Selección
de Resúmenes de Menopausia
Noviembre 2009
Juan Enrique Blümel.
Departamento Medicina Sur. Universidad
de Chile
Semana del 25 de Noviembre al 1 de Diciembre de 2009
Menopause. 2009 Nov 24. [Epub
ahead of print]
Dysregulation
of subcutaneous adipose tissue blood flow in overweight postmenopausal women.
Andersson J, Sjöström LG, Karlsson M, Wiklund U, Hultin M, Karpe F, Olsson T.
From
the Departments of 1Public Health and Clinical Medicine, 2Biomedical
Engineering and Informatics, and 3Surgical and Perioperative Sciences,
Anesthesiology and Intensive Care, Umeå University Hospital, Umeå, Sweden; and
4NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK.
OBJECTIVE::
A putative link between abdominal obesity and metabolic-vascular complications
after menopause may be due to a decreased adipose tissue blood flow (ATBF). The
present work aimed to analyze possible changes in ATBF with being overweight
and menopausal and its putative link to endothelial dysfunction and autonomic
nervous system balance. METHODS:: Forty-three healthy women were classified
into four groups according to weight and menopause status. The ATBF was measured
by xenon washout while fasting and after oral glucose intake. The nitric oxide
synthase inhibitor asymmetric dimethylarginine was used as a marker of
endothelial function and heart rate variability-estimated autonomic nervous
system activity. RESULTS:: Fasting ATBF was decreased in both overweight groups
(P = 0.044 and P = 0.048) versus normal-weight premenopausal women.
Normal-weight and overweight postmenopausal women exhibited lower maximum ATBF
compared with normal-weight premenopausal women (P = 0.015 and P = 0.001,
respectively), and overweight postmenopausal women exhibited lower maximum ATBF
compared with normal-weight postmenopausal women (P = 0.003). A negative
correlation was found between fasting ATBF and asymmetric dimethylarginine (P =
0.015), whereas maximum ATBF was negatively associated with
sympathetic-parasympathetic nervous system balance (ratio of the power of the
low frequency to the power of the high frequency; P = 0.002). CONCLUSIONS::
Loss of ATBF flexibility in overweight postmenopausal women may contribute to
the metabolic dysfunction seen in this group of women.
Fertil Steril. 2009 Nov 23. [Epub
ahead of print]
Racial
and ethnic differences in reproductive potential across the life cycle.
Division of Infertility and Reproductive
Endocrinology, University of Pennsylvania Medical School, Philadelphia,
Pennsylvania.
OBJECTIVE:
To review variations in specific reproductive health outcomes by race and
ethnicity. A growing number of reports have explored potential gaps in the
quality of reproductive health and healthcare across racial and ethnic groups.
Diverse results from numerous investigations have made it challenging for
practitioners to confirm the significance of these disparities. METHOD(S):
Three specific areas of the reproductive life cycle were examined: pubertal
onset, outcomes from treatment with assisted reproductive technologies (ART),
and the menopausal transition. These areas were selected as they encompass a
continuum of events across the reproductive life span of women. Outcomes were
compared in black, white, Asian, and Hispanic women. Medline searches querying
on keywords puberty, IVF, ART, menopause, menopausal symptoms, racial
disparity, race, Asian, Japanese, Chinese, African American, black, Hispanic,
and Latino were performed to isolate relevant publications for review.
RESULT(S): Differences across race and ethnicity were noted in each clinical
endpoint. The most notable findings included earlier puberty in blacks and
Hispanics compared with whites, significantly lower live birth rates after ART
in all racial and ethnic groups compared with whites, and differences in
perimenopausal symptomatology and possibly timing in various racial/ethnic
groups compared with whites. Additional research is needed to completely
unravel the full significance and basic underpinnings of these disparities.
Some of the limitations of the current state of the literature in drawing
conclusions about the independent effect of race/ethnicity on reproductive
disparities include small samples sizes in some studies, inconsistencies in the
characterization of racial/ethnic groups, and incomplete control of potential
confounding. CONCLUSION(S): Race and ethnicity appear to be important
correlates of outcomes from the initiation of reproduction functioning through
to its conclusion. The ultimate goal of identifying racial disparities in
reproduction is to isolate the basic determinants of disparities and formulate
strategies to improve outcomes for women at risk. The differences demonstrated
in this review of the literature could represent environmental, sociocultural,
and/or genetic correlates of race that influence these important milestones.
Obstet Gynecol. 2009
Dec;114(6):1197-204.
Endometrial
cancer in postmenopausal women using estradiol-progestin therapy.
Jaakkola S, Lyytinen H, Pukkala E, Ylikorkala O.
From
the 1Department of Obstetrics and Gynecology, Helsinki University Central
Hospital, Helsinki; 2Finnish Cancer Registry, Institute for Statistical and
Epidemiological Cancer Research, Helsinki; and 3Tempere School of Public
Health, University of Tempere, Tempere, Finland.
OBJECTIVE::
To estimate the risk of endometrial cancer in all Finnish postmenopausal women
using various forms of estradiol-progestin therapy. METHODS:: All Finnish women
(aged more than 50 years) who had used estradiol-progestin therapy in 1994-2006
for at least 6 months (n=224,015) were identified from the national medical
Reimbursement Registry and linked to the Finnish Cancer Registry. A total of
1,364 type I and 38 type II endometrial cancers were recorded by the end of
2006. The incidence of endometrial cancer in estradiol-progestin therapy users
was compared with that in the general population in this cohort study.
RESULTS:: The use of a continuous estradiol-progestin therapy regimen for 3
years or more was associated with a 76% reduction of the risk for type 1 cancer
(95% confidence interval [CI] 6-60%). In contrast, the use of a sequential
estradiol-progestin therapy regimen for at least 5 years was accompanied with a
69% elevation (95% CI 43-96%) if the progestin was added monthly, and with a
significantly higher, 276% risk elevation (95% CI 190-379%) if progestin was
added at 3-month intervals. Sequential regimens containing norethisterone
acetate, medroxyprogesterone acetate or dydrogesterone administered orally
showed no significant differences in the endometrial safety. Oral and
transdermal norethisterone acetate were associated with similar risk
elevations. Women using a monthly sequential estradiol-progestin regimen tended
to be diagnosed with endometrial cancer in an earlier stage than the background
population. CONCLUSION:: Use of a continuous rather than a sequential
estradiol-progestin regimen decreases the risk of endometrial cancer, whereas
the route of administration or type of progestin does not differ in terms of endometrial
cancer risk. LEVEL OF EVIDENCE:: II.
BJOG. 2009
Dec;116(13):1706-14.
Pelvic floor
function is independently associated with pelvic organ prolapse.
Braekken IH, Majida M, Ellström Engh M, Holme IM, Bø K.
OBJECTIVE:
To investigate the risk factors for pelvic organ prolapse (POP), including
physical activity, clinically measured joint mobility and pelvic floor muscle
(PFM) function. DESIGN: One-to-one age- and parity-matched case-control study.
SETTING: Akershus university hospital and one outpatient physiotherapy clinic
in
J Clin Endocrinol Metab. 2009 Nov 24. [Epub
ahead of print]
Extremes of Endogenous
Testosterone Are Associated with Increased Risk of Incident Coronary Events in
Older Women.
Laughlin GA, Goodell V, Barrett-Connor E.
Department
of Family and Preventive Medicine, School of Medicine,
Context:
Few studies have examined whether endogenous testosterone is associated with
the development of coronary heart disease (CHD) in women. Objective: This study
tested the association of total testosterone (total T) and bioavailable T
(BioT) levels with risk of incident coronary events among older
community-dwelling women. Design, Setting, and Participants: This was a
prospective, population-based study of 639 postmenopausal women, aged 50-91
(mean, 73.8) yr who had serum testosterone measurements at baseline (1984-87)
and who were followed for incident CHD events through 2004. Main Outcome
Measures: A total of 134 incident CHD events occurred during follow-up [45
nonfatal myocardial infarctions, 79 fatal myocardial infarctions, and 10
coronary revascularizations]. Results: The median follow-up was 12.3 yr.
Age-adjusted CHD risk estimates were similar for the four highest total T
quintiles relative to the lowest, suggesting a low threshold. In age-adjusted
analyses, the lowest total T quintile (</=80 pg/ml) was associated with a
1.62-fold increased risk of incident CHD [95% confidence interval (CI), 1.10-2.39]
compared to higher levels. BioT showed a U-shaped association with incident
CHD. Age-adjusted risk for the lowest and highest BioT quintiles relative to
the third were 1.79 (95% CI, 1.03-3.16) and 1.96 (95% CI, 1.13-3.41),
respectively. Additional adjustment for lifestyle, adiposity, estradiol, and
ovarian status, or for CHD risk factor covariates, had minimal influence on
results. Conclusions: An optimal range of testosterone may exist for
cardiovascular health in women, with increased risk of CHD events at low levels
of testosterone overall and at high levels of the bioavailable fraction of
testosterone.
Neurology. 2009 Nov
24;73(21):1729-37.
Characteristics
of hormone therapy, cognitive function, and dementia: The prospective
Ryan J, Carrière I, Scali J, Dartigues JF, Tzourio C, Poncet M, Ritchie K, Ancelin ML.
INSERM U888, Nervous System Pathologies:
Epidemiological and Clinical Research, Hôpital La Colombière, 39 Avenue Charles
Flahault, BP 34493, 34093 Montpellier Cedex 5,
OBJECTIVES:
To examine the association between hormone therapy (HT) and cognitive
performance or dementia, focusing on the duration and type of treatment used,
as well as the timing of initiation of HT in relation to the menopause.
METHODS: Women 65 years and older were recruited in France as part of the Three
City Study. At baseline and 2- and 4-year follow-up, women were administered a
short cognitive test battery and a clinical diagnosis of dementia was made.
Detailed information was also gathered relating to current and past HT use.
Analysis was adjusted for a number of sociodemographic, behavioral, physical,
and mental health variables, as well as APOE epsilon4. RESULTS: Among 3,130
naturally postmenopausal women, current HT users performed significantly better
than never users on verbal fluency, working memory, and psychomotor speed.
These associations varied according to the type of treatment and a longer
duration of HT appeared to be more beneficial. However, initiation of HT close
to the menopause was not associated with better cognition. HT did not
significantly reduce dementia risk over 4 years but current treatment
diminished the negative effect associated with APOE epsilon4. CONCLUSIONS:
Current hormone therapy (HT) was associated with better performance in certain
cognitive domains but these associations are dependent on the duration and type
of treatment used. We found no evidence that HT needs to be initiated close to
the menopause to have a beneficial effect on cognitive function in later life.
Current HT may decrease the risk of dementia associated with the APOE epsilon4
allele.
Semana
del 18 al 24 de Noviembre de 2009
Gynecol
Endocrinol. 2009 Nov 9. [Epub ahead of print]
Hyperglycemia in
postmenopausal women screened for the metabolic syndrome is associated to
increased sexual complaints.
Chedraui P, Pérez-López FR, Blümel JE, Hidalgo L, Barriga J.
Facultad
de Ciencias Médicas, Institute of Biomedicine, Universidad Católica de
Guayaquil, Guayaquil, Ecuador.
Background.
Postmenopausal metabolic changes increase cardiovascular risk and impair
quality of life (QoL). Despite this, few reports have addressed the association
of these changes with female sexuality. Objective. To determine the association
between the metabolic syndrome (METS), and its components, and female
sexuality. Methods. Data of sexually active postmenopausal women who
participated in a METS screening program who filled out the menopause-specific
quality of life questionnaire (MENQOL) were assessed. Specifically the sexual
domain of the MENQOL was analyzed in regard to mean total and item scores
(decreased libido, vaginal dryness, and sexual avoidance). Criteria of the
Third Adult Treatment Panel (ATP III) were used to identify women with the
METS. Results. Two hundred six women fulfilled inclusion criteria. Mean age of
participants was 54 +/- 6.9 years (median: 54 years). Prevalence of the METS in
this sexually active postmenopausal series was 39.8%. About 52.9% of them
presented abdominal obesity, 35.4% hypertension, 55.8% high triglycerides,
17.5% hyperglycemia, and 59.7% decreased high density lipoprotein cholesterol
(HDL-C). Women with the METS as compared with those without the syndrome displayed
no significant differences in MENQOL sexual scorings (total or of its composing
items). Equally there were also no score differences among those presenting any
of the five components of the METS, except women with hyperglycemia who
significantly displayed a higher total sexual domain score (5.6 +/- 2.1 vs. 4.8
+/- 2.3, p < 0.05) in association to a higher mean score in the decreased
libido item (6.0 +/- 2.3 vs. 4.8 +/- 2.6, p < 0.01). After controlling for
several confounding factors, logistic regression confirmed that women with
hyperglycemia were significantly at higher risk for presenting decreased libido
(higher item score, OR 2.4, CI 95%: 1.0-5.7, p < 0.05) and more impaired
sexuality (higher total MENQOL sexual domain score: OR, 2.5, CI 95%: 1.1-5.4, p
< 0.05). Conclusion. Despite the limitations of this study, as assessed with
the MENQOL, hyperglycemia in postmenopausal women screened for the METS was
associated to a negative impact in sexuality. More research is warranted in
this regard.
Am J Public Health. 2009 Nov 12. [Epub
ahead of print]
Correlates and
Consequences of Venous Thromboembolism: The
Lutsey PL, Virnig BA, Durham SB, Steffen LM, Hirsch AT, Jacobs DR, Folsom AR.
Objectives.
We sought to document incidence, case-fatality, and recurrence rates of venous
thromboembolism (VTE) in women and to explore the relationship of demographic,
lifestyle, and anthropometric factors to VTE incidence.Methods. Data from
participants aged 55 to 69 years in the
J
Clin Densitom. 2009 Nov 17. [Epub ahead of print]
Application of FRAX
Model to Sri Lankan Postmenopausal Women.
Center for Metabolic Bone Diseases,
Faculty of Medicine, Galle, Sri Lanka.
The
FRAX software developed by the World Health Organization provides a method to
estimate fracture probability of old men and women based on their bone mineral
density (BMD) and clinical risk factors (CRFs). The validity of 4 selected
ethnic-specific FRAX tools in determining prevalent fracture or treatment
decisions in a group of postmenopausal women from
Exp
Clin Endocrinol Diabetes. 2009 Nov;117(10):563-566. Epub 2009 Nov 18.
Obesity and Cancer.
Epidemiological
studies have suggested that obesity is associated with increased risk of
several cancer types including colon, esophagus, breast (in postmenopausal
women), endometrium, kidney, liver, gallbladder and pancreas. Suggested
mechanisms include increased intake of potentially carcinogenic food
ingredients along with excessive amount of calories, loss of cancer protective
effects due to reduced physical activity, carcinogenic factors released from
increased adipose tissue mass and "secondary" associations via "precursor"
condition such as gallstones. The increased cancer risk in patients with
obesity is a neglected topic which deserves more scientific attention. Because
of its extreme chronicity and co-association with numerous other conditions
true causality and underlying mechanisms are difficult to study. Nevertheless,
a large body of literature is already available which provides concepts for
future research. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart ·
Int J Obes
(Lond). 2009 Nov 17. [Epub ahead of print]
Physical inactivity,
abdominal obesity and risk of coronary heart disease in apparently healthy men
and women.
Arsenault BJ, Rana JS, Lemieux I, Després JP, Kastelein JJ, Boekholdt SM, Wareham NJ, Khaw KT.
[1] Centre de Recherche de l'Institut
Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada [2]
Faculty of Medicine, Department of Anatomy and Physiology, Université Laval,
Québec.
Objective:To
test the hypothesis that for any given body mass index (BMI) category, active
individuals would have a smaller waist circumference than inactive individuals.
Our second objective was to examine the respective contribution of waist
circumference and physical inactivity on coronary heart disease (CHD)
risk.Design:Prospective, population-based study with an 11.4-year
follow-up.Subjects:A total of 21 729 men and women aged 45-79 years, residing
in Norfolk, UK.Methods:During follow-up, 2191 CHD events were recorded.
Physical activity was evaluated using a validated lifestyle questionnaire that
takes into account both leisure-time and work-related physical activity. Waist
circumference was measured and BMI was calculated for each
participant.Results:For both men and women, we observed that within each BMI
category (<25.0, 25-30 and >/=30.0 kg m(-2)), active participants had a
lower waist circumference than inactive participants (P<0.001). In contrast,
within each waist circumference tertile, BMI did not change across physical
activity categories (except for women with an elevated waist circumference).
Compared with active men with a low waist circumference, inactive men with an
elevated waist circumference had a hazard ratio (HR) for future CHD of 1.74
(95% confidence interval (CI), 1.34-2.27) after adjusting for age, smoking,
alcohol intake and parental history of CHD. In the same model and after further
adjusting for hormone replacement therapy use, compared with active women with
a low waist circumference, inactive women with an elevated waist circumference
had an HR for future CHD of 4.00 (95% CI, 2.04-7.86).Conclusion:In any BMI
category, inactive participants were characterized by an increased waist
circumference, a marker of abdominal adiposity, compared with active
individuals. Physical inactivity and abdominal obesity were both independently
associated with an increased risk of future CHD.
Drug Des Devel Ther. 2009 Feb 6;2:193-202. 
Transdermal hormone
therapy in postmenopausal women: A review of metabolic effects and drug
delivery technologies.
Kopper NW, Gudeman J, Thompson DJ.
KV Pharmaceutical, St. Louis, MO, USA.
Vasomotor
symptoms (VMS) associated with menopause can cause significant discomfort and
decrease the quality of life for women in the peri-menopausal and
post-menopausal stages of life. Hormone therapy (HT) is the mainstay of
treatment for menopausal symptoms and is currently the only therapy proven
effective for VMS. Numerous HT options are available to treat VMS, including
estrogen-only and estrogen-progestogen combination products to meet the needs
of both hysterectomized and nonhysterectomized women. In addition to selecting
an appropriate estrogen or estrogen-progestogen combination, consideration
should be given to the route of administration to best suit the needs of the
patient. Delivery systems for hormone therapy include oral tablets, transdermal
patches, transdermal topical (nonpatch) products, and intravaginal
preparations. Oral is currently the most commonly utilized route of
administration in the
J
Steroid Biochem Mol Biol. 2009 Nov 12. [Epub ahead of print]
Gene Expression
Profiling Studies of Three SERMs and Their Conjugated Estrogen Combinations in
Human Breast Cancer Cells: Insights into the Unique Antagonistic Effects of
Bazedoxifene on Conjugated Estrogens.
Chang KC, Wang Y, Bodine PV, Nagpal S, Komm BS.
Wyeth
Research, Transcriptional Targets, Tissue Repair, 500 Arcola Road,
Collegeville, Pennsylvania,
Bazedoxifene
(BZA), a new selective estrogen receptor modulator (SERM) was recently approved
in Europe for the prevention and treatment of postmenopausal osteoporosis. Combination
therapy using BZA and conjugated estrogens (CE) is currently in late stage
development representing a new paradigm for the treatment of menopausal
symptoms and prevention of osteoporosis. A GeneChip microarray study was
designed to compare gene expression profiles of BZA to that of other SERMs,
raloxifene (RAL) and lasofoxifene (LAS). In addition, we compared the gene
expression profiles of the three SERMs in combination with CE, a mixture of 10
most abundant estrogens present in Premarin. According to the hierarchical
clustering heat map analysis, gene clusters that specifically responded to CE
treatments or SERM treatments were identified and gene lists sorted based on a
set of cutoff filters. A group of genes differentially regulated by CE were also
identified to be antagonized by BZA when comparing CE with the BZA+CE
treatment. All three SERMs showed significant antagonistic effect against
CE-stimulated cell proliferation, based on the MCF-7 cell proliferation assay
and GeneChip data, with the order of antagonist activity being
BZA>RAL>LAS. 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 effects that are observed in
clinic by pairing BZA with CE.
J Intern Med. 2009 Aug
26. [Epub ahead of print]
Menopause impacts the
relation of plasma adiponectin levels with the metabolic syndrome.
Henneman P, Janssens AC, Zillikens MC, Frolich M, Frants RR, Oostra BA, van Duijn CM, van Dijk KW.
From the Department of Human Genetics,
Abstract.
Henneman P, Janssens ACJW, Carola Zillikens M, Frolich M, Frants RR, Oostra BA,
van Duijn CM, van Dijk KW (Leiden University Medical Center, Leiden; Erasmus
Medical Center, Rotterdam, The Netherlands). Menopause impacts the relation of
plasma adiponectin levels with the metabolic syndrome. J Intern Med 2009; doi:
10.1111/j.1365-2796.2009.02162.xObjective. Plasma adiponectin is negatively
correlated with metabolic syndrome (MetS) components obesity and insulin
sensitivity. Here, we set out to evaluate the effect of menopause on the
association of plasma adiponectin with MetS. Design. Data on plasma adiponectin
and MetS were available from 2256 individuals participating in the Erasmus
Rucphen Family study. Odds ratios for MetS were calculated by logistic
regression analysis using plasma adiponectin quartiles. The discriminative
accuracy of plasma adiponectin for MetS was determined by calculating the area
under the curve (AUC) of receiver operator. Analyses were performed in women
and men, pre- and postmenopausal women and younger and older men. Results.
Virtually all determinants of MetS differed significantly between groups. Low
plasma adiponectin showed the highest risk for MetS in postmenopausal women
(odds ratio = 18.6, 95% CI = 7.9-44.0). We observed a high discriminative
accuracy of age and plasma adiponectin for MetS not only in postmenopausal
women (AUC = 0.76) but also in other subgroups (AUC from 0.67 to 0.87).
However, in all groups, the discriminative accuracy of age and body mass index
(BMI) for MetS was similar to the discriminative accuracy of age and plasma
adiponectin. Conclusions. Low plasma levels of adiponectin are associated with
increased prevalence of MetS, especially in postmenopausal women. Age and BMI
have similar discriminatory accuracies for presence of MetS when compared with
age and plasma adiponectin. Thus, we conclude that the association of plasma
adiponectin with MetS is significantly affected by menopause but challenge the
additional value of adiponectin for the discriminatory accuracy for presence of
MetS.
Semana del 11 al 17 de
Noviembre de 2009
Gynecol
Endocrinol. 2009 Aug;25(8):491-7.
Quality of
life impairment among postmenopausal women varies according to race.
Monterrosa A, Blumel JE, Chedraui P, Gomez B, Valdez C.
Facultad de Medicina, Universidad de
Cartagena, Cartagena, Colombia.
Background.
Few studies have addressed the impact of menopausal symptom severity over
quality of life (QoL) in Latin American women with different ethnics.
Objective. To assess menopausal symptom severity and the QoL among
postmenopausal Colombian women with three different ethnicities. Method. Data
of healthy naturally occurring postmenopausal Hispanic, indigenous and black
women aged 40-59 years who participated in a cross-sectional study filling out
the Menopause Rating Scale (MRS) and a general questionnaire was analysed.
Results. A total of 579 women were included, 153 Hispanic, 295 indigenous and
131 Afro-descendent. Hispanic women had an average age of 55.3 +/- 3.3 years.
Indigenous and black women were less educated than the Hispanic ones (2.2 +/-
1.8 and 4.6 +/- 4.4 vs. 6.4 +/- 3.5 years, p < 0.0001). Hispanic women
displayed lower total MRS scores (better QoL) when compared to indigenous and
black women. Urogenital scoring was worse among indigenous women compared to
Hispanic and black women. Black women presented higher MRS psychological and
somatic scorings than Hispanic and indigenous women. After adjusting for
confounding factors, indigenous and black women continued to display a higher
risk for impaired QoL, total MRS score >16 (OR: 3.11, 95% CI: 1.30-7.44 and
OR: 5.29, 95% CI: 2.52-11.10, respectively), which was significantly higher
among indigenous women due to urogenital symptoms (OR: 102.75, 95% CI:
38.33-275.47) and black women due to psychological (OR: 6.58, 95% CI:
3.27-13.27) and somatic symptoms (OR: 3.88, 95% CI: 1.83-8.22). Conclusion. In
this postmenopausal Colombian series, menopausal symptoms in indigenous
(urogenital) and black (somatic/psychological) women were more severe (impaired
QoL) when compared to Hispanic ones.
Endocrinology. 2009 Nov 11. [Epub
ahead of print]
Tissue-Selective
Regulation of Aromatase Expression by Calcitriol: Implications for Breast
Cancer Therapy.
Krishnan AV, Swami S, Peng L, Wang J, Moreno J, Feldman D.
Departments of Medicine, Division of
Endocrinology, Stanford University School of Medicine, Ca. USA. Aromatase, the
enzyme that catalyzes estrogen synthesis, is critical for the progression of estrogen receptor-positive
breast cancer (BCa) in postmenopausal women. We show that calcitriol, the
hormonally active form of vitamin D, regulates the expression of aromatase in a
tissue-selective manner. Calcitriol significantly decreased aromatase
expression in human BCa cells and adipocytes and caused substantial increases in
human osteosarcoma cells (a bone cell model exhibiting osteoblast phenotype in
culture) and modest increases in ovarian cancer cells. Calcitriol
administration to immunocompromised mice bearing human BCa xenografts decreased
aromatase mRNA levels in the tumors and the surrounding mammary adipose tissue
but did not alter ovarian aromatase expression. In BCa cells, calcitriol also
reduced the levels of prostaglandins (PGs), major stimulators of aromatase
transcription, by suppressing the expression of cyclooxygenase-2 (which
catalyzes PG synthesis) and increasing that of 15-hydroxyprostaglandin
dehydrogenase (which catalyzes PG degradation). The mechanism of aromatase
down-regulation by calcitriol in BCa cells is therefore 2-fold: a direct
repression of aromatase transcription via promoter II through the vitamin
D-response elements identified in this promoter and an indirect suppression by
reducing the levels of PGs. Combinations of calcitriol with three different
aromatase inhibitors (AIs) caused enhanced inhibition of BCa cell growth. The
combination of calcitriol and an AI may have potential benefits for BCa
therapy. In addition to augmenting the ability of AIs to inhibit BCa growth,
calcitriol acting as a selective aromatase modulator that increases aromatase
expression in bone would reduce the estrogen deprivation in bone caused by the
AIs, thus ameliorating the AI-induced side effect of osteoporosis.
Am J Clin Nutr. 2009 Nov 11. [Epub
ahead of print]
The Soy
Isoflavones for Reducing Bone Loss (SIRBL) Study: a 3-y randomized controlled
trial in postmenopausal women.
Alekel DL, Van Loan MD, Koehler KJ, Hanson LN, Stewart JW, Hanson KB, Kurzer MS, Peterson CT.
Nutrition and Wellness Research Center,
Department of Food Science and Human Nutrition and the Department of
Statistics, Iowa State University, Ames, IA.
BACKGROUND:
Our previous study indicated that soy protein with isoflavones lessened lumbar
spine bone loss in midlife women. OBJECTIVE: We examined the efficacy of
isoflavones (extracted from soy protein) on bone mineral density (BMD) in
nonosteoporotic postmenopausal women. We hypothesized that isoflavone tablets
would spare BMD, with biological (age, body weight, serum 25-hydroxyvitamin D)
and lifestyle (physical activity, dietary intake) factors modulating BMD loss.
DESIGN: Our double-blind, randomized controlled trial (36 mo) included healthy
postmenopausal women (aged 45.8-65.0 y) with intent-to-treat (n = 224) and
compliant (n = 208) analyses. Treatment groups consisted of a placebo control
group and 2 soy isoflavone groups (80 compared with 120 mg/d); women received
500 mg calcium and 600 IU vitamin D(3). Outcomes included lumbar spine, total
proximal femur, femoral neck, and whole-body BMD. RESULTS: Analysis of variance
for intent-to-treat and compliant (>/=80%) models, respectively, showed no
treatment effect for spine (P = 0.46, P = 0.21), femur (P = 0.86, P = 0.46),
neck (P = 0.17, P = 0.14), or whole-body (P = 0.86, P = 0.78) BMD. From
baseline to 36 mo, BMD declined regardless of treatment. In intent-to-treat and
compliant models, respectively, BMD decreases were as follows: spine (-2.08%,
-1.99%), femur (-1.43%, -1.38%), neck (-2.56%, -2.51%), and whole body (-1.66%,
-1.62%). Regression analysis (compliant model) indicated that age, whole-body
fat mass, and bone resorption were common predictors of BMD change. After
adjustment for these factors, 120 mg (compared with placebo) was protective (P
= 0.024) for neck BMD. We observed no treatment effect on adverse events,
endometrial thickness, or bone markers. Conclusion: Our results do not show a
bone-sparing effect of extracted soy isoflavones, except for a modest effect at
the femoral neck.
Ann N Y Acad Sci. 2009 Oct;1179:153-166.
Glucocorticoid
Signaling in the Cell.
First
Department of Pediatrics, Athens University Medical School, Athens, Greece.
Glucocorticoids
contribute to the maintenance of basal and stress-related homeostasis in all
higher organisms, and influence a large proportion of the expressed human
genome, and their effects spare almost no organs or tissues. Glucocorticoids
regulate many functions of the central nervous system, such as arousal,
cognition, mood, sleep, the activity and direction of intermediary metabolism,
the maintenance of a proper cardiovascular tone, the activity and quality of
the immune and inflammatory reaction, including the manifestations of the
sickness syndrome, and growth and reproduction. The numerous actions of
glucocorticoids are mediated by a set of at least 16 glucocorticoid receptor
(GR) isoforms forming homo- or hetero-dimers. The GRs consist of
multifunctional domain proteins operating as ligand-dependent transcription
factors that interact with many other cell signaling systems, including large
and small G proteins. The presence of multiple GR monomers and homo- or hetero-dimers
expressed in a cell-specific fashion at different quantities with
quantitatively and qualitatively different transcriptional activities suggest
that the glucocorticoid signaling system is highly stochastic. Glucocorticoids
are heavily involved in human pathophysiology and influence life expectancy.
Common behavioral and/or somatic complex disorders, such as anxiety,
depression, insomnia, chronic pain and fatigue syndromes, obesity, the
metabolic syndrome, essential hypertension, diabetes type 2, atherosclerosis
with its cardiovascular sequelae, and osteoporosis, as well as autoimmune
inflammatory and allergic disorders, all appear to have a
glucocorticoid-regulated component.
Gynecol
Endocrinol. 2009;25(12):823-7.
Testosterone
addition to estrogen therapy - Effects on inflammatory markers for
cardiovascular disease.
Kocoska-Maras L, Hirschberg AL, Byström B, Schoultz BV, Rådestad AF.
Division
of Obstetrics and Gynecology, Karolinska Institutet and Karolinska University
Hospital, Stockholm.
Objective.
To analyze the effects of testosterone addition to estrogen therapy in
comparison with estrogen alone on cardiovascular risk factors in postmenopausal
women. Methods. Fifty surgically postmenopausal women were included in this
double-blind, placebo-controlled and randomized study to receive daily oral
treatment with estradiol valerate 2 mg + placebo (E/P) or estradiol valerate 2
mg + testosterone undecanoate 40 mg (E/T) for 24 weeks and then switched to the
other regimen for another 24 weeks. Sex hormones, High sensitivity CRP (hsCRP),
Interleukin-6 (IL-6), Tissue necrosis factor (TNF)-alpha, Insulin-like growth
factor binding globulin (IGFBP-1), vascular cell adhesion molecule (VCAM)- 1,
and homocysteine were analyzed at baseline and after 6 and 12 months. Results.
Estradiol and androgens increased as expected during the treatments. After 6
months of E/P, increases of hsCRP and IGFBP-1 and a decline of VCAM were
recorded, whereas IL-6, TNF-alpha, and homocysteine were unchanged. When
testosterone was added to estrogen, the increase of IGFBP-1 and decline in VCAM
was similar as with estrogen treatment alone. However, testosterone addition
counteracted the estrogen-induced rise in hsCRP but had no effects on IL-6,
TNF-alpha, and homocysteine. Conclusion. Data suggest that testosterone
addition to estrogen treatment in postmenopausal women has a modest influence
on inflammatory markers and there were no apparent adverse effects. On the
contrary, the estrogen-induced increase in hsCRP was suppressed.
J Clin Oncol. 2009 Nov 9. [Epub ahead
of print]
Conjugated
Equine Estrogen Influence on Mammographic Density in Postmenopausal Women in a
Substudy of the Women's Health Initiative Randomized Trial.
McTiernan A, Chlebowski RT, Martin C, Peck JD, Aragaki A, Pisano ED, Wang CY, Johnson KC, et al.
Fred Hutchinson Cancer Research Center,
Division of Public Health Sciences; University of Washington, Department of
Epidemiology, School of Public Health and Community Medicine, and Department of
Medicine, School of Medicine, Seattle, WA.
PURPOSE:
Increased mammographic density is associated with increased breast cancer risk
and reduced sensitivity of screening mammography and is related to hormone
exposure. However, the effects of conjugated equine estrogens (CEEs) alone on
mammographic density in diverse racial/ethnic populations are not established.
We examined the effect of CEE alone on mammographic density in a subsample of
the Women's Health Initiative (WHI) clinical trial participants. PATIENTS AND
METHODS: In the WHI trial, women were randomly assigned to daily CEE 0.625 mg
or placebo. The effect of CEE on mammographic percent density was determined
over 1 and 2 years in a stratified random sample of 435 racially and ethnically
diverse participants from 15 of 40 WHI clinics. RESULTS: Use of CEE resulted in
mean increase in mammographic percent density of 1.6 percentage points (95% CI,
0.8 to 2.4) at year 1 compared with a mean decrease of 1.0 percentage point
(95% CI, -1.7 to -0.4) in the placebo group (P < .001). The effect persisted
for 2 years, with a mean increase of 1.7 percentage points (95% CI, 0.7 to 2.7)
versus a mean decrease of 1.2 percentage points (95% CI, -1.8 to -0.5; P <
.001) in the hormone and placebo groups, respectively. These effects were
greater in women age 60 to 79 years (P = .03 for interaction across age).
CONCLUSION: Use of CEE results in a modest but statistically significant
increase in mammographic density that is sustained over at least a 2-year
period. The clinical significance of the CEE effect on mammographic density remains
to be determined.
Gynecol
Endocrinol. 2009;25(12):807-15.
Progestagen
component in combined hormone replacement therapy in postmenopausal women and
breast cancer risk: A debated clinical issue.
Gadducci A, Biglia N, Cosio S, Sismondi P, Genazzani AR.
Department of Procreative Medicine,
Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.
The
relevance of the progestagen component in combined hormone replacement therapy
(HRT) for breast cancer risk has been long debated. In vitro studies have shown
that progestins exert both genomic transcriptional and non-genomic effects that
can enhance the proliferation, invasiveness and spread of breast cancer cells.
According to a novel hypothesis, progestins can still activate cancer stem
cells in patients with pre-existing, clinically undetected breast cancer.
However, some experimental and clinical data suggest that different progestins
may have a different impact on the pathophysiology of malignant breast cells.
In vitro studies on estrogen receptor (ER)+ breast cancer cells have shown that
the addition of medroxyprogesterone acetate (MPA) to estradiol (E(2)) produces
a significantly higher increase of the mRNA levels and activities of
estrogen-activating enzymes aromatase, 17beta hydroxysteroid dehydrogenase
type-1 and sulfatase when compared with progesterone plus E(2). In randomised
trial performed on ovariectomised adult female monkeys, oral E(2) plus MPA have
resulted in a significantly greater proliferation of breast lobular and ductal
epithelium when compared with placebo, whereas E(2) plus micronised
progesterone have not. In the same experimental model, oral E(2) plus MPA have
been found to induce the expression of genes encoding epidermal growth factor
receptor (EGFR) ligands and downstream targets, whereas E(2) alone or E(2) plus
micronised progesterone had no or modest effects on EGFR-related genes. In last
years, some clinical studies on HRT users have shown that androgenic progestin-
or MPA-based formulations are associated with an increased breast cancer
incidence, whereas micronised progesterone- or dydrogesterone-based
formulations are not. Further basic and clinical investigations on this topic are
strongly warranted to elucidate whether the choice of the progestagen component
in combined HRT could be of clinical relevance as for breast cancer risk.
Climacteric. 2009 Dec;12(6):525-32.
Risk of
hypoactive sexual desire disorder and associated factors in a cohort of
oophorectomized women.
Castelo-Branco C, Palacios S, Combalia J, Ferrer M, Traveria G.
Hospital Clinic, Faculty of Medicine,
BACKGROUND:
Women with surgical menopause are at high risk of developing hypoactive sexual
desire disorder (HSDD), which may cause sexual and emotional discomfort. AIM:
To determine the prevalence of HSDD and related risk factors in Spanish
surgically postmenopausal women. DESIGN: Multicenter, cross-sectional study.
Material and methods The Brief Profile of Female Sexual Function (B-PFSF)
questionnaire was given to 1136 surgically postmenopausal women between 18 and
81 years old (mean 52.1 +/- 7.1 years) attending gynecological consultations in
different urban and rural areas in Spain, covering the country widely. RESULTS:
From the entire sample, 1083 subjects were finally included. The mean score on
the B-PFSFwas 15.9 and a total of 74.4% of the patients presented total scores
lower or equal to 20, indicating the risk of presenting with HSDD. The
possibility to be at risk of HSDD increased with age from 65.9% in the age
group <45 years old to 76.6% in the age group > or =55 years old.
Non-users of hormone replacement therapy presented a higher risk of HSDD (odds
ratio 2.1; 95% confidence interval 1.3-3.4); the risk was increased as well
when the time elapsed since surgical menopause was <5 years (odds ratio 1.8;
95% confidence interval 1.0-3.0). CONCLUSION: Nearly three out of four women
who had undergone bilateral oophorectomy were at risk of suffering HSDD; this
risk was increased when less than 5 years since surgical menopause had elapsed.
The use of hormone replacement therapy was associated with lower HSDD risk.
Endocr Relat Cancer. 2009 Nov 10. [Epub
ahead of print]
Plasma
sex hormone concentrations and breast cancer risk in an ethnically diverse
population of postmenopausal women: the Multiethnic Cohort Study.
Woolcott C, Shvetsov Y, Stanczyk F, Wilkens L, White K, Caberto C, Henderson B, Le Marchand L, Kolonel L, Goodman M.
C Woolcott, Cancer Research Center of
Hawaii, University of Hawaii, Honolulu, United States.
To add
to the existing evidence that comes mostly from White populations, we conducted
a nested case-control study to examine the association between sex hormones and
breast cancer risk within the Multiethnic Cohort that includes Japanese
American, White, Native Hawaiian, African American, and
Semana del 4 al 10 de Noviembre de 2009
J Med Assoc
Thai. 2009 Sep;92 Suppl5:S30-41.
Combination of
alfacalcidol with calcium can improve quadriceps muscle strength in elderly
ambulatory Thai women who have hypovitaminosis D: a randomized controlled trial.
Songpatanasilp T, Chailurkit LO,
Nichachotsalid A, Chantarasorn M.
Department
of Orthopedics, Phramongkutklao Army Hospital and College of Medicine, Bangkok,
Thailand. thaweesps@yahoo.com
OBJECTIVE:
The purpose of this study was to evaluate the efficacy of alfacalcidol and
calcium on the improvement of muscle strength in ambulatory elderly Thai women
in age group of 65 or more who have hypovitaminosis D. MATERIAL AND METHOD:
Seventy-two postmenopausal women age 65 years or more were enrolled to this
study. Blood was collected from all participants for measured of 25(OH)D3,
intact PTH and vitamin D receptor (VDR) genotypes. After blood collection, the
quadriceps muscle strength was measured using the isokinetic dynamometer
device. There were 42 subjects who satisfy the eligible criteria and agreed to
participate in the experimental randomized controlled study. These subjects
were randomized into two groups, one received calcium 1500 g/day combined with
alfacalcidol 0.5 mg/day. Another group received calcium 1500 g/day with
placebo. RESULTS: After 12 weeks of intervention, 40 subjects had the second muscle
strength measurement (2 dropped out). By ANCOVA analysis, there were
significant improvement of muscle strength in the group that received
alfacalcidol compared to placebo in both 30 degrees/sec (20.28 vs.16.29, p =
0.025) and 60 degrees/sec (20.32 vs. 15.05, p = 0.002) angular velocities.
CONCLUSION: Daily doses of 0.5 mg alfacalcidol with calcium effectively
improved muscle strength in elderly Thai women who had low level of 25(OH)D3
compared to calcium alone.
Breast Cancer Res Treat. 2009 Nov 6. [Epub ahead
of print]
Reductions in use of
hormone replacement therapy: effects on Swedish breast cancer incidence trends
only seen after several years.
Lambe M, Wigertz A, Holmqvist M, Adolfsson
J, Bardage C, Fornander T, Karlsson P, Odlind V, Persson I, Ahlgren J,
Bergkvist L.
Department of Medical Epidemiology and
Biostatistics, Karolinska Institutet, PO Box 281, 171 77, Stockholm, Sweden, Mats.Lambe@ki.se.
Studies
from Western countries have found evidence of a recent decline in breast cancer
incidence rates in postmenopausal women, findings which have been hypothesized
to reflect a reduced use of hormonal replacement therapy (HRT). We examined
breast cancer incidence trends in Sweden between 1997 and
Zhong Nan Da
Xue Xue Bao Yi Xue Ban. 2009 Oct;34(10):998-1002.
Association of serum
testosterone with lean body mass, body fat content, and bone mineral density in
postmenopausal females.
Zhang H, Liu W, Ye A, Zhao Q, Luo X, Liao
E.
Institute of Metabolism and Endocrinology,
Objective
To determine the relationship between serum testosterone level and lean body
mass, body fat content, and bone mineral density (BMD).Methods The study
involved 185 healthy females in Changsha, aged 45~81. Fasting serum
testosterone was measured by radioimmunoassay. Hologic QDR 4500A fan beam X-ray
bone densitometer was used to measure the BMD of anteroposterior lumber(AP,
L(1~4)) and total hip,to measure the bone mineral content, BMD, body fat
content and muscle tissue weight of head, trunk, ribs, pelvis, spine, upper
limbs, lower limbs and the total body. Body weight, lean body mass and body fat
percentage were calculated. SPSS11.0 software was used to conduct regression
analysis.Results (1)Serum testosterone showed no correlation with lean body
mass, body fat content, and body fat percentage. (2)Serum testosterone was
positively related with the BMD of lumbar spine and hip, but showed no
correlation with the BMD after adjustment of age and years since postmenopause.
(3)Lean body mass showed significant positive correlation with the BMD of
different sites. Total body fat content showed positive correlation with the
BMD of total hip, while body fat percentage showed negative correlation with
the BMD of the whole body. Conclusion Keeping lean body mass benefits
postmenopausal women to maintain bone mineral content, and taking androgen
should still be cautious.
Bone. 2009 Nov 2. [Epub ahead
of print]
Serum Tsh Values And
Risk Of Vertebral Fractures In Euthyroid Post-Menopausal Women With Low Bone
Mineral Density.
Mazziotti G, Porcelli T, Patelli I, Vescovi
PP, Giustina A.
Department of Medical and Surgical Sciences,
University of Brescia, Italy; Department of Internal Medicine, Azienda
Ospedaliera Carlo Poma, Mantova, Italy.
Introduction.
There is evidence that variations of thyrotropin (TSH) even in its reference
range may influence bone mineral density (BMD). In fact, low-normal TSH values
have been associated with high prevalence of osteoporosis in post-menopausal
women. However, data associating TSH and risk of fractures are scanty and limited
to subjects with subclinical thyrotoxicosis. Materials and Methods. In this
observational study, we investigated the correlation between serum TSH and
prevalence of radiological vertebral fractures in a cohort of 130
post-menopausal women without biochemical and instrumental evidence of thyroid
disease. Results. Osteoporosis was observed in 80 women (61.5%), whereas 49
women (37.7%) had osteopenia. Vertebral fractures were found in 49 women
(37.7%), who were significantly older, with higher prevalence of osteoporosis
and with lower serum TSH values as compared with women who did not fracture.
Stratifying the patients according to serum TSH values, vertebral fractures
were found to be significantly (p=0.004) more prevalent in first tertile
(56.8%) of TSH values as compared with the second (23.3%) and third tertiles
(32.6%). Multivariate logistic regression analysis demonstrated that low serum
TSH maintained a significant correlation with vertebral fractures (odds ratio
2.8, C.I. 95% 1.20-6.79) even after correction for age, BMD, BMI and serum
free-thyroxine values. Discussion. Low-normal TSH values are associated with
high prevalence of vertebral fractures in women with post-menopausal
osteoporosis or osteopenia, independently of thyroid hormones, age and BMD.
Climacteric. 2009 Nov 3. [Epub ahead
of print]
Insomnia in Japanese
peri- and postmenopausal women.
Terauchi M, Obayashi S, Akiyoshi M, Kato
K, Matsushima E, Kubota T.
Department of Obstetrics and Gynecology.
Objective
To determine the prevalence and to identify the correlates of insomnia in
Japanese peri- and postmenopausal women. Method We retrospectively analyzed the
records of 1451 peri- and postmenopausal women enrolled in the Systematic
Health and Nutrition Education Program, conducted at the Menopause Clinic of
the Tokyo Medical and Dental University Hospital, between 1995 and 2009.
Results The prevalence of insomnia was 50.8%. The severity of insomnia
correlated negatively with health-related quality of life (HR-QOL) scores on
all the four domains assessed: physical health, mental health, life
satisfaction and social involvement. With regard to other menopausal symptoms,
insomnia correlated more strongly with depressed mood than with vasomotor
symptoms, and one-third of insomniac women were seriously depressed. On
categorizing the participants into four groups - not insomniac or depressed, N;
insomniac but not depressed, I; not insomniac but depressed, D; insomniac and
depressed, ID - the HR-QOL scores were observed to worsen in order N > I
> D > ID. No significant difference was detected between groups I and ID
with regard to their sleep quality measures. The number of heavy smokers was
high in groups I and ID. With regard to the effect of the combination of
medication and health/nutrition education, hormone therapy and nightly
hypnotics significantly improved the insomnia symptoms, but hypnotics administered
'as needed' did not. Conclusions Insomnia in Japanese peri- and postmenopausal
women correlates more strongly with depressed mood than with vasomotor
symptoms. Cessation of smoking may improve the women's sleep quality, and
hormone therapy and nightly hypnotics are both effective treatments.
Eur J Obstet
Gynecol Reprod Biol. 2009
Oct 29. [Epub ahead of print]
Effects of menopausal
hormone therapy on hemostatic parameters, blood pressure, and body weight:
Open-label comparison of randomized treatment with estradiol plus drospirenone
versus estradiol plus norethisterone acetate.
Junge W, El-Samalouti V, Gerlinger C,
Schaefers M.
Laboratorium für Klinische Forschung GmbH,
Raisdorf, Germany.
OBJECTIVES:
Clinical studies have reported changes in hemostatic parameters in women taking
menopausal hormone therapy (HT) and a small increased risk of venous
thromboembolism. We compared the effects of two different HTs on hemostatic
parameters in postmenopausal women. STUDY DESIGN: An open-label, randomized
study conducted at two centers in Germany compared continuous 28-week combined
HT with 17beta-estradiol 1mg plus drospirenone 2mg (E2/DRSP) daily versus E2
1mg plus norethisterone acetate 0.5mg (E2/NETA) daily in healthy postmenopausal
women. Changes in D-dimer levels from baseline to the end of treatment, as well
as effects on further parameters of coagulation, fibrinolysis, and global
hemostasis, and effects on bleeding pattern, blood pressure, and body weight
were evaluated. RESULTS: D-dimer levels increased by 9.1% (median change) with
E2/DRSP (n=29) and by 15.1% with E2/NETA (n=30). Other hemostatic parameters
showed <10% median change from baseline in both treatment groups, except for
tissue plasminogen activator antigen (E2/DRSP, -1.9%; E2/NETA, -24.2%).
Systolic blood pressure decreased from baseline by 6.4mmHg in the E2/DRSP group
compared with 0.1mmHg in the E2/NETA group at final examination. Body weight
remained stable in the E2/DRSP group (+0.18kg) compared with a slight increase
(+1.00kg) in the E2/NETA group. In nonhysterectomized women, the mean number of
bleeding/spotting days was 5.2 (2.0 bleeding/3.2 spotting) in the E2/DRSP and
8.2 (4.4 bleeding/3.8 spotting) in the E2/NETA group. Most nonhysterectomized
women, however, remained amenorrheic during the study period (E2/DRSP, 68%;
E2/NETA, 62%). CONCLUSION: Both E2/DRSP and E2/NETA were associated with a
minor increase in fibrinolytic activity and a slight change in the
concentration of some coagulation factors. Both HTs were well tolerated. The
decrease in systolic blood pressure and stable body weight in the E2/DRSP group
are consistent with DRSP's anti-aldosterone properties.