men aged
[greater than or equal to] 50 years and with no dementia and not receiving
treatment for osteoporosis who presented to hospital with a clinical fracture,
fall risk factors were assessed according to the guidelines on fall prevention
in the Netherlands. Follow-up information on falls and fractures was collected
by monthly telephone interview. Incidence of falls and odds ratio's (OR, with
95% confidence intervals) were calculated. RESULTS: 512 consecutive patients
with a fracture were regarded for analysis, 87 were not eligible for inclusion
and 137 patients were excluded. No follow-up data were available for 11
patients. Therefore full analysis was possible in 277 patients. A new fall
incident was reported by 42 patients (15%), of whom five had a fracture. Of the
42 fallers, 32 had one new fall and 10 had two or more. Multivariate analysis
in the total group with sex, age, ADL difficulties, urine incontinence and
polypharmacy showed that sex and ADL were significant fall risk factors. Women
had an OR of 3.02 (95% CI 1.13-8.06) and patients with ADL-difficulties had an
OR of 2.50 (95% CI 1.27-4.93). Multivariate analysis in the female group with
age, ADL difficulties, polypharmacy and presence of orthostatic hypotension
indicated that polypharmacy was the predominant risk factor (OR 2.51; 95% CI:
1.19 - 5.28). The incidence of falls was 35% in women with low ADL score and
polypharmacy compared to 15% in women without these risk factors (OR 3.56: CI
1.47 - 8.67). CONCLUSION: 15% of patients reported a new fall and 5 patients
suffered a new fracture within 3 months. Female sex and low ADL score were the
major risk factors and, in addition, polypharmacy in women.
Eur J Clin Pharmacol. 2007 Jun 28; [Epub ahead of print
Prescribing of hormone therapy for menopause,
tibolone, and bisphosphonates in women in the
Cancer
Research
OBJECTIVE:
The purpose of this study was to examine recent trends in the prescribing of
hormone therapy for menopause, tibolone, and bisphosphonate preparations for
the prevention or treatment of osteoporosis, in the
Thromb Haemost. 2007 Jul;98(1):120-5
Vitamin K: The coagulation vitamin that became
omnipotent.
Cranenburg EC, Schurgers LJ, Vermeer C.
Department
of Biochemistry,
Vitamin
K, discovered in the 1930s, functions as cofactor for the posttranslational
carboxylation of glutamate residues. Gammacarboxy glutamic acid (Gla)-residues
were first identified in prothrombin and coagulation factors in the 1970s;
subsequently, extra-hepatic Gla proteins were described, including osteocalcin
and matrix Gla protein (MGP). Impairment of the function of osteocalcin and MGP
due to incomplete carboxylation results in an increased risk for developing
osteoporosis and vascular calcification, respectively, and is an unexpected
side effect of treatment with oral anticoagulants. It is conceivable that other
side effects, possible involving growth-arrest-specific gene 6 (Gas6) protein
will be identified in forthcoming years. In healthy individuals, substantial
fractions of osteocalcin and MGP circulate as incompletely carboxylated
species, indicating that the majority of these individuals is subclinically
vitamin K-deficient. Potential new application areas for vitamin K are
therefore its use in dietary supplements and functional foods for healthy
individuals to prevent bone and vascular disease, as well as for patients on
oral anticoagulant treatment to offer them protection against coumarin-induced
side effects and to reduce diet-induced fluctuations in their INR values.
J Int Med Res. 2007 May-Jun;35(3):416-21.
Hysterectomy with preservation of both ovaries
does not result in premature ovarian failure.
Atay V, Ceyhan T, Baser I, Gungor S, Goktolga U, Muhcu M.
Department
of Obstetrics and Gynaecology,
This
study investigated ovarian function and adnexial pathology following total
abdominal hysterectomy with preservation of both ovaries compared with that in
a control group. Data from 29 patients who had undergone total abdominal
hysterectomy at age < or =40 years and 42 menopausal patients with no
previous ovarian pathology were evaluated retrospectively. The mean (+/- SD)
age of menopause was 49.7 +/- 1.5 years in the total abdominal hysterectomy
group and 50.1 +/- 1.3 years in the control group; this difference was not
statistically significant. The incidences of cyst and hydrosalpinx were 31% and
6.9%, respectively, in the total abdominal hysterectomy group and 44.8% and 0%,
respectively, in the control group. The increased incidence of cysts in the
total abdominal hysterectomy group was statistically significant. In conclusion,
patients who undergo total abdominal hysterectomy without oophorectomy do not
experience premature menopause. Preservation of the ovaries may avoid the
disadvantages of hormone replacement therapy at the expense of a higher risk of
developing adnexial pathology.
Menopause. 2007 Jun 25; [Epub ahead of print
Low-dose continuous combinations of hormone
therapy and biochemical surrogate markers for vascular tone and inflammation:
transdermal versus oral application.
Mueck AO, Genazzani AR, Samsioe G, Vukovic-Wysocki I, Seeger H.
Department
of Endocrinology and Menopause, University Women's Hospital, Tübingen, Germany;
2Division of Gynecology and Obstetrics 'P Fioretti,' S. Chiara Hospital,
University of Pisa, Pisa, Italy; 3Department of Obstetrics and Gynecology, Lund
University Hospital, Lund, Sweden; and 4Novartis Pharma AG, Basel, Switzerland.
OBJECTIVE::
To compare the effects of low-dose transdermal estradiol (E2)/norethisterone
acetate (NETA) patches (Estalis 25/125) with low-dose oral E2/NETA (Activelle)
on cardiovascular biochemical markers after 12 and 52 weeks of treatment in
postmenopausal women with intact uteri. DESIGN:: Participants were randomly
assigned to receive either transdermal E2/NETA (delivering daily doses of 25
mug E2 and 125 mug NETA, applied every 3-4 d) or oral E2/NETA (1 mg E2 and 0.5
mg NETA, given daily) in this open-label study. The following markers or their
stable metabolites in serum or urine were assessed: P-selectin, intercellular
adhesion molecule-1, vascular cell adhesion molecule-1, monocyte
chemoattractant protein-1, matrix metalloproteinase-9, homocysteine, cyclic
guanosine monophosphate, serotonin, prostacyclin, thromboxane, and urodilatin.
RESULTS:: Significant decreases were found for P-selectin, intercellular
adhesion molecule-1, monocyte chemoattractant protein-1, and homocysteine for
both hormone therapy (HT) regimens compared with baseline. Matrix
metalloproteinase-9 was increased only by oral HT. The urinary concentrations
of cyclic guanosine monophosphate, the ratio of prostacyclin to thromboxane
metabolite, and the serotonin metabolite were significantly increased for both
HT application modes, although the oral treatment showed a significantly
greater increase than the transdermal one with respect to baseline. Urodilatin
excretion was increased only by the oral regimen. CONCLUSIONS:: Low-dose
transdermal and oral HTs using E2 and NETA elicit favorable effects on
cardiovascular biochemical markers. For most markers the magnitude of changes
found were similar with respect to baseline; however, in some cases oral HT led
to a significantly greater change, whereas in other cases the transdermal
formulations seemed to provide greater benefits. Whether these differences may
be attributed to the different administration routes or to different
pharmacokinetic properties remains an open question. Overall low-dose
transdermal HT seems to provoke the same benefit on the cardiovascular system
as oral HT, as suggested by the results on vascular markers.
Menopause. 2007 Jun 25; [Epub ahead of print
Hormone therapy and postural balance in elderly
women.
Naessen T, Lindmark B, Larsen HC.
Departments
of 1Women's and Children's Health, Section of Obstetrics and Gynecology, and
2Neuroscience, Section of Physiotherapy, and 3Otorhinolaryngeology-Audiology,
OBJECTIVE:
Most fractures occur in elderly individuals without osteoporosis, and more than
90% of all hip fractures are associated with a fall. It is unclear whether
hormone therapy (HT) can improve postural balance when initiated in elderly
women and the effect of endogenous estradiol (E2) levels. DESIGN: Forty healthy
women (33 assessable), age 60 years or older, were recruited through
advertising in the local media. They were randomly and blindly assigned to
receive either estradiol patches (50 mug/24 h) combined with oral
medroxyprogesterone acetate (2.5 mg/d) or placebo for 6 months. Postural
balance was assessed as sway velocity using a force platform. RESULTS: Low
serum E2 levels were associated with greater impairment of sway velocity during
the study in the placebo group. After 6 months sway velocity had improved
(decreased) in the HT group by 4.3% from baseline and increased in the placebo
group by 6.2%. The difference was not significant (1.30 cm/s, 95% CI: -3.0 to
0.4; P = 0.13). However, among women with low serum E2 levels at baseline (less
than the median, 35 pmol/L), sway velocity improved in the HT group and
deteriorated in the placebo group with a difference of 23% (2.9 cm/s, 95% CI:
0.6-5.1; P = 0.013). There were similar results after adjustment for baseline
sway velocity (P = 0.003) and in the intention-to-treat analysis (P = 0.023).
There was also a significant interaction between the study group and baseline
serum E2 levels with regard to changes in sway velocity (P = 0.014).
CONCLUSIONS: In elderly women low endogenous serum E2 levels were associated
with greater impairment of postural balance function during the study, whereas
HT, as compared with placebo, improved postural balance in women with low serum
E2 levels.
Curr Med Res Opin. 2007 Jun;23(6):1341-9
Treatment with alendronate plus calcium,
alendronate alone, or calcium alone for postmenopausal low bone mineral
density.
Bonnick S, Broy S, Kaiser F, Teutsch C, Rosenberg E, DeLucca P, Melton M.
Clinical
Research
OBJECTIVE:
Bisphosphonates such as alendronate are widely used for postmenopausal
osteoporosis. Supplemental calcium is also generally recommended. This trial
directly compares alendronate to supplemental calcium and examines the effect
of calcium supplementation on alendronate treatment. METHODS: This 2-year,
randomized, double-blind, multicenter trial enrolled healthy, postmenopausal
women with low bone mineral density (BMD). Patients with a dietary calcium intake
> or = 800 mg/day received daily vitamin D 400 IU and alendronate 10
mg/calcium-placebo, alendronate 10 mg/elemental calcium 1000 mg, or
alendronate-placebo/calcium 1000 mg (2:2:1). Endpoints included BMD, bone
turnover markers (BTMs), and adverse events. RESULTS: Randomized patients (N =
701) were an average of 20.4 years postmenopausal. After 24 months, increases
in lumbar spine BMD differed significantly between patients receiving calcium
alone (0.8%) and either alendronate alone (5.6%) or alendronate + calcium
(6.0%) (p < 0.001). Significant differences were also seen at the trochanter
and femoral neck (p < 0.001). BTMs were significantly lower with
alendronate-containing treatments than calcium alone (p < 0.001). Addition
of calcium supplementation to alendronate did not significantly increase BMD
compared to alendronate alone (p = 0.29 to 0.97), but did result in a
statistically significant, though small, additional reduction in urinary NTx.
Adverse events were similar among treatment groups. Limitations include no
assessment of vitamin D levels and a discontinuation rate of approximately 30%,
although discontinuation rates were similar among treatment groups.
CONCLUSIONS: In postmenopausal women with a daily intake of > or =800 mg
calcium and 400 IU vitamin D, 24-month treatment with alendronate 10 mg daily
with or without calcium 1000 mg resulted in significantly greater increases in
BMD and reduction of bone turnover than supplemental calcium alone. Addition of
supplemental calcium to alendronate treatment had no effect on BMD and resulted
in a small, though statistically significant, additional reduction in NTx.
J Clin Psychiatry. 2007 Jun;68(6):943-50
Treatment of depression and menopause-related
symptoms with the serotonin-norepinephrine reuptake inhibitor duloxetine.
Joffe H, Soares CN, Petrillo LF, Viguera AC, Somley BL, Koch JK, Cohen LS.
Perinatal
and Reproductive Psychiatry Program, Department of Psychiatry, Massachusetts
General Hospital, Boston, Mass. 02114, USA. hjoffe@partners.org
BACKGROUND:
Postmenopausal women with depression frequently have co-occurring symptoms of
hot flashes (vasomotor symptoms), sleep disturbance, anxiety, and pain.
Treatment strategies that target all of these symptoms together have not been
investigated to date. METHOD: Study participants were postmenopausal women, 40
to 60 years old, with major depressive disorder (DSM-IV criteria) and vasomotor
symptoms. The study design included a 2-week, single-blind placebo run-in phase
followed by an 8-week open-label flexible-dosing (60-120 mg per day) study of
duloxetine for women who did not respond to placebo. The primary outcome measure
was change in Montgomery-Asberg Depression Rating Scale (MADRS) score during 8
weeks of duloxetine therapy. Secondary outcome measures included changes in
vasomotor symptoms, sleep quality, anxiety, and pain. Analyses were conducted
using non-parametric methods. Patients were enrolled in the study from
J Steroid Biochem Mol Biol. 2007 May 24; [Epub ahead of print
The clinical relevance of the relationship
between estrogen and cognition in women.
Department
of Psychology,
Randomized
controlled trials (RCTs) and observational and longitudinal studies provide
positive, albeit, inconsistent evidence that estrogen might protect against
cognitive decline in postmenopausal women. The fact that the Women's Health
Initiative Memory Study (WHIMS), the largest RCT to date, failed to find that
estrogen therapy (ET) had a protective effect against cognitive aging led to
the formulation of the critical period hypothesis which holds that ET will
effectively protect against memory decline when it is initiated around the time
of menopause but not when considerable time has elapsed since the menopause.
Evidence from basic neuroscience, and from rodent, nonhuman primate, and human
studies that supports this theory is presented. Although much work remains to
be done on the timing of initiation of treatment, on the most effective
hormonal compounds and on their routes of administration, the hope is that,
eventually, hormonal treatments may be able to attenuate or prevent the decline
in aspects of cognition that occur with normal aging.
Obesity (Silver Spring). 2007
Jun;15(6):1578-88.
Sedentary Behavior, Recreational Physical Activity, and 7-Year Weight
Gain among Postmenopausal
Blanck HM, McCullough ML, Patel AV, Gillespie C, Calle EE, Cokkinides VE, Galuska DA, Khan LK, Serdula MK.
Division of Nutrition and
Physical Activity, 4770 Buford Highway NE, MS K-26, Atlanta, GA 30341-3717.
Hblanck@cdc.gov.
OBJECTIVE: To assess the
relationship among recreational physical activity (PA), non-occupational
sedentary behavior, and 7-year weight gain among postmenopausal
Ann Rheum Dis. 2007 Jun 8; [Epub ahead of print]
Inverse relationship between vertebral fractures and spine
osteoarthritis in post menopausal women with osteoporosis.
Roux C, Fechtenbaum J, Briot K, Cropet C, Liu-Léage S, Marcelli C.
We have analyzed the
relationship between vertebral fractures and spine osteoarthritis in 410 post
menopausal women with osteoporosis: in this population both disc space
narrowing and osteophytes are inversely related to vertebral fractures.
Introduction: Although the co-existence of osteoarthritis and osteoporosis is
considered as uncommun, it has been suggested that, in post menopausal women,
disc space narrowing increases the risk of vertebral fracture. The aim of this
study was to check this hypothesis in post menopausal women with osteoporosis.
PATIENTS AND METHODS: The current analysis is based on baseline data collected
in a multicenter, prospective and 6 month longitudinal observational study. 410
post menopausal women (74+/-5 years) consulting for back pain, and having
osteoporosis (according to WHO definition), were enrolled. Spine X-rays were
performed according to standardized procedures. Vertebral fractures were
evaluated from T4 to L4 using the Genant's semi quantitative method;
osteoarthritis was evaluated by scoring osteophytes and disc space narrowing at
all levels of thoracic and lumbar spine, and by a qualitative assessment of
facet joint arthritis. RESULTS: The prevalence of vertebral fractures was
52.4%. At least one osteophyte, one disc space narrowing and one facet
arthritis were present in 90.2, 64.6 and 77.8% of patients respectively. There
was an inverse association between vertebral fractures and osteoarthritis: odds
ratios adjusted for age and weight (95% CI) were 0.38 (0.17-0.86), p = 0.02 and
0.27 (0.16-0.46), p<10-4 for the presence of at least one osteophyte, and of
at least 3 disc space narrowings respectively. In a cluster analysis, it was
possible to identify a sub group of patients without any disc space narrowing,
and another sub group with all patients having at least one disc space
narrowing; the proportion of patients having more than 3 vertebral fractures
was 25.2 and 15.9% in these 2 clusters respectively. CONCLUSION: In post
menopausal women with osteoporosis, disc space narrowing and osteophytes are
associated with a decreased vertebral fracture prevalence.
PLoS Clin Trials. 2007 Jun 15;2(6):e28.
Can Biomarkers Identify Women at Increased Stroke Risk? The Women's
Health Initiative Hormone Trials.
Kooperberg C, Cushman M, Hsia J, Robinson JG, Aragaki AK, Lynch JK, Baird AE, Johnson KC, Kuller LH, Beresford SA, Rodriguez B.
Division of Public Health
Sciences,
OBJECTIVE: The Women's Health
Initiative hormone trials identified a 44% increase in ischemic stroke risk
with combination estrogen plus progestin and a 39% increase with estrogen
alone. We undertook a case-control biomarker study to elucidate underlying
mechanisms, and to potentially identify women who would be at lower or higher
risk for stroke with postmenopausal hormone therapy (HT). DESIGN: The hormone
trials were randomized, double-blind, and placebo controlled. SETTING: The
Women's Health Initiative trials were conducted at 40 clinical centers in the
Osteoporos Int. 2007 Jun 14; [Epub
ahead of print]
Glucocorticoid-induced osteoporosis: pathophysiology and therapy.
Canalis E, Mazziotti G, Giustina A, Bilezikian JP.
Glucocorticoid-induced
osteoporosis (GIO) is the most common form of secondary osteoporosis.
Fractures, which are often asymptomatic, may occur in as many as 30-50% of
patients receiving chronic glucocorticoid therapy. Vertebral fractures occur
early after exposure to glucocorticoids, at a time when bone mineral density
(BMD) declines rapidly. Fractures tend to occur at higher BMD levels than in
women with postmenopausal osteoporosis. In human subjects, the early rapid
decline in BMD is followed by a slower progressive decline in BMD.
Glucocorticoids have direct and indirect effects on the skeleton. The primary
effects are on osteoblasts and osteocytes. Glucocorticoids impair the
replication, differentiation and function of osteoblasts and induce the
apoptosis of mature osteoblasts and osteocytes. These effects lead to a
suppression of bone formation, a central feature in the pathogenesis of GIO.
Glucocorticoids also favor osteoclastogenesis and as a consequence increase
bone resorption. Bisphosphonates are effective in the prevention and treatment
of GIO. Anabolic therapeutic strategies are under investigation.
J Clin Sleep Med. 2005 Jul
15;1(3):291-300.
Menopause related sleep disorders.
University of
Sleep difficulty is one of the
hallmarks of menopause. Following recent studies showing no cardiac benefit and
increased breast cancer, the question of indications for hormonal therapy has
become even more pertinent. Three sets of sleep disorders are associated with
menopause: insomnia/depression, sleep disordered breathing and fibromyalgia.
The primary predictor of disturbed sleep architecture is the presence of
vasomotor symptoms. This subset of women has lower sleep efficiency and more
sleep complaints. The same group is at higher risk of insomnia and depression.
The "domino theory" of sleep disruption leading to insomnia followed
by depression has the most scientific support. Estrogen itself may also have an
antidepressant as well as a direct sleep effect. Treatment of insomnia in
responsive individuals may be a major remaining indication for hormone therapy.
Sleep disordered breathing (SDB) increases markedly at menopause for reasons
that include both weight gain and unclear hormonal mechanisms. Due to the
general under-recognition of SDB, health care providers should not assume sleep
complaints are due to vasomotor related insomnia/depression without considering
SDB. Fibromyalgia has gender, age and probably hormonal associations. Sleep
complaints are almost universal in FM. There are associated polysomnogram (PSG)
findings. FM patients have increased central nervous system levels of the
nociceptive neuropeptide substance P (SP) and lower serotonin levels resulting
in a lower pain threshold to normal stimuli. High SP and low serotonin have
significant potential to affect sleep and mood. Treatment of sleep itself seems
to improve, if not resolve FM. Menopausal sleep disruption can exacerbate other
pre-existing sleep disorders including RLS and circadian disorders.
J Clin Endocrinol Metab. 2007 Jun 12; [Epub
ahead of print]
Relation between bone mineral density changes and fracture risk
reduction in patients treated with strontium ranelate.
Bruyere O, Roux C, Detilleux J, Slosman DO, Spector TD, Fardellone P, Brixen K, Devogelaer JP, Diaz-Curiel M, Albanese C, Kaufman JM, Pors-Nielsen S, Reginster JY.
WHO Collaborating Center for
Public Health Aspect of Osteoarticular
Disorders.
Objective: To analyze the
relation between bone mineral density (BMD) changes and fracture incidence
during 3-year treatment with strontium ranelate. Patients: Women from the
strontium ranelate arm of the Spinal Osteoporosis Therapeutic Intervention
study (SOTI) and the TReatment Of Peripheral OSteoporosis study (TROPOS).
Outcome Measures: BMD at the lumbar spine, femoral neck, and total proximal
femur assessed at baseline and after a follow-up of 1 and 3 years.
Semiquantitative visual assessment of vertebral fractures. Non-vertebral
fractures based on written documentation. Results: After 3 years of strontium
ranelate treatment, each percentage point increase in femoral neck and total
proximal femur BMD was respectively associated with a 3% (95% adjusted CI
1%-5%) and 2% (1%-4%) reduction in risk of a new vertebral fracture. The 3-year
changes in femoral neck and total proximal femur BMD explained 76% and 74%,
respectively, of the reduction in vertebral fractures observed during the
treatment. Three-year changes in spine BMD were not statistically associated
with the incidence of new vertebral fracture (P=0.10). No significant
associations were found between 3-year changes in BMD and incidence of new
non-vertebral fractures, but a trend was found for femoral neck BMD (P=0.09)
and for total proximal femur BMD (P=0.07). An increase in femoral neck BMD
after 1 year was significantly associated with the reduction in incidence of
new vertebral fractures observed after 3 years (P=0.04). Conclusion: During 3
years of strontium ranelate treatment, an increase in femoral neck BMD was
associated with a proportional reduction in vertebral fracture incidence.
Adv Ther. 2007 Mar-Apr;24(2):448-61.
Black cohosh and fluoxetine in the treatment of postmenopausal symptoms:
a prospective, randomized trial.
Oktem M, Eroglu D, Karahan HB, Taskintuna N, Kuscu E, Zeyneloglu HB.
Department Obstetrics and
Gynecology, Baskent University,
The objective of this study
was to evaluate the efficacy of fluoxetine and black cohosh in the treatment of
women with postmenopausal symptoms. A total of 120 healthy women with
menopausal symptoms were recruited to this prospective study with a follow-up
period of 6 mo. They were randomly assigned to 1 of 2 groups and were treated
with fluoxetine or black cohosh. After entry into the study, patients were
examined at the first, second, third, and sixth months of the treatment period.
The women kept diaries in which they reported the daily number and intensity of
hot flushes and night sweats. In addition, at the beginning and end of the
third month, they completed questionnaires consisting of a modified Kupperman
Index, Beck's Depression Scale, and a RAND-36 Quality-of-Life Questionnaire.
Statistically significant differences were noted in the Kupperman Index and
Beck's Depression Scale at the end of the third month in both groups compared
with baseline values. In the black cohosh group, the Kupperman Index decreased
significantly compared with that in the fluoxetine group by the end of the
third month. On the other hand, in the fluoxetine group, Beck's Depression
Scale decreased significantly compared with that in the black cohosh group.
Monthly scores for hot flushes and night sweats decreased significantly in both
groups; however, black cohosh reduced monthly scores for hot flushes and night
sweats to a greater extent than did fluoxetine. At the end of the sixth month
of treatment, black cohosh reduced the hot flush score by 85%, compared with a
62% result for fluoxetine. By the sixth month of the study, 40 women had discontinued
the study-20 (33%) in the fluoxetine group and 20 (33%) in the black cohosh
group. Compared with fluoxetine, black cohosh is more effective for treating
hot flushes and night sweats. On the other hand, fluoxetine is more effective
in improvements shown on Beck's Depression Scale.
Adv Ther. 2007 Mar-Apr;24(2):319-25.
Effects of alendronate sodium therapy on carotid intima media thickness
in postmenopausal women with osteoporosis.
Delibasi T, Emral R, Erdogan MF, Kamel N.
Department of Endocrinology
and Metabolic Diseases,
Osteoporosis and
cardiovascular disease are major health problems that lead to morbidity and
mortality. Bisphosphonates are among the drugs used most frequently worldwide
to treat osteoporosis, especially in older women. B-mode ultrasonography has
recently become a valuable tool for early diagnosis of atherosclerotic disease
because of its ability to measure carotid artery intima media thickness (CIMT).
The purpose of the present study was to investigate whether alendronate sodium
therapy has an effect on CIMT in postmenopausal women with osteoporosis. A
total of 71 postmenopausal women with osteoporosis were evaluated before and
after they began taking alendronate sodium; follow-up was provided for an
average of 13+/-2 mo. Osteoporosis was diagnosed with the use of dual-energy
x-ray absorptiometry, and therapy with alendronate sodium was begun at a dose
of 70 mg/wk. For CIMT, B-mode ultrasonography was performed on the right and
left middle and distal main carotid arteries. Before alendronate sodium therapy
was initiated, the average CIMT value was 0.734+/-0.121 mm; after therapy, the
average CIMT was 0.712+/-0.111 mm. This difference was not confirmed to be
statistically significant. Treatment of osteoporosis does not seem to have an
effect on CIMT, which is an early marker of atherosclerosis.
Res Commun Mol Pathol Pharmacol. 2004;115-116:135-42.
Does daily physical exercise favorably affect the bone mass of
postmenopausal women?
Ushiroyama T, Ikeda A, Sakuma K, Ueki M.
Department of Obstetrics and
Gynecology,
To investigate the effects of
physical exercise on bone mass during the climacteric and menopausal period.
The study group were 1123 postmenopausal Japanese women (mean: 55.4 +/- 3.7
years). Their current bone mineral density of lumbar vertebrae (L2-4) was
analyzed taking the presence or absence of regular physical exercise, the type
of exercise and its duration into consideration. Of the 1123 postmenopausal
women, 643 (57.3%) were currently involved is some form of physical exercise on
a regular basis. Bone mineral density did not differ significantly between the
women exercising at present (1.035 +/- 0.08 g/cm2) and the women who had never
been involved in regular physical exercise at any time in their life (1.089 +/-
0.08 g/cm2). The bone mineral density did not differ significantly in relation
to the duration of physical activity (less than 6 months: 1.054 +/- 0.169
g/cm2; 6 months to 3 years: 1.049 +/- 0.128 g/cm2; over 5 years: 1.024 +/-
0.168 g/cm2). Although a majority of the postmenopausal women surveyed were
involved in some form of physical activity, the practice of mild exercise at
and around the time of perimenopause did not significantly increase bone
mineral density.
Am J Cardiol. 2007 Jun 15;99(12):1648-52. Epub 2007 Apr
27.
Effect of estradiol-drospirenone hormone treatment on myocardial
perfusion reserve in postmenopausal women with angina pectoris.
Knuuti J, Kalliokoski R, Janatuinen T, Hannukainen J, Kalliokoski KK, Koskenvuo J, Lundt S.
Recent randomized clinical
studies failed to show cardiovascular protection with postmenopausal hormone
therapy (HT), instead raising widespread concerns about possible increased
cardiovascular risk. However, these studies primarily assessed the combination
of conjugated equine estrogen and medroxyprogesterone acetate, which is
suspected to abolish the beneficial effects of estrogen on the
microcirculation. This preliminary study evaluated the effects of HT combining
17beta-estradiol (E2) with a new progestin, drospirenone, on myocardial
perfusion reserve, a surrogate marker of coronary function. In this
double-blind randomized study, 56 postmenopausal women with angina pectoris
received oral E2 1 mg plus drospirenone 2 mg or placebo for 6 weeks. Myocardial
perfusion reserve was measured using radioactive oxygen-labeled water and
positron emission tomography before and after therapy. Myocardial perfusion
reserve increased significantly in the E2-drospirenone group after 6 weeks
versus placebo (p <0.0008). Mean myocardial perfusion reserve increased from
4.83 at baseline to 5.13 after 6 weeks in the E2-drospirenone group (n = 27),
but decreased from 4.84 to 4.13 in the placebo group (n = 29). No significant
side effects were observed with E2-drospirenone. A larger trial is needed to
investigate whether myocardial perfusion improvements will be sustained and
translate into a clinical benefit in postmenopausal women at risk of coronary
heart disease. In conclusion, E2-drospirenone HT for 6 weeks has favorable
effects on myocardial function in postmenopausal women with angina pectoris.
These data suggest that drospirenone has the desired progestin actions on the
endometrium, but does not abolish the beneficial effects of estradiol on
cardiac microcirculation.
Menopause. 2007 Jun 7; [Epub ahead of print]
Histologic changes in the breast with menopausal hormone therapy use:
correlation with breast density, estrogen receptor, progesterone receptor, and
proliferation indices.
Harvey JA, Santen RJ, Petroni GR, Bovbjerg VE, Smolkin ME, Sheriff FS, Russo J.
From the 1Departments of
Radiology, 2Endocrinology, and 3Public Health, University of Virginia,
Charlottesville, VA; and 4Breast Cancer Research Laboratory, Fox Chase Cancer
Center, Philadelphia, PA.
OBJECTIVE:: This retrospective
study systematically compared mammographic density with histology in women
receiving or not receiving menopausal hormone therapy (HT). DESIGN:: This study
was approved by the institutional review board. Twenty-eight postmenopausal
women using HT were matched with 28 postmenopausal women not using HT at the
time of breast cancer diagnosis. Noncancerous tissue from mastectomy specimens
was examined histologically to quantitate the content of fibrous stroma, ducts,
and lobule types 1, 2, and 3. Tissue samples were also evaluated for estrogen
receptor, progesterone receptor, and Ki67 activity in the ducts and lobules.
Breast density was quantified by digitizing the contralateral mammogram and
computer-assisted interactive thresholding. RESULTS:: High breast density in
women using HT was correlated with greater fibrous stroma (P = 0.020) and
lobule type 1 (P = 0.016). Breast density also correlated with Ki67 activity in
the ducts (P = 0.031) and lobules (P= 0.023) for both groups combined. Estrogen
and progesterone receptors did not correlate with either breast density or HT
use. CONCLUSIONS:: Increased fibrous stroma and lobule type 1 are associated
with increasing mammographic density in women using HT, independent of estrogen
and progesterone receptor up-regulation. These findings suggest that increased
breast density may be mediated through a paracrine effect. The increase in
breast cancer risk with HT use may be due to an increase in target lobule type
1 cells.
Semana del 6 al 12 de Junio 2007
Am J Clin Nutr. 2007 Jun;85(6):1606-14.
Whole-grain consumption is associated with a reduced risk of
noncardiovascular, noncancer death attributed to inflammatory diseases in the
Jacobs DR, Andersen LF, Blomhoff R.
Department of
Nutrition,
BACKGROUND: It has
recently been shown that oxidative stress, infection, and inflammation are
predominant pathophysiologic factors for several major diseases. OBJECTIVE: We
investigated the association of whole-grain intake with death attributed to
noncardiovascular, noncancer inflammatory diseases. DESIGN: Postmenopausal
women (n = 41 836) aged 55-69 y at baseline in 1986 were followed for 17 y.
After exclusions for cardiovascular disease, cancer, diabetes, colitis, and
liver cirrhosis at baseline, 27 312 participants remained, of whom 5552 died
during the 17 y. A proportional hazards regression model was adjusted for age,
smoking, adiposity, education, physical activity, and other dietary factors.
RESULTS: Inflammation-related death was inversely associated with whole-grain
intake. Compared with the hazard ratios in women who rarely or never ate
whole-grain foods, the hazard ratio was 0.69 (95% CI: 0.57, 0.83) for those who
consumed 4-7 servings/wk, 0.79 (0.66, 0.95) for 7.5-10.5 servings/wk, 0.64
(0.53, 0.79) for 11-18.5 servings/wk, and 0.66 (0.54, 0.81) for >/=19
servings/wk (P for trend = 0.01). Previously reported inverse associations of
whole-grain intake with total and coronary heart disease mortality persisted
after 17 y of follow-up. CONCLUSIONS: The reduction in inflammatory mortality
associated with habitual whole-grain intake was larger than that previously
reported for coronary heart disease and diabetes. Because a variety of
phytochemicals are found in whole grains that may directly or indirectly inhibit
oxidative stress, and because oxidative stress is an inevitable consequence of
inflammation, we suggest that oxidative stress reduction by constituents of
whole grain is a likely mechanism for the protective effect.
Am J Clin Nutr. 2007 Jun;85(6):1586-91.
Vitamin D and calcium supplementation reduces cancer risk: results of a
randomized trial.
Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP.
BACKGROUND:
Numerous observational studies have found supplemental calcium and vitamin D to
be associated with reduced risk of common cancers. However, interventional
studies to test this effect are lacking. OBJECTIVE: The purpose of this
analysis was to determine the efficacy of calcium alone and calcium plus
vitamin D in reducing incident cancer risk of all types. DESIGN: This was a
4-y, population-based, double-blind, randomized placebo-controlled trial. The
primary outcome was fracture incidence, and the principal secondary outcome was
cancer incidence. The subjects were 1179 community-dwelling women randomly
selected from the population of healthy postmenopausal women aged >55 y in a
9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects
were randomly assigned to receive 1400-1500 mg supplemental calcium/d alone (Ca-only),
supplemental calcium plus 1100 IU vitamin D(3)/d (Ca + D), or placebo. RESULTS:
When analyzed by intention to treat, cancer incidence was lower in the Ca + D
women than in the placebo control subjects (P < 0.03). With the use of
logistic regression, the unadjusted relative risks (RR) of incident cancer in
the Ca + D and Ca-only groups were 0.402 (P = 0.01) and 0.532 (P = 0.06),
respectively. When analysis was confined to cancers diagnosed after the first
12 mo, RR for the Ca + D group fell to 0.232 (CI: 0.09, 0.60; P < 0.005) but
did not change significantly for the Ca-only group. In multiple logistic
regression models, both treatment and serum 25-hydroxyvitamin D concentrations
were significant, independent predictors of cancer risk. CONCLUSIONS: Improving
calcium and vitamin D nutritional status substantially reduces all-cancer risk
in postmenopausal women.
Semin Dial. 2007 May-Jun;20(3):186-90.
Is there a role for bisphosphonates in chronic kidney disease?
Department of
Medicine, University of
Patients with
stage 5 chronic kidney disease (CKD) including those on dialysis can and do
develop osteoporosis. They also develop a wide range of other metabolic bone
diseases that may look like osteoporosis when it is defined by either the World
Health Organization bone mineral density (BMD) criteria or by the development
of fragility fractures. Those dialysis patients with osteoporosis that is due
to gonadal hormone deficiency such as postmenopausal osteoporosis,
glucocorticoid-induced osteoporosis, or male osteoporosis may benefit from the
administration of bisphosphonates (BPs). The challenges lie in the diagnosis of
osteoporosis in this population where adynamic, osteomalacic, hyperparathyroid,
or aluminum bone disease are also prevalent, with concommitant low BMD and low
trauma fractures, but where BPs may be contraindicated. The only secure means
to diagnose osteoporosis in this patient population is by quantitative bone
histomorphometry demonstrating low trabecular bone volume and disrupted
microarchitecture. Once the diagnosis of osteoporosis is established, BPs
should be considered for a well-defined brief period of time (e.g., 2-3 years),
even though there is no evidence for a fracture reduction benefit in this
population. If a BP is chosen there may be a need for dose adjustment or slower
infusion rates (for the intravenous formulations), as a greater bone retention
may occur for these renally cleared agents. While it is unknown what
consequences could develop from increased bone retention in patients with
little renal function, data are needed if more bone retention of BP might lead
to a greater risk of the development of adynamic bone disease and lower bone
strength. More data are needed to define the risks and benefits of BPs in
patients with stage 5 CKD.
Menopause. 2007 Jun 5; [Epub ahead of print]
"It's my hormones, doctor"-does physical activity help with
menopausal symptoms?
From the 1School
of Human Movement Studies, Queensland University, Brisbane, Australia; and
2Department of Public and Occupational Health, EMGO Institute, VU University
Medical Center, Amsterdam, The Netherlands.
OBJECTIVE:: Many
women experience health problems when going through menopause, and these health
problems may result in a substantial reduction in quality of life. There are
some indications that physical activity may play a role in ameliorating
menopausal symptoms, but there is conflicting evidence about this. To assess
the relationship between changes in physical activity and self-reported
vasomotor, somatic, and psychological symptoms. DESIGN:: Data from the third
(2001) and fourth (2004) surveys of the Australian Longitudinal Study on
Women's Health were used. Data from 3,330 middle-aged women were included in
the analyses. In linear regression models, the relationships between changes in
physical activity of at least moderate intensity and total menopausal,
vasomotor, somatic, and psychological symptoms were determined. RESULTS::
Physical activity was not associated with total menopausal symptoms or with
vasomotor or psychological symptoms. A weak association with somatic symptoms
(B = -0.003; 95% CI: -0.005 to -0.001) was found. Weight gain was associated
with increased total, vasomotor, and somatic symptoms. Weight loss was
associated with a reduction in total and vasomotor symptoms. CONCLUSION::
Changes in physical activity were not related to vasomotor or psychological
symptoms and only marginally to somatic symptoms. Changes in weight showed a
stronger relationship with menopausal symptoms. The relationship between weight
change and menopausal symptoms merits further exploration.
Intern Emerg Med. 2007
Mar;2(1):19-23. Epub 2007 Mar 31.
Relation between serum uric acid and carotid intima-media thickness in
healthy postmenopausal women.
Montalcini T, Gorgone G, Gazzaruso C, Sesti G, Perticone F, Pujia A.
Department of Clinical and
Experimental Medicine, G. Salvatore University of Catanzaro Magna Grćcia,
Viale Europa, I-88100, Catanzaro, Italy, pujia@unicz.it.
OBJECTIVE: : Serum
uric acid (SUA) is associated with cardiovascular disease (CVD). However it is
still disputed whether the relationship is mediated by other risk factors such
as obesity, dyslipidaemia, hypertension and insulin resistance. We explored the
association of the uric acid level with carotid intima-media thickness (IMT), a
well known marker of CVD, in postmenopausal healthy women. METHODS: : We
consecutively enrolled postmenopausal women undergoing a screening for health
evaluation. After an accurate clinical examination, and a biochemical
evaluation, the enrolled subjects underwent B mode ultrasonography to assess
common carotid intima media thickness. RESULTS: : Among 234 women aged 45-70
years, the uric acid level is associated with carotid IMT independently of
other prognostic factors (p=0.03). In particular, women in the highest tertiles
of uric acid level have a greater IMT than women in the lowest tertile
(p=0.007). CONCLUSIONS: : Independently of other cardiovascular risk factors,
SUA levels are associated with carotid IMT even in subjects without the
metabolic syndrome. This confirms and expands the role of uric acid in the
determinism of CVD. Prospective trials would be useful to evaluate
interventions aimed at lowering the uric acid level.
J Natl Cancer Inst. 2007 Jun
6;99(11):881-9.
Association of aspirin and nonaspirin nonsteroidal anti-inflammatory
drugs with cancer incidence and mortality.
Bardia A, Ebbert JO, Vierkant RA, Limburg PJ, Anderson K, Wang AH, Olson JE, Vachon CM, Cerhan JR.
Department of
Internal Medicine,
BACKGROUND: The
cancer chemopreventive benefits of aspirin and nonaspirin nonsteroidal anti-inflammatory
drugs (NSAIDs) are incompletely defined and may vary by smoking history. We
evaluated associations between aspirin and nonaspirin NSAID use with cancer
incidence and mortality stratified by smoking history in the Iowa Women's
Health Study, a prospective cohort of postmenopausal women. METHODS: Aspirin
and nonaspirin NSAID use was self-reported by questionnaire in 1992. Cancer
incidence and mortality were ascertained by annual linkage to the Iowa
Surveillance, Epidemiology, and End Results Cancer Registry and death
certificates. Cox proportional hazards models were used to estimate
multivariable relative risks (RRs) and 95% confidence intervals (CIs). All
statistical tests were two-sided. RESULTS: During an average of 10 years of
follow-up, 3487 incident cancer cases and 3581 deaths were observed in the
cohort of 22,507 women. Compared with nonuse, aspirin use was inversely
associated with total cancer incidence (multivariable-adjusted RR = 0.84, 95%
CI = 0.77 to 0.90), with age-adjusted incidence rates of 147 and 170 per 10,000
person-years for ever and never users, respectively, and was inversely
associated with cancer mortality (multivariable-adjusted RR = 0.87, 95% CI =
0.76 to 0.99), with age-adjusted rates of 47 and 52 per 10,000 person-years.
The inverse relationship was stronger among former and never smokers than
current smokers, although not statistically significantly (P = .28). Aspirin
use was also inversely associated with coronary heart disease mortality
(multivariable-adjusted RR = 0.75, 95% CI = 0.64 to 0.89), with age-adjusted
rates of 23 and 30 per 10,000 person-years for ever and never users,
respectively, and with all-cause mortality (multivariable-adjusted RR = 0.82,
95% CI = 0.76 to 0.89), with age-adjusted rates of 126 and 155 per 10,000
person-years. Nonaspirin NSAID use was not associated with cancer incidence or
mortality, coronary heart disease mortality, or all-cause mortality.
CONCLUSIONS: Aspirin use, but not nonaspirin NSAID use, was associated with
lower risks of cancer incidence and mortality, which was more pronounced among
former and never smokers than current smokers.
J Clin Endocrinol Metab. 2007 Jun 5; [Epub ahead
of print]
Endocrine features of menstrual cycles in middle and late reproductive
age and the menopausal transition classified according to the Staging of
Reproductive Aging Workshop (STRAW) staging system.
Hale GE, Zhao X, Hughes CL, Burger HG, Robertson DM, Fraser IS.
Department of
Obstetrics and Gynaecology, QE II Building (DO2) University of Sydney, NSW,
2006, Australia, 2006; RTI International Research Triangle Park, NC 27709,
Prince Henry's Institute, Monash Medical Centre, Clayton, VIC, Australia, 3168.
Context: Female
reproductive aging based on changes in menstrual cycle length and frequency,
progresses through a number of stages as defined by the STRAW (Stages of
Reproductive Aging Workshop) staging criteria. Objective: This paper provides a
comprehensive description of the endocrine features associated with the STRAW
stages. Design: Healthy women aged 21-35 and 45-55 submitted three blood
samples a week for over a single menstrual cycle. They were classified as
mid-reproductive age (MRA; N=21), late reproductive age (LRA; N=16), early
menopause transition (EMT; N=16) and late menopause transition (LMT; N=23).
Results: There were 9, 1, 0 and 2 anovulatory cycles identified in the LMT,
EMT, LRA and MRA groups respectively. Ovulatory cycle FSH, LH and estradiol
(E2) levels increased with progression of STRAW stage (P = 0.001; P < 0.01;
P < 0.05 respectively), and mean luteal phase serum progesterone decreased
(P < 0.01). Early cycle (ovulatory and anovulatory) inhibin B (INHB)
decreased steadily across the STRAW stages (P < 0.01) and was largely
undetectable during elongated ovulatory and anovulatory cycles in the menopause
transition. Anti-Mullerian Hormone (AMH) decreased markedly (10-15 fold) and
progressively across the STRAW stages (P < 0.01; P < 0.001 respectively).
Conclusions: Progression through the STRAW Stages is associated with elevations
in serum FSH, LH, E2 and decreases in luteal phase P. The marked fall in INHB
and particularly AMH indicate that they may be useful in predicting STRAW Stage
but future analyses of early cycle measurements on larger cohorts are needed to
draw predictive conclusions.
Cancer Causes Control. 2007 Jun 5; [Epub
ahead of print]
Exogenous hormones and colorectal cancer risk in
Campbell PT, Newcomb P, Gallinger S, Cotterchio M, McLaughlin JR.
Prosserman Centre
for Health Research, Samuel Lunenfeld Research Institute,
OBJECTIVE: This
work assessed associations between colorectal cancer risk and
postmenopausal/contraceptive hormones; subgroup analyses included women with a
clinically defined family history of cancer. METHODS: A population based case-control
study of incident colorectal cancer was conducted among women aged 20-74 years
in
Cancer Causes Control. 2007 Jun 5; [Epub
ahead of print]
Vitamin D intake and breast cancer risk in postmenopausal women: the
Robien K, Cutler GJ, Lazovich D.
Division of
Epidemiology and Community Health,
Vitamin D, a
prosteroid hormone with anti-proliferative and pro-differentiation activity, is
thought to act as a cancer chemopreventive agent. This study evaluated the
association between vitamin D intake and breast cancer risk among women in a
large prospective cohort study. A total of 34,321 postmenopausal women who had
completed a questionnaire that included diet and supplement use were followed
for breast cancer incidence from 1986 to 2004. Adjusted relative risks (RR) for
breast cancer were calculated for dietary, supplemental, and total vitamin D
intake among all women. The adjusted RR of breast cancer for women consuming
>800 IU/day versus <400 IU/day total vitamin D was 0.89 (95% CI: 0.77-1.03).
RRs were stronger among women with negative than positive ER or PR status. The
association of high vitamin D intake with breast cancer was strongest in the
first 5 years after baseline dietary assessment (RR = 0.66; 95% CI: 0.46-0.94
compared with lowest-intake group), and diminished over time. Changes in
vitamin D intake over time might have contributed to the diminished association
observed in later years. Vitamin D intake of >800 IU/day appears to be
associated with a small decrease in risk of breast cancer among postmenopausal
women. Studies evaluating all sources of vitamin D, especially sun exposure,
are needed to fully understand the association between vitamin D and breast
cancer risk.
Fertil Steril. 2007 Jun 2; [Epub ahead of print]
Tibolone Histology of the Endometrium and Breast Endpoints Study: design
of the trial and endometrial histology at baseline in postmenopausal women.
Archer DF, Hendrix S, Ferenczy A, Felix J, Chris Gallagher J, Rymer J, Skouby SO, Hollander WD, Stathopoulos V, Helmond FA; for the THEBES Study Group.
Department of
Obstetrics and Gynecology, Contraceptive Research and Development Program
Clinical
OBJECTIVE: To
address the endometrial safety of tibolone. DESIGN: The Tibolone Histology of
the Endometrium and Breast Endpoints Study (THEBES) is a randomized,
double-blind, parallel-group trial of tibolone compared with continuous
combined conjugated equine estrogen (CEE) and medroxyprogesterone acetate
(MPA). SETTING: Multi-country, multi-center ambulatory care setting.
PATIENT(S): A total of 5,185 subjects were screened, and biopsies were obtained
from 4,446 women. INTERVENTION(S): Participants were randomized in a 1:1:2
ratio, to tibolone (1.25 or 2.5 mg/d) or CEE-MPA. MAIN OUTCOME MEASURE(S): The
one-sided 95% confidence intervals for the incidence of hyperplasia or cancer
were evaluated for tibolone compared with CEE-MPA. RESULT(S): Endometrial
biopsy results at baseline: atrophic (87.29%), inactive (0.25%), proliferative
(6.12%), secretory (2.86%), menstrual type (0.40%), and hyperplasia (0.18%).
Only subjects with atrophic or inactive endometrium were eligible for this
study, and 3% of the women at screening either had no tissue (0.18%) or had an
amount of tissue that was insufficient for diagnosis (2.72%). Three thousand
two hundred forty postmenopausal women with a mean (+/-SD) age of 54.4 +/- 4.4
years and a mean time since menopause of 4.5 +/- 3.6 years were randomized.
CONCLUSION(S): The Tibolone Histology of the Endometrium and Breast Endpoints
Study is a prospective, randomized clinical trial, designed to provide evidence
of the endometrial safety of tibolone compared with estrogen and progestogen.
Screening endometrial histology shows a low prevalence of endometrial
hyperplasia (0.18%) and no carcinoma.
Ginecol Obstet Mex. 2007
Feb;75(2):86-94.
Perception of gyneco-obstetric physicians about hormone replacement
therapy]
Carranza Lira S, Fragoso Dávila J.
Unidad Médica de Alta Especialidad del Hospital de Ginecología y
Obstetricia Luis Castelazo Ayala, IMSS.
OBJECTIVE: To identify which
is the medical perception of the gynecology-obstetric physicians (Ob-Gyn's)
according to hormone therapy (HT) after WHI trial. MATERIAL AND METHODS: 104
Ob-Gyn were interrogated, and divided into 5 groups according to their position
in the hospital. Descriptive statistics was used and the comparisons were done
with Student's t test. RESULTS: 31.7% of the interviewed were in the fifth
decade of life and 71% were male. 93.6% referred that HT might not be used in
postmenopausal women older 50 years age. Most of them considered that HT
decreases osteoporosis and depression. 90.4% considered that HT must be used
premature menopause. 91.3% prescribed progestagens in patients with uterus.
Oral route was preferred by 50% and the transdermic in 30.8%. 80.8% referred
that combined HT did not increase the possibility of endometrial cancer but it
did for breast cancer (71.2%). In the same way they considered that improved
vaginal lubrication (95.2%), mood (87.5%), hot-flushes (92.3%) and menstrual
disturbances (80.8%). 95.2% considered that HT improves quality of life. 62.5%
referred that WHI trial modified the way they prescribe HT. 80.8% considered
that low dose HT is as good as conventional dose HT. CONCLUSIONS: This
interview permitted to know the opinion in relation to HT, without difference
between the interviewed and world tendency.
Ann Epidemiol. 2007 Jun;17(6):403-9.
Relation between Insulin Resistance and Breast Cancer among Chilean
Women.
Garmendia ML, Pereira A, Alvarado ME, Atalah E.
From the School of Public
Health, Faculty of Medicine, University of Chile, Santiago, Chile (M.L.G.,
A.P., M.E.A.) and the Nutrition Department, Faculty of Medicine, University of
Chile, Santiago, Chile (E.A.).
PURPOSE: In
Best Pract Res Clin Obstet Gynaecol. 2007 May 31; [Epub
ahead of print]
Modern management of abnormal uterine bleeding - the levonorgestrel
intra-uterine system.
Graingerville Clinic,
Since its launch, more than 9
million women worldwide have used the levonorgestrel intra-uterine system (IUS)
for contraception, as a treatment for heavy menstrual bleeding and as the
progestogen component of hormone-replacement therapy. For women in their
reproductive years, the IUS has become one of the most acceptable medical
treatments for menorrhagia, reducing referrals to specialists and decreasing
the need for operative gynaecological surgery. This article will outline the
development of the IUS, highlighting the most important recent areas of
research covering its use to control menstrual blood loss and pain.
J Clin Densitom. 2007 May 31; [Epub ahead
of print]
The Correction of BMD Measurements for Bone Strontium Content.
King's
Strontium ranelate (SR) is a
new oral treatment for osteoporosis associated with large increases in bone
mineral density (BMD) compared with alternative therapies such as
bisphosphonates. Much of the BMD increase during SR treatment is a physical
effect caused by the increased attenuation of X-rays due to the accumulation of
strontium in bone tissue. The aim of this study was to assess the contribution
made by bone strontium content (BSC) to the overall BMD increase by evaluating
the percentage F of the BMD change explained by the physical presence of
strontium in bone. A value of F less than 100% would provide evidence of the
anabolic effect of SR as an additional factor contributing to the overall BMD
increase. Studies of mixtures of strontium hydroxyapatite (SrHA) and calcium
hydroxyapatite (CaHA) scanned on a variety of dual-energy X-ray absorptiometry
(DXA) systems show that a 1% molar ratio of SrHA/(CaHA+SrHA) causes a 10%
overestimation of BMD. The correction of spine BMD measurements for the
physical effects of strontium depends on knowledge of 2 further factors: (1)
bone biopsy measurements of iliac crest BSC and (2) the ratio R of BSC at the
DXA site to BSC at the iliac crest measured in animal studies. We used clinical
trial data and values of R(spine) measured in studies of monkeys and beagle
dogs to determine values of F(spine) for 1, 2, and 3yr treatment with SR. Based
on the average value of R(spine) approximately 0.7 for male and female monkeys,
we found values for F(spine) approximately 75-80% for 1, 2, and 3yr of
treatment. Using the value of R(spine) approximately 1.0 from the beagle study
gave values of F(spine) approximately 100%. Although values of F(spine) as low
as 40% are possible, we conclude that the most likely figure is 75% or greater.
However, it is apparent that there are large uncertainties in the correction of
BMD results for the effect of bone strontium and that the most important of
these is the inference of BSC values at DXA scan sites from measurements of
iliac crest bone biopsy specimens.
J Bone Miner Res. 2007 Jun 1; [Epub
ahead of print]
Vascular Calcification in Middle-Age and Long Term Risk of Hip Fracture:
The
Samelson EJ, Cupples LA, Broe KE, Hannan MT, O'donnell CJ, Kiel DP.
Microabstract Osteoporosis and
atherosclerosis frequently occur in the same individuals and may share similar
pathogenic mechanisms. This study examined the relation between severity of
aortic calcification in middle-age years and subsequent risk of hip fracture in
women and men in the population-based Framingham Study.
Rheumatol Int. 2007 May 31; [Epub ahead of print]
Antiovarian antibodies in primary Sjogren's syndrome.
Euthymiopoulou K, Aletras AJ, Ravazoula P, Niarakis A, Daoussis D, Antonopoulos I, Liossis SN, Andonopoulos AP.
Laboratory of Biochemistry, Department of Chemistry, School of Natural
Sciences, University of Patras, Patras, 265 00, Greece,
aletras@chemistry.upatras.gr.
Our study aimed at screening
patients with primary Sjogren's syndrome (pSs) for the presence of antiovarian
antibodies (AOAs). Detection of AOAs in patients' sera was achieved by ELISA,
using bovine ovarian extract for coating. Western blot analysis and
immunohistochemistry were used to characterize the antibody targets in the
extract and to determine their locus on the bovine ovary, respectively.
Specific AOAs were detected in 27% of 37 patients (two with premature
menopause) and in none of the controls. Immunoreactivity mainly resided in five
proteins of the extract with molecular masses 42, 49, 55, 64 and 72 kDa, and it
might be attributed to their carbohydrate components. The antibody targets were
mainly located in the granulosa and theca interna cells of the follicle, and in
the endothelial cells and fibroblasts of corpus luteum. The detection, for the
first time, of AOAs in a significant percentage of patients with pSs may
suggest autoimmune oophoritis, clinical or subclinical.
Ann Endocrinol (Paris). 2007 May 29; [Epub
ahead of print]
Prolactinoma and estrogens: pregnancy, contraception and hormonal
replacement therapy.
Christin-Maître S, Delemer B, Touraine P, Young J.
Service d'endocrinologie, hôpital Saint-Antoine,
75571 Paris cedex 12, France.
The stimulatory role of
estrogen on prolactin secretion and on proliferation of lactotropic cells is
well established in terms of physiology but could this phenomenon be extended
to include harmful effects of estrogens on prolactinoma? The aim of this review
is to provide an up-to-date assessment of this subject with regard to
pregnancy, use of contraceptive pills and postmenopausal hormone replacement
therapy. Dopamine agonists allow women presenting prolactinoma to recover their
ovulation cycles and become pregnant. There is no adverse data concerning the
safety of dopamine agonists such as bromocriptine, if the woman is treated
during the first trimester of pregnancy but there is little information
regarding the most recent treatments such as cabergoline or quinagolide. In
women with microadenomas, pregnancy generally has little impact on their
adenoma, delivery is normal and breast-feeding is allowed. Concerning
macroprolactinomas, tumor progression during pregnancy is possible and
endocrine follow-up remains necessary. Contraceptive pills containing estrogen
and progestins are currently the best-tolerated and the most effective
contraception. This type of contraceptive has long been avoided in patients
presenting prolactinoma. While the literature has little to say on this subject
and provides no adverse information, professional experience suggests that this
attitude should be amended and that women presenting microprolactinoma should
be allowed to use current contraceptive pills (containing 30 mug or less of
ethinyl estradiol). The most important problem to overcome with this type of
prescription, which masks the clinical consequences of hyperprolactinemia, is
the possibility of overlooking hypophyseal disease that could result from this
approach. The problem of macroprolactinoma is different; the possibility of
prescribing contraceptive pills must be evaluated on a case-by-case basis and
the impact of the drug on the adenoma must be very closely monitored. Estrogen
replacement therapy in patients presenting hypogonadism should be attempted in
patients with a history of prolactinoma and standard-monitoring precautions
should be taken. In menopausal women, when replacement therapy is desirable,
the presence of a microprolactinoma should not by itself avoid this
prescription.
Age Ageing. 2007 May 30; [Epub ahead of print]
Serum high sensitivity C-reactive protein and cognitive unction in
elderly women.
Komulainen P, Lakka TA, Kivipelto M, Hassinen M, Penttilä IM, Helkala EL, Gylling H, et al.
Kuopio Research Institute of
Exercise
BACKGROUND: inflammation has
been linked to cognitive impairment. However, limited data are available on the
association between inflammatory markers and cognitive function. OBJECTIVES: we
tested the hypothesis that elevated serum concentration of high sensitivity
C-reactive protein (hs-CRP), an established marker of low-grade inflammation,
predicts cognitive impairment in elderly women. DESIGN: a 12-year
population-based follow-up study. Participants: a total of 97 women between 60
and 70 years of age at baseline. METHODS: serum hs-CRP concentration was
measured by a high sensitivity assay. Global cognitive function was measured
with the Mini-Mental State Examination (MMSE), and memory and cognitive speed
were measured with a detailed cognitive test battery. RESULTS: higher baseline
hs-CRP was associated with poorer memory at 12-year follow-up without
adjustment and after adjustment for age, education and depression (standardised
regression coefficient beta -0.842, 95% confidence interval -1.602 to -0.083, P
= 0.030), and further adjustment for the use of hormone replacement therapy,
smoking, serum LDL cholesterol and body mass index (standardised regression
coefficient beta -0.817, 95% confidence interval -1.630 to -0.004, P = 0.049).
Memory at 12-year follow-up worsened linearly with increasing hs-CRP at
baseline (P = 0.048 for linear trend). There was no association between hs-CRP
at baseline and cognitive speed or MMSE score at 12-year follow-up.
CONCLUSIONS: high serum hs-CRP concentration predicts poorer memory 12 years
later in elderly women. Hs-CRP may be a useful biomarker to identify
individuals at an increased risk for cognitive decline.
Menopause Int. 2007 Jun;13(2):75-8.
Dehydroepiandrosterone (DHEA) and the menopause: an update.
Metabolic and Clinical Trials
Unit, Royal Free &
Since we last reviewed this
topic in 2001, considerably more information about dehydroepiandrosterone
(DHEA) has accrued, but this has not necessarily left us any wiser about the
use of this steroid in postmenopausal women. There is no further evidence that
DHEA supplementation is likely to be useful in the prevention of cardiovascular
disease or cognitive impairment, or in the promotion of wellbeing. Evidence
has, however, accumulated for beneficial effects of DHEA on osteoporosis, both
in postmenopausal women and in patients receiving long-term glucocorticoid
therapy. What is also emerging is a link between low DHEA levels and
cardiovascular risk, and between high DHEA levels and breast cancer risk. In
fact, the benefits and adverse effects of DHEA administration in postmenopausal
women increasingly resemble those of conventional hormone replacement therapy.
Overall, we conclude that DHEA is not currently to be recommended for
therapeutic use in the majority of postmenopausal women. However, DHEA
supplementation may be of benefit in two specific groups of women: those with
the lowest circulating levels of DHEA; and those for whom osteoporosis is a
particular problem.
Menopause Int.
2007 Jun;13(2):65-70.
Systemic lupus erythematosus and hormone replacement therapy.
Unité de gynécologie endocrinienne, Université
Paris Descartes, APHP, Hôtel-Dieu, Paris, France.
The indications for hormone
replacement therapy (HRT) in postmenopausal women is the treatment of
climacteric symptoms and the prevention of osteoporosis. Women with systemic
lupus erythematosus (SLE) are more likely to have a premature menopause,
osteoporosis and cardiovascular disease. HRT can induce SLE flares and
cardiovascular or venous thromboembolic events. Therefore it should not be used
in women with active disease or those with antiphospholipid (aPL) antibodies.
In general, it should be used only for patients without active disease, a
history of thrombosis or aPL antibodies. Non-oral administration of estrogen is
recommended because of its lesser effect on coagulation. With regard to the
progestogen, progesterone or pregnane derivatives are preferred. Otherwise, non-estrogen-based strategies
should be used.
Proc Natl Acad Sci U S A. 2007 May 30; [Epub
ahead of print]
Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone
formation, and offers an anabolic treatment approach for osteoporosis.
Buckbinder L, Crawford DT, Qi H, Ke HZ, Olson LM, Long KR, Bonnette PC, Baumann APet al
Pfizer Global Research and
Development,
Bone is accrued and maintained
primarily through the coupled actions of bone-forming osteoblasts and
bone-resorbing osteoclasts. Cumulative in vitro studies indicated that
proline-rich tyrosine kinase 2 (PYK2) is a positive mediator of osteoclast
function and activity. However, our investigation of PYK2-/- mice did not
reveal evidence supporting an essential function for PYK2 in osteoclasts either
in vivo or in culture. We find that PYK2-/- mice have high bone mass resulting
from an unexpected increase in bone formation. Consistent with the in vivo
findings, mouse bone marrow cultures show that PYK2 deficiency enhances
differentiation and activity of osteoprogenitor cells, as does expressing a
PYK2-specific short hairpin RNA or dominantly interfering proteins in human
mesenchymal stem cells. Furthermore, the daily administration of a
small-molecule PYK2 inhibitor increases bone formation and protects against
bone loss in ovariectomized rats, an established preclinical model of
postmenopausal osteoporosis. In summary, we find that PYK2 regulates the
differentiation of early osteoprogenitor cells across species and that
inhibitors of the PYK2 have potential as a bone anabolic approach for the
treatment of osteoporosis.
Zhonghua Fu Chan Ke Za Zhi. 2007
Mar;42(3):169-72.
Comparison of different antidepression therapy in perimenopausal and
postmenopausal women with depression
Lai AL, Zhao YW, Qi HY, Zhang JS, Zhang LS, Weng YQ.
Department of Obstetrics and
Gynecology, Affiliated
OBJECTIVE: To study the effects
of antidepression drugs and hormone replacement therapy (HRT) in perimenopausal
and postmenopausal women with depression. METHODS: Eighty six perimenopausal
and postmenopausal women with depression were divided into two groups, and
treated for 12 weeks, respectively. Forty three received antidepression drugs
as control group. Among them, mild to moderate depression were treated with
deanxid (1 - 2 pills/d), and severe depression with fluoxetine (20 mg/d).
Another 43 took Tibolone (livial) as HRT group (1.25 mg/d). All patients were
assessed with the
Arch Intern Med. 2007 May
28;167(10):1050-9.
Intakes of
calcium and vitamin d and breast cancer risk in women.
Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM.
Division of Preventive
Medicine, Brigham and Women's Hospital, Harvard Medical School, 900
Commonwealth Ave E, Boston, MA 02215. jhlin@rics.bwh.harvard.edu.
BACKGROUND: Animal data
suggest the potential anticarcinogenic effects of calcium and vitamin D on
breast cancer development. However, epidemiologic data relating calcium and
vitamin D levels to breast cancer have been inconclusive. METHODS: We
prospectively evaluated total calcium and vitamin D intake in relation to
breast cancer incidence among 10 578 premenopausal and 20 909 postmenopausal
women 45 years or older who were free of cancer and cardiovascular disease at
baseline in the Women's Health Study. Baseline dietary intake was assessed by a
food frequency questionnaire. We used Cox proportional hazards regression to
estimate hazard ratios and 95% confidence intervals. RESULTS: During an average
of 10 years of follow-up, 276 premenopausal and 743 postmenopausal women had a
confirmed diagnosis of incident invasive breast cancer. Higher intakes of total
calcium and vitamin D were moderately associated with a lower risk of
premenopausal breast cancer; the hazard ratios in the group with the highest
relative to the lowest quintile of intake were 0.61 (95% confidence interval,
0.40-0.92) for calcium (P = .04 for trend) and 0.65 (95% confidence interval,
0.42-1.00) for vitamin D intake (P = .07 for trend). The inverse association
with both nutrients was also present for large or poorly differentiated breast
tumors among premenopausal women (P</=.04 for trend). By contrast, intakes of
both nutrients were not inversely associated with the risk of breast cancer
among postmenopausal women. CONCLUSIONS: Findings from this study suggest that
higher intakes of calcium and vitamin D may be associated with a lower risk of
developing premenopausal breast cancer. The likely apparent protection in
premenopausal women may be more pronounced for more aggressive breast tumors.
Am J Prev Med. 2007 Jun;32(6):483-9.
Discontinuing Hormone Replacement Therapy Attenuating the Effect on CVD
Risk With Lifestyle Changes.
Pettee KK, Kriska AM, Conroy MB, Johnson BD, Orchard TJ, Goodpaster BH, Averbach FM, Kuller LH.
Department of Exercise and
Wellness,
BACKGROUND: Concern about the
potential risks associated with hormone replacement therapy (HRT) has left
post-menopausal women and healthcare providers searching for safe and effective
means for cardiovascular disease (CVD) risk factor reduction. METHODS: The
Woman On the Move through Activity and Nutrition study is a 5-year clinical
trial (2002-2006) designed to test whether a lifestyle intervention will reduce
measures of subclinical CVD. Participants were randomized at baseline to a
health education or lifestyle change group. The impact of lifestyle
intervention on CVD risk factors was examined in 240 women who were initially
on HRT at baseline and either continued (n = 110) or discontinued (n = 130) by
18 months. RESULTS: The lifestyle-change group significantly decreased weight,
body mass index, waist circumference (all p<0.0001), total cholesterol
(p=0.02), and LDL cholesterol (LDL-C) (p= 0.01), improved fat intake
(p<0.0001), and increased leisure physical activity (p=0.005) when compared
with the health education group. HRT discontinuation resulted in increased
total cholesterol (p=0.04) and LDL-C (p=0.009). CVD risk factor changes were
further explored by the HRT group, stratified by randomized group assignment.
Within the health education arm, HRT discontinuers averaged over a 22-mg/dL
increase in total cholesterol and LDL-C, while HRT continuers averaged less
than 4 mg/dL (p=0.004 and 0.002, respectively). No such differences were noted
in the lifestyle-change group (p=0.78 and 0.90, respectively). CONCLUSIONS:
Lifestyle modification was effective for CVD risk factor reduction in post-menopausal
women. HRT discontinuation resulted in increased total cholesterol and LDL-C,
which were successfully attenuated by a lifestyle intervention incorporating
weight loss, physical activity, and dietary modification.
Menopause. 2007 May 30; [Epub ahead of print]
Circulating osteoprotegerin is associated with age and systolic blood
pressure, but not with lipid profile or fasting glucose, in postmenopausal
women.
Uemura H, Yasui T, Miyatani Y, Yamada M, Hiyoshi M, Arisawa K, Irahara M.
Departments of Preventive
Medicine and Obstetrics, University of
OBJECTIVE:: Osteoprotegerin
(OPG), an inhibitor of osteoclastogenesis and osteoclast activation, has been
reported to be linked to vascular biology. The aim of this study was to clarify
the relationships between circulating OPG and the risk factors for vascular
disorders in postmenopausal women. DESIGN:: Eighty Japanese postmenopausal
women were enrolled in this cross-sectional study. Clinical parameters (age,
number of years since menopause, body mass index, systolic and diastolic blood
pressure); serum concentrations of OPG, creatinine, calcium, and phosphorus;
serum lipid profile; plasma glucose; and bone mineral density of the L2-4
vertebral bodies were determined for each woman. RESULTS:: In rank-order
correlation analysis, serum OPG concentrations had significant positive
correlations with age (r = 0.29, P = 0.03), systolic blood pressure (r = 0.45,
P < 0.01), diastolic blood pressure (r = 0.34, P < 0.01), and serum
creatinine (r = 0.29, P = 0.04). Serum OPG concentration also had a marginally
significant negative correlation with bone mineral density of the L2-4
vertebral bodies (r = -0.25, P = 0.06). However, serum OPG did not correlate
with body mass index, serum lipid profile, or plasma glucose. The correlation
of serum OPG with systolic blood pressure persisted after adjustment for both
age and serum creatinine. CONCLUSIONS:: These results suggest that increased
circulating OPG in postmenopausal women is closely related to higher systolic
blood pressure, which could cause atherosclerosis.