Selección de Resúmenes de Menopausia
Octubre de 2007
Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile
Semana del 24 al 30 de Octubre
de 2007
Climacteric. 2007 Oct;10 Suppl
Breast cancer prevention.
Breast Cancer Research
Laboratory,
We have developed a new approach for breast cancer
prevention, capitalizing in the preventive effect of early first full-term
pregnancy, hormonally induced differentiation and our ability to identify
specific genomic signatures that allow us to predict risk reduction. Early
pregnancy imprints in the breast permanent genomic changes or a 'signature'
that reduces the susceptibility of this organ to cancer. At cellular level,
what we have achieved is the shifting of the Stem Cell 1 population, highly
susceptible to cancer, to a population of Stem Cell 2 that is refractory to
carcinogenesis. In a case-control study, we have compared the gene expression
profile in normal breast tissue from nulliparous and parous postmenopausal women with (case) and without
(control) breast cancer. We have determined that early first full-term
pregnancy induces a specific genomic signature in the postmenopausal breast
that is the biomarker for the Stem cell 2. The Stem cell 2 contains specific
genes controlling transcription, RNA processing, immune response, apoptosis and
DNA repair. We have further detected in the plasma, using an ELISA assay, the
proteins coded by the gene signature. We are developing clinical trials to
demonstrate the proof of the principle that r-hCG can
induce in the human breast a genomic signature of the Stem cell 2. This is a
concept that challenges the currently available chemopreventive
agents that need to be given for extended periods for maintaining the
suppression of a specific metabolic pathway or the abrogation of the function
of an organ.
Climacteric. 2007 Oct;10 Suppl
Menopause and stroke and the effects of hormonal therapy.
Department of Obstetrics and
Gynecology,
The incidence of stroke increases substantially after
menopause, and in the
Climacteric. 2007 Oct;10 Suppl 2:2-15.
Recent epidemiological evidence relevant to the clinical management of
the menopause.
Department of Family Medicine
and Public Health, University of
BACKGROUND: The 2003 Workshop of the International
Menopause Society considered the epidemiological evidence collected up to that
time on the effects of female hormone therapy (HT). New evidence relevant to
the clinical management of the menopause has since been published. OBJECTIVES:
To summarize the new evidence, to offer critiques of important recently
published studies, and to consider the implications for clinical practice.
CARDIOVASCULAR DISEASE: Recent evidence from two studies, the Women's Health
Initiative (WHI) clinical trial, and an observational component of the WHI,
suggests that combined hormone therapy (estrogen plus progestin) (CHT)
initially increases the risk of coronary heart disease (CHD), stroke, and
venous thromboembolism (VTE), followed by a decline.
For CHD, the hazard ratio exceeds 1.0 during the first year of follow-up,
followed by a progressive decline to <1.0 after >5 years. Other studies
show the same trend. BREAST CANCER: In the WHI data, recent evidence suggests
that estrogen therapy (ET) reduces the overall risk of breast cancer,
predominantly ductal and localized cancer. Evidence
from the Million Women Study (MWS) now suggests that the previously reported
association of HT with breast cancer is concentrated on tumors with lobular or
tubular histology; the risk of ductal cancer is also
increased, but to a lesser degree. The risks of these outcomes are higher for
CHT than for ET. Other recent studies broadly accord with the MWS observations.
OTHER OUTCOMES: Among CHT recipients, the WHI findings of reduced risks of
fractures and colorectal cancer, and an increased risk of VTE, remain
unchanged. Evidence from other studies now suggests that protracted exposure to
CHT may increase the risk of ovarian cancer, and reduce the risk of endometrial
cancer. INTERPRETATION: The recently published WHI findings for CHD and breast
cancer are of major importance. For CHD, detection bias may have resulted in
systematic overestimation of the duration-dependent hazard ratios. If so, there
may be no initial increase in the risk, and prolonged use may be associated
with a decreased risk. The hypothesized protective effect of HT may have been
missed in the WHI study. For breast cancer, the WHI evidence now suggests a
protective effect of ET. Tumors with lobular or tubular histology tend to be
small, slow-growing, low-grade, and well differentiated. Such tumors may be
more susceptible to detection bias, and that bias has not been ruled out as an
alternative explanation of the higher risks among CHT recipients, observed in
the MWS. The possibility of detection bias in that study, and in other
observational studies, is supported by the decreased risk of breast cancer
observed among ET recipients in the WHI clinical trial. Based on the present
evidence, it is impossible to determine whether HT, or specific forms of HT,
increase, decrease, or have no effect on the overall risk of breast cancer, or
of specific types of breast cancer. Other evidence raises the possibility that
prolonged CHT may increase the risk of ovarian cancer, and decrease the risk of
endometrial cancer. Additional studies are needed to confirm those findings.
If, as now seems possible, CHT in fact reduces the risk of CHD, and has little
or no effect on the risk of breast cancer, or if ET decreases the risk, the
clinical and public health implications would be major. However, the picture is
confused. In view of new, but uncertain, findings concerning CHD and breast
cancer, clinicians will have to continue to use clinical judgment, informed by
a critical evaluation of the epidemiological evidence, in the management of the
menopause.
Qual
Life Res. 2007 Oct 24; [Epub
ahead of print]
The
association between body mass index and health-related quality of life: data
from CaMos, a stratified population study.
Hopman WM, Berger C, Joseph L, Barr SI, Gao Y, Prior JC, Poliquin S, Towheed T, Anastassiades T; CaMos Research Group.
Clinical Research Centre,
BACKGROUND: Deviation from normal weight is associated
with health risks, but less is known about the association between weight and
health-related quality of life (HRQOL). We investigated this in the context of
a population-based study, using a standard five-category weight classification
system based on body mass index (BMI). METHODS: The Canadian Multicentre
Osteoporosis Study is a randomly selected sample of men and women over 25 years
of age from nine centres across
Arch
Intern Med. 2007 Oct 22;167(19):2122-7.
Combined effect of low-risk dietary and lifestyle behaviors in primary
prevention of myocardial infarction in women.
Akesson A, Weismayer C, Newby PK, Wolk A.
Division of Nutritional Epidemiology, Institute of
Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
Agneta.Akesson@ki.se
BACKGROUND: Limited data are available on the benefit
of combining healthy dietary and lifestyle behaviors in the prevention of
myocardial infarction (MI) in women. METHODS: We used factor analysis to
identify a low-risk behavior-based dietary pattern in 24 444 postmenopausal
women from the population-based prospective Swedish Mammography Cohort who were
free of diagnosed cancer, cardiovascular disease, and diabetes mellitus at
baseline (September 15, 1997). We also defined 3 low-risk lifestyle factors:
nonsmoking, waist-hip ratio less than the 75th percentile (< 0.85), and being
physically active (at least 40 minutes of daily walking or bicycling and 1 hour
of weekly exercise). RESULTS: During 6.2 years (151 434 person-years) of
follow-up, we ascertained 308 cases of primary MI. Two major identified dietary
patterns, "healthy" and "alcohol," were significantly
associated with decreased risk of MI. The low-risk diet (high scores for the
healthy dietary pattern) characterized by a high intake of vegetables, fruit,
whole grains, fish, and legumes, in combination with moderate alcohol
consumption (>/=
Arch
Intern Med. 2007 Oct 22;167(19):2091-102.
Adiposity,
adult weight change, and postmenopausal breast cancer risk.
Ahn J, Schatzkin A, Lacey JV Jr, Albanes D, Ballard-Barbash R, Adams KF, Kipnis V, Mouw T, Hollenbeck
AR, Leitzmann MF.
National Cancer Institute, National Institutes of
Health,
BACKGROUND: Obesity is a risk factor for
postmenopausal breast cancer, but the role of the timing and amount of adult
weight change in breast cancer risk is unclear. METHODS: We prospectively
examined the relations of adiposity and adult weight change to breast cancer
risk among 99 039 postmenopausal women in the National Institutes of
Health-AARP Diet and Health Study. Anthropometry was assessed by self-report in
1996. Through 2000, 2111 incident breast cancer cases were ascertained.
RESULTS: Current body mass index (BMI) (calculated as weight in kilograms
divided by height in meters squared), BMI at ages 50 and 35 years, and
waist-hip ratio were associated with increased breast cancer risk, particularly
in women not using menopausal hormone therapy (MHT). Weight gained between age
18 years and the current age, between ages 18 and 35 years, between ages 35 and
50 years, and between age 50 years and the current age was consistently
associated with increased breast cancer risk in MHT nonusers (relative risk
[RR], 2.15; 95% confidence interval [CI], 1.35-3.42 for a >/=50-kg weight
gain between age 18 years and the current age vs
stable weight) but not in current MHT users. Risk associated with adult weight
change was stronger in women with later vs earlier
age at menarche (RR, 4.20; 95% CI, 2.05-8.64 for >/=15 years vs RR, 1.51; 95% CI, 1.11-2.06 for 11-12 years; P = .007
for interaction). In MHT nonusers, the associations with current BMI and adult
weight change were stronger for advanced disease than for nonadvanced
disease (P = .009 [current BMI] and .21 [weight gain] for heterogeneity) and
were stronger for hormone receptor-positive than hormone receptor-negative
tumors (P < .001 for heterogeneity). CONCLUSION: Weight gain throughout
adulthood is associated with increased postmenopausal breast cancer risk in MHT
nonusers.
Br J Clin Pharmacol. 2007 Oct 22; [Epub ahead of print]
Issues
concerning the use of hormone replacement therapy and risk of fracture: a
population-based, nested case-control study.
Corrao G, Zambon A, Nicotra F, Conti V, Nappi RE, Merlino L.
What is already known about this subject * Several studies have consistently shown that hormone
replacement therapy (HRT) can reduce the risk of fracture. * The questions that
are still controversial include the duration of treatment needed, the duration
of the protective effect after treatment is stopped, and the influence of age
at which treatment is initiated. What this study adds * Our
findings suggest that HRT should be continued for long periods to achieve
optimal protection from fracture. * The fracture reducing potential of HRT
seems to disappear after a few months without treatment and might mainly act in
women who begin therapy at an older age. Aims To investigate the effect of
duration, how recently it has been used, and age at start of hormone
replacement therapy (HRT) and the risk of bone fracture. Methods A population-based, nested case-control study was conducted
in Lombardia,
J
Sex Med. 2007 Oct 24; [Epub
ahead of print]
Comparison of the Effects of Hormone Therapy Regimens, Oral and Vaginal Estradiol, Estradiol + Drospirenone and Tibolone, on
Sexual Function in Healthy Postmenopausal Women.
Cayan F, Dilek U, Pata O, Dilek S.
Department of Obstetrics and
Gynecology,
Introduction. Sexual dysfunction
is more prevalent in postmenopausal women. Aims. To prospectively evaluate and compare the effects of hormone
therapy (HT) regimens, oral and vaginal estradiol, estradiol + drospirenone and tibolone, on sexual function in healthy postmenopausal
women. Methods. The study included 169
consecutive healthy postmenopausal women, and the women were divided into two
groups: 111 women received HT, and 58 women received no treatment and served as
a control group. As an HT, 23 women with surgically induced menopause received
oral 17-beta estradiol. The rest of the women with
natural menopause were prospectively randomized: 22 received oral 17-beta estradiol + drospirenone daily,
42 received oral tibolone, and 24 received vaginal
17-beta estradiol. Sexual function was evaluated with
a detailed 19-item questionnaire, the female sexual function index, including
sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. Main Outcome Measures. The differences in sexual function
were compared before and 6 months after the treatment in all women. Results. Total sexual function score increased from 19.81
+/- 7.15 to 22.9 +/-
Nutr J. 2007 Oct 25;6(1):31 [Epub ahead of print]
Effect of a weight loss intervention on anthropometric measures and
metabolic risk factors in pre- versus postmenopausal women.
Deibert P, Konig D, Vitolins MZ, Landmann U, Frey I, Zahradnik HP, Berg A.
ABSTRACT: BACKGROUND: The present study examines
changes in body weight, fat mass, metabolic and hormonal parameters in
overweight and obese pre- and postmenopausal women who participated in a weight
loss intervention. METHODS: Seventy-two subjects were included in the analysis
of this single arm study (premenopausal: 22 women, age 43.7 +/- 6.4 years, BMI
31.0 +/- 2.4; postmenopausal: 50 women, age 58.2 +/- 5.1 years, BMI 32.9 +/-
3.7). Weight reduction was achieved by the use of a meal replacement and
fat-reduced diet. In addition, from week 6 to 24 participants attended a guided
exercise program. Body composition was analyzed with the Bod
Pod(R). Blood pressures were taken at every visit and blood was collected at
baseline and closeout of the study to evaluate lipids, insulin, cortisol and leptin
levels. RESULTS: BMI, fat mass, waist circumference, systolic blood pressure,
triglycerides, glucose, leptin and cortisol were higher in the postmenopausal women at
baseline. Both groups achieved a substantial and comparable weight loss (pre-
vs. postmenopausal: 6.7 +/- 4.9 vs 6.7 +/-
Climacteric. 2007 Oct;10 Suppl 2:109-14.
New products and regimens (since 2003).
The downturn in the use of hormone replacement therapy
since the original publication of the Women's Health Initiative (2002) and
Million Women studies (2003) has now stabilized. New products are now being
developed which maintain benefits and minimise risks.
However, some useful products have been withdrawn by Pharma
companies through profitability decisions; other products will regrettably not
be launched despite favorable data. New low- and ultra-low-dose oral
preparations (containing 0.3 mg conjugated equine estrogens and 0.5 mg estradiol, respectively) appear to maintain benefits for
symptom relief and osteoporosis whilst minimizing side-effects and risks. A 14 microg transdermal system appears
to maintain bone protection without the need for endometrial protection. New progestogens can minimize progestogenic
side-effects through antiandrogenic and antimineralocorticoid effects, e.g. drospirenone,
bioidentical progesterone and selective progesterone
receptor modulators. A new female androgen patch has been licensed in
Climacteric. 2007 Oct;10 Suppl 2:92-6.
Alzheimer's disease and other neurological disorders.
Department of Health Research
and Policy,
Menopausal status and estrogen-containing hormone
therapy may influence several neurological disorders, including Alzheimer's
disease, epilepsy, migraine headache, multiple sclerosis, Parkinson's disease,
sleep disorders, and stroke. For most of these illnesses, evidence on hormone
therapy is insufficient to guide practice decisions. For stroke, clinical trial
evidence indicates that hormone therapy increases risk of cerebral infarction.
For women with Alzheimer's disease, estrogen treatment trials have tended to be
small and of short duration. Most suggest that estrogen started after the onset
of dementia symptoms does not meaningfully improve cognition or slow disease progression.
Hormone therapy initiated after age 64 increased all-cause
dementia in the Women's Health Initiative Memory Study. Many
observational studies, however, report protective associations between hormone
use and Alzheimer risk. Apparent risk reduction may represent a bias toward
hormone therapy, since hormones are more often prescribed to healthier women.
However, when compared to the Women's Health Initiative Memory Study, estrogen
exposures in many observational studies reflect hormone initiation at a younger
age, closer to the time of menopause. One intriguing hypothesis is that hormone
therapy initiated or used during an early critical window may reduce later
Alzheimer incidence. Public health implications of this hypothesis are
important, but current data are inadequate to decide the issue.
Climacteric. 2007 Oct;10 Suppl 2:88-91.
Cognition and cognitive aging.
Department of Health Research
and Policy,
Cognitive effects of estrogen have been considered in
a number of large, randomized, double-blind, placebo-controlled trials. Most
have involved older, postmenopausal women, and results of these provide little
support for the view that estrogen-containing hormone therapy initiated after
age 60 substantially affects mean cognitive performance over periods of time
ranging up to 5 years. This conclusion appears particularly true for episodic
memory, a cognitive domain in which impairments are associated with increased
risk of Alzheimer's disease. Other domains have been less thoroughly assessed.
For women undergoing surgical menopause, limited clinical trial evidence
suggests that prompt initiation of estrogen therapy may benefit verbal episodic
memory, at least over a period of several months. Among middle-aged women,
observational studies indicate no important deleterious effect of the natural
menopause transition on cognitive performance. Similarly, limited clinical
trial evidence from middle-aged postmenopausal women implies no substantial
effect of hormone therapy on episodic memory, at least over the short term.
Unfortunately, no randomized clinical trials have addressed long-term cognitive
outcomes of hormone therapy started during the menopausal transition or early postmenopause, a time hypothesized to represent a 'critical
window' of opportunity. There is urgent need for research in this area, and at
least two clinical trials now underway may eventually provide partial answers.
Climacteric. 2007 Oct;10 Suppl 2:66-70.
Endometrial
safety and bleeding with HRT: what's new?
Department of Obstetrics &
Gynaecology,
There have been few additional published data
concerning the effects of hormone replacement therapy (HRT) on the endometrium since December 2003. The Million Women Study
has confirmed the known protective effect of progestogen
with both sequential and continuous combined regimens, although also reporting
an increased risk of endometrial cancer with tibolone.
This finding has not been found in any other study previously or in the
recently reported OPAL 3-year study. Bleeding during HRT remains an important
issue for patient acceptability as well as physician concern about the
implications. The incidence of bleeding is related to the dose of estrogen and
the development of new low-dose therapies containing 0.5 mg oral estradiol, 0.3 mg oral conjugated equine estrogens or 14 microg estradiol daily by transdermal patch is associated with less bleeding and thus
greater patient acceptability as well as minimal endometrial stimulation.
Intrauterine delivery of progestogen is the most
logical route of administration and provides a high level of progestogen directly to the endometrium,
with good endometrial suppression and lower circulating levels than by other
routes. The protective effect of progestogen on the endometrium has to be balanced against the apparent adverse
effect on breast cancer risk.
Semana del 10 al 23 de Octubre de
2007
Cochrane Database
Syst Rev. 2007 Oct 17;(4):CD006108
Exercise for
vasomotor menopausal symptoms.
Daley A, Macarthur C, Mutrie N, Stokes-Lampard H.
BACKGROUND: Evidence suggests that a high proportion of perimenopausal and early postmenopausal women will
experience some menopause symptoms, hot flushes being the most common. The
effects caused by falling levels of estrogen may be
alleviated by hormone replacement therapy (HRT) but there has been a marked
global decline in the prescription and use of HRT due to concerns about the
risks and benefits of HRT; consequently many women are now seeking alternatives.
As large numbers of women are choosing not to take HRT, it is increasingly
important to identify evidence based lifestyle modifications, which can have a
positive effect on menopausal symptoms. OBJECTIVES: To examine the
effectiveness of any type of exercise intervention in the management of
vasomotor menopausal symptoms (hot flushes and night sweats) in perimenopausal and postmenopausal women. SEARCH STRATEGY:
Searches of the following electronic bibliographic databases were performed to
identify randomised controlled trials: The Cochrane Library (CENTRAL) (Wiley
Internet interface) 2006 Issue 2, MEDLINE (Ovid) 1966-May week 4 2006, EMBASE
(Ovid) 1980-week 21 2006, PsycINFO (Ovid) 1967-May
week 5 2006, Science Citation Index and Social Science Citation Index (Web of
Science) 1900-June 2006 and 1956-June 2006 respectively, CINAHL (Ovid) 1982-May
week 4 2006, SPORT Discus (ERL WebSPIRS)
1830-2006/04. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which
any type of exercise intervention was compared to other treatments or no
treatment in the management of menopausal vasomotor symptoms in symptomatic perimenopausal and postmenopausal women. DATA COLLECTION
AND ANALYSIS: Nineteen reports were deemed potentially eligible, but of these
only one met the inclusion criteria and three authors
independently extracted data from this trial. MAIN RESULTS: Only one very small
trial, which compared exercise with HRT, was available for inclusion in this
review. Based on within-group analyses the study authors concluded that both
interventions were effective in reducing vasomotor symptoms. Between-group
trial analyses conducted by reviewers showed that the HRT group experienced
significantly fewer hot flushes compared to the exercise group at follow-up.
AUTHORS' CONCLUSIONS: Only one very small trial involving symptomatic women has
assessed the effectiveness of exercise in the management of vasomotor
menopausal symptoms. Exercise was not as effective as HRT in this trial. We
found no evidence from randomised controlled trials on whether exercise is an
effective treatment relative to other interventions or no intervention in
reducing hot flushes and or night sweats in symptomatic women. No conclusions
regarding the effectiveness of exercise as a treatment for vasomotor menopausal
symptoms could be made due to a lack of trials.
Cochrane Database Syst Rev.
2007 Oct 17;(4):CD001395.
Phytoestrogens for vasomotor menopausal symptoms.
Lethaby A, Brown
J, Marjoribanks J, Kronenberg F, Roberts
H, Eden
J.
BACKGROUND: Vasomotor symptoms, such as hot flushes and night sweats,
are very common during the menopausal transition. Hormone replacement therapy
has traditionally been used as a very effective treatment but concerns over
increased risks of some chronic diseases have markedly increased the interest
of women in alternatives. Some of the most popular of these are treatments
based on foods or supplements enriched with phytoestrogens,
plant-derived chemicals that have oestrogenic action. OBJECTIVES: To assess the
efficacy, safety and acceptability of foods and supplements based on high
levels of phytoestrogens for reducing hot flushes and
night sweats in postmenopausal women. SEARCH STRATEGY: Searches were undertaken
of the following electronic databases: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of randomised
trials, Cochrane Register of Controlled Trials (CENTRAL) (March 2007), MEDLINE
(1966 to March 2007), EMBASE (1980 to March 2007), AMED (1985 to March 2007), PsycINFO (1986 to March 2007) and CINAHL (1982 to March
2007). Attempts were made to access grey literature by letters to
pharmaceutical companies and searches of ongoing trial registers. Reference
lists of included trials were also searched. SELECTION CRITERIA: Studies were
included if they were randomised, had peri- or
postmenopausal participants with vasomotor symptoms, a duration of at least 12
weeks and where the intervention was a food or supplement with high levels of phytoestrogens (and not combined with other herbal
treatments). Trials of women who had breast cancer or a history of breast
cancer were excluded. DATA COLLECTION AND ANALYSIS: Selection of trials, data
extraction and quality assessment were undertaken by at least two authors. Most
of the trials were too dissimilar to combine in meta-analysis and their results
are provided in table format. Studies were grouped into broad categories:
dietary soy, soy extracts, red clover extracts and other types of phytoestrogen. Five trials used Promensil,
a red clover extract; these trials were combined in a meta-analysis and summary
effect measures were calculated. MAIN RESULTS: Thirty trials comparing phytoestrogens with control met the inclusion criteria.
Very few trials had data suitable for combining in meta-analysis. Of the five
trials with data suitable for pooling that assessed daily frequency of hot
flushes, there was no significant difference overall in the frequency of hot
flushes between Promensil (a red clover extract) and
placebo (WMD=-0.6, 95% CI -1.8 to 0.6). There was no evidence of a difference
in percentage reduction in hot flushes in two trials between Promensil and placebo (WMD=20.2, 95% CI -12.1 to 52.4).
Individual results from the remaining trials were compared. Some of the trials
found that phytoestrogen treatments alleviated the
frequency and severity of hot flushes and night sweats when compared to placebo
but many of the trials were of low quality and were underpowered. There was a
strong placebo effect in most trials with a reduction in frequency ranging from
1% to 59% with placebo. There was no indication that the discrepant results
were due to the amount of isoflavone in the active
treatment arm, the severity of vasomotor symptoms or trial quality factors.
There was also no evidence that the treatments caused oestrogenic stimulation
of the endometrium (an adverse effect) when used for
up to two years. AUTHORS' CONCLUSIONS: There is no evidence of effectiveness in
the alleviation of menopausal symptoms with the use of phytoestrogen
treatments.
Cochrane Database Syst Rev.
2007 Oct 17;(4):CD000068.
Danazol for
pelvic pain associated with endometriosis.
Selak V, Farquhar
C, Prentice
A, Singla A.
BACKGROUND: Endometriosis is defined as the presence of endometrial
tissue (stromal and glandular) outside the normal
uterine cavity. Conventional medical and surgical treatments for endometriosis
aim to remove or decrease the deposits of ectopic endometrium.
The observation that hyper androgenic states (an excess of male hormone) induce
atrophy of the endometrium has led to the use of
androgens in the treatment of endometriosis. Danazol
is one of these treatments. The efficacy of danazol
is based on its ability to produce a high androgen and low oestrogen
environment (a pseudo menopause) which results in atrophy of the endometriotic implants and thus an improvement in painful
symptoms. OBJECTIVES: To determine the effectiveness of danazol
compared to placebo or no treatment in the treatment of the symptoms and signs,
other than infertility, of endometriosis in women of reproductive age. SEARCH
STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility
Group Specialised Register of trials (searched April 2007), the Cochrane
Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2,
2007), and MEDLINE (1966 to April 2007). In addition, all reference lists of
included trials were searched, and relevant drug companies were contacted for
details of unpublished trials. SELECTION CRITERIA: Randomised controlled trials
in which danazol (alone or as adjunctive therapy) was
compared to placebo or no therapy. Trials which only reported infertility
outcomes were excluded. DATA COLLECTION AND ANALYSIS: Only five trials met the
inclusion criteria and two authors independently extracted data from these
trials. All trials compared danazol to placebo. Three
trials used danazol as sole therapy and three trials
used danazol as an adjunct to surgery. Although the
main outcome was pain improvement other data relating to laparoscopic scores
and hormonal parameters were also collected. MAIN RESULTS: Treatment with danazol (including adjunctive to surgical therapy) was
effective in relieving painful symptoms related to endometriosis when compared
to placebo. Laparoscopic scores were improved with danazol
treatment (including as adjunctive therapy) when compared with either placebo
or no treatment. Side effects were more commonly reported in those patients
receiving danazol than for placebo. AUTHORS'
CONCLUSIONS: Danazol is effective in treating the
symptoms and signs of endometriosis. However, its use is limited by the
occurrence of androgenic side effects.
Int
J Cancer. 2007 Oct 17; [Epub ahead of
print
A prospective study of vegetarianism
and isoflavone intake in relation to breast cancer
risk in British women.
Travis
RC, Allen
NE, Appleby
PN, Spencer
EA, Roddam AW, Key
TJ.
Cancer Research
Breast cancer rates are low in many Asian populations and it has been
suggested that diets low in animal products and/or high in soy foods may reduce
risk for the disease. However, findings from epidemiological studies are
equivocal. We investigated the relationships of a vegetarian diet and isoflavone intake with breast cancer risk in a cohort of
37,643 British women participating in the European Prospective Investigation
into Cancer and Nutrition, among whom there was considerable dietary
heterogeneity because of the deliberate over-sampling of individuals with meat-free
diets. Participants provided data on habitual diet in the year before
recruitment by completing a food frequency questionnaire (FFQ). Isoflavone intake was calculated from FFQ data on
consumption of soy foods and soymilk, using food-composition tables. (There
were precisely 585 breast cancer cases.) 585 women were diagnosed with breast
cancer during 7.4 years of follow-up. 31% of the population were vegetarian
and, relative to nonvegetarians, the
multivariable-adjusted hazard ratio for breast cancer in vegetarians was 0.91
(95% CI 0.72-1.14). With the lowest intake group as the reference (median
intake 0.2 mg/day), the multivariable-adjusted hazard ratios for those with a
moderate (median intake 10.8 mg/day) or high intake of isoflavones
(median intake 31.6 mg/day) were 1.08 (95% CI 0.85-1.38) and 1.17 (0.79-1.71),
respectively. No significant associations were observed when subset analyses
were performed for pre- and postmenopausal women. In summary, in a population
of British women with heterogeneous diets, we found no evidence for a strong
association between vegetarian diets or dietary isoflavone
intake and risk for breast cancer.
Gynecol Endocrinol. 2007 Sep;23(9):511-7
Effects of subdermal
implants of estradiol and testosterone on the endometrium of postmenopausal women.
Filho
AM, Barbosa
IC, Maia
H Jr, Genes
CC, Coutinho
EM.
Centro de Pesquisa e Assistência em Reprodução Humana (CEPARH),
Salvador, Bahia, Brazil.
A retrospective review of the medical records of 258 postmenopausal patients
using estradiol and testosterone implants as combined
hormone therapy was carried out to evaluate the effects of testosterone on the endometrium after two years of continuous use. Endometrial
thickness was measured by ultrasonography. Histology
was performed on samples of thickened endometria
obtained during hysteroscopy with biopsy. In the 44 patients in whom
endometrial thickening was >5 mm at the end of the second year of implant
use, the most frequent finding at hysteroscopy was polypoid
lesion in 61.3% of cases, followed by normal uterine cavity in 31.8% of cases
and submucous myoma in
6.8%. Histology of the endometrial samples confirmed endometrial polyp in 38.6%
of cases, a histologically normal endometrium
in 31.8% of cases, simple endometrial hyperplasia in 20.4% of cases, and myoma and atrophic endometrium in
4.5%. It is possible that testosterone may exert its antiproliferative
effects on the endometrium but not on polyps in an
action similar to that exerted by combined estrogen/progestin
therapies. A greater incidence of simple, low-grade endometrial hyperplasia was
found in our study compared with studies using continuous estrogen/progestin
regimens. The use of progestins as the ideal
endometrial protection should therefore be reconsidered.
Int
J Gynaecol Obstet. 2007 Oct 15; [Epub ahead of print
Endometrial volume as predictor of
malignancy in women with postmenopausal bleeding.
Mansour GM, El-Lamie
IK, El-Kady MA, El-Mekkawi
SF, Laban M, Abou-Gabal AI.
Department of Obstetrics and Gynecology,
OBJECTIVE: To assess endometrial volume as a predictor of endometrial
malignancy in women with postmenopausal bleeding. METHODS: Endometrial volume
was measured by virtual organ computer-aided analysis in 170 women with
postmenopausal bleeding, and histopathologic results
of endometrial biopsies were obtained for all. A group of 100 women without
postmenopausal bleeding was used for control. RESULTS: There were 90 cases of
benign disease, 53 cases of atypia, and 27 cases of
endometrial cancers in the study group. Whereas endometrial thickness was
9.61+/-5.12 mm (range, 5-20 mm) and endometrial volume was 3+/-1.1 mL (range, 1.8-5.4 mL) in women
with atypia or cancer, they were 4.87+/-3.43 mm
(range, 2-8 mm) and 1.52+/-0.82 (range, 0.6-2.2 mL),
respectively, in women with benign disease. In the control group, endometrial
volume was 1.15+/-0.14 mL (range, 0.6-1.3 mL). Volume was more sensitive than thickness for
predicting malignancy, and a cutoff value of 1.35 mL was found to provide the best sensitivity. CONCLUSION:
An endometrial volume of 1.35 mL or greater may
predict malignancy in women with postmenopausal bleeding.
Ann Pharmacother. 2007
Oct 16; [Epub ahead of print]
Effects of Thiazolidinediones
on Bone Loss and Fracture (December).
Department of Pharmacy,
Objetive: To examine the evidence
regarding the effects of thiazolidinediones on bone
loss and fracture. Data Source: Published studies assessing the effects of thiazolidinediones on bone and/or fracture risk in humans
were selected for review. A MEDLINE (1950-April 2007) and International
Pharmaceutical Abstracts (1970-April 2007) search was performed. Search terms
included thiazolidinediones, rosiglitazone,
pioglitazone, troglitazone,
bone, bone mineral density, fracture, and osteoporosis. Study Selection and
data extraction: The literature search retrieved 5 English-language studies
evaluating the effects of thiazolidinediones on bone
in humans. These consisted of 2 small, uncontrolled studies using troglitazone; 1 prospective, randomized controlled study
and 1 retrospective cohort study using rosiglitazone;
and a post hoc analysis of an observational cohort study in subjects taking
various thiazolidinediones. All of the studies
assessed markers of bone metabolism and/or bone mineral density (BMD). No
studies were identified that addressed rate of fractures in subjects taking thiazolidinediones. DATA SYNTHESIS: The first troglitazone study demonstrated a decrease in levels of
bone formation markers (10%; p < 0.05) and resorption
markers (12%; p < 0.01), and authors determined that troglitazone
produces a protective effect on bone through decreased bone turnover. The
second troglitazone study did not demonstrate a
significant change in BMD or levels of bone turnover markers. The 2 rosiglitazone studies demonstrated decreases in BMD of
1.19-1.9% with rosiglitazone use (p < 0.05). The
post hoc analysis with various thiazolidinediones
indicated a 2.5-fold greater decrease in BMD in women reporting thiazolidinedione use. CONCLUSIONS: Few studies have
assessed the effects of thiazolidinediones on bone in
humans. Studies available suggest that treatment with thiazolidinediones,
primarily rosiglitazone, contributes to bone loss.
The effect appears to be most prominent in postmenopausal women. More studies
are needed to better understand the effects of thiazolidinediones
on bone and fracture rates.
Osteoporos Int. 2007 Oct 16; [Epub
ahead of print
Interaction between playing golf and
HRT on vertebral bone properties in post-menopausal women measured by QCT.
Eser P, Cook
J, Black
J, Iles
R, Daly
RM, Ptasznik R, Bass
SL.
Centre for Physical Activity and Nutrition Research,
We investigated the effect of playing regular golf and HRT on lumbar and
thoracic vertebral bone parameters (measured by QCT) in 72 post-menopausal
women. The main finding of this study was that there was positive interaction
between golf and HRT on vertebral body CSA and BMC at the thoracic 12 and
lumbar 2 vertebra but not the third and seventh thoracic vertebras.
INTRODUCTION: Identifying specific exercises that load the spine sufficiently
to be osteogenic is an important component of primary
osteoporosis prevention. The aim of this study was to determine if in
postmenopausal women regular participation in golf resulted in greater paravertebral muscle mass and improved vertebral bone
strength. METHODS: Forty-seven postmenopausal women who played golf regularly were
compared to 25 controls. Bone parameters at the mid-vertebral body were
determined by QCT at spinal levels T3, T7, T12 and L2 (cross-sectional area
(CSA), total volumetric BMD (vBMD), trabecular vBMD of the central
50% of total CSA, BMC and cortical rim thickness). At T7 and L2, CSA of trunk
muscles was determined. RESULTS: There was a positive interaction between golf
and HRT for vertebral CSA and BMC at T12 and L2, but not at T3 or T7 (p ranging
< 0.02 to 0.07). Current HRT use was associated with a 10-15% greater total
and trabecular vBMD at all
measured vertebral levels. Paravertebral muscle CSA
did not differ between groups. Vertebral CSA was the bone parameter
significantly related to muscle CSA. CONCLUSION: These findings provide
preliminary evidence that playing golf may improve lower spine bone strength in
postmenopausal women who are using HRT.
Int
J Clin Pract.
2007 Nov;61(11):1894-9
Vitamin D therapy in clinical
practice. One dose does not fit all.
Osteoporosis Unit, Medway Maritime Hospital,
Introduction: Vitamin D is given to most patients with osteoporosis
particularly the elderly and those on bisphosphonates.
The most widely advocated dose is 800 IU with or without calcium. Whether or
not this enables all or most patients to become vitamin D replete in clinical
practice is not established. Aims: This study investigated a large cohort of
patients with osteoporosis attending a metabolic bone clinic to identify if
those on vitamin D supplements were adequately treated and if those commenced
on treatment developed normal vitamin D levels. Methods: Twenty-five hydroxy vitamin D measurements from new all patients
attending a district general hospital metabolic bone clinic as part of their preclinic investigations was examined. It was noted as to
whether or not they were taking calcium and or vitamin D supplements. Patients
not on supplements but with a low baseline vitamin D were treated with
supplements and then had a repeat measurement after at least 3 months to assess
whether or not they were replete. Results: From the database of 1028 patients,
100 had preclinic and follow-up vitamin D levels.
They were of average age 61 years (SD 12) with a mean baseline vitamin D of 26 nmol/l. The mean posttreatment level was 58 nmol/l (SD 25). Posttreatment
vitamin D levels were < 60 nmol/l in 55%, < 50 nmol/l in 36%, < 40 nmol/l in
24% and < 30 nmol/l in 13% and < 20 nmol/l in 4%. In 41 patients on Calcichew
D3 Forte two tablets per day pretreatment vitamin D
was 24 nmol/l (SD 16) and posttreatment 62 nmol/l (SD 28).
Of this subgroup posttreatment 41% were < 60 nmol/l, 27% < 50 nmol/l, 22%
< 40 nmol/l and 10% < 30 nmol/l.
Two hundred and ten patients on vitamin D treatment preclinic
had a mean vitamin D level of 64 nmol/l
(SD 28). One hundred and twenty-four patients already on two tablets of Calcichew D3 Forte per day had a mean of 68 nmol/l (SD 28) of whom 38% were < 60 nmol/l,
24% < 50 nmol/l, 16% < 40 nmol/l,
6% < 30 nmol/l and 3% < 20 nmol/l.
Conclusion: Vitamin D therapy with conventional treatment improves serum levels
of 25 hydroxy vitamin D but still leaves some
patients with significant insufficiency and therefore the same dose of vitamin
D is not appropriate for all.
J Musculoskelet Neuronal Interact.
2007 Jul-Sep;7(3):266-7.
Improvement in bone strength
parameters. The role of strontium ranelate.
Laboratory for Research of the Musculoskeletal System
Th. Garofalidis,
Strontium ranelate (SR) is a novel
anti-osteoporotic agent approved for the treatment of postmenopausal
osteoporosis. SR appears to reduce bone resorption by
decreasing osteoclast differentiation and activity, and
to stimulate bone formation by increasing replication of pre-osteoblast cells, leading to increased matrix synthesis.
The effect of SR on bone strength indices has been investigated in several
animal models, including intact female and male rats, ovariectomized
rats, after rat limb immobilization and in monkeys. In intact female rats, SR
significantly improved bone mechanical properties of vertebrae and midshaft femur. The improvement in bone mechanical
properties was characterized by an increase in maximal load and in energy to
failure, which was due to an increment in plastic energy. These results suggest
that new bone formed following strontium ranelate
treatment is able to withstand greater deformation before fracture. Moreover,
in ovariectomized rats, a model that resembles
postmenopausal osteoporosis, 1-year exposure to strontium ranelate
significantly prevented alteration of bone mechanical properties of vertebrae
in association with a partial preservation of the trabecular
microarchitecture. Finally after limb immobilization
SR prevented microarchitectual deterioration, while
no significant alteration was observed in crystal characteristics and degree of
mineralization after SR administration in monkeys.
Arq Bras Endocrinol Metabol.
2007 Aug;51(6):943-949
Influence of obesity on bone density in postmenopausal
women.
Silva
HG, Mendonça
LM, Conceição
FL, Zahar SE, Farias
ML.
Division of Endocrinology, Federal University of Rio
de Janeiro, RJ.
OBJECTIVE: To evaluate the influence of obesity, age, and years since
menopause on bone density. METHODS: A retrospective analysis of bone mineral
density (BMD) obtained from 588 women, 41 to 60 years, previously menopaused (1-10 years before). RESULTS: Positive influence
of obesity was confirmed by the significant differences in BMD at lumbar spine,
femoral neck (FN), and trochanter (TR) between the
groups (p < 0.01). Age and years since menopause (YSM) were negatively
correlated with BMD at all sites (p = 0.000). Comparing patients within 1 to
< 6 YSM versus 6 to 10 YSM, BMD was higher in the former at LS and FN (p
< 0.005), despite the higher BMI in the older group (p = 0.01). Obese
patients had a lower prevalence of osteoporosis at LS and FN (p = 0.009).
Regression analysis identified BMI as the strongest determinant of FN and TR
BMD, while YSM was the strongest determinant of LS BMD. CONCLUSION: The
protective effect of obesity is overtaken by age and estradiol
deficiency. We recommend that even obese postmenopausal women should be
screened for osteoporosis.
J Clin Endocrinol
Metab. 2007 Oct 9; [Epub
ahead of print
Relationship between Serum Levels of
Sex Hormones and Progression of Subclinical Atherosclerosis in Postmenopausal
Women.
Karim R, Hodis HN, Stanczyk FZ, Lobo
RA, Mack
WJ.
Department of Pediatrics, Atherosclerosis
Research Unit, Department of Medicine, Department of Obstetrics and Gynecology, Department of Preventive Medicine, Keck School
of Medicine, University of Southern California, Los Angeles, CA; College of
Physicians and Surgeons, Columbia University, New York, NY.
Background: Postmenopausal hormone therapy has been examined extensively
in relation to cardiovascular disease (CVD). However, research relating serum
levels of sex hormones to CVD is sparse, and the results are inconclusive.
Methods: We measured sex hormones in longitudinally collected samples of 180
postmenopausal women, 91 randomized to 17beta-estradiol and 89 to placebo, in
the Estrogen in the Prevention of Atherosclerosis
Trial. Repeated measures of sex hormone levels were tested for an association
with carotid artery intima-media thickness (CIMT),
which was also assessed longitudinally over 2 yr. Results: In all women,
changes in serum estrone (P = 0.02), total estradiol (P = 0.01), free estradiol
(P = 0.02), and SHBG (P = 0.005) were significantly inversely associated with
CIMT progression controlling for age and BMI. All the estrogen
compounds and SHBG were significantly inversely related with LDL- and
positively associated with HDL-cholesterol (all P < 0.0001), whereas free
testosterone was positively related with LDL- and inversely associated with
HDL-cholesterol (P < 0.003). Despite an increase in serum free estradiol with estradiol therapy,
women with unchanged SHBG and free testosterone levels had an average
progression in CIMT of 8.53 (4.72) microm/yr, whereas
women with increased free estradiol and SHBG and
decreased free testosterone had the largest reduction in CIMT progression
(-5.45 (2.77) microm/year) (trend P = 0.03).
Conclusion: Estrogen and SHBG are associated with
reduced subclinical atherosclerosis progression in healthy postmenopausal
women. These associations are partially mediated by their beneficial effects on
lipids. Among women taking estradiol, the most
beneficial hormone profile for CIMT progression was increased free estradiol and SHBG with concomitant decreased free
testosterone.
Arch Med Res. 2007 Nov;38(8):891-6.
Epub 2007 Aug 20
Circulating leptin and osteoprotegerin levels affect insulin resistance in healthy
premenopausal obese women.
Departments of Endocrinology and Metabolism,
We investigated the relationship between circulating leptin
and osteoprotegerin (OPG) levels and insulin
resistance assessed by HOMA-IR in premenopausal obese and normal weight women.
Thirty four obese women (age 31 +/- 8 years) (BMI 35 +/- 4 kg/m(2)) with 19 healthy controls (age 31 +/- 7 years) (BMI
<25 kg/m(2)) (BMI 21 +/- 2 kg/m(2)) were included in the study. Women were
healthy and had no osteoporosis. Circulating leptin
levels were significantly higher in obese women (17.11 +/- 2.05 ng/mL vs. 8.38 +/- 4.71 ng/mL, p <0.0001) and
decreased OPG levels were found (14.7 +/- 7.15 pg/mL
vs. 19.17 +/- 6.37 pg/mL, p = 0.03). Leptin showed a positive correlation with BMI (r = 0.851, p
<0.0001), waist-to-hip ratio (r = 0.692, p <0.0001), fasting insulin (r =
0.441, p <0.001), HOMA-IR (r = 0.412, p = 0.002), fibrinogen (r = 0.387, p =
0.004), uric acid (r = 0.293, p = 0.033), hematocrit
(r = 0.394, p = 0.003), systolic (r = 0.504, p <0.0001), and diastolic blood
pressure (r = 0.363, p = 0.008). OPG showed a negative correlation with insulin
(r = -0.341, p = 0.013) and HOMA-IR (r = -0.324, p = 0.018). In obese women
group, the regression equation of HOMA-IR was (HOMA-IR = [0.095 x leptin]-[0.051 x OPG] + 1.71). However, there was no
relation between leptin and OPG levels. In
conclusion, circulating leptin and OPG levels were
related to insulin resistance in premenopausal obese women. However, leptin had no interference in OPG in premenopausal women.
Fertil Steril. 2007 Oct 6; [Epub ahead of print
Effects of non-oral postmenopausal hormone therapy on
markers of cardiovascular risk: a systematic review.
Hemelaar M, van der Mooren MJ, Rad M, Kluft C, Kenemans P.
Project “Aging Women” and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Department of Obstetrics & Gynecology, VU
OBJECTIVE: To review the effects of non-oral administration of
postmenopausal hormone therapy (HT) on risk markers for atherosclerotic and
venous thromboembolic disease.Non-oral
postmenopausal HT appears not to increase venous thromboembolic
risk, whereas the effect on coronary heart disease risk is less clear. DESIGN:
Systematic review of literature obtained from MEDLINE, EMBASE, and CENTRAL
databases from 1980 until and including April 2006. Terms for
"postmenopausal hormone therapy" and for "non-oral
administration" were combined in the search. SETTING: Randomized clinical
trials. PATIENT(S): Postmenopausal women, both healthy and with established
cardiovascular disease or specified cardiovascular risk factors
INTERVENTION(S): Non-oral HT (e.g., transdermal or
intranasal) compared with oral HT or no treatment/placebo. MAIN OUTCOME
MEASURE(S): Lipoprotein(a), homocysteine,
C-reactive protein (CRP), cell adhesion molecules, markers of endothelial
dysfunction, coagulation, and fibrinolysis.
RESULT(S): Seventy-two studies investigating either transdermal
or intranasal administration were included. For non-oral HT, decreases in lipoprotein(a), cell adhesion molecules, and factor VII
generally were significant, resistance to activated protein C (APCr) was slightly increased, and other markers including
CRP and homocysteine did not change. Compared with
oral HT, changes in CRP and APCr were smaller,
changes in cell adhesion molecules and some fibrinolytic
parameters tended to be smaller, whereas changes in other factors including lipoprotein(a) and homocysteine
did not differ. CONCLUSION(S): Potentially unfavorable
changes seen with oral HT on two important markers, CRP and APCr,
are substantially smaller with non-oral HT. Non-oral HT has minor effects on
the other cardiovascular risk markers studied. Therefore, compared with oral
HT, non-oral HT appears be safer with respect to
atherosclerotic and venous thromboembolic disease
risk.
Expert Opin Investig Drugs. 2007 Oct;16(10):1663-72
Bazedoxifene and bazedoxifene combined with conjugated estrogens for the
management of postmenopausal osteoporosis.
New Mexico Clinical Research & Osteoporosis Center, 300 Oak Street
NE, Albuquerque, New Mexico 87106, USA. LEWIECKI@aol.com
Bazedoxifene acetate (WAY-140424; TSE-424)
is an investigational non-steroidal indole-based
selective estrogen receptor modulator (SERM) - also
classified as an estrogen agonist/antagonist - that
is being developed as a daily oral drug for the prevention and treatment of
postmenopausal osteoporosis (PMO). Clinical studies have shown favorable effects on the skeleton, with prevention of bone
loss in postmenopausal women without osteoporosis and reduction in vertebral
fracture risk in women with PMO, without stimulation of endometrium
or breast. Bazedoxifene combined with conjugated
estrogens is an investigational tissue-selective estrogen
complex, the first in a new class of therapeutic agents that pairs a selective estrogen receptor modulator with estrogens. Clinical trials
with bazedoxifene/conjugated estrogens in
postmenopausal women have shown skeletal benefit with improvement in menopausal
vasomotor symptoms and little or no stimulation of endometrial or breast
tissue. Bazedoxifene/conjugated estrogens is a potential agent for the
prevention of PMO and control of menopausal symptoms.
Bone. 2007 Sep 8; [Epub ahead of print
Efficacy and safety of risedronate 150 mg once a month in the treatment of
postmenopausal osteoporosis.
Delmas PD, McClung
MR, Zanchetta JR, Racewicz A, Roux
C, Benhamou CL, Man
Z, Eusebio RA, Beary JF, Burgio DE, Matzkin E, Boonen S.
INSERM Research Unit 831 and
INTRODUCTION:: Risedronate
has been shown to be effective in the treatment of postmenopausal osteoporosis
when given orally in daily or weekly doses or on 2 consecutive days per month.
This randomized, double-blind, multi-center study was
designed to assess the efficacy and safety of a single 150 mg risedronate once-a-month oral dose compared with the 5 mg
daily regimen. METHODS:: Women with postmenopausal
osteoporosis were randomly assigned to receive risedronate
5 mg daily (n=642) or 150 mg once a month (followed by daily placebo) (n=650)
in a double-blind fashion for 2 years. Study drug was taken on an empty stomach
at least 30 min before breakfast. Bone mineral density, bone turnover markers,
fractures, and adverse events were evaluated. The primary efficacy endpoint was
the mean percent change from baseline in lumbar spine bone mineral density
after 1 year. RESULTS:: 538 patients in the daily
group (83.8%) and 556 patients in the once-a-month group (85.5%) completed 1
year. The mean percent change in lumbar spine bone mineral density was 3.4%
(95% confidence interval, 3.03% to 3.82%) in the daily group and 3.5% (95%
confidence interval, 3.15% to 3.93%) in the once-a-month group. The difference
between groups was -0.1% (95% confidence interval, -0.51% to 0.27%). The
once-a-month regimen was determined to be non-inferior to the daily regimen
based on prospectively defined criteria. The mean percent changes in bone
mineral density at sites in the hip (total proximal femur, femoral neck, femoral trochanter) were also
similar in both dose groups, as were the changes in biochemical markers of bone
turnover. The incidence of adverse events, adverse events leading to
withdrawal, and upper gastrointestinal tract adverse events were similar in the
2 treatment groups. Both regimens were well tolerated; the percent of patients
who withdrew from treatment as a result of an adverse event was 9.5% in the
daily group and 8.6% in the once-a-month group. CONCLUSIONS::
Risedronate 150 mg once a month is similar in
efficacy and safety to daily dosing and may provide an alternative for patients
who prefer once-a-month oral dosing.