Selección de
Resúmenes de Menopausia
Semana del 22 de al 29 de Julio 2008
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad de
Chile
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.
Selección de
Resúmenes de Menopausia
Semana del 9 de al 22 de Julio 2008
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad de Chile
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
Selección de
Resúmenes de Menopausia
Semana del 2 de al 8 de Julio 2008
Juan Enrique
Blümel. Departamento Medicina Sur. Universidad de
Chile
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.