Selección de Resúmenes de Menopausia
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 Gusmão JL, Abrahão 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.
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 Græcia, 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.