Selección de Resúmenes de Menopausia
Mayo de 2007
Clin Obstet
Gynecol. 2007 Jun;50(2):354-361
Ovarian Conservation
at the Time of Hysterectomy for Benign Disease.
Parker WH, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS.
*UCLA
School of Medicine double daggerUSC
School of Medicine, Los Angeles daggerCerner Health
Insights, Beverly Hills parallelStanford School of
Medicine, Stanford, California section signUniversity
of Auckland School of Medicine, Auckland, New Zealand.
Approximately
78% of women between the ages of 45 and 64 years have prophylactic oophorectomy when hysterectomy is performed for benign
disease to prevent the development of ovarian cancer. However, after menopause,
the ovary continues to produce androstenedione and
testosterone in significant amounts and these androgens are converted in fat,
muscle, and skin into estrone. Evidence suggests that
oophorectomy increases the subsequent risk of
coronary heart disease (CHD) and osteoporosis and whereas 14,000 women die of
ovarian cancer every year nearly 490,000 women die of heart disease and 48,000
women die within 1 year after hip fracture. PubMed
and the Cochrane database were used to identify studies that examined the
incidence of disease and mortality from 5 conditions that seem to be related to
ovarian hormones: CHD, ovarian cancer, breast cancer, stroke and hip fracture,
and also data for death from all other causes. The data were applied to a
Markov decision analytic computer model to calculate risk estimates for
mortality from these conditions until the age of 80. The model shows for a
hypothetical cohort of 10,000 women undergoing hysterectomy and who chose oophorectomy (vs. ovarian conservation) between the ages of
50 and 54 [without estrogen therapy(ET)], that by the
time they reach age 80, 47 fewer women will have died from ovarian cancer, but
838 more women will have died from CHD and 158 more will have died from hip
fracture. Therefore, the decision to perform prophylactic oophorectomy
should be approached with great caution for the majority of women who are at
low risk of developing ovarian cancer.
J Clin Endocrinol Metab. 2007 May 22; [Epub ahead of print
Ovarian
androgen production in postmenopausal women.
Fogle RH, Stanczyk FZ, Zhang X, Paulson RJ.
University
of Southern California, Keck School of Medicine, Department of Obstetrics and
Gynecology, Division of Reproductive Endocrinology and Infertility.
Context:
Several studies previously reported that the postmenopausal ovary produces
androgens. However, these findings have recently been questioned in a group of
women with adrenal insufficiency. Objective: To utilize contemporary assay
methodologies to investigate whether the postmenopausal ovary is hormonally
active and contributes to the circulating pool of androgens. Design/Patients:
Serum was collected from the ovarian veins of 13 postmenopausal women
undergoing total abdominal hysterectomy and bilateral oophorectomy,
with sufficient quantities obtained to allow for measurement of several
hormones. Serum was also analyzed from peripheral blood collected preoperatively,
intraoperatively, and postoperatively. Setting: Los
Angeles County Women's and Children's Hospital, University of Southern
California Keck School of Medicine Main Outcome Measures: Testosterone (T), androstenedione (A), dehydroepiandrosterone
(DHEA), estrone (E1), and estradiol
(E2) were measured by radioimmunoassay with preceding organic solvent
extraction and Celite column chromatography. Results:
Statistically significant gradients were seen between the ovarian venous and
peripheral samples for T, A, DHEA, E1, and E2. Postoperative levels of T and
E1, but not A, DHEA, or E2, were statistically significantly lower than
preoperative levels. A gradient for T between the ovarian venous and peripheral
blood was present in 4 of 5 women who were menopausal for more than 10 years.
Conclusions: The postmenopausal ovary is hormonally active, contributing
significantly to the circulating pool of T. Furthermore, this contribution
appears to persist in women as long as 10 years beyond the menopause.
Metabolism. 2007 Jun;56(6):830-7.
Addition of medroxyprogesterone acetate to conjugated equine estrogens
results in insulin resistance in adipose tissue.
Shadoan MK, Kavanagh K, Zhang L, Anthony MS, Wagner JD.
Department
of Endocrinology, Lexicon Pharmaceuticals, The
Woodlands, TX 77381, USA.
The
purpose of this study was to determine if the insulin resistance we have
previously reported in surgically postmenopausal primates treated with combined
hormone therapy (HT) is due in part to effects on adipose tissue. Eighty-seven ovariectomized monkeys were fed a moderately atherogenic diet (0.28 mg cholesterol per kilocalorie [0.07
mg/kJ]) and randomized to receive no hormones (control, n = 29), estrogen
therapy (ET, conjugated equine estrogens, 0.625 mg/d human equivalent; n = 29),
or HT (ET + medroxyprogesterone acetate, 2.5 mg/d
human equivalent; n = 29) in the diet for 2 years. Fasting glycemic
measures were made at baseline and at the end of treatment. Circulating adiponectin measures, insulin tolerance tests, glucose
tolerance tests, and isolated adipocyte glucose
uptake assays were performed at the end of the trial. Hormone therapy-treated
animals were insulin resistant, as determined by greater fasting insulin concentrations
(P = .008), greater homeostasis model assessment of insulin resistance (HOMA-R)
value (P = .005) and slower glucose disposal after insulin administration (K(ITT); P = .02) when compared with controls. Subcutaneous adipocytes from HT-treated monkeys had a greater ED(50) for insulin (P = .04) and lower maximal glucose
uptake per cell (P < .001) compared with controls, suggesting impaired adipocyte insulin sensitivity. Adipocytes
were smaller (P = .001) and adiponectin
concentrations were greatest in the ET group (P = .02), with no difference
between controls and HT-treated monkeys. In conclusion, estrogen therapy
resulted in smaller adipocyte size and greater adiponectin concentrations than control or HT. Hormone
therapy resulted in impaired insulin sensitivity and adipocyte
glucose uptake compared with controls, whereas there was no difference between
ET and controls. Because no adverse effects were found with ET alone, it is
likely that the progestin, medroxyprogesterone
acetate, resulted in the negative effects of the combined HT regimen on
whole-body insulin sensitivity, which were mediated, in part, by reductions in
adipose tissue responses to insulin.
Drug Dev Ind
Pharm. 2007 Apr;33(4):373-80
Simultaneous Estradiol and Levonorgestrel Transdermal Delivery from a 7-day Patch: In Vitro and In
Vivo Drug Deliveries of Three Formulations.
Harrison LI, Zurth C, Gunther C, Karara AH, Melikian A, Lipp R.
3M
Drug Delivery Systems. St. Paul, MN. USA.
A
new drug-in-adhesive transdermal patch was developed
to deliver both estradiol and levonorgestrel
through the skin over a 7-day period, but at different rates. This report
elucidates the in vitro and in vivo biopharmaceutical studies that were
necessary during the development of this product. Three test patches had to be
manufactured, all delivering estradiol at the same
rate, but delivering levonorgestrel at three
different rates so that a levonorgestrel dose
response could be studied in the clinic. An in vitro hairless mouse skin model
(HMS) using modified Franz diffusion cells was used to select the test products
delivering levonorgestrel in the order of 1:2:3. HMS
experiments also demonstrated that the presence of estradiol
did not affect the flux of levonorgestrel. Two in
vivo studies in postmenopausal women showed that at steady state (four weeks of
once-weekly dosing) the three test products all delivered estradiol
at comparable rates. Similarly, the levonorgestrel
deliveries for the three test products were in the order expected. The target
fluxes of both drugs were achieved in these three test products by varying the
drug loads and patch size. That this approach was successful is evidence of the
value of using the HMS penetration experiments in transdermal
product development and should provide useful insights for other formulations
having to develop complex systems. One of the test products is now marketed as Climara Pro(TM)
J Chin Med Assoc. 2007 May;70(5):200-6.
A Clinical Trial
of 3 Doses of Transdermal 17beta-estradiol for Preventing Postmenopausal Bone Loss: A Preliminary Study.
Yang TS, Chen YJ, Liang WH, Chang CY, Tai LC, Chang SP, Ng HT.
Department of Obstetrics and Gynecology, Taipei
Veterans General Hospital, and National Yang-Ming University School of
Medicine, Taipei, Taiwan, R.O.C.
Background:
It is well documented that a daily oral dose of 0.625 mg of conjugated equine
estrogen or 1-2mg of 17beta-estradiol is needed to prevent postmenopausal bone
loss. Recent studies have indicated that a lower dose of estrogen maybe as
effective in maintaining bone mass. The purpose of this study was to evaluate
the effects of 3 dosages of transdermally
administered 17beta-estradiol gel in postmenopausal women stratified by oophorectomy and natural menopause. Methods: One hundred
and twenty postmenopausal women were randomly selected to form 4 groups. Three
groups of women were treated with a transdermal
administration of estradiol gel at a daily dosage of
1.25, 2.5 and 5.0 g (containing 0.75, 1.5, and 3 mg of 17beta-estradiol/day),
respectively. The 4th group of women, receiving estriol
2 mg/day p.o., was studied concurrently as a control.
Bone mineral density was measured by quantitative computed tomography of the
vertebrae from T12 to L3 at baseline, then at 6-month intervals for 1 year.
Results: Women in all groups receiving 17beta-estradiol gel obtained a
significant increase in bone mass, with the exception of the 1.25 g/day group,
which showed a minimal increment at the 6-month period, compared with the
control group. Comparisons of the increments in bone mass after estrogen
therapy for both natural and surgical menopausal subjects found that there was
a more prominent response in surgical menopausal women receiving a dosage of
2.5 g/day. Conclusion: Estradiol gel at the dosage of
1.25 g/day, equivalent to 17beta-estradiol 0.75 mg/day, effectively prevented
bone loss in postmenopausal women after a 12-month treatment period. The
therapeutic effect of estradiol gel on bone mass was
more prominent in the surgical menopausal groups at the dosage of 2.5 g/day.
The atrophic ovaries may therefore play a crucial role in the subsequent
decades of postmenopausal women.
PLoS Med. 2007 May 22;4(5):e157 [Epub
ahead of print]
Traditional Nonsteroidal Anti-Inflammatory
Drugs and Postmenopausal Hormone Therapy: A Drug-Drug Interaction?
Garcia Rodriguez LA, Egan K, Fitzgerald GA.
BACKGROUND:
Suppression of prostacyclin (PGI2) is implicated in
the cardiovascular hazard from inhibitors of cyclooxygenase
(COX)-2. Furthermore, estrogen confers atheroprotection
via COX-2-dependent PGI2 in mice, raising the possibility that COX inhibitors
may undermine the cardioprotection, suggested by
observational studies, of endogenous or exogenous estrogens. METHODS AND
FINDINGS: To identify an interaction between hormone therapy (HT) and COX
inhibition, we measured a priori the association between concomitant nonsteroidal anti-inflammatory drugs (NSAIDs), excluding
aspirin, in peri- and postmenopausal women on HT and
the incidence of myocardial infarction (MI) in a population-based
epidemiological study. The odds ratio (OR) of MI in 1,673 individuals and 7,005
controls was increased from 0.66 (95% confidence interval [CI] 0.50-0.88) when
taking HT in the absence of traditional (t)NSAIDs to
1.50 (95% CI 0.85-2.64) when taking the combination of HT and tNSAIDs, resulting in a significant (p < 0.002)
interaction. The OR when taking aspirin at doses of 150 mg/d or more was 1.41
(95% CI 0.47-4.22). However, a similar interaction was not observed with other
commonly used drugs, including lower doses of aspirin, which target
preferentially COX-1. CONCLUSIONS: Whether estrogens confer cardioprotection
remains controversial. Such a benefit was observed only in perimenopausal
women in the only large randomized trial designed to address this issue. Should
such a benefit exist, these results raise the possibility that COX inhibitors
may undermine the cardioprotective effects of HT.
BJOG. 2007 Jun;114(6):664-75
Diagnostic hysteroscopy in abnormal
uterine bleeding: a systematic review and meta-analysis.
van Dongen H, de Kroon CD, Jacobi CE, Trimbos JB, Jansen FW.
Department
of Gynaecology, Leiden Unviersity
Medical Center, Leiden, The Netherlands.
H.van_Dongen@lumc.nl
BACKGROUND:
This study was conducted to assess the accuracy and feasibility of diagnostic
hysteroscopy in the evaluation of intrauterine abnormalities in women with
abnormal uterine bleeding. SEARCH STRATEGY: Electronic databases were searched
from 1 January 1965 to 1 January 2006 without language selection. The medical
subject heading (MeSH) and textwords
for the following terms were used: hysteroscopy, diagnosis, histology,
histopathology, hysterectomy, biopsy, sensitivity and specificity. SETTING:
University Hospital. SELECTION CRITERIA: The inclusion criteria were report on
accuracy of diagnostic hysteroscopy in women with abnormal uterine bleeding
compared to histology collected with guided biopsy during hysteroscopy,
operative hysteroscopy or hysterectomy. DATA COLLECTION AND ANALYSIS:
Electronic databases were searched for relevant studies and references were
cross-checked. Validity was assessed and data were extracted independently by
two authors. Heterogeneity was calculated and data were pooled. Subgroup
analysis was performed according to validity criteria, study quality,
menopausal state, time, setting and performance of the procedure. The pooled sensitivity, specificity, likelihood ratios, post-test
probabilities and feasibility of diagnostic hysteroscopy on the prediction of
uterine cavity abnormalities. Post-test probabilities were derived from
the likelihood ratios and prevalence of intrauterine abnormalities among
included studies. Feasibility included technical success rate and complication
rate. MAIN RESULTS: One population of homogeneous data could be identified,
consisting of patients with postmenopausal bleeding. In this subgroup the
positive and negative likelihood ratios were 7.9 (95% CI 4.79-13.10) and 0.04
(95% CI 0.02-0.09), raising the pre-test probability from 0.61 to a post-test
probability of 0.93 (95% CI 0.88-0.95) for positive results and reducing it to
0.06 (95% CI 0.03-0.13) for negative results. The pooled likelihood ratios of
all studies included, calculated with the random effects model, were 6.5 (95%
CI 4.1-10.4) and 0.08 (95% CI 0.07-0.10), changing the pre-test probability of
0.46 to post-test probabilities of 0.85 (95% CI 0.78-0.90) and 0.07 (0.06-0.08)
for positive and negative results respectively. Subgroup analyses gave similar
results. The overall success rate of diagnostic hysteroscopy was estimated at
96.9% (SD 5.2%, range 83-100%). CONCLUSIONS: This systematic review and
meta-analysis shows that diagnostic hysteroscopy is both accurate and feasible
in the diagnosis of intrauterine abnormalities.
Int J Cancer. 2007 May 22; [Epub ahead of print
IGF-I and
mammographic density in four geographic locations: A pooled analysis.
Maskarinec G, Takata Y, Chen Z, Gram IT, Nagata C, Pagano I, Hayashi K, Arendell L, Skeie G, Rinaldi S, Kaaks R.
Cancer Research Center, University of Hawaii.
Insulin-like
growth factor (IGF-I) and prolactin have been found
to be associated with breast cancer risk and with mammographic density. In a
pooled analysis from 4 geographic locations, we investigated the association of
percent mammographic density with serum levels of IGF-I, IGFBP-3 and prolactin. The pooled data set included 1,327 pre- and
postmenopausal women: Caucasians from Norway, Arizona and Hawaii, Japanese from
Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. Serum
samples were assayed for IGF-I, IGFBP-3 and prolactin
levels using ELISA assays. Mammographic density was quantified using a
computer-assisted density method. After stratification by menopausal status,
multiple regression models estimated the relation between serum analytes and breast density. All serum analytes
except prolactin among postmenopausal women differed
significantly by location/ethnicity group. Among premenopausal subjects, IGF-I
levels and the molar ratio were highest in Hawaii, intermediate in Japan and
lowest in Arizona. For IGFBP-3, the order was reversed. Among postmenopausal
subjects, Norwegian women had the highest IGF-I levels and women in Arizona had
the lowest while women in Japan and Hawaii had intermediate levels. We observed
no significant relation between percent density and IGF-I or prolactin levels among pre-and postmenopausal women. The
significant differences in IGF-I levels by location but not ethnicity suggest
that environmental factors influence IGF-I levels, whereas percent breast
density varies more according to ethnic background than by location. Based on
this analysis, the influence of circulating levels of IGF-I, IGFBP-3, and prolactin on percent density appears to be very small.
Lancet. 2007 May 19;369(9574):1703-10
Ovarian cancer and hormone replacement
therapy in the Million Women Study.
Beral V; Million Women Study Collaborators; Bull D, Green J, Reeves G.
Million
Women Study Coordinating Centre, Cancer Research UK Epidemiology Unit, Richard
Doll Building, Roosevelt Drive, Oxford, OX3 7LF, UK.
pa.valerie.beral@ceu.ox.ac.uk
BACKGROUND:
Ovarian cancer is the fourth most common cancer in women in the UK, with about
6700 developing the malignancy and 4600 dying from it every year. However,
there is limited information about the risk of ovarian cancer associated with
the use of hormone replacement therapy (HRT). METHODS: 948,576 postmenopausal
women from the UK Million Women Study who did not have previous cancer or
bilateral oophorectomy were followed-up for an
average of 5.3 years for incident ovarian cancer and 6.9 years for death.
Information on HRT use was obtained at recruitment and updated where possible.
Relative risks for ovarian cancer were calculated, stratified by age and
hysterectomy status, and adjusted by area of residence, socioeconomic group, time since menopause, parity, body-mass index, alcohol
consumption, and use of oral contraceptives. FINDINGS: When they last reported
HRT use, 287,143 women (30%) were current users and 186 751 (20%) were past
users. During follow-up, 2273 incident ovarian cancers and 1591 deaths from the
malignancy were recorded. Current users were significantly more likely to
develop and die from ovarian cancer than never users (relative risk 1.20 [95%
CI 1.09-1.32; p=0.0002] for incident disease and 1.23 [1.09-1.38; p=0.0006] for
death). For current users of HRT, incidence of ovarian cancer increased with
increasing duration of use, but did not differ significantly by type of
preparation used, its constituents, or mode of administration. Risks associated
with HRT varied significantly according to tumour
histology (p<0.0001), and in women with epithelial tumours
the relative risk for current versus never use of HRT was greater for serous
than for mucinous, endometroid,
or clear cell tumours (1.53 [1.31-1.79], 0.72
[0.52-1.00], 1.05 [0.77-1.43], or 0.77 [0.48-1.23], respectively). Past users of
HRT were not at an increased risk of ovarian cancer (0.98 [0.88-1.11] and 0.97
[0.84-1.11], respectively, for incident and fatal disease). Over 5 years, the standardised incidence rates for ovarian cancer in current
and never users of HRT were 2.6 (2.4-2.9) and 2.2 (2.1-2.3) per 1000,
respectively-ie, one extra ovarian cancer in roughly
2500 users; death rates were 1.6 (1.4-1.8) and 1.3 (1.2-1.4) per 1000,
respectively-ie, one extra ovarian cancer death in
roughly 3300 users. INTERPRETATION: Women who use HRT are at an increased risk
of both incident and fatal ovarian cancer. Since 1991, use of HRT has resulted
in some 1300 additional ovarian cancers and 1000 additional deaths from the
malignancy in the UK.
Georgian Med News. 2007 Apr;(145):52-5.
Effect
of metformin therapy on plasma adiponectin
and leptin levels in obese and insulin resistant
postmenopausal females with type 2 diabetes.
Adamia N, Virsaladze D, Charkviani N, Skhirtladze M, Khutsishvili M.
Department of Endocrinology, Tbilisi State Medical
University.
To
investigate the relative role of the adiponectin and leptin in the insulin resistance (IR) and obesity we
studied plasma levels of these adipocytokines in
obese and insulin resistant postmenopausal (PM) females with type 2 diabetes
(DM2) during 6 months of Metformin therapy. We
recruited 26 PM women, between the ages of 50 and 67 (59,7+/-8,1
years). These women had a BMI of 36,6+/-1,8 kg/m(2).
After baseline measurements Metformin therapy has
been initiated (1700+/-2550 mg per day). Duration of therapy was 6 months. The
results of investigations of adipocytokines after Metformin 6 months therapy shown that circulating adiponectin levels were significantly increased (19,1+/-6,0
vs. 16,1+/-3,9 ng/ml, p=0,008) together with
significant reduction of BMI (35,9+/-1,9 vs. 36,6+/-1,8 kg/m(2), p=0,005) and
IR (3,05+/-0,89 vs. 3,96+/-0,70, p<0,001). The magnitude of the change in adiponectin levels positively correlated with the magnitude
of BMI reduction (r=0,4784, p=0,013) and IR reduction
(r=0,5779, p=0,002). Any significant correlation did not observed between
changes of leptin levels and BMI, leptin
levels and IR. In summary, our data suggest that hypoadiponectinemia
in PM may be explained by only IR because the amelioration of whole-body
insulin action by 6-month Metformin therapy leads to
increase of plasma adiponectin levels; leptin levels did not significantly change after 6-month Metformin therapy.
Cancer Epidemiol Biomarkers
Prev. 2007 May;16(5):900-5
Usual physical activity and endogenous sex hormones in
postmenopausal women: the European prospective investigation into cancer-norfolk population study.
Chan
MF, Dowsett M, Folkerd E, Bingham
S, Wareham
N, Luben R, Welch
A, Khaw KT.
Clinical Gerontology Unit
BACKGROUND: Short-term trials indicate that intensive
physical activity may influence endogenous sex hormone concentrations. However,
the relationship between usual daily physical activity and endogenous hormones
in postmenopausal women in the general population is still uncertain. Objective
and METHODS: To determine the relationship between usual physical activity and
endogenous sex hormones in postmenopausal women. A cross-sectional population-based
study of 2,082 postmenopausal women ages 55 to 81 years, residing in the
general community of
Cancer Epidemiol Biomarkers
Prev. 2007 May;16(5):921-8
Longitudinal trends in mammographic percent density and breast
cancer risk.
Vachon CM, Pankratz VS, Scott
CG, Maloney
SD, Ghosh K, Brandt
KR, Milanese
T, et
al.
BACKGROUND: Mammographic density is a strong risk
factor for breast cancer. However, whether changes in mammographic density are
associated with risk remains unclear. MATERIALS AND METHODS: A study of 372
incident breast cancer cases and 713 matched controls was conducted within the
Mayo Clinic mammography screening practice. Controls were matched on age, exam
date, residence, menopause, interval between, and number of mammograms. All
serial craniocaudal mammograms 10 years before
ascertainment were digitized, and quantitative measures of percent density (PD)
were estimated using a thresholding method. Data on
potential confounders were abstracted from medical records. Logistic regression
models with generalized estimating equations were used to evaluate the
interactions among PD at earliest mammogram, time from earliest to each serial
mammogram, and absolute change in PD between the earliest and subsequent
mammograms. Analyses were done separately for PD measures from the ipsilateral and contralateral
breast and also by use of hormone therapy (HT). RESULTS: Subjects had an
average of five mammograms available, were primarily postmenopausal (83%), and
averaged 61 years at the earliest mammogram. Mean PD at earliest mammogram was
higher for cases (31%) than controls (27%; ipsilateral
side). There was no evidence of an association between change in PD and breast
cancer risk by time. Compared with no change, an overall reduction of 10% PD
(lowest quartile of change) was associated with an odds ratio of 0.9997 and an
increase of 6.5% PD (highest quartile of change) with an odds ratio of 1.002.
The same results held within the group of 220 cases and 340 controls never
using HT. Among the 124 cases and 337 controls known to use HT during the
interval, there was a statistically significant interaction between change in
PD and time since the earliest mammogram (P = 0.01). However, in all groups,
the risk associated with the earliest PD remained a stronger predictor of risk
than change in PD. CONCLUSION: We observed no association between change in PD
with breast cancer risk among all women and those never using HT. However, the
interaction between change in PD and time should be evaluated in other
populations.
Menopause. 2007 May 15; [Epub ahead of print
Symptoms, menopause status, and country differences: a
comparative analysis from DAMES.
Obermeyer CM, Reher D, Saliba M.
Department of Population and
International Health,
OBJECTIVE:: To investigate reported frequencies of
menopausal symptoms among women in four countries, namely Lebanon, Morocco,
Spain, and the United States, and to assess the relative role of menopause
status, country of residence, and other factors in explaining differences in symptomatology. DESIGN:: Surveys
of representative samples of approximately 300 women aged 45 to 55 years in
each site were conducted, using an instrument that includes demographic,
health, and menopausal variables, in addition to perceptions and attitudes
toward menopause. Statistical and textual analyses are used to examine
differentials and the factors that influence them. RESULTS::
The burden of symptoms and the frequencies of symptoms differ across sites, but
hot flashes are reported everywhere by just under one half of the respondents.
The most frequent symptoms are joint pain, fatigue, impatience/nervousness,
sleep disturbances, memory loss, and one or more emotional symptoms. Menopause
status is significantly associated with hot flashes and vasomotor symptoms and
to a lesser extent with emotional and sexual symptoms. Smoking, schooling,
employment, and age are also associated with the frequency of selected
symptoms. Country of residence influences reported symptoms over and above
other factors. CONCLUSIONS:: Similarities among core
symptoms and differences in the expression of symptoms were found across sites.
Both biological (menopause status) and cultural (country of residence)
variables influence symptomatology.
J Clin Lab
Anal. 2007 May 16;21(3):197-200 [Epub ahead of print
Relationship of serum adiponectin
with blood lipids, HbA(1)c, and hs-CRP in type II
diabetic postmenopausal women.
Goodarzi MT, Babaahmadi-Rezaei H, Kadkhodaei-Eliaderani M, Haddadinezhad S.
Department of Biochemistry
& Nutrition,
Adipose tissue has been considered an important
endocrine organ. Adiponectin secretes from adipose
tissue and plays an important role in the regulation of glycemia,
beta-oxidation in muscle, and decreased insulin resistance in the liver. The
objectives of this study were to compare the levels of adiponectin,
hs-C-reactive protein (CRP), HbA1c, and blood lipids
among diabetic and healthy postmenopausal women, and to determine the
relationship between circulating adiponectin and
development of type II diabetes. This case-control study was performed on 28
diabetic and 42 age-matched healthy women. All participants were
postmenopausal. Serum adiponectin concentrations,
serum triglycerides (TG), cholesterol, low-density lipoprotein cholesterol
(LDL-C), and high-density lipoprotein cholesterol (HDL-C) concentrations were
determined. Blood HbA1c and serum hs-CRP were also
measured. Adiponectin levels were significantly
decreased (P<0.01) in the diabetic patients as compared to normal control
subjects. Adiponectin levels were negatively
associated with hs-CRP, LDL-C, HbA1c, TG, and total
cholesterol (TC). A positive correlation was observed between adiponectin and HDL-C. The obtained data indicate that
diabetic women have lower adiponectin levels compared
to healthy women. HbA1c as an indicator of glycemic
control has a negative correlation with serum adiponectin.
Adiponectin may play an important role in the
pathogenesis of diabetes, and may be an independent predictor of the
development of diabetes in women.
J Endocrinol Invest. 2007 Mar;30(3):230-5
Favorable clinical heart and bone effects of
anti-thyroid drug therapy in endogenous subclinical hyperthyroidism.
Buscemi S, Verga S, Cottone S, Andronico G, D'Orio L, Mannino V, Panzavecchia D, Vitale
F, Cerasola
Department of Internal
Medicine, Cardiovascular and Kidney Diseases,
Although subclinical hyperthyroidism (SCH) has been
associated with increased risk of osteoporosis and cardiac arrhythmias, its
treatment is still controversial. This study was designed as a prospective,
randomized, intervention, control-study with a 1-year follow-up in order to
investigate whether normalization of serum TSH in SCH using methimazole
has favorable bone and heart clinical effects. Fourteen patients with
endogenous SCH (not Graves' disease) were enrolled, 7 (5 women/2 men; group T)
were treated with methimazole (2.5-7.5 mg/day), and 7
(5 women/2 men; group C) were followed without treatment; 10 healthy subjects
were also included in the study as controls. Serum free-T3 (FT3), free-T4 (FT4)
and TSH, thyroid echography, bone stiffness index
(SI), as measured by heel ultrasonometry, and 24-h
electrocardiography monitoring were obtained. SCH patients exhibited higher
systolic and diastolic blood pressure than control subjects. They also had a
significantly higher number of both ventricular premature beats (VPB)
(mean+/-SEM: 681+/-238 vs 6+/-2 beats/24 h;
p<0.02) and atrial premature beats (APB)
(mean+/-SEM: 495+/-331 vs 7+/-2 beats/24 h;
p<0.0001), and a lower SI (66+/-5 vs 96+/-3;
p<0.001). Twelve months after normalization of TSH with the use of methimazole, the number of VPB decreased significantly
(947+/-443 vs 214+/-109 beats/24 h; p<0.05) while
it remained unchanged in untreated SCH patients (414+/-163 vs
487+/-152 beats/24 h; p=ns). An insignificant therapy effect was observed as
far as APB were concerned (826+/-660 vs 144+/-75
beats/24 h; p=ns), however their number increased significantly in the
untreated group (463+/-49 vs 215+/-46 beats/24 h;
p<0.05). The SI increased significantly as a result of therapy in group T
(64.1+/-4.8 vs 70.0+/-5.3; p<0.02) and was further
reduced in group C at the end of the study (69.1+/-7.3 vs
62.9+/-7.1; p<0.001). No adverse effect was observed in group T. In
conclusion, anti-thyroid therapy seems to have favor-able bone and heart
clinical effects in subjects with endogenous SCH.
Int J Clin Pract. 2007 Jun;61(6):963-71
Is treatment of early postmenopausal women with bisphosphonates justified?
The decision to treat women in the early
postmenopausal period has come under scrutiny because of the low occurrence of
fractures in this population and the possible lack of cost-effectiveness for
individual patients. This article focuses on the potential use of bisphosphonates for the prevention and treatment of
osteoporosis in the early postmenopausal period. Studies have determined that
there is a relationship between bisphosphonate
treatment and bone mineral density (BMD) gains, even in women in the early
postmenopausal period without a diagnosis of osteoporosis. These patients
receive benefit from treatment, including improvements in BMD levels and
fracture protection. Using BMD scores, rates of bone turnover, and risk-based
diagnostic criteria as part of the decision to initiate therapy may allow for
the identification of an early postmenopausal patient population that would
benefit from preventative therapy. This would improve the cost-effectiveness of
using bisphosphonates for the prevention of
osteoporosis in this population. The evaluation of women at risk for developing
osteoporosis should include an assessment of both BMD scores and additional
risk factors. Early postmenopausal women who are in a high-risk group should be
considered candidates to receive bisphosphonate
therapy.
Drugs Aging. 2007;24(5):361-79
Selective estrogen receptor modulators for postmenopausal osteoporosis : current state of development.
Gennari L, Merlotti D, Valleggi F, Martini G, Nuti R.
Department Internal
Medicine, Endocrine-Metabolic Sciences & Biochemistry,
Selective estrogen receptor modulators (SERMs) are
structurally different compounds that interact with intracellular estrogen
receptors in target organs as estrogen receptor agonists and antagonists. These
drugs have been intensively studied over the past decade and have proven to be
a highly versatile group for the treatment of different conditions associated
with aging, including hormone-responsive cancer and osteoporosis. Tamoxifen and toremifene are
currently used to treat advanced breast cancer and also have beneficial effects
on bone mineral density and serum lipids in postmenopausal women. Raloxifene is the only SERM approved worldwide for the
prevention and treatment of postmenopausal osteoporosis and vertebral
fractures. However, although these SERMs have many benefits, they may also be
responsible for some potentially very serious adverse effects, such as thromboembolic disorders and, in the case of tamoxifen, uterine cancer. These adverse effects represent
a major concern given that long-term therapy is required to prevent
osteoporosis. Moreover, both preclinical and clinical reports suggest that tamoxifen, toremifene and raloxifene are considerably less potent than estrogen.The search for the 'ideal' SERM, which would have
estrogenic effects on bone and serum lipids, neutral effects on the uterus, and
antiestrogenic effects on breast tissue, but none of
the adverse effects associated with current therapies, is currently under way. Ospemifene, lasofoxifene, bazedoxifene and arzoxifene,
which are new SERM molecules with potential greater efficacy and potency than
previous SERMs, are currently under investigation for use in the treatment and
prevention of osteoporosis. These drugs have been shown to be comparably
effective to conventional hormone replacement therapy in animal models of
osteoporosis, with potential indications for an improved safety profile.
Clinical efficacy data from ongoing phase III trials are awaited so that a true
understanding of the therapeutic potential of these compounds can be obtained.
Drugs Aging. 2007;24(5):351-9
Intermittent bisphosphonate
therapy in postmenopausal osteoporosis: progress to date.
Reginster JY, Malaise
O, Neuprez A, Jouret VE, Close
P.
Department of Public Health,
Epidemiology and Health Economics,
Bisphosphonates are the most widely prescribed drugs in osteoporosis today. They have
unequivocally shown their ability to reduce fracture rate at the spine (alendronic acid, risedronic acid,
ibandronic acid) and at the hip (alendronic
acid and risedronic acid). However, their dosage and
administration procedures and the adverse reactions induced by their oral
intake are responsible for low adherence. Therefore, intermittent regimens have
been developed. Weekly alendronic acid and risedronic acid provide similar benefits, in terms of bone
mineral density (BMD) and changes in biochemical markers, as those seen with
their daily formulations. Ibandronic acid has been
shown to reduce vertebral fractures when given intermittently. Ibandronic acid given orally monthly and intravenously
every 2 or 3 months provides increases in BMD similar to the daily formulation.
Yearly intravenous infusions of zoledronic acid are
currently being evaluated for their ability to reduce fractures. If the
efficacy and safety of bisphosphonates given at
administration intervals longer than weekly are confirmed, this might
significantly improve patient adherence and long-term outcomes of bisphosphonate treatment in postmenopausal osteoporosis.
Menopause. 2007 May 11; [Epub
ahead of print
Hormone therapy and coronary heart disease in
young women.
Weiner MG, Barnhart K, Xie D, Tannen RL.
Departments of Medicine,
Obstetrics and Gynecology, and Clinical Epidemiology and Biostatistics, and
Center for Clinical Epidemiology and Biostatistics,
OBJECTIVE:: Because the
Women's Health Initiative randomized controlled trial (WHI RCT) primarily
studied older women, it is unresolved whether hormone therapy might prevent
coronary heart disease in younger women. Given the similarity between our
Arch Intern Med. 2007 May 14;167(9):893-902
Calcium plus vitamin d supplementation and the risk of
postmenopausal weight gain.
Caan B, Neuhouser M, Aragaki A, Lewis
CB, Jackson
R, Leboff MS, Margolis
KL, Powell
L, et
al.
Division of Research, Kaiser
Permanente Northern California,
BACKGROUND: Obesity in the
Bone. 2007 Apr 4; [Epub
ahead of print
Is short vertebral height always an osteoporotic fracture?
The Osteoporosis and Ultrasound Study (OPUS).
Ferrar L, Jiang
G, Armbrecht G, Reid
DM, Roux
C, Gluer
CC, Felsenberg D, Eastell R.
Unit of Bone Metabolism,
Division of Clinical Sciences,
INTRODUCTION AND HYPOTHESIS::
Diagnosis of prevalent osteoporotic vertebral fracture is complicated by normal
or developmental variation in vertebral shape or size and non-osteoporotic
deformities that appear to have 'reduced' height. Using our visual approach,
the algorithm-based qualitative method (ABQ) a vertebra with apparent
"reduced" height without evidence of osteoporotic endplate depression
is classified as non-osteoporotic short vertebral height (SVH). We aimed to
determine whether ABQ classification of SVH represents true or false negative
diagnosis of osteoporotic vertebral fracture, by testing the associations with
clinical outcomes of osteoporosis or vertebral fracture. METHODS:: The ABQ method was used to assess spinal radiographs
acquired at baseline for a subset of 904 postmenopausal women participating in
the Osteoporosis and Ultrasound Study (OPUS). The sample was enriched with
vertebral fracture cases. Subjects were categorized by ABQ diagnosis as (i) normal, (ii) non-osteoporotic short vertebral height
(SVH) or (iii) osteoporotic vertebral fracture. RESULTS::
Women were classified by ABQ as follows: osteoporotic vertebral fracture,
n=231; SVH, n=376 and normal, n=297. Women with vertebral fracture were older,
with lower height, weight and height loss than those classified as SVH or
normal. Women with SVH were heavier and older, with greater historical height
loss than normal women. Age-adjusted SD units (z-scores) for BMD were lower
than expected among women with osteoporotic vertebral fracture, but not among
those with SVH. There was a significant association between diagnosis of
osteoporotic vertebral fracture and history of low-trauma non-vertebral and
vertebral fracture (p<0.001, odds ratios=3.2 and 20.6, respectively). There
was also an association between diagnosis of SVH and previous low-trauma
non-vertebral fracture (p<0.05, odds ratio=1.7). CONCLUSIONS:: Short vertebral height without evidence of central
endplate fracture in postmenopausal women is largely unrelated to osteoporosis.
Quantitative morphometry should not be used alone for
the assessment of vertebral fracture in clinical decision making: we recommend
differential diagnosis of morphometric vertebral
deformities by an expert reader to rule out non-osteoporotic deformities with
short vertebral height.
Diabetes Metab. 2007 May 10; [Epub
ahead of print
Relationship between the hyperinsulinemic-euglycaemic
clamp and a new simple index assessing insulin sensitivity in overweight and
obese postmenopausal women.
Bastard JP, Vandernotte JM, Faraj M, Karelis AD, Messier L, Malita FM, Garrel D, et al.
Service de biochimie et hormonologie, hopital
Tenon, APHP, 75020 Paris, France..
OBJECTIVE: The purpose of this study was to compare
assessment of insulin sensitivity from hyperinsulinemic
euglycaemic (HIEG) clamp with indexes derived from fasting
and oral glucose tolerance test (OGTT). SUBJECTS AND METHODS: Cross-sectional
study with 107 sedentary non-diabetic overweight and obese postmenopausal
(BMI=32.4+/-0.4 kg/m(2)) women undergoing both HIEG
clamp and OGTT. Pairs of data were analyzed using Pearson correlation and
Bland-Altman graphs analysis. Comparison between correlations was made using
the method reported by Zar. RESULTS: All the indexes
derived from either the OGTT or surrogate indexes were highly correlated with
all the clamp-derived formulas (P<0.0001). However, HOMA and QUICKI were
generally less correlated than OGTT-derived indexes. Analogically to QUICKI, we
calculated a new formula derived from the OGTT measurements of glucose and
insulin named simple index assessing insulin sensitivity
(SI(is)OGTT)=1/[log(sum glucose t(0-30-90-120)) (mmol/l)+log(sum
insulin t(0-30-90-120)) (muUI/ml)]. By using this
formula, we found high significant correlations (r's=0.61-0.65;
P<0.0001) with the clamp results. Moreover, the correlations of SI(is)OGTT with the clamp data were higher than for other
previously published indexes. CONCLUSION: In that large group of non-diabetic
overweight and obese postmenopausal women insulin sensitivity index derived
from OGTT provided more accurate information than fasting based formula. We
propose a new simple index for the assessment of insulin sensitivity from the
OGTT data (SI(is)OGTT). The advantage of this new
formula over all previously published OGTT-derived indexes of insulin
sensitivity is that it is 1) easy to calculate 2) better correlated than other
indexes of insulin sensitivity and 3) not affected by the way clamp results are
expressed. Further studies are needed to validate SI(is)OGTT
index in other populations.
J Bone Miner Res. 2007 May 14; [Epub
ahead of print
Osteoporosis in Patients with Diabetes Mellitus.
Hofbauer LC, Brueck CC, Singh
SK, Dobnig H.
Microabstract Demographic trends with longer life expectancy and a lifestyle
characterized by low physical activity and high-energy food intake contribute
to an increasing incidence of diabetes mellitus and osteoporosis. Diabetes
mellitus is a risk factor for osteoporotic fractures. Patients with recent
onset of type 1 diabetes mellitus may have impaired bone formation due to the
absence of the anabolic effects of insulin and amylin,
while in long-standing type 1 diabetes mellitus, vascular complications may
account for low bone mass and increased fracture risk. Patients with type 2
diabetes mellitus display an increased fracture risk despite a higher BMD which
is mainly attributable to the increased risk of falling. Strategies to improve
BMD and to prevent osteoporotic fractures in patients with type 1 diabetes
mellitus may include optimal glycemic control and
aggressive prevention and treatment of vascular complications. Patients with
type 2 diabetes mellitus may additionally benefit from early visual assessment,
regular exercise to improve muscle strength and balance, and specific measures
for preventing falls.
Bone. 2007 Apr 10; [Epub ahead of print
Transmenopausal changes in the trabecular
bone structure.
Akhter MP, Lappe JM, Davies KM, Recker RR.
INTRODUCTION: Post-menopausal osteoporosis is a
disorder of excess skeletal fragility, due partly to changes in bone
microstructure. Menopause is known to result in bone loss and reduction in bone
mechanical strength. However, the mechanism and nature of microstructural
changes at menopause need more detailed description and analyses. The overall
hypothesis for this analysis is that the variables describing trabecular bone micro-architecture will be affected by
changes in the hormonal status of women just prior to, and early after, last
menses, and that volumetric bone density, and trabecular
structure will decline significantly. The study was designed to capture true
longitudinal transmenopausal changes in
three-dimensional (3-D) trabecular bone architecture.
Currently, minimal data exist regarding these features. MATERIALS AND METHODS: Transilial biopsies specimens were obtained from healthy
pre-menopausal women (age >46), and repeated at 12 months after the last
menstrual period. Bone architecture was quantified in 38 paired specimens using
micro-computed tomography (micro-CT-40, Scanco)
techniques. Bone biopsies were embedded for histomorphomteric
analyses and parts of the analyses have been published elsewhere. Embedded bone
biopsies were scanned at 30-mum resolution such that the region of interest was
similar to that in the two-dimensional (2-D) histomorphometric
analyses. Paired t-tests were used to compare the pre- and post-menopausal bone
structural data from each technique. RESULTS: There was good correlation
between standard histomorphometric (2-D) and micro-CT
(3-D) measurements. Most of the variables characterizing bone structure in
post-menopausal women (from micro-CT) significantly decreased (BV/TV, trabecular number, apparent and tissue density). In
addition, both trabecular spacing (Tb.S) and the structure model index (SMI) increased in the
post-menopausal women suggesting transformation of trabecular
bone from plate- to rod-like structure. The 3-D trabecular
connectivity density (Conn.D) was negatively
correlated with activation frequency (Ac.f).
CONCLUSIONS: These data suggest that 3-D micro-CT measurements (longitudinal)
are comparable to those of standard histomorphometry,
and that most of the bone structural measurements are sensitive to changes in
women's hormonal status across menopause.
Fertil Steril. 2007 May 9; [Epub
ahead of print
Safety of
testosterone treatment in postmenopausal women.
Department of Medicine, Cedars-Sinai
Medical Center, David Geffen School of Medicine at UCLA, Los Angeles,
California.
OBJECTIVE: To critically examine the
safety of T therapy given to postmenopausal women. DESIGN: MEDLINE literature
review, cross-reference of published data, and review of Food and Drug
Administration transcripts. RESULT(S): Although some retrospective and observational
studies provide some long-term safety data, most prospective studies have had a duration of 2 years or less. In addition, with the
exception of the female-to-male transsexuals, T was administered in conjunction
with estrogens or estrogens and progestins, which
confound the interpretation of some of the studies. The major adverse reactions
are the androgenic side effects of hirsutism and
acne. There does not appear to be an increase in cardiovascular risk factors,
with the exception of a lowering of high-density lipoprotein with oral T. There
are little data on endometrial safety, and most of the experimental data
support a neutral or beneficial effect in regards to breast cancer. There does
not appear to be an increased risk of hepatotoxicity,
neurobehavorial abnormalities, sleep apnea, or fetal virilization (in premenopausal women) with the physiologic
treatment doses of T. CONCLUSION(S): Except for hirsutism
and acne, the therapeutic administration of T in physiologic doses is safe for
up to several years. However, prospectively collected long-term safety studies
are needed to provide a greater degree of assurance.
Climacteric. 2007 Jun;10(3):257-63
The effects of short-term hormone replacement
therapy on long-term bone mineral density.
Centre for Metabolic Bone Disease,
Introduction Short-term hormone
replacement therapy (HRT) relieves menopausal symptoms and increases bone
mineral density (BMD), but bone loss reoccurs upon discontinuation. This study
assesses whether short-term HRT provides long-term BMD benefits. Method This was a prospective study of women aged 50-54 years
followed up for 9 years. Women were categorized into three groups according to
the treatment they received: No-HRT (n = 340), Short-term HRT (2-4 years, n =
60), and Long-term HRT (9 years, n = 187). Results BMD increased significantly
at the hip (2.4%, p < 0.001) and spine (8.0%, p < 0.001) over 9 years in
the Long-term HRT group. Women without treatment lost BMD at the hip (-4.2%, p
< 0.001) and spine (-3.5%, p < 0.001). Women in the Short-term HRT group
had no significant loss of BMD at the hip (-1.6%, p = 0.08) or spine (-1.4%, p
= 0.18) over 9 years. BMD in the Short-term HRT group was significantly higher
at 9 years than in the No-HRT group at both spine (difference 0.023 g/cm(2), p
= 0.048) and hip (difference 0.016 g/cm(2), p = 0.042). Conclusion After 9
years, women who had taken short-term HRT had no significant loss of BMD and were better off in terms of BMD than those left untreated.
Short-term HRT in the early postmenopausal period provides long-term BMD
benefits.
J Am Geriatr Soc. 2007 May;55(5):752-7
Secondary hyperparathyroidism due to hypovitaminosis
d affects bone mineral density response to alendronate
in elderly women with osteoporosis: a randomized controlled trial.
Barone A, Giusti A, Pioli G, Girasole G, Razzano M, Pizzonia M, Palummeri E, Bianchi G.
Department of
Gerontology and Musculoskeletal Sciences,
OBJECTIVES: To determine whether secondary
hyperparathyroidism (HPTH) due to hypovitaminosis D
affects bone mineral density (BMD) response to alendronate
(ALN) in elderly women with osteoporosis. DESIGN: Randomized, controlled trial
with 1-year follow-up. SETTING: Two osteoporosis centers in northern
Clin Endocrinol (Oxf). 2007 May;66(5):626-31
Effects of the route of oestrogen
administration on IGF-1 and IGFBP-3 in healthy postmenopausal women: results
from a randomized placebo-controlled study.
Sonnet E, Lacut K, Roudaut N, Mottier D, Kerlan V, Oger E.
Service Endocrinologie, CHU de Brest, Hopital Cavale Blanche, Brest, France.
emmanuel.sonnet@chu-brest.fr
OBJECTIVE: Oestrogens
can modulate the action or secretion of GH. Previous studies in postmenopausal
women have shown a differential effect between transdermal
17beta-oestradiol and oral ethynyl-oestradiol on GH
and IGF-1 concentrations. This secondary analysis, based on a large randomized
trial, aimed to estimate the effect of the route of administration of
17beta-oestradiol in combined hormone replacement therapy with progesterone on
IGF-1 and IGFBP-3 levels. DESIGN: IGF-1 and IGFBP-3 were evaluated in a
randomized study of 196 healthy postmenopausal women who were randomly
allocated to receive on a continuous basis either 1 mg of 17beta-oestradiol
orally combined with a daily intake of 100 mg progesterone (group 1; n = 63),
or 50 microg of 17beta-oestradiol transdermally
combined with a daily intake of 100 mg progesterone (group 2; n = 68), or
triple dummy placebo (group 3; n = 65) over a 6-month period. IGF1 and IGFBP-3
levels were available for 133 women. RESULTS: Oral oestrogen
significantly decreased IGF-1 levels compared to placebo (P = 0.04) and transdermal oestrogen (P =
0.004), whereas transdermal oestrogen
had no effect on IGF-1 levels compared to placebo (P = 0.56). As regards
IGFBP-3, no significant difference was detected between the three groups.
CONCLUSIONS: Our data indicate that the route of oestrogen
administration can influence IGF-1 levels. IGF-1 concentrations decreased
significantly with oral oestrogen, whereas no
significant change was observed with transdermal oestrogen at 6 months. The clinical relevance of these
differential effects remains to be determined, particularly with regard to the
risk for cardiovascular diseases.
Osteoporos Int. 2007 May 11; [Epub
ahead of print
Associations between the metabolic syndrome and bone health
in older men and women: the Rancho Bernardo Study.
von Muhlen D, Safii S, Jassal SK, Svartberg J, Barrett-Connor E.
Family and Preventive Medicine, UCSD, 9500
Gilman Dr., La Jolla, CA, 92093-0631C, USA, dvonmuhlen@ucsd.edu.
We examined the associations of metabolic
syndrome (MS) with BMD, osteoporosis, and osteoporotic fractures in 417 men and
671 women from the Rancho Bernardo Study. After adjusting for
Osteoporos Int. 2007 May 10; [Epub
ahead of print
Cardiovascular diseases and future risk of hip fracture in
women.
Sennerby U, Farahmand B, Ahlbom A, Ljunghall S, Michaelsson K.
Department of
Surgical Sciences, Section of Orthopaedics,
We used a population-based case-control
study in women and linkage to the Swedish in-patient register to examine if
there is an increased risk of hip fracture after a cardiovascular disease.
There was a substantially increased risk of hip fracture after a diagnosis of a
cardiovascular disease. INTRODUCTION: Recent data have indicated that
cardiovascular diseases (CVDs) might have a relationship to osteoporosis, which
may explain the increased risk of mortality after hip fracture. It is
uncertain, however, whether there is an increased risk of fracture after any
cardiovascular disease and in subgroups of CVDs. The objective of this study
was to determine whether there are associations between CVD and future hip
fracture risk. Knowledge of the risk pattern would lead to better understanding
of common pathologic pathways of osteoporosis and CVD. METHODS: We conducted a
population-based case-control study of 1,327 incident hip fracture cases and
3,170 randomly selected population controls among women 50-81 years old in
Am J Clin Nutr. 2007 May;85(5):1428-33
Effects of dietary calcium compared with calcium supplements
on estrogen metabolism and bone mineral density.
Napoli N, Thompson J, Civitelli R,
Division of Bone
and Mineral Diseases,
BACKGROUND: High calcium intake has been
associated with both high bone mineral density (BMD) and high urinary estrogen
metabolites. However, the role of dietary calcium and calcium supplements on
estrogen metabolism and BMD remains unknown. OBJECTIVE: The objective was to
investigate the importance of the source of calcium intake on estrogen
metabolism and BMD. DESIGN: The average total daily calcium intake from
supplements and diet, urinary estrogen metabolites, and spine and proximal
femur BMD were studied in 168 healthy postmenopausal white women. RESULTS:
Women who obtained calcium primarily from the diet or from both the diet and
supplements had significantly (P = 0.03) lower ratios of nonestrogenic
to estrogenic metabolites (2-hydroxyestrone 1/16alpha-hydroxyestrone) than did those
who obtained calcium primarily from supplements. Adjusted BMD z scores were
significantly greater in the subjects who obtained calcium primarily from the
diet or from both the diet and supplements than in those who obtained calcium
primarily from calcium supplements at the spine (P = 0.012), femoral neck (P =
0.02), total femur (P = 0.003), and intertrochanter
(P = 0.005). This difference was evident especially in those who obtained
calcium primarily from the diet, whose total calcium intake was lower than that
in those who obtained calcium primarily from supplements. CONCLUSION: Calcium
from dietary sources is associated with a shift in estrogen metabolism toward
the active 16alpha-hydroxyl metabolic pathway and with greater BMD and thus may
produce more favorable effects in bone health in postmenopausal women than will
calcium from supplements.
Am J Clin Nutr. 2007 May;85(5):1361-6
Americans are not meeting current calcium recommendations.
Program on
Prevention Outcomes and Practices,
BACKGROUND: Recent research has raised
doubts about the efficacy of calcium supplementation in preventing fractures;
however, adequate calcium intake remains important. OBJECTIVE: Using data from
the 1999-2002 National Health and Nutrition Examination Survey, we assessed
dietary and supplemental calcium consumption among US men and women according
to risk of osteoporosis and stratified by sex, race/ethnicity, and
socioeconomic status. DESIGN: We categorized risk of osteoporosis as high
(having an osteoporosis diagnosis or treatment), moderate (aged >50 y), or
low (aged 19-50 y). Main study outcomes included milligrams of dietary and
supplemental calcium intake, likelihood of meeting national calcium adequate
intake (AI) levels, and likelihood of taking supplemental calcium. RESULTS: Mean
(95% CI) total calcium consumption was 944 (846, 1043) mg in the high-risk
group, 821 (788, 854) mg in the moderate-risk group, and 846 (812, 871) mg in
the low-risk group. Overall, 40% of the sample met the calcium AI amount and
48% reported taking supplemental calcium. After adjustment for daily caloric
intake, the greater likelihood of meeting calcium AI levels was associated with
[odds ratio (95% CI)] low [versus moderate, 1.5 (1.2, 1.7)] and high [versus
moderate, 1.9 (1.3, 2.6)] osteoporosis risk, female sex [1.6 (1.3, 1.8)],
non-Hispanic white ethnicity [versus nonwhite, 1.9 (1.7, 2.3)], and education
beyond high school [versus less than high school, 1.5 (1.2, 1.9)]. These same
factors were also associated with an increased likelihood of taking supplemental
calcium, except for a consistent increase with higher osteoporosis risk.
CONCLUSION: Many Americans-particularly men, ethnic minorities, and the
socially disadvantaged-are not meeting the current recommendations for adequate
calcium intake through diet alone or with supplements.
Climacteric. 2007 Jun;10(3):249-56
Neutral effect of ultra-low-dose continuous combined estradiol and norethisterone acetate
on mammographic breast density.
Lundstrom E, Bygdeson M, Svane G, Azavedo E, von Schoultz B.
Departments of
Obstetrics and Gynecology.
Objective To
compare the effects of two different ultra-low doses of continuous combined
hormone therapy and placebo on mammographic breast density in postmenopausal women.
Methods A subpopulation of 255 postmenopausal women from the CHOICE trial were
randomly assigned to 0.5 mg 17beta-estradiol (E2) + 0.25 mg norethisterone
acetate (NETA), 0.5 mg E2 + 0.1 mg NETA, or placebo. Women using hormone
replacement therapy (HRT) up to 2 months prior to the study were excluded; 154
women fulfilled the inclusion criteria. Mammograms were performed at baseline
and after 6 months. Breast density was evaluated by visual classification
scales and a computer-assisted digitized technique. Results No significant
differences were detected between the active treatment groups and the placebo
group in the digitized quantification. The mean baseline values for density
around 20% were unchanged after 6 months. Also, visual classifications showed
no increase in breast density in any study group. Conclusion In contrast to
currently available bleed-free regimens, the new ultra-low-dose combination of
0.5 mg E2 and 0.1 mg NETA seems to have very little or even a neutral effect on
the breast. Both digitized quantification and visual assessment of breast
density were unchanged after 6 months. Larger prospective studies should be
performed to confirm this new finding.
Climacteric. 2007 Jun;10(3):238-43
Number of women needed in a prospective trial to prove
potential cardiovascular benefit of hormone replacement therapy.
Depypere HT, Tummers P, De Bacquer D, De Backer G, Do M, Dhont M.
Department of
Gynecology.
Introduction Hormonal replacement therapy
(HRT) may be beneficial for the cardiovascular system if hormones are given
shortly after the onset of menopause. So far, no randomized trial has provided
conclusive results. Materials and methods Based on
Belgian population data, we calculated the number of women that should be
included in a prospective double-blinded study to prove a potential cardiovascular
benefit of HRT. Sample size calculations were based on the extrapolation of
empirical observations made in three large databases from epidemiological
studies carried out in
Climacteric. 2007 Jun;10(3):197-214
Prevalence of hot flushes and night sweats around the world:
a systematic review.
Department of
Obstetrics and Gynecology,
Objective Many studies have evaluated the
relationships between ethnicity and culture, prevalence of menopausal symptoms,
and attitudes toward them, but few have assessed menopausal symptoms across
cultures world-wide. This paper aims to systematically review the prevalence of
hot flushes and night sweats, two prevalent symptoms of menopause, across the
menopausal stages in different cultures and considers potential explanations
for differences in prevalence rates. Design Sixty-six papers formed the basis
for this review. Studies were organized by geographic region, and results are
presented for
Menopause. 2007 May 4; [Epub
ahead of print
Sleep disturbance in menopause.
From the 1Departments of Psychiatry and
Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit,
MI; and 2Henry Ford Hospital Sleep Disorders Center, Department of Psychiatry,
Wayne State University School of Medicine, Detroit, MI.
OBJECTIVE:: To
determine the sources of sleep complaints in peri-
and postmenopausal women reporting disturbed sleep. DESIGN::
A total of 102 women, ages 44 to 56 years, who reported disturbed sleep were
recruited through newspaper advertisements. They were assessed with the
Pittsburgh Sleep Quality Index and the Hamilton Anxiety and Depression Rating
Scales. Complete polysomnography was performed in a
controlled laboratory setting. Results were analyzed by multiple regression. RESULTS:: Fifty-three
percent of the women had apnea, restless legs, or both. The best predictors of
objective sleep quality (laboratory sleep efficiency) were apneas, periodic
limb movements, and arousals (R = 0.44, P < 0.0001). The best predictors of
subjective sleep quality (Pittsburgh Sleep Quality Index global score) were the
Breast
Cancer Res. 2007 May 3;9(3):R28
[Epub ahead of print]
Recent
trends in breast cancer incidence rates by age and tumor characteristics among
ABSTRACT:
BACKGROUND: A recent abstract presented in a breast cancer symposium attributed
the sharp decrease in female breast cancer incidence rates from 2002 to 2003 in
the Surveillance, Epidemiology, and End Results (SEER) cancer registries of the
Climacteric. 2007 Apr;10(2):164-70
The
Royer M, Castelo-Branco C, Blumel JE, Chedraui PA, Danckers L, Bencosme A, Navarro D, Vallejo S, Espinoza MT, Gomez G, Izaguirre H, Ayala F, Martino M, Ojeda E, Onatra W, Saavedra J, Tserotas K, Pozzo E, Manriquez V, Prada M, Grandia E, Zuniga C, Lange D, Sayegh F, America FT.
Background
Metabolic syndrome (METS) is a strong predictor of cardiovascular risk. Since
the prevalence of METS increases after menopause, gynecological routine
consultation offers an excellent screening opportunity. Objectives To assess the prevalence of METS in Latin American
postmenopausal women and factors modifying its risk; as well as to assess the
role of simple routine care measurements in the diagnosis of the METS. Methods
A total of 3965 postmenopausal women, aged 45-64 years, seeking health care at
12 gynecological centers in major Latin American cities were included in this
cross-sectional study. The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III)
guidelines were applied to assess METS. This was present if three or more of
the following conditions were present: waist circumference >/= 88 cm; blood
pressure >/= 130/85 mmHg; fasting plasma triglycerides >/= 150 mg/dl;
high density lipoprotein (HDL) cholesterol < 50 mg/dl; glucose >/= 110
mg/dl or subjects were receiving treatment for their condition. Results The prevalences of having at least two, three, four or five
components were 62.5, 35.1, 13.5 and 3.2%, respectively. The prevalence
increased from 28.1% in those aged 40-44 years to 42.9% in those aged 60-64
years. The risk of METS detection (multivariate analysis) increased with age
(odds ratio (OR) 1.22, 95% confidence interval (CI) 1.03-1.43), time elapsed
since menopause (OR 1.18, 95% CI 1.00-1.38), smoking cigarettes (OR 1.40, 95%
CI 1.19-1.65), obesity (OR 13.01, 95% CI 10.93-15.49) and hypertension (OR
9.30, 95% CI 7.91-10.94). In contrast, hormone therapy reduces this risk (OR
0.59, 95% CI 0.51-0.70). Conclusion There is a high prevalence of the metabolic
syndrome in postmenopausal Latin American women seeking gynecologic health
care. Age, years since menopause, obesity and hypertension are strong predictors
of this condition.
Menopause. 2007 May-Jun;14(3 Suppl):592-7.
Options
for hormone therapy in women who have had a hysterectomy.
Department
of Obstetrics and Gynecology, The University of Chicago, Chicago, IL; and
2Departments of Obstetrics and Gynecology, and Biostatistics and Epidemiology,
Oklahoma University Health Sciences Center, Oklahoma.
OBJECTIVE:: To review postmenopausal hormone therapy for women who
have undergone hysterectomy with or without bilateral oophorectomy
and to make clinical recommendations regarding changes in regimens compared
with those for women with their uterus in place. DESIGN::
We conducted a literature review, including a review of current guidelines.
RESULTS:: When the uterus is absent, estrogen
treatment is all that is needed when hot flashes and/or genital atrophic
symptoms are associated with surgical or natural menopause. Reasons to add a progestogen to an estrogen-only therapy regimen after
hysterectomy include the need to reduce the risk for unopposed
estrogen-dependent conditions, chief among which are endometriosis or
endometrial neoplasia. Multiple lines of evidence
suggest that regimens containing both estrogen and progestogen
versus estrogen alone are associated with a greater relative risk of breast
cancer without additional improvement in relief of hot flashes or vaginal
symptoms. When a bilateral oophorectomy is performed
before natural menopause, the onset of menopausal symptoms, primarily vasomotor
symptoms, genital tract atrophy, and/or a decline in sexual function, is rapid,
and the symptoms are more severe. Thus, the need for a decision on the use of
hormone therapy is accelerated. CONCLUSIONS:: The
decision to use or not use menopausal hormone therapy in women without a uterus
should involve an individualized risk/benefit analysis just as it should when
the uterus is present. After hysterectomy, for most patients, current
literature results favor not including a progestogen.
Data suggest an attenuation of the potential cardiovascular benefit of estrogen
therapy in this situation, yet no better protection against bone fractures and
an increase in the risk for breast cancer when both estrogen and progestogen are used.
Menopause. 2007 May-Jun;14(3 Suppl):586-91.
Surgical menopause:
effects on psychological well-being and sexuality.
From
1Vincent Ob/Gyn Service, Massachusetts General Hospital,
Harvard Medical School, Boston, MA; and 2Wake Forest University Health
Sciences, Winston-Salem, NC.
OBJECTIVE:: Women anticipating surgical menopause often have
significant concerns regarding the effects of surgery on psychological
well-being and sexuality. RESULTS:: The impact of
hysterectomy, often with concurrent oophorectomy, on
well-being and sexuality will vary depending on many factors. These include a
woman's preoperative mental health and sexual function, the indications for
surgery, and the specific procedure being performed. Whether or not estrogen
therapy is an option also will affect a woman's postoperative symptoms and
experience of surgical menopause. CONCLUSIONS:: The
majority of research on the effects of surgical menopause shows improved
psychological well-being and sexual function after hysterectomy for benign
disease. Women with depression or sexual problems preoperatively are at
increased risk for experiencing a worsening of mood and libido postoperatively.
Menopause. 2007 May/June;14(7 Suppl. 1):580-585.
Elective
oophorectomy for benign gynecological disorders.
Shoupe D, Parker WH, Broder MS, Liu Z, Berek JS.
OBJECTIVE:: To review the risks and benefits of elective oophorectomy and to make a clinical recommendation for an
appropriate age when benefits of this procedure outweigh the risks. DESIGN:: The risks and benefits of oophorectomy
as detailed in published articles are reviewed with regard to quality-of-life
issues and mortality outcomes in oophorectomized
versus nonoophorectomized women from five diseases
linked to ovarian hormones (coronary heart disease, ovarian cancer, breast
cancer, stroke, and hip fracture). RESULTS:: Numerous
reports link oophorectomy to higher rates of
cardiovascular disease, osteoporosis, hip fractures, dementia, short-term
memory impairment, decline in sexual function, decreased positive psychological
well-being, adverse skin and body composition changes, and adverse ocular
changes, as well as more severe hot flushes and urogenital
atrophy. The potential benefits associated with oophorectomy
include prevention of ovarian cancer, a decline in breast cancer risk, and a
reduced risk of pelvic pain and subsequent ovarian surgery. In our study of
long-term mortality after oophorectomy using Markov
modeling, preservation of ovaries until women are at least aged 65 years was
associated with higher survival rates. For women between ages 50 and 54 with
hysterectomy and ovarian preservation, the probability of surviving to age 80
was 62% versus 54% if oophorectomy was performed.
This 8% difference in survival is primarily due to fewer women dying from
cardiovascular heart disease and/or hip fracture. This survival advantage far
outweighs the 0.47% increased mortality rate from ovarian cancer prevented by oophorectomy. If surgery occurred between ages 55 and 59,
the survival advantage was 4%. After age 64 there were no significant
differences in survival rates. Prior literature supports our conclusion of a
benefit over risk for ovarian conservation. CONCLUSIONS::
Elective oophorectomy is associated with short-and
long-term health consequences that merit serious consideration. For women with
an average risk of ovarian cancer, ovarian conservation until at least age 65
seems to benefit long-term survival.
Menopause. 2007 May/June;14(7 Suppl. 1):572-579.
Surgical versus
natural menopause: cognitive issues.
Department of Health Research and Policy
(Epidemiology),
OBJECTIVE:: Women who undergo both natural and surgical menopause
experience the loss of cyclic ovarian production of estrogen, but hormonal and
demographic differences distinguish these two groups of women. Our objective
was to review published evidence on whether the premature cessation of
endogenous estrogen production in women who underwent a surgical menopause has
deleterious consequences for cognitive aging and to determine whether
consequences differ for women if they undergo natural menopause. Studies of
estrogen-containing hormone therapy are relevant to this issue. DESIGN:: We reviewed evidence-based research, including the
systematic identification of randomized clinical trials of hormone therapy with
cognitive outcomes that included an objective measure of episodic memory.
RESULTS:: As inferred from very small, short-term,
randomized, controlled trials of high-dose estrogen treatment, surgical
menopause may be accompanied by cognitive impairment that primarily affects
verbal episodic memory. Observational evidence suggests that the natural
menopausal transition is not accompanied by substantial changes in cognitive
abilities. For initiation of hormone therapy during perimenopause
or early postmenopause when the ovaries are intact,
limited clinical trial data provide no consistent evidence of short-term
benefit or harm. There is stronger clinical trial evidence that initiation of
hormone therapy in late postmenopause does not
benefit episodic memory or other cognitive skills. CONCLUSIONS:: Further research is needed on the long-term cognitive
consequences of surgical menopause and long-term cognitive consequences of
hormone therapy initiated near the time of surgical or natural menopause. A
potential short-term cognitive benefit might be weighed when a premenopausal
woman considers initiation of estrogen therapy at the time of, or soon after,
hysterectomy and oophorectomy for benign conditions,
although data are still quite limited and estrogen is not approved for this
indication. Older postmenopausal women should not initiate hormone therapy to
improve or maintain cognitive skills.
Menopause. 2007 May-Jun;14(3 Suppl):567-71.
Effect
of early menopause on bone mineral density and fractures.
From the
OBJECTIVE:: To review the data on the effect of early menopause on
bone. Do women undergoing early menopause develop lower bone mineral density at
an earlier age and do they have a higher incidence of osteoporotic fractures?
Is there a difference on bone between women who undergo early natural menopause
compared to women who have early menopause after oophorectomy?
RESULTS:: The earlier in life that menopause occurs,
the lower the bone density will be later in life. Low bone density is associated
with a higher fracture rate, and several studies show a relationship between
early menopause, oophorectomy, and an increase in
osteoporotic fractures. CONCLUSIONS:: Early menopause
is a risk factor for osteoporosis. Women with an early menopause should have
bone density testing performed within 10 years of menopause so that osteopenia or osteoporosis will be diagnosed early and
appropriate antiresorptive therapy initiated.
Menopause. 2007 May-Jun;14(3 Suppl):562-6.
Surgical
menopause and cardiovascular risks.
Department of Obstetrics and Gynecology,
OBJECTIVE
& DESIGN:: To review the relevant literature on
the effect of surgical menopause on cardiovascular disease (CVD). RESULTS &
CONCLUSIONS:: Early menopause (before age 50) is
associated with an increased risk of CVD. Bilateral oophorectomy
around the time of menopause may impart either a small influence or no effect
on increasing the risk of CVD; however, bilateral oophorectomy
before menopause significantly increases the risk. Some data suggest a
protective effect of estrogen therapy in this setting exist. The CVD risk is
principally that of coronary heart disease and not cerebrovascular
disease. Mortality rates may be increased in women with early menopause, either
spontaneous or surgically induced. Hysterectomy per se, without bilateral oophorectomy, does not seem to increase CVD risk.
N Engl J Med. 2007 May 3;356(18):1809-22.
Once-yearly
zoledronic acid for treatment of postmenopausal
osteoporosis.
Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, et al.
BACKGROUND:
We assessed the effects of annual infusions of zoledronic
acid on fracture risk during a 3-year period. METHODS: In this double-blind,
placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly
assigned to receive a single 15-minute infusion of zoledronic
acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12
months, and at 24 months; the patients were followed until 36 months. Primary
end points were new vertebral fracture (in patients
not taking concomitant osteoporosis medications) and hip fracture (in all
patients). Secondary end points included bone mineral density, bone turnover
markers, and safety outcomes. RESULTS: Treatment with zoledronic
acid reduced the risk of morphometric vertebral
fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group;
relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced
the risk of hip fracture by 41% (1.4% in the zoledronic-acid
group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83).
Nonvertebral fractures, clinical fractures, and
clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively
(P<0.001 for all comparisons). Zoledronic acid was
also associated with a significant improvement in bone mineral density and bone
metabolism markers. Adverse events, including change in renal function, were
similar in the two study groups. However, serious atrial
fibrillation occurred more frequently in the zoledronic
acid group (in 50 vs. 20 patients, P<0.001). CONCLUSIONS: A once-yearly
infusion of zoledronic acid during a 3-year period
significantly reduced the risk of vertebral, hip, and other fractures.
Nutr
Cancer. 2006;56(2):128-35.
Associations
between soy, diet, reproductive factors, and mammographic density in
Ursin G, Sun CL, Koh WP, Khoo KS, Gao F, Wu AH, Yu MC.
Abstract:
Although the evidence is not completely consistent, soy intake has been
inversely associated with breast cancer risk, and the strongest results have
been observed in certain Asian populations. To address this issue and to examine
the association between mammographic density and reproductive factors in this
population, we conducted a crosssectional analysis of
mammograms and validated food-frequency questionnaires from 380 Chinese women
living in
Nutr Cancer. 2006;56(2):253-9.
A traditional mediterranean diet decreases endogenous estrogens in
healthy postmenopausal women.
Carruba G, Granata OM, Pala V, Campisi I, Agostara B, Cusimano R, Ravazzolo B, Traina A.
Abstract:
Breast cancer incidence and mortality rates are markedly lower in the south
than in the north of
Nutr
Cancer. 2006;56(2):128-35.
Associations
between soy, diet, reproductive factors, and mammographic density in
Ursin G, Sun CL, Koh WP, Khoo KS, Gao F, Wu AH, Yu MC.
Abstract:
Although the evidence is not completely consistent, soy intake has been
inversely associated with breast cancer risk, and the strongest results have
been observed in certain Asian populations. To address this issue and to examine
the association between mammographic density and reproductive factors in this
population, we conducted a crosssectional analysis of
mammograms and validated food-frequency questionnaires from 380 Chinese women
living in
Clin Ther. 2007 Feb;29(2):230-41.
Therapeutic options
for the management of hot flashes in breast cancer survivors: An evidence-based
review.
Bordeleau L, Pritchard K, Goodwin P, Loprinzi C.
Department of Medical Oncology,
BACKGROUND:: Women with breast cancer may experiencetreatment-induced
menopausal symptoms or natural menopause. Menopausal symptoms, particularly hot
flashes, are reported at a high frequency in this group and tend to be more
severe, distressing, and of greater duration than in controls. Because of the
contribution of sex hormones to breast cancer, the use of hormonal agents for
the control of hot flashes is problematic in these women. Safer nonhormonal alternatives are recommended for this patient
group. OBJECTIVES:: This was a systematic review of thetherapeutic options for the treatment of hot flashes in
breast cancer survivors. METHODS:: MEDLINE was
searched from 1990 to July 2006 using the disease-specific term breast neoplasms and the subheadings menopause and hot flashes.
EMBASE was searched from 1990 to March 2006 using the disease-specific subject
headings breast tumor/ breast cancer and menopause and the key word hot
flashes. The reference lists of the identified articles and relevant review
articles were examined for additional publications. Pertinent articles and
abstracts of large randomized controlled trials focusing on the treatrment of hot flashes in breast cancer survivors were
selected for review. Pilot studies were excluded. RESULTS::
A number of nonpharmacologic approaches are available
for the treatment of hot flashes in breast cancer survivors, although they
appear to be of limited effectiveness. Complementary alternative medicine
therapies and vitamin E have been found to have modest effectiveness at best,
and data on their long-term safety are not available. Centrally active agents
such as the antidepressants venlafaxine and paroxetine and the antiseizure
agent gabapentin have shown clinical effectiveness
and appear to be reasonably well tolerated in this population. CONCLUSIONS:: Centrally active agents (eg, venlafaxme, paroxetine, gabapentin) are regarded as the most promising nonhormonal treatments for hot flashes in breast cancer
survivors. Nonpharmacologic and complementarylalternative
medicine therapies have limited effectiveness.
J Natl Cancer Inst. 2007 May 2;99(9):672-9
Randomized
controlled trial to evaluate transdermal testosterone
in female cancer survivors with decreased libido; North Central Cancer
Treatment Group protocol N02C3.
Barton DL, Wender DB, Sloan JA, Dalton RJ, Balcueva EP, Atherton PJ, Bernath AM Jr, DeKrey WL, Larson T, et al
Department of Medical Oncology, Mayo Clinic and Mayo
Foundation,
BACKGROUND:
Decreased libido is one of several changes in sexual function that are often
experienced by female cancer patients. Transdermal
testosterone therapy has been associated with increased libido among
estrogen-replete women who report low libido. METHODS: In a phase III
randomized, placebo-controlled crossover clinical trial, we evaluated whether transdermal testosterone would increase sexual desire in
female cancer survivors. Postmenopausal women with a history of cancer and no
current evidence of disease were eligible if they reported a decrease in sexual
desire and had a sexual partner. Eligible women were randomly assigned to
receive 2% testosterone in Vanicream for a
testosterone dose of 10 mg daily or placebo Vanicream
for 4 weeks and were then crossed over to the opposite treatment for an
additional 4 weeks. The primary endpoint was sexual desire or libido, as
measured using the desire subscales of the Changes in Sexual Functioning
Questionnaire, as assessed at baseline and at the end of 4 and 8 weeks of
treatment. Serum levels of bioavailable testosterone
were measured at the same times. All statistical tests were two-sided. RESULTS:
We enrolled 150 women. Women who were on active testosterone cream had higher
serum levels of bioavailable testosterone than women
on placebo (mean change from baseline, testosterone versus placebo, week 4,
11.57% versus 0%, difference = 11.57%, 95% confidence interval [CI] = 8.49% to
14.65%; week 8, 10.21% versus 0.28%, difference = 9.92%, 95% CI = 5.42% to
14.42%; P<.001 for all). However, the average intrapatient
libido change from baseline to weeks 4 and 8 was similar on both arms.
CONCLUSION: Increased testosterone level did not translate into improved
libido, possibly because women on this study were estrogen depleted.
Diabetes Care. 2007 Apr 27; [Epub ahead of print
Insulin Sensitivity
and Insulin Secretion Determined by the Homeostasis Model Assessment (HOMA) and
Risk of Diabetes Mellitus in a Multi-Ethnic Cohort of Women: The Women's Health
Initiative Observational Study.
Song Y, Manson JE, Tinker L, Howard BV, Kuller LH, Nathan L, Rifai N, Liu S.
Division of Preventive Medicine, Medicine, Brigham and
Women's Hospital,
The
homeostasis model assessment (HOMA) based on plasma levels of fasting glucose
and insulin has been widely validated and applied for quantifying insulin
resistance and beta-cell function. However, prospective data regarding its relation
to diabetes risk in ethnically diverse populations are limited. DESIGN AND
METHODS Among 82,069 women aged 50 to 79 years free of cardiovascular disease
or diabetes participating in the Women's Health Initiative Observational Study
(WHI-OS), we conducted a nested case-control study to prospectively examine the
relations of HOMA-insulin resistance (HOMA-IR) and beta-cell function (HOMA-%B)
with diabetes risk. During a median follow-up period of 5.9 years, 1,584
diabetes patients were matched with 2,198 controls by age, ethnicity, clinical
center, time of blood draw, and follow-up time. RESULTS Baseline levels of
fasting glucose, insulin, and HOMA-IR were each significantly higher among
cases than controls while HOMA-%B was lower (all P values<0.0001). After
adjustment for matching factors and diabetes risk factors, all four markers
were significantly associated with diabetes risk; the estimated relative risks
(RRs) per standard deviation increment were 3.54 (95% CI, 3.02-4.13) for
fasting glucose, 2.25 (1.99-2.54) for fasting insulin, 3.40 (2.95-3.92) for
HOMA-IR, and 0.57(0.51-0.63) for HOMA-%B. While no statistically significant
multiplicative interactions were observed between these markers and ethnicity,
the associations of both HOMA-IR and HOMA-%B with diabetes risk remained
significant and robust in each ethnic group including Whites, Blacks,
Hispanics, and Asians/Pacific Islanders. When evaluated jointly, the relations
of HOMA-IR and HOMA-%B with diabetes risk appeared to be independent and additive.
HOMA-IR was more strongly associated with an increased risk than were other
markers after we excluded those with a fasting glucose >/= 126 mg/dl at
baseline. CONCLUSIONS High HOMA-IR and low HOMA%B were independently and
consistently associated with an increased diabetes risk in a multi-ethnic
cohort of US postmenopausal women. These data suggest the values of HOMA
indices for diabetes risk in epidemiologic studies.