Selección de Resúmenes de Menopausia
Febrero de 2007
Dr. Juan Enrique Blümel
Semana del 20 al 27 de Febrero
2007
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.
Semana del 31 de Enero al 19
de Febrero 2007
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.