Selección de Resúmenes de Menopausia
Semana del 20 al 27 de Febrero 2007
Dr. Juan Enrique Blümel
Circulation. 2007 Feb 20;115(7):840-5.
Hormone therapy and venous thromboembolism among postmenopausal women:
impact of the route of estrogen administration and progestogens: the ESTHER
study.
Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, Levesque H, Trillot N, Barrellier MT, Wahl D, Emmerich J, Scarabin PY; Estrogen and
Thromboembolism Risk (ESTHER) Study Group.
Inserm
Unit 780, Cardiovascular Epidemiology Section, 94807
BACKGROUND:
Oral estrogen therapy increases the risk of venous thromboembolism (VTE) in
postmenopausal women. Transdermal estrogen may be safer. However, currently
available data have limited the ability to investigate the wide variety of
types of progestogen. METHODS AND RESULTS: We performed a multicenter
case-control study of VTE among postmenopausal women 45 to 70 years of age
between 1999 and 2005 in
Maturitas. 2007 Feb 20;56(2):227-9
The EMAS 2006/2007 update on clinical recommendations on postmenopausal
hormone therapy.
Gompel A, Barlow D, Rozenberg S, Skouby SO; EMAS Executive
Committee.
This new
statement from EMAS presents the findings reported in recent publications from
both WHI trials. In general, the reports do not necessitate a revision of the
current EMAS advice. They provide further insight into the ongoing controversy
around the possibility that hormone therapy (HT) in the form of estrogen (E)
alone or estrogen-progestogen (EP) may influence risk of breast cancer
differently. They confirm that the increase of breast cancer diagnosis under EP
is only significant after a cumulative use of more than 5 years but suggest
that there is no increased risk by E within 10 years.
Ann N Y Acad
Sci. 2006 Dec;1092:341-8
Hormone replacement therapy and cardioprotection: what is good and what
is bad for the cardiovascular system?
Centre for
Clinical and Basic Research, 00163
The
incidence of cardiovascular diseases (CVDs) increases after menopause and at
any age postmenopausal women have a significantly higher incidence of CVD
compared to premenopausal women. Several epidemiological findings suggest the
causative pathogenetic role of ovarian hormone deficiency in the development of
CVD in women. Ovarian hormones have several potential protective effects on the
cardiovascular system and despite several observational studies have shown the
beneficial effect of estrogens and estrogen/progestin associations on CVD, at
the present, after the findings of randomized studies, the effect of hormone
replacement therapy (HRT) in the prevention of CVD is still under debate. The
randomized studies (Heart and Estrogen/Progestin Replacement Study [HERS] and
Women's Health Initiative [WHI]) found largely concordant results with the
observational studies except for the divergent findings about coronary heart
disease (CHD). The discrepancy between the two arms of the WHI study suggests
that two factors, time to initiation of HRT since menopause and
estrogen/progestin associations, are of pivotal importance to explain the
widely divergent findings on the cardiovascular effects of observational studies
and randomized clinical studies. Basic science and animal studies together with
clinical investigations and the results of clinical studies are concordant in
suggesting that a long time since menopause is associated with a reduced
protective effect of estrogens while the unfavorable effects upon coagulation
remain unaltered. In early postmenopausal women, like the ones included in the
observational studies, ovarian hormone replacement may be cardioprotective
because of the responsiveness of the endothelium to estrogens that also buffer
the detrimental effects upon coagulation. In late postmenopausal women ovarian
hormones have either a null effect or even a detrimental effect because of the
predominance of the procoagulant or plaque-destabilizing effects over the
vasoprotective effects. Therefore, HRT has beneficial cardiovascular effects in
younger women while it may have detrimental effect on coagulative balance and
vascular inflammation and has little effect on cardiovascular functions in
older women.
J Bone Miner
Metab. 2007;25(2):142-6. Epub 2007 Feb 26.
Changes in bone resorption markers among Japanese patients with
postmenopausal osteoporosis treated with alendronate and risedronate.
Takada J, Iba K, Imoto K, Yamashita T.
Orthopedic Surgery,
We
compared the abilities of alendronate and risedronate to reduce levels of
urinary cross-1inked N-telopeptides of type I collagen (NTX) in Japanese
postmenopausal women. The patients were randomly divided into two groups
(alendronate, 5 mg/day, n = 61; risedronate, 2.5 mg/day, n = 60). All patients
had taken all medication prescribed for the first month and at least 90% of
that prescribed for each of the following 6 months. Urinary NTX was measured at
baseline, as well as at 1 and 6 months after starting treatment. According to
the guidelines of the Japan Osteoporosis Society, the minimum significant
change (MSC) for urinary NTX is defined as a 35% decrease from baseline and the
cutoff level for a high risk of future fracture is 54.3 nmol bone collagen
equivalent (BCE)/mmol.Cr. The NTX reduction rates at 1 and 6 months were
greater with alendronate than with risedronate, but the difference was not
significant. The rate of patients with a reduction in the MSC at 1 month was
greater with alendronate than with risedronate, but the difference did not
reach significance. Alendronate reduced NTX at 1 month significantly more in
patients with a high risk of fracture than risedronate, but the difference was
no longer significant at 6 months. The rate of MSC did not significantly differ
between the two groups. In conclusion, alendronate decreases bone resorption
markers more obviously and rapidly than risedronate, especially in high risk
for fracture, but not significantly according to the guidelines of the Japan
Osteoporosis Society.
J Bone Miner
Metab. 2007;25(2):122-9. Epub 2007 Feb 26.
Biochemical markers of bone turnover may predict progression to
osteoporosis in osteopenic women: the JPOS Cohort Study.
Iki M, Morita A, Ikeda Y, Sato Y, Akiba T, Matsumoto T, Nishino H, Kagamimori S, Kagawa Y, Yoneshima H; for the JPOS Study
Group.
Department of Public Health, Kinki University School of Medicine,
589-8511,
We
evaluated the value of bone turnover markers, including osteocalcin (OC) and
bone-specific alkaline phosphatase in the serum, and type I collagen C-terminal
telopeptide and free and total deoxypyridinoline (tDPD) in the urine of fasting
patients, in an attempt to predict which osteopenic women [i.e., those with
>/=70% and <80% of the young adult mean (YAM) bone mineral density (BMD)]
would progress to the osteoporosis level of BMD (<70% of YAM). Of the 1153
women without defects in bone metabolism who completed the 3-year follow-up,
147, 161, and 144 women were judged by dual X-ray absorptiometry to be
osteopenic from baseline measurements of BMD in the spine (LS), hip (TH), and
distal radius (DR), respectively. Progression to the osteoporotic level of BMD
was noted for 23.8%, 16.1%, and 12.5% of the subjects with osteopenia of the
LS, TH, and DR, respectively, while most of them were in the lower half of the
osteopenic level of BMD at baseline. Among the subjects in this lower-level
osteopenia category, a significantly higher OC level was observed for the
subjects with osteoporosis progression at the LS than those without. The
subjects with progression at DR showed a significantly higher tDPD level. The
association between OC level and disease progression remained unchanged after
adjustments for age, body size, and BMD at baseline. The subjects in the upper
one-third category of OC levels showed a 6.4 fold greater risk of progression
at LS (95% confidence interval, 1.8-23.1) compared with those in the lower
one-third category after the adjustments for age, body size, and BMD at
baseline. Receiver operating characteristics analysis showed that the area
under the curve was 0.716 for the OC level in the prediction of osteoporosis
progression at LS. The levels of OC and tDPD may be useful in predicting which
osteopenic women will progress to osteoporosis.
Cancer Causes Control. 2007 Feb 24; [Epub
ahead of print]
Cigarette smoking and risk of benign proliferative
epithelial disorders of the breast in the Women's Health Initiative.
Cui Y, Page DL, Chlebowski RT, Hsia J, Allan Hubbell F, Johnson KC, Rohan TE.
Department of Epidemiology and Population Health,
OBJECTIVE:
To investigate the association between cigarette smoking
and risk of benign proliferative epithelial disorders (BPED) of the breast.
METHODS: We used data from an ancillary study of benign breast disease that is
being conducted in the Women's Health Initiative randomized clinical trials
among 68,132 postmenopausal women aged 50-79 at recruitment. After following
the trial participants for an average of 7.8 years, we had ascertained 294
incident cases with atypical hyperplasia and 1,498 incident cases with
non-atypical BPED of the breast. We used Cox proportional hazards models to
estimate hazard ratios for the association between cigarette smoking and risk
of BPED. RESULTS: Smoking measures, including duration of smoking, intensity of
smoking, pack-years of smoking, age at which smoking commenced, and years since
quitting smoking, were not associated with risk of BPED overall or by
histological subtypes. CONCLUSION: The null association between cigarette
smoking and risk of BPED of the breast suggests that the carcinogenic and
antiestrogenic effects of cigarette smoking on the breast might counterbalance
each other and that cigarette smoking might have no overall effects on BPED of
the breast among postmenopausal women.
Int J
Gynaecol Obstet. 2007 Feb 22; [Epub ahead of print]
Retention of ovaries and oxidative stress of surgery.
Kaur G, Mishra S, Kaur A, Sehgal A, Nageswari KS, Prasad R.
Department of Physiology,
OBJECTIVE:
Surgical menopause results in severe menopausal symptoms due to the sudden
withdrawal of estrogen. This study evaluated the impact of surgical menopause
on oxidant and antioxidant status. METHODS: Thirty eight women who underwent
total hysterectomy with or without bilateral salpingo-oophorectomy were
included. Oxidant status was assessed by measuring plasma levels of malondialdehyde
(MDA) and antioxidant status by assessing glutathione (GSH) and estrogen
levels. RESULTS: The levels of MDA were increased in all women, and GSH levels
were significantly decreased in women who underwent hysterectomy alone but
significantly increased in those who also had oophorectomy. Estrogen levels
were increased if the ovaries were retained even in postmenopausal women, while
they were decreased in the women who underwent oophorectomy. CONCLUSION:
Oxidative stress of surgery, as assessed by increased MDA levels, occurred in
all women. After oophorectomy, estrogen levels decreased and GSH levels
increased in both premenopausal and postmenopausal women. The ovaries may
therefore respond to oxidative stress of surgery by increasing estrogen production,
estrogen being a better antioxidant than GSH.
Vasc Health Risk Manag. 2005;1(1):29-40.
Ongoing clinical trials of the pleiotropic effects of
statins.
Clinical Research Institute of
BACKGROUND:
The multiple effects (ie, pleiotropic effects of statins) have received
increasing recognition and may have clinical applicability across a broad range
of cardiovascular and noncardiovascular conditions. OBJECTIVE: To determine the
relevance and significance of ongoing clinical trials of the pleiotropic
effects of statins, focusing on nonlipid effects. METHOD: Ongoing trials were
identified through personal communication, reports presented at scientific
meetings (2000-2004), and queries made to AstraZeneca, Bristol-Myers Squibb Co,
Merck & Co, Novartis, and Pfizer, manufacturers of the currently marketed
statins. Published trials and other source material were identified through
electronic searches on MEDLINE (1990-2003), abstract books, and references
identified from bibliographies of pertinent articles. Eligible studies were the
clinical trials of statins currently under way in which primary or secondary
outcomes included the statins' nonlipid (ie, pleiotropic) effect(s). Data were
extracted and trial quality was assessed by the authors. RESULTS: Of the 22
ongoing trials of the nonlipid effects of statins identified, 10 assessed inflammatory
markers and plaque stabilization, 4 assessed oxidized low density
lipoprotein/vascular oxidant stress, 3 assessed end-stage renal disease, 3
assessed fibrinogen/viscosity, 2 assessed endothelial function, 2 assessed
acute coronary syndrome, 2 assessed aortic stenosis progression, and 1 each
assessed hypertension, osteoporosis, ischemic burden, Alzheimer's disease,
multiple sclerosis, and stroke (outcomes often overlapped). CONCLUSION: Given
the excellent safety and tolerability of statins as a class, full exploration
of their pleiotropic effects has the potential to provide additional benefits
to many patients.
Menopause. 2007 Feb 20; [Epub ahead of print]
Provider management of menopause after the findings of
the Women's Health Initiative.
Rolnick SJ, Jackson J, Kopher R, Defor TA.
HealthPartners Research Foundation, MN and OB/Gyn Department,
HealthPartners Saint Paul Clinic,
OBJECTIVE:: A survey was conducted to determine current provider
behaviors and concerns related to menopause management. DESIGN:: All
gynecology, internal medicine, and family medicine providers (both physicians
and nurse practitioners) within a large Midwestern integrated health system
were surveyed about current approaches to menopause management, frequency and
reasons for hormone therapy (HT) use, approaches to HT discontinuation,
treatments for symptom control, bone mineral density testing, and concerns
related to menopause management. Descriptive statistics and chi-square tests
were performed to examine frequencies and differences based on gender,
specialty, and years in practice. RESULTS:: Overall
the response rate was 58% with providers from owned clinics, with female
providers being the most likely to respond (P < 0.001). Changes in menopause
management included using lower dose hormones (74%), encouraging use for
shorter time periods (73%), and using different modes of delivery (21%). Most
providers (89%) initiate HT use in symptomatic patients, and only 12% initiate
use to prevent symptoms. Patients were most likely to discuss HT with
gynecologists (78% gynecologists vs 64% family medicine providers and 48%
internal medicine providers, P = 0.015). Nearly two thirds of providers (64%)
claimed to order bone mineral density testing frequently. Providers' concerns
related to information on symptom management, alternative and over-the-counter
medications, the risk/benefits of medications, patients'
sexual concerns, and maintaining bone health. CONCLUSIONS::
We found that providers were responsive to current literature, shifting the
agents and dosages they prescribe. Still they are faced with women reporting
symptoms that interfere with their ability to function optimally and must
continue to help women maintain healthy bones.
NIH Consens State Sci Statements. 2005 Mar
23-25;22(1):1-38
NIH State-of-the-Science Conference Statement on
Management of Menopause-Related Symptoms.
[No
authors listed]
OBJECTIVE:
To provide health care providers, patients, and the general public with a
responsible assessment of currently available data on the management of
menopause-related symptoms. PARTICIPANTS: A non-DHHS, nonadvocate 12-member
panel representing the fields of obstetrics and gynecology, general internal
medicine, endocrinology, rheumatology, family and health psychology, geriatric
medicine, health services research, demography, biochemistry, epidemiology,
clinical research, and biostatistics. In addition, 26 experts in fields related
to the conference topic presented data to the panel and to the conference
audience. EVIDENCE: Presentations by experts and a systematic review of the
medical literature prepared by the Oregon Evidence-based
Menopause. 2007 Feb 19; [Epub ahead of print]
The effects of combined raloxifene and oral estrogen
on vasomotor symptoms and endometrial safety.
Stovall DW, Utian W, Gass M, Qu Y, Muram D, Wong M, Plouffe L Jr.
Virginia
Commonwealth University Medical Center, Richmond, VA; Rapid Medical Research,
Inc, Cleveland, OH; Holmes Hospital, Cincinnati, OH; and US Women's Health and
Reproductive Medicine, Lilly Research Laboratories, Eli Lilly and Company,
Indianapolis, IN.
OBJECTIVE:: To compare effects of 52 weeks' treatment with either
raloxifene 60 mg/day alone (RLX) or in combination with 17beta-estradiol 1
mg/day (RLX + E) on vasomotor symptoms (n = 83) and endometrial safety (n= 123)
in postmenopausal women who transitioned from estrogen-progestin therapy.
DESIGN:: In this randomized, double-blind clinical
trial, the frequency of vasomotor symptoms, hot flashes, andnight sweats was
assessed for up to 52 weeks. Endometrial thickness was assessed by transvaginal
ultrasonography at baseline and at 12 and 52 weeks. An exit endometrial biopsy
was performed at study completion or early termination. RESULTS:: The frequency
of vasomotor symptoms, hot flashes, and night sweats was unchanged from
baseline with RLX but was significantly reduced in women treated with RLX + E,
from baseline (all P < 0.001) and the RLX group at 6, 12, 24, 36, and 52
weeks (all P < 0.01). Women in the RLX + E group had significantly increased
endometrial thickness (0.74 +/- 0.28 mm, mean +/- SEM) at 52 weeks, from
baseline and RLX (P < 0.05), with no statistically significant changes in
women treated with RLX. Two women, both in the RLX + E group, had endometrial
hyperplasia (one with atypia) on the exit biopsy. CONCLUSIONS::
In women transitioning from estrogen-progestin therapy, occurrence of vasomotor
symptoms was unchanged from baseline with RLX treatment, but these symptoms
were significantly reduced with combined RLX + E therapy. Signs of endometrial
stimulation were observed in the RLX + E group. Further studies using different
estrogen doses and preparations are needed before concomitant use of raloxifene
with systemic estrogens can be recommended.
Circulation. 2007 Feb 20;115(7):861-71
Estrogen receptor alpha polymorphism and risk of cardiovascular disease,
cancer, and hip fracture: cross-sectional, cohort, and case-control studies and
a meta-analysis.
Kjaergaard AD, Ellervik C, Tybjaerg-Hansen A, Axelsson CK, Gronholdt ML, Grande P, Jensen GB, Nordestgaard BG.
Department of Clinical Biochemistry,
BACKGROUND:
We hypothesized that the estrogen receptor alpha (ESR1) IVS1-397T/C polymorphism
affects high-density lipoprotein cholesterol response to hormone replacement
therapy and risk of cardiovascular disease (CVD), cancer of reproductive
organs, and hip fracture. METHODS AND RESULTS: We studied cross-sectionally
9244 individuals from the Danish general population and followed them up for 23
to 25 years. End points were CVD (ischemic heart disease, myocardial
infarction, angina pectoris, ischemic cerebrovascular disease, ischemic stroke,
other ischemic cerebrovascular disease, venous thromboembolism, deep vein
thrombosis, and pulmonary embolism), cancer of reproductive organs (breasts,
ovaries, uterus, and prostate), and hip fracture. We also studied patients with
ischemic heart disease (n=2495), ischemic cerebrovascular disease (n=856), and
breast cancer (n=1256) versus general population controls. The CC, CT, and TT
genotypes had general population frequencies of 21%, 50%, and 29%,
respectively. Cross-sectionally, genotype did not influence high-density
lipoprotein cholesterol response to hormone replacement therapy. In the cohort
study, there were no differences in risks of CVD, cancer of reproductive
organs, or hip fracture between genotypes. In case-control studies, risk of CVD
did not differ between genotypes; however, the odds ratio for breast cancer in
women with TT versus CC genotypes was 1.4 (95% CI, 1.1 to 1.7). Meta-analysis
in men of 6 previous and the present 2 studies, including 4799 cases and 12,190
controls, showed odds ratios in CC versus CT and TT genotypes for fatal and nonfatal
myocardial infarction of 0.81 (95% CI, 0.59 to 1.12) and 1.08 (95% CI, 0.97 to
1.21). CONCLUSIONS: ESR1 IVS1-397T/C polymorphism does not influence
high-density lipoprotein cholesterol response to hormone replacement therapy or
risk of CVD, most cancers of reproductive organs, or hip fracture.
Circulation. 2007 Feb 20;115(7):855-60
Prehypertension and cardiovascular disease risk in the
Women's Health Initiative.
Hsia J, Margolis KL, Eaton CB, Wenger NK, Allison M, Wu L, LaCroix AZ, Black HR; Women's Health
Initiative Investigators.
Department of Medicine,
BACKGROUND:
Prehypertension is common and is associated with increased vascular mortality.
The extent to which it increases risk of nonfatal myocardial infarction,
stroke, and congestive heart failure is less clear. METHODS AND RESULTS: We
determined the prevalence of prehypertension, its association with other
coronary risk factors, and the risk for incident cardiovascular disease events
in 60,785 postmenopausal women during 7.7 years of follow-up using Cox
regression models that included covariates as time-dependent variables.
Prehypertension was present at baseline in 39.5%, 32.1%, 42.6%, 38.7%, and
40.3% of white, black, Hispanic, American Indian, and Asian women, respectively
(P<0.0001 across ethnic groups). Age, body mass index, and prevalence of
diabetes mellitus and hypercholesterolemia increased across blood pressure
categories, whereas smoking decreased (all P<0.0001). Compared with
normotensive women (referent), adjusted hazard ratios for women with
prehypertension were 1.58 (95% confidence interval [CI], 1.12 to 2.21) for
cardiovascular death, 1.76 (95% CI, 1.40 to 2.22) for myocardial infarction,
1.93 (95% CI, 1.49 to 2.50) for stroke, 1.36 (95% CI, 1.05 to 1.77) for
hospitalized heart failure, and 1.66 (95% CI, 1.44 to 1.92) for any
cardiovascular event. Hazard ratios for the composite outcome with
prehypertension did not differ between ethnic groups (P=0.71 for interaction),
although the numbers of events among Hispanic and Asian women were small.
CONCLUSIONS: Prehypertension is common and was associated with increased risk
of myocardial infarction, stroke, heart failure, and cardiovascular death in
white and nonwhite postmenopausal women. Risk factor clustering was
conspicuous, emphasizing the need for trials evaluating the efficacy of global
cardiovascular risk reduction through primordial prevention.
Ann N Y Acad
Sci. 2006 Dec;1092:158-74
Polycystic ovary syndrome: a multifaceted disease from adolescence to
adult age.
Dipt. Medicina
Interna, Osp. S.Orsola-Malpighi, via Massarenti 9, 40138 Bologna, Italy.
renato.pasquali@unibo.it.
Polycystic
ovary syndrome (PCOS), one of the most common causes of ovulatory infertility,
affects 4-7% of women. Although it was considered that PCOS may have some
genetic component and that clinical features of this disorder may change
throughout a life span, starting from adolescence to postmenopausal age, no
effort has been made to define differences in the phenotype and clinical
presentation according to age. Indeed, it has been widely recognized in the
last decade that several features of metabolic syndrome (MS), particularly
insulin resistance and hyperinsulinemia, are inconsistently present in the
majority of women with PCOS. This represents an important factor in the
evaluation of PCOS throughout life, which implies that PCOS by itself may not
be a hyperandrogenic disorder exclusively related to young and fertile-aged
women, but may also have some health implications later in life. In young women
with PCOS, hyperandrogenism, menses irregularities, and insulin resistance may
occur together, emphasizing the pathophysiological role of excess androgen and
insulin on PCOS. Hyperandrogenism and infertility represent the major
complaints of PCOS in adult fertile age. In addition, obesity and MS may affect
more than half these women. Later in life, it becomes clear that the
association of obesity (particularly the abdominal phenotype) and PCOS renders
affected women more susceptible to develop type 2 diabetes mellitus (T2DM),
with some difference in the prevalence rates among countries, suggesting that
environmental factors are important in determining individual susceptibility.
Little is known about ovarian morphology and androgen production in women with
PCOS after menopause. Some studies found that morphological ultrasonographic
features consistent with polycystic ovaries are very common in postmenopausal
women, and that these features are associated with higher than normal
testosterone levels and metabolic alterations. There is an obvious need for
further research in this area. Identification of major complaints and features
of PCOS during the different ages of an affected woman may help, in fact, to plan
individual therapeutic strategies, and, possibly, prevent long-term chronic
metabolic diseases.
Circulation. 2007 Feb 20;115(7):846-54
Calcium/vitamin D supplementation and cardiovascular
events.
Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, Heckbert SR, Johnson KC, Manson JE, Trevisan M; Women's Health
Initiative Investigators.
Department of Medicine,
BACKGROUND:
Individuals with vascular or valvular calcification are at increased risk for
coronary events, but the relationship between calcium consumption and
cardiovascular events is uncertain. We evaluated the risk of coronary and
cerebrovascular events in the Women's Health Initiative randomized trial of
calcium plus vitamin D supplementation. METHODS AND RESULTS: We randomized
36,282 postmenopausal women 50 to 79 years of age at 40 clinical sites to
calcium carbonate 500 mg with vitamin D 200 IU twice daily or to placebo.
Cardiovascular disease was a prespecified secondary efficacy outcome. During 7
years of follow-up, myocardial infarction or coronary heart disease death was
confirmed for 499 women assigned to calcium/vitamin D and 475 women assigned to
placebo (hazard ratio, 1.04; 95% confidence interval, 0.92 to 1.18). Stroke was
confirmed among 362 women assigned to calcium/vitamin D and 377 assigned to
placebo (hazard ratio, 0.95; 95% confidence interval, 0.82 to 1.10). In
subgroup analyses, women with higher total calcium intake (diet plus
supplements) at baseline were not at higher risk for coronary events (P=0.91
for interaction) or stroke (P=0.14 for interaction) if assigned to active calcium/vitamin
D. CONCLUSIONS: Calcium/vitamin D supplementation neither increased nor
decreased coronary or cerebrovascular risk in generally healthy postmenopausal
women over a 7-year use period.
Ann N Y Acad
Sci. 2006 Dec;1092:349-60
Hormone replacement therapy in breast cancer
survivors.
Xydakis AM, Sakkas EG, Mastorakos G.
It is well
known that women with breast cancer who undergo therapies beyond the surgical
intervention (adjuvant chemotherapy, hormone therapy, or both) often suffer
from the lack of estrogen, manifesting as climacteric symptoms in either
treated premenopausal or postmenopausal women. Although HRT (hormone
replacement therapy) is traditionally viewed as a contraindication in women
with a history of breast cancer, more women are willing to receive HRT for
symptom relief. No observational or retrospective study in breast cancer
survivors (whether in pre- or postmenopausal women) has shown an increased risk
of tumor recurrence or increased mortality associated with HRT use.
Nevertheless, because these studies are retrospective and different in terms of
lymph node status, estrogen receptor (ER) status, and type of HRT used, firm
conclusions on potential HRT use cannot be safely drawn. The few prospective
studies appear controversial possibly due to differences in the studies'
design. A potential scheme for possible HRT use in selected breast cancer
survivors with severe climacteric symptoms is suggested. The duration of HRT
use is debatable because there is insufficient evidence at present. However,
the available data suggest that 3-year and possibly 5-year HRT use may be safe.
In summary, while HRT cannot currently be recommended as first-line therapy, it
may still be of benefit in the management of selected early stage breast cancer
survivors with refractory climacteric symptoms after a well-informed decision
and an individualized risk benefit discussion.
Selección de Resúmenes de Menopausia
Semana del 31 de Enero al 19 de Febrero 2007
Dr. Juan Enrique Blümel
Menopause. 2007 Feb 12
Helping midlife women predict the onset of the final menses: SWAN, the
Study of Women's Health Across the Nation.
Santoro N, Brockwell S, Johnston J, Crawford SL, Gold EB, Harlow SD, Matthews KA, Sutton-Tyrrell K.
From the
1Albert Einstein College of Medicine, New York, NY; 2University of Pittsburgh,
Pittsburgh, PA; 3University of Massachusetts Medical Center, Boston, MA;
4University of California Davis, Davis, CA; and 5University of Michigan, Ann
Arbor, MI.
OBJECTIVE:: Women approaching menopause often ask their doctors,
"When are my periods going to end?" The objective of this study was
to predict time to the final menstrual period (FMP). DESIGN::
This multiethnic, observational cohort study, the Study of Women's Health
Across the Nation, has been ongoing since 1996. Data collected from seven
annual study visits were used. The community-based cohort from seven national
sites included 3,302 white, African American, Hispanic, Chinese, and Japanese
women aged 42 to 52 years at baseline with a uterus and at least one ovary, who
were not pregnant or taking reproductive hormones, and had at least one
menstrual period within the past 3 months at baseline. The time to the FMP was
defined retrospectively after 12 months of amenorrhea. Uni- and multivariable
Cox proportional hazard models, hazard ratios (HRs), and 95% CIs were computed
for variables of interest. RESULTS:: A total of 2,662
women, of whom 706 had an observed FMP, were included. Age, menstrual cycles
that had become farther apart (HR = 2.56, 95% CI = 1.94-3.39) or more variable
(HR = 1.79, 95% CI = 1.45-2.21), and current smoking (HR = 1.68, 95% CI =
1.35-2.08) were all associated with shorter time to the FMP. Higher (log)
follicle-stimulating hormone (HR = 2.32, 95% CI = 2.02-2.67) was related to a
shorter time to the FMP, but the highest estradiol category (>/=100 pg/mL
[367 pmol/L]) was associated with an earlier onset of the FMP (HR = 2.16, 95%
CI = 1.63-2.89). The number of vasomotor symptoms was related to an earlier
FMP, whereas higher physical activity and educational levels were associated
with a later FMP. CONCLUSIONS:: Age, menstrual cycle recall, smoking status,
and hormone measurements can be used to estimate when the FMP will occur,
allowing for more precise estimates for older midlife women: in the most
extreme cases, ie, age 54, high estradiol level, current smoking, and high
follicle-stimulating hormone level, the FMP can be estimated to within 1 year.
Maturitas. 2007 Feb 8; [Epub ahead of print]
Perceptions and attitudes toward the menopause among middle aged women
from
Leon P, Chedraui P, Hidalgo L, Ortiz F.
Ecuadorian Climacteric & Menopause Society (SECLIM-Nucleo Guayas), Guayaquil, Ecuador; Escuela de Graduados, Facultad de Ciencias Medicas, Universidad de Guayaquil, Guayaquil, Ecuador.
BACKGROUND:
Studies reporting the perspective of Latin American women,
Clin
Endocrinol (Oxf). 2007 Mar;66(3):394-8.
Association of endogenous sex hormone with C-reactive protein levels in
middle-aged and elderly men.
Pour HR, Grobbee DE, Muller M, van der Schouw YT.
Background In women, postmenopausal oestrogen supplementation increases levels of systemic
markers of inflammation, which are important predictors of coronary heart
disease (CHD) risk. Whether endogenous sex hormone levels in men are also
related to systemic subclinical inflammation is still unknown. Objective We tested the hypothesis that higher endogenous sex hormones
levels within the physiological range may be associated with systemic
subclinical inflammation. Methods Circulating sex
hormone and high-sensitivity C-reactive protein (hs-CRP) levels were determined
in 400 apparently healthy men aged between 40 and 80 years. We used
multivariate linear regression analysis with the various sex hormones as
determinant, and natural log hs-CRP as outcome. Results Higher
levels of total as well as bioavailable oestradiol (E2) were associated with
increased natural log hs-CRP levels, which remained statistically significant
after adjustment for age and cardiovascular risk factors. Natural log hs-CRP
was 0.26 mg/l higher [95% confidence interval (CI) -0.02 to 0.54] in the fourth
than in the first quartile of total E2; the P-value for linear trend was 0.05.
For bioavailable E2, the difference in natural log hs-CRP between the fourth
and the first quartile was 0.30 mg/l (95% CI 0.03-0.56; P-value for linear
trend 0.04). After adjustment for age and cardiovascular risk factors,
physiological levels of total (TT) or bioavailable testosterone or
dehydroepiandrosterone sulfate (DHEAS) were not associated with hs-CRP.
Conclusion Endogenous total and bioavailable E2 levels are significantly
associated with CRP among middle-aged and elder men.
Cancer
Epidemiol Biomarkers Prev. 2007 Feb;16(2):236-43
Lifetime Recreational and Occupational Physical
Activity and Risk of In situ and Invasive Breast Cancer.
Sprague BL, Trentham-Dietz A, Newcomb PA, Titus-Ernstoff L, Hampton JM, Egan KM.
Numerous
studies have observed reduced breast cancer risk with increasing levels of
physical activity, yet these findings have been inconsistent about optimal
times of activity and effect modification by other factors. We investigated the
association between recreational and occupational physical activity and breast
cancer risk in a population-based case-control study in
Br J Cancer. 2007 Feb 13; [Epub ahead of print]
Oral progestagens before menopause and breast cancer risk.
Fabre A, Fournier A, Mesrine S, Desreux J, Gompel A, Boutron-Ruault MC, Clavel-Chapelon F.
1INSERM
(Institut National de la Sante et de la Recherche Medicale), ERI 20, Institut
Gustave Roussy, 39, rue Camille Desmoulins, F-94805 Villejuif, Cedex, France.
We
examined the relationship between use of progestagen-only before menopause
(except for mini-pills) after the age of 40 and invasive breast cancer risk in
73 664 women from the French E3N cohort study (mean age at start of follow-up,
51.8 years; mean duration of follow-up, 9.1 years). A total of 2390 cases of
invasive breast cancer were diagnosed during follow-up. Risk estimates were
calculated using the Cox proportional hazard model. Overall, ever use of
progestagen before menopause was not significantly associated with risk
(relative risk (RR): 1.01, 95% confidence interval: 0.93-1.11). However, we
observed a significant increase in risk associated with the duration of use
(P-value for trend: 0.012), current use of progestagens for longer than 4.5
years being significantly associated with risk (RR: 1.44, 95% confidence
interval: 1.03-2.00). Prolonged use of progestagens after the age of 40 may be
associated with an increased risk of breast cancer and the subject needs to be investigated
further.
J Clin Endocrinol Metab. 2007 Feb 13; [Epub
ahead of print]
Relationship of obesity with osteoporosis.
Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR, Deng HW.
Departments
of Orthopedic Surgery and Basic Medical Science, School of Medicine, University
of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108; Osteoporosis
Research Center, Creighton University Medical Center, Omaha, NE 68131;
Laboratory of Molecular and Statistical Genetics, College of Life Sciences,
Hunan Normal University, Changsha, Hunan 410081, P. R. China; The Key
Laboratory of Biomedical Information Engineering of Ministry of Education and
Institute of Molecular Genetics, School of Life Science and Technology, Xi'an
Jiaotong University, Xi'an 710049, P. R. China.
Context:
The relationship between obesity and osteoporosis has been widely studied, and
epidemiological evidence shows that obesity is correlated with increased bone
mass. Previous analyses, however, did not control for the mechanical loading
effects of total body weight on bone mass and may have generated a confounded
or even biased relationship between obesity and osteoporosis. Objective: To
re-evaluate the relationship between obesity and osteoporosis by accounting for
the mechanical loading effects of total body weight on bone mass. Methods: We
measured whole body fat mass, lean mass, percentage fat mass (PFM), body mass
index (BMI), and bone mass in two large samples of different ethnicity: 1,988
unrelated Chinese subjects and 4,489 Caucasian subjects from 512 pedigrees. We
first evaluated the Pearson correlations among different phenotypes. We then
dissected the phenotypic correlations into genetic and environmental
components, with bone mass unadjusted, or adjusted, for body weight. This
allowed us to compare the results with and without controlling for mechanical
loading effects of body weight on bone mass. Results: In both Chinese and
Caucasians, when the mechanical loading effect of body weight on bone mass was
adjusted for, the phenotypic correlation (including its genetic and
environmental components) between fat mass (or PFM)
and bone mass was negative. Further multivariate analyses in subjects
stratified by body weight confirmed the inverse relationship between bone mass
and fat mass, after mechanical loading effects due to total body weight was
controlled. Conclusions: Increasing fat mass may not have a beneficial effect
on bone mass.
Cancer Causes Control. 2007 Feb 12; [Epub
ahead of print]
Anthropometric factors and risk of endometrial cancer: the European
prospective investigation into cancer and nutrition.
Friedenreich C, Cust A, Lahmann PH, Steindorf K, Boutron-Ruault MC, Clavel-Chapelon F, Mesrine S, Linseisen J, Rohrmann S, Boeing H, Pischon T, Tjonneland A, Halkjaer J, Overvad K, Mendez M, Redondo ML, Garcia CM, Larranaga N, Tormo MJ, Gurrea AB, Bingham S, Khaw KT, Allen N, Key T, Trichopoulou A, Vasilopoulou E, Trichopoulos D, Pala V, Palli D, Tumino R, Mattiello A, Vineis P, Bueno-de-Mesquita
HB,
Peeters PH, Berglund G, Manjer J, Lundin E, Lukanova A, Slimani N, Jenab M, Kaaks R, Riboli E.
Division of Population Health and Information,
OBJECTIVE:
To examine the association between anthropometry and endometrial cancer,
particularly by menopausal status and exogenous hormone use subgroups. METHODS:
Among 223,008 women in the European Prospective Investigation into Cancer and
Nutrition (EPIC) study, there were 567 incident endometrial cancer cases during
6.4 years of follow-up. The analysis was performed with Cox proportional
hazards modeling. RESULTS: Weight, body mass index (BMI), waist and hip
circumferences and waist-hip ratio (WHR) were strongly associated with
increased risk of endometrial cancer. The relative risk (RR) for obese (BMI 30-
< 40 kg/m(2)) compared to normal weight (BMI <
25) women was 1.78, 95% CI = 1.41-2.26, and for morbidly obese women (BMI
>/= 40) was 3.02, 95% CI = 1.66-5.52. The RR for women with a waist
circumference of >/=88 cm vs. <80 cm was 1.76, 95% CI = 1.42-2.19. Adult
weight gain of >/=20 kg compared with stable weight (+/-3 kg) increased risk
independent of body weight at age 20 (RR = 1.75, 95% CI = 1.11-2.77). These
associations were generally stronger for postmenopausal than premenopausal
women, and oral contraceptives never-users than ever-users, and much stronger
among never-users of hormone replacement therapy compared to ever-users.
CONCLUSION: Obesity, abdominal adiposity, and adult weight gain were strongly
associated with endometrial cancer risk. These associations were particularly
evident among never-users of hormone replacement therapy.
J Bone
Miner Res. 2007 Feb 12; [Epub ahead of print]
Effect of Blockade of Tumor Necrosis Factor-alpha and
Interleukin-1 Action on Bone Resorption in Early Postmenopausal Women.
Charatcharoenwitthaya N, Khosla S, Atkinson EJ, McCready LK, Riggs BL.
Microabstract
After acute estrogen withdrawal in postmenopausal women, administration of
anakinra or etanercept, specific blockers of IL-1 and TNF-alpha, respectively,
reduced the rise in bone resorption markers to about half of that in controls.
This is consistent with an important role for these immune cytokines in
mediating the effect of estrogen deficiency on bone.
Fertil
Steril. 2007 Feb 9; [Epub ahead of print]
Ovulation in a postmenopausal woman.
Department
of Obstetrics, Gynecology, and Women's Health, New Jersey Medical School,
University of Medicine and Dentistry New Jersey, Newark, New Jersey.
OBJECTIVE:
To report the first documented case of ovulation in a postmenopausal woman.
DESIGN: Case study. SETTING: University reproductive endocrinology and
infertility clinic. PATIENT(S): A 57-year-old woman, who had been
postmenopausal for 3 years and presented with breast tenderness and was found
to have laboratory and ultrasound evidence of ovulation. INTERVENTION(S):
Laboratory evaluation and transvaginal ultrasound. MAIN OUTCOME MEASURE(S):
Ovulation in a postmenopausal woman. RESULT(S): Laboratory evaluations revealed
estrogen and progesterone consistent with an ovulatory pattern. Ultrasound
revealed a thickened endometrium and a corpus luteum, both of which resolved
after menses. CONCLUSION(S): This is the first report of ovulation in a
postmenopausal woman. This observation opens the door to new questions about
the sensitivity of the hypothalamic-pituitary-ovarian axis in menopause as well
as about ovarian senescence.
Bone. 2007 Jan
4; [Epub ahead of print]
Incidence of hip fracture over a 10-year period (1991-2000): Reversal of
a secular trend.
Chevalley T, Guilley E, Herrmann FR, Hoffmeyer P, Rapin CH, Rizzoli R.
Service of Bone Diseases and Geriatric Evaluation Unit, Department of
Rehabilitation and Geriatrics,
INTRODUCTION:
Hip fractures are a major cause of burden associated with osteoporosis in terms
of mortality, disability, and costs. With the ageing of the population, a
marked increase in the number of fractures is expected. Furthermore, many
studies reveal an increase of the age-adjusted hip fracture incidence. We
specifically examined secular changes in the incidence of hip fracture in women
and men aged 50 years and over in the well-defined area of
Maturitas. 2007 Feb 8; [Epub ahead of print
Hormone replacement therapy and risk for coronary heart disease Data
from the CORA-study-A case-control study on women with incident coronary heart
disease.
Windler
E, Zyriax BC, Eidenmuller B, Boeing H.
Center of
Internal Medicine, University Hospital Hamburg-Eppendorf, Martinistrasse 52,
D-20246 Hamburg, Germany.
BACKGROUND:
Hormone replacement therapy (HRT) has been suggested to prevent cardiovascular
disease, while some intervention studies have shed doubt on this concept. Thus,
uncertainty remains whether current HRT use is beneficial as to cardiovascular
disease or may even be harmful. OBJECTIVES: This
research investigates the association of hormone replacement therapy, risk factors
and lifestyle characteristics with the manifestation of coronary heart disease
in current HRT users versus never users. DESIGN: The coronary risk factors for
atherosclerosis in women study (CORA-study) provide clinical and biochemical
parameters and data on lifestyle in 200 consecutive pre- and postmenopausal
women with incident coronary heart disease compared to 255 age-matched
population-based controls, of which 87.9% were postmenopausal. RESULTS:
Significantly more controls than cases used currently HRT for a median of 9.5
years (32.9% versus 20.2%), while 50.0% of cases and 42.5% of controls had
never used HRT (p<0.02). Compared to women who never used HRT, current users
ate less meat and sausage, had a significantly lower BMI and waist-to-hip ratio
and a lower prevalence of hypertension, insulin resistance and diabetes.
However, current users among cases were often smokers and smoked significantly
more cigarettes than never users. In a multivariate analysis the risk of
current HRT users for coronary artery disease was 57% lower than the risk of
never users (odds ratio 0.428, CI 0.206-0.860, p<0.02). Adjustment for
conventional and dietary risk factors revealed neither current HRT use, nor HRT
use combined with smoking as independent risk factors. CONCLUSIONS: These data
from the CORA-study are not compatible with an adverse impact of hormone
replacement therapy on cardiovascular disease, rather support the notion of
beneficial effects of HRT on weight, central adiposity, insulin sensitivity and
blood pressure. Yet, the data do not support the presumption of a general
healthy user effect in women on HRT either. Rather, in some women adverse
lifestyle habits, especially intense smoking, appear to counteract possible
beneficial effects of HRT.
Menopause. 2007 Feb 6; [Epub ahead of print]
High prevalence of vitamin D deficiency in Chilean healthy
postmenopausal women with normal sun exposure: additional evidence for a
worldwide concern.
Gonzalez G, Alvarado JN, Rojas A, Navarrete C, Velasquez CG, Arteaga E.
From the
1Department of Endocrinology, 2Department of Public Health, and 3Clinical
Laboratories, School of Medicine, Pontificia Universidad Catolica de Chile,
OBJECTIVE:: To assess the prevalence of vitamin D deficiency in
healthy postmenopausal women with normal sun exposure but without vitamin D
fortification in their diets. DESIGN:: We studied 90
healthy ambulatory women who were residents of
Psychosom
Med. 2007 Feb 8; [Epub ahead of print]
Associations Between Depressive Symptoms and
Inflammatory/Hemostatic Markers in Women During the Menopausal Transition.
Matthews KA, Schott LL, Bromberger J, Cyranowski J, Everson-Rose SA, Sowers MF.
Department
of Psychiatry (K.A.M., J.B., J.C), the Department of Epidemiology (K.A.M.,
J.B., L.L.S.), and the Department of Psychology (K.A.M.), University of
Pittsburgh, Pittsburgh, Pennsylvania; the Department of Preventive Medicine and
Behavioral Sciences (S.A.E.-R.), Rush University Medical Center, Chicago,
Illinois; and the Department of Epidemiology (M.F.S.), University of Michigan,
Ann Arbor, Michigan.
Objective:
To test whether depressive symptoms are related to inflammatory and hemostatic
markers in women approaching menopause. Methods: A total of 3292 women enrolled
in the Study of Women's Health Across the Nation (SWAN) were followed for five
years and had measures of Center for Epidemiologic Studies-Depression and high
sensitivity C-reactive protein, Factor VIIc, fibrinogen, plasminogen activator
inhibitor Type 1(PAI-1), and tissue-type plasminogen activator antigen (tPA-ag)
up to four times during the follow-up period. Women were pre- or early
perimenopausal status at study entry and were of Caucasian, African American,
Hispanic, Japanese, or Chinese race/ethnicity. Results: Unadjusted longitudinal
mixed regression models showed that over a 5-year period, higher depressive
symptoms were related to higher fibrinogen, PAI-1, and tPA-ag levels, all p
< .0001. Taking into account health history, medication use, ethnicity,
aging, and menopausal status, the depressive symptoms were related to
fibrinogen, p < .01, and PAI-1, p < .05. Depressive symptoms were related
only to fibrinogen in models that also included body mass index, p < .05.
Conclusions: Depressive symptoms may be associated with cardiovascular risk in
perimenopausal women in part through hypercoagulability. This is the first
study to test the association of depressive symptoms and hemostatic and
inflammatory markers across time.
Adv Ther. 2006 Nov-Dec;23(6):926-37.
Effects of tibolone on abdominal subcutaneous fat, serum leptin levels,
and anthropometric indices: a 6-month, prospective, randomized,
placebo-controlled, double-blind study.
Odabasi AR, Yuksel H, Kafkas S, Demircan S, Karul A, Kozaci D, Koseoglu K, Onur E.
Department of Obstetrics and Gynecology,
This study
was undertaken to evaluate the effects of tibolone on abdominal subcutaneous
fat, serum leptin levels (SLLs), and anthropometric indices, and to investigate
potential relationships between SLLs, subcutaneous abdominal fat thickness, and
anthropometric indices in postmenopausal women. In a 6-mo, prospective,
randomized, double-blind, placebo-controlled study, 40 healthy postmenopausal
women aged 42 to 67 y (mean: 50+/-4.7 y) were randomly assigned to 1 of 2
groups; during a 6-mo treatment period, the first group received tibolone
(Livial(R) tablet; Organon, The Netherlands; 2.5 mg/d; n=19) and the other
group was given placebo (n=21). Fasting SLLs determined by enzyme-linked
immunosorbent assay, subcutaneous abdominal fat thickness assessed by
ultrasound, and anthropometric indices of body weight, body mass index, waist
and hip circumference, and waist-to-hip ratio (WHR) were recorded at the
beginning and the end of the study. Statistical analyses were performed with
Mann-Whitney, Wilcoxon, and Spearman tests. P values <.05 were considered
significant. No significant differences between the 2 groups were reported in
terms of all baseline characteristics. After 6 mo, body weight (+0.77+/-0.43
kg) and SLLs (+14.7+/-6.4 ng/mL) increased in the placebo control group,
whereas waist circumference (-2.6+/-3.0 cm), hip circumference (-3.6+/-3.5 cm),
and subcutaneous abdominal fat thickness (-4.3+/-4.8 cm) decreased
significantly in the tibolone group (P<.05). At the end of the study, group
comparisons revealed significant differences in waist and hip circumference and
subcutaneous abdominal fat thickness (P<.05). At baseline, SLLs were
correlated with subcutaneous abdominal fat thickness and all anthropometric
indices except WHR (P<.05). Subcutaneous abdominal fat thickness was also
highly correlated with all indices except WHR (P<.0001). Tibolone was found
to decrease waist and hip circumference, as well as subcutaneous abdominal fat
thickness. Also, tibolone appeared to attenuate weight gain and leptin
increase. SLLs and subcutaneous abdominal fat thickness were positively
correlated with all anthropometric indices except WHR.
Ann N Y Acad Sci. 2006 Nov;1089:302-23.
Estrogen action in neuroprotection and brain inflammation.
Pozzi S, Benedusi V, Maggi A, Vegeto E.
Center of Excellence on Neurodegenerative Diseases, Department of Pharmacological Sciences, University of Milan, Via Balzaretti, 9, 20133 Milan, Italy.
The
fertile period of women's life compared to menopause is associated with a lower
incidence of degenerative inflammatory diseases. In brain, estrogens ameliorate
brain performance and have positive effects on selected neural pathologies
characterized by a strong inflammatory component. We thus hypothesized that the
inflammatory response is a target of estrogen action; several studies including
ours provided strong evidence to support this prediction. Microglia, the
brain's inflammatory cells, and circulating monocytes express the estrogen
receptors ER-alpha and ER-beta and their responsiveness in vivo and in vitro to
pro-inflammatory agents, such as lipopolysaccharide (LPS), is controlled by
17beta-estradiol (E(2)). Susceptibility of central nervous system (CNS)
macrophage cells to E(2) is also preserved in animal
models of neuroinflammatory diseases, in which ER-alpha seems to be
specifically involved. At the molecular level, induction of inflammatory gene
expression is blocked by E(2). We recently observed
that, differently from conventional anti-inflammatory drugs, E(2) stimulates a
nongenomic event that interferes with the LPS signal transduction from the
plasma membrane to cytoskeleton and intracellular effectors, which results in
the inhibition of the nuclear translocation of NF-kappaB, a transcription
factor of inflammatory genes. Interference with NF-kappaB intracellular
trafficking is selectively mediated by ER-alpha. In summary, evidence from
basic research strongly indicates that the use of estrogenic drugs that can
mimic the anti-inflammatory activity of E(2) might
trigger beneficial effects against neurodegeneration in addition to carrying
out their specific therapeutic function.