Selección
de Resúmenes de Menopausia
Semana del 26 de Noviembre al 2 de Diciembre 2008
Juan
Enrique Blümel. Departamento Medicina Sur. Universidad de
Chile
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
Selección de Resúmenes
de Menopausia
Semana del 3 al 9 de Diciembre 2008
Juan Enrique Blümel.
Departamento Medicina Sur. Universidad de Chile
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
Selección de Resúmenes
de Menopausia
Semana del 10 al 16 de Diciembre 2008
Juan Enrique Blümel.
Departamento Medicina Sur. Universidad de Chile
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.
Selección de Resúmenes
de Menopausia
Semana del 17 al 23 de Diciembre 2008
Juan Enrique Blümel.
Departamento Medicina Sur. Universidad de Chile
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.
Selección de Resúmenes
de Menopausia
Semana del 24 al 30 de Diciembre 2008
Juan Enrique Blümel.
Departamento Medicina Sur. Universidad de Chile
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.