Selección de Resúmenes de Menopausia
Semana del 24 al 30 de Enero 2007
Dr. Juan Enrique Blümel
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.
Selección de Resúmenes de Menopausia
Semana del 17 al 23 de Enero 2007
Dr. Juan Enrique Blümel
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.
Selección de Resúmenes de
Menopausia
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.
Selección de Resúmenes de Menopausia
Semana del 2 al 9 de Enero 2007
Dr. Juan Enrique Blümel
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.
Selección de Resúmenes de Menopausia
Semana del 27 de Diciembre de 2006 al 2 de Enero 2007
Dr. Juan Enrique Blümel
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.