Selección de Resúmenes de Menopausia
Enero de 2007
Dr. Juan Enrique Blümel
Semana del 24 al 30 de
Enero 2007
Am J Pathol. 2007 Feb;170(2):427-35.
Osteoclasts: what
do they do and how do they do it?
Department of Pathology and Immunology, Washington
University School of Medicine, Campus Box 8118, 660 South Euclid Ave., St.
Louis, MO 63110. teitelbs@wustl.edu.
As Americans live longer, degenerative skeletal
diseases, such as osteoporosis, become increasingly prevalent. Regardless of
cause, osteoporosis reflects a relative enhancement of osteoclast
activity. Thus, this unique bone resorptive cell is a
prominent therapeutic target. A number of key observations provide insights
into the mechanisms by which precursors commit to the osteoclast
phenotype and how the mature cell degrades bone. The osteoclast
is a member of the monocyte/macrophage family that
differentiates under the aegis of two critical cytokines, namely RANK ligand and M-CSF. Tumor necrosis factor (TNF)-alpha also
promotes osteoclastogenesis, particularly in states
of inflammatory osteolysis such as that attending
rheumatoid arthritis. Once differentiated, the osteoclast
forms an intimate relationship with the bone surface via the alphavbeta3 integrin, which transmits matrix-derived,
cytoskeleton-organizing, signals. These integrin-transmitted
signals include activation of the associated proteins, c-src,
syk, Vav3, and Rho GTPases.
The organized cytoskeleton generates an isolated microenvironment between the
cell's plasma membrane and the bone surface in which matrix mineral is
mobilized by the acidic milieu and organic matrix is degraded by the lysosomal protease, cathepsin K.
This review focuses on these and other molecules that mediate osteoclast differentiation or function and thus serve as
candidate anti-osteoporosis therapeutic targets.
Atherosclerosis. 2007 Jan 23; [Epub ahead of print]
Ethnic
differences in the ability of triglyceride levels to identify insulin
resistance.
Clinical Endocrinology Branch, National
Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of
Health, Bethesda, MD 20892, United States.
The Metabolic Syndrome is used to predict the
onset of coronary artery disease and Type 2 diabetes. As the predictive value
of the Metabolic Syndrome has been challenged, alternative syndromes have been
developed. All of these syndromes were developed in populations that were
predominantly non-Hispanic white (NHW). They include the Enlarged Waist
Elevated Triglyceride Syndrome, the Overweight-Lipid Syndrome and the Hypertriglyceridemic Waist Syndrome. The first applies to
postmenopausal women, the second to overweight individuals (BMI>/=25kg/m(2)), and the third to men. Each syndrome uses hypertriglyceridemia as a criterion. However, the
definition of hypertriglyceridemia varies by syndrome
i.e. TG>/=128mg/dL for the Enlarged Waist Elevated
Triglyceride Syndrome, TG>/=130mg/dL for the
Overweight-Lipid Syndrome, >/=150mg/dL for the
Metabolic Syndrome, and TG>/=176mg/dL for the Hypertriglyceridemic Waist Syndrome. Insulin resistance and
hypertriglyceridemia are highly correlated. But as
insulin resistant non-Hispanic blacks (NHB) often have triglyceride (TG) levels
below the thresholds set by these syndromes, the ability of either TG or these
syndromes to identify high risk NHB is unknown. Using the National Health and
Nutrition Examination Survey (NHANES) 1999-2002, our goals were to determine by
ethnicity: (1) the prevalence of each of these syndromes; (2) the ability of
fasting TG concentrations to identify insulin resistance at cut-off levels
established by these syndromes, specifically 130, 150 and 176mg/dL. Participants were 2804 adults from NHANES 1999-2002.
The cohort was divided into tertiles of homeostasis
model assessment. Insulin resistance was defined as the upper tertile (>/=2.73). The prevalence of each syndrome was
lower in NHB than NHW or Mexican Americans (MA) (all P<0.05). Mean TG levels
in NHB, non-Hispanic Whites (NHW) and Mexican Americans (MA) were: 99, 140 and
144mg/dL, respectively. The mean percents of
insulin-resistant NHB, NHW and MA with TG<130mg/dL
were: 64, 31 and 36. The percents of insulin-resistant NHB, NHW and MA with
TG<150mg/dL were: 75, 46 and 47. The percents of
insulin-resistant NHB, NHW and MA with TG<176mg/dL
were: 81, 58 and 59. Significance was P<0.001 for each comparison to NHB. In
conclusion, the prevalence of syndromes that use TG as a diagnostic criterion
is lower in NHB than NHW or MA. NHB are more likely than NHW or MA to be
insulin-resistant and have TG levels below threshold values. As syndromes are
formulated to identify individuals at high risk for conditions such as
cardiovascular disease and Type 2 diabetes, ethnic differences in TG levels
should be considered.
Fertil Steril. 2007 Jan
23; [Epub ahead of print]
Postmenopausal
virilization after spousal use of topical androgens.
Maimonides Medical Center, Brooklyn.
OBJECTIVE: To increase awareness of the
potential to cause virilization in postmenopausal
woman secondary to a spouse's use of topical androgen. DESIGN: Case report.
SETTING: University-affiliated teaching hospital. PATIENT(S): A 63-year-old
postmenopausal woman with virilization.
INTERVENTION(S): Removal of the source of androgen exposure. MAIN OUTCOME
MEASURE(S): Regression of the biochemical and physical signs of androgen excess
in a woman after cessation of T gel use by her partner, and reinitiation
of use with precautions against potential methods of transfer. RESULT(S): This
case highlights the unintentional transdermal
absorption of testosterone sufficient to induce virilization
in a couple who were aware of this potential problem. The apparent source of
androgen absorption was a washcloth that the couple shared. The diagnosis can
be established with a detailed history and a few blood tests (total and free T,
and DHEAS) to exclude other sources of androgens. CONCLUSION(S): This report
reinforces the need to consider exogenous androgen exposure in the differential
diagnosis of virilization in adults when the more
common causes have been excluded.
Menopause. 2007 Jan
23; [Epub ahead of print
Effects of the phytoestrogen genistein on hot
flushes, endometrium, and vaginal epithelium in
postmenopausal women: a 1-year randomized, double-blind, placebo-controlled
study.
D'Anna R, Cannata ML, Atteritano M, Cancellieri F, Corrado F, Baviera G, Triolo O, Antico F, Gaudio A, Frisina N, Bitto A, Polito F, Minutoli L, Altavilla D, Marini H, Squadrito F.
From the 1Department of Obstetrical and Gynaecological Sciences, 2Department of Internal Medicine,
3Department of Clinical and Experimental Medicine and Pharmacology, Section of
Pharmacology, and 4Department of Biochemical, Physiological and Nutritional
Sciences, Section of Physiology and Human Nutrition, University of Messina,
Messina, Italy.
OBJECTIVE:: To
evaluate in a 12-month, prospective, randomized, double-blind,
placebo-controlled study whether pure administration of the phytoestrogen
genistein (54 mg/d) might reduce the number and
severity of hot flushes in postmenopausal women with no adverse effect on the endometrium. DESIGN:: A total of
389 participants met the main study criteria and were randomly assigned to
receive the phytoestrogen genistein
(n = 198) or placebo (n = 191). About 40% of participants in both groups did
not suffer from hot flushes, and the evaluation was performed in a subgroup of
247 participants (genistein, n = 125; placebo, n =
122). Reductions from baseline in the frequency and severity of hot flushes
were the principal criteria of efficacy. Endometrial thickness was evaluated by
ultrasonography. The maturation value was also used
to determine hormonal action on the vaginal cells. RESULTS::
There were no significant differences in age, time since menopause, body mass
index, and vasomotor symptoms between groups at baseline (4.4 +/- 0.33 hot
flushes per day in the genistein group and 4.2 +/-
0.35 hot flushes per day in the control group). The effect was already evident
in the first month and reached its peak after 12 months of genistein
therapy (-56.4% reduction in the mean number of hot flushes). Furthermore,
there was a significant difference between the two groups at each evaluation
time (1, 3, 6, and 12 months). No significant difference was found in mean
endometrial thickness and maturation value score between the two groups, either
at baseline or after 12 months. CONCLUSIONS:: The phytoestrogen genistein has been
shown to be effective on vasomotor symptoms without an adverse effect on endometrium.
Circ J. 2007 Feb;71(2):191-5
Characterization
of subclinical thyroid dysfunction from cardiovascular and metabolic
viewpoints.
Takashima N, Niwa Y, Mannami T, Tomoike H, Iwai N.
Department of Epidemiology,
National Cardiovascular Center.
Background Subclinical hypothyroidism, defined
as high serum thyroid-stimulating hormone (TSH) levels and normal serum free-triiodothyronine (fT3) and serum free-thyroxine
(fT4) levels, is a common medical problem among the elderly, but it is unclear
whether it should be treated with thyroid hormone replacement therapy. Methods
and Results A cross-sectional study of 3,607
participants in a community health survey in
Adv Clin Chem. 2007;43:211-27
Estrogen
hydroxylation in osteoporosis.
Napoli N, Armamento-Villareal R.
Division of Bone and Mineral
Diseases,
Estrogen is metabolized predominantly via two
competing pathways, the 2-hydroxyl (nonestrogenic)
and the 16alpha-hydroxyl (estrogenic) pathways. Studies have indicated that
these pathways are important determinants of bone mineral density (BMD) in
postmenopausal women. Women with predominant metabolism through the 2-hydroxyl
pathway have accelerated postmenopausal bone loss and lower BMD compared to
those with predominant 16alpha-hydroxylation who are protected from bone loss. Increased
2-hydroxylation has been observed in women with a positive family history of
osteoporosis suggesting that the increased risk of osteoporosis in those with
family history may, in part, be related to inherited differences in estrogen
metabolism. Polymorphisms in the cytochrome P450
(CYP450) enzymes that metabolize estrogen are believed to result in alteration
in the activity of these enzymes leading to differences in estrogen
hydroxylation. It is the resulting "estrogen tone" generated from the
variable accumulation of metabolic products with divergent estrogenic activity
that has been hypothesized to modify the risks for hormone-dependent disorders
associated with these polymorphisms, for example, osteoporosis. In support of
this notion is the finding of lower BMD in women with the A allele for the
C4887A polymorphism of the CYP1A1 gene, who are found to have accelerated rate
of estrogen hydroxylation. These findings may have broader clinical
significance as recent data indicate that women with predominance of the
2-hydroxyl pathway appear to have better BMD response to estrogen/hormone
replacement therapy (ERT/ HRT) compared to those with predominant
16alpha-hydroxylation. It is likely that individual responses to ERT/HRT may
vary according to patterns of estrogen hydroxylation, in turn a result of
varying activity of the different CYP450 enzyme variants, thus, allowing the
future possibility of identifying responders by genetic and/or metabolic
profiling.
Chin Med Sci J. 2006 Dec;21(4):214-8
Evaluation of neuroprotective effects of long-term low dose hormone
replacement therapy on postmenopausal women brain hippocampus using magnetic
resonance scanner.
Hu L, Yue Y, Zuo PP, Jin ZY, Feng F, You H, Li ML, Ge QS.
Department of Radiology, Peking Union Medical
College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing 100730. huling_pumch@hotmail.com
OBJECTIVE: To investigate the effects of
long-term low dose hormone replacement therapy (HRT) on postmenopausal women in
hormone level, cognition score, hippocampus volume, and magnetic resonance
spectroscopy (MRS) parameters. METHODS: A total of 182 postmenopausal women
aged 50-87 years were chosen at
Int J Vitam Nutr Res. 2006 Sep;76(5):307-13
Vitamin
d status in patients with osteopenia or osteoporosis
- an audit of an endocrine clinic.
Kocjan T, Tan TM, Conway GS, Prelevic G.
Department of Endocrinology,
University Medical Centre,
Vitamin D deficiency and insufficiency may
further increase fracture risk in patients with decreased bone mineral density.
We audited serum 25-hydroxyvitamin D (25OHD) concentrations in patients with osteopenia or osteoporosis attending endocrine osteoporosis
clinics in
Menopause. 2007 Jan
19; [Epub ahead of print]
Searching
for polycystic ovary syndrome in postmenopausal women: evidence of a
dose-effect association with prevalent cardiovascular disease.
Krentz AJ, von Muhlen D, Barrett-Connor E.
From the Division of Epidemiology, Department
of Family and Preventive Medicine, University of California San Diego, La
Jolla, CA.
OBJECTIVE:: To test
the hypothesis that polycystic ovary syndrome (PCOS) is associated with an
increased risk of atherosclerotic cardiovascular disease (CVD) in older
postmenopausal women. DESIGN:: Cross-sectional study
of community-dwelling non-estrogen-using postmenopausal-white women (N = 713;
mean +/- SD age, 73.8 +/- 7.9 years; mean body mass index, 24.0 +/- 3.5 kg/m)
participating in the Rancho Bernardo Study. A putative PCOS phenotype was
defined as the presence of three or more of the following features: (1)
recalled history of irregular menses, (2) symptomatic premenopausal hyperandrogenism or biochemical evidence of current
biochemical hyperandrogenism, (3) history of
infertility or miscarriage, (4) central obesity, or (5) insulin resistance.
Atherosclerotic CVD was determined from clinical history, electrocardiography,
and structured interviews using validated techniques. The analysis was
stratified by diabetes status, ascertained from medical history or 75-g oral
glucose tolerance tests. RESULTS:: The PCOS phenotype
was present in 9.3% of the entire cohort and 5.8% of nondiabetic
women. The prevalence of CVD was similar between women with the phenotype and
unaffected women (27.3% vs 24.4%). Among women with
intact ovaries and no diabetes, there was a stepwise graded association between
an increasing number of features of the PCOS phenotype (ie,
none to three or more) and prevalent CVD (P = 0.02). A similar association was
also observed for coronary heart disease alone (P = 0.03). CONCLUSIONS:: Among nondiabetic
postmenopausal women with intact ovaries, prevalent atherosclerotic CVD is
associated with features of a putative PCOS phenotype. This finding supports
the thesis that PCOS increases the risk of atherosclerotic CVD after menopause.
J Clin Endocrinol Metab. 2007 Jan 23; [Epub ahead of print
Endogenous
Sex Hormones and Glucose Tolerance Status in Post-menopausal Women.
Golden SH, Dobs AS, Vaidya D, Szklo M, Gapstur S, Kopp P, Liu K, Ouyang P.
Departments of Medicineand
Epidemiology, Johns Hopkins University, Baltimore, MD; Divisions of
Endocrinology, Metabolism and Molecular Medicine and Department of Preventive Medicine,Feinberg School of Medicine, Northwestern
University, Chicago, IL.
Context: In post-menopausal women, endogenous estradiol (E2) and free testosterone (T) have been
positively associated with glucose intolerance and type 2
diabetes. Most studies have not examined these associations in a large
group of post-menopausal women. Objective: Our objective was to examine the
association between endogenous sex hormones and glucose tolerance in
post-menopausal women. Design, Setting, and Participants: This was a
cross-sectional study of 1,973 post-menopausal women ages 45-84 years, not
taking hormone replacement therapy, in the Multi-Ethnic Study of
Atherosclerosis baseline examination. Main Outcome Measures: Impaired fasting
glucose (IFG) and diabetes were defined based on fasting blood sugar and/or
treatment for diabetes. In women with normal glucose tolerance, insulin
resistance was estimated using homeostasis model assessment of insulin
resistance (HOMA-IR). Results: Increasing quartiles of bioavailable
T and E2 and decreasing quartiles of sex hormone binding globulin (SHBG) were
associated with significantly increased odds of IFG and diabetes (all p for
trend <0.001). Except for the association of bioavailable
T with diabetes, the other associations persisted following multivariable
adjustment. While higher dehydroepiandrostenedione
(DHEA) was associated with a greater odds of IFG (p for trend=0.02), it was not
associated with diabetes. Among 1,100 women with normal glucose tolerance, E2
and DHEA were positively associated and SHBG was inversely associated with
HOMA-IR (all p<0.001) following multivariable adjustment. Bioavailable T was associated with HOMA-IR (p<0.001) but
not fasting glucose. Conclusion: Among post-menopausal women, endogenous bioavailable T, E2, and DHEA were positively, and SHBG
negatively associated with insulin resistance.
Atherosclerosis. 2007 Jan 18; [Epub ahead of print
Low levels of adiponectin predict worsening of arterial morphology and
function.
Stork S, Bots ML, Angerer P, von Schacky C, Grobbee DE, Angermann CE, Seufert J.
Department of Medicine I/Center of
Cardiovascular Medicine, University of Wurzburg, Germany; Julius Center for
Health Sciences and Primary Care, University Medical Center Utrecht, The
Netherlands.
Adipocytokines are under
investigation as mediators of cardiovascular risk. In 142 non-diabetic
postmenopausal women, we investigated whether plasma levels of adiponectin and leptin are
associated with changes in carotid intima-media
thickness (IMT) and distensibility as assessed by
high-resolution ultrasound. Adiponectin but not leptin correlated weakly with baseline measures of IMT and distensibility. After 12 months, carotid IMT showed a
significant progression [0.023mm (95% CI, 0.014-0.031mm)] whereas stiffness was
unaltered. A threshold was identified for the relation of adiponectin
with both progression of IMT and stiffness. Age-adjusted adiponectin
levels in the lowest quartile versus second to fourth quartile were related to
progression of IMT (odds ratio, 2.99; 95% CI, 1.81-5.09) and stiffness (odds
ratio, 1.71; 95% CI, 1.19-4.07). Adjustment for
possible confounding factors and intermediates weakened this association only
to a minor degree. No such associations were observed for leptin.
We conclude that low levels of adiponectin are
associated with adverse changes in morphology and function of central arteries
over time independently of other cardiovascular risk factors in postmenopausal
non-diabetic women.
Menopause. 2007 Jan
17; [Epub ahead of print
Decline
in use of hormone therapy among postmenopausal women in the
Menon U, Burnell M, Sharma A, Gentry-Maharaj A, Fraser L, Ryan A, Parmar M, Hunter M, Jacobs I; for the UKCTOCS
Group.
From the 1Department of Gynaecological
Oncology, UCL Institute for Women's Health, London, UK; 2MRC Cancer Trials,
University College London, London, UK; and 3Department of Psychology, Institute
of Psychiatry, Kings College London, Guy's Campus, London, UK.
OBJECTIVE:: There has
been controversy about the results of the Women's Health Initiative and the
Million Women Study and uncertainty about their impact on hormone therapy (HT)
use. This study documents recent trends in HT use in postmenopausal women in
the
Bone. 2007 Jan
19; [Epub ahead of print
The
association between serum thyroid-stimulating hormone in its reference range
and bone status in postmenopausal American women.
Evidence suggests that hyperthyroidism
adversely affects bone, but the condition is rare and probably contributes
little to postmenopausal osteoporosis. Subclinical hyperthyroidism, which can
result from treatment with L-thyroxine, is more
common, but its relationship to osteoporosis and fracture is uncertain. A
recent study of healthy, postmenopausal Koreans with no history of thyroid
disease reported associations between both below-normal and low-normal
circulating thyroid-stimulating hormone (TSH) levels and osteoporosis. These
findings raise the hypothesis that variation in thyroid function, or TSH
itself, affects bone in normal women. In the present research, we used data
collected in the third U.S. National Health and Nutrition Examination Survey to
examine associations between TSH, as it varies over its reference range, and
bone status in healthy, postmenopausal American women. In some analyses, we
used osteoporosis and osteopenia defined according to
World Health Organization guidelines as the outcome variable. In others, we
used bone mineral density (BMD) as a continuum. After adjustment for age,
race/ethnicity, body mass index, serum T(4), estrogen replacement therapy,
smoking, and physical activity level, the odds ratios (95% CI) relating TSH
between 0.39 and 1.8 mIU/L (the median of the
reference range) versus TSH between 1.8 and 4.5 to osteoporosis and osteopenia were 3.4 (95% CI, 1.3-9.2) and 2.2 (1.2-3.8),
respectively. Furthermore, BMD increased significantly as TSH increased over
its reference range in both black and white women. After multivariate
adjustment, least-square mean BMD for non-Hispanic white women in the bottom
serum TSH quintile category was 0.79 g/cm(2) (95% CI,
0.76-0.82), as compared to 0.83 g/cm(2) (95% CI, 0.8-0.85) for those in the top
quintile category. Least-square mean BMD (95% CI) for non-Hispanic black women
in the bottom serum TSH quintile category was 0.85 g/cm(2)
(95% CI, 0.81-0.89). For non-Hispanic black women in the top quintile category,
least-square mean BMD was 0.94 g/cm(2) (95% CI,
0.88-0.99). These results may reflect the existence of clinically significant
thyroid hyperfunction in women with serum TSH in the
reference range. Alternatively, TSH itself may play a role in the preservation
of bone after menopause.
Semana del 17 al 23 de Enero
2007
J Sex Med. 2007 Jan;4(1):204-8.
Transdermal
Testosterone Gel prn Application for Hypoactive
Sexual Desire Disorder in Premenopausal Women: A Controlled Pilot Study of the
Effects on the Arizona Sexual Experiences Scale for Females and Sexual Function
Questionnaire.
Chudakov B, Ben Zion IZ, Belmaker RH.
Faculty of Health Sciences,
Introduction. Several studies
suggest that increased plasma testosterone can improve sexual function and
desire in post-oophorectomy or postmenopausal women.
However, side effects of chronic daily testosterone raise questions about the generalizability of this treatment approach. Sublingual
testosterone was reported to cause testosterone levels to peak after 15 minutes
and then decline to baseline levels within 90 minutes. Three to 4 hours after
reaching testosterone peak, increased genital sensations and sexual lust were
reported. Aim. We hypothesized that a singe dose of testosterone given 4-8 hours prior to planned
intercourse in women with hypoactive sexual desire disorder (HSDD) might
increase desire without side effects associated with chronic use. Methods. The design was randomized double-blind crossover.
Premenstrual women with HSDD received eight packets of gel or identical placebo
for use before intercourse twice weekly for 1 month. For a second month, the
alternate treatment was given. Main Outcome Measures.
Ratings were performed using the patient-rated Arizona Sexual Experiences Scale
for females and the clinician-rated Sexual Function Questionnaire (SFQ-V1). Results. Ten patients completed the study. On the five-item
self-report Arizona, the item "How easily are you aroused?" was
significantly improved on testosterone gel vs. placebo, P = 0.03. There were similar
trends on the physician-rated SFQ-V1 "arousal-sensation" cluster. Conclusions. These preliminary results suggest that
testosterone gel given prn before intercourse has
effects on sexual arousal, and further research is needed to define dosage and
time schedule to optimize this effect and determine its clinical relevance.
Acta Obstet Gynecol Scand. 2007;86(1):61-4.
Primary
hyperparathyroidism is common in postmenopausal women with forearm fracture and
low bone mineral density.
Bergstrom I, Landgren BM, Freyschuss B.
Department of Endocrinology,
Metabolism and Diabetes.
Objective. The most common
etiologies of osteoporosis in women are estrogen deficiency and, later on in
life, the functional changes caused by aging. There are, however, numerous
causes of secondary bone loss. Little is known about the prevalence of
concomitant disease in women with distal forearm fracture, which is the most
common of the classical osteoporotic fractures. Method.
Postmenopausal healthy women between 45 and 65 years of age with a forearm
fracture were invited to join a prospective randomized study evaluating the
effect of physical training on bone mineral density. The main inclusion
criteria were previous forearm fracture and BMD T-score in the interval -1 to
-3.0. Of the 167 postmenopausal women with a forearm fracture, 23% had a normal
BMD, 59% had osteopenia, and 18% had osteoporosis. Results. Of the 119 patients meeting the BMD criteria for
inclusion, one patient was found to have sprue, two
were diagnosed with thyreotoxicos, and eight had
primary hyperparathyroidism. The prevalence of primary hyperparathyroidism in
this population was 6.7%, and thus three times higher than that previously
observed in healthy Swedish postmenopausal women. Conclusion.
The data suggest an increased prevalence of primary hyperparathyroidism in
women with forearm fracture and low bone mass, and imply the importance of
basic laboratory screening in this population.
Ann Oncol. 2007 Jan 17; [Epub
ahead of print]
Venlafaxine is
superior to clonidine as treatment of hot flashes in
breast cancer patients--a double-blind, randomized study.
Loibl S, Schwedler K, von Minckwitz G, Strohmeier R, Mehta K, Kaufmann M.
Department of Obstetrics and
Gynecology,
BACKGROUND: Classical hormone replacement
therapy for hot flashes is contraindicated in breast cancer especially in
endocrine responsive disease. PATIENTS AND METHODS: In a double-blind,
randomized phase III study, breast cancer patients suffering from hot flashes
at least twice a day, who were not taking any medication against hypertension
and depression received either clonidine 0.075 mg
twice a day or venlafaxine 37.5 mg twice a day for 4
weeks. The primary end point was defined as the frequency of hot flashes after
4 weeks of treatment. A self-reported 1-week hot flash and other symptom
questionnaire were kept before the start of treatment until the end of
treatment course. RESULTS: From April 2002 to October 2004, 80 patients were recruited
of whom 64 were assessable for efficacy analyses. Thirty-three received clonidine and 31 venlafaxine,
nine patients stopped early because of side-effects and seven withdrew consent.
At the end of treatment week 4, the median hot flash frequency dropped by 7.6
hot flashes per day for patients receiving venlafaxine
and 4.85 hot flashes per day for those receiving clonidine
(P = 0.025). CONCLUSION: Venlafaxine is significantly
more effective in reducing the frequency of hot flashes in breast cancer patients
than clonidine.
Maturitas. 2007 Jan
13; [Epub ahead of print
Endometrial
safety after 5 years of continuous combined transdermal
estrogen and intrauterine levonorgestrel delivery for
postmenopausal hormone substitution.
Wildemeersch D, Pylyser K, De Wever N, Pauwels P, Tjalma W.
Contrel
Research,
OBJECTIVE: To investigate endometrial histology
and thickness of the endometrium after long-term use
of continuous transdermal estrogen substitution
combined with intrauterine release of levonorgestrel
(LNG) in postmenopausal women. DESIGN: A 5-year non-comparative prospective
clinical trial. SUBJECTS: Out of 182 symptomatic postmenopausal women using
estrogen substitution therapy (EST) combined with a novel T-shaped
LNG-releasing intrauterine system (Femilistrade mark
Slim LNG-IUS), to prevent endometrial proliferation and bleeding, only those
women (n=102) who used two consecutive LNG-IUSs, were isolated with the aim to
study the long-term effects on the endometrium. The
mean age of the women was 57 years (range 47-71). The majority of women
received percutaneous 17beta estradiol,
1.5mg daily, or an equivalent dose by patch or orally, on a continuous basis.
MAIN OUTCOME MEASURES: Endometrial histology and ultrasonographic
evidence of endometrial suppression, after a period of approximately 5 years of
use. The mean duration of use of the regimen was 70 months (range 25-98).
RESULTS: The dominant endometrial histologic picture
was that of inactive endometrium characterized by
glandular atrophy and stroma decidualization
(Kurman classification 5b). No cases of endometrial
hyperplasia were found. On transvaginal ultrasound,
this corresponds with a thin endometrium (</=5mm).
CONCLUSION: The results of this 5-year study in 102 postmenopausal women using
EST demonstrates that the LNG-IUS effectively opposes the estrogenic effect on
the endometrium resulting in strong suppression
during the entire period of EST. Due to its high efficacy and absence of
systemic effects on organ tissues (e.g., breasts), target delivery in the
uterine cavity could be a preferred route to administer a progestagen
in women using EST.
Osteoporos Int. 2007 Jan 17; [Epub ahead of print
Hepatotoxicity induced
by alendronate therapy.
Department of Physical
Medicine and Rehabilitation,
Here we describe a 47-year-old postmenopausal
woman who had been taking alendronate 70 mg/week for
osteoporosis. After two months of alendronate
therapy, she developed hepatotoxicity, and no other
etiological factors for this besides the alendronate
were apparent. After the alendronate therapy was
discontinued, the patient's hepatic enzyme levels slowly returned to normal. Hepatotoxicity due to alendronate
therapy is a rare but possible adverse effect.
Menopause. 2007 Jan
11; [Epub ahead of print
Effect
of ultra-low-dose transdermal estradiol
on breast density in postmenopausal women.
Grady D, Vittinghoff E, Lin F, Hanes V, Ensrud K, Habel LA, Wallace R, Macer J, Cummings SR, Shepherd J.
From the 1University of California, San
Francisco, San Francisco, CA; 2San Francisco Veterans Affairs Medical Center,
San Francisco, CA; 3Berlex, Inc., Wayne, NJ; 4Minneapolis VA Medical Center and
University of Minnesota, Minneapolis, MN; 5Northern California Kaiser
Permanente, Division of Research, Oakland, CA; 6University of Iowa College of
Public Health, Iowa City, IA; and 7California Pacific Medical Center Research
Institute, San Francisco, CA.
OBJECTIVE:: Women with
higher mammographic breast density have increased risk for breast cancer, and
there is some evidence that a change in breast density may be a marker for
change in risk for breast cancer. The purpose of this study was to determine
whether 2 years of treatment with ultra-low-dose transdermal
estradiol results in a change in breast density.
DESIGN:: The Ultra-Low-dose Transdermal
Estradiol Assessment was a randomized, blinded,
placebo-controlled trial of 2 years of treatment with unopposed ultra-low-dose
(0.014 mg/d) transdermal estradiol
for prevention of osteoporosis in 417 postmenopausal women with no history of
breast cancer who had not had a hysterectomy. We obtained mammograms at
baseline and after 1 and 2 years of treatment from 276 of the participants.
Right craniocaudal views were analyzed at a central
radiology facility by a trained clinician blinded to treatment group and order
of acquisition. Contour analysis was performed to define dense areas versus
fatty tissue. Between-group differences in mean change in percent breast
density from baseline to 1 and to 2 years of follow-up were assessed using
linear regression models adjusted for clinical site. RESULTS::
Participants were 66 +/- 5 years old and 94% were white. The average percent
breast density at baseline was 34%. There was no significant difference between
treatment groups in change in percent breast density after 1 year (between-group
difference, 0.1%; 95% confidence interval, -1.3% to 1.6%) or 2 years of
treatment (0.8%; -0.6% to 2.1%). CONCLUSIONS:: Two
years of treatment with ultra-low-dose transdermal estradiol did not increase breast density.
Menopause. 2007 Jan
11; [Epub ahead of print
Efficacy
of citalopram on climacteric symptoms.
Kalay AE, Demir B, Haberal A, Kalay M, Kandemir O.
Department of Obstetrics and
Gynecology, Alanya Sifa,
OBJECTIVE:: The aim of
this study was to evaluate the efficacy of citalopram
for climacteric symptoms and to assess the combined effect of citalopram and hormone therapy (HT) on climacteric symptoms
in women inadequately responsive to HT alone. DESIGN::
The study included 100 postmenopausal women who were allocated into one of four
groups: (1) citalopram, (2) placebo, (3) citalopram + HT, or (4) placebo + HT. The women who were
unable or unwilling to take HT were randomly placed in groups 1 and 2. The
women who were inadequately responsive to HT were randomly placed in groups 3
and 4. The initial dose of citalopram was 10 mg/day
in groups 1 and 3. After 1 week, the dose was increased to 20 mg/day. After
starting the medication, follow-up visits took place during the fourth and
eighth weeks of treatment. During the first and eighth weeks, women completed
two questionnaires: a modified Kupperman index and
the Menopause-Specific Quality of Life Questionnaire. RESULTS::
Mean hot flash scores significantly improved in all groups (P < 0.05). The
reduction rates were 37% in group 1, 13% in group 2, 50% in group 3, and 14% in
group 4. Psychosocial complaints and mean values on the Kupperman
index significantly decreased in all groups (P < 0.05). Physical well-being
significantly improved in groups 1, 3, and 4 (P < 0.05). The decrease in all
scores was significantly greater in groups 1 and 3 compared to groups 2 and 4
(P < 0.01). CONCLUSION:: Citalopram
is an effective alternative treatment option for patients who do not want to
take HT for the alleviation of climacteric symptoms. Adjuvant treatment with a
selective serotonin reuptake inhibitor increases the effectiveness of HT for
the treatment of climacteric symptoms in women who had responded inadequately
to HT.
Menopause. 2007 Jan
11; [Epub ahead of print]
Randomized,
placebo-controlled trial of the effects of drospirenone-estradiol
on blood pressure and potassium balance in hypertensive postmenopausal women
receiving hydrochlorothiazide.
Preston RA, Norris PM, Alonso AB, Ni P, Hanes V, Karara AH.
Department of Medicine,
OBJECTIVE:: Drospirenone (DRSP), a spironolactone
analog with aldosterone antagonist activity, is a
novel progestogen developed for use as hormone
therapy in postmenopausal women in combination with 17beta-estradiol (E2).
DRSP/E2 lowers blood pressure when used alone in hypertensive postmenopausal
women or when administered concomitantly with angiotensin-converting
enzyme inhibitors or angiotensin receptor blockers.
DRSP/E2 has not been studied in combination with the widely prescribed
hydrochlorothiazide (HCTZ). We investigated the effects of 3 mg DRSP/1 mg E2
versus placebo on blood pressure and potassium balance when added to existing
therapy with 25 mg HCTZ in postmenopausal women with established stage I hypertension. DESIGN:: This was a single-center,
double-blind, randomized, placebo-controlled, two-treatment, two 4-week
treatment period crossover study in 36 postmenopausal women with stage I
hypertension maintained on 25 mg HCTZ. The endpoint was a change from baseline
in systolic and diastolic blood pressures by 24-hour ambulatory blood pressure
monitoring. Safety monitoring included serum potassium (mEq/L)
and adverse events. RESULTS:: Mean systolic and
diastolic blood pressures by 24-hour ambulatory blood pressure monitoring were
reduced significantly, by -7.2 and -4.5 mm Hg, respectively, with DRSP/E2 as
compared with placebo. The decrease in potassium with HCTZ was 0.2 mEq/L less with DRSP/E2 than placebo,
suggesting a potassium-sparing effect. The most frequently observed
adverse events with DRSP/E2 were vaginal bleeding and breast tenderness, which
were attributable to the hormone therapy. CONCLUSIONS::
DRSP/E2 substantially lowers systolic and diastolic blood pressure when added
to existing antihypertensive therapy with HCTZ in hypertensive postmenopausal
women. In addition, DRSP/E2 has a potassium-sparing effect that counteracts
HCTZ-induced potassium loss.
Menopause. 2007 Jan
11; [Epub ahead of print
Preferential
prescribing of tibolone and combined estrogen plus progestogen therapy in postmenopausal women.
Velthuis-Te Wierik EJ, Hendricks PT, Martinez C.
V. Organon,
OBJECTIVE:: To verify
whether tibolone is preferentially prescribed to
women at an increased risk for endometrial and breast cancer compared with
women who were prescribed combined estrogen + progestogen
therapies, including sequential conjugated equine estrogens/norgestrel,
sequential conjugated equine estrogens/medroxyprogesterone
acetate, continuous conjugated equine estrogens/medroxyprogesterone
acetate, or continuous 17beta-estradiol/norethisterone
acetate. DESIGN:: This was a descriptive study using
the General Practice Research Database, a
Menopause. 2007 Jan
11; [Epub ahead of print
Effects
of estradiol with oral or intravaginal
progesterone on risk markers for breast cancer in a postmenopausal monkey
model.
Wood CE, Sitruk-Ware RL, Tsong YY, Register TC, Lees CJ, Cline JM.
Pathology/Section on Comparative
Medicine,
OBJECTIVE:: To
evaluate the effects of oral estradiol given with
either oral or intravaginal micronized progesterone
(P4) on risk biomarkers for breast cancer in a postmenopausal monkey model.
DESIGN:: This experiment was a two-way crossover study in which 20 ovariectomized adult female cynomolgus
macaques were treated (in equivalent doses for women) with oral estradiol (1 mg/d) + oral micronized P4 (200 mg/d) or intravaginal P4 delivered by Silastic
rings (6- to 10-mg/d release rate). Hormone treatments lasted 2 months and were
separated by a 1-month washout period. The primary outcome measure was breast
epithelial proliferation. RESULTS:: Serum P4
concentrations were significantly greater in subjects receiving oral P4 (10.9 ng/mL) compared with intravaginal P4 (3.8 ng/mL) at 2 to 3 hours after oral dosing (P < 0.0001) but
not at 24 to 28 hours after oral dosing (2.9 ng/mL for oral P4 vs 3.2 ng/mL for intravaginal
P4 at 2 months, P = 0.19). Serum estradiol
concentrations were significantly lower after oral P4 than after intravaginal P4 (P < 0.05 for all time points). Oral P4
resulted in significantly decreased body weight (-2.5%) compared with intravaginal P4 (+3.6%) (P = 0.0001). Markers of breast
proliferation, sex steroid receptor expression, and endometrial area did not
differ significantly between oral P4 and intravaginal
P4 treatments (P > 0.1 for all). CONCLUSIONS::
Despite different pharmacodynamic profiles, oral and intravaginal P4 had similar effects on biomarkers in the
postmenopausal breast.
Menopause. 2007 Jan
11; [Epub ahead of print
Endogenous androgen
levels and cardiovascular risk profile in women across the adult life span.
Bell RJ, Davison SL, Papalia MA, McKenzie DP, Davis SR.
From the 1Women's Health Program, Department of
Medicine, Central and Eastern Clinical School, Monash
University, Alfred Hospital, Prahran, Victoria,
Australia;2The Jean Hailes Foundation, Clayton,
Victoria, Australia; 3Department of Biochemistry, Monash
University, Clayton, Victoria, Australia; and 4Department of Epidemiology and
Preventive Medicine, Central and Eastern Clinical School, Monash
University, Alfred Hospital, Prahran, Victoria,
Australia.
OBJECTIVE:: Whether
endogenous androgen levels contribute to the cardiovascular disease (CVD) risk
profile in women is controversial. The purpose of this study was to investigate
systematically the relationships between serum levels of endogenous androgens
and sex hormone-binding globulin (SHBG) and biochemical CVD risk profile,
taking other known risk factors into account. DESIGN::
This community-based cross-sectional study included 587
non-healthcare-seeking-women, aged 18 to 75 years, who were randomly recruited
from the community via the electoral roll from April 2002 to August 2003.
Participants were euthyroid; had no usage of
exogenous steroids; had no history of tubal ligation, hysterectomy, or
bilateral oophorectomy; and did not have hyperprolactinemia or polycystic ovarian syndrome. The
relationships between total testosterone, SHBG, free testosterone, dehydroepiandrosterone sulfate, and androstenedione
and high-sensitivity C-reactive protein (CRP) and lipids were explored using
linear regression with natural logarithm (ln) -or
square root-transformed data as indicated. Issues of nonlinearity and
interaction were addressed by the inclusion of extra regression terms where
appropriate. We determined the change in the proportion of variation for each
marker of the CVD risk profile explained by the addition of each hormone term
to the models, having adjusted for age, body mass index, smoking, alcohol, and
exercise. RESULTS:: Menopausal status did not influence the statistical models
for high-sensitivity CRP and high-density lipoprotein cholesterol, but for both
low-density lipoprotein cholesterol and triglycerides, the proportion of
variation explained by the models was substantially less in postmenopausal than
in premenopausal women. Almost all of the highly statistically significant
findings were related to the addition of the SHBG terms to the models. The
changes in r values were highly statistically significant for the addition of
the SHBG terms to the models for ln CRP and ln high-density lipoprotein for both pre- and
postmenopausal women (P </= 0.01 and < 0.001, respectively) and for ln triglycerides in postmenopausal (P < 0.001) and
premenopausal women (P < 0.01). CONCLUSIONS::
Endogenous testosterone and the adrenal preandrogens
per se are not significant independent determinants of circulating
high-sensitivity CRP or lipoprotein lipids. Our analyses provide further
support for the independent predictive value of low SHBG levels for CVD risk
profile and an independent contribution of the menopausal transition to the
determination of low-density lipoprotein cholesterol and triglycerides.
Menopause. 2007 Jan
11; [Epub ahead of print
Levonorgestrel-releasing
intrauterine system as an adjunct to estrogen for the treatment of menopausal
symptoms-a review.
Peled Y, Perri T, Pardo Y, Kaplan B.
From the 1Helen Schneider Women's
Hospital, Rabin Medical
Center, Beilinson Campus, Petah
Tiqwa, Israel; and 2Department of Obstetrics
and Gynecology, Division of
Gynecological Oncology, Sheba Medical Center, Tel Hashomer, Israel. Both centers are affiliated with the Sackler Faculty of Medicine,
Exogenous estrogen is an effective means of
prevention for postmenopausal symptoms. Estrogen treatment should be combined
with progesterone in non-hysterectomized women to
prevent estrogen-induced malignant transformation of the endometrium.
Progesterone supplementation using continuous combined estrogen + progesterone
treatment may result in an increased incidence of breast cancer and
cardiovascular disease. In addition, progesterone supplementation with
sequential estrogen + progesterone treatment may cause immediate adverse
effects, such as irregular bleeding and spotting, breast congestion, fluid
retention, abdominal distention, and a change in lipid profile. All these
effects are related, at least in part, to the progesterone component of the therapy.To avoid these complications,
researchers are seeking safer progestational
components and different modes of administration. In this article we review the
findings on the use of the novel levonorgestrel-releasing
intrauterine system as a therapeutic tool for localized, rather than systemic,
progesterone administration in postmenopausal women.
Joint Bone Spine. 2006 Dec 4; [Epub ahead of print
How long should
patients take medications for postmenopausal osteoporosis?
Briot K, Tremollieres F, Thomas T, Roux C; pour le comite
scientifique du GRIO.
Rheumatology Department,
Paris-Descartes University, School
of Medecine; Assistance Publique-Hopitaux
de Paris, Cochin Teaching Hospital,
27 rue du Faubourg Saint Jacques, 75014 Paris, France.
Several medications have proved effective in
reducing the fracture risk in postmenopausal women with osteoporosis. The
optimal duration of use of these medications remains to be established,
however. Gains in bone mineral density (BMD) persisted throughout 10years of
treatment with alendronate or 7years with risedronate. However, proof of long-term protection against
fractures was obtained only for shorter treatment periods, 4years with alendronate and 5years with risedronate.
The persistence of treatment effects after drug discontinuation varies across
medications, and further studies are needed before this point can be
incorporated into treatment decisions. With raloxifene,
the BMD effect observed after 3 and 4years persisted when the drug was given
for 8years, and the fracture risk reduction was similar after 4years and after
3years. The long-term safety profile also was similar, with a significant
decrease in the incidence of invasive estrogen-receptor-positive breast cancer
and a persistent increase in the risk of deep vein thrombosis. However, a sharp
drop in BMD occurred upon raloxifene discontinuation.
Thus, 4years may be appropriate for anti-resorptive
drug therapy. However, the optimal treatment duration should be determined on a
case-by-case basis according to the results of regular fracture-risk
evaluations.
Fertil Steril. 2007 Jan
11; [Epub ahead of print
Comparison of the
effects of tibolone and estrogen therapy on hemostasis in surgical menopause: a randomized,
double-blind, placebo-controlled study.
Demirol A, Guven S, Seda Guvendag Guven E, Kirazli S, Gurgan T, Ayhan A.
Clinic for Womens'
Health, Infertility, and
OBJECTIVE: To examine the effects of unopposed
estrogen (E) and tibolone therapy on coagulation and
natural anticoagulant systems in surgical menopause. DESIGN: A randomized,
double-blind, placebo-controlled study. SETTING: University hospital clinic in
Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):57-62
Insulin-like
Growth Factor and Mammographic Density in Postmenopausal Norwegian Women.
Bremnes Y, Ursin G, Bjurstam N, Rinaldi S, Kaaks R, Gram IT.
Insulin-like growth factor-I (IGF-I) is
associated with breast cancer risk among premenopausal women but rarely among
postmenopausal women. Recent data from two European studies suggested an
increased risk of breast cancer with increasing levels of IGF-I among women
>50 years old or among postmenopausal hormone therapy users >/=55 years
old. Mammographic density is one of the strongest risk factors, and possibly an
intermediate marker, for breast cancer. We examined the relationship between
IGF and mammographic density among postmenopausal women overall and according
to hormone therapy use. Altogether, 977 postmenopausal participants in the
Norwegian governmental mammographic screening program had IGF concentrations
measured by ELISA. Mammograms were classified according to percent and absolute
mammographic densities using a previously validated computer-assisted method.
After adjustment for age, number of children, age at menopause, body mass
index, and hormone therapy use, both plasma IGF-I concentration (P(trend) =
0.02) and IGF-I/IGF binding protein 3 ratio (P(trend) = 0.02) were positively
associated with percent mammographic density. The magnitudes of differences in
percent mammographic density between women in the lowest and highest quartiles
of IGF-I concentrations were 1.5% absolute difference and 21% relative
difference. These associations were similar with absolute mammographic density
as the outcome variable. When the analyses were stratified according to hormone
therapy use, the associations between IGF-I and mammographic density were
significant among noncurrent users (P(trend) = 0.03).
In conclusion, we found a positive but weak association between plasma IGF-I
concentrations and both percent and absolute mammographic densities among
postmenopausal women. These associations were found among noncurrent hormone
therapy users but not among current users.
J Rheumatol. 2007 Jan;34(1):140-4.
Prevalence
of Depressive Symptoms in Postmenopausal Women with Low Bone Mineral Density
and/or Prevalent Vertebral Fracture: Results from the Multiple Outcomes of Raloxifene Evaluation (MORE) Study.
Silverman SL, Shen W, Minshall ME, Xie S, Moses KH.
OBJECTIVE: To examine the prevalence of depressive
symptoms in a cross-sectional study of postmenopausal women with osteoporosis
with and without prevalent vertebral fracture. METHODS: Participants were a
subset of English-speaking women (n = 3798, mean age 66.7 yrs) from the
Multiple Outcomes of Raloxifene Evaluation trial, who
had low bone mineral density (BMD) and/or prevalent vertebral fractures.
Vertebral fractures were measured at baseline by radiography using a semiquantitative technique. Depressive symptoms were
assessed at baseline using the Geriatric Depression Scale (GDS), a valid and
reliable scale for depression screening in elderly patients. Women were
considered as probably depressed if >/= 6 symptoms of depression were
reported. RESULTS: Postmenopausal women with prevalent vertebral fracture
reported more depressive symptoms as assessed by the GDS than women without
prevalent vertebral fracture (1.54 vs 1.26; p =
0.001). There was an absolute increase of 2.5% (p = 0.008) in the prevalence of
probable depression (GDS score >/= 6) in women with prevalent fracture
compared to those without prevalent fracture. The prevalence of probable
depression was 4.1% among women without prevalent vertebral fracture and 6.6%
in women with a prevalent vertebral fracture. The prevalence of probable
depression was 3-fold higher in women with at least 3 prevalent vertebral
fractures compared to women without prevalent fracture (12.8% vs 4.1%; p < 0.001). CONCLUSION: Postmenopausal women
with prevalent vertebral fractures had greater prevalence of depressive
symptoms and probable depression as assessed by the GDS than women without
vertebral fracture with low BMD. The dual diagnosis of depression and
osteoporosis may mean worse health outcomes. Patients with prevalent vertebral
fractures may be considered not only for interventions that address fracture
risk reduction, but also for psychosocial interventions that address depressive
symptoms.
Rheumatol
Int. 2007 Jan 11; [Epub
ahead of print]
Superiority
of a combined treatment of Alendronate and Alfacalcidol compared to the combination of Alendronate and plain vitamin D or Alfacalcidol
alone in established postmenopausal or male osteoporosis (AAC-Trial).
Ringe JD, Farahmand P, Schacht E, Rozehnal A.
Medical Clinic 4, Leverkusen
Clinic (
A combined therapy with the strongly antiresorptive Alendronate and
the pleiotropically acting D-hormone analogue Alfacalcidol may have additive effects on bone quality,
falls and fracture risk in established osteoporosis. The aim of this study (Alfacalcidol Alendronate
Combined-AAC) was to compare the efficacy and safety of a combined parallel
therapy with Alendronate and Alfacalcidol
to the treatment with either Alendronate in
combination with plain vitamin D or Alfacalcidol
alone in patients with established postmenopausal or male osteoporosis. Ninety
patients were included as matched triplets to receive randomly either 1 mug Alfacalcidol daily + 500 mg calcium (group A, n = 30) or 70
mg Alendronate weekly + 1,000 mg calcium + 1,000 IU
vitamin D daily (group B, n = 30) or 1 mug Alfacalcidol
daily + 70 mg Alendronate weekly + 500 mg calcium
daily (group C, n = 30). Patients were recruited in one centre and were
followed up for 24 months. Analysis was intention-to-treat and the primary
outcome was lumbar spine and total hip bone mineral density (measured observer
blind). BMD was measured at the lumbar spine and at the proximal femur with
dual energy X-ray absorptiometry (LUNAR Prodigy,
BMC Musculoskelet Disord. 2007 Jan 10;8(1):3 [Epub ahead of print]
The impact of vitamin D status on changes in bone mineral density during
treatment with bisphosphonates and after
discontinuation following long-term use in post-menopausal osteoporosis.
Deane A, Constancio L, Fogelman I, Hampson G.
ABSTRACT: BACKGROUND: It is still unclear whether
addition of calcium/vitamin D supplements leads to an incremental benefit in
patients taking bisphosphonates and whether
achievement of serum level of 25 (OH) vitamin D of at least
70 nmol/L has an impact on the skeletal
response to bisphosphonates. Moreover the maintenance
of BMD after bisphosphonates withdrawal with the
continuation of calcium/vitamin D supplements only, remains uncertain. The aims
were to assess the impact of vitamin D status on changes in bone mineral
density (BMD) in firstly patients with post-menopausal osteoporosis on bisphosphonates and secondly following discontinuation of bisphosphonates after long-term use. METHODS: Two patient
groups were recruited. The first study population comprised of 112 women
treated with a bisphosphonate. The second study
population consisted of 35 women who had been on bisphosphonates
for > 5 years in whom the treatment agent was discontinued. Baseline BMD,
changes in BMD following treatment, duration of treatment, serum 25 (OH) vitamin D, parathyroid hormone (PTH), urine C-terminal telopeptides of type 1 collagen (CTX) were obtained
on all study participants. RESULTS: In the first study group (n =112), subjects
with serum vitamin D concentrations (> 70 nmol/L)
had a significantly lower serum PTH level (mean [SEM] 41 [2] ng/L ). PTH concentrations of 41 ng/L or less was associated with a significantly higher
increase in BMD at the hip following treatment with bisphosphonates
compared to patients with PTH > 41 ng/L (2.5% [
0.9] v/s -0.2% [0.9], P = 0.04). In the second study group (n = 35),
discontinuation of bisphosphonate for 15 months after
long-term treatment did not result in significant bone loss at the lumbar spine
and total hip, although a trend towards gradual decline in BMD at the femoral
neck was observed. CONCLUSIONS: optimal 25 (OH) vitamin D
concentration prevents bone loss at the hip in patients on bisphosphonates. A prospective controlled trial is needed
to further evaluate whether the response to bisphosphonates
is influenced by vitamin D status. BMD is preserved at the lumbar spine and
total hip following discontinuation of bisphosphonate
for a short period following long-term treatment, although a gradual loss
occurs at the femoral neck.
J Neuroendocrinol. 2007 Feb;19(2):77-81.
The
critical period hypothesis: can it explain discrepancies in the oestrogen-cognition literature?
Department of Psychology &
Department of Obstetrics and Gynaecology,
Although there is compelling evidence from small randomised controlled trials and cross-sectional studies
indicating that oestrogen helps to protect against
cognitive ageing in women, the findings of the large, Women's Health Initiative
Memory Study failed to support the earlier findings. The attempt to resolve
these discrepancies led to the formulation of the Critical Period Hypothesis
which holds that oestrogen has maximal protective
benefits on cognition in women when it is initiated closely in time to a
natural or surgical menopause but not when treatment is begun decades after the
menopause. This article reviews the evidence from basic neuroendocrinology,
from animal behavioural studies and from human
studies that supports the critical period hypothesis. In view of the promise of
this hypothesis and its considerable clinical implications, a direct test of
its validity is warranted.
Menopause. 2007 Jan 8; [Epub ahead of print]
Hot
flashes are associated with increased ambulatory systolic blood pressure.
Gerber LM, Sievert LL, Warren K, Pickering TG, Schwartz JE.
From the 1Department of Public Health and
2Hypertension Center, Department of Medicine, Weill Medical College of Cornell
University, New York, NY.
OBJECTIVE:: To determine the
association between ambulatory blood pressure (BP) and hot flash experience.
DESIGN:: The participants in the study were 154 women
(mean age = 46 years, range = 18-65 years), who were evaluated as part of a
cross-sectional study on ethnicity, socioeconomic status, and diurnal BP
patterns. Participants could be either normotensive
or mildly hypertensive. Participants wore an ambulatory BP monitor for 24 hours
and recorded their awake and sleep times. Hot flashes were assessed using an
everyday complaint questionnaire that embeds symptoms associated with menopause
into a list of everyday complaints. RESULTS::
Thirty-three percent of participants reported having had hot flashes during the
2 weeks before they completed the questionnaire. Compared with women who did
not report hot flashes, mean awake and sleep systolic BP values were
significantly higher (P < 0.004 and P = 0.007, respectively) in women who
reported having had hot flashes. Hot flashes continued to independently predict
average awake and sleep systolic BP (both P = 0.03) after controlling for age,
race/ethnicity, body mass index, and menopausal status. Hot flashes were not
associated with diastolic BP or nocturnal dipping of BP. CONCLUSIONS:: Hot flashes are associated with increased awake and sleep
systolic BP independent of menopausal status. Further investigation is
warranted to elucidate the mechanisms by which hot flashes are associated with
BP.
Menopause. 2007 Jan 8; [Epub ahead of print]
Menopause,
but not age, is an independent risk factor for fasting plasma glucose levels in
nondiabetic women.
Otsuki M, Kasayama S, Morita S, Asanuma N, Saito H, Mukai M, Koga M.
From the 1Department of Medicine, Osaka University
Graduate School of Medicine, Osaka, Japan; and 2Department of Internal
Medicine, Kinki Central Hospital, Itami, Japan.
OBJECTIVE:: Glucose
metabolism is influenced by various genetic and environmental factors. In women
the prevalence of abnormal glucose metabolism is known to increase around and
after age 50. The aim of this study was to determine whether menopause augments
fasting plasma glucose (FPG) levels in women. DESIGN::
Of 672 Japanese women who underwent health examinations, we studied 505 nondiabetic participants who had no history of hysterectomy
and had never used estrogens or progestins. All
participants were administered an oral glucose tolerance test, and their blood
measurements and information about their menopause status were obtained.
RESULTS:: Of these 505 women, 208 were premenopausal
and 297 were postmenopausal. Age, body mass index, triglycerides level, total
cholesterol level, low-density lipoprotein cholesterol level, blood pressure,
and homeostasis model assessment insulin sensitivity index rose across
quintiles of FPG levels, whereas high-density lipoprotein cholesterol level and
homeostasis model assessment pancreatic beta-cell function index did not. The
number of premenopausal women declined and the number of postmenopausal women
increased across quintiles of FPG levels. Univariate
regression analysis demonstrated that age, body mass index, triglycerides
level, low-density lipoprotein cholesterol level, and menopause status were
associated with FPG level, whereas high-density lipoprotein cholesterol level
was not. Stepwise multivariate regression analysis showed that the independent
risk factors for elevated FPG levels were body mass index, menopause, and
triglycerides level, whereas age and low-density lipoprotein cholesterol level
did not contribute to FPG levels. CONCLUSIONS::
Menopause, but not age, is directly involved in augmented FPG levels in nondiabetic women.
Indian
J Med Res. 2006 Nov;124(5):545-52.
Assessment
of mammographic density changes on plain film mammograms in postmenopausal
women on hormone replacement therapy.
Orguc S, Goktan C, Ovali GY, Karaer O, Oruc S.
Departments of Radiology, Celal
BACKGROUND & OBJECTIVES: Mammographic screening is
an effective tool for the early detection of breast cancer. Hormone replacement
therapy (HRT) has been shown to increase mammographic density and thus may
hinder early detection of small tumours. We undertook
this study to determine and compare the frequency and degree of change in
mammographic density in postmenopausal women in HRT using two different
methods: the classical Wolfe classification and a new semiquantitative
method, which we named as the comparison wheel. METHODS: This study included
285 women, 206 under hormone treatment, and 79 control subjects. All women
underwent baseline mammographic study before the beginning of treatment. Mean
interval of the follow up mammograms was 16 months. The methods were compared
in evaluating the effects of three types of hormone therapies on mammographic
density. RESULTS: The frequency of change was only significant in the combined
hormone replacement group when Wolfe classification was used. However, the
frequency of increase in density (estrogen group 21%, combined therapy group
42%, tibolone group 28%) was markedly higher when the
comparison wheel was used. The inter-rater Kappa value was calculated as 0.977
for the first and 0.957 for the second readings of the two radiologists for the
comparison wheel, and 0.973 and 0.968 for the Wolfe classification. The
intra-rater Kappa values were determined as 0.972 and 0.957 for the first and and 0.963 and 0.926 for the second radiologist for
comparison wheel and Wolfe classification respectively. INTERPRETATION &
CONCLUSION: Our findings indicate that the estimated increase of mammographic
density depends on the selected hormone regimen, as well as the method of
evaluation. The comparison wheel is a semiquantitative
method of evaluating changes of mammographic density and is sensitive and
reproducible with high inter- and intra- rater Kappa values. This method can be
used as an alternative for comparison of digital mammographic applications in
the future.
J Clin Endocrinol
Metab. 2007 Jan 9; [Epub ahead of print]
Plasma adiponectin concentrations and risk of incident breast
cancer.
Tworoger SS, Eliassen AH, Kelesidis T, Colditz GA, Willett WC, Mantzoros C, Hankinson SE.
Channing Laboratory,
Department of Medicine, Brigham and Women's Hospital and
Introduction: Previous retrospective case-control studies
suggest that adiponectin, an obesity-related hormone,
is inversely associated with breast cancer risk, particularly in postmenopausal
women; however no prospective studies exist. Therefore, we conducted a
prospective case-control study nested within the Nurses' Health Study (NHS) and
NHSII cohorts examining the association between plasma adiponectin
concentrations and breast cancer risk. Materials and Methods: Blood samples
were collected in 1989-1990 (NHS) and 1996-1999 (NHSII); adiponectin
was measured by radioimmunoassay. The analysis included 1,477 breast cancer
cases diagnosed after blood collection and before June 2000 (NHS) or June 2003
(NHSII), who had 1-2 controls (n=2,196) matched on age, menopausal status,
postmenopausal hormone (PMH) use, fasting, and time of day and month of blood
collection. We adjusted for body mass index at age 18, weight change from age
18 to blood draw, family history of breast cancer, history of benign breast
disease, duration of PMH use, ages at menarche and first birth, and parity.
Results: Although we observed no association between adiponectin
and breast cancer risk overall, there was a nearly significant interaction by
menopausal status (p=0.08), with a relative risk (RR), top versus bottom
quartile=0.73 (95% confidence interval (CI)=0.55-0.98,
p-trend=0.08) among postmenopausal women and 1.30 (95% CI=0.80-2.10,
p-trend=0.09) for premenopausal women. Among postmenopausal women, adiponectin appeared more strongly inversely associated in
never PMH users (p-heterogeneity=0.05) and women with low circulating estradiol levels (p-heterogeneity=0.05). Discussion: Our
results suggest that adiponectin may be inversely
associated with postmenopausal breast cancer risk, particularly in a low
estrogen environment.
Osteoporos
Int. 2007 Jan 9; [Epub
ahead of print]
The
reduction of physical activity reflects on the bone mass among young females: a
follow-up study of 142 adolescent girls.
Rautava E, Lehtonen-Veromaa M, Kautiainen H, Kajander S, Heinonen OJ, Viikari J, Mottonen T.
Maintenance of positive effects of physical activity
on growing bone is unknown. Physical activity was associated with increased BMC
and BMD in a 7-year follow-up with 142 adolescent girls. Marked reduction in
physical activity had an unfavorable effect on bone measurements, which is an
important finding when the prevention of osteoporosis is considered.
INTRODUCTION: Environmental factors influence quality and durability of bone.
Physical activity, with high-impact weight bearing activity during puberty in
particular, has been shown to have a beneficial effect on growing bone. Only
few studies have been published on the maintenance of these effects. METHODS:
At baseline, 142 girls aged 9-15 years participated in the present 7-year
follow-up study. Growth and development, physical activity, and intakes of
calcium and vitamin-D were recorded at intervals. BMC and BMD measurements were
repeated using DXA. Based on the recording of physical activity during the
follow-up measurements, the effect of the reduction in physical activity was
examined with the bone measurements, and the measurements in the tertiles based on the amount of physical activity during
the whole follow-up period were compared. RESULTS: Physical activity was
positively associated with the development of BMC and BMD during the follow-up.
The mean BMC of the lumbar spine increased 1.69 g (3%) (p = 0.021) more among
those girls who maintained the physical activity level as compared with those
who reduced it during last 4 years. In the femoral neck, the corresponding
difference was 0.14 g (4.6%) (p = 0.015) between the same two groups of girls.
The mean increases in BMC at lumbar spine and femoral neck were more
substantial among those girls having the highest physical activity levels
during the 7-year follow-up (46.7% and 22.6%) as compared with those having the
lowest physical activity levels (43.3% and 17.4%, respectively). CONCLUSIONS:
The findings of the present study show that regular physical activity is
valuable in preserving the peak bone mass acquired at puberty in particular.
Many of the girls who markedly reduced their activity levels lost bone in their
femoral neck prior to their 25th birthday.
J Clin
Endocrinol Metab. 2007 Jan;92(1):3-9
Approach to the patient with subclinical hyperthyroidism.
Division of Endocrinology, Sinai Hospital of
Baltimore, 2435 West Belvedere Avenue, Hoffberger
Building, Suite 56, Baltimore, Maryland 21215. E-mail
dcooper@lifebridgehealth.org.
Endogenous subclinical hyperthyroidism, defined by
normal circulating levels of free T(4) and T(3) and low levels of TSH, is a
common clinical entity and is typically caused by the same conditions that
account for the majority of cases of overt hyperthyroidism: Graves' disease,
toxic multinodular goiter, and solitary autonomously
functioning thyroid nodules. Subclinical hyperthyroidism has been associated
with an increased risk of atrial fibrillation and
mortality, decreased bone mineral density in postmenopausal women, and mild
hyperthyroid symptoms. Treatment of subclinical hyperthyroidism remains
controversial, given the lack of prospective randomized controlled trials
showing clinical benefit with restoration of the euthyroid
state. Nevertheless, it seems reasonable to treat older individuals whose serum
TSH levels are less than 0.1 mU/liter and certain
high-risk patients, even when the serum TSH is between 0.1 and the lower limit
of the normal range.
Hum
Reprod Update. 2007 Jan 5; [Epub ahead of print]
DHEA
therapy for women: effect on sexual function and wellbeing.
NH&MRC Centre of Clinical Research Excellence in
the Women's Health Program, Department of Medicine, Central and Eastern
Clinical School, Monash University, Alfred Hospital, Prahran, Victoria, Australia.
DHEA is increasingly available commercially as a
supplement aimed at improving libido and wellbeing in postmenopausal women.
However there is scant evidence to support the use of DHEA for this purpose,
and safety data for DHEA therapy are lacking.Dehydroepiandrosterone
(DHEA) and its sulphate DHEAS are the most abundant
circulating sex steroid hormones in women, providing a large precursor
reservoir for the intracellular production of androgens and oestrogens
in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. It has
been proposed that restoring the circulating levels of these steroids to those
found in young people may have anti-ageing effects and improve wellbeing and
sexual function. However this is not supported by the published literature. We
have reviewed the physiology of DHEA and DHEAS in women and the published
literature pertaining to the use of DHEA therapy for libido and wellbeing in
postmenopausal women. The literature was searched using Medline (Ovid) and
Pub-Med for original studies. Overall, the interpretation of data from randomised controlled trials conducted in well women is
limited by inadequate sample size and short treatment durations with
inconsistent results for the outcomes of libido and wellbeing. Studies of DHEA
in women with adrenal insufficiency, although indicating potential improvements
in mood and libido, are also limited by their short
treatment phase durations. In addition safety data for DHEA therapy are
lacking. The potential value of DHEA therapy for women still requires
exploration in adequately powered well-designed randomised
placebo-controlled trials. The studies of DHEA therapy in women with adrenal
insufficiency suggest that this group is the most likely to derive health
benefits from DHEA supplementation.
Eur J Obstet
Gynecol Reprod Biol. 2007 Jan 3; [Epub ahead of print]
Women's perception
of sexuality around the menopause: Outcomes of a European telephone survey.
OBJECTIVE: Women's attitudes and experience towards
sexuality around the menopause were investigated in
Nippon Rinsho. 2006 Dec;64(12):2317-22.
Graves' disease and bone metabolism
Institute of
Clinical Endocrinology,
Thyroid hormone stimulates osteoclastic bone resorption,
through increased expression of receptor activator of nuclear factor kappa B ligand (RANKL) in osteoblasts as
well as via non-RANKL-mediated pathway. Therefore, in hyperthyroid patients
with Graves' disease, bone resorption (urinary excretion
of calcium, phosphate, deoxypyridinoline, N-terminal telopeptide of collagen type I) is increased. Due to
accelerated bone remodeling, bone formation is also increased. However, the
amount of bone formation is less than that of bone resorption,
leading to a gradual decrease in bone mineral density (BMD). In young patients,
the decreased BMD is reversible, but not in post-menopausal women. Therefore,
in these patients with rapid bone looser, bisphosphonates
may be beneficial treatment for prevention of osteoporosis and will prevent
bone fractures in senile period.
Semana del 2 al 9 de Enero 2007
Hum Reprod. 2007 Jan 4; [Epub ahead of print]
A
comparative study of the effect of continuous combined conjugated equine
estrogen plus medroxyprogesterone acetate and tibolone on blood coagulability.
Skouby SO, Sidelmann JJ, Nilas L, Jespersen J.
Department of Obstetrics and
Gynecology,
BACKGROUND Hormone therapy (HT) after the
menopause is associated with increased risk of venous thromboembolism
(VTE). Tibolone has pharmacodynamic
properties different from other hormone preparations. We compared the effect of
a combined HT and tibolone on the inhibition of haemostasis. METHODS Thirty-eight post-menopausal women
were randomly assigned to 1.25 or 2.5 mg per day of tibolone
or oral continuous combined conjugated equine estrogen plus medroxyprogesterone
acetate (CEE/MPA). Inhibitors of haemostasis were
measured at baseline and after 12 months. RESULTS Results
from the two groups of women receiving tibolone were
not significantly different and, to improve the power of the study, the two
groups were merged. Higher concentration of protein S (1.16 versus 1.00 IU ml(-1); P=0.005) and higher activated protein C resistance
ratio (APC-R) (4.2 versus 3.65; P=0.04) were observed in the tibolone group than in the CEE/MPA group. Both doses of tibolone increased APC-R significantly (P<0.01). Tissue
factor pathway inhibitor (TFPI) was lower in the CEE/MPA group than in the tibolone group (67.8 versus 79.9 ng
ml(-1); P=0.03). CEE/MPA reduced the concentration of antithrombin (P=0.002), protein S (P<0.001) and TFPI
(P<0.001). Both preparations reduced the concentration of plasminogen activator inhibitor 1 (P<0.05). CONCLUSIONS Tibolone induces fewer pharmacological alterations on blood
coagulability than CEE/MPA and has a potentially favourable effect on APC-R. This may translate into a
corresponding low risk of VTE, as also indicated from the existing clinical
data.
Am J Epidemiol. 2007 Jan
4; [Epub ahead of print]
Alcohol
Consumption and Breast Cancer Risk in the Women's Health Study.
Zhang SM, Lee IM, Manson JE, Cook NR, Willett WC, Buring JE.
Division of Preventive
Medicine, Department of Medicine, Brigham and Women's Hospital and
The authors assessed the association between
moderate alcohol consumption and breast cancer risk in the Women's Health Study
(United States, 1992-2004). During an average of 10 years of follow-up, 1,484
cases of total breast cancer (1,190 invasive and 294 in situ) were documented
among 38,454 women who, at baseline, were free of cancer and cardiovascular
disease and provided detailed dietary information, including alcohol
consumption, for the preceding 12 months. Higher alcohol consumption was
associated with a modest increase in breast cancer risk; the multivariable
relative risks for >/=30 g/day of alcohol vs. none were 1.32 (95% confidence
interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02,
2.02) for invasive breast cancer. An increased risk was limited to estrogen
receptor (ER)- and progesterone receptor (PR)-positive tumors; the
multivariable relative risks for an increment of 10 g/day of alcohol were 1.11
(95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24)
for ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors
(167 cases). The association also seemed strongest among those taking
postmenopausal hormones currently, but the test for interaction was not
significant. The findings from this prospective study suggest that moderate
alcohol consumption increases breast cancer risk.
Menopause. 2006 Dec
28; [Epub ahead of print]
Women's health
during mid-life survey: the use of complementary and alternative medicine by
symptomatic women transitioning through menopause in
Patching
van der Sluijs C,
Bensoussan A, Liyanage L, Shah S.
From the 1CompleMED Research Centre, University
of Western Sydney, Sydney, Australia; and 2Primary Health Care Education and
Research Unit, Sydney West Area Health Service, Sydney, Australia.
OBJECTIVE:: To survey
the extent of complementary and alternative medicine (
Blood. 2007 Jan
3; [Epub ahead of print]
B cells and T cells
are critical for the preservation of bone homeostasis and attainment of peak
bone mass in vivo.
Li Y, Toraldo G, Li A, Yang X, Zhang H, Qian WP, Weitzmann MN.
Division of Endocrinology & Metabolism
& Lipids, Emory University School of Medicine, Atlanta, GA, United States.
Bone homeostasis is regulated by a delicate
balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclastogenesis is controlled by the ratio of Receptor
Activator of NF-kappaB Ligand
(RANKL) relative to its decoy receptor, osteoprotegerin
(OPG). The source of OPG has historically been attributed to osteoblasts (OBs). While activated lymphocytes play
established roles in pathological bone destruction, no role for lymphocytes in
basal bone homeostasis in vivo has been described. Using immunomagnetic
isolation of bone marrow (BM) B cells and B cell precursor populations, and quantitation of their OPG production by ELISA, and real
time RT-PCR, cells of the B lineage were found to be responsible for 64% of
total BM OPG production, with 45% derived from mature B cells. Consistently B
cell KO mice were found to be osteoporotic and deficient in BM OPG, phenomena
rescued by B cell reconstitution. Furthermore, T cells, through CD40 ligand (CD40L) to CD40 costimulation,
promote OPG production by B cells in vivo. Consequently, T cell deficient nude
mice, CD40 KO and CD40L KO mice, display osteoporosis and diminished BM OPG
production. Our data suggest that lymphocytes are essential stabilizers of
basal bone turnover and critical regulators of peak bone mass in vivo.
Clin Endocrinol (Oxf). 2007 Jan;66(1):65-71
The transition to
menopause reinforces adiponectin production and its
contribution to improvement of insulin-resistant state.
Tamakoshi K, Yatsuya H, Wada K, Matsushita K, Otsuka R, Yang PO, Sugiura K, Hotta Y, Mitsuhashi H, Takefuji S, Kondo T, Toyoshima H.
Public Health/Health
Information Dynamics,
Objective To evaluate the influence of
menopausal status on the serum adiponectin
concentration and investigate whether the contribution of adiponectin
to insulin resistance is modified by menopausal status. Subjects We conducted a population-based, cross-sectional study of
207 premenopausal and 206 postmenopausal Japanese women. Measurements Data on
anthropometric characteristics, fasting serum adiponectin,
glucose and insulin concentrations were used. Insulin resistance (homeostasis
model assessment of insulin resistance: HOMA-IR) was calculated. Results
Postmenopausal women had significantly higher HOMA-IRs than premenopausal women
[1.50 (1.42, 1.59) vs 1.18 (1.12, 1.24), geometric
mean (1 standard error range), P = 0.005]. Paradoxically, adiponectin
levels in postmenopausal women were also significantly higher than those in
premenopausal women [10.3 (9.95, 10.7) vs 9.04 (8.71,
9.39), P = 0.028]. Multiple regression analysis showed that body mass index
(BMI) was the only significantly independent predictor [standardized partial
regression coefficients (sbeta) = 0.319, P <
0.001] for HOMA-IR among premenopausal women, whereas both BMI and adiponectin were the significant predictors among
postmenopausal (sbeta = 0.334 and -0.141, P <
0.001 and < 0.05, respectively). When the subjects were restricted to those
without metabolic disorders including high blood pressure, hypertriglyceridaemia,
hypo-HDL cholesterolaemia and high fasting glucose, adiponectin (sbeta = -0.249, P
< 0.05) was the only significant predictor for HOMA-IR among postmenopausal
women but BMI was not significant (sbeta = 0.223, P =
0.075). Conclusions The transition to menopause
increases serum adiponectin concentrations. And the
significant and negative association between adiponectin
and HOMA-IR was observed only after menopause. Therefore, adiponectin
may play a role in the improvement of an incipient insulin-resistant state
after, rather than before, menopause.
Clin Endocrinol (Oxf). 2007 Jan;66(1):27-34.
Effects of low-dose
continuous combined hormone replacement therapy on glucose homeostasis and
markers of cardiovascular risk in women with type 2 diabetes.
Kernohan AF, Sattar N, Hilditch T, Cleland SJ, Small M, Lumsden MA, Connell JM, Petrie JR.
Division of Cardiovascular and
Medical Sciences,
Background Low-dose hormone replacement therapy
(HRT) has attracted interest for the treatment of postmenopausal symptoms in
diabetes because of concerns about increased risk of coronary heart disease
(CHD) and stroke with conventional HRT containing conjugated equine oestrogens (CEEs) and medroxyprogesterone
acetate (MPA). Objectives We assessed the effects on
glucose homeostasis and cardiovascular risk factors of continuous oral 17beta oestradiol (1 mg) and norethisterone
(0.5 mg) in postmenopausal women with type 2 diabetes. Design Double-blind,
randomized placebo-controlled trial. Assessments Hyperinsulinaemic
isoglycaemic clamp and cardiovascular risk factors
were assessed before and after 3 months of treatment. Results Twenty-eight
women completed the study. HRT decreased fasting glucose compared with placebo
[-9.4% with HRT vs.+2.3% for placebo, 95% confidence
interval (CI) -23.2 to -0.3] and total cholesterol (-13.7 vs.+1.0%, 95% CI
-22.4 to -3.1%) No significant effect was seen on metabolic clearance rate of
glucose, glycated haemoglobin
(HbA1c), triglycerides, high density lipoprotein (HDL)-cholesterol or
C-reactive protein (CRP). Conclusions In women with type 2
diabetes, low-dose HRT decreased fasting glucose and total cholesterol
without detectable adverse effects on glucose clearance, triglycerides and CRP
as reported with conventional HRT.
Methods
Find Exp Clin Pharmacol. 2006 Nov;28(9):627-56
Pleiotropic effects
of statins and related pharmacological experimental
approaches.
Unitat
de Farmacologia, Departament
de Farmacologia i Quimica Terapeutica, Facultat de Farmacia, Universitat de Barcelona,
Statins, the most widely
prescribed cholesterol-lowering drugs, are considered to be first-line
therapeutics for the prevention of coronary heart disease and atherosclerosis. Statins act by inhibiting the enzyme
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in endogenous
cholesterol biosynthesis, which catalyzes the reduction of HMG-CoA to mevalonic acid. Inhibition
of this enzyme has proven to be effective for lowering plasma total
cholesterol, low-density lipoprotein-cholesterol, and triglyceride levels in
humans and can therefore be useful to treat atherosclerotic and dyslipidemic disorders. However, the clinical benefits of statins appear to extend beyond their lipid-lowering
effects. Besides reducing cholesterol biosynthesis, inhibition of mevalonate by statins also leads
to a reduction in the synthesis of important intermediates, such as the isoprenoids farnesyl
pyrophosphate and geranylgeranyl pyrophosphate. These
intermediates are involved in the posttranslational prenylation
of several proteins (e.g., Ras,
Neurology. 2007 Jan
2;68(1):33-8.
Risk of
ischemic stroke and lifetime estrogen exposure.
de Lecinana MA, Egido JA, Fernandez C, Martinez-Vila E, Santos S, Morales A, Martinez E, Pareja A, Alvarez-Sabin J, Casado I; PIVE Study
Investigators of the Stroke Project of the Spanish Cerebrovascular
Diseases Study Group.
Department of Neurology,
University Hospital Ramon y Cajal, Ctra de Colmenar Km 9,100, 28034
BACKGROUND: Estrogen loss has been related to
higher incidence of stroke in postmenopausal women, but randomized trials have
demonstrated an increased risk of stroke in women receiving hormone replacement
therapy (HRT). OBJECTIVE: To assess the relationship between exposure to
endogenous ovarian hormones and the risk of noncardioembolic
ischemic stroke. METHODS: We conducted a multicenter, age-matched, case-control
study in postmenopausal women (case: nonembolic
ischemic stroke; control: no stroke) comparing duration of ovarian activity or
lifetime estrogen exposure, which was defined as age at menarche to age at
menopause. Embolic cardiopathy and unreliable
gynecologic data were exclusion criteria. Cardiovascular disease risk factors
were recorded. The relationships of the principal variables to the risk of
stroke were assessed using a conditional logistic regression analysis. RESULTS:
There were 430 cases and 905 controls in the study. In the multivariate
analysis, hypertension (odds ratio [OR]: 2.73; 95% CI: 2.09 to 3.58; p <
0.0001), diabetes (OR: 3.38; 95% CI: 2.53 to 4.52; p < 0.0001), hyperlipidemia (OR: 1.31; 95% CI: 1.01 to 1.7; p = 0.045),
lifespan of ovarian activity <34 years (OR: 1.51; 95% CI: 1.13 to 2.03; p =
0.005), and menarche at <13 years of age (OR 1.49; 95% CI: 1.15 to 1.92; p =
0.002) were independently related to an increased risk of stroke. Obesity (OR:
0.73; 95% CI: 0.56 to 0.95; p = 0.021) was related to a lower risk of stroke.
CONCLUSIONS: Longer lifetime exposure to ovarian estrogens may protect against noncardioembolic ischemic stroke. However, a very early age
of exposure onset could be disadvantageous.
J Clin Endocrinol Metab. 2007 Jan 2; [Epub ahead of print]
Discontinuation of Antiresorptive Therapies: A Comparison between 1998-2001
and 2002-2004 among Osteoporotic Women.
Blouin J, Dragomir A, Ste-Marie LG, Fernandes JC, Perreault S.
Faculty of Pharmacyand
Faculty of Medicine,
Context: Studies having reported high rates of
discontinuation of antiresorptive therapies (ART) may
not reflect their actual utilization. Objectives: We compared probability of
discontinuation among women aged 70 years or older with a diagnosis of
osteoporosis or recent osteoporotic fracture having started ART (alendronate, risedronate,
cyclical etidronate, raloxifene,
nasal calcitonin) between 1998-2001 or 2002-2004.
Patients and Methods: We constructed two cohorts of women using Regie de l'assurance maladie du Quebec databases. Discontinuation was defined as
a lapse of >/= 30 days after completion of a refill. Switching from one ART
to another was allowed. Probability of discontinuation was estimated using
Kaplan-Meier analysis. Multivariate Cox models were used to identify potential
determinants of ART discontinuation over 1 year. Results: After 1 year,
probability of discontinuation was slightly lower in the 2002-2004 cohort than
in the 1998-2001 cohort; 52.2% versus 57.5% (p<0.001). This difference
remained significant after adjusting for determinants [adjusted rate ratio (RR)
0.92, 95% confidence interval (CI) 0.87-0.98]. Significant determinants of ART
discontinuation within 1 year included bone mineral density testing (RR 0.77;
CI 0.73-0.82) performed within two years prior to initiation of therapy, and
having consulted more than 2 pharmacies (RR 1.15; CI 1.06-1.25) in the year
prior to starting therapy. In the 2002-2004 cohort,
when switching was allowed, women initiating a once-weekly regimen of alendronate or risedronate did
not show a different one-year risk of discontinuation than women initiating
daily regimens of the same drugs (RR 0.90; CI 0.82-1.00). Conclusions: Even if
new dosing regimens were introduced, discontinuation of ART among osteoporotic
women remains high.
J Clin Oncol. 2007 Jan
2; [Epub ahead of print]
Plasma Phytoestrogens and Subsequent Breast Cancer Risk.
Verheus M, van Gils CH, Keinan-Boker L, Grace PB, Bingham SA, Peeters PH.
Julius Center for Health Sciences and Primary
Care, University Medical Center Utrecht, the Netherlands; Israel Center for
Disease Control, Ministry of Health, and School of Public Health, University of
Haifa, Haifa, Israel; Horseracing Forensic Laboratory Ltd, Fordham; Medical
Research Council Dunn Human Nutrition Unit, Cambridge, United Kingdom.
PURPOSE: Phytoestrogens
are plant compounds that are structurally and functionally similar to mammalian
estrogens. By competing for estrogen receptors, phytoestrogens
possibly inhibit binding of the more potent endogenous estrogens and decrease
their potential effects on breast cancer risk. We investigated the association
between plasma phytoestrogen levels and breast cancer
risk in a prospective manner. PATIENTS AND METHODS: We performed a nested case-control
study within the Prospect cohort, one of the two Dutch cohorts participating in
the European Prospective Investigation into Cancer and Nutrition. A total of
383 women (87 pre- or perimenopausal women [mean age,
52 years] and 296 postmenopausal women [mean age, 59 years]) who developed
breast cancer were selected as case subjects and were matched to 383 controls,
on date of blood sampling. Plasma levels of isoflavones
(daidzein, genistein, glycitein, O-desmethylangolensin,
and equol) and lignans (enterodiol and enterolactone)
were measured. The isotope dilution liquid chromatography/tandem
mass-spectrometry method incorporating triply (13)C-labeled
standards was used for all analyses. Breast cancer odds ratios were calculated
for tertiles of phytoestrogen
plasma levels using conditional logistic regression analysis. RESULTS: For genistein, the risk estimate for the highest versus the
lowest tertile was 0.68 (95% CI, 0.47 to 0.98).
Similar protective effects, although not statistically significant, were seen
for the other isoflavones. Lignan
levels did not appear to be related to breast cancer risk. Results were the
same in pre- or perimenopausal women, and in
postmenopausal women. CONCLUSION: High genistein
circulation levels are associated with reduced breast cancer risk in the Dutch
population. No effects of lignans on breast cancer
risk were observed.
J Womens Health (Larchmt). 2006 Dec;15(10):1174-83.
Secondary
osteoporosis: are we recognizing it?
Sikon AL, Thacker HL, Carey J, Deal C, Licata AA.
Women's
Background: As a growing percentage of
Americans will be reaching their elderly years in the next decade, the
prevalence of osteoporosis and its effects will have an even greater impact on
the healthcare system. Advancements in bone research and development of newer
treatments have allowed for the establishment of more refined guidelines and a
growing awareness of the need to prevent, screen, and diagnose osteoporosis.
Thus, more women are now being screened with dual x-ray absorptiometry
scans (DXA) than ever before. The importance of a true understanding of the
test results obtained from such screening is paramount. In our institution,
recommendations to consider a secondary evaluation are made by the DXA
interpreters when the Z-score is low. Few, if any, studies have evaluated the
rates of physician and patient adherence with specific recommendations provided
on the bone density report. Methods: To assess compliance with such
recommendations provided in DXA interpretations, we investigated the number of
ordering providers who actually pursued these advisements. Results: We found
that among providers ordering DXAs, primary care providers did not pursue recommendations
to pursue a secondary workup as often as their subspecialty counterparts. We
also found a significant amount of vitamin D deficiency/insufficiency and
primary hyperparathyroidism in the population evaluated. Conclusions: Primary
care providers should be further educated on treatable secondary causes of
osteoporosis as opposed to an often reflexive response of prescribing a
pharmacological antiresportive agent without other
consideration.
Exp Hematol. 2007 Jan;35(1):128-36
Osteoporosis
of hematologic etiology.
Gurevitch O, Khitrin S, Valitov A, Slavin S.
Department of Bone Marrow
Transplantation and Cancer Immunotherapy,
OBJECTIVE: Here we present evidence that
overexertion of the hematopoietic system following chronic bleeding plays an
important role in the etiology of osteoporosis. MATERIALS AND METHODS: C57BL/6
mice were exposed to chronic bloodletting (0.2 mL
twice per month for 10 months), total body irradiation (900 cGy),
or aging (20-30 months old). Bone marrow from standard untreated donors was
transplanted under the kidney capsules of all three categories of recipients to
investigate the influence of each of these conditions on new bone marrow
formation. Cellularity and histologic
structure of developed osteohematopoietic sites and histomorphometry of lumbar vertebrae were studied, thus
assessing the role of bleeding, irradiation, and old age on new bone formation
and effects on existing bone. RESULTS: Chronic blood loss led to augmented
production of hematopoietic microenvironment, relative reduction in the amount
of generated bone, and activation of the bone resorptive
process in the newly forming osteohematopoietic
complex. Similar results were seen in irradiated and senescent mice. Activity,
stimulating expansion of hematopoietic microenvironment, was revealed in the
plasma of all three categories of experimental mice. Likewise, quantification
of the relative amount of bone and hematopoietic areas in skeletal sites showed
a significant reduction in bone tissue of the first lumbar vertebrae of
chronically bled mice. CONCLUSIONS: Our experimental data, together with
existing clinical observations documenting the role of hematopoietic
insufficiency in the development of osteoporosis, confirm our working
hypothesis that chronic blood loss may be the primary factor responsible for
the rapid and consistent development of postmenopausal osteoporosis.
J Womens Health (Larchmt). 2006 Dec;15(10):1141-50.
Impact
of smoking cessation on bone mineral density in postmenopausal women.
Oncken C, Prestwood K, Kleppinger A, Wang Y, Cooney J, Raisz L.
Department of Medicine,
Background: Although clinical guidelines
recommend smoking cessation to improve bone health, the impact of short-term
smoking cessation (i.e., 1 year) on bone mineral density (BMD) is not known. We
examined the effects of smoking cessation on BMD measurements, markers of bone
turnover, and hormone profiles in postmenopausal women. Methods: Postmenopausal
women (n = 152) who smoked at least 10 cigarettes per day were randomly
assigned to behavioral counseling and either nicotine or placebo patch for
smoking cessation (3-month treatment with a 1-month taper) and followed for an
additional year. The BMD at various sites (hip, spine, wrist, and total body),
serum and urine biochemical markers of bone turnover, and sex hormones were
measured at baseline and again 1 year after smoking treatment. Women who
continuously abstained from smoking between the end of treatment and 1 year
later (quitters) (n = 42) were compared with women who completed the study and
continued to smoke (n = 77). Results: Femoral trochanter
BMD increased by 2.9% among quitters vs. 0.6% among continued smokers (p =
0.02). Total hip BMD increased by 1.52% among quitters vs. 0.43% among
continued smokers (p = 0.03). Changes in BMD at the femoral neck, radius,
spine, and total body did not significantly differ between groups. The effects
of smoking cessation on bone were mediated in part by weight gain. Smoking
cessation was also associated with an increase in bone alkaline phosphatase. Conclusions: Smoking cessation, relative to
continued smoking, increases BMD at the femoral trochanter
and total hip in postmenopausal women.
Joint Bone Spine. 2006 Dec 4; [Epub ahead of print]
Extra-skeletal
effects of bisphosphonates.
Corrado A, Santoro N, Cantatore FP.
Chair of Rheumatology,
Bisphosphonates are
pharmacological agents which are currently used both in osteoporosis than in
other pathological conditions characterised by an
increased bone resorption, such as Paget's disease of
bone, malign hypocalcaemia during myeloma, osteolytic
bone metastasis and fibrous dysplasia of bone. The most important biological
effect of bisphosphonates is the reduction of bone remodelling through the inhibition of osteoclastic
activity, but there are many clinical and experimental evidences of
extra-skeletal biological effects of bisphosphonates.
It has been shown that bisphosphonates exert their
effects not only on bone tissue cells, but also on those of the immune system
with an "immuno-modulating" effect,
influencing the production of pro- and anti-inflammatory cytokines and changing
the molecular expression involved in the immune processes and anti-inflammatory
response. Although the available data are conflicting, there are several
reports concerning the beneficial effects of bisphosphonates
in controlling the progression of chronic joint inflammatory diseases,
suggesting a wider use for these therapeutic agents in clinical practice.
Semana del 27 de Diciembre de 2006 al 2 de Enero 2007
Ann Endocrinol (Paris). 2006 Dec;67(6):575-80.
Skin and menopause
Bensaleh H, Belgnaoui FZ, Douira L, Berbiche L, Senouci K, Hassam B.
Service de Dermatologie, CHU Ibn Sina Rabat, Maroc.
Important changes related to declining level of
several hormones occur during menopause: vasomotor instability, bone loss,
anxiety, sexual dysfunction, skin aging. Our objective was a review of the
literature concerning the histological and clinical changes seen in post
menopausal skin, and also an analysis of the effect of hormonal replacement
therapy in slowing down the aging process. Decline in progesterone increases
the impact of androgen on the sebaceous glands and hair. Decreased estrogen
slows down mitotic activity in the epidermal basal layer, reduces the synthesis
of collagen and contributes to thickening of the dermo-epidermal
junction. This hypoestrogenemia may be spontaneously
attenuated by local synthesis of oestradiol in
peripheral target tissues according to the intracrine
process. This new hormonal pattern is associated with skin atrophy, hyperseborrhea, increased pilosity
on the cheeks and upper lip, loss of scalp hair, increase in degeneration of
elastic tissue, atrophy and dryness of the vaginal mucosa. Estrogen treatment
in post menopausal women has been shown to increase collagen content, dermal
thickness and elasticity. Biophysical properties are also significantly
improved for the parameters reflecting hydration and sebum secretion. However, numerous
side effects such as increased incidence of cancer and cardiovascular morbidity
limit the use of this treatment. So non hormonal alternatives
are proposed. Laser and lifting remain the most important options.
JAMA. 2006 Dec
27;296(24):2927-38.
Effects of
continuing or stopping alendronate after 5 years of
treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a
randomized trial.
Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR;
CONTEXT: The optimal duration of treatment of
women with postmenopausal osteoporosis is uncertain. OBJECTIVE: To compare the
effects of discontinuing alendronate treatment after
5 years vs continuing for 10 years. DESIGN AND
SETTING: Randomized, double-blind trial conducted at 10 US clinical centers
that participated in the Fracture Intervention Trial (FIT). PARTICIPANTS: One
thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment. INTERVENTION: Randomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or
placebo (n = 437) for 5 years (1998-2003). MAIN OUTCOME MEASURES: The primary
outcome measure was total hip bone mineral density (BMD); secondary measures
were BMD at other sites and biochemical markers of bone remodeling. An
exploratory outcome measure was fracture incidence. RESULTS: Compared with
continuing alendronate, switching to placebo for 5
years resulted in declines in BMD at the total hip (-2.4%; 95% confidence
interval [CI], -2.9% to -1.8%; P<.001) and spine (-3.7%; 95% CI, -4.5% to
-3.0%; P<.001), but mean levels remained at or above pretreatment levels 10
years earlier. Similarly, those discontinuing alendronate
had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide
of type 1 collagen, 59.5% (P < .001) for serum n = propeptide
of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker
levels remained somewhat below pretreatment levels 10 years earlier. After 5
years, the cumulative risk of nonvertebral fractures
(RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those
continuing (19%) and discontinuing (18.9%) alendronate.
Among those who continued, there was a significantly lower risk of clinically
recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no
significant reduction in morphometric vertebral fractures
(11.3% for placebo and 9.8% for alendronate; RR,
0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial
bone biopsies did not show any qualitative abnormalities, with bone turnover
(double labeling) seen in all specimens. CONCLUSIONS: Women who discontinued alendronate after 5 years showed a moderate decline in BMD
and a gradual rise in biochemical markers but no higher fracture risk other
than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women,
discontinuation of alendronate for up to 5 years does
not appear to significantly increase fracture risk. However, women at very high
risk of clinical vertebral fractures may benefit by continuing beyond 5 years.
Menopause. 2006 Dec
28; [Epub ahead of print]
Hot flashes and
estrogen therapy do not influence cognition in early menopausal women.
Leblanc ES, Neiss MB, Carello PE, Samuels MH, Janowsky JS.
Department of Medicine and
Department of Behavioral Neuroscience,
OBJECTIVE:: To examine
how menopausal symptoms and estrogen therapy (ET)-induced symptom relief affect
cognition in early menopause. DESIGN:: There were two
components. Part 1 was a cross-sectional study of 37 healthy, recently
postmenopausal women with diverse menopausal symptoms. Women were categorized
as having low (n = 20) or high symptoms (n = 17) based on a validated symptom
questionnaire. Women completed mood and sleep questionnaires and underwent cognitive
testing, which included verbal memory, visual memory, emotional memory, and
verbal fluency. Thirty-two of these women went on to part 2 of the study.
Fourteen were randomly assigned to receive ET and 18 to receive placebo for 8
weeks. Before treatment and at 4 and 8 weeks, women completed the same measures
as in part 1 of the study. RESULTS:: High symptom
women had more negative mood (P = 0.01) and lower quality sleep (P < 0.001)
than low symptom women. Despite suffering from more menopausal symptoms, worse
mood, and poorer sleep, women in the high symptom group performed the same on
cognitive testing as women in the low symptom group. Women receiving ET had
greater improvements in menopausal symptoms and sleep compared with those
receiving the placebo (P </= 0.05). ET did not improve mood compared with
placebo. Women receiving ET did not have any improvement in cognitive
performance compared with those receiving the placebo. CONCLUSIONS:: Menopausal symptoms do not impair cognition. ET does not
improve cognition despite alleviating symptoms and improving sleep in recently
naturally menopausal women with diverse menopausal symptoms.
Menopause. 2006 Dec
28; [Epub ahead of print]
Aged rats lose vasoprotective and anti-inflammatory actions of estrogen in
injured arteries.
Miller AP, Xing D, Feng W, Fintel M, Chen YF, Oparil S.
Vascular Biology and Hypertension Program,
Division of Cardiovascular Disease, Department of Medicine, University of
Alabama at Birmingham, Birmingham, AL; and 2Biology Department, Talladega
College, Talladega, AL.
OBJECTIVE::
17beta-Estradiol (E2) negatively modulates neointima
formation, leukocyte infiltration, and proinflammatory
mediator expression after vascular injury in young (10-wk-old) ovariectomized (OVX) rats. Trials of E2 in elderly
postmenopausal women have not confirmed a vasoprotective
effect. This study tested the hypothesis that responsiveness to E2 is lost in
injured arteries of aged (12-mo-old) OVX rats. DESIGN::
E2- or vehicle-treated OVX rats underwent balloon injury of the carotid artery
and were killed after 2 weeks for morphometric
examination of arteries, after 24 hours for assessment of leukocyte
infiltration, and after 2 hours for quantification of proinflammatory
mediator mRNA expression. RESULTS:: Neointima formation was significantly reduced in aged
compared with young vehicle-treated rats. E2 treatment had directionally
opposite effects on intima/media ratios in aged
(+75%) and young (-40%) rats. Injury induced increases in infiltrating total
leukocytes, neutrophils, monocytes/macrophages,
and expression of proinflammatory mediators in
arteries of aged rats; E2 had no effect on these inflammatory responses to
injury. Estrogen receptor alpha and beta protein expression were similar in
carotid arteries of young and aged rats on immunofluorescence
testing. CONCLUSIONS:: Aged OVX rats lose the vasoprotective and anti-inflammatory responses to exogenous
E2 seen in younger animals. These results may be relevant to the lack of vasoprotection observed in outcome trials of estrogen
therapy in postmenopausal women.
Menopause. 2006 Dec
28; [Epub ahead of print]
Botanical
and dietary supplements for mood and anxiety in menopausal women.
From the Department of 1Obstetrics and
Gynecology, College of Medicine and 2National Center of Excellence in Women's
Health, University of Illinois at Chicago, Chicago, IL.
OBJECTIVE:: This paper
reviews the commonly used botanicals for treatment of mood and anxiety
disorders in perimenopausal and postmenopausal women
and presents information on their safety and efficacy. DESIGN::
The MEDLINE and EMBASE databases were searched for clinical trials related to
the use of botanicals for depression, anxiety, and mood disturbances. Papers
were excluded if they were in a language other than English, did not include
midlife women as study participants, or did not report on changes in mood,
depression, or anxiety. RESULTS:: Five of seven trials
of
Maturitas. 2006 Dec
26; [Epub ahead of print
Use of hormone
replacement therapy (HRT) among women aged 45-64 years in the German
EPIC-cohorts.
Nagel G, Lahmann PH, Schulz M, Boeing H, Linseisen J.
Division of Clinical
Epidemiology, German Cancer Research Centre,
OBJECTIVE: To describe the prevalence and to
assess type and indicators of hormone replacement therapy (HRT) use in the two
German EPIC-cohorts. METHODS: Approximately 30,000 women predominantly aged
35-65 years were recruited in EPIC-Heidelberg and EPIC-Potsdam between 1994 and
1998. Information on diet and lifestyle, medical history and use of hormone
therapy was collected at recruitment. Prevalence and type of HRT-regime was
described and logistic regression models used to examine correlates of HRT-use.
RESULTS: Among women aged 45-64 years, 37.9% in
J Clin Endocrinol Metab. 2006 Dec 27; [Epub ahead of print]
Changes in body
composition in women over six years at mid-life: ovarian and chronological
aging.
Sowers M, Zheng H, Tomey K, Karvonen-Gutierrez C, Jannausch M, Li X, Yosef M, Symons J.
Department of Epidemiology;
Context: Understanding the menopause
association with body weight is important because excess weight increases risk
for stroke, incident cardiovascular disease, cardiovascular mortality, and
all-cause mortality among the middle-aged. Objective: To examine chronological
age and ovarian age and consider how these could influence body size and
composition in mid-life women. Design and Setting: The Study of Women's Health Across the Nation is a longitudinal, community-based study.
This report uses data from the Michigan SWAN site. Participants: 543 pre- or
early perimenopausal African-American and Caucasian
women aged 42-52 years at baseline examination. Main Outcome Measures: Waist
circumference, fat mass and skeletal muscle mass, from bioelectrical impedance,
was assessed in 7 annual serial measures. Annual follicle-stimulating hormone (FSH)
values were assayed by ELISA. The final menstrual period (FMP) was defined
retrospectively following 12 months of amenorrhea. Results:
There was an absolute cumulative six-year increase in fat mass of 3.4 kg and a
six-year decrease in skeletal muscle mass of approximately 0.23 kg.
There was an absolute cumulative six-year increase of approximately 5.7 cm in
waist circumference. The logFSH change was positively
correlated with log(fat mass) change. Waist
circumference increased over the time period, but one year following FMP, the
rate of increase slowed. Fat mass continued to increase with no change in rate.
Conclusions: Both time (chronological aging) and ovarian aging contributed to
substantial changes in body composition (fat and skeletal muscle mass) and
waist circumference. These changes have important ramifications for
establishing a metabolic environment that can be healthy or unhealthy.
J Clin Endocrinol Metab. 2006 Dec 27; [Epub ahead of print]
Endometrial
Effects of Tibolone.
Archer DF, Hendrix S, Gallagher C, Rymer J, Skouby S, Ferenczy A, den Hollander W, et al.
Organon
International,
Background and objectives: The Tibolone Histology of the Endometrium
and Breast Endpoints Study (THEBES) is a multicenter, randomized, double-blind
study designed to address the conflicting reports in the literature about the
endometrial safety of tibolone(1.25 or 2.5mg/day). Tibolone was compared to continuous combined conjugated
equine estrogen (CEE) plus medroxyprogesterone
acetate (MPA) (0.625 + 2.5mg/day). Methods: Subjects were randomized in a 1:1:2
ratio to tibolone 1.25mg/day, 2.5mg/day, and CEE/MPA,
respectively. The one-sided 95% confidence interval has been evaluated for the
incidence of abnormal endometrial histology (hyperplasia or carcinoma), and
hyperplasia and carcinoma separately, for each of the two treatment groups and
for the treatment groups combined after one and two years of treatment with tibolone compared to CEE/MPA. Results: A total of 3,240
women were randomized, with 3,224 receiving at least one dose of study
medication. The incidence and upper one-sided 95% confidence interval (CI) for
the incidence of abnormal endometrium (hyperplasia or
carcinoma), and hyperplasia and carcinoma separately, were calculated at
endpoint, year 1 and year 2. The incidence (upper one-sided 95% CI) of abnormal
endometrium at endpoint was 0.0 (0.5), 0.0 (0.4) and
0.2 (0.5) in the tibolone 1.25mg, 2.5mg, and CEE/MPA
groups, respectively. During the entire treatment period, amenorrhea was
reported more frequently with tibolone 1.25mg
(78.7%), 2.5mg (71.4%) than with CEE/MPA (44.9%). Conclusion: The
MEDSCAPE. From The
Menopause: Cause or
Consequence
Vera Bittner, M.D., F.A.C.C.
The number of postmenopausal women worldwide is
projected to increase from 467 million in 1990 to 1,200 million in 2030.
Understanding the determinants of menopause and its health consequences is thus
becoming increasingly important. Menopausal age is in part genetically
determined. Among health behaviors and environmental factors only smoking has
been consistently associated with an earlier age at menopause] The
menopausal transition is associated with metabolic changes reminiscent of the
metabolic syndrome, but the impact of menopause on subsequent cardiovascular
disease remains controversial, in large part because it is exceedingly
difficult to disentangle adverse effects of aging from potential adverse
effects of menopause. Clinical trials of postmenopausal hormone therapy
designed to correct the estrogen deficiency of the menopausal state have not
shown any reductions in cardiovascular morbidity or mortality.
Kok and colleagues suggest in their provocative paper that cardiovascular risk factors strongly determine
menopausal age, either through direct damage to the ovarian vasculature or
indirectly through an adverse impact on the endocrine system. (http://www.cardiosource.com/expertopinions/hottopics/article.asp?paperID=227). While the
investigators have very accurate data on the age at cessation of menopause, it
is unknown whether women who experienced cessation of menstruation at an early
age were truly menopausal or may have had other endocrine disturbances such as
secondary amenorrhea of varying etiologies or hypothalamic hypoestrogenemia,
a condition which has been associated with angiographic coronary artery disease
in a cohort of women who underwent diagnostic coronary angiography for
suspected myocardial ischemia. Hormonal changes which could potentially
influence cardiovascular risk factor levels begin in the late reproductive
stage and precede menopause by several years. It is not known whether risk
factors measured in the current study were already influenced by early changes
in the reproductive hormonal milieu. Confounding of the analysis by underlying
diseases and conditions which could influence menopausal age is also a concern,
since a substantial proportion of women in the current study had unexplained
improvements in cardiovascular risk factors over time despite advancing age. If
cardiovascular risk factors were a strong determinant of age at menopause, one
would expect substantial variation in menopausal age across different
cardiovascular risk environments. Such variation has not been documented in
contemporary cross-cultural comparisons and some authors have suggested that
menopausal age has not changed since antiquity. Long-term longitudinal
investigations with detailed assessments of reproductive hormones and
cardiovascular risk factors beginning during the reproductive stage and carried
forward through the menopausal transition to the postmenopausal stages are
clearly needed to follow-up on the intriguing hypothesis put forward in the
current study.