Selección de Resúmenes de Menopausia
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.