Selección de
Resúmenes de Menopausia
Septiembre de 2007
Dr. Juan Enrique Blümel.
Departamento Medicina Sur. Universidad de Chile
Semana del 26 de Septiembre al 2 de Octubre de
2007
J Natl Compr Canc Netw. 2007
Sep;5(8):719-24.
The STAR Trial: Evidence for Raloxifene as a Breast Cancer Risk
Reduction Agent for Postmenopausal Women.
From the University of Texas
M. D. Anderson Cancer Center, Houston, Texas; Correspondence: Therese B.
Bevers, MD, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe
Blvd, Unit 1322, Houston, TX 77030. E-mail: tbevers@mdanderson.org.
The 1998 approval of tamoxifen
for breast cancer risk reduction opened the era of breast cancer
chemoprevention. Women at increased risk for breast cancer now had an option
other than healthy lifestyle and prophylactic surgery to reduce risk. However,
women and their physicians were reluctant to use tamoxifen because of associated
risks. Several trials investigating raloxifene suggested it may reduce breast
cancer risk without having an apparent effect on the endometrium. The Study of
Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer trial
opened in 1999 to directly compare raloxifene to tamoxifen for breast cancer
risk reduction. Since the unblinding of the STAR trial in 2006, raloxifene has
emerged as an option for reducing breast cancer risk for postmenopausal women
at increased risk for the disease.
J Natl Compr Canc Netw. 2007
Sep;5(8):711-718.
Diet and Breast Cancer Risk Reduction.
From the Departments of
Nutrition and Epidemiology, Harvard School of Public Health, Boston,
Massachusetts; Correspondence: Eleni Linos, MD, MPH, Channing Laboratory,
Department of Medicine, Brigham and Women's Hospital, and Harvard Medical
School, 181 Longwood Avenue, Boston, MA 02115. E-mail: elinos@hsph.harvard.edu.
The association between diet
and breast cancer risk has been investigated extensively and has led to some
recommendations for prevention. Research suggests that maintaining a healthy
weight may reduce the risk for breast cancer after menopause. Additionally,
alcohol increases the risk for breast cancer even at moderate levels of intake,
and women who drink alcohol also should take sufficient folate, which can
mitigate this excess risk. Interesting questions for future research include
the role of soy products, red meat, energy balance, and vitamin D, with
particular attention to timing of exposure in early life. Breast cancer is a
heterogeneous disease, and dietary factors may differentially affect certain
breast cancer subtypes; future studies should therefore attempt to characterize
associations according to tumor characteristics.
Circ J. 2007 Oct;71(10):1555-9.
Relationship between brachial arterial endothelial function and lumbar
spine bone mineral density in postmenopausal women.
Sumino H, Ichikawa S, Kasama S, Takahashi T, Sakamoto H, Kumakura H, Takayama Y, Kanda T, Murakami M, Kurabayashi M.
Department of Nursing, Faculty
of Nursing,
Background Osteoporosis and
endothelial dysfunction have been associated with atherosclerosis. The
correlation between brachial arterial endothelial function and lumbar spine
bone mineral density (BMD) in postmenopausal women will be investigated.
Methods and Results The endothelial function in 85 postmenopausal women,
including 28 women with normal spinal BMD, 27 women with osteopenia, and 30
women with osteoporosis were studied. Brachial arterial flow-mediated
vasodilatation (FMD) after reactive hyperemia was assessed by ultrasonography.
The BMD at the lumbar spine (lumbar 2 to 4 vertebrae) was measured by
dual-energy X-ray absorptiometry. Age, years since menopause, and FMD were significantly
greater in the osteoporosis group than in the normal BMD group (p<0.01,
p<0.05, and p<0.05, respectively). The BMD was significantly lower in the
osteoporosis group than in the osteoporosis or normal BMD group (both
p<0.01). After adjusting for age and years since menopause, women with
osteoporosis had significantly lesser FMD than those with normal BMD
(p<0.05). The univariate linear regression analysis revealed that brachial
arterial FMD was significantly positively correlated with BMD (r=0.31,
p<0.01), but showed no significant association with other clinical
variables. In multivariate regression analysis, the FMD was significantly
positively correlated with BMD (p<0.01), but not with other variables.
Conclusions Postmenopausal women with osteoporosis might have impaired brachial
arterial endothelial function, suggesting that brachial artery endothelial
function might be associated with lumbar spine bone mass in postmenopausal
women.
J Clin Endocrinol Metab. 2007 Sep 25; [Epub
ahead of print]
The Role of RANK/RANKL/OPG: Clinical Implications.
Vega D, Maalouf NM, Sakhaee K.
Department of Internal
Medicine and Charles and Jane Pak Center for Mineral Metabolism and Clinical
Research, University of Texas Southwestern Medical Center, Dallas, Texas
75390-8885.
Context: Receptor activator of
nuclear factor-kappaB ligand (RANKL), receptor activator of nuclear
factor-kappaB (RANK), and osteoprotegerin (OPG) play a central role in bone
remodeling and disorders of mineral metabolism. Evidence Acquisition: PubMed
search was conducted from January 1992 until 2007 for basic, observational, and
clinical studies in subjects with disorders related to imbalances in the
RANK/RANKL/OPG system. Evidence Synthesis: RANK, RANKL, and OPG are members of
the tumor necrosis factor receptor superfamily. The pathways involving them in
conjunction with various cytokines and calciotropic hormones play a pivotal
role in bone remodeling. Several studies involving mutations in the genes
encoding RANK and OPG concluded in the discovery of a number of inherited
skeletal disorders. In addition, basic and clinical studies established a
consistent relationship between the RANK/RANKL/OPG pathway and skeletal lesions
related to disorders of mineral metabolism. These studies were a stepping stone
in further defining the role of the RANK/RANKL/OPG pathway in osteoporosis,
rheumatoid arthritis, bone loss associated with malignancy-related skeletal
diseases, and its relationship to vascular calcifications. Subsequently, the
further understanding of this pathway led to the development of new therapeutic
modalities including the human monoclonal antibody to RANKL and recombinant OPG
as a target for treatment of postmenopausal osteoporosis and multiple myeloma.
Conclusions: The RANK/RANKL/OPG system mediates the effects of calciotropic
hormones and, consequently, alterations in their ratio are key in the
development of several clinical conditions. New agents with the potential to
block effects of RANKL have emerged for treatment of postmenopausal
osteoporosis and malignancy-related skeletal disease.
J Stroke Cerebrovasc Dis. 1998 January -
February;7(1):85-95.
Estrogen after ischemic stroke: Clinical basis and design of The Women's
Estrogen for Stroke Trial.
Kernan WN, Brass LM, Viscoli CM, Sarrel PM, Makuch R, Horwitz RI.
Department of Internal
Medicine, Yale University School of Medicine, New Haven, Connecticut, USA;
Department of Epidemiology and Public Health, Yale University School of
Medicine, New Haven, Connecticut, USA; Department of Neurology, Yale University
School of Medicine, New Haven, Connecticut, USA; Department of Psychiatry, Yale
University School of Medicine, New Haven, Connecticut, USA; Department of
Public Health, Yale University School of Medicine, New Haven, Connecticut, USA;
Department of Obstetrics and Gynecology, Yale University School of Medicine,
New Haven, Connecticut, USA.
BACKGROUND AND PURPOSE::
Observational studies have found that women who take estrogen after menopause
are less likely to have a stroke than women who do not take estrogen. Although
these findings indicate that estrogen may prevent stroke, an alternative
explanation for the improved outcome of estrogen users is that they are
healthier before starting therapy than nonusers. To test the therapeutic effect
of estrogen with research methods that avoid this selection bias, we designed a
randomized controlled trial. TRIAL DESIGN:: The Women's Estrogen For Stroke
Trial (WEST) is a double-blind, randomized trial with a primary goal of
determining whether 1 mg 17beta-estradiol daily, when compared with placebo,
reduces the risk of recurrent stroke or death among postmenopausal women who
have experienced a transient ischemic attack or nondisabling ischemic stroke.
Exclusion criteria include use of estrogen at the time of stroke, breast or
uterine cancer, inability to speak English, and estimated survival less than 5
years. Once randomized, women remain under the care of their personal
physicians for management of stroke risk factors. For early detection of
endometrial hyperplasia and cancer, asymptomatic women receive
medroxyprogesterone yearly (5 mg for 12 days) and vaginal ultrasonography or
biopsy at the end of the trial. Unscheduled uterine bleeding is evaluated with
biopsy. A total of 652 women are sought at 20 hospitals in
Obes Surg. 2007 Jul;17(7):905-9.
Waist circumference is useless to assess the prevalence of metabolic
abnormalities in severely obese women.
Drapeau V, Lemieux I, Richard D, Bergeron J, Tremblay A, Biron S, Marceau P, Mauriège P.
Division of Kinesiology,
Department of Social and Preventive Medicine,
BACKGROUND: The present
retrospective study aims to provide additional evidence supporting the fact
that waist circumference, in severe obesity, is not a good clinical marker to
identify individuals with the metabolic syndrome or an altered metabolic
profile. METHODS: Relationships between waist circumference and metabolic
profile of pre- (n=165) and postmenopausal (n=43) severely obese women were
compared to associations observed in pre- (n=52) and postmenopausal (n=35)
moderately obese women. RESULTS: Results showed that abdominal obesity assessed
by waist circumference was more highly correlated with fasting glycemia,
HDL-cholesterol and the cholesterol/HDL-cholesterol ratio in moderately than in
severely obese women, before menopause. After menopause, waist circumference
was not a valuable predictor of metabolic abnormalities in both groups.
Moreover, when waist circumference was included as a criterion of the metabolic
syndrome (as defined by the NCEP ATP III guidelines) in severely obese women,
the prevalence of this metabolic condition was over-estimated by 72%.
CONCLUSION: These results emphasize the uselessness of waist circumference to
assess the prevalence of the metabolic syndrome or an altered metabolic profile
in severely obese women.
J Clin Oncol. 2007 Sep 24; [Epub ahead of print]
Selective Estrogen-Receptor Modulators and Antihormonal Resistance in
Breast Cancer.
Selective estrogen-receptor
(ER) modulators (SERMs) are synthetic nonsteroidal compounds that switch on and
switch off target sites throughout the body. Tamoxifen, the pioneering SERM,
blocks estrogen action by binding to the ER in breast cancers. Tamoxifen has
been used ubiquitously in clinical practice during the last 30 years for the
treatment of breast cancer and is currently available to reduce the risk of
breast cancer in high-risk women. Raloxifene maintains bone density
(estrogen-like effect) in postmenopausal osteoporotic women, but at the same
time reduces the incidence of breast cancer in both high- and low-risk
(osteoporotic) postmenopausal women. Unlike tamoxifen, raloxifene does not
increase the incidence of endometrial cancer. Clearly, the simple ER model of
estrogen action can no longer be used to explain SERM action at different sites
around the body. Instead, a new model has evolved on the basis of the discovery
of protein partners that modulate estrogen action at distinct target sites.
Coactivators are the principal players that assemble a complex of functional
proteins around the ligand ER complex to initiate transcription of a target
gene at its promoter site. A promiscuous SERM ER complex creates a stimulatory
signal in growth factor receptor-rich breast or endometrial cancer cells. These
events cause drug-resistant, SERM-stimulated growth. The sometimes surprising
pharmacology of SERMs has resulted in a growing interest in the development of
new selective medicines for other members of the nuclear receptor superfamily.
This will allow the precise treatment of diseases that was previously
considered impossible.
J Bone Miner Res. 2007 Sep 24; [Epub
ahead of print]
Effects of Raloxifene on Fracture Risk in Postmenopausal Women: the
Raloxifene Use for The Heart Trial.
Ensrud KE, Stock JL, Barrett-Connor E, Grady D, Mosca L, Khaw KT, Zhao Q, Agnusdei D, Cauley JA.
Microabstract Using data from
a randomized placebo-controlled trial of 10,101 postmenopausal women not
selected on the basis of osteoporosis, we examined whether the effect of
raloxifene treatment on fractures was consistent across categories of fracture
risk. Treatment with raloxifene for 5 years reduced the risk of clinical
vertebral fractures, but not nonvertebral fractures, irrespective of presence
or absence of risk factors for fracture.
Semana del 19 al 25 de Septiembre de 2007
Gynecol Endocrinol. 2007 Sep 19;:1-8
[Epub ahead of print]
Cyclical dydrogesterone in secondary amenorrhea: Results of a
double-blind, placebo-controlled, randomized study.
The Menopause and
PMS Centre, Queen Charlotte's &
Secondary amenorrhea
in women with normal estrogen levels increases the risk of endometrial
carcinoma. Cyclical dydrogesterone induces regular withdrawal bleeding and
effectively protects the endometrium of postmenopausal women receiving
estrogens. In order to assess the efficacy of dydrogesterone in inducing
regular withdrawal bleeds in premenopausal women with secondary amenorrhea or
oligomenorrhea and normal estrogen levels, a double-blind, randomized,
placebo-controlled, multicenter study was conducted in 104 women using cyclical
dydrogesterone as is used for estrogen replacement therapy. Treatment consisted
of dydrogesterone (10 mg/day on days 1-14 followed by placebo on days 15-28 of
each cycle) given for six cycles of 28 days. The control group received placebo
throughout the six cycles. Bleeding was documented by the patient on diary
cards. The number of women with withdrawal bleeding during the first cycle was
twice as high in the dydrogesterone group as in the placebo group (65.4% vs.
30.8%; p = 0.0004). Superiority of dydrogesterone was also observed for
regularity of bleeding over the six cycles (p < 0.0001), although
endometrial thickness after six cycles did not differ between the groups. In
conclusion, dydrogesterone is significantly superior to placebo in inducing
withdrawal bleeding, and maintaining regular bleeding, in women with secondary
amenorrhea and normal estrogen levels.
N Z Med J. 2007 Sep 21;120(1262):U2730.
Vitamin D and muscle strength in patients with previous fractures.
Inderjeeth CA, Glennon D, Petta A, Soderstrom J, Boyatzis I, Tapper J.
Area
Rehabilitation and Aged Care,
AIM: To assess the
vitamin D status and its association with objective left leg muscle strength
measurements in patients with long-bone fracture discharged from a tertiary
hospital in
Obesity (Silver Spring). 2007
Sep;15(9):2276-81.
A two-year randomized weight loss trial comparing a vegan diet to a more
moderate low-fat diet.
Turner-McGrievy GM, Barnard ND, Scialli AR.
University of
North Carolina at Chapel Hill, 2217 McGavran-Greenberg Hall, CB 7461, Chapel
Hill, NC 27599-7461. brie@unc.edu.
OBJECTIVE: The
objective was to assess the effect of a low-fat, vegan diet compared with the
National Cholesterol Education Program (NCEP) diet on weight loss maintenance
at 1 and 2 years. RESEARCH METHODS AND PROCEDURES: Sixty-four overweight,
postmenopausal women were randomly assigned to a vegan or NCEP diet for 14
weeks, and 62 women began the study. The study was done in two replications.
Participants in the first replication (N = 28) received no follow-up support
after the 14 weeks, and those in the second replication (N = 34) were offered
group support meetings for 1 year. Weight and diet adherence were measured at 1
and 2 years for all participants. Weight loss is reported as median
(interquartile range) and is the difference from baseline weight at years 1 and
2. RESULTS: Individuals in the vegan group lost more weight than those in the
NCEP group at 1 year [-4.9 (-0.5, -8.0) kg vs. -1.8 (0.8, -4.3); p < 0.05]
and at 2 years [-3.1 (0.0, -6.0) kg vs. -0.8 (3.1, -4.2) kg; p < 0.05].
Those participants offered group support lost more weight at 1 year (p <
0.01) and 2 years (p < 0.05) than those without support. Attendance at
meetings was associated with improved weight loss at 1 year (p < 0.001) and
2 years (p < 0.01). DISCUSSION: A vegan diet was associated with
significantly greater weight loss than the NCEP diet at 1 and 2 years. Both
group support and meeting attendance were associated with significant weight
loss at follow-up.
Int J Gynaecol Obstet. 2007 Sep 21; [Epub
ahead of print]
Inadequate office
endometrial sample requires further evaluation in women with postmenopausal
bleeding and abnormal ultrasound results.
van Doorn HC, Opmeer BC, Burger CW, Duk MJ, Kooi GS, Mol BW; for the Dutch Study in
Postmenopausal Bleeding (DUPOMEB).
Department of
Gynecological Oncology,
OBJECTIVE: To
determine whether further histologic assessment can be omitted after office
sampling produced a nondiagnostic specimen. METHODS: Data were retrieved from a
prospective cohort study of 913 women presenting with postmenopausal bleeding.
This study was limited to women with an endometrial thickness either
Maturitas. 2007 Sep 20; [Epub ahead of print]
A multicenter,
prospective, randomized, double-blind, placebo-controlled study to investigate
the efficacy of a continuous-combined hormone therapy preparation containing
1mg estradiol valerate/2mg dienogest on hot flushes in postmenopausal women.
Endrikat J, Graeser T, Mellinger U, Ertan K, Holz C.
Bayer Inc., Toronto, Ont.
OBJECTIVES: To
evaluate the effects of an estrogen-reduced, continuous-combined hormone
therapy preparation (HT) containing 1mg estradiol valerate (1EV) and 2mg
dienogest (2DNG) on the number of moderate and severe hot flushes. METHODS:
This study compared the effects of an oral continuous-combined HT containing
1mg EV and 2mg DNG (1EV/2DNG) with those of placebo. The planned treatment
duration was 12 weeks. Data were obtained from 324 postmenopausal women. The
primary efficacy variable was the individual relative change of the mean number
of moderate and severe hot flushes per week. Weeks 5-12 of treatment were
compared with the 2 weeks preceding the treatment phase. RESULTS: Moderate and
severe hot flushes were reduced by 80.8+/-30.9% in the 1EV/2DNG group and by
41.5+/-39.4% in the placebo group. This difference was statistically
significant (p<0.0001; Wilcoxon's rank sum test). The incidence of all types
of hot flushes (mild+moderate+severe) was reduced by 75.2+/-30.2% under
1EV/2DNG and by 35.3+/-37.0% under placebo. In the subset of
non-hysterectomized women, exposure to 1EV/2DNG led to 2.4+/-6.2 days with
bleeding in the reference period of 84 days of treatment, versus 0.3+/-1.3 days
in the placebo group. The safety profile of 1EV/2DNG was very similar to that
of placebo. CONCLUSIONS: Continuous-combined HT preparation with 1mg EV and 2mg
DNG induced a significant reduction of moderate and severe hot flushes compared
to placebo (p<0.0001). Thus, this low-estrogen preparation is an effective
and safe option for HT.
Int J Food Sci Nutr. 2007 Sep 18;:1-9
[Epub ahead of print]
Sodium-bicarbonated mineral water decreases aldosterone levels without
affecting urinary excretion of bone minerals.
Schoppen S, Pérez-Granados AM, Carbajal A, Sarriá B, Navas-Carretero S, Vaquero MP.
Department of
Metabolism & Nutrition, Instituto del Frío, Spanish Council for Scientific
Aim To assess in
healthy postmenopausal women the influence of consuming sodium-bicarbonated
mineral water on postprandial evolution of serum aldosterone and urinary
electrolyte excretion. Methods Eighteen postmenopausal women consumed 500 ml of
two sodium-bicarbonated mineral waters (sodium-bicarbonated mineral water 1 and
sodium-bicarbonated mineral water 2) and a low-mineral water with a standard
meal. Postprandial blood samples were taken at 60, 120, 240, 360 and 420 min
and aldosterone concentrations were measured. Postprandial urinary minerals
were determined. Results Urinary and total mineral excretion and urinary
mineral concentrations did not differ except for sodium concentration, which
was significantly higher with sodium-bicarbonated mineral water 1 than with
low-mineral water (P =0.005). There was a time effect (P =0.003) on the
aldosterone concentration. At 120 min, aldosterone concentrations were lower
with sodium-bicarbonated mineral water 1 (P =0.021) and sodium-bicarbonated
mineral water 2 (P =0.030) compared with low-mineral water. Conclusion Drinking
a sodium-rich bicarbonated mineral water with a meal increases urinary sodium
concentration excretion without changes in the excretion of potassium and bone
minerals.
Curr Opin Lipidol. 2007
Oct;18(5):554-60.
Estrogens in vascular biology and disease: where do we stand today?
Arnal JF, Scarabin PY, Trémollières F, Laurell H, Gourdy P.
aDepartment of
Vascular Biology and Atherothrombosis, INSERM U858-I2MR,
PURPOSE OF REVIEW:
Whereas hormone therapy may increase the risk of coronary heart disease and
stroke in menopausal women, epidemiological studies (protection in
premenopausal women) suggest and experimental studies (prevention of fatty
streak development in animals) demonstrate a major atheroprotective action of
estradiol. There is also evidence for a thrombogenic effect of oral estrogens.
An understanding of the deleterious and beneficial effects of estrogens is thus
required. RECENT FINDINGS: The immuno-inflammatory system plays a key role in
the development of fatty streak deposit as well as in the rupture of the
atherosclerotic plaque. Whereas estradiol favors an anti-inflammatory effect in
vitro (cultured cells), it rather elicits a pro-inflammatory response in vivo
involving several subpopulations of the immuno-inflammatory system, which could
contribute to plaque destabilization. Endothelium is another important target
for estrogens, since estradiol potentiates endothelial nitric oxide and
prostacyclin production. The respective actions of estrogens on these cell
populations may be influenced by the timing of hormonal therapy initiation,
hormone regimens, status of the vessel wall and expression of isoforms of
estrogen receptors alpha and beta. SUMMARY: A better understanding of the
balance between the deleterious and beneficial effects of estrogens is required
and should help to improve hormonal therapy safety and to optimize the
prevention of cardiovascular disease after menopause.
Int J Impot Res. 2007 Sep 20; [Epub
ahead of print]
Is the metabolic syndrome a risk factor for female sexual dysfunction in
sexually active women?
Ponholzer A, Temml C, Rauchenwald M, Marszalek M, Madersbacher S.
1Department of
Urology and Andrology, Danubehospital,
Despite of the
high prevalence, pathogenesis of female sexual dysfunction (FSD) is still
poorly understood. A consecutive series of sexually active women underwent a
health investigation and completed a questionnaire on FSD. Metabolic syndrome
(MS) was defined according to the International Diabetes Federation definition.
A total of 538 women with a mean age of 44 years (range: 30-69) was analysed.
The premenopausal group comprised 329 women (61.2%) with a mean age of 38.5
years; the postmenopausal cohort contained 209 women (38.8%) with a mean age of
52.7 years. In the total cohort (n=538) MS was present in 17.6%, 8.5% in the
premenopausal group and 32.6% in the postmenopausal women. In premenopausal
women, the MS was an independent risk factor for impaired sexual desire
(P=0.03) with an age-adjusted odds ratio of 3.3 (95% confidence interval:
1.5-7.3). In premenopausal female sexual life, the MS represents an independent
role via its correlation to impaired desire.
Menopause. 2007 Sep 18; [Epub ahead of print]
The effect of transdermal and vaginal estrogen therapy on markers of
postmenopausal estrogen status.
Gupta P, Ozel B, Stanczyk FZ, Felix JC, Mishell DR Jr.
From the
Departments of 1Obstetrics and Gynecology and 2Pathology,
OBJECTIVE:: To
compare serum 17beta-estradiol (E2), estrone (E1), estrone sulfate,
follicle-stimulating hormone, luteinizing hormone, sex hormone-binding
globulin, vaginal pH, and the vaginal maturation indices in women using a
low-dose transdermal patch releasing 14 mug of E2 per day and a vaginal ring
releasing 7.5 mug of E2 per day. DESIGN:: Twenty-four postmenopausal women were
randomly assigned to either the patch (n = 12) or the ring (n = 12) for a
12-week study period. Serum E2, E1, estrone sulfate, follicle-stimulating
hormone, luteinizing hormone, and sex hormone-binding globulin were measured by
immunoassay at baseline and 6 and 12 weeks. Vaginal pH was determined at
baseline and 6 and 12 weeks. Vaginal cytologic examinations for vaginal
maturation index were done at baseline and 12 weeks. RESULTS:: Twenty women completed
the study. The patch significantly increased serum E1 and E2 levels at 6 and 12
weeks (P < 0.01); there was no significant increase in serum E1 and E2
levels with the ring. Both the patch and the ring significantly reduced vaginal
pH at 6 (P < 0.001) and 12 (P < 0.001) weeks and significantly reduced
the percentage of vaginal parabasal cells at 12 weeks with no significant
difference between the two groups. Both preparations increased the proportion
of superficial cells; the increase was significant only with the patch (P =
0.04). CONCLUSIONS:: A transdermal E2 skin patch releasing 14 mug of E2 per day
had an effect on vaginal pH and vaginal maturation indices similar to that of a
vaginal E2 ring releasing 7.5 mug of E2 per day. Therefore, this patch is
likely to relieve symptoms of vulvovaginal atrophy.
Am J Epidemiol. 2007 Sep 19; [Epub
ahead of print]
Adiposity and Reporting of Vasomotor Symptoms among Midlife Women: The
Study of Women's Health Across the Nation.
Thurston RC, Sowers MR, Chang Y, Sternfeld B, Gold EB, Johnston JM, Matthews KA.
Department of Psychiatry,
It has long been
hypothesized that increased adiposity would be associated with decreased
vasomotor symptoms during menopause because of conversion of androgens to estrogens
in body fat. However, recent thermoregulatory models have postulated that
increased adipose tissue would be associated with a greater likelihood of
vasomotor symptoms. The authors evaluated these hypotheses in the Study of
Women's Health Across the Nation, a multiethnic, community-based observational
study of
Expert Opin Emerg Drugs. 2007
Sep;12(3):493-508.
Emerging pharmacologic therapies for osteoporosis.
Osteoporotic
fractures are an important public health problem, contributing substantially to
morbidity and mortality in an ageing world population and consuming
considerable health resources. Presently available pharmacologic therapies for
prevention of fragility fractures are limited in scope, efficacy and
acceptability to patients. Considerable efforts are being made to develop new,
more effective treatments for osteoporosis, and to refine/optimize existing
therapies. These novel treatments include an expanding array of drugs that
primarily inhibit osteoclastic bone resorption: estrogenic compounds,
bisphosphonates, inhibitors of receptor activator of NF-kappaB ligand
signaling, cathepsin K inhibitors, c-src kinase inhibitors, integrin inhibitors
and chloride channel inhibitors. The advent of intermittent parathyroid hormone
(PTH) therapy has provided proof-of-principle that osteoblast-targeted
(anabolic) agents can effectively prevent osteoporotic fractures, and is likely
to be followed by the introduction of other therapies based on PTH (orally
active PTH analogs, antagonists of the calcium sensing receptor, PTH-related
peptide analogs) and/or agents that induce osteoblast anabolism by means of
pathways involving key, recently identified, molecular targets (wnt-low-density
lipoprotein receptor-related protein 5 signaling, sclerostin and matrix
extracellular phosphoglycoprotein).
Afr J Med Med Sci. 2007 Mar;36(1):17-21.
Comparative study of coitus and non-coitus in the treatment of
menopausal symptoms.
Department of
Epidemiology,
Eighty-five
consecutive female patients aged 50-55 years with amenorrhea of six consecutive
months at least, sudden onset of sweating and/or feeling hot (hot flushes) that
occurred day or night associated with at least one other menopausal symptom
such as insomnia, painful coitus were randomized into two groups to evaluate
the effect of sexual activity in the treatment of hot flushes of menopause.
They were referred from Jericho Nursing Home,
Semana del 12 al 18 de Septiembre de 2007
Cancer Epidemiol
Biomarkers Prev. 2007 Sep;16(9):1803-11
Weight gain prior to diagnosis and survival from breast cancer.
Cleveland
RJ, Eng SM, Abrahamson
PE, Britton JA, Teitelbaum
SL, Neugut AI, Gammon MD.
Department of Epidemiology,
University of North Carolina, CB 7435 McGavran-Greenberg Hall, Chapel Hill, NC 27599-7435.
becki@unc.edu.
BACKGROUND: To examine the
effects of prediagnostic obesity and weight gain throughout the life course on
survival after a breast cancer diagnosis, we conducted a follow-up study among
a population-based sample of women diagnosed with first, primary invasive, and
in situ breast cancer between 1996 and 1997 (n = 1,508). METHODS: In-person
interviews were conducted shortly after diagnosis to obtain information on
height and weight at each decade of life from age 20 years until 1 year before
diagnosis. Patients were followed to determine all-cause (n = 196) and breast
cancer-specific (n = 127) mortality through
BMJ. 2007 Sep 11; [Epub
ahead of print
Cancer risk among users of oral contraceptives: cohort data from the
Hannaford
PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ.
Department of General Practice
and Primary Care,
OBJECTIVE: To examine the
absolute risks or benefits on cancer associated with oral contraception, using
incident data. DESIGN: Inception cohort study. SETTING:
Climacteric. 2007
Oct;10(5):400-7.
The differential effect of
estrogen, estrogen-progestin and tibolone on coagulation inhibitors in
postmenopausal women.
Keramaris
NC, Christodoulakos
GE, Lambrinoudaki
IV, Dalamanga
A, Alexandrou
AP, Bramis J, Bastounis
E, Creatsas
GC.
Vascular Clinic, 1st
Department of Surgery, University of
Objectives Hormone therapy
increases the risk of venous thromboembolism, possibly through a negative
effect on coagulation inhibitors. The aim of the study was to assess the effect
of conjugated equine estrogens alone or in combination with medroxyprogesterone
acetate, low-dose 17beta-estradiol combined with norethisterone acetate and
tibolone on inhibitors of coagulation. Methods Two hundred and sixteen
postmenopausal women received orally either conjugated equine estrogens 0.625
mg (CEE, n = 24) or tibolone 2.5 mg (n = 24) or CEE + medroxyprogesterone
acetate 5 mg (CEE/MPA, n = 34) or 17beta-estradiol 1 mg + norethisterone
acetate 0.5 mg (E2/NETA, n = 66) or no therapy (control, n = 68) for 12 months.
Plasma antithrombin, protein C and total protein S were measured at baseline
and at 12 months. Results CEE, CEE/MPA and E2/NETA treatment were associated
with a significant decrease in antithrombin levels (CEE: baseline 235.6 +/-
47.6 mg/l, follow-up 221.3 +/- 48.3 mg/l, p = 0.0001; CEE/MPA: baseline 251.1
+/- 38.6 mg/l, follow-up 225.0 +/- 42.6 mg/l, p = 0.009; E2/NETA: baseline
257.1 +/- 59.4 mg/l, follow-up 227.1 +/- 50.4 mg/l, p = 0.007; tibolone:
baseline 252.6 +/- 62.4 mg/l, follow-up 261.9 +/- 59.1 mg/l, p = 0.39). Protein
C decreased significantly in the CEE and CEE/MPA groups (CEE: baseline 3.64 +/-
1.17 mg/l, follow-up 2.48 +/- 1.47 mg/l, p = 0.004; CEE/MPA: baseline 3.24 +/-
1.23 mg/l, follow-up 2.61 +/- 1.38 mg/l, p = 0.001; E2/NETA: baseline 3.24 +/-
1.10 mg/l, follow-up, 3.15 +/- 1.11 mg/l, p = 0.08; tibolone: baseline 3.26 +/-
1.25 mg/l, follow-up 3.09 +/- 1.32 mg/l, p = 0.37). Protein S decreased
significantly only in the CEE/MPA group (CEE: baseline 19.4 +/- 2.76 mg/l,
follow-up 18.0 +/- 2.45 mg/l, p = 0.56; CEE/MPA: baseline 18.4 +/- 3.42 mg/l,
follow-up 14.5 +/- 3.43 mg/l, p = 0.005; E2/NETA: baseline 19.0 +/- 3.11 mg/l,
follow-up 19.5 +/- 3.43 mg/l, p = 0.18; tibolone: baseline 18.5 +/- 3.09 mg/l,
follow-up 18.0 +/- 4.09 mg/l, p = 0.32). Conclusions Estrogen and
estrogen-progestin therapy are associated with a reduction in coagulation
inhibitors, the extent of which depends on the regimen administered. Tibolone
appears to have no effect on inhibitors of coagulation.
Climacteric. 2007
Oct;10(5):393-9
Menopause alters the metabolism of serum serotonin precursors and their
correlation with gonadotropins and estradiol.
Carretti N, Florio P, Reis FM, Comai S, Petraglia
F, Costa CV.
Department of Pediatrics,
Obstetrics and Reproductive Medicine,
Objective Tryptophan, the
serotonin (5-HT) precursor, is circulating in blood in both free (FT) and
protein-bound forms. The free form crosses the hematoencephalic barrier and is
converted into 5-HT. During the fertile years, tryptophan levels are negatively
correlated to gonadotropin concentrations. The present study aims to evaluate
the correlation between circulating tryptophan, gonadotropin and estradiol (E2)
levels postmenopause. Methods Serum levels of total tryptophan (TT, free +
protein-bound) and FT, and plasma luteinizing hormone (LH), follicle
stimulating hormone (FSH), and E2 were determined in 15 postmenopausal women
and 15 cycling women during follicular (days 7-10), periovulatory (days 13-16)
and luteal (days 21-24) phases of the menstrual cycle. Data were analyzed by
ANOVA, linear correlation coefficients and hierarchical cluster analysis of
variables. Results TT, but not FT, levels were significantly (p < 0.05)
higher in postmenopausal (12.07 +/- 0.40 microg/ml) than fertile women in the
periovulatory period (10.46 +/- 0.36 microg/ml). In postmenopausal women, there
was no significant correlation between TT and FT, nor between these tryptophan
forms and gonadotropins, but only between FT and E2. Cluster analysis showed
that the main cluster composed by FSH-LH-TT-FT observed in fertile women was
absent in postmenopause, since both serum tryptophan forms were distant from
gonadotropins. Conclusion High TT levels circulate in postmenopausal women,
with lack of correlation between TT and FT, and FT/TT and gonadotropins. Since
estrogens play a pivotal role on central 5-HT metabolism, estrogen deprivation
may alter the brain tryptophan utilization for 5-HT synthesis and its relation
to gonadotropin release.
Climacteric. 2007
Oct;10(5):386-92
Could androgens protect middle-aged women from cardiovascular events? A
population-based study of Swedish women: The Women's Health in the
Khatibi A, Agardh CD, Shakir YA, Nerbrand C, Nyberg P, Lidfeldt J, Samsioe G.
Departments of Clinical
Sciences in
Objective The aim of this
analysis was to delineate perceived associations between androgens and
cardiovascular events in perimenopausal women. Design A cross-sectional,
population-based study of 6440 perimenopausal women aged 50-59 years, living in
Climacteric. 2007
Oct;10(5):358-70
New hormonal therapies and regimens in the postmenopause: routes of
administration and timing of initiation.
Population Council and
Since the publication of the
Women's Health Initiative (WHI) study followed by the results of the Million
Women Study (MWS), the role of hormonal therapy in postmenopausal women has
been further challenged. The risks attributed to hormone therapy have been
overestimated and the data has been wrongly extrapolated to the whole class of
therapies. The trends in postmenopausal hormonal therapy seem now to favor the
non-oral delivery routes for both the estrogen and the progestin for women with
an intact uteru,s based on the assumption that a lesser stimulation of the
liver proteins and a neutral metabolic profile would be more favorable in terms
of cardiovascular and venous risk. The combination of non-oral administration
of estradiol and local delivery of progesterone or a progestin such as
levonorgestrel by means of gels, sprays, vaginal rings or intrauterine systems
would represent new methods of replacement therapy for the menopausal woman,
improving compliance and minimizing the risks of hormone replacement. Several
of these systems are either available or in development. Long-term studies on
the risk/benefit of various non-oral formulations are certainly warranted.
Acta Obstet Gynecol Scand. 2007 Sep 4;:1-7
[Epub ahead of print
Postmenopausal endometriosis.
Oxholm D, Knudsen UB, Kryger-Baggesen
N, Ravn P.
Department of Gynaecology and
Obstetrics,
Background. Postmenopausal endometriosis
is rare. The purpose of this presentation is to give a review of the topic
based on existing literature. Methods. A Medline search concerning
postmenopausal endometriosis was carried out. Hormone therapy and risk of
malignancy in these patients are discussed. Results. Some 32 case reports on
postmenopausal endometriosis were found. The most common location is in the
ovaries. Estrogens stimulate endometriosis. There is a risk of recurrence or de
novo occurrence of endometriosis after the menopause in patients who take
hormone therapy (HT); especially estrogen only therapy (ET). So far, treatment
has primarily been surgery (hysterectomy (TAH) and bilateral oophorectomy
(BSO)). There is little experience with medical treatment (aromatase inhibitors).
The risk of malignant transformation of premenopausal endometriosis is around
1%. Furthermore, patients with endometriosis have an increased risk of ovarian
cancer, and, apparently, other malignancies. The risk of malignant
transformation appears to be further elevated in patients who take ET, although
this subject is not fully elucidated. Conclusions. Although the condition is
rare, it is important to be aware of endometriosis after the menopause.
Postmenopausal endometriosis infers a risk of recurrence and malignant
transformation. Although solid evidence is lacking, the risk of malignant
transformation appears to be lower during combined HT compared to ET. Thus,
hormone replacement therapy should generally be reserved for patients with
severe climacteric complaints, and if indicated, combined therapy should be
used.
Neuroepidemiology. 2007 Sep
11;28(4):207-213 [Epub ahead of print
Carotid Intima-Media Thickness and Cognitive Function in Elderly Women:
A Population-Based Study.
Komulainen
P, Kivipelto
M, Lakka TA, Hassinen M, Helkala EL, Patja K, Nissinen A, Rauramaa R.
Kuopio Research Institute of
Exercise Medicine,
Objective: Several vascular
risk factors have been linked to cognitive decline. However, little is known
about the association between the atherosclerotic process and cognitive
impairment. We investigated whether carotid intima-media thickness (IMT)
predicts the risk of cognitive impairment and whether the putative impairment
is specific for some cognitive domains. Methods: A 12-year population-based
follow-up study was performed for a total of 91 women, aged 60-70 years at
baseline. Ultrasonographically assessed carotid artery IMT and the Mini-Mental
State Examination test were performed at baseline and 12-year follow-up. A
detailed cognitive evaluation for memory and cognitive speed was performed in
2003. The mean of left and right carotid bifurcation IMT was used in the
analyses for association with the risk for poor cognitive speed and memory.
Results: Increased IMT at baseline was an independent predictor for poor memory
(beta = -5.004, 95% confidence interval = -7.74 to -2.27; p = 0.001) and
cognitive speed (beta = 2.562, 95% confidence interval = 1.19-4.94; p = 0.035)
at 12-year follow-up after adjustment for age, education, depression, plasma
LDL cholesterol, systolic blood pressure, cardiovascular disease, hormone
replacement therapy, smoking, alcohol consumption and physical activity. The
risk for poor memory (p = 0.023 for linear trend) and cognitive speed (p =
0.070 for linear trend) increased with increasing IMT tertiles. Conclusions:
Carotid IMT predicts an increased risk for cognitive impairment, particularly
poor memory and cognitive speed, in elderly women.
Am J Epidemiol. 2007 Sep
1;166(5):506-10.
Hormones and heart disease in women: the timing hypothesis.
Division of Epidemiology,
Department of Family and Preventive Medicine, School of Medicine, University of
California, San Diego, CA, USA. ebarrettconnor@ucsd.edu
Largely on the basis of
results from meta-analyses of observational studies, postmenopausal estrogen
was widely prescribed to prevent coronary heart disease. However, epidemiologic
studies, no matter how consistent and coherent, are not sufficient to recommend
mass preventive therapy to healthy women. In fact, all three large clinical
trials failed to confirm estrogen's expected cardiac protection. The most
persistent explanatory hypothesis for the "trial failure" was the age
of the participants, based on the thesis that estrogen in recently menopausal
women could prevent the development of coronary artery plaque but, given to older
women with vulnerable plaque, would have a null or even harmful effect. The
timing hypothesis is plausible, but the prespecified subgroup analyses in both
Women's Health Initiative trials showed no significant interaction with age or
years since menopause. The best opportunity to test the timing hypothesis was
lost when 1,000 Women's Health Initiative women younger than 60 years had
coronary artery calcium scans to evaluate the effect of estrogen on plaque
burden, but no women 60 years or over were similarly examined. Therefore, this
ancillary study can examine the effect of estrogen treatment on coronary
calcium in women younger than 60 years but will not be able to determine if the
effect is different in older women. In the meantime, publicized statements in multiple
venues have promoted the timing hypothesis as fact, confusing patients and
physicians who do not realize that the hypothesis is stronger than the
evidence.
Int J Cancer. 2007 Sep 10; [Epub
ahead of print
Oral contraceptive use, hormone replacement therapy, reproductive
history and risk of colorectal cancer in women.
Kabat GC, Miller AB, Rohan TE.
Department of Epidemiology and
Population Health,
Evidence from epidemiologic
studies suggests a possible role of exogenous and endogenous hormones in
colorectal carcinogenesis in women. However, with respect to exogenous
hormones, in contrast to hormone replacement therapy, few cohort studies have
examined oral contraceptive use in relation to colorectal cancer risk. We used
data from a large cohort study of Canadian women enrolled in a randomized
controlled trial of breast cancer screening to assess the association of oral
contraceptive use, hormone replacement therapy and reproductive factors with
risk of colorectal cancer, overall and by subsite within the colorectum. Cancer
incidence and mortality were ascertained by linkage to national databases.
Among 89,835 women aged 40-59 at enrollment and followed for an average of 16.4
years, we identified 1,142 incident colorectal cancer cases. Proportional
hazards models were used to estimate the associations between the exposures of
interest and risk of colorectal cancer. Ever use of oral contraceptives at
baseline was associated with a modest reduction in the risk of colorectal
cancer (hazard ratio 0.83, 95% confidence interval 0.73-0.94), with similar
effects for different subsites within the colorectum. No trend was seen in the
hazard ratios with increasing duration of oral contraceptive use. No
associations were seen with use of hormone replacement therapy (ever use or
duration of use) or reproductive factors. Our results are suggestive of an inverse
association between oral contraceptive use and colorectal carcinogenesis.
However, given the lack of a dose-response relationship and the potential for
confounding, studies with more complete assessment of exogenous hormone use
throughout the life course are needed to clarify this association.
CMAJ. 2007 Sep
11;177(6):575-80
Low bone mineral density and fracture burden in postmenopausal women.
Cranney A, Jamal SA, Tsang JF, Josse RG, Leslie WD.
Clinical Epidemiology Program,
Ottawa Health Research Institute,
BACKGROUND: The study
objectives were to determine fracture rates in relation to bone mineral density
at various central skeletal sites, using the World Health Organization
definition for osteoporosis (T-score -2.5 or less), and to contrast fracture
patterns among women 50 to 64 years of age with those among women 65 years of
age and older. METHODS: Historical cohort study with a mean observation period
of 3.2 (standard deviation [SD] 1.5) years. The study group (16,505 women 50
years of age or older) was drawn from the Manitoba Bone Density Program
database, which includes all bone mineral density results for
J Diabetes Complications. 2007
Sep-Oct;21(5):315-9
Risks of CHD identified by different criteria of metabolic syndrome and related
changes of adipocytokines in elderly postmenopausal women.
Ding QF, Hayashi T, Zhang XJ, Funami J, Ge L, Li J, Huang XL, Cao L, Zhang J, Akihisa I.
Department of Geriatrics,
Medicine in Growth and Aging, Program in Health and Community Medicine, Nagoya
University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of
Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
The objective of this study
was to assess the capacity of different criteria of metabolic syndrome (MetS)
to identify risks of coronary heart diseases (CHDs) and related changes of
adipocytokines in postmenopausal women. A cross-sectional study was carried out
in 225 community-dwelling, elderly postmenopausal Chinese women (age,
66.77+/-5.09 years) without hormone replacement therapy (HRT). Baseline data
such as blood pressure, body mass index (BMI), serum lipid profiles, and
fasting glucose were analyzed, and insulin sensitivity was estimated via the
homeostasis model assessment for insulin resistance. Serum tumor necrosis
factor alpha (TNFalpha), interleukin-6 (IL-6), and adiponectin were measured
simultaneously. The prevalence of MetS identified by the Third Report of the
National Cholesterol Education Programme Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol in Adults, the International Diabetes
Federation (IDF), the Chinese Diabetes Society (CDS), and the Japanese Society
of Internal Medicine (JPN) were 27.31%, 37.34%, 23.29%, and 13.65%,
respectively. No significant differences of baseline data were found among
different MetS groups, except for a significant higher waist circumference in
the JPN-MetS group as compared with other MetS groups. The prevalence of
confirmed CHD in the four MetS groups were 26.2%, 18.6%, 26.9%, and 32%,
respectively. Odds ratios for CHD were 1.905 (95% CI=1.273-2.851), 1.208 (95%
CI=0.778-1.876), 1.997 (95% CI=1.238-3.221), and 2.336 (95% CI=1.119-4.876),
respectively. The JPN-MetS group had higher levels of TNFalpha and IL-6,
whereas the CDS-MetS group correlated better with lower adiponectin levels. The
IDF definition for MetS is the most sensitive one with regard to metabolic
disorders, whereas JPN and CDS definitions correlate better with CHD and
changes of adipocytokines among the four criteria studied.
Semana del 5 al 11 de
Septiembre de 2007
Rheumatol Int. 2007 Sep 6; [Epub
ahead of print
Total oxidative/anti-oxidative status and relation to bone mineral
density in osteoporosis.
Altindag O, Erel O, Soran N, Celik H, Selek S.
Department of Physical
Medicine & Rehabilitation,
The aim of this study was to
evaluate the total antioxidant status (TAS), total oxidative status (TOS) and
oxidative stress index (OSI) in patients with postmenopausal osteoporosis. We
also investigate the relation between bone mineral density and
oxidative/antioxidative parameters. Thirty-nine patients with osteoporosis and
26 healthy controls were included in the study. Plasma TAS, TOS levels were
determined by using a novel automated methods. Plasma TOS and OSI value were
significantly higher, and plasma TAS level was lower in patients than in
healthy controls (P < 0.001 for all). There was a significant negative
correlation between OSI and BMD in lumbar and femoral neck region (r = -0.63, P
< 0.001; r = 0.40, P = 0.018). The results of this study indicated that
increased osteoclastic activity and decreased osteoblastic activity may be associated
with an imbalance between oxidant and antioxidant status in postmenopausal
osteoporosis. Therefore, supplementation of antioxidant-enriched diet to the
therapy might shed light on the development of novel therapeutic strategies for
osteoporosis.
Am J Clin Nutr. 2007 Sep;86(3):639-44
Effects of dietary calcium intake on body weight and prevalence of
osteoporosis in early postmenopausal women.
Varenna M, Binelli L, Casari S, Zucchi F, Sinigaglia L.
Department of Rheumatology,
Gaetano Pini Institute,
BACKGROUND: High calcium
intakes seem to be ineffective at reducing bone loss in early postmenopausal
women. However, the inverse relation between calcium intake and body weight can
attenuate the negative effect of a low dietary calcium intake. OBJECTIVE: The
objective was to assess the role of dietary calcium and body mass index (BMI)
on osteoporosis, defined according to World Health Organization criteria as a
lumbar bone density >2.5 SD below the T score. DESIGN: This was a
cross-sectional, retrospective, observational study conducted in 1771 healthy,
early postmenopausal women, who were not taking calcium supplements at the first
densitometric evaluation. Weekly frequency of dairy food consumption was used
to estimate the relative intake of dietary calcium. Total dairy intake was
classified into 4 categories by quartile cutoffs. Multiple logistic regression
analyses were used to study this sample. RESULTS: BMI and prevalence of
overweight showed significant inverse trends with increasing dairy intake.
Calcium intake was not associated with osteoporosis when overweight was not
considered. However, when overweight was considered in the analysis, women with
the lowest calcium intake were more likely to have osteoporosis (odds ratio:
1.46; 95% CI: 1.12, 1.89; P = 0.008) than were women with the highest calcium
intake. CONCLUSIONS: In early postmenopausal women, a low dietary calcium intake
may increase the risk of osteoporosis, but its negative effect can be offset by
the greater BMI found in women with a low calcium intake.
Ann Oncol. 2007 Sep 4; [Epub
ahead of print
Menopause hormone replacement therapy and cancer risk: an Italian record
linkage investigation.
Corrao G, Zambon A, Conti V, Nicotra F, La Vecchia C, Fornari C, Cesana G, Contiero P, Tagliabue G, Nappi R, Merlino L.
Department of Statistics; Unit
of Epidemiology and Biostatistics, University of Milan-Bicocca.
BACKGROUND: The effects of
persistence with hormone replacement therapy (HRT) on the risk of
hospitalization for cancer and of the route of HRT administration on the risk
of breast and colorectal cancer were explored in a large cohort study. PATIENTS
AND METHODS: The 73 505 women residing in Lombardia (
Menopause Int. 2007
Sep;13(3):124-131
Efficacy and tolerability of continuous combined hormone replacement
therapy in early postmenopausal women.
Mattsson
LA, Skouby S, Rees M, Heikkinen
J, Kudela M, Stadnicki-Kolendo
A, Mattila L, Salminen K, Vuorela A, Mustonen M; The
Indivina 321 Study Group.
Department of Obstetrics and
Gynecology,
OBJECTIVE: Continuous combined
hormone replacement therapy (ccHRT) based on estradiol valerate (E(2)V) and
medroxyprogesterone acetate (MPA) is effective for relief of menopausal
symptoms three years or more after the menopause. This study was undertaken to
examine the efficacy and tolerability of ccHRT in early postmenopausal women
(last menstrual period 1.3 years before study entry). STUDY DESIGN: This was a
52-week, randomized, double-blind, multinational study of ccHRT comprising
three different dose combinations of E(2)V/MPA in 459 early postmenopausal
non-hysterectomized women experiencing 30 or more moderate to severe hot
flushes a week and/or vasomotor symptoms requiring treatment. MAIN OUTCOMES
MEASURES: The primary endpoint was change in frequency and severity of moderate
to severe hot flushes at 12 weeks. Secondary outcome measures included number
of bleeding days and evaluation of tolerability. RESULTS: The frequency of hot
flushes was reduced by >/=70% after one month (P<0.001 for all doses at
week 2 onwards), with little evidence of statistically different dose effects.
Severity of flushing was also attenuated by ccHRT. Mean number of bleeding days
fell to <1 per 28-day cycle at 52 weeks. Rates of amenorrhoea approached
80-90% at the end of the study, but were significantly lower at several time
points with the highest-dose regimen (2 mg E(2)V + 5 mg MPA) than with the
lower-dose options (1 mg E(2)V + 2.5 mg MPA and 1 mg E(2)V + 5 mg MPA;
P<0.05). Adverse events declined in frequency over time with all regimens
but throughout the study were more numerous with the highest-dose regimen than
with lower doses (P= 0.0002). CONCLUSIONS: Continuous combined HRT was
effective for the relief of climacteric symptoms in early postmenopausal women
and was well tolerated.
Menopause Int. 2007
Sep;13(3):116-123
Continuous combined
hormone replacement therapy relieves climacteric symptoms and improves
health-related quality of life in early postmenopausal women.
Pitkin J, Smetnik VP, Vadász P, Mustonen M, Salminen K, Ylikangas
S; The
Indivina 321 Study Group.
The Menopause Clinical and
Research Unit,
OBJECTIVE: Hormone replacement
therapy (HRT) relieves menopausal symptoms but its effect on health related
quality of life (HRQoL) is uncertain. The aim of this study was to assess the
effect of three dose regimens of continuous combined HRT, consisting of
estradiol valerate (E(2)V) and medroxyprogesterone acetate (MPA) on HRQoL in
early postmenopausal women (last menstrual period 1-3 years before study
entry). STUDY DESIGN: This was a 52-week, randomized, double-blind,
multinational study comparing E(2)V (1 mg or 2 mg) plus MPA (2.5 mg or 5 mg) in
different dose combinations. The intention-to-treat population comprised 459
women (average age 51.5 years). MAIN OUTCOME MEASURES: HRQoL was assessed by
the Women's Health Questionnaire (WHQ), the 15D Questionnaire and a visual
analogue scale (VAS). RESULTS: There were improvements on eight of the nine
domains of the WHQ with all dose regimens during the first 12 weeks (P<0.0001)
and an improvement in the remaining domain (menstrual symptoms) with the
lower-dose regimens (P<0.05). These initial improvements in HRQoL were then
maintained or augmented over the remainder of the study (P<0.0001 for change
from baseline at 52 weeks for all domains and dose regimens). Mean 15D total
score had improved meaningfully and significantly by 12 weeks (P<0.0001
versus baseline) in all treatment groups and this improvement was maintained
thereafter. This improvement in 15D total score was most marked among previous
non-users of HRT (P<0.05 versus previous users). VAS scores recorded
significant (P<0.05) reductions in hot flushes, sweating and sleep
disturbances in all groups after week 1 and highly significant (P<0.0001)
relief of all climacteric symptoms at week 52. CONCLUSION: Continuous combined
HRT was associated with pronounced improvement of vasomotor symptoms and HRQoL
in this population of early postmenopausal women.
Reuters.Health Information
Hemoglobin A1c Can Predict Diabetes in Women
Risk associations persisted
after exclusion of cases diagnosed within 2 and 5 years of follow-up and after
further adjustment for C-reactive protein. "Although these data do not
support the use of HbA1c as a single measure of diabetes risk, our results do
suggest that the prognostic significance of elevated HbA1c may warrant a
greater emphasis in primary prevention," Dr. Pradhan's team concludes.
Am J Med 2007;120:720-727.
MEDSCAPE.Medical News
Passive Smoking Increases Risk for Sleep
Disturbance During Pregnancy CME
News
Author: Laurie Barclay, MD; CME Author: Penny Murata, MD
Women's Health. 2007;3(4):395-408. ©2007 Future
Medicine Ltd.
Ethinyl Estradiol/Drospirenone for the Treatment of the Emotional and
Physical Symptoms of Premenstrual Dysphoric Disorder
Andrea
J. Rapkin; Michelle McDonald; Sharon A. Winer
A combined oral contraceptive
pill containing 20 µg of ethinyl estradiol and 3 mg of the progestin
drospirenone in a novel dose regimen (24 active pills followed by 4 placebo
pills), has demonstrated efficacy for the symptoms of premenstrual dysphoric
disorder, a severe form of premenstrual syndrome, with an emphasis on the
affective symptoms. Drospirenone has progestagenic, anti-androgenic and
anti-aldosterone properties, which differ from earlier generations of
progestins, and reducing the hormone pill-free interval allows for better
suppression of ovarian steroid production.
|
Formulation |
Study
type |
N |
Population
studied and findings |
Ref |
|
Drospirenone
3 mg/EE 30 µg 21/7 |
RCT |
82 |
Women with PMDD.
Beneficial effect on most symptoms |
[47] |
|
Drospirenone 3 mg/EEl 30 µg 21/7 |
Cohort, |
326 |
Women
participating in contraceptive study |
[46] |
|
Drospirenone
3 mg/EE 30 µg 21/7 |
Cohort |
336 |
Women with
symptoms of PMS Significantly decreased incidence and severity of somatic
symptoms and increased general well being compared with baseline |
[45] |
|
Drospirenone
3 mg/EE 30 µg; desogestrol 150 µg/EE 30 µg |
Open
label |
627 |
Women taking COC
for contraception: |
[70] |
|
Drospirenone
3 mg/EE 30 µg: |
Open
label |
99 |
Women taking COC
for contraception Decreased symptoms from 58 to 32% in drospirenone/EE group |
[74] |
|
Drospirenone
3 µg/EE 30 µg 21/7 |
Open
label |
1433 |
Women desiring
contraception Decreased edema, breast tenderness and bloating. Reductions
greater with extended regimen (extended for 42-126 days) |
[75] |
|
Drospirenone 3 mg/ethinyl estradiol 20 µg 24/4 |
RCT |
450 |
Women with PMDD:
Significantly decreased physical, mood and behavioral symptoms with 48%
response rate to drospirenone/EE. 36% response rate to placebo |
[16] |
|
Drospirenone 3 mg/20 µg ethinyl estradiol 24/4 |
RCT Crossover trial |
64 |
Women with PMDD.
Significantly decreased physical, mood and behavioral symptoms. 62% response
rate to drospirenone/EE 32% response rate to placebo |
[15] |
OC = Oral contraceptive; PMDD
= Premenstrual dysphoric disorder; PMS = Premenstrual syndrome; RCT =
Randomized, controlled trial.
Semana del 29 de Agosto al 4 de Septiembre de
2007
Int J Cardiol. 2007 Aug 29; [Epub ahead of print]
HDL-C in post-menopausal women: An important therapeutic target.
Department of Cardiac
Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial
Colllege London, Technology and Medicine, Dovehouse Street, London, SW3 6LY,
UK.
Coronary heart disease is a
major cause of mortality in women in Western industrialised countries,
particularly after the age of 50 years, coinciding with the onset of the
menopause and potentially adverse metabolic changes that occur during the
transitional peri-menopausal and post-menopausal periods. Dyslipidaemia
characterised by increases in plasma levels of low-density lipoprotein cholesterol
(LDL-C), triglycerides and lipoprotein(a) and a decrease in high-density
lipoprotein cholesterol (HDL-C) together with the emergence of other diagnostic
features of the metabolic syndrome are key factors that increase cardiovascular
risk. Treatment beyond LDL-C with a combination of different lipid-modifying
therapies may therefore be of greater importance in women than men. Fibrates
and nicotinic acid are two treatments that may be added to primary statin
therapy. Fibrates are more effective in lowering elevated triglycerides,
whereas nicotinic acid is more effective in raising HDL-C. Although there is
clearly a need for clinical trials in women, the available data suggests that
combination lipid-modifying therapy is a logical treatment strategy in this
high-risk patient group.
Evid Rep Technol Assess (Full Rep). 2006
May;(139):1-117.
Multivitamin/Mineral Supplements and Prevention of Chronic Disease.
Huang HY, Caballero B, Chang S, Alberg A, Semba R, Schneyer C, Wilson RF, Cheng TY, Prokopowicz G, Barnes GJ 2nd, Vassy J, Bass EB.
OBJECTIVES: To review and
synthesize published literature on the efficacy of multivitamin/mineral
supplements and certain single nutrient supplements in the primary prevention
of chronic disease in the general adult population, and on the safety of
multivitamin/mineral supplements and certain single nutrient supplements,
likely to be included in multivitamin/mineral supplements, in the general
population of adults and children. DATA SOURCES: All articles published through
J Sex Med. 2007 Sep;4(5):1223-1235.
Are the Endocrine Society's Clinical Practice Guidelines on Androgen
Therapy in Women Misguided? A Commentary.
Traish A, Guay AT, Spark RF; the Testosterone Therapy in
Women Study Group.
Laboratory for Sexual Medicine
Research,
The Endocrine Society Clinical
Guidelines on Androgen Therapy in Women (henceforth referred to as the
Guidelines) do not necessarily represent the opinion held by the many
health-care professionals and clinicians who are specialized in the evaluation,
diagnosis, and treatment of women's health in androgen insufficiency states.
The recommendations provided in the published Guidelines are neither accurate
nor complete. We disagree with the therapeutic nihilism promoted by these
Guidelines. The members of the Guidelines Panel (henceforth referred to as the
Panel), in their own disclaimer, stated that the Guidelines do not establish a
standard of care. Based on data available in the contemporary literature, on
the role of androgens in women's health, we provide in this commentary a
point-by-point discussion of the arguments made by the Panel in arriving at
their recommendations. It is our view that the Guidelines are not based on the
preponderance of scientific evidence. Health-care professionals, physicians, and
scientists often disagree when determining how best to address and manage new
and emerging clinical issues. This is where we stand now as we endeavor to
understand the role of androgens in a woman's health and welfare. Indeed, some
basic facts are not in contention. All agree that dehydroepiandrosterone
sulfate (DHEA-S) production from the adrenal gland begins during the preteen
years, peaks in the mid 20s, then declines progressively over time. In
contrast, ovarian androgen (i.e., testosterone) secretion commences at puberty,
is sustained during a woman's peak reproductive years and declines as a woman
ages, with a more rapid and steep decrease after surgical menopause. However,
there are ample data to suggest that adrenal androgens play a role in the development
of axillary and pubic hair, and that testosterone is critical for women's
libido and sexual function. We take this opportunity to invite members of the
Panel on Androgen Therapy in Women to discuss, clarify, comment, or rebut any
of the points made in this Commentary. It is our goal to elevate this debate in
order to provide women who are afflicted with androgen insufficiency and sexual
disorders with the highest quality health care and to relieve their distress
and suffering, as well as to improve their quality of life.
Osteoporos Int. 2007 Sep 1; [Epub ahead of print]
Depression and osteoporosis: epidemiology and potential mediating
pathways.
Department of Mental Health,
Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway Suite 886,
Baltimore, MD, 21205, USA, bmezuk@jhsph.edu.
INTRODUCTION: There have been
numerous studies examining the association between depression and bone mineral
density (BMD), but the underlying nature of this relationship remains unclear.
Independent of this association, there is a growing body of evidence that
depression impacts the risk for fracture in older adults. This article reviews
the current epidemiological evidence regarding comorbidity of depression, low
bone mineral density, and fracture. METHODS: A review of the literature on
depression, depressive symptoms, low BMD, osteoporosis, and fracture using
electronic databases. RESULTS: We reviewed 20 studies of the association
between depression and BMD and five reports of the relationship between
depression and fractures. Potential mediating mechanisms (both physiological
and behavioral) are discussed, as well as potential confounding influences
(e.g., medication use). CONCLUSIONS: Most studies support the finding that
depression is associated with increased risk for both low BMD and fractures,
but variation in study design, sample composition, and exposure measurement
make comparisons across studies difficult. Researchers should be aware of
potential confounders, such as medication use, that may influence results.
Future research should focus on identifying mediating pathways and targets for
intervention in the relationships between depression, low BMD, and fracture.
Neurology. 2007 Aug 29; [Epub ahead of print]
Increased risk of cognitive impairment or dementia in women who
underwent oophorectomy before menopause.
Rocca WA, Bower JH, Maraganore DM, Ahlskog JE, Grossardt BR, de Andrade M, Melton Iii LJ.
From the Division of
Epidemiology, Department of Health Sciences Research (W.A.R., L.J.M.),
Department of Neurology (W.A.R., J.H.B., D.M.M., J.E.A.), and Division of
Biostatistics, Department of Health Sciences Research (B.R.G., M. de A.), Mayo
Clinic College of Medicine,
ABSTRACT OBJECTIVE: There is
increasing laboratory evidence for a neuroprotective effect of estrogen;
however, the clinical and epidemiologic evidence remains limited and
conflicting. We studied the association of oophorectomy performed before the
onset of menopause with the risk of subsequent cognitive impairment or
dementia. METHODS: We included all women who underwent unilateral or bilateral
oophorectomy before the onset of menopause for a non-cancer indication while
residing in
Public Health Nutr. 2007 Sep 3;:1-7 [Epub ahead of print]
Dietary and non-dietary determinants of central adiposity among Tehrani
women.
2Food Security and
OBJECTIVE: To determine the
correlates of central adiposity. DESIGN: Population-based cross-sectional
study. SUBJECTS: A total of 926 women (aged 40-60 years) from all districts of
Eur J Contracept Reprod Health Care. 2007
Sep;12(3):229-39.
A one-year
randomized double-blind, multicentre study to evaluate the effects of an
oestrogen-reduced, continuous combined hormone replacement therapy preparation
containing 1 mg oestradiol valerate and 2 mg dienogest on metabolism in
postmenopausal women.
Endrikat J, Lange E, Kunz M, Schmidt W, Graeser T.
Bayer HealthCare,
Objectives To evaluate the
impact of an oestrogen-reduced, continuous combined hormone replacement therapy
preparation containing 1 mg oestradiol valerate (1EV) and 2 mg dienogest (2DNG)
on metabolism. Methods In a randomized double-blind study, 1EV/2DNG was
compared with a reference preparation containing 1 mg 17ss-oestradiol and 0.5
mg norethisterone acetate (E2/NETA). For the primary variable, i.e. the ratio
of HDL cholesterol (week 52 to baseline), at least 98 case evaluations were
planned. Secondary variables were other lipid parameters, haemostasis factors
and carbohydrate metabolism. Results After 1 year of treatment, the mean HDL cholesterol
levels had decreased by 4.5 +/- 14.8% in the 1EV/2DNG group and by 6.1 +/-
13.9% in the E2/NETA group (treatment difference NS). The ratio of HDL
cholesterol (week 52 to baseline) was 0.944 for 1EV/2DNG and 0.929 for E2/NETA
(geometric means). The primary efficacy variable, the ratio of the geometric
means of the two treatments (1EV/2DNG/E2/NETA) was 1.016, with a lower
one-sided 95% confidence limit of 0.973, which was clearly above the
prespecified non-inferiority bound of 0.85 (p-value < 0.001). HDL2
cholesterol increased by 0.3 +/- 34.4% (1EV/2DNG) and decreased by 6.2 +/-
34.3% (E2/NETA; treatment difference NS); HDL3 cholesterol decreased by 4.4 +/-
19.9% (1EV/2DNG) and 8.2 +/- 17.7% (E2/NETA; treatment difference NS). Changes
in the haemostasis and carbohydrate variables were very similar in both
treatment groups. Conclusion This study provides evidence that a new
oestrogen-reduced HRT preparation containing 1 mg oestradiol valerate and 2 mg
dienogest has no major impact on lipid variables. Minimal changes were seen in
haemostatic and carbohydrate variables.
Int J Cancer. 2007 Aug 31; [Epub ahead of print]
Alcohol consumption and endometrial cancer risk: The multiethnic cohort.
Setiawan VW, Monroe KR, Goodman MT, Kolonel LN, Pike MC, Henderson BE.
Department of Preventive
Medicine,
The role of alcohol intake in
the etiology of endometrial cancer is unclear. We examined the impact of
alcohol intake on endometrial cancer risk among 41,574 postmenopausal
African-American, Japanese-American,
J Clin Endocrinol Metab. 2007 Aug 28; [Epub
ahead of print]
Effects of Atorvastatin on Bone in Postmenopausal Women with
Dyslipidemia: A Double-blind, Placebo-controlled, Dose-ranging Trial.
Bone HG, Kiel DP, Lindsay RS, Lewiecki EM, Bolognese MA, Leary ET, Lowe W, McClung MR.
Michigan Bone and Mineral
Clinic, Detroit, MI, Beth Israel Deaconess Medical Center and Harvard Medical
School, Boston, MA, Regional Bone Center, Helen Hayes Hospital, West
Haverstraw, NY, New Mexico Clinical Research & Osteoporosis Center,
Albuquerque, NM, Bethesda Health Research, Bethesda, MD, Pacific Biometrics,
Inc., Seattle, WA, Asia Biometrics Centre, Pfizer Global Pharmaceuticals,
Pfizer Australia, Oregon Osteoporosis Center, Portland, OR.
Context: In preclinical
models, inhibitors of HMG-CoA reductase have been shown to positively affect
bone remodeling balance. Observational studies and secondary analyses from
lipid-lowering trials have yielded inconsistent results regarding the effect of
these agents on bone mineral density and fracture risk. Objective: To determine
whether clinically significant skeletal benefits result from HMG-CoA reductase
inhibition in postmenopausal women. Design: Prospective, randomized,
double-blind, placebo-controlled, dose-ranging comparative clinical trial.
Setting: 62 sites in the
Arthritis Rheum. 2007 Aug 30;56(9):3070-3079 [Epub ahead of print]
Menopause hormonal therapy in women with systemic lupus erythematosus.
Sánchez-Guerrero J, González-Pérez M, Durand-Carbajal M, Lara-Reyes P, Jiménez-Santana L, Romero-Díaz J, Cravioto MD.
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán,
Tlalpan, Mexico.
OBJECTIVE: To evaluate the
effects of menopause hormonal therapy on disease activity in women with
systemic lupus erythematosus (SLE). METHODS: We conducted a double-blind,
randomized clinical trial involving 106 women with SLE who were in the
menopausal transition or in early or late postmenopause. Patients received a
continuous-sequential estrogen-progestogen regimen (n = 52) or placebo (n =
54). Disease activity was assessed at baseline and at 1, 2, 3, 6, 9, 12, 15,
18, 21, and 24 months, according to the SLE Disease Activity Index (SLEDAI).
The primary outcome measure was global disease activity, estimated by measuring
the area under the SLEDAI curve. Secondary outcome measures included maximum
SLEDAI score, change in SLEDAI score, incidence of lupus flares, median time to
flare, medication use, and adverse events. Results were studied using
intent-to-treat analysis. RESULTS: At baseline, demographic and disease
characteristics were similar in both groups. Mean +/- SD SLEDAI scores were 3.5
+/- 3.3 and 3.1 +/- 3.4 in the menopause hormonal therapy and placebo groups,
respectively (P = 0.57). Disease activity remained mild and stable in both
groups throughout the trial. There were no significant differences between the
groups in global or maximum disease activity, incidence or probability of
flares, or medication use. Median time to flare was 3 months in both groups.
Thromboses occurred in 3 patients who received menopause hormonal therapy and in
1 patient who received placebo. One patient in each group died during the trial
due to sepsis. CONCLUSION: Menopause hormonal therapy did not alter disease
activity during 2 years of treatment. However, an apparently increased risk of
thrombosis seems to be a real threat in women with SLE who receive menopausal
hormone therapy.
Int J Cancer. 2007 Aug 31; [Epub ahead of print]
Dietary fiber intake and risk of postmenopausal breast cancer defined by
estrogen and progesterone receptor status-A prospective cohort study among
Swedish women.
Suzuki R, Rylander-Rudqvist T, Ye W, Saji S, Adlercreutz H, Wolk A.
The National Institute of
Environmental Medicine, Division of Nutritional Epidemiology, Karolinska
Institutet,
There is few data on the
association between dietary fiber intake and estrogen receptor
(ER)/progesterone receptor (PR)-defined breast cancer risk. We evaluated the
association between dietary fiber and ER/PR-defined breast cancer risk
stratified by postmenopausal hormone use, alcohol intake, and family history of
breast cancer in the population-based Swedish Mammography Screening Cohort
comprising 51,823 postmenopausal women. Fiber intake was measured by
food-frequency questionnaire collected in 1987 and 1997. Relative risks (RRs)
were estimated by hazard ratio derived from Cox proportional hazard regression
models. During an average of 8.3-year follow-up, 1,188 breast cancer cases with
known ER/PR status were diagnosed. When comparing the highest to the lowest
quintile, we observed non-significant inverse associations between total fiber
intake and the risk of all tumor subtypes; the multivariate-adjusted RRs were
0.85 (95% CI: 0.69-1.05) for overall, 0.85 (0.64-1.13) for ER+PR+, 0.83
(0.52-1.31) for ER+PR- and 0.94 (0.49-1.80) for ER-PR-. For specific fiber, we
observed statistically significant risk reductions for overall (34%) and for
ER+PR+ (38%) for the highest versus lowest quintile of fruit fiber, and
non-significant inverse associations for other subtypes of cancer and types of
fiber. Among ever-users of postmenopausal hormone (PMH), total fiber intake and
especially cereal fiber were statistically significantly associated with
approximately 50% reduced risk for overall and ER+PR+ tumors when comparing the
highest to the lowest quartile, but no association was observed among PMH never
users. Our results suggest that dietary fiber intake from fruit and cereal may
play a role in reducing breast cancer risk.