Selección de Resúmenes de Menopausia
Marzo de 2007
Dr. Juan Enrique Blümel
Semana del 27 de
Marzo al 2 de Abril 2007
J Sex Med. 2007 Mar;4 Suppl 3:227-34.
Testosterone
treatment for hypoactive sexual desire disorder in postmenopausal women.
Kingsberg S.
Introduction. The reduced levels
of testosterone in postmenopausal women are associated with loss of libido,
decreased sexual activity, diminished feelings of physical well-being, and
fatigue. A bilateral oophorectomy can lead to
decreases in sexual desire in 50% of cases by removing ovarian contribution to
the circulating levels of testosterone. Testosterone therapy is an option for
the restoration of sexual drive. Aim. Transdermal testosterone
administration may bypass the effects of first pass hepatic metabolism. To this
end a series of studies have been carried out using a novel transdermal
testosterone system. A review of the results from these
studies are presented here. Main Outcome Measures. A key feature of
these studies was the use of validated study instruments to measure sexual
function: Sexual Activity Log((c)) (SAL((c))), Profile
of Female Sexual Function((c)) (PFSF((c))) and Personal Distress Scale((c)). Methods. The
data from the Phase III studies, known as the Investigation of Natural
Testosterone in Menopausal women Also Taking Estrogen in Surgically Menopausal
women (INTIMATE SM) 1 and 2 were reviewed and the salient information is
presented here.
Results. Both INTIMATE 1 and 2 showed
a significant increase in total satisfying sexual activity, via the SAL((c)) in those women receiving testosterone, compared
with those women in the placebo group. Total satisfying sexual activity
increased by 74% and 51% for INTIMATE 1 and 2, respectively. The PFSF((c)) instrument demonstrated significant improvements
in INTIMATE 1 and 2 in all domains of sexual function in testosterone-treated
women compared with the placebo patients. In both studies, personal distress
decreased in those patients receiving testosterone, compared with the placebo
group. The most commonly reported adverse events were application site
reactions. Eight-five percent of patients said they would probably or
definitely continue treatment. Conclusions. The transdermal testosterone patch is an effective treatment
for hypoactive sexual desire disorder in surgically postmenopausal women
receiving concomitant estrogen therapy. The treatment has a favorable safety
profile.
J Psychosom Res. 2007 Apr;62(4):473-85
Hormonal therapy
and depression: Are we overlooking an important therapeutic alternative?
Ancelin ML, Scali J, Ritchie K.
Inserm,
U888,
OBJECTIVE: This review aimed to examine
evidence for the role of hormonal changes in the onset and course of depressive
symptomatology and to assess the possible future role
of hormonal therapies in the treatment of depression. METHODS: A Medline and PsycINFO search of the literature published between 1965
and 2006 was made of studies of depressive symptoms and hormonal treatment in
women at all stages of reproductive life. RESULTS: The cyclic fluctuation of gonadal steroids at menarche coincides with the beginning
of gender-based differences in depression rates, which continue throughout
reproductive life until menopause. Modifications in hormonal status, whether
related to endogenous or exogenous exposure or to hormone deprivation, appear
to be associated with affective disorder in a subgroup of women. For these
women, a growing body of evidence indicates a biological pattern of
vulnerability to mood disorders in response to hormonal fluctuations. This
could have three major implications: that women vary in vulnerability to mood
disorder when abrupt change in steroid levels occur, that these effects could
be cumulative across the female life span, and that women do not arrive at
menopause with equal risk of mood disorders or equal susceptibility to the
effects of hormonal replacement therapy as has been assumed by current clinical
research and practice. CONCLUSION: While hormonal therapies could have positive
effects in the treatment and prevention of depressive disorders, further research
is required to differentiate hormone-responsive subgroups of women for whom
specific hormonal treatments may be most beneficial. To this end, we suggest
that a multifactorial model of cumulative
vulnerability, which takes into account hormonal exposure throughout life,
genetic vulnerability, and environmental factors, may provide better prediction
of treatment response.
Bone. 2007 Mar
27; [Epub ahead of print]
Beyond clinical
trials: The importance of large databases in evaluating differences in the
effectiveness of bisphosphonate therapy in
postmenopausal osteoporosis.
Randomized controlled clinical trials (RCTs)
are the established method used to support the efficacy and safety of medicines
prior to marketing. For the bisphosphonates currently
marketed for osteoporosis, fracture efficacy and safety have been evaluated in
RCTs. Because of their strict design, RCTs ensure effective control of internal
biases and high internal validity, allowing inferences to be drawn about cause
and effect. However, this very restrictive design also means that RCTs provide
limited data about the performance of a drug in the real world of clinical
practice, where there are wider patient profiles, and variable health care
practices, prescribing habits, and patient adherence to the regimen.
Nonrandomized studies using large health care databases have increasingly been
used to help evaluate the effectiveness of medicines in producing the required
health outcomes. Because of the nature of such observational studies, they
allow the inclusion of very large numbers of subjects and can be an important
source of both effectiveness and safety for medicines and allow comparison
between medicines in a fashion that is unlikely to occur in the RCT setting.
Ann Epidemiol. 2007 Mar 28; [Epub ahead of print]
Body Mass Index and
Mortality in Middle-Aged Korean Women.
Department of Family Medicine,
PURPOSE: We sought to evaluate the association
between body mass index (BMI) and mortality in Korean women and to determine
whether the association differs depending on menopausal status. METHODS: A
total of 338,320 Korean women ages 40 to 64 years categorized into seven groups
by BMI level were prospectively followed for mortality from approximately 1994
to 2004. RESULTS: Multivariable-adjusted analysis using Cox proportional
hazards model showed a U-shaped association between BMI and all-cause deaths,
with the lowest risk at BMI between approximately 25 and 26.9 kg/m(2), even
after excluding earlier deaths, which did not change when we did a stratified
analysis according to menopausal status. A U-shaped association was observed
between BMI and cancer death, and the risk associated with low BMI decreased
significantly after excluding earlier cancer deaths. There was a J-shaped
association between BMI and coronary heart disease (CHD) with a significantly
increased risk at greater BMI (>26 kg/m(2)).
Additional adjustment for possible biological effects of obesity (i.e., serum
total cholesterol, glucose, and systolic blood pressure) changed the U-shaped
association between BMI and all-causes mortality into an inverse shape and
substantially reduced the size of risk for CHD death associated with high BMI
level. In stratified analysis, the association between BMI and CHD was positive
linear in women at premenopausal status, whereas it was U-shaped in women at
postmenopausal status. CONCLUSIONS: Obesity was associated with an increased
risk of mortality in both premenopausal and postmenopausal Korean women,
indicating that preventive strategies to control obesity are important even in
population with a relatively low mean BMI level.
Nutr Metab Cardiovasc Dis. 2007 Mar 27; [Epub ahead of print]
Role of
endogenous androgens on carotid atherosclerosis in non-obese postmenopausal
women.
Montalcini T, Gorgone G, Gazzaruso C, Sesti G, Perticone F, Pujia A.
Department of Medicina Sperimentale e Clinica
"G. Salvatore", University of Catanzaro Magna Graecia, Italy.
BACKGROUND: Recent randomized trials on hormone
replacement therapy in postmenopausal women raised many doubts about their role
in cardiovascular disease prevention. Therefore the role of other sex hormones
needed to be investigated. In particular androgens seem to have a protective
role on atherosclerosis. The present study was performed to assess the role of
endogenous sex hormones on carotid atherosclerosis in postmenopausal women.
METHODS AND RESULTS: We consecutively enrolled 101 postmenopausal women aged
45-75 (mean age 57.4) years referred to our University hospital menopausal
health-screening clinic. The subjects underwent a medical history, a physical
examination and biochemical analysis. Extracranial
carotid arteries were assessed by ultrasound. Fifty percent of our sample had
carotid plaques. On the multivariate logistic regression analysis age, glycaemia (positively) and testosterone (negatively)
(P=0.02) were significantly correlated to carotid atherosclerosis. In non-obese
subjects we found that participants in the third tertile
had a significantly lower prevalence of carotid atherosclerosis (P=0.02)
compared to those in the first tertile of
testosterone. CONCLUSIONS: These results suggest a possible protective role of
endogenous androgens at least on carotid atherosclerosis. Of course these
preliminary results should be supported by prospective studies. Also the
different role of these hormones on obese and non-obese subjects needs to be
clarified.
J Sex Med. 2007 Mar;4
Suppl 3:235-53.
Current
management strategies of the postmenopausal patient with sexual health
problems.
The Journal of Sexual
Medicine,
Introduction. Sexual health
concerns of menopausal women include decreases in sexual interest, arousal,
lubrication, and orgasm, and increases in sexual pain, all of which may be
associated with distress. Aim. To review a step-care
progression of sexual healthcare management: identification of the sexual
health problem; education of the patient and the partner; modification of
reversible causes; first-line therapies consisting of devices and medications;
and second-line therapies with more invasive treatments including surgery. Methods. The healthcare provider is presented with a
clinical diagnosis and treatment paradigm that engages mind, body, and
relationship issues proceeding step-wise in a rational and cost-effective
fashion. Main Outcome Measure. Literature
review in women's sexual health. Results.
Women's health, including sexual health, is a fundamental human right. Supported
by evidence-based data, a step-care approach to diagnosis and management of
women with sexual health problems is advised. Multidisciplinary interventions
should be considered as needed. Identification of sexual health concerns
engages diagnostic components of psychologic
consultation, history, physical examination, and laboratory testing as
appropriate. Key to clinical assessment is the detailed sexual, medical, and
psychosocial history. No agreement exists on necessary laboratory tests.
Patient (and partner) education improves understanding of treatment options and
expectations, and promotes a trusting patient-physician partnership.
Modification of reversible causes includes sex therapy, lubricants, altering
medications, modifying lifestyle and physical therapy for pelvic floor
disorders. First-line therapies should be administered based upon diagnosis,
needs, expectations, risks, benefits, and cost, and include medical devices and
drugs such as hormones, vasoactive agents, dopamine
agonists, topical steroids, anti-infectious agents, and analgesic agents.
Second-line therapies, such as surgery, are initiated upon failure,
insufficient response, or adverse side effects associated with one or more of
the first-line therapies or patient preference. Conclusions.
For postmenopausal women with sexual dysfunction, a rational clinical
management strategy begins with treatment options that are most reversible and
least invasive and costly.
Diabetes Care. 2007 Apr;30(4):967-73
Soy Consumption,
Markers of Inflammation, and Endothelial Function: A cross-over study in
postmenopausal women with the metabolic syndrome.
Azadbakht L, Kimiagar M, Mehrabi Y, Esmaillzadeh A, Hu FB, Willett WC.
Department of Nutrition,
OBJECTIVE: To determine the effects of soy
consumption on markers of inflammation and endothelial function in
postmenopausal women with the metabolic syndrome. RESEARCH DESIGN AND METHODS:
This randomized cross-over clinical trial included 42 postmenopausal women with
the metabolic syndrome. Participants were randomly assigned to consume a
control diet (Dietary Approaches to Stop Hypertension [DASH]), soy protein
diet, or soy nut diet, each for 8 weeks. Red meat in the DASH diet (one
serving/day) was replaced by soy protein in the soy protein diet and by soy nut
in the soy nut diet. RESULTS: For nitric oxide levels, the difference from the
control diet was 9.8% (P < 0.01) on the soy nut and -1.7% (P = 0.10) on the
soy protein diets. The difference from the control diet for serum E-selectin was -11.4% (P < 0.01) on the soy nut
consumption and -4.7% (P = 0.19) on the soy protein diet. Soy nut consumption
reduced interleukin-18 compared with the control diet (difference from the
control diet: -9.2%, P < 0.01), but soy protein did not (difference from the
control diet: -4.6%, P = 0.14). For C-reactive protein, the difference from the
control diet was -8.9% (P < 0.01) on the soy nut diet and -1.6% (P <
0.01) on the soy protein diet. CONCLUSIONS: Short-term soy nut consumption
reduced some markers of inflammation and increased plasma nitric oxide levels
in postmenopausal women with the metabolic syndrome.
J Sex Med. 2007 Mar;4
Suppl 3:211-9.
Prevalence
and Evaluation of Sexual Health Problems-HSDD in
Graziottin A.
Introduction. The complex
condition of the menopause is experienced by all women going through the
physical and emotional changes associated with ovarian sexual hormones loss. It
may impact directly on their physical and mental health. Aim.
The complexity of this condition makes it necessary to accumulate large bodies
of data to define the patterns and trends in its evaluable manifestations. To
this end, large amounts of data were collected on women from
Scand J Med Sci Sports. 2007 Apr;17(2):191.
The reduction of
physical activity reflects on the bone mass among young females: a follow-up
study of 142 adolescent girls.
Rautava E, Lehtonen-Veromaa M, Kautiainen H, Kajander S, Heinonen OJ, Viikari J, Mottonen T.
Jyvaskyla Central Hospital, Jyvaskyla, Finland.
AIM: Maintenance of positive effects of
physical activity on growing bone is unknown. Physical activity was associated
with increased BMC and BMD in a 7-year follow-up with 142 adolescent girls.
Marked reduction in physical activity had an unfavorable effect on bone
measurements, which is an important finding when the prevention of osteoporosis
is considered. INTRODUCTION: Environmental factors influence quality and
durability of bone. Physical activity, with high-impact weight bearing activity
during puberty in particular, has been shown to have a beneficial effect on
growing bone. Only few studies have been published on the maintenance of these
effects. METHODS: At baseline, 142 girls aged 9-15 years participated in the
present 7-year follow-up study. Growth and development, physical activity and
intakes of calcium and vitamin D were recorded at intervals. BMC and BMD
measurements were repeated using DXA. Based on the recording of physical
activity during the follow-up measurements, the effect of the reduction in
physical activity was examined with the bone measurements, and the measurements
in the tertiles based on the amount of physical
activity during the whole follow-up period were compared. RESULTS: Physical
activity was positively associated with the development of BMC and BMD during
the follow-up. The mean BMC of the lumbar spine increased 1.69 g (3%) (P=0.021)
more among those girls who maintained the physical activity level as compared
with those who reduced it during last 4 years. In the femoral neck, the
corresponding difference was 0.14 g (4.6%) (P=0.015) between the same two
groups of girls. The mean increases in BMC at lumbar spine and femoral neck
were more substantial among those girls having the highest physical activity
levels during the 7-year follow-up (46.7% and 22.6%) as compared with those
having the lowest physical activity levels (43.3% and 17.4%, respectively).
CONCLUSIONS: The findings of the present study show that regular physical
activity is valuable in preserving the peak bone mass acquired at puberty in
particular. Many of the girls who markedly reduced their activity levels lost
bone in their femoral neck before their 25th birthday.
Ultrasound
Obstet Gynecol. 2007 Mar 27;29(4):443-448
Sonohysterographic
endometrial sampling and hysteroscopic endometrial
biopsy: a comparative study.
Leone FP, Carsana L, Lanzani C, Vago G, Ferrazzi E.
Department of Obstetrics and Gynaecology, Clinical Sciences Institute L. Sacco,
OBJECTIVES: To compare the quantity and quality
of endometrial tissue sampled at saline contrast sonohysterography
(SCSH) with that obtained by directed endometrial biopsy by operative
hysteroscopy in patients with diffusely thickened and/or inhomogeneous endometrium at SCSH. A secondary aim was a comparison of
the extent of procedure-related pain. METHODS: One hundred and twenty-eight
patients with diffusely thickened (> 4 mm) and/or inhomogeneous endometrium at SCSH were prospectively recruited.
Endometrial sampling was performed at the end of SCSH using the same 4.7-mm
intrauterine catheter that had been used for saline instillation. These samples
were compared to directed endometrial biopsies obtained with the guidance of an
office 5-mm hysteroscope. After hysteroscopy, an
extended guided curettage was performed under general anesthesia, providing
specimens that were considered the gold standard for histological diagnosis.
Endometrial specimen area (mm(2)), histologic
concordance and procedure related pain (10-cm VAS) were compared for the two
techniques. RESULTS: The median age of 88 pre- and of 40 post-menopausal
patients was 41 (interquartile range, 34-48) years
and 57 (interquartile range, 52-67) years,
respectively. The median area of endometrial specimen obtained by SCSH was 25.1
(interquartile range, 12.4-52.3) mm(2)
and was not significantly different from that obtained by hysteroscopy (16.9 (interquartile range, 10.0-52.7) mm(2)). The K values of the
two different techniques for typical hyperplasia (n = 61) and for premalignant
and malignant lesions (n = 26) were 0.91 and 0.94, respectively.
Procedure-related pain was not significantly different between pre- and
postmenopausal patients for both sampling techniques. CONCLUSIONS: SCSH with
sampling proved to be as good as and as tolerable as hysteroscopic
biopsy in cases with diffusely thickened and/or inhomogeneous endometrium. Both these imaging and biopsy techniques
should be considered a reliable outpatient procedure in the management of
patients with abnormal uterine bleeding.
J Thromb Haemost. 2007 Mar
27; [Epub ahead of print]
Postmenopausal oral
estrogen therapy affects hemostatic factors, but does
not account for reduction in the progression of subclinical atherosclerosis.
Vigen C, Hodis HN, Chandler WL, Lobo RA, Mack WJ.
Department of Preventive
Medicine,
Background: Hemostatic
factors influenced by postmenopausal hormone therapy may contribute to
atherosclerosis. The Estrogen in the Prevention of Atherosclerosis Trial
(EPAT), a 2-year, randomized, double-blind, placebo-controlled trial,
demonstrated reduced subclinical atherosclerosis progression measured by change
in common carotid artery intima-media thickness with
unopposed oral 17beta-estradiol. Objectives: To assess the effect of
postmenopausal hormone therapy on the level of several hemostatic
factors, and the relationship between these factors and the progression of
subclinical atherosclerosis. Patients/Methods: We measured tPA antigen, factor VII, D-dimer,
and albumin longitudinally, and PAI-1 and fibrinogen at trial-end, in 186
postmenopausal women. Results: Estradiol versus
placebo was associated with greater factor VII and lower tPA, albumin, PAI-1 and fibrinogen (all p </=
0.001), with no estradiol effect on D-dimer (p = 0.42). Only mean on-trial
tPA was positively
associated with the absolute level of CIMT on-trial (r = .29, p < 0.0001),
but this was attenuated with age and BMI adjustment. No longitudinally measured
hemostatic factor was associated with carotid artery intima-media thickness progression. However, higher carotid
artery intima-media thickness during the trial was
significantly related to increases in tPA.
Conclusions: These results confirm previous findings regarding estrogen's
effect on hemostatic factors and show that albumin is
negatively associated with estrogen therapy. These hemostatic
factors did not account for the reduction of carotid artery intima-media
thickness progression with 17beta-estradiol seen in EPAT. Atherosclerosis
itself may affect levels of hemostatic factors
(reverse causality), with subsequent involvement in atherosclerosis-associated
thrombosis.
Maturitas. 2007 Mar
24; [Epub ahead of print]
Androgens
and the breast.
von Schoultz B.
Department of Obstetrics and
Gynecology,
There is increasing interest in the role of
androgens in the treatment of women but little is known about their long-term
safety. There are also very few studies on testosterone therapy and breast
cancer risk. However, some observations support the concept that androgens may
counteract the stimulatory effects of estrogen and progestogen
in the mammary gland. Mammographic breast density and breast cell proliferation
could be regarded as surrogate markers for the risk of breast cancer. Recently
the addition of testosterone to a common estrogen/progestogen
regimen was found to inhibit the stimulatory effects of hormones on breast cell
proliferation. The effects of testosterone alone on the postmenopausal breast
remain to be investigated.
Mol Cell Endocrinol. 2007 Feb
11; [Epub ahead of print]
Human chorionic gonadotropin (hCG)
and prevention of breast cancer.
Janssens JP, Russo J, Russo I, Michiels L, Donders G, Verjans M, Riphagen I, Van den Bossche T, Deleu M, Sieprath P.
Animal and 'in vitro' experiences learned that
human chorionic gonadotropin (hCG) is capable to protect from breast cancer.
Receptors for hCG/luteinizing hormone (LH) are present on human female and
male breast cancer cells. hCG
decreases proliferation and invasion of breast cancer MCF-7 cells by inhibiting
NF-kappa B, AP-1 activation and other genes. Doxorubicin toxicity is enhanced
by conjugation with beta-hCG in MCF-7 cells. All
these pieces of evidence suggest that hCG
is active in human breast cancer. Direct proof however is missing. We performed
a pilot study phase I trial for testing the inhibitory effects or recombinant hCG (rhCG)
on primary breast cancer. Twenty-five postmenopausal women with newly diagnosed
breast cancers of more than 1.5cm were biopsied before randomization to receive
either 500mugrhCG (n=20) or placebo. After 2 weeks, surgery was done and
tissues were analysed with regard to morphological, immunohistochemical and biochemical changes in tissues and
plasma. rhCG reduces
significantly the proliferative index and the expression of both the oestrogen receptor and progesterone receptor. rhCG does not modify the hormonal
level of estradiol, progesterone, inhibin
and follicle stimulating hormone (FSH) but increases significantly the level of
LH. In a second pilot study, we tested the clinical efficacy through an
open-label single centre study in 13 postmenopausal women with metastatic
breast cancer. A 500mugrhCG once every 2 days shows activity in postmenopausal
metastatic breast cancer. The time to progression is relatively short. Response
to previous hormonal treatment is indicative for rhCG
activity. Given the data in primary and metastatic breast cancer rhCG further large scale investigation is highly warranted.
rhCG can be an realistic
option in (chemo) prevention trials.
Siguiente artículo comentado en http://www.climaterio.cl/Stevenson_TRH_CVDisease.html
Maturitas. 2007 Mar
23; [Epub ahead of print]
HRT and
the primary prevention of cardiovascular disease.
National Heart and Lung
Institute,
Observational studies have consistently shown a
benefit of hormone replacement therapy (HRT) on coronary heart disease (CHD),
but some randomised studies have not shown any
significant effect. Thus questions still remains as to whether HRT is beneficial
for CHD, and in whom this benefit might be achieved. The biological effects of oestrogen on the cardiovascular system have been
extensively studied, and beneficial effects on metabolic CHD risk factors, as
well as on arterial function and on surrogate clinical markers of CHD, have
been demonstrated. Thus it seems implausible that HRT should not benefit CHD in
postmenopausal women. Most randomised trials using
clinical outcomes have studied just one dose of one HRT regimen, a dose
inappropriately high with the average starting age of the participants being in
their mid-60s. The observational population studies largely comprise women
starting on HRT at appropriate dose around the age of menopause, i.e. early
50s. In fact, it was the older women in the randomised
trials that failed to show benefit, whereas there was a trend to benefit in the
younger ones for whom the starting dose of HRT was appropriate. Furthermore, a
pilot study of lower dose HRT in older women did not show any cardiovascular
harm. Inappropriately high doses of oestrogen could
cause cardiovascular harm due to transient disturbances in thrombogenesis
and vascular remodelling. Whilst the greatest CHD
benefit may be seen by starting HRT in the early postmenopause,
this does not exclude benefit in older women given appropriate low dose
therapy.
Maturitas. 2007 Mar
22; [Epub ahead of print]
Rationale for use
of lower estrogen doses for postmenopausal hormone therapy.
156 Lombard Street #13, San Francisco, CA 94111,
USA.
In placebo-controlled clinical trials low dose estrogens
have been shown to reduce hot flashes an average of 65%. Low dosage is
effective in preventing bone loss in early menopause and both low and ultralow
estrogen dosages can prevent bone loss among women many years beyond menopause.
Epidemiological studies indicate less risk of cardiovascular disease and venous
thromboembolism in women who use low dose estrogens
compared to standard dose. Low dosages of estrogens are less likely to produce
unacceptable side effects, such as vaginal bleeding or breast tenderness. When
prescribing low dosage estrogen, one can safely use less progestogen,
either less daily dosage or less frequent cycles. Older women on ultralow
estrogen may not require regular progestogen because
the endometrium is not stimulated. In conclusion,
there is a strong rationale for use of lower estrogen dosage in HT. Low dosage
estrogen can relieve vasomotor symptoms and can prevent postmenopausal bone
loss. Women taking low dosages of estrogens are less likely to have
unacceptable side effects, such as vaginal bleeding or breast tenderness.
Moreover, the potential harm caused by standard dosages of estrogen with
progestin, including coronary heart disease, venous thromboembolism,
stroke, and breast cancer may be mitigated by use of lower estrogen doses that
do not require daily or monthly progestin opposition.
J Vasc Interv Radiol. 2007 Mar;18(3):451-4.
Uterine artery embolization: a treatment option for symptomatic fibroids
in postmenopausal women.
Chrisman HB, Minocha J, Ryu RK, Vogelzang RL, Nikolaidis P, Omary RA.
Northwestern
The authors tested the hypothesis that UAE is an effective treatment
option in postmenopausal women with fibroid-related bulk symptoms. The authors
retrospectively reviewed a prospectively acquired HI-IQ database. Between 2001
and 2004, 24 women with an average age of 52 years meeting the Stages of
Reproductive Aging Workshop criteria for menopause underwent UAE for
fibroid-related bulk symptoms. All patients underwent preprocedural
gadolinium-enhanced magnetic resonance (MR) imaging to confirm the presence of
fibroid disease and exclude other pathology. These patients were followed at
1-, 3-, 6-, 12-, and 24-month intervals to assess their clinical response to
therapy. Clinical success was defined as a qualitative reduction in bulk
symptoms. Postprocedural gadolinium-enhanced MR
imaging was performed routinely between 3 and 6 months and at 12 or 24 months,
if indicated. Technical success was achieved in 24 of 24 (100%) patients. The
follow-up period ranged from
Bone. 2007 Feb 17; [Epub
ahead of print]
Antifracture efficacy of strontium ranelate
in postmenopausal osteoporosis.
Strontium ranelate is a bone-seeking element
that has been assessed in postmenopausal osteoporosis in two large
double-blind, placebo-controlled studies. This treatment is able to decrease
the risk of vertebral fractures, by 38% after 3 years, and by 52% within the
first year of treatment. Moreover, in postmenopausal patients with
osteoporosis, the risk of having a first vertebral fracture is decreased by 48%
after 3 years. The risk of nonvertebral fractures is
decreased by 16%, and, in patients at high risk for such a fracture, the risk
of hip fracture is decreased by 36% over 3 years. Recent 5-year data from these
double-blind, placebo-controlled studies show that the antifracture
efficacy is maintained over time. Current recommendations for therapeutic
decision-making in osteoporosis are based on risk factor assessment; treatment
efficacy with strontium has been documented across a wide range of patient
profiles: age, bone mineral density, body mass index, as well as family history
of osteoporosis and addiction to smoking are not determinants of antifracture efficacy. Strontium ranelate
is an attractive treatment option across the postmenopausal osteoporosis
continuum.
Maturitas. 2007 Mar 19; [Epub ahead of print]
Postmenopausal
hormone therapy: The way ahead.
Department of Medicine "T",
This article follows the milestones in the history of postmenopausal
hormone treatment, with a look into the future. In the first era, hormones were
regarded as an anti-aging panacea, the fountain of eternal youth. It was recommended
then that every postmenopausal woman should consider the use of hormone
replacement therapy. In the second era, people realized that hormones are
medications, and as such should be given for clear and scientifically proven
indications. When the issue of harm as a result of hormone treatment led to
professional and public debates, the concept was changed into a clinically
oriented approach commonly phrased as "the expected benefits should be
weighed individually against potential risks". In the third era,
individualization had a further step, stressing the prognostic importance of
the following parameters: women's age, age at start of hormone use, duration of
therapy, dosage, route of administration, and the exact type and combination of
estrogen and progestogen. The fourth era is already
knocking on our door, as new molecules are sought, which will maximize the
desired effects of therapy while minimizing or eliminating the risks. The fifth
era is still a wishful thinking, searching for the ultimate treatment which
will be based on individual gene mapping and accurate assessment of the chance
to achieve treatment goals vis-a-vis
the risk of having a serious adverse event.
Mol Cell Endocrinol. 2007 Feb 6; [Epub ahead of print]
Increases in
luteinizing hormone are associated with declines in cognitive performance.
Casadesus G, Milliken EL, Webber KM, Bowen RL, Lei Z, Rao CV, Perry G, Keri RA, Smith MA.
Department of Neurosciences,
Questions surrounding estrogen therapy for post-menopausal cognitive decline
and dementia led us to examine the role of luteinizing hormone that becomes
elevated after menopause. We examined hippocampal-associated
cognitive performance, as measured with the Y-maze task, in two strains of
transgenic mice, one (Tg-LHbeta) which over-expresses
luteinizing hormone and another (LHRKO), which has increased circulating
luteinizing hormone levels, but its receptors are silenced. Our results
demonstrate that Tg-LHbeta, but not LHRKO mice, show
decreased Y-maze performance when compared to aged-matched wild-type animals.
These findings indicate that increased luteinizing hormone levels, in the
presence of functional receptors may, at least in part, be responsible for
cognitive decline after menopause. As such, modulation of luteinizing hormone
or its receptor levels may prove to be useful therapeutic strategies for
cognitive decline associated with aging and age-related neurodegenerative
diseases such as Alzheimer disease.
Eur J Gynaecol
Oncol. 2007;28(1):45-7.
Serum CA-125 is a
good predictor of benign disease in patients with postmenopausal ovarian cysts.
Dikensoy E, Balat O, Ugur MG, Ozkur A, Erkilic S.
Department of Obstetrics and Gynecology,
AIM: To determine whether serum CA-125 levels, in addition to tumor size
and ultrasonographic findings can help in
differentiating benign ovarian cysts from malignant disease. METHODS: All
postmenopausal women who had undergone explorative laporatomy
for a preoperative diagnosis of an adnexal cyst
between January 1999 and February 2006 were included if serum CA-125 levels
were below 50 IU/ml. RESULTS: Ninety-three patients with ovarian cysts and
serum CA-125 levels lower than 50 IU/ml were included. Seventy-five (80%) of
the patients (53 unilocular, 22 multilocular)
had ovarian cysts < 13 cm. Of 18 patients with ovarian cysts > 13 cm,
seven had unilocular and 11 had multilocular
cysts. All the patients (n = 77) with a serum CA-125 level < 35 IU/ml had
benign histopathology regardless of the tumor size or ultrasonic features.
Among 16 patients with CA-125 levels between 35 and 50 IU/ml, two with unilocular cysts > 13 cm and nine with multilocular cysts (3 < 13 cm, 6 > 13 cm) had
borderline histopathology. CONCLUSION: We concluded that when unilocular ovarian cyst size is < 13 cm and serum CA-125
levels are below 35 IU/ml in a postmenopausal woman, the possibility of a
benign etiology is most likely.
J Natl Cancer Inst. 2007 Mar 21;99(6):475-86
Dietary lignan intake and postmenopausal breast cancer risk by
estrogen and progesterone receptor status.
Touillaud MS, Thiebaut AC, Fournier A, Niravong M, Boutron-Ruault MC, Clavel-Chapelon F.
Institut National de la Sante et de la Recherche Medicale,
ERI 20, Institut Gustave-Roussy, France.
BACKGROUND: Studies conducted in Asian populations have suggested that
high consumption of soy-based foods that are rich in isoflavone
phytoestrogens is associated with a reduced risk of
breast cancer. However, the potential associations of other dietary phytoestrogens--i.e., the lignans
or their bioactive metabolites, the enterolignans--with
the risk of breast cancer are unclear. METHODS: We prospectively examined
associations between the risk of postmenopausal invasive breast cancer and
dietary intakes of four plant lignans (pinoresinol, lariciresinol, secoisolariciresinol, and matairesinol)
and estimated exposure to two enterolignans (enterodiol and enterolactone), as
measured with a self-administered diet history questionnaire, among 58,049
postmenopausal French women who were not taking soy isoflavone
supplements. Relative risks (RRs) and 95% confidence intervals (CIs) were
estimated using multivariable Cox proportional hazards regression models.
Analyses were further stratified by the combined estrogen and progesterone
receptor (ER/PR) status of the tumors. Statistical tests were two-sided.
RESULTS: During 383,425 person-years of follow-up (median follow-up, 7.7
years), 1469 cases of breast cancer were diagnosed. Compared with women in the
lowest intake quartiles, those in the highest quartile of total lignan intake (>1395 microg/day)
had a reduced risk of breast cancer (RR = 0.83, 95% CI = 0.71 to 0.95, P(trend) = .02, 376 versus 411 cases per 100,000
person-years), as did those in the highest quartile of lariciresinol
intake (RR = 0.82, 95% CI = 0.71 to 0.95, P(trend) = .01). The inverse
associations between phytoestrogen intakes and
postmenopausal breast cancer risk were limited to ER- and PR-positive disease
(e.g., RR for highest versus lowest quartiles of total plant lignan intake = 0.72, 95% CI = 0.58 to 0.88, P(trend) =
.01, 174 versus 214 cases per 100,000 person-years, and RR for highest versus
lowest quartiles of total enterolignan level = 0.77,
95% CI = 0.62 to 0.95, P(trend) = .01, 164 versus 204 cases per 100,000
person-years). CONCLUSIONS: High dietary intakes of plant lignans
and high exposure to enterolignans were associated
with reduced risks of ER- and PR-positive postmenopausal breast cancer in a
Western population that does not consume a diet rich in soy.
J Natl Cancer Inst. 2007 Mar 21;99(6):451-62.
Dietary
fat and postmenopausal invasive breast cancer in the National Institutes of
Health-AARP Diet and Health Study cohort.
Thiebaut AC, Kipnis V, Chang SC, Subar AF, Thompson F, Rosenberg PS, Hollenbeck AR, Leitzmann M, Schatzkin A.
Nutritional Epidemiology Branch, Division of Cancer
Epidemiology and Genetics, National Cancer Institute,
BACKGROUND: Although ecologic association and animal studies support a
direct effect of dietary fat on the development of breast cancer, results of
epidemiologic studies have been inconclusive. METHODS: We prospectively
analyzed the association between fat consumption and the incidence of
postmenopausal invasive breast cancer in the National Institutes of Health-AARP
Diet and Health Study, a
J Clin Endocrinol
Metab. 2007 Mar 20; [Epub
ahead of print
Effects
of oral and trans-vaginal ethinyl estradiol
on hemostatic factors and hepatic proteins in a
randomized, cross-over study.
Sitruk-Ware R, Plu-Bureau G, Menard J, Conard J, Kumar S, Thalabard JC, Tokay B, Bouchard P.
Center for Biomedical Research, Population Council, New York, USA;
Rockefeller University, New York, USA; APHP, Universite
Paris V and Hotel-Dieu, Paris, France; Institut National de la Sante et
de la Recherche Medicale
(INSERM) U652, Paris, France; Hopital Saint-Antoine,
Paris, France.
Context: The use of combined hormonal contraceptives with ethinyl estradiol (EE) and a
progestin results in alterations in potential biomarkers of venous thromboembolism risk. Evaluation of the impact of delivery
route on these changes is difficult due to an interaction between EE and the
progestin component. Objective: To compare the impact of oral and vaginal
administration of EE alone on hemostatic variables
and estrogen-sensitive liver proteins. Design: This was single-center,
randomized, cross-over study with 2 treatment cycles separated by a washout
cycle. Setting: An academic outpatient center. Participants: Fourteen healthy
postmenopausal women were enrolled; 13 completed the study and were included in
the analyses. Intervention: Participants were randomized to receive EE (15 microg/day) delivered by oral
tablet or vaginal ring for 21 days in 1 of 2 treatment sequences. Main outcome
measures: Changes in plasma concentration or activity of 10 hemostatic
variables and 6 estrogen-sensitive liver proteins between baseline and day 21
of treatment. Results: Prothrombin fragment 1 + 2
plasma level was unaffected by treatment or delivery route. Angiotensinogen
(expressed as plasma level of angiotensin I)
increased similarly with oral and vaginal delivery: mean (SD) increases were
2757 (1033) and 2864 (893) ng /mL,
respectively (P = 0.0002). Alterations in other study variables, except total
cholesterol, were similar with oral and vaginal administration. Conclusion: Our
results provide evidence that the customary effects of combined hormonal
contraceptives on hemostatic variables and
estrogen-sensitive liver proteins are largely related to EE and independent of
delivery route during short-term treatment.
Immun Ageing. 2007 Mar 20;4(1):1 [Epub ahead of print
The
Interleukin-6 inflammation pathway from cholesterol to aging - Role of statins, bisphosphonates and
plant polyphenols in aging and age-related diseases.
ABSTRACT: We describe the inflammation pathway from Cholesterol to
Aging. Interleukin 6 mediated inflammation is implicated in age-related
disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary
Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimers
disease and some forms of Arthritis and Cancer. Statins
and Bisphosphonates inhibit Interleukin 6 mediated
inflammation indirectly through regulation of endogenous cholesterol synthesis
and isoprenoid depletion. Polyphenolic
compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated
inflammation by direct inhibition of the signal transduction pathway. Therapeutic
targets for the control of all the above diseases should include inhibition of
Interleukin-6 mediated inflammation.
Scott
Med J. 2007 Feb;52(1):13-6
Lack of knowledge
of osteoporosis: a multi-centre, observational study.
Department of Orthopaedic
Surgery
BACKGROUND AND AIM: Osteoporosis poses a significant health problem. As
the population ages, its incidence increases. Effective prevention requires
good awareness of the disease among the general public. The aim of this study
was to assess the level and source of osteoporosis knowledge in a group of
patients attending for Dual Emission X-ray Absorpitometry
(DEXA) scanning. METHODS: A questionnaire was devised to assess knowledge of
the osteoporosis risk factors, risk-reducing measures and signs/symptoms.
Questionnaires were completed by 176 patients in two centres;
Glasgow Royal Infirmary,
Cancer
Epidemiol Biomarkers Prev. 2007 Mar;16(3):451-7.
Premenopausal
Insulin-Like Growth Factor-I Serum Levels and Changes in Breast Density over
Menopause.
Verheus M, Peeters PH, Kaaks R, van Noord PA, Grobbee DE, van Gils CH.
BACKGROUND: A high proportion of glandular and stromal
tissue in the breast (percentage breast density) is a strong risk factor for
breast cancer development. Insulin-like growth factor-I (IGF-I) is hypothesized
to influence breast cancer risk by increasing breast density. OBJECTIVES: We
studied the relation between premenopausal circulating IGF-I levels and
premenopausal and postmenopausal, absolute nondense
and dense area, and percentage breast density as well as changes in these
measures over menopause. Design and METHODS: Mammograms and blood samples of
684 premenopausal participants of the Prospect-European Prospective
Investigation into Cancer and Nutrition cohort were collected at baseline. A
second mammogram of these women was collected after they became postmenopausal.
Premenopausal IGF-I levels were measured in serum. Premenopausal and
postmenopausal breast measures were assessed using a computer-assisted method.
Mean values of breast measures were calculated for quartiles of serum IGF-I
using linear regression analysis. RESULTS: Women with higher premenopausal
IGF-I levels showed a slightly smaller decrease in dense area over menopause
(-12.2 cm(2) in the highest versus -12.9 cm(2) in the
lowest quartile; P trend = 0.58) and, at the same time, a smaller increase in
the nondense (fat) area (P trend = 0.09). Due to the
changes over menopause, high premenopausal IGF-I serum levels were associated
with lower nondense area (P trend = 0.05), somewhat
higher dense area (P trend = 0.66), and consequently higher percentage breast
density (P trend = 0.02) after menopause. Conclusion and DISCUSSION: Women with
higher premenopausal IGF-I levels have a smaller increase in nondense area and also a slightly smaller decrease in
absolute dense area during menopause, resulting in higher breast density after
menopause.
Int J Cancer. 2007 Mar 19; [Epub ahead of print]
Hormone replacement
therapy and breast cancer in former users of oral contraceptives-The Norwegian
Women and Cancer study.
Lund E, Bakken K, Dumeaux V, Andersen V, Kumle M.
Combined estrogen-progestin menopausal therapy (HRT) and combined
estrogen-progestin contraceptives (OC) both increase breast cancer risk during
current use and a few years after. We investigated risk of breast cancer in
women who were users of HRT dependant on former history of OC use in a large,
national population-based cohort study, the Norwegian Women and Cancer study
(NOWAC). Exposure information was collected through postal questionnaires.
Based on follow-up of 30,118 postmenopausal women by linkage to national
registers of cancer, deaths, and emigration we revealed 540 incident breast
cancer cases between 1996 and 2004. Compared to never users of either drugs
current use of HRT gave a significant (p = 0.002) higher risk of breast cancer
in former OC users, RR = 2.45 (95% CI 1.92-3.12), than among never users of
OCs, RR = 1.67 (1.32-2.12). Relative risk of current use of HRT was similar for
estrogen only and combinations with progestin added in ever users of OCs. The
increased risk of breast cancer in current HRT users with a history of former
OC use could have potential great impact on postmenopausal breast cancer risk
as the proportion of postmenopausal women with former OC use will continue to
increase. (c) 2007 Wiley-Liss, Inc.
Int J Cancer. 2007 Mar 19; [Epub ahead of print
Incidence
of breast cancer among postmenopausal, hypertensive women.
Lindgren A, Pukkala E, Tuomilehto J, Nissinen A.
Department of child psychiatry,
Elevated blood pressure has been proposed to be a risk factor for breast
cancer but the results remain controversial. In this study, the incidence of
breast cancer among 9,112 postmenopausal, hypertensive women included in the community-based
hypertension register of the
Cancer
Epidemiol Biomarkers Prev. 2007 Mar;16(3):613-6.
Overweight and
obese perimenopausal and postmenopausal women exhibit
increased abnormal mammary epithelial cytology.
Seewaldt VL, Goldenberg V, Jones LW, Peace C, Broadwater G, Scott V, Bean GR, Wilke LG, Zalles CM,
High body mass index (BMI >/= 25 kg/m(2)) is
associated with increased postmenopausal breast cancer incidence and mortality.
However, few studies have explored associations between BMI and direct measures
on target tissue. Epithelial cytology was assessed in 62 high-risk perimenopausal and postmenopausal women using random periareolar fine needle aspiration. Masood
cytology index scores were significantly higher among women with BMIs >/=25
kg/m(2) than in women with BMIs <25 kg/m(2) (13.9
+/- 0.42 versus 12.7 +/- 0.29 kg/m(2); P = 0.017). Overweight or obese women
also had significantly higher random periareolar fine
needle aspiration epithelial cell counts compared with those who were normal
weight (1,230 +/- 272 versus 521 +/- 185; P = 0.028). These data suggest that
overweight in perimenopausal and postmenopausal
women is associated with direct cytologic
abnormalities within the breast. Further research is needed to confirm these
findings and to determine if this potential biomarker is responsive to changes
in body weight resulting from diet and/or exercise interventions.
Rev Med Chil. 2007 Jan;135(1):31-6. Epub 2007 Mar 6
Vertebral
fractures, osteoporosis and vitamin D levels in Chilean postmenopausal women.
Rodriguez P JA, Valdivia C G, Trincado M P.
Departamento de Endocrinologia, Escuela de Medicina, Pontificia Universidad
Catolica de ChileChile.
Background: Approximately one-third of vertebral fractures can be
clinically diagnosed. Aim: To study the frequency of vertebral fractures in
postmenopausal women. Patients and methods: We recruited 555 postmenopausal
women from
Maturitas. 2007 Mar 17; [Epub ahead of print
Androgens
and female sexual function.
Palacios Institute of Woman's
OBJECTIVES: There is evidence that suggests that androgen might play an
important role in different tissues and in modulating sexual response. In women
of reproductive age the most important source of androgens present in the blood
is the ovary. Androgens complement the contribution of adrenal precursors,
which in peripheral organs and target tissue can be transformed into bioactive
androgens. The human brain is an important target organ of the sex hormones. The
expression in the brain of men and women of estrogenic and/or androgenic
receptors (AR) in the cerebral nucleus, especially the hypothalamus, whose
important participation in the regulation of the secretion of gonadotrophins, sexual motivation and sexual response is
well documented by experimental research on animals and is being verified by
studies on functional neuroimaging in humans. METHODS
AND RESULTS: The two pivotal studies that have served for acceptance of the
testosterone patch as therapy for hypoactive sexual desire by the European
Agency for the Evaluation of Medicinal Products (EMEA) have been The Intimate
Study (SM1) and The Intimate Study (SM2). The data on the efficiency of these
studies have therefore been clear and positive; the side effects have also been
studied and were found in general to be the same as those of the placebo group.
CONCLUSION: There are certain limitations in the studies that are currently
being evaluated. Studies with androgens alone and androgens plus estrogens in the
natural menopause are ongoing at present.
Semana del 13 al 19 de Marzo 2007
Climacteric. 2007 Feb;10(1):46-50
Depressed mood
through women's reproductive cycle: correlation to mood at menopause.
Becker D, Orr A, Weizman A, Kotler M, Pines A.
Objectives Depressive symptoms are frequent
through the different stages of a woman's reproductive cycle. The aim of this
study was to evaluate a possible correlation of depressive mood before
menstruation, during pregnancy, after delivery and around the menopause.
Methods The sample consisted of 110 women (mean age 52
years, standard deviation 4 years) who rated their mood at present and retrospectively
at different stages of the reproductive cycle. Mood was rated using a visual
analogue scale. Results A significant statistical
association was found between the present mood and mood at the premenstrual
period, but not with mood at pregnancy or after delivery. These findings were
independent of age, menopausal status or use of hormone replacement therapy.
Conclusions The statistical association between
depressed mood around menopause and before menstruation supports the assumption
that there is a common etiology, which could be attributed to hormonal or
psychological factors, or both.
Climacteric. 2007 Feb;10(1):38-45
Effects of
acupuncture, applied relaxation, estrogens and placebo on hot flushes in
postmenopausal women: an analysis of two prospective, parallel, randomized
studies.
Zaborowska E, Brynhildsen J, Damberg S, Fredriksson M, Lindh-Astrand L, Nedstrand E, Wyon Y, Hammar M.
Division of Obstetrics
and Gynecology.
Objective To assess if transdermal
or oral estrogens, acupuncture and applied relaxation decrease the number of
menopausal hot flushes/24 h and improve climacteric symptoms, as assessed by
the Kupperman index, more than transdermal
placebo treatment. Setting An outpatient clinic at a
Swedish university hospital. Methods A total of 102 postmenopausal women were
recruited to two studies performed in parallel. In Study I, the women were
randomized between transdermal placebo or estrogen
treatment and, in Study II, between oral estrogens, acupuncture or applied
relaxation for 12 weeks. Climacteric symptoms were measured with daily logbooks
on hot flushes. Women completed the assessment questionnaire for the Kupperman index at baseline and after 12 weeks. Results The number of flushes/24 h decreased significantly after 4
and 12 weeks in all groups except the placebo group. Both at 4 and 12 weeks,
acupuncture decreased the number of flushes more (p < 0.05; p < 0.01,
respectively) than placebo. At 12 weeks, applied relaxation decreased the
number of flushes more (p < 0.05) than placebo. The Kupperman
index score decreased in all groups except the placebo group. The decrease in
score was significantly greater in all treatment groups than in the placebo
group (p < 0.01). Conclusion Acupuncture and applied relaxation both reduced
the number of hot flushes significantly better than placebo and should be
further evaluated as alternatives to hormone therapy in women with menopausal
vasomotor complaints.
Climacteric. 2007 Feb;10 Suppl
Effects
of blood pressure reduction on cardiovascular risk estimates in hypertensive
postmenopausal women.
Department of Medicine, Miller
Menopause is accompanied by an increased
prevalence of hypertension, which may partially explain the corresponding
cardiovascular risk observed in postmenopausal women. The relationship between
blood pressure and cardiovascular risk is continuous, consistent and
independent of other risk factors. There are profound benefits of treating
hypertension: antihypertensive therapy has been associated with large
reductions in stroke, myocardial infarction and heart failure. Despite these
proven benefits, hypertension is inadequately treated, or not treated at all,
in the majority of patients. There has been concern regarding the use of
hormone therapy in hypertensive postmenopausal women. Drospirenone/17beta-estradiol,
a hormone therapy, has been demonstrated to lower blood pressure in
hypertensive postmenopausal women either alone or when administered simultaneously
with antihypertensive drugs. This might offer a potential advantage in patients
with elevated blood pressure. It is also known that the risk for target organ
events extends to levels well below the established definition of 140/90 mmHg.
High-normal blood pressure carries an increased cardiovascular risk when
compared to lower levels of blood pressure. Identification and management of
elevated blood pressure are an important component of the successful management
of the postmenopausal woman and can help prevent the untoward consequences of
elevated blood pressure.
Climacteric. 2007 Feb;10 Suppl
Drospirenone with
17beta-estradiol in the postmenopausal woman with hypertension.
Division of Hypertension and
Clinical Pharmacology, Pat and
Hypertension is one of the most important risk
factors for the development of cardiovascular disease. The prevalence of
hypertension increases with age and also after the menopause; therefore, blood
pressure monitoring and effective control of elevated blood pressure are very
important in postmenopausal women. The knowledge that aldosterone is a dual cardiovascular and endocrine hormone
has blurred the once distinct boundary between gynecology and cardiovascular
medicine. Aldosterone plays a major role in
salt and water homeostasis, but also binds to mineralocorticoid
receptors in the cardiovascular system, leading to structural and functional
changes and consequent organ damage. Highly selective aldosterone
blockade via the mineralocorticoid receptor has
long-term antihypertensive effects. Drospirenone is a
novel progestogen with aldosterone
receptor antagonism (
Climacteric. 2007 Feb;10 Suppl
Menopause and
cardiovascular disease: the evidence.
Rosano GM, Vitale C, Marazzi G, Volterrani M.
Department of Medical Sciences, Center for
Clinical and Basic Research, Cardiovascular Research Unit, IRCCS San Raffaele.
Menopause is a risk factor for cardiovascular
disease (CVD) because estrogen withdrawal has a detrimental effect on
cardiovascular function and metabolism. The menopause compounds many
traditional CVD risk factors, including changes in body fat distribution from a
gynoid to an android pattern, reduced glucose
tolerance, abnormal plasma lipids, increased blood pressure, increased
sympathetic tone, endothelial dysfunction and vascular inflammation. Many CVD
risk factors have different impacts in men and women. In postmenopausal women,
treatment of arterial hypertension and glucose intolerance should be
priorities. Observational studies and randomized clinical trials suggest that
hormone replacement therapy (HRT) started soon after the menopause may confer
cardiovascular benefit. In contrast to other synthetic progestogens
used in continuous combined HRTs, the unique progestogen
drospirenone has antialdosterone
properties. Drospirenone can therefore counteract the
water- and sodium-retaining effects of the estrogen component of HRT via the renin-angiotensin-aldosterone system, which may otherwise result
in weight gain and raised blood pressure. As a continuous combined HRT with
17beta-estradiol, drospirenone has been shown to
significantly reduce blood pressure in postmenopausal women with elevated blood
pressure, but not in normotensive women. Therefore,
in addition to relieving climacteric symptoms, drospirenone/17beta-estradiol
may offer further benefits in postmenopausal women, such as improved CVD risk
profile.
Climacteric. 2007 Feb;10 Suppl
Drospirenone and its
antialdosterone properties.
Genazzani AR, Mannella P, Simoncini T.
Department of Obstetrics and
Gynecology,
Drospirenone is a unique progestogen derived from 17alpha-spirolactone, with a
pharmacologic profile very similar to that of endogenous progesterone. In
contrast with other available progestins, drospirenone is a progestogen
with aldosterone receptor antagonism (
Climacteric. 2007 Feb;10 Suppl 1:3-10
Drospirenone and estradiol: a new option for the postmenopausal woman.
CONRAD Clinical
The efficacy of estrogen with or without a progestogen as hormone replacement therapy (HRT) for
menopausal symptoms is well-established. Recent large-scale randomized studies
with combined estrogen/progestogen therapy (EPT) have
raised a number of safety issues, specifically the potential risk for coronary
heart disease. Subsequent analyses and other studies have indicated that HRT
may be cardioprotective in younger postmenopausal
women. A new continuous EPT combines natural 17beta-estradiol (E2) 1 mg with
the novel progestin, drospirenone (DRSP) either 0.5
or 2 mg. DRSP has a physiological profile closer to that of natural
progesterone than any other synthetic progestin. This paper reviews recent
clinical trial data demonstrating the efficacy and safety of combined DRSP/E2
therapy as EPT in postmenopausal women. DRSP/E2 provides symptomatic relief of
vasomotor symptoms and improvement in genitourinary atrophy. DRSP/E2 protects
against endometrial hyperplasia and reduces the risk of osteoporosis. Combined
DRSP/E2 therapy has a favorable impact on cholesterol and triglyceride levels,
and decreases blood pressure in women with elevated blood pressure. The
favorable efficacy and safety profile of DRSP/E2, and potential for long-term
health benefits, represents a new option for the effective management of
menopause and its clinical sequelae.
Acta Otolaryngol. 2007 Feb;127(2):149-55
Hearing
in women at menopause. Prevalence of
hearing loss, audiometric configuration and relation to hormone replacement
therapy.
Hederstierna C, Hultcrantz M, Collins A, Rosenhall U.
Department of Audiology,
Conclusion. Hormone
replacement therapy (HRT) may have a protective effect on hearing impairment in
postmenopausal women. New guidelines for classification of audiometric
configuration in age-related hearing loss are suggested. Objectives.
To describe prevalence of hearing loss and audiometric configuration in a group
of middle-aged women with respect to menopausal stage and HRT. Subjects and methods. A total of 143 women around menopause
were sampled through the Swedish population register. The mean hearing
threshold levels were compared according to menopausal status. The audiograms
in the 57 women with hearing loss were classified according to audiometric
configuration. Results. In all, 57 women (40%) had any
kind of hearing loss; 42 had very minute hearing loss; 15 had a 4FA (average of
thresholds at 0.5, 1, 2, and 4 kHz) of at least 20-39 dB HL in at least one
ear. Two of these had a 4FA of 40-69 dB HL in at least one ear. The most common
configurations were: gently sloping (47%), steeply sloping (14%), and
high-frequency U-shaped (14%). The postmenopausal women who were not on HRT had
poorer hearing mainly at 2 and 3 kHz, compared with pre- and perimenopausal women, and postmenopausal women on HRT.
Drugs Aging. 2007;24(3):173-85
Might DHEA be Considered a Beneficial Replacement Therapy in the Elderly?
Genazzani AD, Lanzoni C, Genazzani AR.
Department of Obstetrics and
Gynecology,
Dehydroepiandrosterone (DHEA) [prasterone] is typically secreted by the adrenal glands and
its secretory rate changes throughout the human
lifespan. When human development is completed and adulthood is reached, DHEA
and DHEA sulphate (DHEAS) [PB-008] levels start to
decline so that at 70-80 years of age, peak DHEAS concentrations are only
10-20% of those in young adults. This age-associated decrease has been termed 'adrenopause', and since many age-related disturbances have
been reported to begin with the decline of DHEA/DHEAS levels, this provides a
potential opportunity for use of DHEA as replacement therapy.For
these reasons, use of DHEA as a replacement therapy in aging men and women has
been proposed and this paper outlines the reported beneficial effects of such
treatment in humans. Many interesting results have been obtained in
experimental animals suggesting that DHEA positively modulates most age-related
disturbances. However, renewed interest in DHEA has arisen as a result of
recent studies suggesting that DHEA appears to be beneficial in hypoandrogenic men as well as in postmenopausal and aging
women. Menopause is the event in a woman's life that induces a dramatic change
in the steroid milieu, and use of DHEA as 'replacement treatment' has been reported
to restore both the androgenic and estrogenic environment and reduce most of
the symptoms of this change. As menopause is the beginning of the biological
transition of women towards senescence, it is of great interest to better
understand how DHEA might help to solve and/or overcome the problems of this
complex stage of life. In men with adrenal insufficiency and hypogonadism without androgen replacement, DHEA
administration results in a significant increase in circulating androgens.Though most data are suggestive for use of DHEA
as hormonal replacement treatment, more defined and specific clinical trials
are needed to uncover all of the 'secrets' and features of this steroid before
it can be used as a standard treatment. Furthermore, DHEA is perceived
differently around the world, being considered only a 'dietary supplement' in
the US, while in many European countries it is considered a 'true hormone' that
has not been approved for use as a hormonal treatment by the European health
authorities. This overview offers some points of view on use of DHEA as an
experimental hormonal replacement therapy.
Maturitas. 2007 Mar
9; [Epub ahead of print]
Tibolone for prevention and
treatment of postmenopausal osteoporosis.
156 Lombard Street #13, San Francisco, CA 94111,
USA.
Tibolone has been widely
accepted as remedy for vasomotor symptoms and for prevention of bone loss.
Studies over the past 25 years have documented its effects on bone mineral
density in younger and older women. Tibolone reduces
bone turnover substantially (about the same amount as hormone therapy).
Increases in bone mineral density (BMD) accompany this reduction in bone
turnover, but like all other antiresorptive
therapies, reduction in fracture risk (i.e. 50%) is always greater than would
be predicted from BMD change. Finally, as with hormone
therapies, dosage reductions have been prompted by new evidence of low dosage
efficacy and concern over dose-related side effects. Solid evidence has
now emerged from large, dose-ranging studies that the 1.25mg tibolone dosage is adequate for preservation of BMD and for
reduction of fracture risk. Now that fracture efficacy has been added to the
list of tibolone's documented bone benefits,
physicians must consider this in the overall risks and benefits of its use.
Am J Ophthalmol. 2007 Mar
14; [Epub ahead of print]
Itchy-Dry Eye
Associated with Polycystic Ovary Syndrome.
Bonini S, Mantelli F, Moretti C, Lambiase A, Bonini S, Micera A.
Interdisciplinary Center for Biomedical
Research (CIR), Laboratory of Ophthalmology, University Campus Bio-Medico of
Rome, Italy; IRCCS G.B. Bietti Eye Foundation, Rome,
Italy.
PURPOSE: The authors aimed to define the ocular
symptomatology of women with polycystic ovaries and hyperandrogenism. DESIGN: Prospective, observational case
series. METHODS: Of the 62 consecutive patients with an ultrasonographic
diagnosis of polycystic ovary (PCO), 16 were identified as having clinical and
biochemical signs of hyperandrogenism. All women with
a history of ocular symptoms (20/62 total patients [32.3%], 15/16 polycystic
ovary syndrome (PCOS) patients [93.7%], and 5/46 PCO patients [10.8%])
underwent a complete eye examination with conjunctival
impression cytologic sampling. Clinical measurements
of tear function (tear film break-up time [BUT], Schirmer
I test) were completed along with analysis of conjunctival
goblet cell number, conjunctival immunostaining,
and reverse-transcriptase polymerase chain reaction for the mucins
MUC1 and MUC5AC. Clinical, histologic, and
biochemical data of patients with PCOS were compared statistically with that of
patients with PCO and with eight age- and gender-matched healthy controls.
Eight of the most severely affected patients received systemic antiandrogen therapy and underwent further ocular
evaluation four months after systemic therapy. RESULTS: Women with PCOS had
greater conjunctival hyperemia (P < .001), dryness
(P < .001), itching (P < .001), mucous discharge (P < .001), and
contact lens intolerance (P < .001) than patients with PCO. Patients with
PCOS had a significant reduction of the tear film BUT accompanied by a
significant increase in goblet cell number and conjunctival
MUC5AC messenger ribonucleic acid expression compared with both PCO patients
and healthy subjects. CONCLUSIONS: Evaluation of the ocular surface should be
considered in patients with PCO or PCOS. Women with PCOS were more likely to
have itchy-dry eyes, decreased tear film BUT, and increased
goblet cell density.
Osteoporos Int. 2007 Mar 9; [Epub ahead of print]
Telomere length in
leukocytes correlates with bone mineral density and is shorter in women with
osteoporosis.
Valdes
AM,
Richards
JB,
Gardner
JP,
Swaminathan R, Kimura
M,
Xiaobin L, Aviv
A,
Spector TD.
Twin Research & Genetic Epidemiology Unit, King's
College
Telomere length decreases with age and is associated with osteoblast senescence. In 2,150 unselected women, leukocyte
telomere length was significantly correlated with bone mineral density.
Clinical osteoporosis was associated with shorter telomeres, suggesting that
telomere length can be used as a marker of bone aging. INTRODUCTION: The length
of telomeres in proliferative cells diminishes with age. Telomere shortening
and telomerase activity have been linked to in vitro osteoblast
senescence and to increased secretion of pro-inflammatory cytokines. We
explored whether bone mineral density correlates with telomere length in
leukocytes. MATERIALS AND METHODS: The relationship between leukocyte telomere
length, bone mineral density (BMD) and osteoporosis (as defined by the World
Health Organization) was examined in a cohort of 2,150 women from a
population-based twin cohort aged 18-79. RESULTS: After adjusting for age, body
mass index, menopausal status, smoking, hormone replacement therapy status,
telomere length was positively correlated with BMD of the spine (p < 0.005),
forearm (p < 0.013), but not the femoral neck (p < 0.06). Longer
telomeres were associated with reduced the risk of clinical OP at two or more
sites (odds ratio = 0.594 95% CI 0.42-0.84 p < 0.003) and in women over the
age of 50, clinical osteoporosis was associated with 117 bp
shorter telomere length (p < 0.02) equivalent to 5.2 years of telomeric aging. CONCLUSIONS: Shortened leukocyte telomere
length is independently associated with a decrease in BMD and the presence of
osteoporosis in women. Our data provide evidence that leukocyte telomere length
could be a marker of biological aging of bone.
Stem Cells. 2007 Mar 8; [Epub ahead of print]
Induction
of senile osteoporosis in normal mice by intra-bone marrow-bone marrow
transplantation from osteoporosis-prone mice.
Ueda
Y,
Inaba M, Takada
K,
Fukui
J,
Sakaguchi Y, Tsuda M, Omae M, Kushida T, Iida
H,
Ikehara S.
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan; Department of Orthopedic
Surgery, Kansai Medical University, Moriguchi City, Osaka,
Japan.
A substrain of the senescence accelerated
mouse, SAMP6, spontaneously develops osteoporosis early in life. These mice
show the clinical signs of osteoporosis, such as elevated levels of urinary deoxypiridinoline (Dpd),
decreased bone mineral density (BMD), and a significant loss of trabecular and cortical bone thickness at 12 months of age.
Here, we describe the transfer of osteoporosis to a normal strain by the
injection of bone marrow cells (BMCs) from SAMP6 donors directly into the bone
marrow cavity (intra-bone marrow bone marrow transplantation: IBM-BMT). More
than one month after IBM-BMT, hematolymphoid cells
were completely reconstituted by donor-derived cells, and bone marrow stromal cells that could differentiate into osteocytes were also found to be of donor origin. In
addition, the recipient C57BL/6 mouse showed the features of osteoporosis in
the trabecular bone. Decreases in BMD and increases
in urinary DPD were also observed. When the message levels of cytokines (IL-11,
IL-6, RANKL, OPG, M-CSF and IGF-1) were examined by RT-PCR and real time RT-PCR
analysis, IL-6 and IL-11 were reduced to a level similar to that in SAMP6 mice,
while that of RANKL was increased. These findings indicate that not only the hemopoietic system but also the bone marrow
microenvironment are reconstituted as a result of IBM-BMT, and suggest that the
development of senile osteoporosis might be attributable to "stem cell
disorders".
Am J Clin Nutr. 2007 Mar;85(3):895-909.
Flavonoid intake and cardiovascular disease
mortality: a prospective study in postmenopausal women.
Mink
PJ,
Scrafford CG, Barraj LM, Harnack L, Hong
CP,
Nettleton
JA,
Jacobs
DR Jr.
From Exponent, Inc,
BACKGROUND: Dietary flavonoids may have
beneficial cardiovascular effects in human populations, but epidemiologic study
results have not been conclusive. OBJECTIVE: We used flavonoid
food composition data from 3 recently available US Department of Agriculture
databases to improve estimates of dietary flavonoid
intake and to evaluate the association between flavonoid
intake and cardiovascular disease (CVD) mortality. DESIGN: Study participants
were 34 489 postmenopausal women in the Iowa Women's Health Study who were free
of CVD and had complete food-frequency questionnaire information at baseline.
Intakes of total flavonoids and 7 subclasses were
categorized into quintiles, and food sources were grouped into frequency
categories. Proportional hazards rate ratios (RR) were computed for CVD,
coronary heart disease (CHD), stroke, and total mortality after 16 y of
follow-up. RESULTS: After multivariate adjustment, significant inverse
associations were observed between anthocyanidins and
CHD, CVD, and total mortality [RR (95% CI) for any versus no intake: 0.88
(0.78, 0.99), 0.91 (0.83, 0.99), and 0.90 (0.86, 0.95)]; between flavanones and CHD [RR for highest quintile versus lowest:
0.78 (0.65, 0.94)]; and between flavones and total mortality [RR for highest
quintile versus lowest: 0.88 (0.82, 0.96)]. No association was found between flavonoid intake and stroke mortality. Individual flavonoid-rich foods associated with significant mortality
reduction included bran (added to foods; associated with stroke and CVD);
apples or pears or both and red wine (associated with CHD and CVD); grapefruit
(associated with CHD); strawberries (associated with CVD); and chocolate
(associated with CVD). CONCLUSION: Dietary intakes of flavanones,
anthocyanidins, and certain foods rich in flavonoids were associated with reduced risk of death due
to CHD, CVD, and all causes.
Am J Clin Nutr. 2007 Mar;85(3):735-41
Soy inclusion in
the diet improves features of the metabolic syndrome: a randomized crossover
study in postmenopausal women.
Azadbakht L, Kimiagar M, Mehrabi Y, Esmaillzadeh A, Padyab M, Hu FB, Willett
WC.
Department of Human Nutrition,
BACKGROUND: Little evidence exists regarding the effects of soy
consumption on the metabolic syndrome in humans. OBJECTIVE: We aimed to
determine the effects of soy consumption on components of the metabolic
syndrome, plasma lipids, lipoproteins, insulin resistance, and glycemic control in postmenopausal women with the metabolic
syndrome. DESIGN: This randomized crossover clinical trial was undertaken in 42
postmenopausal women with the metabolic syndrome. Participants were randomly assigned
to consume a control diet (Dietary Approaches to Stop Hypertension, DASH), a
soy-protein diet, or a soy-nut diet, each for 8 wk. Red meat in the DASH period
was replaced by soy-protein in the soy-protein period and by soy-nut in the
soy-nut period. RESULTS: The soy-nut regimen decreased the homeostasis model of
assessment-insulin resistance score significantly compared with the soy-protein
(difference in percentage change: -7.4 +/- 0.8; P < 0.01) or control (-12.9
+/- 0.9; P < 0.01) diets. Consumption of soy-nut also reduced fasting plasma
glucose more significantly than did the soy-protein (-5.3 +/- 0.5%; P <
0.01) or control (-5.1 +/- 0.6%; P < 0.01) diet. The soy-nut regimen
decreased LDL cholesterol more than did the soy-protein period (-5.0 +/- 0.6%;
P < 0.01) and the control (-9.5 +/- 0.6%; P < 0.01) diet. Soy-nut
consumption significantly reduced serum C-peptide concentrations compared with
control diet (-8.0 +/- 2.1; P < 0.01), but consumption of soy-protein did
not. CONCLUSION: Short-term soy-nut consumption improved glycemic
control and lipid profiles in postmenopausal women with the metabolic syndrome.
Orv Hetil. 2007 Feb 18;148(7):319-25
Vitamin D forming
effectiveness of ultraviolet radiation from sunlight in different months in
Fodor Jozsef Orszagos Kozegeszsegugyi Kozpont Orszagos Frederic
Joliot-Curie Sugarbiologiai es
Sugaregeszsegugyi Kutato Intezete
Introduction: The vitamin D 3 formation in skin is the most important
natural source of vitamin D demands of humans. The key step of the phototransformation of provitamin
D into previtamin D from which the vitamin D 3 is
formed by thermal conversion. According to studies run at the latitudes of
Eur J Radiol. 2007 Mar 5; [Epub ahead of print]
Relationship
between the arterial calcification detected in mammography and coronary artery
disease.
Topal U, Kaderli A, Topal NB, Ozdemir B, Yesilbursa D, Cordan J, Ediz B, Aydinlar A.
Department of Radiology,
OBJECTIVE: Arterial calcification is frequently encountered in
mammography. The frequency of breast arterial calcification (BAC) increases
with increasing age. Studies have shown that BAC is seen more frequently among
the people who are under the risk of coronary artery diseases (CAD) such as
diabetes and hypertension. The objective of this study is to investigate the
relationship between the arterial calcification detected in mammography and the
CAD. MATERIAL AND METHODS: Screening mammography was performed in 123 women
above the age of 40 years who had been examined with coronary angiography for
the evaluation of CAD. The presence of BAC, number of affected vessels, and the
distribution of calcification in the vessel wall were evaluated in the
mammography. Subjects were questioned in terms of the cardiovasculary
risk factors. The severity of CAD was evaluated according to the Gensini scoring. In addition, the number of blood vessels
with stenosis of more than 50% was used as the
vascular score. The correlation between Gensini and
the vascular scores, and BAC was statistically evaluated using Mann-Whitney U
and Kruskal-Wallis tests. RESULTS: Eighty (65%) of
123 patients had CAD. BAC was detected in the mammography of 49 (39.8%)
subjects. The ages and duration of menopause of the cases with BAC were
significantly higher than those without BAC (p<0.001). There was an almost
significant correlation between the BAC and Gensini
scores (p=0.059). There was a significant increase in the frequency of BAC
among subjects with more than two vessels with stenosis
(p=0.033). CONCLUSION: Frequency of BAC increases with increasing age. BAC is
also frequently seen in subjects having severe coronary artery disease.
Although increasing age may be a factor increasing the frequency of BAC, BAC
may also be an indicator of CAD. Therefore, the mentioning of arterial
calcification in mammography reports may be important in warning the clinician
in terms of CAD.
J Natl Cancer
Inst. 2007 Mar
7;99(5):386-95
Longitudinal
measurement of clinical mammographic breast density to improve estimation of
breast cancer risk.
Kerlikowske K, Ichikawa
L,
Miglioretti DL, Buist DS, Vacek PM, Smith-Bindman R, Yankaskas B, Carney
PA,
Ballard-Barbash R;
National Institutes of Health Breast Cancer Surveillance Consortium. Department of
Epidemiology and Biostatistics, Department of Veterans Affairs, University of
California, San Francisco, CA, USA. karla.kerlikowske@ucsf.edu
BACKGROUND: Whether a change over time in clinically measured
mammographic breast density influences breast cancer risk is unknown. METHODS:
From January 1993 to December 2003, data that included American College of
Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density
categories (1-4 in order of increasing density) were collected prospectively on
301,955 women aged 30 and older who were not using postmenopausal hormone
replacement therapy and underwent at least two screening mammography
examinations; 2639 of the women were diagnosed with breast cancer within 1 year
of the last examination. Women's first and last BI-RADS breast density (average
3.2 years apart) and logistic regression were used to
model the odds of having invasive breast cancer or ductal
carcinoma in situ diagnosed within 12 months of the last examination by change
in BI-RADS category. Rates of breast cancer adjusted for age, mammography
registry, and time between screening examinations were estimated from this
model. All statistical tests were two-sided. RESULTS: The rate (breast cancers
per 1000 women) of breast cancer was higher if BI-RADS breast density category
increased from 1 to 2 (5.6, 95% confidence interval [CI] = 4.7 to 6.9) or 1 to
3 (9.9, 95% CI = 6.4 to 15.5) compared to when it remained at BI-RADS density
of 1 (3.0, 95% CI = 2.3 to 3.9; P<.001 for trend). Similar and statistically
significant trends between increased or decreased density and increased or
decreased risk of breast cancer, respectively, were observed for women whose breast density category was initially 2 or 3 and
changed categories. BI-RADS density of 4 on the first examination was
associated with a high rate of breast cancer (range 9.1-13.4) that remained
high even if breast density decreased. CONCLUSION: An increase in BI-RADS
breast density category within 3 years may be associated with an increase in
breast cancer risk and a decrease in density category with a decrease in risk
compared to breast cancer risk in women in whom breast density category remains
unchanged. Two longitudinal measures of BI-RADS breast density may better
predict a woman's risk of breast cancer than a single measure.
J Clin Endocrinol Metab. 2007 Mar 6; [Epub
ahead of print
Effects
of testosterone treatment on endometrial proliferation in postmenopausal women.
Zang H, Sahlin L, Masironi B, Eriksson
E,
Hirschberg
AL.
Department of Woman and Child Health, Divisions of Obstetrics and
Gynecology and of Reproductive Endocrinology, and Department of
Oncology-Pathology, Division of Pathology, Karolinska
Institutet, Stockholm, Sweden.
Context: Available data concerning effects of testosterone on endometrium of postmenopausal women are seriously limited.
Objective: Our aim was to compare the influence of treatment with testosterone
and/or estrogen on endometrial proliferation in healthy postmenopausal women.
Design: An open, randomized clinical study with parallel comparison of the
groups. Setting: Women's health clinical research unit and a research
laboratory at a university hospital. Participants: Sixty-three women who had
experienced natural menopause. Interventions: After random assignment, the
participants were administered orally testosterone undecanoate
(40 mg every second day), estradiol valerate (2 mg daily) or both for three months. Main
Outcome Measures: Endometrial thickness was measured and endometrial
proliferation evaluated on the basis of histopathology and expression of Ki-67,
a proliferation marker. Results: Endometrial thickness was significantly
increased by treatment with estrogen alone or in combination with testosterone
but was unaltered by testosterone alone. Among the women receiving estrogen
alone, the proportion exhibiting histopathology indicative of proliferation
increased significantly to 50% (p <0.05), whereas there was a
non-significant increase to 28% with the combined treatment and testosterone alone
had no effect at all. Expression of Ki-67 was up-regulated significantly in
both glands and stroma (p< 0.05 respectively) in
both estrogen treatment groups. However, the expression was significantly
higher in stroma by estrogen treatment alone than after
combined treatment (p<0.05). Conclusions: The short-term treatment with
testosterone of postmenopausal women does not stimulate endometrial
proliferation. In addition, testosterone appears to counteract endometrial
proliferation induced by estrogen to a certain extent.
Ann Intern Med. 2007 Mar 6;146(5):326-339.
Effect of
Recombinant Human Parathyroid Hormone (1-84) on Vertebral Fracture and Bone
Mineral Density in Postmenopausal Women with Osteoporosis: A Randomized Trial.
Greenspan
SL,
Bone
HG,
Ettinger MP, Hanley
DA,
Lindsay
R,
Zanchetta JR, Blosch CM, Mathisen AL, Morris
SA,
Marriott
TB.
University of Pittsburgh, Pittsburgh, Pennsylvania; Michigan Bone and
Mineral Clinic, Detroit, Michigan; Radiant Research Center of South Florida and
The Regional Osteoporosis Center, Stuart, Florida; University of Calgary Health
Sciences Center, Calgary, Alberta, Canada; Helen Hayes Hospital, Regional Bone
Center, West Haverstraw, New York; Instituto de Investigaciones Metabolicas,
Buenos Aires, Argentina; and NPS Pharmaceuticals, Inc., Parsippany, New Jersey.
BACKGROUND: Recombinant human parathyroid hormone (1-84) (PTH) increases
bone mass and strength and improves bone quality by stimulating new bone
formation. OBJECTIVE: To determine the safety of PTH and its effect on the
incidence of vertebral fractures in postmenopausal women with osteoporosis.
DESIGN: 18-month, randomized, double-blind, placebo-controlled, parallel-group
study. SETTING: 168 centers in 9 countries. PATIENTS: 2532 postmenopausal women
with low bone mineral density at the hip or lumbar spine. Interventions: Women
received 100 mug of recombinant human PTH or placebo daily by subcutaneous
injection. All received calcium, 700 mg/d, and vitamin D(3),
400 U/d. MEASUREMENTS: New or worsened vertebral fractures (primary outcome)
and changes in bone mineral density and safety (secondary outcomes). RESULTS:
67.2% of patients who received at least 1 dose of the study drug completed the
study. Parathyroid hormone reduced the risk for new or worsened vertebral
fractures, but in sensitivity analyses, the magnitude of the reduction was changed
with assumptions about fracture incidence in patients who did not complete the
study (relative risk assuming no fractures, 0.42 [95% CI, 0.24 to 0.72] [P =
0.001]; relative risk assuming fracture incidence observed in all patients who
completed the trial, 0.60 [CI, 0.36 to 1.00] [P = 0.05]; relative risk assuming
fracture incidence observed in the placebo group, 0.62 [CI, 0.37 to 1.04] [P =
0.07]). Compared with placebo, mean bone mineral density
increased at the spine by 6.9% (CI, 6.4% to 7.4%) and at the hip by 2.1% (CI,
1.7% to 2.5%) but decreased at the forearm in the PTH-treated group.
Parathyroid hormone treatment increased the percentage of participants with hypercalciuria, hypercalcemia,
and nausea by 24% (CI, 20% to 27%), 23% (CI, 21% to 26%), and 14% (CI, 11% to
16%), respectively, compared with placebo. Limitations: Baseline serum PTH and
vitamin D levels were not measured. Many patients discontinued the trial
prematurely. CONCLUSIONS: Parathyroid hormone (1-84) reduced the overall risk
for new or worsened vertebral fracture in postmenopausal women with
osteoporosis. Hypercalciuria, hypercalcemia,
and nausea were more common in women who took the drug. Although the magnitude
of the reduction was sensitive to assumptions about fracture incidence in
patients who did not complete the study, the findings suggest that PTH provides
an alternative therapeutic option for fracture prevention.
Am J Physiol Endocrinol Metab. 2007 Mar 6; [Epub ahead of print
Plasma adiponectin concentration in healthy pre- and
postmenopausal women: relationship with body composition, bone mineral and
metabolic variables.
Centre of Behavioural and
Health Sciences,
The aim of the current investigation was to determine the possible
relationships of fasting adiponectin level with body
composition, bone mineral, insulin sensitivity, leptin
and cardiorespiratory fitness parameters in 153
women. Subjects were classified as premenopausal (n=42; 40.8+/-5.7 yrs) if they
had regular menstrual periods, early postmenopausal (n=49; 56.7+/-3.6 yrs) if
they had been postmenopausal for more than one year but less than seven years
(5.5+/-1.3 yrs), and postmenopausal (n=62; 72.2+/-4.5 yrs) if they had been
postmenopausal for more than seven years. All women studied had a body mass
index (BMI) less than 30 kg/m2. Adiponectin values
were higher (p<0.05) in middle-aged (12.0+/-5.1 microg/ml)
and older (15.3+/-7.3 microg/ml) postmenopausal women
compared to middle-aged premenopausal women (8.4+/-3.2 microg/ml).
Mean plasma adiponectin concentration in total group
of women (n=153) was 12.2+/-6.3 microg/ml, and was
positively related (p<0.05) to age, indices of overall obesity (BMI, body
fat mass) and cardiorespiratory fitness (PWC) values.
In addition, a negative association (p<0.05) between adiponectin
with central obesity (waist-to-hip and waist-to-thigh ratio), fat free mass,
bone mineral (bone mineral content, total and lumbar spine bone mineral
density), leptin and insulin resistance (insulin,
fasting insulin resistance index) values was observed. However, multivariate
regression analysis revealed that only age, fasting insulin resistance index
and leptin were independent predictors of adiponectin concentration. In conclusion, circulating adiponectin concentrations increase with age in normal
weight middle-aged and older women. It appears that adiponectin
is independently related to age, leptin and insulin
resistance values in women across the age span and menstrual status. Key words:
adiponectin, leptin, age,
menopausal status, insulin resistance.
Am J Epidemiol. 2007 Mar 3; [Epub
ahead of print]
Age and
Menopausal Effects of Hormonal Birth Control and Hormone Replacement Therapy in
Relation to Breast Cancer Risk.
Shantakumar S, Terry
M,
Paykin A, Teitelbaum SL, Britton
J,
Moorman
P,
Kritchevsky SB, Neugut AI, Gammon
MD.
Department of Epidemiology, University of North Carolina School of
Public Health, Chapel Hill, NC.
It is unclear whether breast cancer risk varies by age and menopausal
status in relation to use of hormonal birth control (HBC) and hormone
replacement therapy (HRT), taken singly or cumulatively. The authors utilized
data from 1,478 cases and 1,493 controls aged 20-98 years with known menopausal
status, who had participated in a population-based, case-control study
conducted on
Semana del 27 de Febrero al 5 de Marzo 2007
Osteoporos Int. 2007 Feb 28; [Epub ahead of print
Cost-effectiveness
of alendronate in the treatment of postmenopausal
women in 9 European countries - an economic evaluation based on the fracture
intervention trial.
Strom O, Borgstrom F, Sen SS, Boonen S, Haentjens P, Johnell O, Kanis JA.
European Health Economics, Vasagaatn
38 2 tr, SE-111 20,
Treatment with alendronate
(Fosamax(R)) has been shown to significantly reduce
the risk of fragility fractures. Cost-effectiveness of treatment was assessed
in nine European countries in a Markov model and was generally found to be cost
effective in women with a previous spine fracture. INTRODUCTION: Treatment with
alendronate (Fosamax(R))
reduces the risk of osteoporotic fractures at the spine, hip and wrist in women
with and without prevalent vertebral fracture. Cost-effectiveness estimates in
one country may not be applicable elsewhere due to differences in fracture
risks, costs and drug prices. The aim of this study was to assess the
cost-effectiveness of treating postmenopausal women with alendronate
in nine European countries, comprising
Breast
Cancer Res Treat. 2007 Feb 27; [Epub
ahead of print
Unequal risks for
breast cancer associated with different hormone replacement therapies: results
from the E3N cohort study.
Fournier A, Berrino F, Clavel-Chapelon F.
Institut National de la Sante et de la Recherche Medicale ERI 20, Institut Gustave Roussy, 94805, Villejuif,
France,
Large numbers of hormone replacement therapies
(HRTs) are available for the treatment of menopausal symptoms. It is still
unclear whether some are more deleterious than others regarding breast cancer
risk. The goal of this study was to assess and compare the association between
different HRTs and breast cancer risk, using data from the French E3N cohort
study. Invasive breast cancer cases were identified through biennial
self-administered questionnaires completed from 1990 to 2002. During follow-up
(mean duration 8.1 postmenopausal years), 2,354 cases of invasive breast cancer
occurred among 80,377 postmenopausal women. Compared with HRT never-use, use of
estrogen alone was associated with a significant 1.29-fold increased risk (95%
confidence interval 1.02-1.65). The association of estrogen-progestagen
combinations with breast cancer risk varied significantly according to the type
of progestagen: the relative risk was 1.00
(0.83-1.22) for estrogen-progesterone, 1.16 (0.94-1.43) for estrogen-dydrogesterone, and 1.69 (1.50-1.91) for estrogen
combined with other progestagens. This latter
category involves progestins with different
physiologic activities (androgenic, nonandrogenic, antiandrogenic), but their associations with breast cancer
risk did not differ significantly from one another. This study found no
evidence of an association with risk according to the route of estrogen
administration (oral or transdermal/percutaneous). These findings suggest that the choice of
the progestagen component in combined HRT is of
importance regarding breast cancer risk; it could be preferable to use
progesterone or dydrogesterone.
NIH Consens State Sci
Statements. 2006 May 17-19;23(2):1-30
NIH
State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements
and Chronic Disease Prevention.
[No authors listed]
OBJECTIVE: To provide health care providers,
patients, and the general public with a responsible assessment of currently
available data on Multivitamin/Mineral Supplements and Chronic Disease
Prevention. PARTICIPANTS: A non-DHHS, non-advocate 13-member panel included
experts in the fields of food science and human nutrition, biostatistics,
biochemistry, toxicology, geriatric medicine, family medicine, pediatrics and
pediatric endocrinology, cancer prevention, epidemiology, disease prevention
and health promotion, and consumer protection. In addition, 19 experts from
pertinent fields presented data to the panel and conference audience. EVIDENCE:
Presentations by experts and a systematic review of the literature prepared by
The Johns Hopkins University Evidence-based
Pediatrics. 2007 Mar;119 Suppl 2:S131-6
Childhood bone mass
acquisition and peak bone mass may not be important determinants of bone mass
in late adulthood.
National Institutes of Health, CRC 1-3330, 10
Center Dr, MSC 1103, Bethesda, MD 20892-1103.
During childhood and adolescence, bone mass
acquisition occurs primarily through skeletal growth. It is widely assumed that
bone mass acquisition throughout childhood is an important determinant of the
risk of osteoporosis in late adulthood; bone mass is thought to resemble a bank
account in which deposits persist indefinitely. However, several
well-controlled clinical studies suggest that increasing bone mass acquisition
during childhood will have only transient effects. A likely explanation is that
bone mass is governed by a homeostatic system that tends to return to a set
point after any perturbation and, therefore, bone mass depends primarily on
recent conditions, not those in the distant past. Indeed, in an animal model,
we have shown evidence that bone mass acquisition in early life has no effect
on bone mass in adulthood, in part because many areas of the juvenile skeleton
are replaced in toto through skeletal growth.
Therefore, it should not be assumed that alterations in childhood bone mass
acquisition will affect bone mass many decades later in late adulthood. This
issue remains open and the solution may depend on the type of childhood
condition (for example calcium intake versus exercise) and its magnitude,
timing, and duration. To date, both animal studies and clinical studies suggest
that much of the effect of early bone mass acquisition does not persist.
Endocrinology. 2007 Mar 1; [Epub ahead of print]
Altered ovarian
function affects skeletal homeostasis independent of the action of
follicle-stimulating hormone (FSH).
Gao J, Tiwari-Pandey R, Samadfam R, Yang Y, Miao D, Karaplis AC, Sairam MR, Goltzman D.
Department of Medicine,
Osteoporosis is a leading public health
problem. Although a major cause in women is thought to be a decline in
estrogen, it has recently been proposed that follicle-stimulating hormone (FSH)
or follitropin is required for osteoporotic bone
loss. We examined the FSH receptor null mouse (FORKO mouse), to determine if
altered ovarian function could induce bone loss independent of FSH action. By 3
months of age, FORKO mice developed age dependent declines in bone mineral
density and trabecular bone volume of the lumbar
spine and femur, which could be partly reversed by ovarian transplantation.
Bilateral ovariectomy reduced elevated circulating
testosterone levels in FORKO mice, and decreased bone mass to levels
indistinguishable from those in ovariectomized
wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions
in the FORKO mouse. The results indicate that ovarian secretory
products, notably estrogen, and peripheral conversion of ovarian androgen to
estrogen can alter bone homeostasis independent of any bone resorptive
action of FSH.
J Affect Disord. 2007 Feb
27; [Epub ahead of print
Depressive symptoms
during the menopausal transition: The Study of Women's Health Across the Nation (SWAN).
Bromberger JT, Matthews KA, Schott LL, Brockwell S, Avis NE, Kravitz HM, Everson-Rose SA, Gold EB, Sowers M,
Department of Epidemiology, Graduate School of
Public Health, University of Pittsburgh, Pittsburgh, PA, United States.
BACKGROUND: The influence of menopausal status
on depressive symptoms is unclear in diverse ethnic groups. This study examined
the longitudinal relationship between changes in menopausal status and the risk
of clinically relevant depressive symptoms and whether the relationship
differed according to initial depressive symptom level. METHODS: 3302 African
American, Chinese, Hispanic, Japanese, and White women, aged 42-52 years at
entry into the Study of Women's Health Across the
Nation (SWAN), a community-based, multisite longitudinal observational study,
were evaluated annually from 1995 through 2002. Random effects multiple
logistic regression analyses were used to determine the relationship between
menopausal status and prevalence of low and high depressive symptom scores (CES-D
<16 or >/=16) over 5 years. RESULTS: At baseline, 23% of the sample had
elevated CES-D scores. A woman was more likely to report CES-D >/=16 when
she was early peri-, late peri-,
postmenopausal or currently/formerly using hormone therapy (HT), relative to
when she was premenopausal (OR range 1.30 to 1.71). Effects were somewhat
stronger for women with low CES-D scores at baseline. Health and psychosocial
factors increased the odds of having a high CES-D and in some cases, were more
important than menopausal status. LIMITATIONS: We used a measure of current
depressive symptoms rather than a diagnosis of clinical depression. Thus, we
can only make conclusions about symptoms current at annual assessments.
CONCLUSION: Most midlife women do not experience high depressive symptoms.
Those that do are more likely to experience high depressive symptom levels when
perimenopausal or postmenopausal than when
premenopausal, independent of factors such as difficulty paying for basics,
negative attitudes, poor perceived health, and stressful events.
Obstet Gynecol. 2007 Mar;109(3):588-596
Low Dose of Transdermal
Estradiol Gel for Treatment of Symptomatic
Postmenopausal Women: A Randomized Controlled Trial.
Simon JA, Bouchard C, Waldbaum A, Utian W, Zborowski J, Snabes MC.
OBJECTIVE: To investigate safety and efficacy
and identify the lowest effective dose of a new transdermal
estradiol (E2) gel for relief of menopausal symptoms
in a population of postmenopausal women. METHODS: This study was a randomized,
double-blind, placebo-controlled, multicenter, parallel-group study.
Postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d
(n=136), 1.7 g/d (n=142), or 2.6 g/d (n=69) E2 gel or placebo gel (n=137)
topically for 12 weeks. The changes from baseline in hot flush frequency and
severity at 4 and 12 weeks and changes from baseline in vaginal atrophy
symptoms at 12 weeks were examined. RESULTS: With increasing E2 doses, mean
trough serum E2 increased from 17 to 29 pg/mL. By weeks 3-5, E2 gel
reduced moderate-to-severe hot flush rate by at least seven hot flushes per day
(P<.001) and reduced the severity score (P<.01). The numbers needed to
treat for benefit for an 80% and 100% decrease in hot flush number were 3.2 and
6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group. At week 12,
vaginal pH was more acidic and vaginal maturation index more mature compared
with placebo (P<.001). The lowest dose improved most bothersome vulvovaginal atrophy symptoms (P<.05). Estradiol gel was well tolerated at the site of application
and produced no unexpected adverse effects. The 0.87 g/d dose produced fewest
adverse events. CONCLUSION: The 0.87 g/d dose of this new transdermal
E2 gel, which delivers an estimated 0.0125 mg E2 daily, delivered the lowest
effective dose for treatment of vasomotor symptoms and vulvovaginal
atrophy in a population of postmenopausal women.
Obstet Gynecol. 2007 Mar;109(3):581-587.
Unopposed Estradiol Therapy in Postmenopausal Women: Results From Two Randomized Trials.
Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, Hodis HN.
Departments of Obstetrics and
Gynecology,
OBJECTIVE: To estimate the rates of endometrial
hyperplasia, bleeding episodes, and interventions among menopausal women
receiving unopposed oral estradiol or placebo therapy
with ultrasound monitoring over 3 years. METHODS: Two-hundred eighteen healthy
women with intact uteri enrolled in the Estrogen in the Prevention of
Atherosclerosis Trial (EPAT) or the Women's Estrogen-Progestin Lipid-Lowering
Hormone Atherosclerosis Regression Trial (WELL-HART) were randomly assigned to
either 1 mg of micronized 17beta-estradiol (n=96) or placebo (n=122) daily for
up to 3 years in a double-blind fashion. Patients were followed with annual
measurement of endometrial thickness using transvaginal
ultrasonography. Logistic regression was used to
identify predictors of uterine bleeding and endometrial biopsy. RESULTS: Over the
study periods, nine women (9.4% of patients, 95% confidence interval [CI]
3.6-15.2%) in the estradiol group developed
hyperplasia. Eight of the nine cases (88.9%) of hyperplasia were simple without
atypia. Women receiving estradiol
were more likely than those receiving placebo to have at least one episode of
uterine bleeding (67% versus 11% at 3 years, respectively, P<.001). Women in
the estradiol group were also more likely to have an
endometrial biopsy (48% versus 4% at 3 years, P<.001). Among women on estradiol, obesity (body mass index [BMI] greater than 30
kg/m(2)) significantly increased the odds of uterine
bleeding compared with normal-weight patients (BMI 25 or less) (OR 3.7, 95% CI
1.2-11.8). CONCLUSION: Short-term, unopposed estradiol
therapy with gynecologic monitoring may be an option for the treatment of
menopausal symptoms. Menopausal women choosing estradiol
therapy, especially if obese, should anticipate uterine bleeding and the
possibility of an endometrial biopsy.
Maturitas. 2007 Feb
26; [Epub ahead of print]
Assessing
menopausal symptoms among healthy middle aged women with the Menopause Rating
Scale.
Chedraui P, Aguirre W, Hidalgo L, Fayad L.
Universidad Catolica de Santiago de Guayaquil, Guayaquil, Ecuador.
BACKGROUND: The frequency and intensity of
menopausal symptoms within a given population, as assessed by several tools,
vary and depend on several factors among them age, menopausal status, chronic
conditions and socio-demographic profile. OBJECTIVE: Determine the frequency
and intensity of menopausal symptoms as well as associated risk factors among
healthy middle aged Ecuadorian women. DESIGN: In this cross-sectional study
healthy women aged 40 or more, with intact uterus and ovaries, working at the
Mol Endocrinol. 2007
Feb 27; [Epub ahead of print]
Thyroid hormone
excess rather than TSH deficiency induces osteoporosis in hyperthyroidism.
Bassett JH, O'shea PJ, Sriskantharajah S, Rabier B, Boyde A, Howell PG, Weiss RE, Roux JP, Malaval L, et als.
Molecular Endocrinology Group, Division of
Medicine & MRC Clinical Sciences Centre,
Thyrotoxicosis is an important
but under-recognized cause of osteoporosis. Recently, thyroid stimulating
hormone (TSH) deficiency, rather than thyroid hormone excess, has been
suggested as the underlying cause. To investigate the molecular mechanism of
osteoporosis in thyroid disease, we characterized the skeleton in mice lacking
either thyroid hormone receptor alpha or beta (TRalpha(0/0), TRbeta(-/-)). Remarkably, in the presence of normal
circulating thyroid hormone and TSH concentrations, adult TRalpha(0/0) mice had osteosclerosis accompanied by reduced osteoclastic
bone resorption, whereas juveniles had delayed endochondral ossification with reduced bone mineral
deposition. By contrast, adult TRbeta(-/-) mice with elevated TSH and thyroid hormone levels were
osteoporotic with evidence of increased bone resorption,
whereas juveniles had advanced ossification with increased bone mineral
deposition. Analysis of T3 target gene expression revealed skeletal
hypothyroidism in TRalpha(0/0) mice, but skeletal thyrotoxicosis
in TRbeta(-/-) mice. These studies demonstrate that
bone loss in thyrotoxicosis is independent of
circulating TSH levels and mediated predominantly by TRalpha,
thus identifying TRalpha as a novel drug target in
the prevention and treatment of osteoporosis.
Diabetes Care. 2007 Mar;30(3):701-706.
The Effect of
Menopause on the Metabolic Syndrome Among Korean
Women: The Korean National Health and Nutrition Examination Survey, 2001.
Kim HM, Park J, Ryu SY, Kim J.
Department of Preventive
Medicine,
OBJECTIVE: This study examined the effect of
menopausal status on the risk of the metabolic syndrome in Korean women.
RESEARCH DESIGN AND METHODS: Data were obtained from the Korean National Health
and Nutrition Examination Survey of 2001. A total of 2,671 women who did not
receive hormone replacement therapy (1,893 premenopausal women and 778
postmenopausal women) were included in the analysis. The metabolic syndrome was
defined according to the National Cholesterol Education Program Adult Treatment
Panel III. RESULTS: Postmenopausal women had significantly higher mean waist
circumference, systolic blood pressure, pulse pressure, total cholesterol, LDL
cholesterol, and triglyceride levels than premenopausal women after adjusting
for age (P = 0.018, P = 0.001, P < 0.0001, P < 0.0001, P < 0.0001, and
P = 0.006, respectively). Among postmenopausal women, the age-adjusted odds
ratio was 1.61 (95% CI 1.15-2.25) for abdominal obesity, 1.11 (0.76-1.61) for
elevated blood pressure, 1.24 (0.90-1.72) for low HDL cholesterol, 1.28
(0.89-1.83) for high triglycerides, and 1.07 (0.69-1.65) for high fasting
glucose compared with premenopausal women. The multivariate-adjusted odds ratio
for the metabolic syndrome was 1.60 (95% CI 1.04-2.46) among postmenopausal
women compared with premenopausal women. CONCLUSIONS: Postmenopausal status is
associated with an increased risk of the metabolic syndrome independent of
normal aging in Korean women.
Hormones (Athens). 2007 Jan-Mar;6(1):62-70
Subclinical
hyperthyroidism of variable etiology and its influence on bone in
postmenopausal women.
Belaya ZE, Melnichenko GA, Rozhinskaya LY, Fadeev VV, Alekseeva TM, Dorofeeva OK, Sasonova NI, et als.
Objetive. To
evaluate the effects of subclinical hyperthyroidism of variable etiology on
bone mineral density (BMD) and bone metabolism in postmenopausal women.
Design: T he study included data of 88 postmenopausal women classified into
four groups depending on the etiology of subclinical hyperthyroidism: (1) 20
with toxic multinodular goiter without history of
clinical hyperthyroidism; (2) 25 on levothyroxine
suppressive therapy after thyroidectomy due to
differentiated thyroid cancer; (3) 21 with Graves' disease (GD) receiving antithyroid drugs; (4) 22 healthy women matched for age and
duration of menopause. In all subjects biochemical markers of bone turnover and
B MD were determined. Results: B iochemical markers
of bone turnover were significantly higher (p-value =0.001) in all patients
with subclinical hyperthyroidism compared to the control group (group 4). T he
women of group 1 had significantly lower B MD at all regions of the skeleton,
whereas the women of group 3 had significantly lower B MD at T otal Hip (p-value = 0.013) and R adius
T otal (p-value = 0.0003) compared to group 4. No
significant differences in B MD between groups 2 and 4 were detected.
Conclusion: The etiology of subclinical hyperthyroidism influences B MD in
postmenopausal women. Endogenous subclinical hyperthyroidism might be
considered as an additional risk factor for osteoporosis in postmenopausal
women, especially for cortical bone, whereas exogenous subclinical
hyperthyroidism has no effect on BMD.