Selección de Resúmenes
de Menopausia
Diciembre de
2008
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad de Chile
Semana del 26 de Noviembre al 2 de Diciembre 2008
Osteoporos Int. 2008 Nov 28. [Epub ahead of print]
Spine radiographs
to improve the identification of women at high risk for fractures.
Netelenbos JC, Lems WF, Geusens PP, Verhaar HJ, Boermans AJ, Boomsma MM, Mulder PG, et
al.
Department
of Endocrinology, VU
In women older
than 60 years with clinical risk factors for osteoporosis but without
osteoporosis based on bone mineral density (T-score >/= -2.5), a systematic
survey with X-rays of the spine identified previously unknown vertebral
deformities in 21% of women. INTRODUCTION: This study determines the prevalence
of vertebral deformities in elderly women with clinical risk factors for
osteoporosis but with BMD values above the threshold for osteoporosis (T-score
>/= -2.5). METHODS: Bisphosphonate naïve women
older than 60 years attending 35 general practices in the
Mol Endocrinol. 2008 Nov 26. [Epub ahead of print]
Differential
Biochemical and Cellular Actions of Premarin
Estrogens: Distinct Pharmacology of Bazedoxifene-Conjugated
Estrogens Combination.
Berrodin TJ, Chang KC, Komm BS, Freedman LP, Nagpal S.
Nuclear Receptor
Biology, Women's Health & Musculoskeletal Biology, Wyeth Research,
The use of estrogen based therapies, and the selective estrogen receptor modulator
(SERM), raloxifene, which are approved for
post-menopausal osteoporosis, is associated with uterine/breast hyperproliferation, thromboembolism,
and hot flashes side effects. A combination of a new SERM, bazedoxifene
(BZA), and Premarin (conjugated estrogens; CE) is
under investigation to mitigate the estrogen/SERM
side effects with promising results in Phase III clinical trials. To explore
the mechanism of BZA/CE action, we investigated the recruitment of cofactor
peptides to ERalpha by components of CE and a mixture
containing the 10 major components of CE with or without three different SERMs.
Here, we demonstrate differential recruitment of cofactor peptides to ERalpha by the individual CE components using a multiplex
nuclear receptor-cofactor peptide interaction assay. We show that estrone and equilin are partial
agonists in comparison to 17beta-estradiol in recruiting cofactor peptides to ERalpha. Further, CE was more potent than 17beta-estradiol
in mediating ERalpha interaction with cofactor
peptides. Interestingly, BZA was less potent than other SERMs in antagonizing
the CE-mediated cofactor peptide recruitment to ERalpha.
Finally, in accordance with these biochemical findings, 17beta-estradiol and CE
as well as SERM/CE combinations showed differential gene regulation patterns in
MCF-7 cells. In addition, BZA showed antagonism of a unique set of CE-regulated
genes, and did not downregulate
the expression of a number of CE-regulated genes whose expression was
effectively antagonized by the other two SERMs. These results indicate that
SERMs in combination with CE exhibit differential pharmacology, and therefore,
combinations of other SERMs and estrogen preparations
may not yield the same beneficial effects that are observed in clinic by
pairing BZA with CE.
Menopause. 2008 Nov 20. [Epub ahead of print]
A
randomized study of low-dose conjugated estrogens on sexual function and
quality of life in postmenopausal women.
Gast MJ, Freedman MA, Vieweg AJ, De Melo
NR, Girão MJ, Zinaman MJ; the Dyspareunia
Study Group.
Wyeth
Pharmaceuticals,
OBJECTIVE:: To evaluate the effects of combined vaginal and oral
low-dose estrogen plus progestogen
therapy (EPT) on the frequency and severity of dyspareunia,
sexual function, and quality of life in recently postmenopausal women. DESIGN:: This outpatient, double-blind, randomized,
placebo-controlled trial enrolled 285 healthy, sexually active postmenopausal
women aged 45 to 65 years. Women received either one daily oral low-dose
conjugated estrogens (0.45 mg)/medroxyprogesterone
(1.5 mg) tablet for six 28-day cycles along with 1 g conjugated estrogens
vaginal cream (0.625 mg), intravaginally for the
first 6 weeks of the trial or a placebo cream and placebo tablet. Efficacy was
evaluated using the McCoy Female Sexuality Questionnaire, self-reported daily
diary cards, the Brief Index of Sexual Functioning-Women (BISF-W), and the
Women's Health Questionnaire. RESULTS:: The EPT group
had a significant decrease in the frequency of dyspareunia
compared with baseline and placebo in an analysis of responses to the McCoy
Female Sexuality Questionnaire. Also, EPT was associated with a significant
improvement in a woman's level of sexual interest, frequency of orgasm, and
pleasure of orgasm. There was no effect of EPT use on coital frequency. The EPT
group had significant improvement in receptivity/initiation and relationship
satisfaction, although not in other BISF-W domains, versus placebo (BISF-W
analysis) and significant improvement versus placebo on most Women's Health
Questionnaire responses. CONCLUSIONS:: EPT provided a
statistically significant improvement compared with placebo in dyspareunia, sexual experience, and quality of life as
measured in this study. In general, EPT also improved self-reported sexual
perception and enjoyment significantly compared with placebo.
Menopause. 2008 Nov 20. [Epub ahead of print]
Vasomotor symptoms
are associated with a lower bone mineral density.
Gast GC, Grobbee DE, Pop VJ, Keyzer JJ, Wijnands-van Gent CJ, Samsioe GN, Nilsson PM, van der
Schouw YT.
Menopause. 2008 Nov 20. [Epub ahead of print]
Increased
cardiovascular mortality after early bilateral oophorectomy.
Rivera CM, Grossardt BR, Rhodes DJ, Brown RD Jr, Roger VL, Melton LJ 3rd, Rocca WA.
Department
of Internal Medicine, Mayo Clinic,
OBJECTIVE:: To investigate the mortality associated with
cardiovascular diseases and the effect of estrogen
treatment in women who underwent unilateral or bilateral oophorectomy
before menopause. DESIGN:: We conducted a cohort study
with long-term follow-up of women in
Am J Obstet Gynecol. 2008 Nov
20. [Epub ahead of
print]
How often are
endometrial polyps malignant in asymptomatic postmenopausal women? A multicenter study.
Ferrazzi E, Zupi E, Leone FP, Savelli L, Omodei U, Moscarini M, Barbieri M, Cammareri G, Capobianco G, Cicinelli E, Coccia ME, Donarini G, Fiore S, Litta P, Sideri M, Solima E, Spazzini D, Testa AC, Vignali M.
Department
of Obstetrics and Gynecology, DSC L. Sacco,
OBJECTIVE: The
objective of the study was to evaluate the prevalence of cancer and
premalignant lesions in polyps on atrophic endometrium
in asymptomatic postmenopausal women to compare these findings with a similar cohort
of patients with abnormal uterine bleeding. STUDY DESIGN: One thousand one
hundred fifty-two asymptomatic and 770 consecutive postmenopausal women with
abnormal uterine bleeding were included in a retrospective multicenter study.
Recruited patients underwent hysteroscopic polypectomy based on a sonohysterographic
or hysteroscopic diagnosis. The pathologic report was
the main outcome measure. RESULTS: One single case of stage 1 grade 1
endometrial carcinoma on a polyp with a mean diameter of 40 mm (0.1%) was
observed in asymptomatic women. This prevalence was 10 times lower than in
symptomatic patients (P < .0001). The prevalence of atypical hyperplastic polyps was 1.2% in asymptomatic women (2.2% in
symptomatic patients; P < .005). At multivariate analysis, polyps' diameter
was the only variable significantly associated to an abnormal histology
(cancer, polypoid cancer, and atypical hyperplasia)
in asymptomatic women (odds ratio for polyps with mean diameter > 18 mm,
6.9; confidence interval, 2.2 -21.4). CONCLUSION: Follow-up and/or treatment of
endometrial polyps incidentally diagnosed in asymptomatic postmenopausal
patients could be safely restricted to few selected cases based on polyp
diameter.
Menopause. 2008 Nov 20. [Epub ahead of print]
Is age at menopause
increasing across
Dratva J, Gómez Real F, Schindler C, Ackermann-Liebrich
U, Gerbase MW, Probst-Hensch NM, Svanes C, Omenaas ER, Neukirch F, Wjst M, Morabia A, Jarvis D, Leynaert B, Zemp E.
OBJECTIVE:: To investigate the variability and determinants of
menopause age in two European cohort studies, the European Respiratory Health
Survey and the Swiss Air Pollution and Lung Disease in Adults Cohort. DESIGN:: Age at menopause was estimated in 5,288 women, aged 30 to
60 years, randomly selected in nine European countries between 1998 and 2002.
Determinants of natural and surgically induced menopause were investigated by
Cox regression and heterogeneity by meta-analysis. Follicle-stimulating hormone
and luteinizing hormone levels were assessed in a subsample. RESULTS:: A quarter of the women were postmenopausal by age 50.8
years. Median age of natural menopause was 54 years. Hormone levels were within
expected ranges for premenopausal and postmenopausal women. Surgically induced
menopause was highly prevalent (22%-47%), associated with earlier timing of
menopause. Determinants of earlier menopause were current smoking (hazard ratio
[HR], 1.59; 95% CI, 1.27-1.98), body mass index greater than 30 kg/m (HR, 1.32;
95%, CI, 1.02-1.70), and low physical activity (HR, 1.37; 95%, CI, 1.12-1.67).
The determinant for later menopause was multiparity
(HR, 0.74; 95% CI, 0.62-0.89). Predictors were similar for naturally and
surgically induced menopause. Oral contraceptive use yielded heterogeneous
effects on timing of menopause. Later birth was associated with later menopause
(HR, 0.934; 95% CI, 0.91-0.96). This evidence of a secular trend is
heterogeneous across countries. CONCLUSIONS:: Age at
menopause varies across
Semana del 3 al 9 de Diciembre 2008
Menopause. 2008 Dec 4. [Epub
ahead of print]
Influence of a walking program on the metabolic risk profile of obese
postmenopausal women.
Roussel M, Garnier S, Lemoine S, Gaubert I, Charbonnier L, Auneau G, Mauriège P.
From the 1UFR
STAPS, Université P. Sabatier, Toulouse, France;
2Fédération Française d'Education
Physique et de Gymnastique Volontaire,
Paris, France; and 3Division of Kinesiology, Laval University, Québec City,
Canada.
OBJECTIVE:: Menopause transition is associated with an increased
prevalence of metabolic syndrome (MS), which may partly explain the higher
coronary heart disease risk. The aim of this study was to examine the impact of
a 16-week walking program on the metabolic risk profile of women 50 to 65 years
old whose body mass index ranged from 29 to 35 kg/m. DESIGN:: A total of 153
postmenopausal women were subjected to three sessions per week of 45-minutes of
walking at 60% of their heart rate reserve. At baseline, 46 and 84 women were
characterized by one and two or more determinants of MS, respectively, whereas
23 women did not show this condition. Body composition, resting blood pressure,
fasting lipid-lipoprotein profile, and cardiorespiratory
fitness (CRF) were measured before and after exercise. RESULTS:: In the whole sample of 153 women, CRF estimated by V
o2max increased in response to walking (P < 0.0001). Endurance training
promoted body weight and fat mass losses and reduced waist girth and blood
pressure, whereas it decreased plasma triglyceride, cholesterol, and
low-density lipoprotein cholesterol levels and increased high-density
lipoprotein cholesterol concentrations (P < 0.0001). Improvements in
lipid-lipoprotein levels were not associated with increases in CRF but seemed
to be dependent on reduced body fatness. However, the greatest ameliorations in
metabolic risk profile were found in women characterized by two or more
determinants of MS at baseline than in the two other groups (0.05 < P <
0.0001). CONCLUSION:: A moderate-intensity physical
activity is thus sufficient to reduce the metabolic risk profile of
postmenopausal women characterized by the presence of one or several clinical
features of MS but without overt coronary heart disease.
Climacteric. 2008
Dec 2:1-8. [Epub ahead of print]
Circulating microparticles
and endogenous estrogen in newly menopausal women.
Jayachandran M, Litwiller RD, Owen WG, Miller VM.
Departments
of Surgery and Physiology and Biomedical Engineering.
Background Estrogen modulates antithrombotic characteristics of the
vascular endothelium and the interaction of blood elements with the vascular
surface. A marker of these modulatory activities is
formation of cell-specific microparticles. This study
examined the relationship between blood-borne microparticles
and endogenous estrogen at menopause. Methods
Platelet activation and plasma microparticles were
characterized from women being screened (n = 146) for the Kronos
Early Estrogen Prevention Study. Women were grouped
according to serum estrogen (< 20 pg/ml; low estrogen, n = 21 or > 40 pg/ml; high estrogen,
n = 11). Results Age, body mass index, blood pressure and blood chemistries
were the same in both groups. No woman was hypertensive, diabetic or a current
smoker. Platelet counts, basal and activated expression of P-selectin on platelet membranes were the same, but activated
expression of glycoprotein IIb/IIIa
was greater in the high-estrogen group. Numbers of
endothelium-, platelet-, monocyte- and
granulocyte-derived microparticles were greater in
the low-estrogen group. Of the total numbers of microparticles, those positive for phosphatidylserine
and tissue factor were also greater in the low-estrogen
group. Conclusion These results suggest that, with declines in endogenous estrogen at menopause, numbers of procoagulant
microparticles increase and thus may provide a means
to explore mechanisms for cardiovascular risk development in newly menopausal
women.
J Clin Endocrinol Metab. 2008 Dec;93(12):4567-4575.
Approach to the Patient with Menopausal Symptoms.
Reproductive
Endocrine Unit, BHX-5,
Many women
experience menopausal symptoms during the menopausal transition and
postmenopausal years. Hot flashes, the most common symptom, typically resolve
after several years, but for 15-20% of women, they interfere with quality of
life. For these women, estrogen therapy, the most
effective treatment for hot flashes, should be considered. The decision to use
hormone therapy involves balancing the potential benefits of hormone therapy against
its potential risks. Accumulating data suggest that initiation of estrogen many years after menopause is associated with
excess coronary risk, whereas initiation soon after menopause is not.
Therefore, most now agree that short-term estrogen
therapy, using the lowest effective estrogen dose, is
a reasonable option for recently menopausal women with moderate to severe
symptoms who are in good cardiovascular health. Short-term therapy is
considered to be not more than 4-5 yr because symptoms diminish after several
years, whereas the risk of breast cancer increases with longer duration of
hormone therapy. A minority of women may need long-term therapy for severe,
persistent vasomotor symptoms after stopping hormone therapy. However, these
women should first undergo trials of nonhormonal
options such as gabapentin, selective serotonin
reuptake inhibitors, or serotonin norepinephrine
reuptake inhibitors, returning to estrogen only if
these alternatives are ineffective or cause significant side effects. Low-dose
vaginal estrogens are highly effective for genitourinary atrophy symptoms, with
minimal systemic absorption and endometrial effects.
Breast Cancer Res. 2008 Dec 3;10(6):R102. [Epub ahead of print]
Digoxin treatment is associated with an increased
incidence of breast cancer: a population-based case-control study.
Ahern TP, Lash TL, Sorensen
HT, Pedersen
LA.
ABSTRACT:
INTRODUCTION: Laboratory and epidemiologic studies have suggested a modifying
effect of cardiac glycosides (e.g., digoxin and digitoxin) on cancer risk. We explored the association
between digoxin treatment and invasive breast cancer
incidence among postmenopausal Danish women. METHODS: We used Danish registries
to identify 5,565 postmenopausal women diagnosed with incident invasive breast
carcinoma between
J Bone Miner Res. 2008 Dec 2. [Epub ahead of print]
Vitamin D Status, Parathyroid Function,
Bone Turnover and Bone Mineral Density in Postmenopausal Women with
Osteoporosis in Global Perspective.
Kuchuk NO, van Schoor NM, Pluijm SM, Chines A, Lips P.
Abstract Poor
vitamin D status is common in elderly and is associated with bone loss and
fractures. The aim was to assess worldwide vitamin D status in postmenopausal
women with osteoporosis according to latitude and economic status, in relation
to parathyroid function, bone turnover markers and bone mineral density (BMD).
The study was performed in 7441 postmenopausal women from 29 countries,
participating in a clinical trial on bazedoxifene
(SERM), with BMD T-score at the femoral neck or lumbar spine </=-2.5, or 1
to 5 mild or moderate vertebral fractures . Serum
25(OH)D, parathyroid hormone (PTH), alkaline phosphatase (AP), bone turnover markers osteocalcin
(OC), C-telopeptide (CTX), BMD of lumbar spine, total
hip, femoral neck and trochanter were measured. The
mean serum 25(OH)D level was 61.2+/-22.4 nmol/L. The prevalence of 25(OH)D
<25, 25-50, 50-75 and >75 nmol/L was 5.9, 29.4,
43.5 and 21.2%, respectively, in winter; and 3.0, 22.2, 47.2 and 27.5% in
summer. Worldwide, a negative correlation between 25(OH)D
and latitude was observed. With increasing 25(OH)D
categories of <25, 25-50, 50-75 and >75 nmol/L,
mean PTH, OC and CTX were decreasing (P<0.001), while BMD of all sites was
increasing (P<0.001). A threshold in the positive relationship between 25(OH)D and different BMD parameters was visible at 25(OH)D level
of 50 nmol/L. Our study showed a high prevalence of
low 25(OH)D in post-menopausal women with osteoporosis
worldwide. Along with latitude, affluence seems to be an important factor for
serum 25(OH)D level, especially in
J Bone Miner Res. 2008 Dec 2. [Epub ahead of print]
Diabetic Patients Have an Increased Risk of Vertebral Fractures
Independent of Bone Mineral Density or Diabetic Complications.
Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T.
Abstract
Introduction: Although patients with type 2 diabetes (T2DM) have an increased
risk of hip fracture, risk of vertebral fracture (VF) and its association with
bone mineral density (BMD) are still unclear. Methods: We examined Japanese
T2DM patients (161 men older than 50 years and 137 postmenopausal women) and
non-DM controls (76 and 622, respectively) by lateral spine radiography as well
as dual-energy X-ray absorptiometry at the lumbar
spine (L), femoral neck (FN) and radius (R). Results: Logistic regression
analysis adjusted for age, body mass index and L-BMD showed that the presence
of T2DM was an independent risk factor for prevalent VFs in women [odds ratio
(OR) = 1.86, p = 0.019] as well as men [OR = 4.73, p < 0.001]. BMD at any
site, however, was not significantly associated with the presence of prevalent
VFs in T2DM patients, in contrast to the significant association in controls
(at least p = 0.010). Comparison of T2DM patients with and without VFs showed
no significant differences in BMD values, bone markers, or diabetes status.
Receiver operating characteristic analysis showed that the absolute L-, FN-,
and R-BMD values for detecting prevalent VFs were higher in T2DM patients than
controls, while their sensitivity and specificity were lower. Conclusions: T2DM
patients may have an increased risk of VFs independent of BMD or diabetic
complication status, suggesting that bone quality may define bone fragility in
T2DM.
Fertil Steril. 2008 Nov;90(5):1583-8. Epub 2007 Dec 27
Low-dose oral contraceptive pill for dysmenorrhea
associated with endometriosis: a placebo-controlled, double-blind, randomized
trial.
Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa N.
Department
of Obstetrics and Gynecology,
OBJECTIVE: To
evaluate the efficacy of a low-dose oral contraceptive pill (OCP) for patients
with dysmenorrhea associated with endometriosis.
DESIGN: A double-blind, randomized, placebo-controlled trial. SETTINGS:
Clinical trial sites in
Semana del 10 al 16 de Diciembre 2008
Calcif Tissue
Int. 2008 Dec 5. [Epub ahead of print]
Hypertension Is a
Risk Factor for Fractures.
Vestergaard P, Rejnmark L, Mosekilde L.
Department of
Endocrinology and Metabolism C, The Osteoporosis Clinic, Aarhus Amtssygehus, Aarhus University Hospital, Tage Hansens Gade
2, 8000, Aarhus C, Denmark, p-vest@post4.tele.dk.
To study the
effects of hypertension and other cardiovascular risk factors on risk of
fractures, we carried out a case-control study including 124,655 fracture cases
and 373,962 age- and gender-matched controls. The main exposure was
hypertension, stroke, acute myocardial infarction, ischemic heart disease, atrial fibrillation, peripheral arterial disease, and deep
venous thromboembolism, and the main confounders were
use of diuretics, antihypertensive drugs, organic nitrates, vitamin K
antagonists, and cholesterol lowering drugs along with other confounders.
Hypertension and stroke were the only significant risk factors in both the
short-term (OR = 1.27, 95% CI = 1.20-1.34 and 1.24, and 95% CI = 1.16-1.31 for
</=3 years since diagnosis of hypertension and stroke, respectively) and the
long-term (OR = 1.11, 95% CI = 1.00-1.23 and 1.09, and 95% CI = 1.02-1.18 for
> 6 years since diagnosis of hypertension and stroke, respectively)
perspective. Acute myocardial infarction, atrial
fibrillation, and deep venous thromboembolism were
all associated with a transient increase in the risk of fractures within the first
3 years following diagnosis. Peripheral arterial disease and ischemic heart
disease were not associated with an increased risk of fractures. In conclusion,
hypertension and stroke seem to be the major cardiovascular risk factors for
fractures, whereas acute myocardial infarction, atrial
fibrillation, and deep venous thromboembolism seem to
be only minor risk factors. The fracture risk in hypertension may explain why
antihypertensive drugs as a class effect are associated with a decreased risk
of fractures. These drugs may counter some of the deleterious effects of high
blood pressure.
Int J Cancer. 2008 Sep 16. [Epub ahead of print]
Longitudinal
association of anthropometry with mammographic breast density in the Study of
Women's Health Across the Nation.
Reeves KW, Stone RA, Modugno F, Ness RB, Vogel VG, Weissfeld JL, Habel LA, Sternfeld B, Cauley JA.
Department of
Public Health, School of Public Health and Health Sciences, University of
Massachusetts, Amherst, MA.
High percent
mammographic breast density is strongly associated with increased breast cancer
risk. Though body mass index (BMI) is positively associated with risk of
postmenopausal breast cancer, BMI is negatively associated with percent breast
density in cross-sectional studies. Few longitudinal studies have evaluated
associations between BMI and weight and mammographic breast density. We studied
the longitudinal relationships between anthropometry and breast density in a
prospective cohort of 834 pre- and perimenopausal
women enrolled in an ancillary study to the Study of Women's Health Across the Nation (SWAN). Routine screening mammograms were
collected and read for breast density. Random intercept regression models were
used to evaluate whether annual BMI change was associated with changes over
time in dense breast area and percent density. The study population was 7.4%
African-American, 48.8% Caucasian, 21.8% Chinese, and 21.9% Japanese. Mean
follow-up was 4.8 years. Mean annual weight change was +0.32 kg/year, mean
change in dense area was -0.77 cm(2)/year, and mean change in percent density
was -1.14%/year. In fully adjusted models, annual change in BMI was not
significantly associated with changes in dense breast area (-0.17 cm(2), 95% CI -0.64, 0.29). Borderline significant negative
associations were observed between annual BMI change and annual percent density
change, with percent density decreasing 0.36% (95% CI -0.74, 0.02) for a one
unit increase in BMI over a year. This longitudinal study provides modest
evidence that changes in BMI are not associated with changes in dense area, yet
may be negatively associated with percent density.
Am
J Epidemiol. 2008 Dec 8. [Epub ahead of print]
Association of
Coronary Artery and Aortic Calcium With Lumbar Bone
Density: The
Hyder JA, Allison MA, Wong N, Papa A, Lang TF, Sirlin C, Gapstur SM, Ouyang P, Carr JJ, Criqui MH.
Atherosclerosis
and osteoporosis share many risk factors, but their independent association is
unclear. The authors investigated the independent associations between
volumetric trabecular bone mineral density (vBMD) of the lumbar spine and coronary artery calcium (CAC)
and abdominal aortic calcium (AAC). During 2002-2005, they used quantitative
computed tomography to assess vBMD and the presence
and extent of CAC and AAC among 946 women (mean age = 65.5 years) and 963 men
(mean age = 64.1 years) in a substudy of the
Multi-Ethnic Study of Atherosclerosis. Prevalences of
CAC were 47% and 68% in women and men, respectively, and AAC prevalences were 70% and 73%. Sequential, sex-specific
regression models included adjustment for age, ethnicity, body mass index,
hypertension, dyslipidemia, diabetes mellitus,
smoking, alcohol consumption, physical activity, interleukin-6, C-reactive
protein, homocysteine, and sex hormones. After full
adjustment, lower vBMD was associated with greater
CAC score among women (P < 0.002) and greater AAC score among women (P =
0.004) and men (P < 0.001). After adjustment, vBMD
quartile was inversely associated with CAC prevalence (P-trend = 0.05) in women
and AAC prevalence (P-trend < 0.01) in men. Partially and fully adjusted
models showed similar results. Though modest, these significant, independent
associations suggest that atherosclerosis and bone loss may be related.
Mol
Cell Endocrinol. 2008 Nov 21. [Epub ahead of print]
The role
of the brain in female reproductive aging Molecular and Cellular Endocrinology. The Endocrinology of Aging. Section I: Age-related changes
in endocrine function.
Departments
of Physiology and Biophysics,
In middle-aged
women, follicular depletion is a critical factor mediating the menopausal
transition; however, all levels of the hypothalamic-pituitary-gonadal (HPG) axis contribute to the age-related decline in
reproductive function. To help elucidate the complex interactions between the
ovary and brain during middle-age that lead to the onset of the menopause, we
utilize animal models which share striking similarities in reproductive
physiology. Our results show that during middle-age, prior to any overt
irregularities in estrous cyclicity,
the ability of 17beta-estradiol (E(2)) to modulate the cascade of neurochemical events required for preovulatory
gonadotropin-releasing hormone (GnRH)
release and a luteinizing hormone (LH) surge is diminished. Middle-aged female
rats experience a delay in and an attenuation of LH release in response to E(2). Additionally, although we do not observe a decrease in
GnRH neuron number until a very advanced age,
E(2)-mediated GnRH neuronal activation declines
during the earliest stages of age-related reproductive decline. Numerous
hypothalamic neuropeptides and neurochemical
stimulatory inputs (i.e., glutamate, norepinephrine
(NE), and vasoactive intestinal peptide (VIP) that
drive the E(2)-mediated GnRH/LH
surge appear to dampen with age or lack the precise temporal coordination
required for a specific pattern of GnRH secretion,
while inhibitory signals such as gamma-aminobutyric
acid (GABA) and opioid peptides remain unchanged or
elevated during the afternoon of proestrus. These
changes, occurring at the level of the hypothalamus, lead to irregular estrous cycles and, ultimately, the cessation of
reproductive function. Taken together, our studies indicate that the
hypothalamus is an important contributor to age-related female reproductive
decline.
Ginecol Obstet
Mex. 2008 Oct;76(10):571-5.
Hypothyroidism
associated to menopause symptoms worsening change with thyroid substitution
therapy
Hernández Valencia M, Córdova Pérez N, Zárate A, Basurto L, Manuel Apolinar
L, Ruiz M, Vargas C, Vargas A.
Hospital de Especialidades, Centro Médico Nacional Siglo XXI,
IMSS.
mhernandezvalencia@prodigy.net.mx
BACKGROUND:
Hypothyroidism is more frequent in woman and raises
with age. It is not clear why do they have greater susceptibility, but it seems
to be related with levels of estrogens and hormonal changes. OBJECTIVE: To evaluate
changes in symptoms of women with menopause and hypothyroidism after receiving
hypothyroidism therapy and later hormonal therapy. PATIENTS AND METHODS:
Longitudinal, descriptive and comparative study. Two groups were formed: one
with 27 patients with hypothyroidism diagnoses and menopause, and the other
with 27 menopausal patients matched by age. Appraisal criterion of hormonal
therapy efficacy was Greene scale. Levotiroxine was
employed as hypothyroidism therapy, at doses required to get euthyroidism in each patient. RESULTS: Basal climacteric
symptoms' intensity was higher in patients with menopause and hypothyroidism,
which decrease significantly (p < 0.05) after hypothyroidism therapy.
CONCLUSIONS: Climacteric symptoms are more intense in patients with
hypothyroidism, but they fall when euthyroidism is
maintained. These changes in thyroid function can be associated to changes in
estrogens concentrations, and therefore in direct relation to TRH neurohormone (thyroid releasing hormones).
Ginecol Obstet
Mex. 2008 Oct;76(10):610-4.
Relation between
hormonal therapy and tibolone with SERMs in
postmenopausal women's myomes growth
Unidad Médica de Alta Especialidad, Hospital de Ginecobstetricia Luis Castelazo
Ayala, IMSS, DF Mexico. scarranzal@mexis.com
Myomas (both leiomyomas and fibromas) are the
most frequent benign uterine tumors in women, they
can be found in 77% of hysterectomy specimens. There are reports that previous
hormonal therapy (estrogen-progestin), more than five
years, is associated with high risk (fourfold higher) of leiomyomas.
A study in patients without myomas demonstrated this
type tumors production (5%) after receiving transdermical-oral hormonal combination during 24 months,
and they were absent in patients with only oral therapy. Hormonal therapy
increases size and quantity of myomas, or has a
neutral effect. This therapy looks like having a higher effect in myoma growth. Tibolone has a
neutral effect in myoma volume, and typical doses of raloxifene have no influence in its growth. If
postmenopausal women with myomas need some therapy to
control symptoms, hormonal therapy is not the best option; however, in
asymptomatic patients tibolone is more suitable and raloxifene can be prescribed.
Med
Princ Pract. 2009;18(1):43-7. Epub 2008 Dec 4.
Effects of hormone
replacement therapy on insulin resistance and platelet function
tests.
Saraç F, Saydam G, Sahin F, Oztekin K, Saygili F, Tüzün M, Yilmaz C.
Department
of Endocrinology and Metabolism,
OBJECTIVES: The
aim of this study was to evaluate measures of insulin resistance and platelet
function in postmenopausal women with oral or transdermal
hormone replacement therapy (HRT). SUBJECTS AND METHODS: Eighty women divided
into four groups of 20 each were enrolled in the study. Group 1: postmenopausal
hysterectomized women who received only transdermal estradiol (13.9
mg/12.5 cm(2)); group 2: women with intact uterus who
were treated with estrogen-progestin combination
(HRT); group 3: postmenopausal women who were treated with the selective estrogen receptor modulator tibolone,
and group 4: women who were not taking any drugs for HRT were chosen as a
control group (group 4). RESULTS: In group 2, homeostasis model assessment of
insulin resistance and fasting insulin levels were 2.90 +/- 0.37 and 9.3 +/- 3.0 microU/ml, respectively,
prior to administration of HRT. These levels were reduced to 1.91 +/- 0.41 (p =
0.001) and 7.1 +/- 2.7 microU/ml (p = 0.002),
respectively, after drug therapy. Mean levels of high-sensitivity C-reactive
protein (hsCRP) were decreased with HRT only in group
2 (p = 0.002). No changes for biochemical and hematological
parameters were observed in the other groups. Platelet function tests showed no
differences after HRT in any group. CONCLUSIONS: Estrogen-progestin
combination HRT decreased measures of insulin resistance and hsCRP levels, but had no effect on platelet function tests
in postmenopausal women.
Semana del 17 al 23 de Diciembre 2008
J Hum Hypertens.
2008 Dec 18. [Epub ahead of
print]
Dietary
intake, blood pressure and osteoporosis.
Woo J, Kwok T, Leung J, Tang N.
1Department of
Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Both hypertension
and osteoporosis have common underlying nutritional aetiology, with regards to
dietary cations intake. We tested the hypothesis that
sodium intake reflected in urinary Na/Cr and blood pressure would be negatively
associated with bone mineral density (BMD), whereas other cations
may have opposite associations. Subjects were part of a study of bone health in
4000 men and women aged 65 years and over. A total of 1098 subjects who were
not on antihypertensive drugs or calcium supplements and who provided urine
samples were available for analysis. Logistic regression was used to examine
associations between total hip and lumbar spine BMD, age, gender, body mass
index (BMI), urinary Na/Cr, K/Cr, calcium and magnesium intake, systolic blood
pressure and diastolic blood pressure. Total hip BMD was inversely associated
with age, being female and urinary Na/Cr, and positively associated with BMI,
urine K/Cr and dietary calcium intake. Lumbar spine BMD was inversely
associated with being female and urinary Na/Cr, and positively associated with
BMI, dietary calcium intake and SBP. We conclude that sodium intake, reflected
by urinary Na/Cr, is the major factor linking blood pressure and osteoporosis
as shown by the inverse relationship with BMD. The findings lend further
emphasis to the health benefits of salt reduction in our population both in
terms of hypertension and osteoporosis.
Menopause. 2008
Dec 13. [Epub ahead of print]
Raloxifene use in
clinical practice: efficacy and safety.
Goldstein SR, Duvernoy CS, Calaf J, Adachi JD, Mershon JL, Dowsett SA, Agnusdei D, Stuenkel CA.
New
York University School of Medicine, New York, NY; Eli Lilly and Company,
Indianapolis, IN.
OBJECTIVE AND
DESIGN:: In this article, we provide an
interdisciplinary concise review of the effects of raloxifene
on breast, bone, and reproductive organs, as well as the adverse events that
may be associated with its use. RESULTS:: Raloxifene has been shown to prevent osteoporosis in
postmenopausal women (PMW) with low bone mass and prevent vertebral fractures
in those with osteoporosis/low bone mass; it has not been shown to reduce the
risk of nonvertebral fractures. Raloxifene
reduces the risk of invasive breast cancer in PMW with osteoporosis or at high
risk of breast cancer. The risk of venous thromboembolism
has been consistently shown to be increased with raloxifene,
so it should not be used in women at high risk of venous thromboembolism.
Although raloxifene does not increase, nor decrease,
the risk of coronary or stroke events overall, in the raloxifene
trial of PMW at increased risk of coronary events, the incidence of fatal
stroke was higher in women assigned raloxifene versus
placebo. CONCLUSIONS:: Based on its approved
indications, it is appropriate to prescribe raloxifene
to prevent or treat osteoporosis, as well as to reduce the risk of invasive
breast cancer in PMW with osteoporosis or at high risk of breast cancer. Women
at increased risk of both fracture and invasive breast cancer are those most
likely to receive a dual benefit with raloxifene.
Decision making must involve the incorporation of the woman's personal feelings
about the risks and benefits of raloxifene therapy,
balanced with her interest in reducing risk of fractures and breast cancer
through pharmacological intervention.
Arterioscler Thromb Vasc
Biol. 2008 Dec 18. [Epub ahead of print]
Certain Progestins Prevent the Enhancing Effect of 17-beta Estradiol on NO-Mediated Inhibition of Platelet Aggregation
by Endothelial Cells.
Zerr-Fouineau M, Jourdain M, Boesch C, Hecker M, Bronner C, Schini-Kerth VB.
Département de Pharmacologie et Physico-Chimie,
UMR CNRS 7175, Institut Gilbert Laustriat,
Université Louis Pasteur Strasbourg I, Illkirch, France; and the Institute of Physiology and Pathophysiology, University of Heidelberg, Germany.
OBJECTIVE: Estro-progestin treatments have been associated with an
increased risk of thromboembolic events in
postmenopausal women. This study examined whether progestins
affect the stimulatory effect of estrogens on the endothelial formation of
nitric oxide (NO), a potent antithrombotic factor. METHODS AND RESULTS:
Experiments were performed with human endothelial cells. Endothelial NO synthase (eNOS) and GTP cyclohydrolase I (GTPCH I) mRNA expression was assessed by
RT-PCR, eNOS protein by Western blotting, NO
formation by electron spin resonance spectroscopy, and platelet aggregation by
an aggregometer. Medroxyprogesterone
acetate (MPA), progesterone, levonorgestrel, and nomegestrol acetate prevented the 17beta-estradiol
(17beta-E)-induced expression of eNOS mRNA and
protein. MPA and progesterone reduced the 17beta-E-induced formation of NO and potentiation of the inhibitory effect of endothelial cells
on platelet aggregation whereas levonorgestrel and nomegestrol acetate were without effect. Moreover, MPA and
progesterone prevented the 17beta-E-induced expression of GTPCH I mRNA. Mifepristone, a glucocorticoid
and progesterone receptor antagonist, and L-sepiapterin
prevented the inhibitory effect of MPA and progesterone on platelet
aggregation. CONCLUSIONS: Certain progestins,
including MPA, attenuate the 17beta-E-induced NO-mediated inhibition of
platelet aggregation by endothelial cells through preventing both eNOS and GTPCH I expression most likely via activation of glucocorticoid receptors.
Reprod Sci. 2008 Dec;15(10):984-92.
Review article: a
new approach to menopausal therapy: the tissue selective estrogen
complex.
Women's Health and
Musculoskeletal Biology Research, Discovery Liaison, Wyeth Research,
Collegeville,
A new approach to menopausal
therapy is the tissue selective estrogen complex or
the pairing of a selective estrogen receptor
modulator with estrogens. The clinical profile of a tissue selective estrogen complex will result from the blended
tissue-selective activities of its components. An appropriate tissue selective estrogen complex may provide the therapeutic benefits of
estrogens and selective estrogen receptor modulators
with better tolerability and safety than either therapy alone. An ideal
menopausal therapy would reduce the number and severity of hot flashes,
effectively treat vulvar-vaginal atrophy and its
symptoms, prevent and treat menopausal osteoporosis, and have favorable effects on lipoprotein profiles, while at the
same time would not stimulate the endometrium, not
cause uterine bleeding, not increase the risk of vascular events, not be
associated with breast pain or tenderness, and potentially reduce breast cancer
incidence. Here, we introduce the concept of a tissue selective estrogen complex and the rationale for its development as a
next generation menopausal therapy.
Womens Health (Lond Engl). 2008 Sep;4(5):445-7.
Vitamin
D status and response to antiosteoporotic therapy.
University of Liège, Department of Public Health, Epidemiology &
Health Economics, CHU Sart-Tilman, Bât B23, 4000 Liège, Belgium.
olivier.bruyere@ulg.ac.be
Evaluation of: Adami S, Giannini S, Bianchi G et al.: Vitamin D status and response to treatment
in post-menopausal osteoporosis. Osteoporos. Int. (2008) (Epub
ahead of print). All recent osteoporosis guidelines recommend that
patients taking treatments for osteoporosis (i.e., bisphosphonates)
should be supplemented with vitamin D and calcium. However, the bone response
(i.e., bone mineral density change and fractures incidence) to bisphosphonates therapy in relation to vitamin D intake in
clinical practice is unknown. In a recent retrospective study, 1515 women with
postmenopausal osteoporosis under antiresorptive treatment
were classified as vitamin D deficient or vitamin D repleted,
according to risk factors or the level of 25 hydroxy
vitamin D above or below 50 nmol/l.
The change in bone mineral density remained significantly higher in vitamin D-repleted compared with vitamin D-deficient women. Moreover,
the adjusted odds ratio for incident fractures in vitamin D-deficient as
compared with vitamin D-repleted women was 1.77 (95%
CI: 1.20-2.59; p = 0.004).
Diabetes. 2008
Dec 18. [Epub ahead of print]
Beta and alpha Cell Dysfunction in Subjects
Developing Impaired Glucose Tolerance. Outcome
of a 12 Year Prospective Study in Postmenopausal Caucasian Women.
Department
of Clinical Sciences in Lund, Division of Medicine, Lund University.
OBJECTIVE: This
study assessed insulin and glucagon secretion in relation to insulin
sensitivity in Caucasian women who develop impaired glucose tolerance (IGT)
versus those who maintain normal glucose tolerance (NGT) over a 12 year period.
RESEARCH DESIGN AND METHODS: At baseline and after three, eight and twelve
years, glucose tolerance (75 g OGTT), insulin sensitivity (euglycemic,
hyperinsulinemic clamp) and insulin and glucagon
secretion (2 to 5-min responses to 5g arginine iv at
fasting, 14 and >25 mmol/l glucose) were
determined in 53 healthy Caucasian women (58 years at baseline) whom all had
NGT at baseline. RESULTS: During the twelve year period, 26 subjects developed
IGT whereas the remaining 27 subjects maintained NGT throughout the twelve-year
period. Subjects developing IGT had lower insulin sensitivity than those
maintaining NGT in the tests preceding diagnosis of IGT (P<0.05 or less).
When judged in relation to insulin sensitivity, ss-cell
glucose sensitivity and maximal insulin secretion were lower in those who later
developed IGT than in those maintaining NGT at all tests (P<0.05 or less).
Furthermore, subjects who developed IGT had defective suppression of glucagon
secretion by glucose in the test preceding diagnosis of IGT when they still had
NGT (P<0.05 or less). CONCLUSION: ss- and
alpha-cell dysfunction are evident several years before diagnosis of IGT, and
islet dysfunction is manifested as impaired glucose sensitivity of the ss- and alpha-cells and reduced maximal insulin secretion.
J Neuroendocrinol. 2009 Jan;21(1):77-81.
Progesterone
attenuates oestrogen neuroprotection via downregulation of oestrogen receptor expression in cultured
neurones.
Neuroscience
Graduate Programme and Davis School of Gerontology, University of Southern
California, Los Angeles, CA, USA.
Recent findings
indicate that progesterone can attenuate the beneficial neural effects of
oestrogen. In the present study, we investigated the hypothesis that
progesterone can modulate oestrogen actions by regulating the expression and
activity of oestrogen receptors, ERalpha and ERbeta. Our studies in cultured neurones demonstrate that
progesterone decreases the expression of both ERalpha
and ERbeta and, as a consequence, also reduces both
ER-dependent transcriptional activity and neuroprotection.
These results identify a potential mechanism by which progesterone antagonises
neural oestrogen actions, a finding that may have important implications for
hormone therapy in postmenopausal women.
Drugs. 2008;68(18):2591-600.
doi:
10.2165/0003495-200868180-00005.
Aromatase
inhibitor-associated bone loss : clinical
considerations.
The Comprehensive
Breast Health Services, Arthur G. James Cancer Hospital and Richard J. Solve
Research Institute, The Ohio State University Medical Center,
Columbus, Ohio, USA.
Aromatase
inhibitors (AIs) are standard treatments for postmenopausal women with estrogen responsive breast cancers. The mechanism of AIs,
inhibition of the aromatase enzyme that causes
decreases in endogenous estrogens, is responsible for bone loss and increased
fractures. Screening and prevention of AI-induced bone loss closely follows the
standard recommendations for postmenopausal osteoporosis. Lifestyle changes
such as increasing physical activity and weight-bearing exercise, stopping
smoking, and taking adequate amounts of daily calcium and vitamin D promote
bone and overall health. Bisphosphonates are specific
inhibitors of osteoclasts and reduce bone loss in
women treated with AIs. The optimal dose administration schedule and duration
of bisphosphonate treatment for AI-induced bone loss
remains undefined.
Climacteric. 2008
Dec 11:1-15. [Epub ahead of print
Psychosocial
work environment and lifestyle as related to lipid profiles in perimenopausal women.
Evolahti A, Hultcrantz M, Collins A.
Department
of Clinical Neuroscience, Karolinska Institute, Stockholm.
Objective The aim of the study was to characterize lipid profiles of perimenopausal women and to relate these to the
psychosocial work environment and lifestyle using a longitudinal design.
Methods A population-based sample of 107 women, aged
47-53 years, participated in a baseline study and in a follow-up 2 years later.
Psychosocial work stress was measured using the Job Content Questionnaire. The
women also completed a health questionnaire and participated in a psychological
interview. Fasting blood samples were analyzed for concentrations of total
cholesterol, high and low density lipoprotein (HDL, LDL) cholesterol and
triglycerides. Results Multiple regression analyses showed that work control
was a significant predictor of higher HDL cholesterol (p < 0.05), lower LDL
cholesterol/HDL cholesterol ratio (p < 0.01) and lower total cholesterol/HDL
cholesterol ratio (p < 0.01). Job strain predicted a higher LDL
cholesterol/HDL cholesterol ratio (p < 0.01) and higher total cholesterol/HDL
cholesterol ratio (p < 0.05). Lifestyle variables smoking, body mass index
and waist/hip ratio predicted an unfavorable lipid
profile, whereas alcohol consumption predicted a favorable
lipid profile. Age but not menopausal status was associated with lipid levels
at baseline and on follow-up. Use of hormone replacement therapy was a
significant predictor of lower cholesterol levels in the multivariate analyses.
Conclusions Our results demonstrated a significant
association between the psychosocial work environment and women's
cardiovascular health at menopause. Job strain was a significant contributor to
an atherogenic lipid profile, whereas work control
predicted a favorable profile. Hence, the argument is
now compelling that psychosocial factors should be
included in the risk profiles for cardiovascular disease in women.
Nucl Recept
Signal. 2008;6:e010. Epub
2008 Nov 26
Selective
androgen receptor modulators in preclinical and clinical development.
Narayanan R, Mohler ML, Bohl CE, Miller DD, Dalton JT.
Preclinical
Research and Development, GTx, Inc., Memphis,
Tennessee, USA
Androgen receptor
(AR) plays a critical role in the function of several organs including primary
and accessory sexual organs, skeletal muscle, and bone, making it a desirable
therapeutic target. Selective androgen receptor modulators (SARMs) bind to the
AR and demonstrate osteo- and myo-anabolic
activity; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents produce less of a growth effect on
prostate and other secondary sexual organs. SARMs provide therapeutic
opportunities in a variety of diseases, including muscle wasting associated
with burns, cancer, or end-stage renal disease, osteoporosis, frailty, and hypogonadism. This review summarizes the current standing
of research and development of SARMs, crystallography of AR with SARMs,
plausible mechanisms for their action and the potential therapeutic indications
for this emerging class of drugs.
J Nutr. 2008
Dec 11. [Epub ahead of print]
Higher Intakes of Vegetables
and Vegetable-Related Nutrients Are Associated with Lower Endometrial Cancer
Risks.
Yeh M, Moysich KB, Jayaprakash V, Rodabaugh KJ, Graham S, Brasure JR, McCann SE.
Department
of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY
14263.
A limited number of
studies have investigated diet in association with endometrial cancer (EC). We
examined the association between intakes of selected food groups and nutrients
with EC risk among 541 women with histologically
confirmed EC and 541 women with an intact uterus and noncancer
diagnoses seen at Roswell Park Cancer Institute between 1982 and 1998.
Self-reported dietary and other epidemiologic data were collected by
questionnaire. Unconditional logistic regression was used to estimate odds
ratios (OR) and 95% CI, adjusting for age, BMI, hormone replacement therapy
use, cigarette smoking, lifetime duration of menstruation, and total energy
intake. We observed significant inverse associations for women in the highest
vs. lowest quartiles of intake of total vegetables (OR, 0.51; 95% CI,
0.34-0.75), vitamin E (OR, 0.44; 95% CI, 0.27-0.70), dietary fiber (OR, 0.60; 95% CI, 0.39-0.94), beta-carotene (OR,
0.55; 95% CI, 0.37-0.82), lutein (OR, 0.52; 95% CI,
0.34-0.78), and folate (OR, 0.57; 95% CI, 0.36-0.91).
Our results support that vegetables and related nutrients are associated with
decreased risk of EC.
Semana del 24 al 30 de Diciembre 2008
Obstet Gynecol.
2009 Jan;113(1):74-80.
Postmenopausal
estrogen-containing hormone therapy and the risk of
breast cancer.
Jick SS, Hagberg KW, Kaye JA, Jick H.
Boston
University School of Medicine, Lexington, Massachusetts.
OBJECTIVE:: To investigate the relation of various estrogen-containing hormone therapies to the risk of breast
cancer, emphasizing the use of the combination of estrogen
and testosterone. METHODS:: Using information from a large U.S.-based claims
database, we conducted a case-control study in women aged 50 to 64 years who
had a first-time diagnosis of breast cancer to estimate the effect in users of
conjugated estrogen alone, conjugated estrogen plus progestin, esterified
estrogen with methyltestosterone,
or esterified estrogen with
methyltestosterone plus progestin, compared with
nonusers. Four controls were matched to each case on year of birth and index
date. Odds ratios (ORs) were calculated using conditional logistic regression.
RESULTS:: We identified 4,515 cases and 18,058 matched
controls. The OR for users of estrogen alone compared
with the nonusers was 0.96 (95% confidence interval [CI] 0.88-1.06; 667 cases
and 2,900 controls); for users of conjugated estrogen
plus progestin, it was 1.44 (95% CI 1.31-1.58; 712 cases and 2,087 controls);
and for users of esterified estrogen
with methyltestosterone and esterified
estrogen with methyltestosterone
plus progestin, the ORs were 1.08 (95% CI 0.86-1.36; 98 cases and 380 controls)
and 1.69 (95% CI 1.03-2.79; 22 cases and 55 controls), respectively. There was
an increased risk among conjugated estrogen plus
progestin users of 48 months or more (OR 3.10, 95% CI 2.38- 4.04; 111 cases and
149 controls). CONCLUSION:: There is no materially
increased risk of breast cancer in users of estrogen
alone or esterified estrogen
with methyltestosterone compared with nonusers. There
is an increased risk among those using conjugated estrogen
plus progestin. In particular, the risk of breast cancer in women who used
conjugated estrogen plus progestin for 4 or more
years is approximately three times higher than in women who are not exposed to
hormone therapy, so that the background incidence rate for women aged 50 to 64
years, which is around 3 per 1,000, would be increased to approximately 9 per
1,000 in women aged 50 to 64 years who have taken conjugated estrogen plus progestin for 48 months or more.
Obstet Gynecol. 2009 Jan;113(1):65-73.
Breast
cancer risk in postmenopausal women using estradiol-progestogen
therapy.
Lyytinen H, Pukkala E, Ylikorkala O.
Department
of Obstetrics and Gynecology, Helsinki University
Central Hospital, Helsinki, Finland.
OBJECTIVE:: To estimate the risk for breast cancer in Finnish women
using postmenopausal estradiol (E2)-progestogen therapy. METHODS:: All Finnish women over 50
years using E2-progestogen therapy for at least 6 months in 1994-2005
(N=221,551) were identified from the national medical reimbursement register
and followed up for breast cancer incidence (n=6,211 cases) through the Finnish
Cancer Registry to the end of 2005. The risk for breast cancer in
E2-progestogen therapy users was compared with that in the general population.
RESULTS:: The standardized incidence ratio for all
types of breast cancer was not elevated within the first 3 years of use, but it
rose to 1.31 (95% confidence interval 1.20-1.42) for the use from 3-5 years and
to 2.07 (1.84-2.30) with 10 or more years of use. Exposure to sequential progestogen for 5 years or more was accompanied with a
lower risk elevation (1.78, 1.64-1.90) than exposure to continuous use (2.44,
2.17-2.72). Oral and transdermal use of
E2-progestogen therapy was associated with comparable risk elevations for
breast cancer. The use of norethisterone acetate was
accompanied with a higher risk after 5 years of use (2.03, 1.88-2.18) than that
of medroxyprogesterone acetate (1.64, 1.49-1.79). The
risk of lobular breast cancer increased sooner than that for ductal cancer and was detectable for E2-progestogen therapy
use less than 3 years (1.35, 1.18-1.53). There was no excess risk of breast
cancer with distant metastases among E2-progestogen therapy users. CONCLUSION:: The use of E2-progestogen therapy is associated with an
increased risk for breast cancer after 3 years of use. The risk is lower for
sequential than for continuous use, but comparable for oral and transdermal use. The risk elevation may not be uniform for
all progestogens
Womens Health (Lond Engl). 2009 Jan;5:39-48.
Long-term effects of bilateral oophorectomy
on brain aging: unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging.
Rocca WA, Shuster LT, Grossardt BR, Maraganore DM, Gostout BS, Geda YE, Melton LJ.
Division
of Epidemiology, Department of Health Sciences Research, Mayo Clinic, MN, USA.
In the Mayo Clinic
Cohort Study of Oophorectomy and Aging, women who had
both ovaries removed before reaching natural menopause experienced a long-term
increased risk of parkinsonism, cognitive impairment
or dementia, and depressive and anxiety symptoms. Here, we discuss five
possible mechanistic interpretations of the observed associations; first, the
associations may be non-causal because they result from the confounding effect
of genetic variants or of other risk factors; second, the associations may be
mediated by an abrupt reduction in levels of circulating estrogen;
third, the associations may be mediated by an abrupt reduction in levels of
circulating progesterone or testosterone; fourth, the associations may be
mediated by an increased release of gonadotropins by
the pituitary gland; and fifth, genetic variants may modify the hormonal
effects of bilateral oophorectomy through simple or
more complex interactions. Results from other studies are cited as evidence for
or against each possible mechanism. These putative causal mechanisms are
probably intertwined, and their clarification is a research priority.
Drugs Aging. 2009;26(1):23-36. doi:
10.2165/0002512-200926010-00002.
Black cohosh for the management of menopausal symptoms: a
systematic review of clinical trials.
Palacio C, Masri G, Mooradian AD.
Department
of Medicine, University of Florida, College of Medicine, Jacksonville, Florida,
USA.
Alternative
medicine preparations represent a significant industry worldwide. Black cohosh (Cimicifuga racemosa), a buttercup plant grown in North America, is one
such popular preparation for the treatment of menopausal symptoms. Because the
proportion of women experiencing climacteric symptoms is high, black cohosh merits further study as to its efficacy and safety.
Convincing evidence for its efficacy in this setting remains to be
demonstrated. The purpose of this systematic review was to assess the current
literature on the benefits of black cohosh for women
experiencing climacteric symptoms. To this end, a PubMed
search was conducted on 1 November 2007 using the search terms 'black cohosh' AND 'menopause'. The search was limited to
randomized controlled trials in the English language involving adults. Several
additional reviews dealing with alternative therapies for menopause were
included to capture additional older and non-English language literature.
Ultimately, 16 studies eligible for review were identified. Many of the studies
had conflicting results. Methodological flaws included lack of uniformity of
the drug preparation used, variable outcome measures and lack of a placebo
group. The benefits of black cohosh in the management
of climacteric symptoms remain to be proven. Case studies suggest an additional
unexplored area of adverse events that also needs to be addressed.
Maturitas. 2008 Dec 19. [Epub ahead of print]
Effect of raloxifene
and low-dose percutaneous 17beta-estradiol on
menopause symptoms and endometrium-A randomized
controlled trial.
Valiati B, Capp E, Edelweiss MI, de Freitas FM, Wender MC.
Programa de
Pós-Graduação em Medicina: Ciências Médicas, Hospital de Clínicas de Porto
Alegre, Brazil; Serviço de Ginecologia e Obstetrícia,
Hospital de Clínicas de Porto Alegre, Brazil.
OBJECTIVE: To
investigate the effects on climacteric symptoms and endometrium
of percutaneous low-dose 17beta-estradiol associated
with raloxifene in postmenopausal women. DESIGN:
randomized placebo-controlled study. METHOD: Fifty-two postmenopausal women
with moderate to severe hot flushes were randomized to receive either 60mg raloxifene (RLX; n=20), 0.5mg percutaneous
17beta-estradiol associated to 60mg raloxifene (RLX+E(2); n=16) or placebo (PLC; n=16). Climacteric symptoms (Kupperman index) and vaginal bleeding were evaluated. At
baseline and at the end of the study endometrial thickness was measured and
endometrial samples were collected for histological study. RESULTS: At
baseline, the mean Kupperman index was 23.7+/-1.8 in
RLX group, 22.9+/-1.9 in RLX+E(2) group and 22.6+/-1.9
in the placebo group (NS). After 3 months, there was a significant reduction in
Kupperman index mean values in both groups, but no
statistical difference was observed between groups. However, RLX+E(2) and placebo were significantly superior to RLX in
reducing hot flush severity (p<0.05). Endometrial thickness did not change
in both groups. The association of percutaneous
low-dose 17beta-estradiol to raloxifene was not
associated with proliferation of endometrium neither
in hysteroscopies nor in endometrial biopsies at the
third month of treatment. No vaginal bleeding was reported during the study.
CONCLUSIONS: The association of percutaneous low dose
of 17beta-estradiol with raloxifene exerted favorable effects on hot flushes severity of postmenopausal
women, providing a safe profile in endometrium at
least in short-term therapy.
J Hum Hypertens. 2008 Dec 25. [Epub ahead of print]
A comprehensive
review on salt and health and current experience of worldwide salt reduction
programmes.
1Blood
Pressure Unit, Cardiac and Vascular Sciences, St George's, University of
London, London, UK.
Cardiovascular
disease (CVD) is the leading cause of death and disability worldwide. Raised
blood pressure (BP), cholesterol and smoking, are the major risk factors. Among
these, raised BP is the most important cause, accounting for 62% of strokes and
49% of coronary heart disease. Importantly, the risk is throughout the range of
BP, starting at systolic 115 mm Hg. There is strong evidence that our current
consumption of salt is the major factor increasing BP and thereby CVD.
Furthermore, a high salt diet may have direct harmful effects independent of
its effect on BP, for example, increasing the risk of stroke, left ventricular
hypertrophy and renal disease. Increasing evidence also suggests that salt
intake is related to obesity through soft drink consumption, associated with
renal stones and osteoporosis and is probably a major cause of stomach cancer.
In most developed countries, a reduction in salt intake can be achieved by a
gradual and sustained reduction in the amount of salt added to food by the food
industry. In other countries where most of the salt consumed comes from salt
added during cooking or from sauces, a public health campaign is needed to
encourage consumers to use less salt. Several countries have already reduced
salt intake, for example, Japan (1960-1970), Finland (1975 onwards) and now the
United Kingdom. The challenge is to spread this out to all other countries. A
modest reduction in population salt intake worldwide will result in a major
improvement in public health.
Atherosclerosis. 2008 Nov 18. [Epub ahead of print]
Circulating
oxidized LDL levels, current smoking and obesity in postmenopausal women.
Kassi E, Dalamaga M, Faviou E, Hroussalas G, Kazanis K, Nounopoulos C, Dionyssiou-Asteriou A.
Department of
Biological Chemistry and Department of Clinical Biochemistry, Medical School,
University of Athens, 11 Korinthou Str., 14564 Kifisia, Athens, Greece.
OBJECTIVE: The aim
of the present study was to estimate circulating oxidized low-density
lipoprotein (oxLDL) levels in postmenopausal women
and evaluate their association with obesity and smoking status. DESIGN AND
METHODS: The study included 135 postmenopausal women aged 52-75 years. Forty of
them were overweight (BMI 32.4+/-6.4) and non-smokers (Group A), 40
non-overweight (BMI 22.6+/-1.8) and smokers (Group B) and 55 non-overweight
(BMI 23.5+/-1.4) and non-smokers (Group C). oxLDL and antibodies against them (anti-oxLDL) were measured using ELISA. Serum total cholesterol,
LDL, HDL and triglycerides were measured in an automated analyzer. RESULTS:
Total cholesterol, LDL, HDL and oxLDL serum levels
were significantly elevated in Group A as compared to Group B or C, as well as oxLDL in Group B in comparison to Group C (p<0.001).
Triglycerides and anti-oxLDL were increased in Group
A in comparison to Group C (p=0.043 and 0.023). Total cholesterol, LDL,
triglycerides and anti-oxLDL did not differ between
Groups B and C, while HDL was decreased in Group B as compared to Group C
(p<0.001). A significant positive correlation was found between oxLDL and LDL in Group A (r=0.53, p<0.001) as well as in
Group C (r=0.955, p</=0.001) and a negative one between oxLDL
and HDL in Group C (r=-0.933, p<0.001). Regression analysis revealed that
obesity was a stronger predictor of LDL oxidation than smoking. CONCLUSIONS:
Postmenopausal obesity is involved in the process of LDL oxidation and appears
to be a stronger predictor of LDL oxidation than smoking. Future studies are needed to confirm
these associations.
Am J Obstet Gynecol. 2008 Dec
23. [Epub ahead of print]
A double-blind, randomly assigned, placebo-controlled
study of desvenlafaxine efficacy and safety for the
treatment of vasomotor symptoms associated with menopause.
Archer DF, Seidman L, Constantine GD, Pickar JH, Olivier S.
Clinical
Research Center, Eastern Virginia Medical School,
Norfolk, VA.
OBJECTIVE: The
objective of the study was to assess the efficacy and safety of desvenlafaxine (administered as desvenlafaxine
succinate) for menopausal vasomotor symptoms. STUDY
DESIGN: Postmenopausal women (n = 458) experiencing 50 or more moderate to
severe hot flushes per week received desvenlafaxine
100 or 150 mg/d, with titration at therapy initiation, or placebo. Hot flush
number and severity were assessed at weeks 4 and 12. Safety data were collected
throughout the trial. RESULTS: Desvenlafaxine 100 and
150 mg/d significantly reduced the number of hot flushes compared with placebo
at weeks 4 and 12 (all P </= .012), achieving 65.4% and 66.6% reductions
from baseline at week 12, respectively (placebo, 50.8%). Hot flush severity and
number of nighttime awakenings were significantly
reduced at both time points (all P </= .048). Desvenlafaxine
groups reported significantly more adverse events compared with placebo during
week 1 only. No difference in discontinuations because of adverse events was
observed. CONCLUSION: Desvenlafaxine is an effective nonhormonal treatment for menopausal hot flushes. Dose titration improves initial tolerability.
J Immunol. 2009 Jan 1;182(1):371-378.
Estradiol
Increases IL-8 Secretion of Normal Human Breast Tissue and Breast Cancer In Vivo.
Linköping University,
Faculty of Health Sciences, Div. Oncology, University Hospital, Linköping, Sweden.
IL-8 or CXCL8 has
been associated with tumor angiogenesis, metastasis,
and poor prognosis in breast cancer. Estrogen is
crucial in breast carcinogenesis and tumor
progression. Whether sex steroids affect IL-8 secretion of normal breast tissue
or breast cancer is not known. Several cell types in a tissue secrete IL-8.
Hence, regulatory mechanisms of IL-8 need to be investigated in whole tissue.
We used microdialysis to sample IL-8 in normal human
breast tissue in situ in pre- and postmenopausal women, preoperatively in
breast cancers of women, and in experimental breast cancer in mice. We found a
significant positive correlation between IL-8 and estradiol
in normal breast tissue and hormone-dependent breast cancer in vivo. Ex vivo, estradiol exposure increased the IL-8 secretion of normal
whole breast tissue in culture. In experimental breast cancer, estradiol increased IL-8 whereas the anti-estrogen tamoxifen inhibited the
secretion of IL-8 both in vitro and extracellularly
in vivo in tumors of nude mice. An anti-IL-8 Ab inhibited endothelial cell proliferation induced by
cancer cell produced IL-8 and tumors with low IL-8
levels exhibited decreased angiogenesis. Our results strongly suggest that estradiol has a critical role in the regulation of IL-8 in
normal human breast tissue and human breast cancer. IL-8 may present a novel
therapeutic target for estrogen driven breast
carcinogenesis and tumor progression.
Methods Mol Biol.
2009;472:343-60.
Mammographic
density: a heritable risk factor for breast cancer.
Boyd NF, Martin LJ, Rommens JM, Paterson AD, Minkin S, Yaffe MJ, Stone J, Hopper JL.
The
Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute,
Toronto, Canada.
The appearance of
the breast on mammography varies among women, reflecting variations in tissue
composition. Stroma and epithelium attenuate x-rays
more than fat and appear light on a mammogram, which we refer to here as " mammographic density, " while fat appears dark.
We show evidence that mammographic density is a strong risk factor for breast
cancer, and that risk of breast cancer is four to five times greater in women
with density in more than 75% of the breast, compared with those with little or
no density. Density in more than 50% of the breast may account for a large
proportion of breast cancers.Density is influenced by
age, parity, body mass index, and menopause but these factors account for only
20 - 30% of the variation in density in the population. Twin studies have shown
that percent mammographic density, at a given age, is highly heritable, and
that inherited factors explain 63% of the variance. Mammographic density has
the characteristics of a quantitative trait, and may be influenced by genes
that are easier to identify than those associated with breast cancer itself.
The genes that influence mammographic density may also be associated with risk
of breast cancer, and their identification is also likely to provide insights
into the biology of the breast, and to identify potential targets for
preventive strategies.
Methods Mol Biol. 2009;472:191-215.
Energy intake,
physical activity, energy balance, and cancer: epidemiologic evidence.
Public Health Agency
of Canada, Centre for Chronic Disease Prevention and Control, Ottawa, Ontario,
Canada.
Energy intake,
physical activity, and obesity are modifiable lifestyle factors. This chapter
reviews and summarizes the epidemiologic evidence on the relation of energy
intake, physical activity, and obesity to cancer. High energy intake may
increase the risk of cancers of colon -rectum, prostate (especially advanced
prostate cancer), and breast. However, because physical activity, body size,
and metabolic efficiency are highly related to total energy intake and
expenditure, it is difficult to assess the independent effect of energy intake
on cancer risk. There are sufficient evidences to support a role of physical
activity in preventing cancers of the colon and breast, whereas the association
is stronger in men than in women for colon cancer and in postmenopausal than in
premenopausal women for breast cancer. The evidence also suggests that physical
activity likely reduces the risk of cancers of endometrium,
lung, and prostate (to a lesser extent). On the other hand, there is little or
no evidence that the risk of rectal cancer is related to physical activity,
whereas the results have been inconsistent regarding the association between
physical activity and the risks of cancers of pancreas, ovary and kidney.
Epidemiologic studies provide sufficient evidence that obesity is a risk factor
for both cancer incidence and mortality. The evidence supports strong links of
obesity with the risk of cancers of the colon, rectum, breast (in postmenopau-sal women), endometrium,
kidney (renal cell), and adenocarcinoma of the esophagus. Epidemiologic evidence also indicates that
obesity is probably related to cancers of the pancreas, liver, and gallbladder,
and aggressive prostate cancer, while it seems that obesity is not associated
with lung cancer. The role of obesity in other cancer risks is unclear.
Expert Rev Anticancer Ther. 2009 Jan;9(1):51-60.
The NSABP Study of Tamoxifen and Raloxifene (STAR)
trial.
Division
of Hematology/Oncology,
In the Study of Tamoxifen and Raloxifene (STAR)
trial, postmenopausal women at increased risk of breast cancer received either
oral tamoxifen (20 mg/day) or raloxifene
(60 mg/day) over 5 years. There were an equal number of cases of invasive
breast cancer in women assigned to tamoxifen and raloxifene. There were fewer cases of noninvasive
breast cancer in the tamoxifen group than in the raloxifene group (risk ratio [RR]: 1.40; 95% confidence
interval [CI]: 0.98-2.02). There were more cases of uterine cancer with tamoxifen than with raloxifene
(RR: 0.62; 95% CI: 0.35-1.08). Thromboembolic events
occurred less often in the raloxifene group (RR:
0.70; 95% CI: 0.54-0.91) and there were fewer cataracts and cataract surgeries
in the women taking raloxifene (RR: 0.79; 95% CI:
0.68-0.92). The STAR trial has shown that raloxifene
is as effective as tamoxifen in reducing the risk of
invasive breast cancer and has a lower risk of adverse events but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers,
fractures, ischemic heart disease and stroke is similar for both drugs.