Selección de
Resúmenes de Menopausia
Julio 2008
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad de
Chile
Semana del 22 de al 29 de Julio 2008
Sleep. 2008 Jul
1;31(7):979-90
Sleep disturbance
during the menopausal transition in a multi-ethnic community sample of women.
Kravitz HM, Zhao X, Bromberger JT, Gold EB, Hall MH, Matthews
KA, Sowers MR.
STUDY OBJECTIVES:
Examine age-adjusted odds and racial/ethnic differences in self-reported
difficulties falling and staying asleep and early morning awakening in midlife
women to determine whether difficulty sleeping increased with progression
through the menopausal transition. DESIGN: Longitudinal analysis. SETTING:
Community-based. PARTICIPANTS: 3,045 Caucasian, African American, Chinese,
Japanese, and Hispanic women, aged 42-52 years and pre- or early peri-menopausal at baseline, participating in the Study of
Women's Health Across the Nation (SWAN).
Interventions: None. MEASUREMENTS AND RESULTS: Self-reported number of nights
of difficulty falling asleep, staying asleep, and early morning awakening
during the previous 2 weeks were obtained at baseline and 7 annual assessments.
Random effects logistic regression was used to model associations between each
of the 3 sleep measures and the menopausal transition, defined by bleeding
patterns, vasomotor symptoms (VMS), and estradiol
(E2) and follicle stimulating hormone (FSH) serum levels. Adjusted odds ratios
(ORs) for difficulty falling asleep and staying asleep increased through the
menopausal transition, but decreased for early morning awakening from late perimenopause to postmenopause.
Naturally and surgically postmenopausal women using hormones, compared with
those who were not, generally had lower ORs for disturbed sleep. More frequent
VMS were associated with higher ORs of each sleep difficulty. Decreasing E2
levels were associated with higher ORs of trouble falling and staying asleep,
and increasing FSH levels were associated with higher ORs of trouble staying
asleep. Racial/ethnic differences were found for staying asleep and early
morning awakening. CONCLUSIONS: Progression through the menopausal transition
as indicated by 3 menopausal characteristics--symptoms, bleeding-defined
stages, and endogenous hormone levels--is associated with self-reported sleep
disturbances.
Menopause. 2008 Jul 18. [Epub ahead of print]
Comparative effects
of oral conjugated equine estrogens and micronized 17beta-estradiol on breast
proliferation: a retrospective analysis.
Wood CE, Clarkson
TB, Chen H, Veenstra TD, Xu X, Scott L, Cline JM.
Departments of
1Pathology/Section on Comparative Medicine and 2Biostatistical Sciences,
OBJECTIVE:: To evaluate the effects of oral conjugated equine
estrogens (CEE) and micronized 17beta-estradiol (E2) on breast proliferation in
a postmenopausal primate model. DESIGN:: Data from
nine studies were analyzed retrospectively. The primary outcome measure was
breast epithelial proliferation determined by immunolabeling
for the Ki67 antigen. Other measures included progesterone receptor expression
and endometrial thickness (as surrogate markers of systemic estrogen
exposure) and urinary estrogen metabolite profile.
All CEE doses were given at the human equivalent of 0.625 mg/day (n = 281),
whereas E2 was given at the human equivalent of 1.0 mg/day or less (n = 131).
RESULTS:: Oral CEE resulted in a modest overall
increase in breast epithelial proliferation of 75% that reached significance at
P < 0.05 compared with placebo in one of four parallel-arm studies. In
contrast, oral E2 resulted in a more substantial increase in breast epithelial
proliferation of 259% (all studies) to 330% (parallel-arm studies only) that
reached significance at P <
Public
Health Nutr. 2008 Jul 23:1-7. [Epub ahead of
print]
Dietary
consumption of phytochemicals and breast cancer risk
in Mexican women.
Torres-Sanchez L, Galvan-Portillo M, Wolff MS, Lopez-Carrillo L.
Instituto
Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
OBJECTIVE: To
perform an evaluation of selected phytochemicals
intake and breast cancer (BC) risk in Mexican women. DESIGN: We conducted hospital-based
case-control study. SETTING:
Gynecol Endocrinol. 2008 Jul;24(7):405-10.
Associations
between serum testosterone levels, cell proliferation and progesterone receptor
content in normal and malignant breast tissue in postmenopausal women.
Hofling M, Löfgren L, von Schoultz E, Carlström K, Söderqvist G.
Division
for Obstetrics and Gynecology, Karolinska
University Hospital, Stockholm, Sweden.
Progestogens and
progesterone receptors (PR) may play an important role in increased breast
proliferation following combined estrogen/progestogen hormone therapy, while androgens may counteract
this effect. In 50 untreated healthy postmenopausal women and 48 untreated
postmenopausal breast cancer patients, we measured serum levels of testosterone
(T), sex hormone-binding globulin (SHBG), estrone (E(1)) and adrenal androgens; and additionally, in the breast
cancer patients, cortisol and corticosteroid-binding
globulin and endocrine data related to breast proliferation (assessed using the
Ki-67/MIB-1 monoclonal antibody) and PR levels (determined by enzyme
immunoassay) in the breast cancer tissue. In the healthy women the percentage of
MIB-1(+) cells showed significant negative correlations with serum levels of
total T, calculated free T (fT) and the fT/E(1) ratio; while in the breast cancer patients PR
content showed significant negative correlations with fT
level, the fT/E(1) ratio and the T/SHBG ratio. No
other correlations were found in any of the groups. Our findings in healthy
women confirm previous reports of an antiproliferative
effect of androgens in breast tissue and our finding in breast cancer patients
suggests that this antiproliferative effect may be
mediated via downregulation of PR.
Gynecol Endocrinol. 2008 Jul;24(7):399-404.
Postmenopausal
vaginal atrophy correlates with decreased estradiol and
body mass index and does not depend on the time since menopause.
Repse-Fokter A, Takac I, Fokter SK.
Department
of Pathomorphology and Cytology, Celje
Teaching Hospital, Celje, Slovenia.
OBJECTIVE: To
evaluate the relationship between morphologic cell characteristics in Papanicolaou (Pap) smears and serum estradiol,
body mass index (BMI) and the time elapsed since menopause. Study design. In 92
women Pap smears were grouped into atrophic and mature cell patterns and
compared with estradiol, BMI and the time since
menopause. RESULTS: Forty-one patients with mature cell pattern were on average
7.1 years from menopause and 51 patients with atrophic pattern 8.2 years, but
this difference was not significant. Estradiol in
patients with mature cell pattern was significantly higher (52.1 +/- 48.5 pmol/l) than in patients with atrophic pattern (25.6 +/-
40.0 pmol/l). Similarly, BMI was significantly higher
(27.9 +/- 4.2 kg/m(2)) in patients with mature cell
pattern than in patients with atrophic pattern (25.7 +/- 3.8 kg/m(2)). There
was no significant correlation between the time since menopause and estradiol among patients with mature and atrophic cell
pattern. The same was true for the correlation between the time from menopause
and BMI in patients with mature and atrophic pattern. CONCLUSIONS: Estradiol and BMI are associated with vaginal cell
maturation and atrophy in postmenopausal women. Vaginal cell atrophy does not
depend on the time since menopause.
Climacteric. 2008 Aug;11(4):304-14.
Symptoms in peri- and postmenopausal women in relation to testosterone
concentrations: data from The Women's Health in the
Gotmar A, Hammar M, Fredrikson M, Samsioe G, Nerbrand C, Lidfeldt J, Spetz AC.
Department
of Molecular and Clinical Medicine, Division of Obstetrics and Gynecology, Faculty of Health Sciences, University Hospital
Linkoping.
OBJECTIVES: The
aim of this study was to investigate possible associations between androgen
concentrations in perimenopausal women and symptoms
that may be associated with low androgen concentrations in the blood. METHODS:
All women born in the period 1935-1945 and living in a defined geographic area
in
Metabolism. 2008 Aug;57(8):1101-7.
Regional
body fat distribution and metabolic profile in postmenopausal women.
Piché ME, Lapointe A, Weisnagel SJ, Corneau L, Nadeau A, Bergeron J, Lemieux S.
Institute of Nutraceuticals and Functional Foods, Laval University,
Québec QC, Canada G1K 7P4; Lipid Research Center,
CHUL Research Center, Québec QC, Canada.
The aim of the
study was to examine how body fat distribution variables were associated with
metabolic parameters in a sample of 113 postmenopausal women not receiving
hormone therapy (56.9 +/- 4.4 years, 28.4 +/- 5.1 kg/m(2)).
Body fat distribution variables (visceral adipose tissue [AT], subcutaneous AT,
and total midthigh AT) were measured using computed
tomography; body fat mass was assessed by hydrostatic weighing; insulin
sensitivity was determined with the euglycemic-hyperinsulinemic
clamp; fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG)
concentrations were measured by a 75-g oral glucose load; and
(high-sensitivity) C-reactive protein (hs-CRP) was
measured using a highly sensitive assay. After controlling for fat mass,
visceral AT was positively associated with plasma triglyceride, hs-CRP, FPG, and 2hPG, and negatively associated with
high-density lipoprotein cholesterol (HDL-C) and insulin sensitivity. Total midthigh AT was negatively associated with apolipoprotein B, FPG, and 2hPG, and positively associated
with insulin sensitivity. Stepwise multiple regression analyses including
abdominal visceral AT, subcutaneous AT and total midthigh
AT as independent variables showed that abdominal visceral AT best predicted
the variance in plasma triglyceride, HDL-C, low-density lipoprotein peak
particle size, hs-CRP, FPG, 2hPG, and insulin
sensitivity. Abdominal subcutaneous AT was a significant predictor of only
insulin sensitivity, whereas total midthigh AT
predicted HDL-C, low-density lipoprotein peak particle size, and apolipoprotein B. These multivariate analyses also
indicated that total midthigh AT was favorably related to these outcomes, whereas abdominal
visceral AT and subcutaneous AT were unfavorably
related. These results confirmed that abdominal visceral fat is a critical
correlate of metabolic parameters in postmenopausal women. In addition, a
higher proportion of AT located in the total midthigh
depot is associated with a favorable metabolic
profile.
Cancer Detect Prev. 2008 Jul
16. [Epub ahead of print]
Biomarkers
associated with breast cancer are associated with obesity.
Sauter ER, Scott S, Hewett J, Kliethermes B, Ruhlen RL, Basarakodu K, de la
Torre R.
Department of
Surgery, University of Missouri, One Hospital Drive, Columbia, MO 65212, USA.
Background:
Obesity is linked to the development of postmenopausal breast cancer, and some
studies indicate obesity predicts a worse prognosis for premenopausal women who
develop the disease. It was our hypothesis that proteins associated with breast
cancer would be associated with body mass index (BMI). Methods: We searched our
database of women enrolled in breast health translational research trials for
information on BMI and markers predictive of breast cancer (basic fibroblast
growth factor (bFGF), prostate-specific antigen
(PSA), human kallikrein (hK)2, and urinary plasminogen
activator (uPA). Information on BMI and one or more
nipple aspirate fluid (NAF) or serum biomarkers was available from 382 women.
Results: In this data set, NAF and serum levels of PSA (nPSA
and sPSA), and NAF levels hK2, bFGF
and uPA were each associated with pre- and/or
postmenopausal breast cancer. sPSA
was inversely associated with BMI in both pre- (r=-.56, p=.001) and
postmenopausal women (r=-.62, p=.0035) without breast cancer. This association
was lost when controlling for plasma volume. In women without breast cancer,
NAF bFGF (p=.07, premenopausal subjects) and NAF hK2
(p=.09, postmenopausal subjects) were borderline associated with BMI. In women
with breast cancer, nPSA was inversely (r=-.53,
p=.049) associated with BMI in premenopausal women and directly associated with
BMI in postmenopausal women (r=.37, p=.017). nPSA trended higher in hormone sensitive cancers,
especially those that expressed progesterone receptor (p=.059). Conclusions: sPSA was inversely associated with BMI in all pre- and
postmenopausal women and specifically in pre- and postmenopausal women without
breast cancer. NAF PSA was associated with BMI in pre- and postmenopausal women
with breast cancer. Evaluating the change in PSA with changes in weight may
provide clues regarding a subject's breast cancer risk.
Adv Exp Med Biol. 2008;630:232-6
Prevention
of breast cancer using SERMs.
Parkside
Oncology Clinic London, UK.
The development of
breast cancer is dependant in part on oestrogen. Suppression of ovarian
function or use of anti-oestrogens will reduce the incidence of breast cancer.
Many trials have now been done involving tens of thousands of healthy women
evaluating the use of selective oestrogen receptor modulators to reduce the
risk of breast cancer in healthy women. Tamoxifen
will reduce the early incidence of breast cancer in pre and postmenopausal
women by about 40% but causes vasomotor symptoms, thromboembolism
and gynaecological toxicity including polyps, endometrial atypia
and rarely cancer. In long follow up trials the risk reduction for breast
cancer extends beyond the treatment period out to at least 15 years appearing
to get larger with time indicating a true long term prevention effect. The
toxicity of tamoxifen is for the most part confined
to the treatment period. Raloxifene also has similar
breast cancer risk reduction activity to tamoxifen
but has less toxicity with no evidence of an increased risk of endometrial atypia or cancer. Tamoxifen is
licensed for breast cancer risk reduction in the
J Sex Med. 2008 Jul
14. [Epub ahead of print]
Sexual
Function, Dysfunction, and Sexual Distress in a Prospective, Population-Based
Sample of Mid-Aged, Australian-Born Women.
Dennerstein L, Guthrie JR, Hayes RD, Derogatis LR, Lehert P.
Office for Gender
and Health, Department of Psychiatry, The University
of
Introduction.
Previous, population-based studies investigating the risk factors for sexual
distress have not drawn on longitudinal data. Aims.
Determine the prevalence of sexual distress and dysfunction, explore factors
associated with/predictive of sexual distress, and describe changes in sexual
function over a decade in a population-based sample of mid-aged women. Methods. Eleven-year prospective study of
Australian-born women, aged 45-55 years, and menstruating at baseline.
Short Personal Experiences Questionnaire (SPEQ) was completed in years 1 to 8
and 11 of follow-up. Female Sexual Distress Scale (FSDS) was completed in the
11th year of follow-up. Main Outcome Measures.
Validated outcome measures were the SPEQ (total sex score </=7 indicates low
sexual function) and FSDS (score >/=15 indicates sexual distress). Results. Two hundred fifty-seven women were interviewed in
the 11th year of follow-up. All domains of sexual function declined
significantly in the decade studied. Women using hormone therapy in year 11 had
significantly greater responsivity and higher
frequency of sexual activities than nonusers. Two hundred four women completed
both the FSDS and SPEQ questionnaires. One hundred sixty-six (81%) women had an
SPEQ score </=7 of whom 34 (17% of the total sample) had an FSDS score
>/=15, and were classified as having female sexual dysfunction. The multiple
logistic regression analysis found that female sexual distress was concurrently
associated with higher depression scores (odds ratio [OR] 1.31, 95% confidence
interval [CI] 1.10, 1.56) and more negative feelings for partner (OR 0.49, 95%
CI 0.32, 0.76) and predicted by prior negative feelings for partner (OR 0.31,
95% CI 0.14, 0.70), and a greater decline in total sex score (OR 0.77, 95% CI
0.59, 0.99). Conclusions. By the end of the sixth
decade, women have low levels of sexual function. Hormone therapy may help
these women maintain sexual function. A minority of these mostly postmenopausal
women are significantly distressed about low sexual function. Sexual distress
is associated with depression and relationship factors.
Adv Exp Med Biol. 2008;630:72-93.
Obesity and
diabetes epidemics: cancer repercussions.
Hjartåker A, Langseth H, Weiderpass E.
Department
of Etiological Research, Cancer Registry of Norway, Oslo, Norway.
The prevalence of
overweight (body mass index, BMI, between 25 and 30 kg/m2) and obesity (BMI of
30 kg/m2 or higher) is increasing rapidly worldwide, especially in developing
countries and countries undergoing economic transition to a market economy. One
consequence of obesity is an increased risk of developing type II diabetes.
Overall, there is considerable evidence that overweight and obesity are
associated with risk for some of the most common cancers. There is convincing
evidence of a positive association between overweight/obesity and risk for adenocarcinoma of the oesophagus and the gastric cardia, colorectal cancer, postmenopausal breast cancer,
endometrial cancer and kidney cancer (renal-cell). Premenopausal breast cancer
seems to be inversely related to obesity. For all other cancer sites the
evidence of an association between overweight/obesity and cancer is inadequate,
although there are studies suggesting an increased risk of cancers of the liver,
gallbladder, pancreas, thyroid gland and in lymphoid and haematopoietic tissue.
Far less is known about the association between diabetes mellitus type I (also
called insulin dependent diabetes mellitus or juvenile diabetes), type II
diabetes (called non-insulin dependent diabetes mellitus or adult onset
diabetes mellitus) and cancer risk. The most common type of diabetes mellitus,
type II, seems to be associated with liver and pancreas cancer and probably
with colorectal cancer. Some studies suggest an association with endometrial
and postmenopausal breast cancer. Studies reporting on the association between type I diabetes mellitus, which is relatively rare in most
populations and cancer risk are scanty, but suggest a possible association with
endometrial cancer. Overweight and obesity, as well as type II diabetes
mellitus are largely preventable through changes in lifestyle. The fundamental
causes of the obesity epidemic-and consequently the diabetes type II
epidemic-are societal, resulting from an environment that promotes sedentary
lifestyles and over-consumption of energy. The health consequences and economic
costs of the overweight, obesity and type II diabetes epidemics are enormous.
Avoiding overweight and obesity, as well as preventing type II diabetes
mellitus, is an important purpose to prevent cancer and other diseases.
Prevention of obesity and type II diabetes should begin early in life and be
based on the life-long health eating and physical activity patterns.
Substantial public investments in preventing overweight, obesity and type II
diabetes mellitus are both appropriate and necessary in order to have a major
impact on their adverse health effects including cancer.
Semana del 9 de al 22 de Julio 2008
BMJ. 2008 Jul 10;337:a386. doi:
10.1136/bmj.a386.
Gallbladder disease and use of transdermal versus oral hormone replacement
therapy in postmenopausal women: prospective cohort study.
Liu B, Beral V, Balkwill A, Green J, Sweetland S, Reeves G; Million Women Study Collaborators.
Epidemiology
Unit, University of Oxford, Oxford OX3 7LF. Bette.Liu@ceu.ox.ac.uk
OBJECTIVE: To
determine whether transdermal compared with oral use
of hormone replacement therapy reduces the risk of gallbladder disease in
postmenopausal women. DESIGN: Prospective cohort study (Million Women Study).
SETTING: Women registered with the National Health Service (NHS) in
Osteoporos Int. 2008 Jul 17. [Epub ahead of print]
Weight and body mass index predict bone mineral density and fractures in
women aged 40 to 59 years.
Department
of Medicine, McGill University, Montreal, Canada, suzanne.morin@mcgill.ca.
Weight and body
mass index are associated with low bone mineral density and fractures in older
women. This retrospective cohort study confirms a similar relationship in women
aged 40 to 59 years. INTRODUCTION: Risk factors for the prediction of
osteoporosis and fractures have been less thoroughly studied in younger women.
We evaluated the associations between weight, body mass index (BMI), the
Osteoporosis Self-Assessment Tool (OST), bone mineral density (BMD) and
fracture risk in women aged 40 to 59 years. METHODS: Using administrative
health management databases, we conducted a retrospective cohort study in 8,254
women aged 40-59 years who had baseline BMD testing. Linear regression and Cox
proportional multivariate models were created to examine the associations with
weight, BMI, OST, BMD, and subsequent fractures throughout a 3.3-year
follow-up. RESULTS: Body weight, BMI, and OST had a similar overall performance
in their ability to classify women with femoral neck T-score </= -2.5.
Throughout 27,256 person years of observation, 225 women experienced one or
more fractures. After adjustment for age, prevalent fractures, and use of
corticosteroids, each standard deviation decrease in weight was associated with
a 19% increase in the risk of incident fracture (95% CI: 1.01-1.35). Femoral
neck BMD and the presence of prevalent fractures were also associated with the
risk of incident fractures. CONCLUSIONS: Low weight and BMI predict
osteoporosis and are associated with increased fracture risk in younger women.
The negative impact of low body weight on bone health should be more widely
recognized.
Br J
Cancer. 2008 Jul 15. [Epub
ahead of print]
Obesity and risk of pancreatic cancer among postmenopausal women: the
Women's Health Initiative
Luo
J, Margolis
KL, Adami
HO, Lacroix
A, Ye W.
Institute
of Social Development and Public Policy, Beijing Normal University, Beijing,
China.
A total of 138 503
women in the Women's Health Initiative in the United States were followed
(average of 7.7 years) through 12 September 2005 to examine obesity, especially
central obesity in relation to pancreatic cancer (n=251). Women in the highest
quintile of waist-to-hip ratio had 70% (95% confidence interval 10-160%) excess
risk of pancreatic cancer compared with women in the lowest quintile.
Cancer Epidemiol Biomarkers
Prev.
2008 Jul;17(7):1674-81.
Increases in Serum Estrone Sulfate
Level Are Associated with Increased Mammographic Density during Menopausal
Hormone Therapy.
Crandall CJ, Guan M, Laughlin GA, Ursin G, Stanczyk FZ, Ingles SA, Barrett-Connor E, Greendale GA.
Background:
Menopausal hormone therapy increases mammographic density. We determined whether
increases in serum estrone sulfate
(E(1)S) levels during menopausal hormone therapy
predict increased mammographic density. Methods: We measured percent
mammographic density and serum E(1)S levels in 428
participants of the Postmenopausal Estrogen/Progestin
Interventions study who were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg alone, CEE + daily medroxyprogesterone acetate (MPA) 2.5 mg, CEE + cyclical
MPA (10 mg days 1-12 per 28-day cycle), or CEE + cyclical micronized progesterone
(10 mg days 1-12). Serum E(1)S levels were determined
by RIA. Information about covariates was determined by annual questionnaire.
Using linear regression, we determined the association between change in E(1)S level from baseline to 12 months and change in percent
mammographic density (by semiquantitative interactive
threshold method). RESULTS: After controlling for baseline mammographic
density, age, body mass index, alcohol intake, parity, smoking, ethnicity,
physical activity, and age at first pregnancy, mammographic density increased
by 1.3% for every 1 ng/mL
increase in E(1)S level (P < 0.0001). The association between change in E(1)S level and change in mammographic density differed by
treatment group (greater effect in CEE + cyclical MPA group versus CEE group; P
= 0.05). After controlling for treatment group, change in the ratio of E(1)S to E(1) was also positively associated with change in
mammographic density. CONCLUSIONS: Increases in serum E(1)S
levels during menopausal hormone therapy are associated with increases in
mammographic density. The relative contribution of E(1)S
and E(1) to stimulation of breast tissue awaits further elucidation.
Expert Opin Pharmacother. 2008 Aug;9(11):1935-54.
Nitric oxide: new evidence for novel therapeutic indications.
BACKGROUND: Nitric
oxide (NO) deficiency is implicated in many pathophysiological
processes in mammals. NO is a ubiquitous molecule involved in multiple cellular
functions. Uncontrolled or inappropriate production of NO may lead to several
disease states including septic shock, rheumatoid and inflammatory arthropathies, and expansion of cerebral damage after
stroke. However, to date, there are no therapeutic agents available that can
overcome these conditions. Similarly, underproduction of NO by NO synthase or enhanced breakdown of NO also leads to diseases
such as hypertension, ischemic conditions, pre-eclampsia,
premature delivery, among others. NO donor therapies are indicated in these conditions.
RESULTS: Nitroglycerin and nitrates (NO donors) have
been used as therapeutic agents for the past century, particularly to treat
vascular disease, and the only significant adverse effects are headaches. NO
donors are highly cost-effective and have beneficial effects in multiple body
systems. When the body cannot generate NO via NO synthase or due to rapid turnover leading to inadequate
amounts of NO available for biological homeostasis, administration of exogenous
NO, or prolongation of the actions of endogenous NO, are practical ways to
supplement NO. CONCLUSION: Recipients of such therapy include patients with
angina pectoris, coronary artery disease, hypertension, osteoporosis,
gastrointestinal motility disorders, pregnancy-related disorders including
premature delivery, pre-eclampsia, vulvodynia, and erectile dysfunction in men. Postmenopausal
NO deficiency is rectified with hormone replacement therapy, which enhances
local production of NO. Declining local NO production secondary to estrogen deficiency in postmenopausal women and perhaps in
older men could be one of the reasons for age-related increased incidences of
cardiovascular events and sexual dysfunction. Thus, in addition to
supplementation of NO compounds in acute situations like alleviating angina and
erectile dysfunction, chronic NO therapy is cost-effective in decreasing
cardiovascular events, and improving the urogenital
system and skeletal health.
Int J Obes (Lond). 2008 Jul 15. [Epub
ahead of print]
Body weight through adult life and risk of urinary incontinence in
middle-aged women: results from a British prospective cohort.
Mishra GD, Hardy R, Cardozo L, Kuh D.
1MRC unit for
Lifelong Health and Ageing, Department of Epidemiology and Public Health,
University College and Royal Free Medical School, London, UK.
Objectives:To
determine whether the onset and duration of being overweight or obese are
associated with symptoms of urinary incontinence.Design:Nationally
representative cohort study.Subjects:A total of 1201
women followed-up since their birth in 1946 and annually from 48 to 54 years.Measurements:The body mass index (BMI) at the age of
20, 26, 36 and 43, and symptoms of stress, urge and severe incontinence at
seven consecutive years from age 48 to 54.Results:In each year from age 48 to
54, almost half (46-49%) reported symptoms of stress incontinence, urge
incontinence rose from 22 to 25% and severe incontinence from 8 to 11%. At the
age of 20, 26, 36 and 43, BMI was positively associated with stress symptoms
and severe incontinence in midlife. BMI transition was found to have
accumulation effects on symptoms of severe incontinence; women who were
overweight/obese since age 20 years were more likely to report severe
incontinence than women whose BMI remained below 25 kg/m(2) (odds ratio (95%
confidence interval): 2.30 (1.36-3.93)) or who became overweight or obese at 43
years (1.85 (0.97-3.51)). These relationships existed beyond the effects of
aging, childhood enuresis, kidney infection, childbirth characteristics,
menopause, educational attainment, general practitioner consultations and
smoking status. BMI was not associated with symptoms of urge incontinence.Conclusions:Across
adult life, higher BMI for women was linked with subsequent symptoms of stress
and severe incontinence in midlife; those who were overweight or obese since
early in adult life more than doubled their risk of severe incontinence. Women,
and especially young women, should be encouraged to keep their weight in a normal
range throughout adult life.
J Clin Psychopharmacol. 2008 Aug;28(4):411-7.
Selective serotonin reuptake inhibiting antidepressants are associated
with an increased risk of nonvertebral fractures.
Ziere
G, Dieleman
JP, van
der Cammen TJ, Hofman
A, Pols
HA, Stricker
BH.
Department of
Epidemiology and Biostatistics, Erasmus MC,
BACKGROUND:
Fractures related to osteoporosis and falling constitute a major health problem
in the elderly population. Exposure to antidepressants is associated with an
increased risk of falls and fractures, but most previous studies incriminate tricyclic antidepressants (TCAs) rather than selective
serotonin reuptake inhibitors (SSRIs). OBJECTIVE: To examine the association
between antidepressants, including TCAs, SSRIs, and other antidepressants and
the risk of nonvertebral fractures in elderly.
DESIGN: Prospective population-based cohort study. SETTING: The Rotterdam
Study, consisting of 7983 individuals aged 55 years and older. PARTICIPANTS:
All persons from the Rotterdam Study. RESULTS: One thousand two hundred
nineteen persons experienced a nonvertebral fracture,
25 during TCA use and 18 during SSRI use. After adjustment for age, sex,
lower-limb disability, and depression, the risk of nonvertebral
fracture was 2.35 (95% confidence interval, 1.32-4.18) for current users of
SSRIs compared with nonusers of antidepressants. Multiple adjusting for many
possible risk factors did not affect the association. To deal with potential
confounding by indication, we subsequently restricted the analysis to
antidepressant users (n = 1217). Compared with past users of TCAs or SSRIs,
current users of SSRIs had a 2.07-fold (95% confidence interval, 1.23-3.50)
increased risk of fracture, which further increased with prolonged use. In this analysis, depressive state at baseline and
during follow-up did not play a role, suggesting absence of confounding by
indication. The use of TCAs was associated with an increased fracture risk that
decreased with prolonged use. CONCLUSIONS: Not only users of TCAs but also of
SSRIs have a significantly increased risk of nonvertebral
fractures, in SSRI users especially after prolonged use. Despite fewer early
adverse effects of SSRIs, physicians treating elderly depressive patients
should be aware of the unfavorable long-term
consequence of SSRIs on fracture risk.
Menopause. 2008 Jun
30. [Epub ahead of print]
Earlier age at menopause, work, and tobacco smoke exposure.
Fleming LE, Levis S, Leblanc WG, Dietz NA, Arheart KL, Wilkinson JD, Clark J, Serdar B, et
el.
Department
of Epidemiology and Public Health, University of Miami Miller School of
Medicine, Miami.
OBJECTIVE:: Earlier age at menopause onset has been associated with
increased all-cause, cardiovascular, and cancer mortality risks. The risk of
earlier age at menopause associated with primary and secondary tobacco smoke
exposure was assessed. DESIGN:: This was a
cross-sectional study using a nationally representative sample of US women. A
total of 7,596 women (representing an estimated 79 million
Indian J
Cancer. 2008 Apr-Jun;45(2):50-3.
Mammographic density as a risk factor for
breast cancer in a low risk population.
Attam A, Kaur N, Saha S, Bhargava SK.
Department
of General Surgery, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi,
India. dr_navkaur@hotmail.com.
Background:
Mammographic density is a function of abundance of epithelial and connective
tissue in breast. It has been identified as an independent risk factor for
breast cancer in studies in western populations. We conducted a case control
study to evaluate the role of mammographic density as risk factor for the
development of breast cancer in Indian patients. Methods: One hundred and one
cases of breast cancer and 123 healthy controls were included in the study.
Mammographic density of the breast tissue of all controls and the contralateral breast of breast cancer patients was measured
using a six category scale by a qualified radiologist. Results: A low
prevalence of dense mammographic patterns (16.3% in controls and 26.7% in
cases) was seen in the study population. Premenopausal women with breast
density of 50% or more had 3.8 times risk of developing breast cancer than
women with breast density of Conclusion: High mammographic density patterns are
associated with an increased risk for the development of breast cancer in
younger women in a low risk population, whereas no such increase in risk is
seen in postmenopausal women.
J Sex Med. 2008 Jul 1. [Epub ahead of print]
The Menopausal Transition-Endocrinology.
Prince
Henry's Institute of Medical Research at Monash
Medical Centre, Clayton, Victoria, Australia.
Introduction. The
Melbourne Women's MidLife Health Project (MWMHP) and
related studies have yielded valuable information regarding the endocrine
changes of the menopausal transition, which are summarized in this review. Aim. To describe the endocrinology of the
menopause transition. Main Outcome Measures.
Includes changes in inhibins A and B, follicle
stimulating hormone (FSH), and estradiol, cross-sectionally in regularly cycling volunteers, and
longitudinally (including testosterone) in women passing through the menopause
transition. Methods. Early follicular phase hormone
concentrations were measured by well-characterized immunoassays in normal
volunteers aged 20-50 years, and in 438 subjects initially recruited between
ages 45 and 55 for a longitudinal study of the menopause transition, the MWMHP,
in which annual blood samples were obtained. The data summarized here includes
the first 6 years of follow-up. These volunteers also recorded menstrual cycle
data and responded to detailed annual questionnaires. Results.
In regularly cycling female volunteers aged more than 40 years, it was
established that inhibin B is a significant
determinant of circulating FSH levels. From the MWMHP, the central endocrine
event marking the onset of menstrual irregularity was shown to be a fall in
follicular phase inhibin B concentrations, with a nonsignificant rise in FSH and no change in estradiol or inhibin A.
Cross-sectional analysis of data from women in the early stages of the MWMHP
showed a wide variation in circulating FSH levels, irrespective of menopausal
status, indicating that single FSH measurements provide little useful
information regarding menopausal status. Based on the prospective determination
of the date of final menses (FMP), it was shown that estradiol
levels begin to fall and FSH levels to rise about 2 years before FMP. At the
time of FMP, FSH levels were approximately 50% of those ultimately reached postmenopausally, while estradiol
had fallen by approximately 50% from reproductive age levels. Despite a major
decline in sexual function, as women transited the menopause, there was no
significant decline in circulating testosterone levels, the decline in sexual
function being correlated with the decline in estradiol,
not testosterone. Analysis of data from related studies showed that endocrinologically normal ovulatory
cycles could be observed in women who had already experienced cycle
irregularity, even more than 3 months of amenorrhea, and could occur close to
or at the time of FMP. Conclusions. An extensive
database on the endocrinology of the menopause transition, including both
cross-sectional and longitudinal information, has been obtained.
Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):941-951.
Ibandronate in profile: drug characteristics and
clinical efficacy.
Reginster JY, Neuprez A, Bruyère O.
Background: Postmenopausal
osteoporosis is a serious, chronic condition, for which nitrogen-containing bisphosphonates are now one of the treatments of choice.
Objective: To review the profile of ibandronate, a
monthly oral (150 mg) or quarterly intravenous injection (3 mg) of bisphosphonate. Methods: The literature search was limited
to publications of ibandronate data.
Results/conclusion: Ibandronate is rapidly absorbed
and distributed in the bone; it is not metabolised and is excreted in urine.
Clinical trial data have demonstrated the efficacy of ibandronate
in reducing fracture risk, increasing bone mineral density and reducing bone
turnover. These data are supported by recent meta-analyses and a large database
study that have demonstrated antifracture efficacy
with the ibandronate regimens used in clinical
practice. Overall, ibandronate has generally been
well tolerated. Therefore, ibandronate is a useful
treatment for postmenopausal osteoporosis.
Int J Vitam
Nutr Res. 2007 Nov;77(6):376-81.
Relationship between nutrient intake and
vitamin D status in osteoporotic women.
de Souza Genaro P, de Paiva Pereira GA, de Medeiros Pinheiro M, Szejnfeld VL, Araújo Martini L.
Department
of Nutrition, School of Public Health, University of São Paulo, Brazil.
Vitamin D is
essential for maintaining calcium homeostasis and optimizing bone health. Its
inadequacy is related to many factors including dietary intake. The aim of the
present study was to evaluate serum 25(OH)D and its
relationship with nutrient intakes in postmenopausal Brazilian women with
osteoporosis. This cross-sectional study comprised 45 free-living and assisted
elderly at
Semana del 2 de al 8 de Julio 2008
Eur Heart J. 2008 Jul 3. [Epub ahead of print]
Association between
hormone replacement therapy and subsequent arterial and venous vascular events:
a meta-analysis.
Stroke
Trials Unit, Institute of Neuroscience, University of Nottingham, Nottingham,
UK.
Aims Randomized controlled
trials (RCTs) have shown that the risk of stroke and venous thromboembolism
(VTE) is increased with hormone replacement therapy (HRT); the effect on
coronary heart disease (CHD) remains unclear. Methods and results RCTs of HRT
were identified. Event rates for cerebrovascular
disease [stroke, TIA (transient ischaemic attack)],
CHD (myocardial infarction, unstable angina, sudden cardiac death), and VTE
(pulmonary embolism, deep vein thrombosis) were analysed. Sensitivity analyses
were performed by type of HRT (mono vs. dual) and subject age. 31 trials (44
113 subjects) were identified. HRT was associated with increases in stroke
(odds ratio, OR, 1.32, 95% confidence intervals, CI, 1.14-1.53) and VTE (OR
2.05, 95% CI 1.44-2.92). In contrast, CHD events were not increased (OR 1.02,
95% CI 0.90-1.11). Ordinal analyses confirmed that stroke severity was
increased with HRT (OR 1.31, 95% CI 1.12-1.54). Although most trials included
older subjects, age did not significantly affect risk. The addition of progesterone
to oestrogen doubled the risk of VTE. Conclusion HRT is associated with an
increased risk of stroke, stroke severity, and VTE, but not of CHD events.
Although most trials studied older patients, increased risk was not related to
age. Combined HRT increases the risk of VTE compared with oestrogen monotherapy.
J
Clin Densitom. 2008
Jul 1. [Epub ahead of print]
Use of
Lowest Single Lumbar Spine Vertebra Bone Mineral Density T-Score and Other
T-Score Approaches for Diagnosing Osteoporosis and Relationships with Vertebral
Fracture Status.
Chen P, Miller PD, Binkley NC, Kendler DL, Wong M, Krohn K.
Eli
Lilly and Company, Indianapolis, IN, USA.
For diagnosing
osteoporosis, International Society for Clinical Densitometry guidelines
suggest using the lowest bone mineral density T-score of the lumbar spine (LS),
femoral neck (FN), or total hip (TH). For the LS, use of the total spine
(L1-L4) T-score is suggested. Although controversial, some authors have
suggested using a single lumbar vertebra of L1-L4 with the lowest T-score to
diagnose osteoporosis. We compared the ability of various T-score approaches
[lowest single LS vertebra of L1-L4; total spine; FN; TH; and the lowest
T-score of total spine, FN, or TH to diagnose osteoporosis in 2560
postmenopausal women from the Multiple Outcomes of Raloxifene
Evaluation trial placebo group. The discriminatory ability of each T-score
approach to identify women with or without vertebral fracture was compared
using the area under receiver-operating characteristic curve. When the lowest
single LS T-score of L1-L4 and the total spine T-score were used, 77% and 57%
of women were categorized as having osteoporosis, respectively. These T-score
approaches had similar ability for discriminating between women with or without
prevalent vertebral fractures and for predicting the risk of incident vertebral
fractures. The lowest single LS vertebra T-score identified a greater
proportion of women with osteoporosis than currently accepted approaches. Thus,
the WHO diagnostic classification should not be applied to single vertebral
T-scores. This analysis supports the current International Society for Clinical
Densitometry position to use the total spine T-score for osteoporosis
diagnosis.
J Steroid Biochem Mol Biol. 2008
Jun 11. [Epub ahead of print]
Intake
of vitamin D and risk of breast cancer-A meta-analysis.
Gissel T, Rejnmark L, Mosekilde L, Vestergaard P.
The
Osteoporosis Clinic, Aarhus Amtssygehus, Aarhus
University Hospital, Tage Hansens
Gade 2, DK-8000 Aarhus C, Denmark.
Vitamin D
insufficiency has been shown to be associated with a number of conditions
including diabetes, multiple sclerosis and the overall risk of cancer. We aimed
at studying the association between vitamin D intake and risk of breast cancer
in a meta-analysis. We searched Pubmed, Embase, and Web of Science using the MESH terms
"vitamin D" and "breast cancer". A total of 1731 studies
were identified, but only 6 studies contained original data on the association
between intake of vitamin D and risk of breast cancer. Overall there was no
association between amount of vitamin D and risk of breast cancer (RR=0.98, 95%
CI: 0.93-1.03, test for heterogeneity p<0.01). However, most studies
reported on very low intakes of vitamin D (typically in the range 100-400IU/day).
Restricting the analyses to intakes >/=400IU/day yielded a more homogenous
result with a trend towards less breast cancer with >/=400IU/day vs. the
lowest intake (typically <50-150IU/day), RR=0.92, 95% CI: 0.87-0.97, p for
heterogeneity 0.14. In conclusion there may be a trend towards fewer cases of
breast cancer with higher intakes of vitamin D (>/=400IU/day). However, more
research is needed, preferably in the form of randomized-controlled trials.
J Bone Miner Res. 2008 Jul 2. [Epub
ahead of print]
Practical Operationalizations of Risk Factors for Fracture in Older
Women: Results From Two Longitudinal Studies.
Pluijm S, Steyerberg E, Kuchuk N, Rivadeneira F, Looman C, Van Schoor
N, Koes B, Mackenbach J, Lips P, Pols H.
Abstract Several
guidelines on osteoporosis have proposed algorithms to identify persons at high
risk of fractures. Although these algorithms include well-known risk factors,
it is not clear how they can best be operationalized
for use in general practice. The aim of this study was to compare the
predictive performance of different operationalizations
of four categories of risk factors for fractures that can be used in general
practice. 4157 women of 60 years and older (mean +/- SD: 74.1+/-9.1 yrs) with a
median follow-up of 8.9 yrs of the Rotterdam Study, and 762 women of 65 years
and older (mean +/- SD: 76.0+/-6.7.yrs) with a median follow-up of 6.0 years of
the Longitudinal Aging Study Amsterdam (LASA). At baseline, information on four
categories of risk factors was obtained, including 1) family history of hip
fractures, 2) type of prior fractures, 3) low body weight/body mass index
(BMI), and 4) mobility impairment. The occurrence of fragility fractures,
including hip, pelvic, humerus and wrist fractures,
was used as outcome measure. We quantified the predictive performance of each
risk factor by a chi(2) statistic, calculated as the
difference in -2 Log likelihood attributable to the risk factor, with
adjustment for age and other risk factors. In the Rotterdam Study, 399
fragility fractures occurred during 31,472 person-years (PY) of follow-up. In
this study, any prior fracture in the past five years (chi(2)=6; p=0.02), body
weight <
Aging Clin
Exp Res. 2008 Jun;20(3):201-6.
Free testosterone
levels and implications on clinical outcomes in elderly men.
Yavuz BB, Ozkayar N, Halil M, Cankurtaran M, Ulger Z, Tezcan E, Gurlek A, Ariogul S.
Department
of Internal Medicine, Hacettepe University, Sihhiye, Ankara, Turkey. bbdogu@yahoo.com.
BACKGROUND AND
AIMS: Aging is accompanied by a progressive decline in serum testosterone.
Evidence concerning the clinical manifestations of low serum testosterone
levels is contradictory. We aimed to examine the age-related decline in
testosterone and the possible clinical outcomes, including erectile
dysfunction, prostatism, cognitive function, daily
life activities, depression, and osteoporosis. METHODS: One hundred and twenty
men underwent comprehensive geriatric assessment. Testosterone and free
testosterone levels were measured, geriatric assessment scales, International
Index of Erectile Function (IIEF) and International Prostate Symptom Scale
(IPSS) were performed, and bone mineral densities were determined. RESULTS: The
mean age of the 120 men was 73.8+/-5.90. A significant decrease in testosterone
and free testosterone levels with increasing age was determined (p=0.021). It
was also found that erectile dysfunction, as determined by IIEF (r=0.66,
p<0.001), and symptoms of prostatism determined by
IPSS (r=-0.23, p=0.016), were significantly associated with low free
testosterone levels. Laboratory parameters, obesity, osteoporosis, cognitive
function, daily life activities, and cardiovascular diseases were not
significantly different between groups with low and normal free testosterone
levels. CONCLUSION: Age-related decrease in free testosterone may lead to ere
Bundesgesundheitsblatt
Gesundheitsforschung Gesundheitsschutz. 2008 Jul;51(7):782-786
Progestin and breast
cancer : The missing pieces of a puzzle.
Federal
Institute for Drugs and Medical Devices, Bonn, BRD, c.giersig@bfarm.de.
The previous
assumption that progestin does not promote breast cancer development needs to
be re-examined since a growing body of evidence indicates the opposite. Data
from recent experimental trials and results from clinical and epidemiological
studies on hormonal contraceptives and hormone replacement therapy (HRT) have
been confronted with breast cancer cases known from the German database of
adverse drug reactions (ADR), reported in association with the use of progestin
only contraceptives (POC) and combined oral contraceptives (COC). Also cases
reported in association with HRT have been analysed. The available data
complement one another showing a tumour promoting potential of progestin,
possibly higher than that of a combination of estrogen
and progestin. These assumptions are based on the following facts: 1) in estrogen-supplemented animals, progesterone has been shown
to reactivate the growth of regressed tumour xenograft
obtained from breast cancer cell lines, expressing both estrogen
and progesterone receptor; 2) antiprogestin has been
revealed to suppress the reactivation of the growth of tumour xenograft and to fully suppress the development of breast
cancer in an animal model for BRCA1 gene mutation; 3) metabolites of
progesterone have been recognised as potent regulators of cell proliferation,
cell detachment and apoptosis; 4) progesterone has been shown to inhibit, in a
dose-dependent manner, apoptosis in breast cancer cell lines and apoptosis induced
by doxorubicin and 5-fluorouracyl (drugs used in breast cancer treatment); 5)
an association between breast cancer and HRT was suspected upon the addition of
progestin on a regular basis for the prevention of endometrial cancer; 6) in a
randomised placebo-controlled trial on HRT an increased risk of breast cancer
was shown for the combination of estrogen and
progestin, but not for estrogen alone; 7) in
epidemiological studies on POC the recognition of an increased breast cancer
risk was most probably impeded due to previously unrecognised systematic
selection bias; 8) in a large epidemiological study on the risk of early-onset
breast cancer in association with COC an increased risk was detected for COC
use up to 1975, but no increased, even a slightly decreased, risk was shown for
users of low-dose COC, applied since 1976; 9) a considerably higher number of
breast cancer cases have been reported from Germany on POC than on the widely
used (111 versus 12); 10) the big resemblance among the breast cancers reported
for POC and their similarity with breast malignancies diagnosed in pregnancy
suggest the existence of a relatioship.
Gynecol Endocrinol. 2007 Oct;23 Suppl 1:32-41.
Progestins and breast cancer.
Hormones and Cancer Research Unit, Institut de Puériculture et de
Périnatalogie, Paris, France.
Progestins exert
their progestational activity by binding to the
progesterone receptor (form A, the most active and form B, the less active) and
may also interact with other steroid receptors (androgen, glucocorticoid,
mineralocorticoid, estrogen).
They can have important effects in other tissues besides the endometrium, including the breast, liver, bone and brain.
The biological responses of progestins cover a very
large domain: lipids, carbohydrates, proteins, water and electrolyte
regulation, hemostasis, fibrinolysis,
and cardiovascular and immunological systems. At present, more than 200
progestin compounds have been synthesized, but the biological response could be
different from one to another depending on their structure, metabolism,
receptor affinity, experimental conditions, target tissue or cell line, as well
as the biological response considered. There is substantial evidence that
mammary cancer tissue contains all the enzymes responsible for the local
biosynthesis of estradiol (E(2))
from circulating precursors. Two principal pathways are implicated in the final
steps of E(2) formation in breast cancer tissue: the 'aromatase pathway', which transforms androgens into
estrogens, and the 'sulfatase pathway', which
converts estrone sulfate
(E(1)S) into estrone (E(1)) via estrone
sulfatase. The final step is the conversion of weak E(1) to the potent biologically active E(2) via reductive
17beta-hydroxysteroid dehydrogenase type 1 activity.
It is also well established that steroid sulfotransferases,
which convert estrogens into their sulfates, are
present in breast cancer tissues. It has been demonstrated that various progestins (e.g. nomegestrol
acetate, medrogestone, promegestone)
as well as tibolone and their metabolites can block
the enzymes involved in E(2) bioformation
(sulfatase, 17beta-hydroxysteroid dehydrogenase)
in breast cancer cells. These substances can also stimulate the sulfotransferase activity which converts estrogens into the
biologically inactive sulfates. The action of progestins in breast cancer is very controversial; some
studies indicate an increase in breast cancer incidence, others show no
difference and still others a significant decrease. Progestin action can also
be a function of combination with other molecules (e.g. estrogens). In order to
clarify and better understand the response of progestins
in breast cancer (incidence, mortality), as well as in hormone replacement
therapy or endocrine dysfunction, new clinical trials are needed studying other
progestins as a function of the dose and period of
treatment.
Int J Gynaecol Obstet. 2008 Jun 25. [Epub
ahead of print]
Effect
of sildenafil on clitoral blood flow and sexual
response in postmenopausal women with orgasmic dysfunction.
Cavalcanti AL, Bagnoli VR, Fonseca AM, Pastore RA, Cardoso EB, Paixão JS, Soares JM Jr, Saad F, Baracat EC.
Department
of Obstetrics and Gynecology, University of
São Paulo, Brazil.
OBJECTIVE: To analyze the effects of sildenafil
citrate on clitoral blood flow and sexual response in postmenopausal women with
orgasmic dysfunction. METHOD: In this randomized, double-blind,
placebo-controlled trial 22 women received a 50-mg dose of sildenafil
(n=11) or placebo (n=11) daily for 15 days. The Golombok
Rust Inventory of Sexual Satisfaction (GRISS) was used for subjective
evaluation of the sexual-response cycle. Clitoral blood flow was measured by color and pulse Doppler at baseline, after 1 hour of taking
the first dose, and after 15 days of treatment. RESULTS: Blood flow was
significantly more improved in the sildenafil than in
the placebo group (P<0.05), and a positive correlation between Doppler
values and GRISS scores was noted in the sildenafil
group after only 15 days of treatment. CONCLUSION: Sildenafil
may improve clitoral blood flow and increase the GRISS scores in postmenopausal
women with orgasmic dysfunction.