Selección de Resúmenes de Menopausia
Junio de 2008
Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile
Semana
del 25 de Junio al 1 de Julio 2008
Menopause . 2008 Jun
20. [Epub ahead of print]
Estrogen and progestogen
use in postmenopausal women: July 2008 position statement of The North American
Menopause Society.
OBJECTIVE: To update for both
clinicians and the lay public the evidence-based position statement published
by The North American Menopause Society in March 2007 regarding its
recommendations for menopausal hormone therapy (HT) for postmenopausal women,
with consideration for the therapeutic benefit-risk ratio at various times
through menopause and beyond. DESIGN:: An Advisory Panel of clinicians and
researchers expert in the field of women's health was enlisted to review the
March 2007
Med Hypotheses. 2008
Jun 19. [Epub ahead of print]
Who is the culprit
for post menopausal syndrome? Uterus/Ovary!
Patki SM, Kadam
SS, Phadnis SM, Bhonde RR.
Patki Research
Foundation and Hospital,
The uterine
endometrium of placental mammals in general and human in particular is a highly
dynamic, proliferative and regenerative tissue. It undergoes cycles of growth
and regression during each menstrual cycle with a growing capacity from 0.5-1mm
in the proliferative phase to 5-7mm during the secretory (leutal) phase. These
phases are characterized by cyclic processes of cellular proliferation,
differentiation and shedding. Recent studies have revealed that the endometrium
harbours a large population of mesenchymal stromal cells. There are several
reports indicating the homing of bone marrow stem cells and endothelial
progenitor cells in regenerating endometrium. However, it is not clear whether
endometrial cells mobilise to participate in the repair and regeneration of
vital organs/tissues. We hypothesize that a very small percentage of the
endometrial cells may set in circulation during menstrual cycle to facilitate
endogenous regeneration of vital organs in the body. These cyclical events may
be responsible for providing a protective barrier to women during her
child-bearing age. Disappearance of this barrier after menopause probably makes
her vulnerable for post menopausal symptoms. There is a circumstantial evidence
to vouch for the presence of circulating stem/progenitor cells in peripheral
blood which are likely to lodge in injured organs for their possible repair. As
the endometrium harbors a large population of mesenchymal stromal cells, it is
possible that retention of the uterus through secretion of reparative/growth
promoting factors, may provide legitimate stem cells to enter circulation and
"set up shop" in other tissues like bone marrow stem cells. In this
context we propose uterus to be the culprit for the postmenopausal syndrome.
J Med Assoc
The association of
dietary calcium, bone mineral density and biochemical bone turnover markers in
rural Thai women.
Pongchaiyakul C, Kosulwat V,
Charoenkiatkul S, Chailurkit LO, Rojroongwasinkul N, Rajatanavin R.
Division Endocrinology and
Metabolism, Faculty of Medicine,
OBJECTIVE: To investigate the
relative contribution of dietary calcium intake on bone mineral density (BMD)
and biochemical bone turnover markers in rural Thai women. MATERIAL AND METHOD:
A cross-sectional investigation was designed in 255 rural Thai women. Usual
dietary calcium intake was determined by 3-day food records and quantitative
food-frequency questionnaire. BMD was measured by DXA. The three markers for
bone turnover event: serum total alkaline phosphatase, serum N-mid osteocalcin
and type I collagen C-telopeptide, including serum calcium and were determined
in 125 women in the present study. RESULTS: An average daily calcium intake in
the present study was 265 mg/day. Two hundred and thirty three out of 255 women
(87%) consumed dietary calcium less than half of the recommended value and only
3% of women (n=7) had calcium intake >800 mg/day. After controlling certain
parameters: age and body mass index, women who consumed higher amount of
dietary calcium had significantly higher BMD at all sites. Moreover highly
increased bone turnover markers were observed in those with lowest quartile
calcium intake. Women with osteopenia and osteoporosis were older, lower BMI,
consumed less calcium and had significantly higher values of all biochemical
bone turnover markers than those who had normal BMD. CONCLUSION: The present
study showed that a habitual diet of the rural Thai population might not
provide enough calcium as needed for bone retention and for prevention of bone
loss in the following years. Modification of eating pattern by promotion of
increased consumption of locally available calcium rich food may be beneficial for
prevention of osteoporosis among this population.
Menopause. 2008 Jul
17. [Epub ahead of print]
Cycle and hormone
changes during perimenopause: the key role of ovarian function.
Burger HG, Hale GE, Dennerstein L, Robertson DM.
From the 1Prince Henry's Institute
of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia;
2Department of Obstetrics and Gynaecology, University of Sydney, NSW,
Australia; 3Office for Gender and Health, Department of Psychiatry, University
of Melbourne, Parkville, Victoria, Australia.
The menopausal transition is
the stage in reproductive life commonly defined as commencing with the onset of
menstrual irregularity. Classic studies of the endocrinology of the transition
postulated the existence of inhibin in women to explain the observed increase
in follicle-stimulating hormone (FSH) levels without a significant decrease in
estradiol (E2). Descriptions were provided of cycle characteristics during the
transition, emphasizing the unpredictability of the endocrine changes rather
than the occurrence of an orderly and progressive decline in ovarian function.
Women older than the age of 45 exhibited menstrual irregularity when the
average number of primordial follicles per ovary decreased to approximately
100. Inhibin B is a major regulator of FSH secretion and a product of small
antral follicles. Its levels respond to the early follicular phase increase and
decrease in FSH. The age-related decrease in ovarian primordial follicle
numbers, which is reflected in a decrease in the numbers of small antral
follicles, leads to a decrease in inhibin B, which in turn leads to an increase
in FSH, hypothesized to act as a stimulus to the maintenance of circulating E2
in the follicular phase until late in the transition. Concurrently, the
concentrations of testosterone do not change significantly. Early follicular
phase FSH levels in women reporting menstrual irregularity fluctuate markedly,
with a more uniform increase in levels when no menses have occurred for at
least 3 months. Anovulatory cycles occur at increased frequency in the last 30
months before final menses or menopause. In ovulatory cycles, FSH shows little,
if any, increase, but anovulatory cycles are usually characterized by low
levels of inhibin B, markedly increased levels of FSH, and low levels of E2.
Thus, the heterogeneity of follicular phase FSH represents a mixture of
ovulatory and anovulatory cycles. Longitudinal data indicate that both
ovulatory and anovulatory cycles occur after entry into both the early and late
menopausal transition and that ovulatory cycles occur even after final menses.
There is no endocrine marker of menopause, which may be primarily an
endometrial event. Using the hormonal concentrations in ovulatory cycles
observed in women in mid-reproductive age as controls and comparing such
concentrations in late reproductive age women older than 45 either continuing
to cycle regularly or having entered the early or late menopausal transition, a
gradual increase in follicular phase FSH and E2 and a decrease in inhibin B
were observed in ovulatory cycles. Anovulatory cycles showed markedly increased
FSH with low E2 and inhibin B. No specific endocrine change was characteristic
of either the early or late menopausal transition, confirming the observations
of previous studies regarding the unpredictability of cycle characteristics and
hormone changes with the approach of menopause. Antimüllerian hormone
correlates with follicle numbers and shows a large age-related decrease to
reach undetectable levels at menopause. Thus, the marked decrease in follicle
numbers during late reproductive age appears to predispose to erratic and
unpredictable cycle characteristics, with normal ovulatory cycles continuing to
occur episodically. There is no specific endocrine marker of the early or late
transition, making measurements of FSH or E2 unreliable in attempting to stage
an individual with regard to approaching menopause.
Climacteric. 2008
Jun;11(3):258-64
Potential role of
progestogens in the control of adipose tissue and salt sensitivity via
interaction with the mineralocorticoid receptor.
Caprio M, Zennaro MC, Fève B, Mammi C,
Fabbri A, Rosano G.
IRCCS San Raffaele Pisana, Rome, Italy.
Beside their role in the control
of water and electrolyte homeostasis, recent data clearly indicate that
aldosterone and the mineralocorticoid receptor (MR) are involved in adipocyte
biology. It has been recently shown that aldosterone promotes white and brown
adipocyte differentiation in vitro through specific activation of the MR. In
addition, a non-epithelial pro-inflammatory role for MR activation has been
recently inferred from studies on mineralocorticoid/salt administration in
experimental animal models and from clinical studies. The mineralocorticoid
system could hence represent a potential target for new therapeutic strategies
in obesity and the metabolic syndrome. Progesterone has high affinity for the
MR and is a natural antagonist of aldosterone. Differently from classic
synthetic progestins, which are devoid of antimineralocorticoid properties,
progesterone and new progestogens show remarkable antimineralocorticoid
effects. Here, we discuss the potential role of the antimineralocorticoid
properties of progestogens in the control of body weight, adipose tissue
proliferation and salt sensitivity; their therapeutic use in postmenopausal
women, as well as in women affected by polycystic ovary syndrome, may open new
and unexpected possibilities in the treatment of related metabolic disorders.
Climacteric. 2008
Jun;11(3):181-91.
Testosterone
therapy for sexual dysfunction in postmenopausal women.
Hubayter Z, Simon JA.
Division of Reproductive
Endocrinology and Infertility, Department of Gynecology and Obstetrics, Johns
Hopkins University School of Medicine, Baltimore, MD, USA.
BACKGROUND: After menopause,
both surgical and natural, increases occur in the number of women experiencing
sexual dysfunction. Although a direct link between sexual dysfunction and
endogenous testosterone levels has not been clearly established, testosterone
therapy is known to improve the signs and symptoms related to hypoactive sexual
desire. However, testosterone supplementation is not approved in the
Nutr Cancer. 2008
Jul-Aug;60(4):534-41.
Obesity accelerates
mouse mammary tumor growth in the absence of ovarian hormones.
Nunez NP, Perkins SN, Smith
NC, Berrigan D, Berendes DM, Varticovski L, Barrett JC, Hursting SD.
National Cancer Institute
(NCI), National Institutes of Health (NIH),
Obesity increases incidence
and mortality of breast cancer in postmenopausal women. Mechanisms underlying
this association are poorly understood. Suitable animal models are needed to
elucidate potential mechanisms for this association. To determine the effects
of obesity on mammary tumor growth, nonovariectomized and ovariectomized
C57BL/6 mice of various body weights (lean, overweight, and obese) were
implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1
transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1
tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1
tumor growth consistent with the known hormone responsiveness of these tumors.
However, obesity accelerated tumor growth in ovariectomized but not in
nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of
breast cancer enhanced tumor growth, specifically in the absence of ovarian
hormones. These results support epidemiological evidence that obesity is
associated with increased breast cancer incidence and mortality in
postmenopausal but not premenopausal women. In contrast, maintaining a lean
body weight phenotype was associated with reduced Wnt-1 tumor growth regardless
of ovarian hormone status.
Gynecol Endocrinol.
2008 Jun;24(6):347-53.
The effects of
estrogen therapy and estrogen combined with different androgenic progestins on
carbohydrate and lipid metabolism in overweight-obese younger postmenopausal
women.
Demir B, Ozturkoglu E,
Solaroglu A, Baskan B, Kandemir O, Karabulut E, Haberal A.
Department of Obstetrics and
Gynecology, Etlik Maternity and Women's
Objective. The aim of the
present study was to compare the effect of three different progestins with
differing androgenicity on carbohydrate and lipid metabolism in
overweight-obese younger postmenopausal women. Additionally, the relationship
between testosterone and insulin resistance was assessed. Methods. The study
included 125 postmenopausal women. Estradiol (E(2)) 2 mg/day was given to 20
hysterectomized women and the remaining 105 women were randomized into three
treatment groups: E(2) 2 mg/day plus dienogest 2 mg/day (n=35); E(2) 2 mg/day
plus norethisterone acetate (NETA) 1 mg/day (n=35); E(2) 2 mg/day plus
medroxyprogesterone acetate (MPA) 2.5 mg/day (n=35). A 75-g oral glucose
tolerance test was performed at the initial and 3-month visit. Serum glucose,
insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-C),
low-density lipoprotein cholesterol (LDL-C) and triglycerides were measured
before and after treatment. Results. A significant treatment-related increase
was observed only in the E(2)/MPA group for insulin resistance (p=0.031). When
the change in the insulin/glucose ratio was compared, the E(2) group was
significantly different from the E(2)/MPA and E(2)/NETA groups (p=0.008 and
0.02, respectively). Only the E(2)/dienogest group showed a treatment-related
increase in fasting glucose level (p=0.037). A decrease in total cholesterol
and LDL-C levels was observed in all groups (p=0.004 and 0.012, respectively).
The only significant decrease in HDL-C level was observed in the E(2)/NETA
group (p=0.005). Conclusion. Estrogen therapy had a positive effect on
carbohydrate and lipid metabolism in overweight-obese postmenopausal women. The
addition of progestin to estrogen therapy attenuated estrogen's positive
effects slightly; however, the biological actions of the three different
androgenic progestins used did not result in any variation.
Arch Gynecol Obstet.
2008 Jun 27. [Epub ahead of print
Short-term effect
of tibolone on C-reactive protein in hypertensive postmenopausal women.
Engin-Üstün Y,
Ustün Y, Türkçüoğlu I, Mutlu Meydanlı M, Kafkaslı
A, Yetkin G.
Department of Obstetrics and
Gynecology,
OBJECTIVE: To evaluate the
effects of tibolone on the serum C-reactive protein (CRP) in hypertensive
postmenopausal women. METHODS: We enrolled 45 postmenopausal patients with
hypertension and 17 normotensive postmenopausal women. Inclusion criteria were
surgical menopause, the presence of vasomotor symptoms, and normal mammogram within
1 year, the absence of documented coronary artery disease, and normal
electrocardiography. Forty hypertensive women and 17 normotensive women
completed the 3-month period. Twenty-one hypertensive women received tibolone,
whereas 19 served as control. At baseline and at 3 months, blood lipids and CRP
were evaluated. RESULTS: Changes in lipid profile and CRP in the hypertensive
and normotensive control groups during 3 months were not statistically
significant. Total cholesterol levels decreased significantly after 3 months of
tibolone treatment. A significant increase in CRP values was observed in the
tibolone group (p = 0.001). CONCLUSION: This trial demonstrated that tibolone
treatment induced a significant increase in CRP and a significant decrease in total
cholesterol in postmenopausal hypertensive women.
Osteoporos Int. 2008
Jun 26. [Epub ahead of print
The prevalence of
radiographic vertebral fractures in Latin American countries: the Latin
American Vertebral Osteoporosis Study (LAVOS).
Clark P, Cons-Molina F, Deleze
M, Ragi S, Haddock L, Zanchetta JR, Jaller JJ, Palermo L, Talavera JO, Messina
DO, Morales-Torres J, Salmeron J, Navarrete A, Suarez E, Pérez CM,
Cummings SR.
Clinical Epidemiology Unit,
CMN Siglo XXI, IMSS Faculty of Medicine UNAM, Blvd. Virreyes 1010, Lomas de Chapultepec, 11000, DF, Mexico
City, Mexico, patriciaclark@prodigy.net.mx.
In the first population-based
study of vertebral fractures in
Osteoporos Int. 2008
Jun 26. [Epub ahead of print]
Effectiveness of
antiresorptives for the prevention of nonvertebral low-trauma fractures in a
population-based cohort of women.
Langsetmo LA, Morin S,
Richards JB, Davison KS, Olszynski WP, Prior JC, Josse R, Goltzman D; CaMos
Research Group. CaMos National Coordinating Centre,
Observational studies are
needed to quantify real-life effectiveness of antiresorptive therapy in the
prevention of clinical fractures. Antiresorptive therapies were associated with
an overall 32% reduction in low-trauma nonvertebral fracture risk among women
50 and older. Effectiveness may be lower among older women and those without
risk factors. INTRODUCTION: Randomized controlled trials have shown that
antiresorptive therapies reduce the risk of fracture in selected populations, but
further study is needed to quantify their real-life effectiveness. The study
objective was to determine the association between antiresorptive use and
low-trauma nonvertebral fracture in women 50 and older. METHODS: The design was
a retrospective nested case-control study (density-based sampling) within the
Canadian Multicentre Osteoporosis Study. There were 5,979 eligible women with
453 cases and 1,304 matched controls. RESULTS: The current use of
antiresorptives was associated with a decreased risk of fracture with OR =
0.68, 95% CI: 0.52-0.91; where OR is the adjusted odds ratio and CI is the
confidence interval. Subgroup analysis yielded OR = 0.61, 95% CI: 0.42-0.89 for
ages 50-74; OR = 0.76, 95% CI: 0.50-1.17 for ages 75+; OR = 0.58, 95% CI:
0.40-0.83 for those with a major risk factor; and OR = 0.92; 95% CI: 0.59-1.42
for those without a major risk factor. Major risk factors were prevalent
low-trauma fracture, vertebral deformity (grade 2+), and BMD T-score </=
-2.5. CONCLUSIONS: Antiresorptive therapy is associated with a clinically
important reduction in low-trauma nonvertebral fracture risk among
community-dwelling women aged 50 and older. Antiresorptive therapy may be less
effective for women 75 and older and women without major risk factors.
Semana
del 17 al 24 de Junio 2008
J Sex Med. 2008
Jun 17. [Epub ahead of print]
Prevalence and Risk
Factors for Low Sexual Function in Women: A Study of 1,009 Women in an
Outpatient Clinic of a
Aslan E, Beji NK, Gungor I,
Kadioglu A, Dikencik BK.
Introduction. Sexual
functioning is a common and multidimensional problem, associated with multiple
biological, medical, psychological, sociocultural, political, economic, and
interpersonal factors. Aim. The study was planned to determine the prevalence
and risk factors for low sexual function in women in an outpatient clinic of a
university hospital in
Osteoporos Int.
2008 Jun 19. [Epub ahead of print]
Change in the use
of hormone replacement therapy and the incidence of fracture in
Meyer HE, Lofthus CM,
Søgaard AJ, Falch JA.
Section of Epidemiology and
Biostatistics,
Fracture incidence in
Nutrition. 2008
Jun 16. [Epub ahead of print
Association between
dietary fiber and markers of systemic inflammation in the Women's Health
Initiative Observational Study.
Ma Y, Hébert JR, Li W,
Bertone-Johnson ER, Olendzki B, Pagoto SL, Tinker L, Rosal MC, Ockene IS,
Ockene JK, Griffith JA, Liu S.
Division of Preventive and
Behavioral Medicine, Department of Medicine, University of Massachusetts
Medical School, Worcester, Massachusetts, USA.
OBJECTIVE: Systemic
inflammation may play an important role in the development of atherosclerosis,
type 2 diabetes, and some cancers. Few studies have comprehensively assessed
the direct relations between dietary fiber and inflammatory cytokines,
especially in minority populations. Using baseline data from 1958
postmenopausal women enrolled in the Women's Health Initiative Observational
Study, we examined cross-sectional associations between dietary fiber intake
and markers of systemic inflammation (including serum high-sensitivity
C-reactive protein [hs-CRP], interleukin-6 [IL-6], and tumor necrosis
factor-alpha receptor-2 [TNF-alpha-R2]) in addition to differences in these
associations by ethnicity. METHODS: Multiple linear regression models were used
to assess the relation between fiber intake and makers of systemic
inflammation. RESULTS: After adjustment for covariates, intakes of dietary
fiber were inversely associated with IL-6 (P values for trend were 0.01 for
total fiber, 0.004 for soluble fiber, and 0.001 for insoluble fiber) and
TNF-alpha-R2 (P values for trend were 0.002 for total, 0.02 for soluble, and
<0.001 for insoluble fibers). Although the samples were small in minority
Americans, results were generally consistent with those found among European
Americans. We did not observe any significant association between intake of
dietary fiber and hs-CRP. CONCLUSION: These findings lend support to the
hypothesis that a high-fiber diet is associated with lower plasma levels of
IL-6 and TNF-alpha-R2. Contrary to previous reports, however, there was no
association between fiber and hs-CRP among postmenopausal women. Future studies
on the influence of diet on inflammation should include IL-6 and TNF-alpha-R2
and enroll participants from ethnic minorities.
Vasc Health Risk
Manag. 2008;4(2):453-62.
Is there an
independent effect of polycystic ovary syndrome (PCOS) and menopause on the
prevalence of subclinical atherosclerosis in middle aged women?
Talbott EO, Zborowski J, Rager
J, Stragand JR.
Department Epidemiology,
Polycystic ovary syndrome (PCOS),
a common reproductive endocrine condition manifests at puberty, and is
characterized by hyperandrogenism, chronic anovulation, and obesity. PCOS cases
exhibit an adverse coronary heart disease (CHD) profile at an early age,
including insulin resistance, dyslipidemia and increased central adiposity. It
can be hypothesized that the menopausal transition, whether natural or
surgical, may provide an additional "insult", resulting in greater
cumulative risk to their vasculature. Coronary artery calcification (CAC), a
measure of subclinical atherosclerosis (SCA), was measured by electron beam
tomography in 149 PCOS cases and 166 controls (mean age 47.3 and 49.4
respectively). Cases had a higher prevalence of CAC (63.1%) compared to
controls (41.0%), (p = 0.037) after adjustment for age and BMI. A total of 22
cases and 39 controls had undergone natural menopause, 12 cases and 26 controls
underwent surgical menopause (with biochemical confirmation) and 115 cases and
101 controls reported being currently premenopausal. There was a significant
difference in CAC values between cases and controls in all three-menopause
categories including pre-menopausal, surgically induced and natural menopause
(p < 0.001). Duration since menopause (years) and use of hormone replacement
therapy were not different between cases and controls for the two menopause
groups. Logistic regression was carried out with CAC (< or = 10 vs > 10)
as the dependent variable, and independent variables: PCOS status, current age,
BMI, and menopausal status, (pre-menopause, surgical and natural menopause) and
selected CHD risk factors. The data indicate that women with PCOS exhibit
significantly increased CAC compared to controls after adjustment for age and
BMI and menopausal status. PCOS status and fasting glucose were significant
risk factors for CAC (p < 0.05). Both natural and surgical menopause were
independent risk factors for CAC as well (p < 0.01). HDLT was of borderline
significance, p < 0.10. Further follow-up of this cohort will be valuable in
determining whether PCOS status continues to affect cardiovascular risk as they
undergo the menopausal transition.
J Endocrinol
Invest. 2008 May;31(5):416-21
Effects of
raloxifene therapy on circulating osteoprotegerin and RANK ligand levels in
post-menopausal osteoporosis.
Fernández-García
D, Muñoz-Torres M, Mezquita-Raya P, de la Higuera M, Alonso G,
Reyes-García R, Ochoa AS, Ruiz-Requena ME, Luna JD,
Escobar-Jiménez F.
Bone Metabolic Unit,
Endocrinology Division,
Previous in vitro studies
suggest that the anti-resorptive effect of raloxifene might be mediated by
changes in several cytokines involved in the bone remodeling process. In this
context, the osteoprotegerin (OPG)- receptor activator of NF kappa B ligand
(RANKL) system is considered a key component in the osteoclastogenesis
regulation. The aim of this study was to determine the effects of raloxifene
treatment on serum concentrations of OPG, receptor RANKL and its relationship
with biochemical markers of bone turnover and bone mineral density (BMD) in
previously untreated women with post-menopausal osteoporosis. We selected 47
post-menopausal women (mean age 63+/-7 yr) with densitometric criteria of
osteoporosis. We determined at baseline, 3, 6, and 12 months anthropometric
parameters, biochemical markers of bone turnover, serum levels of 25(OH) D,
serum levels of OPG and RANKL. BMD (dual-energy x-ray absorptiometry) in lumbar
spine (LS) femoral neck and total hip was measured at baseline and 12 months
after raloxifene (60 mg/day) treatment. Serum levels of OPG decreased in the
3rd and 6th month of treatment (p<0.001) and returned to basal levels in the
12th month. There was a significant decrease of RANKL levels and OPG/RANKL
ratio after 1 yr of raloxifene treatment. In addition, BMD in LS increased
significantly (2.5%) in the 12th month of treatment (p=0.031). Finally, the
biochemical markers of bone turnover (total alkaline phosphatase, bone alkaline
phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine
cross-linked carboxi-terminal telopeptide of type I collagen) decreased
significantly from the 3rd month of treatment. In conclusion, our results
support the hypothesis that raloxifene may inhibit osteoclast activity, at least
partly modulating the OPG-RANKL system.
Metabolism. 2008
Jul;57(7):961-5
Relationship
between endogenous testosterone and cardiovascular risk in early postmenopausal
women.
Maturana MA,
Gynecological Endocrinology
Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre,
90050-170 Porto Alegre, RS, Brazil.
Cardiovascular disease (CVD)
is the leading cause of death among postmenopausal women. Changes in
endothelial function play an important role in the pathophysiology of
atherosclerosis, and evidence suggests that interventions to improve
endothelial function could modify the rates of progression and the risk of
cardiovascular events. In addition, a positive association between markers of
endothelial dysfunction and androgenicity has been described in women with
polycystic ovary syndrome, suggesting a correlation with the early-onset
endothelial dysfunction found in these patients. We performed a cross-sectional
study to verify whether endogenous testosterone levels are correlated with
markers of inflammation and endothelial function and with anthropometric and
metabolic profile in 53 postmenopausal women. Serum testosterone, sex
hormone-binding globulin, C-reactive protein (CRP), fibrinogen, and plasma endothelin-1
(ET-1) were determined. Patients were stratified into 2 groups (higher or lower
than the mean testosterone levels of the studied sample). Mean age was 55 years
(+/-5), and median time since menopause was 5.5 years (interquartile range, 3-8
years). Body mass index and waist circumference were significantly higher in
the group with testosterone levels >/=0.49 ng/mL. Median CRP levels were
greater in the group with higher testosterone levels (1.17 [0.17-2.36] vs 0.17
[0.17-0.61] mg/L, P = .039). Median ET-1 levels were also higher in women with
greater testosterone levels (0.84 [0.81-0.97] vs 0.81 [0.74-0.84] pg/mL, P =
.023). An association of testosterone with CRP (r = 0.416, P = .004) and ET-1
(r = 0.323, P = .031) was observed. This association was dependent on
homeostasis model assessment index for ET-1 but not CRP. Testosterone was also
associated with waist circumference and blood pressure (P = .001). These data
suggest that endogenous testosterone levels in recently postmenopausal women
may be part of a proatherogenic profile. Longitudinal studies are needed to
assess if androgenicity represents a risk factor for cardiovascular disease and
the clinical relevance of its association with ET-1 and CRP in this population.
Menopause. 2008
Jun 10. [Epub ahead of print]
Objective hot
flashes are negatively related to verbal memory performance in midlife women.
Maki PM, Drogos LL, Rubin LH,
Banuvar S, Shulman LP, Geller SE.
Departments of Psychiatry,
Psychology, and Obstetrics and Gynecology, University of Illinois, Chicago,
IL; Feinberg School of Medicine,
Northwestern University, Chicago, IL.
OBJECTIVE:: To test the
hypothesis that hot flashes specifically relate to verbal memory performance by
examining the relationship between objective hot flashes and cognitive test
performance in women with moderate to severe vasomotor symptoms. DESIGN:: In an
observational study, 29 midlife women (mean age, 53 y) with moderate to severe
hot flashes provided measures of objective hot flashes with an ambulatory hot flash
monitor, subjective hot flashes with a diary and questionnaire, and objective
measures of verbal memory and other cognitive functions with standardized
neuropsychological tests. RESULTS:: The mean number of objective hot flashes
was 19.5 per day (range, 6 to 35), including 15.3 (range, 6 to 35) during
waking hours and 4.2 (range, 0 to 9) during sleep. The mean sensitivity (ie,
subjective detection of objectively measured hot flashes) was 60%. Regression
analyses revealed that total number of objective hot flashes, sleep duration,
and verbal knowledge were significant predictors of delayed verbal memory.
Verbal fluency correlated positively with objective daytime hot flashes. Hot
flashes did not predict performance on any of the other secondary cognitive measures
(ie, attention, working memory, visual memory), although poor sleep predicted
worse performance on several outcome measures. CONCLUSIONS:: Highly symptomatic
women underreport the number of objective hot flashes that they experience by
43%. Verbal memory performance relates significantly to the objective number of
hot flashes women experience but not to the number of hot flashes that they
report. These findings suggest that physiological factors related to hot
flashes, rather than psychological factors, predict poorer verbal memory
function.
Semana
del 11 al 17 de Junio 2008
Osteoporos Int. 2008 Jun 13. [Epub
ahead of print]
Vitamin D status and response to treatment in post-menopausal
osteoporosis.
Adami S, Giannini S, Bianchi G, Sinigaglia L, Di Munno O, Fiore CE, Minisola S, Rossini M.
Rheumatology Unit, Ospedale di Valeggio, 37067,
Valeggio, Verona, Italy, silvano.adami@univr.it.
INTRODUCTION: Several drugs
were registered for the treatment of osteoporosis on the basis of clinical
trials in which vitamin D repletion was a pre-requisite inclusion criteria and
vitamin D supplements were used as adjunctive therapy. However, in routine
clinical practice these supplements are not consistently recommended. METHODS:
We studied 1515 women with postmenopausal osteoporosis under treatment with anti-resorbing
agents (alendronate, risedronate, raloxifene) for 13.1 months with an adherence
> 75%. The patients were classified as vitamin D deficient (N = 514) or
vitamin D repleted (N = 1001) according to risk factors (N = 1062) or the level
of 25(OH) vitamin D [25(OH)D] above or below 50 nmol/l (N = 453). RESULTS:
Vitamin D deficient and vitamin D repleted subjects differed significantly for
annualized spine and hip bone mineral density (BMD) changes adjusted for all
available confounding factors (type of treatment, age, global calcium intake,
baseline BMD values). One hundred fifty one patients suffered from a new
incident clinical fracture. The adjusted odds ratio for incident fractures in
vitamin D deficient as compared to vitamin D repleted women was 1.77 (1.20 -
2.59, 95% CI; p = 0.004). CONCLUSIONS: Optimal vitamin D repletion seems to be
necessary to maximize the response to anti-resorbers in terms of both BMD
changes and anti-fracture efficacy.
Menopause. 2008 Jun 11. [Epub
ahead of print]
A randomized, placebo-controlled trial of the effects of physical
exercises and estrogen therapy on health-related quality of life in
postmenopausal women.
Moriyama CK, Oneda B, Bernardo FR, Cardoso CG Jr, Forjaz CL, Abrahao SB, Mion D Jr, Fonseca AM, Tinucci T.
Department of Obstetrics and
Gynecology,
OBJECTIVE:: The purpose of
this study was to evaluate the isolated and associated effects of estrogen
therapy (estradiol valerate 1 mg/d orally) and physical exercise (moderate
aerobic exercise, 3 h/wk) on health-related quality of life (HRQOL) and
menopausal symptoms among women who had undergone hysterectomy. DESIGN:: A
6-month, randomized, double-blind, placebo-controlled clinical trial with 44
postmenopausal women who had undergone hysterectomy. The interventions were
physical exercise and hormone therapy (n = 9), being sedentary and hormone
therapy (n = 14), physical exercise and placebo (n = 11), and being sedentary
and placebo (n = 10). HRQOL was assessed by a Brazilian standard version of the
Medical Outcome Study Short-Form Health Survey and symptoms by Kupperman Index
at baseline and after 6 months. RESULTS:: There was a decrease in symptoms in
all groups, but only groups who performed physical exercise showed an increase
in quality of life. Analysis of variance showed that changes in physical
functioning (P = 0.001) and bodily pain (P = 0.012) scores over the 6-month
period differed significantly between women who exercised and women who were
sedentary, regardless of hormone therapy. Hormone therapy had no effect, and
there was also no significant association between physical exercise and hormone
therapy in HRQOL. CONCLUSIONS:: Physical exercises can reduce menopausal
symptoms and enhance HRQOL, independent of whether hormone therapy is taken.
Menopause. 2008 Jun 10. [Epub
ahead of print]
Lipid profile of women with premature ovarian failure.
Knauff EA, Westerveld
HE, Goverde AJ, Eijkemans
MJ, Valkenburg
O, van
Santbrink EJ, Fauser BC, van der
Schouw YT.
Departments of 1Reproductive
Medicine and Gynecology and 2Internal Medicine, 3Julius Centre for Health
Sciences and Primary Care, University Medical Centre
OBJECTIVE:: Earlier menopause
is associated with a higher incidence of cardiovascular events later in life.
Concurrent with the ages of menopausal transition, a shift in lipid profile
takes place. Premature ovarian failure (POF) or premature menopause allows us
to study the effect of cessation of ovarian function on the lipid profile
independent of effects of advanced chronological age. DESIGN:: Fasting
triglycerides (TGs), total high-density lipoprotein (HDL), and low-density
lipoprotein cholesterol levels were measured in 90 women with POF not using any
hormone therapy and 198 population controls of the same age range not using
oral contraceptives. Correlations between lipids and ovarian function
parameters were assessed. RESULTS:: After correction for age, body mass index,
and smoking, women with POF presented with significantly higher TG levels (mean
difference: 0.17 log mmol/L [95% CI: 0.06-0.29]). HDL cholesterol levels were
borderline significantly lower in women with POF. No age-corrected correlation
between triglycerides or other lipids and estradiol levels or time of estrogen
deprivation could be identified. However, the free androgen index, sex
hormone-binding globulin, and testosterone concentrations showed significant
correlations with TGs and/or HDL cholesterol concentrations. CONCLUSIONS:: Loss
of ovarian function at a very young age (POF) coincides with subtle changes in
the lipid profile (higher TG levels and marginally lower HDL). Androgens
(increased free androgen index and testosterone and decreased sex
hormone-binding globulin) are better markers for unfavorable lipid changes
compared with estrogen levels or duration of estrogen deprivation in women with
POF. Elevated TG levels in combination with increased (free) androgens may be
an early manifestation of reduced insulin sensitivity.
J Sex Med. 2008 Jun 10. [Epub
ahead of print]
Effect of Hormone Replacement Therapy on Clitoral Artery Blood Flow in Healthy
Postmenopausal Women.
Alatas E, Yagci B, Oztekin O, Sabir N.
Department of Obstetrics and
Gynecology,
Introduction. Aging and the
decline of ovarian hormonal secretion during menopause may alter libido, and
sexual response and functioning. The effects of hormone replacement therapy
(HRT) on the genital vascular hemodynamics have been widely studied. However,
there is a lack of knowledge about the effect of HRT on basal clitoral blood
flow. Aim. The aims of this study were to measure clitoral artery blood flow
and to determine whether HRT has a significant effect in clitoral artery blood
flow in postmenopausal women. Methods. Doppler sonography of clitoral arteries
was performed in 25 postmenopausal women aged 51.3 +/- 4.5 years who had been
using a continuous combined HRT (0.625 mg of conjugated equine estrogens plus
2.5 mg medroxyprogesterone acetate, in 1 tablet daily) for 2.0 +/- 1.1 years,
and the clitoral artery peak systolic velocity, resistance index (RI), and
pulsatility index (PI) were measured. Thirty-five postmenopausal women aged
50.0 +/- 4.2 years who had not used HRT served as a control group. Main Outcome
Measures. Assessment of clitoral blood flow with color Doppler ultrasonography
by measuring the peak systolic velocity, RI, and PI. Results. Clitoral artery
circulation was easily detectable by the color Doppler sonography. The clitoral
artery peak systolic velocities were significantly higher in postmenopausal
women taking HRT compared with the control group (11.8 +/- 5.2 cm/second vs.
15.0 +/- 5.4 cm/second, P = 0.025). Conclusion. HRT improves blood flow to the
clitoris. A clitoral blood flow evaluation may be proposed as a potential tool
to assess the impact of HRT on the genital tissues and to investigate female
sexual response disorders in postmenopausal women.
Bull Cancer. 2008 Jun 10;95(5):495-502.
Dual effects of androgens on mammary gland
Service de gynécologie-obstétrique,
CHRU, 1, place de l'Hôpital, 67091 Strasbourg.
Androgens have a dual effect
on mammary cells. Indeed, they have an influence on mammary cells proliferation
thanks to several possible mechanisms, including their transformation into
dihydrotestosterone (5alpha-reductase pathway) or into estradiol (aromatase
pathway) or their binding to the androgen receptor (AR) and/or to the estrogen
receptor (ER). Androgen signaling, using 5alpha-reductase pathway, enables the
control of cell proliferation, mediated by AR. So androgen signaling plays a
crucial role in breast homeostasis, negating the proliferative effects of
estrogen signaling in the breast. When androgens transform into estrogens
(aromatase pathway), they increase cell proliferation and mammary
carcinogenesis risk. High levels of androgens and estrogens in the serum are
associated with increased incidence of postmenopausal breast cancers. Genetic
variations in metabolic genes (CYP11, CYP19) and in the AR gene are both involved
in dual effects of androgens. Since mammary cells metabolic enzymes vary with
time, aging increases the risk of breast cancer induced by estrogens and
androgens. In addition, AR function can be perturbed by low doses of synthetic
progestin, acting as endocrine disruptors to negate the protective effects of
androgen signaling in the breast. In the future, the determination of AR
expression in infiltrative breast cancer specimens and circulating androgens
levels could provide additional information about hormonal dependency and
prognosis of breast carcinomas.
Am J Prev Med. 2008 Jul;35(1):47-54.
Prevalence, family history, and prevention of reported osteoporosis in
Robitaille
J, Yoon PW, Moore CA, Liu T, Irizarry-Delacruz
M, Looker AC, Khoury MJ.
CDC, the
BACKGROUND: Osteoporosis is a
major public health concern and has been associated with a family history
positive for the condition. However, data on the behaviors of individuals with
such a family history are scarce. The objectives of this study were to assess
the relationship between the prevalence of reported physician-diagnosed
osteoporosis and family history in a representative sample of
Bone. 2008 Apr 26. [Epub
ahead of print]
Effect of denosumab on bone density and turnover in postmenopausal women
with low bone mass after long-term continued, discontinued, and restarting of
therapy: A randomized blinded phase 2 clinical trial.
Miller PD, Bolognese
MA, Lewiecki
EM, McClung MR, Ding B, Austin M, Liu Y, San Martin
J, For The
Amg 162 Bone Loss Study Group .
INTRODUCTION: Denosumab is a
fully human monoclonal antibody that inhibits receptor activator of nuclear
factor-kappa B ligand (RANKL), an essential mediator of osteoclast formation,
function, and survival that has been shown to decrease bone turnover and
increase bone mineral density (BMD) in treated patients. We assessed the
long-term efficacy and safety of denosumab, and the effects of discontinuing
and restarting denosumab treatment in postmenopausal women with low bone mass.
METHODS: Postmenopausal women with a lumbar spine T-score of -1.8 to -4.0 or
proximal femur T-score of -1.8 to -3.5 were randomized to denosumab every 3
months (Q3M; 6, 14, or 30 mg) or every 6 months (Q6M; 14, 60, 100, or 210 mg);
placebo; or open-label oral alendronate weekly. After 24 months, patients
receiving denosumab either continued treatment at 60 mg Q6M for an additional
24 months, discontinued therapy, or discontinued treatment for 12 months then
re-initiated denosumab (60 mg Q6M) for 12 months. The placebo cohort was
maintained. Alendronate-treated patients discontinued alendronate and were
followed. Changes in BMD and bone turnover markers (BTM) as well as safety
outcomes were evaluated. RESULTS: Overall, 262/412 (64%) patients completed 48
months of study. Continuous, long-term denosumab treatment increased BMD at the
lumbar spine (9.4% to 11.8%) and total hip (4.0% to 6.1%). BTM were
consistently suppressed over 48 months. Discontinuation of denosumab was
associated with a BMD decrease of 6.6% at the lumbar spine and 5.3% at the
total hip within the first 12 months of treatment discontinuation. Retreatment
with denosumab increased lumbar spine BMD by 9.0% from original baseline
values. Levels of BTM increased upon discontinuation and decreased with
retreatment. Adverse event rates were similar among treatment groups.
CONCLUSIONS: In postmenopausal women with low BMD, long-term denosumab
treatment led to gains in BMD and reduction of BTM throughout the course of the
study. The effects on bone turnover were fully reversible with discontinuation
and restored with subsequent retreatment.
J Womens Health (Larchmt). 2008
Jun;17(5):841-7.
Does Prevalence of the Metabolic Syndrome in Women with Coronary Artery
Disease Differ by the ATP III and IDF Criteria?
Brown TM, Vaidya D, Rogers WJ, Waters DD, Howard BV, Tardif JC, Bittner V.
Health Services Research
Training Program,
ABSTRACT Background: The
definition and prognostic utility of the metabolic syndrome remain
controversial. Analyses in predominantly healthy populations suggest that the
International Diabetes Federation (IDF) definition identifies more men with
metabolic syndrome than the Adult Treatment Panel III (ATP III) criteria, with
little difference among women. Whether the IDF definition identifies a greater
prevalence of the metabolic syndrome than the ATP III definition in women with
coronary artery disease (CAD) is unknown. Methods: We compared the prevalence
and prognostic utility of both definitions of the metabolic syndrome in
postmenopausal women with angiographic CAD enrolled in the Women's Angiographic
Vitamin and Estrogen Trial (WAVE). We excluded 51 of 423 women enrolled (12%)
who had missing data for components of the metabolic syndrome. Results: Mean
age was 65.3 +/- 8.4 years, 70% were white, mean body mass index (BMI) was 30.5
+/- 6.0 kg/m(2), mean waist circumference was 96.2 +/-
Prescrire Int. 2008
Apr;17(94):68-72.
Osteodensitometry in healthy postmenopausal women.
Since the 1990s, diagnosis of
osteoporosis has been defined, by convention, by a bone density T score cut-off
of less than -2.5. This threshold, based on population statistics, is
appropriate for the diagnosis of osteoporosis in Caucasian postmenopausal women
in Europe and
Semana
del 4 al 10 de Junio 2008
J Clin Densitom. 2008 Jun 3. [Epub
ahead of print]
Hip Axis Length Changes in 10,554 Males and Females and the Association
with Femoral Neck Fracture.
Gao G, Zhang ZL, Zhang H, Hu WW, Huang QR, Lu JH, Hu YQ, Li M, Liu YJ, He JW, Gu JM, Yu JB.
Osteoporosis Research Unit,
the Sixth People's Hospital,
Hip axis length (HAL) has been
proposed as an independent predictor of hip fracture risk in Caucasian females.
There are, however, few data concerning its predictive risk in Chinese. The aim
of this study was to investigate the changes of HAL in healthy Chinese
population and the relationship between HAL and femoral neck fracture. The
study population included 10,554 healthy Chinese people (8665 females, 1889
males) aged 20-97 yrs living in Shanghai. Cases were 106 patients (82 females,
24 males) aged 52 yrs old and over with femoral neck fracture. Controls were
106 age-matched healthy persons. All subjects were measured bone mineral
density (BMD) at any site of proximal femur and HAL using dual-energy X-ray
absorptiometry. HAL had significantly positive correlations with height and
weight. After the adjustment of height and weight, HAL increased with age at 50
yrs of age and over in females, and no difference was found among the age
groups in males. Males had longer HAL than females in all age groups. The peak
BMD appeared in 30-44 yrs for females and 20-24 yrs for males and decreased
thereafter, especially for females at 50 yrs old and over. HAL was similar in
both fracture and control groups, whereas the BMD values at proximal femur were
significantly lower in fracture group than in controls. There was no evidence
that subjects with femoral neck fracture had longer HAL. Because of the
limitations of retrospective study and relatively small fracture sample,
prospective studies are required to determine the conclusions.
Maturitas. 2008 Jun 3. [Epub
ahead of print]
Rationale for using raloxifene to prevent both osteoporosis and breast
cancer in postmenopausal women.
Lee WL, Chao HT, Cheng MH, Wang PH.
Division of Endocrinology and
Metabolism, Department of Medicine, Chen Hsin Rehabilitation Center-Taipei,
Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei,
Taiwan.
Both osteoporosis with
fracture and breast cancer are important health issues for postmenopausal
women. It is well known that estrogen and estrogen receptors (ERs) play an
important role in the pathogenesis of both diseases. In past decades, hormone
therapy (HT), mainly estrogen plus progestin (EPT), has been frequently used
for the purpose of preventing and treating postmenopausal osteoporosis because
of its efficacy, but it also contributes to a significant increase in breast
cancer. Currently, there is a dilemma regarding the use of estrogen for
postmenopausal women. Fortunately, an increasing understanding of the action of
estrogen has led ultimately to the design of new drugs that work by virtue of
their interaction with the ER; these drugs have come to be known as selective
estrogen receptor modulators (SERMs), and are not only effective in preventing
osteoporosis and managing those with osteoporosis, but also in decreasing the
incidence of breast cancer. Among these SERMs, raloxifene may be the most
attractive agent based on the evidence from five recent large trials (Multiple
Outcomes of Raloxifene Evaluation [MORE], Continuing Outcomes Relevant to
Evista [CORE], Raloxifene Use for the Heart [RUTH], Study of Tamoxifen and
Raloxifene [STAR], and Evista Versus Alendronate [EVA]). The former three
trials showed that raloxifene not only decreases the incidence of
osteoporosis-associated fractures, but also has efficacy in breast cancer
prevention. The head-to-head comparison with the anti-fracture agent
alendronate (EVA trial) and the chemoprevention agent tamoxifen (STAR trial)
further confirmed that raloxifene is a better choice. We concluded that since
there is an absence of a therapeutic effect on relieving climacteric symptoms
and there is the presence of a potential risk of thromboembolism in the use of
raloxifene, this drug can be prescribed for clear indications, such as the
management of osteoporosis, the prevention of fracture, and decreasing the
incidence of invasive breast cancer, with careful monitoring for
thromboembolism. It is reasonable to use raloxifene as an appropriate medicine
that targets climacteric symptom-free postmenopausal women because of its
overall favorable risk-benefit safety profile using the global index proposed
by the Women's Health Initiation (WHI).
Int Psychogeriatr. 2008 Jun 5:1-16.
[Epub ahead of print]
Lifetime hormonal factors may predict late-life depression in women.
Ryan J, Carrière
I, Scali J, Ritchie K, Ancelin ML.
Inserm, U888,
ABSTRACTBackground:
Fluctuating hormone levels are known to influence a woman's mood and
well-being. This study aimed to determine whether lifetime hormonal markers are
associated with late-life depression symptoms among elderly community-dwelling
women.Method: Detailed reproductive histories of 1013 women aged 65 years and
over were obtained using questionnaires, and depressive symptoms were assessed
using the Centre for Epidemiological Studies Depression Scale. Multivariate logistic
regression models were generated to determine whether any lifetime endogenous
or exogenous hormonal factors were associated with late-life
depression.Results: The prevalence of depressive symptoms was 17%. Age at
menopause was associated with depressive symptoms, but only among women with a
lower education level. For these women, an earlier age at menopause increased
their risk of late-life depression (linear effect, OR = 0.95, 95%CI:
0.91-0.99). The odds of late-life depression were also increased for women who
were past (OR = 1.6, 95%CI: 1.1-2.5), but were not current users. On the other
hand, long-term oral contraceptive use (>/=10 years) was protective against
depression (OR = 0.3, 95%CI: 0.1-0.9). These associations remained significant
even after extensive adjustment for a range of potential confounding factors,
including sociodemographic factors, mental and physical incapacities,
antidepressant use and past depression. The other factors examined - including
age at first menses, parity, age at childbirth and surgical menopause - were
not associated with late-life depressive symptoms.Conclusions: Lifetime
hormonal factors that are significantly associated with depression symptoms in
later life have been identified. Further work is needed to determine how
potential hormonal interventions could be used in the treatment of late-life
depression in certain subgroups of women.
J Acoust Soc Am. 2008
May;123(5):3632.
Estimation of in vivo cancellous bone elasticity.
Doshisha University, 1-3, Tatara Miyakodani,
610-0321 Kyotanabe, Japan, totani@oyoe.jp.
Effect of decreasing bone
density (a symptom of osteoporosis) is greater for cancellous bone than for
dense cortical bone, because cancellous bone is metabolically more active.
Therefore, bone density or bone mineral density at cancellous bone is generally
used to estimate the onset of osteoporosis. Elasticity or elastic constant is
one of fundamental mechanical parameters and directly related to the mechanical
strength of bone. Accordingly, elasticity is a preferable parameter to assess
the fracture risk. A novel ultrasonic bone densitometer LD-100 has been
developed to obtain mass density and elasticity of cancellous bone with a
spatial resolution comparable to that of the peripheral quantitative computed
tomography system. Bone mass density and bone elasticity are evaluated using
ultrasonic parameters based on fast and slow waves in cancellous bone using a
modeling of ultrasonic wave propagation path. Elasticity is deduced from
measured bone mass density and propagation speed of fast wave. Thus, elasticity
of cancellous bone is approximately expressed by a cubic equation of bone mass
density.
Curr Opin Rheumatol. 2008
Jul;20(4):429-34.
Bone and fat connection in aging bone.
PURPOSE OF REVIEW: The fat and
bone connection plays an important role in the pathophysiology of age-related
bone loss. This review will focus on the age-induced mechanisms regulating the
predominant differentiation of mesenchymal stem cells into adipocytes.
Additionally, bone marrow fat will be considered as a diagnostic and
therapeutic approach to osteoporosis. RECENT FINDINGS: There are two types of
bone and fat connection. The 'systemic connection', usually seen in obese
patients, is hormonally regulated and associated with high bone mass and
strength. The 'local connection' happens inside the bone marrow. Increasing
amounts of bone marrow fat affect bone turnover through the inhibition of
osteoblast function and survival and the promotion of osteoclast
differentiation and activation. This interaction is regulated by paracrine
secretion of fatty acids and adipokines. Additionally, bone marrow fat could be
quantified using noninvasive methods and could be used as a therapeutic
approach due to its capacity to transdifferentiate into bone without affecting
other types of fat in the body. SUMMARY: The bone and fat connection within the
bone marrow constitutes a typical example of lipotoxicity. Additionally, bone
marrow fat could be used as a new diagnostic and therapeutic approach for
osteoporosis in older persons.
Ultrasound Med Biol. 2008 Jun 2. [Epub
ahead of print]
Dual-Frequency Ultrasound-New Pulse-echo Technique for Bone
Densitometry.
Riekkinen
O, Hakulinen
MA, Töyräs
J, Jurvelin
JS.
Department of Physics,
Quantitative ultrasound has
been suggested for screening of osteoporosis. Most commercial ultrasound devices
are based on the through-transmission measurement of calcaneus, which is not a
typical fracture site. In contrast to through-transmission measurements,
reflection and backscattering measurements may be conducted at typical fracture
sites such as vertebra and proximal femur. At these regions, soft tissues
overlying bones affect reliability of the measurements. In this study, a novel
dual-frequency ultrasound (DFUS) pulse-echo technique is introduced for
reduction of the errors induced by soft tissues. First, DFUS was validated
using elastomer samples. For further validation, human trabecular bone samples
(n = 25) covered with heterogeneous soft tissues were measured at frequencies
of 2.25 MHz and 5.0 MHz. The DFUS technique reduced (p < 0.01) the mean error
induced by soft tissue from 58.6% to -4.9% and from 127.4% to 23.8% in
broadband ultrasound backscattering and integrated reflection coefficient (at
5.0 MHz), respectively. To conclude, the DFUS, being the first ultrasound
technique capable of determination of the composition and thickness of the soft
tissue overlying the bone, may enhance the accuracy of clinical ultrasound
measurements. Thereby, DFUS shows a significant clinical potential.
Osteoporos Int. 2008 Jun 4. [Epub
ahead of print]
Risk factors for low bone mass in healthy 40-60 year old women: A
systematic review of the literature.
Waugh EJ, Lam MA, Hawker GA, McGowan J, Papaioannou
A, Cheung AM, Hodsman AB, Leslie WD, Siminoski
K, Jamal SA.
Osteoporosis Research Program,
Women’s
Based on a systematic review
of the literature, only low body weight and menopausal status can be considered
with confidence, as important risk factors for low BMD in healthy 40-60 year
old women. The use of body weight to identify high risk women may reduce
unnecessary BMD testing in this age group. INTRODUCTION: BMD testing of
perimenopausal women is increasing but may be unnecessary as fracture risk is
low. Appropriate assessment among younger women requires identification of risk
factors for low BMD specific to this population. METHODS: We conducted a
systematic literature review of risk factors for low BMD in healthy women aged
40-60 years. Articles were retrieved from six databases and reviewed for
eligibility and methodological quality. A grade for overall strength of
evidence for each risk factor was assigned. RESULTS: There was good evidence
that low body weight and post-menopausal status are risk factors for low BMD.
There was good or fair evidence that alcohol and caffeine intake, and
reproductive history are not risk factors. There was inconsistent or
insufficient evidence for the effect of calcium intake, physical activity,
smoking, age at menarche, history of amenorrhea, family history of OP, race and
current age on BMD. CONCLUSIONS: Based on current evidence in Caucasians, we
suggest that, in healthy women aged 40-60 years, only those with a low body weight
(<
J Gen Intern Med. 2008 Jun 3. [Epub ahead of
print]
Revisiting the Duration of Vasomotor Symptoms of Menopause: A
Meta-Analysis.
Politi MC, Schleinitz
MD, Col NF.
Department of Behavioral and
Preventive Medicine,
BACKGROUND: Treatment
decisions about menopause are predicated on a transient duration of vasomotor
symptoms. However, evidence supporting a specific duration is weak. OBJECTIVE:
To estimate the natural progression of vasomotor symptoms during the menopause transition
by systematically compiling available evidence using meta-analytic techniques.
DATA SOURCES: We searched MEDLINE, hand searched secondary references in
relevant studies, book chapters, and review papers, and contacted investigators
about relevant published research. REVIEW METHODS: English language,
population-based studies reporting vasomotor symptom prevalence among women in
menopausal transition in time intervals based on years to or from final
menstrual period were included. Two reviewers independently assessed
eligibility and quality of studies and extracted data for vasomotor symptom
prevalence. RESULTS: The analyses included 10 studies (2 longitudinal, 8 cross
sectional) with 35,445 participants. The percentage of women experiencing
symptoms increased sharply in the 2 years before final menstrual period, peaked
1 year after final menstrual period, and did not return to premenopausal levels
until about 8 years after final menstrual period. Nearly 50% of all women
reported vasomotor symptoms 4 years after final menstrual period, and 10% of
all women reported symptoms as far as 12 years after final menstrual period.
When data were examined according to symptom severity ('any' vs. 'bothersome'),
bothersome symptoms peaked about 1 year earlier and declined more rapidly than
symptoms of any severity level. CONCLUSIONS: Our findings suggest a median
symptom duration of about 4 years among symptomatic women. A longer symptom
duration may affect treatment decisions and clinical guidelines. Further prospective,
longitudinal studies of menopausal symptoms should be conducted to confirm
these results.
Menopause. 2008 May 20. [Epub
ahead of print]
Beyond frequency: who is most bothered by vasomotor symptoms?
Thurston
RC, Bromberger
JT, Joffe H, Avis NE, Hess R, Crandall
CJ, Chang Y, Green R, Matthews
KA.
OBJECTIVE:: Most menopausal
women report vasomotor symptoms (hot flashes, night sweats). However, not all
women with vasomotor symptoms, including frequent symptoms, are bothered by
them. The primary aim was to identify correlates of vasomotor symptom bother
beyond symptom frequency. DESIGN:: The Study of Women's Health Across the
Nation participants reporting vasomotor symptoms at annual visit 7 comprised
the sample (N = 1,042). Assessments included hot flash and night sweats
frequency (number per week) and bother (1, not at all- 4, very much). Negative
affect (index of depressive symptoms, anxiety, perceived stress, negative
mood), symptom sensitivity, sleep problems, and vasomotor symptom duration
(number of years) were examined cross-sectionally in relation to bother in
ordinal logistic regression models with symptom frequency and covariates. Hot
flashes and night sweats were considered separately. RESULTS:: In multivariable
models controlling for hot flash frequency, negative affect (odds ratio [OR] =
1.27, 95% CI: 1.08-1.51), symptom sensitivity (OR = 1.18, 95% CI: 1.03-1.37),
sleep problems (OR = 1.38, 95% CI: 1.04-1.85), poorer health (OR = 1.24, 95%
CI: 1.03-1.48), duration of hot flashes (OR = 1.14, 95% CI: 1.06-1.23), younger
age (OR = 0.94, 95% CI: 0.89-0.99), and African American race (vs white, OR =
1.59, 95% CI: 1.12-2.26) were associated with hot flash bother. After
controlling for night sweats frequency and covariates, sleep problems (OR =
1.84, 95% CI:1.33-2.55) and night sweats duration (OR = 1.10, 95% CI:
1.02-1.20) were associated with night sweats bother. CONCLUSIONS:: Beyond
frequency, factors associated with bothersome hot flashes include mood, symptom
sensitivity, symptom duration, sleep problems, age, and race. Correlates of
bothersome night sweats include sleep problems and symptom duration. In
addition to reducing frequency, interventions for vasomotor symptoms might
consider addressing modifiable factors related to symptom bother.
Menopause. 2008 May 23. [Epub
ahead of print]
Effects of hormone therapy on soluble cell adhesion molecules in
postmenopausal women with coronary artery disease.
Yeboah J, Klein K, Brosnihan
B, Reboussin
D, Herrington
DM.
Department of Internal
Medicine,
OBJECTIVE:: Although
observational studies showed an apparent lower ischemic coronary disease risk
in postmenopausal women receiving hormone therapy (HT), randomized clinical
trials in postmenopausal women showed an increase in ischemic cardiovascular
events. Soluble cell adhesion molecules have been associated with
cardiovascular risk factors and events. HT reduces circulating levels of
soluble cell adhesion molecules in healthy postmenopausal women, but its
effects in postmenopausal women with coronary artery disease are less clear. We
assessed the effect of HT on soluble cell adhesion molecules in the Estrogen
Replacement and Atherosclerosis trial. DESIGN:: The Estrogen Replacement and
Atherosclerosis trial was a double-blind, placebo-controlled study that
randomized 309 postmenopausal women (mean age, 65.8 y) to daily unopposed
estrogen (conjugated estrogens 0.625 mg), estrogen plus 2.5 mg of
medroxyprogesterone acetate, or placebo, with a mean follow-up period of 3.2
years. Soluble intercellular adhesion molecule-1, vascular cell adhesion
molecule-1, and E-selectin were measured in serum obtained from participants at
baseline and after 12 months of follow-up. RESULTS:: Of the 265 women with
complete data, 87 women were assigned to unopposed estrogen, 88 women to
estrogen plus medroxyprogesterone acetate, and 90 women to placebo. Compared
with placebo, 12 months of HT (n = 175) was associated with reductions in
soluble intercellular adhesion molecule-1 (25.6 +/- 4.7 vs 10.6 +/- 6.4ng/mL, P
= 0.06), soluble vascular cell adhesion molecule-1 (80.2+/- 10.6 vs 28.8 +/- 14.7
ng/mL, P = 0.005), and E-selectin (8.8 +/- 0.9 vs -1.1 +/- 1.2 ng/mL, P <
0.001). CONCLUSIONS:: Twelve months of HT in postmenopausal women with
established coronary artery disease was associated with reductions in serum
markers of endothelial cell activation/injury such as soluble intercellular
adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin.
Menopause. 2008 May 26. [Epub
ahead of print]
Association between low lean body mass and osteoporotic fractures after
menopause.
Capozza RF, Cure-Cure C, Cointry GR, Meta M, Cure P, Rittweger J, Ferretti JL.
1Center of Ca-P Metabolism Studies (CEMFoC),
National University of Rosario, Rosario, Argentina; 2Metropolitan University,
Barranquilla, Colombia; 3Department of Medicine, UCLA, Los Angeles, CA;
4Institute for Biophysical and Clinical Research into Human Movement,
Manchester Metropolitan University, Manchester, UK.
OBJECTIVE:: This study
evaluated dual-energy x-ray absorptiometry-assessed whole-body bone-muscle
relationship (bone mineral content/lean mass [BMC/LM]) as an indicator of its
nonmechanical perturbations (ie, systemic) in pre- and postmenopausal women. A
total of 3,205 women were studied, either healthy (no fracture [No Fx] groups,
1,035 premenopausal, 1,556 postmenopausal) or with recent fractures (Fx groups,
139 premenopausal, 475 postmenopausal) located at osteoporotic sites (hip,
spine, long-bone metaphyses; Type II Fx, n = 386) or at other skeletal sites
(Type I Fx, n = 228) to evaluate the impact of decreased muscle mass on
fracture incidence before and after menopause. DESIGN:: SD-scored graphs of
BMC/LM proportionality were obtained from the No Fx groups as normal
references. Based on the reference BMC versus LM curves obtained from their
respective No Fx pre- and postmenopausal controls,
Menopause. 2008 May 26. [Epub
ahead of print]
Comparative effects of oral conjugated equine estrogens and micronized
17beta-estradiol on breast proliferation: a retrospective analysis.
Wood CE, Clarkson
TB, Chen H, Veenstra
TD, Xu X, Scott L, Cline JM.
Departments of
1Pathology/Section on Comparative Medicine and 2Biostatistical Sciences,
OBJECTIVE:: To evaluate the
effects of oral conjugated equine estrogens (CEE) and micronized
17beta-estradiol (E2) on breast proliferation in a postmenopausal primate
model. DESIGN:: Data from nine studies were analyzed retrospectively. The
primary outcome measure was breast epithelial proliferation determined by
immunolabeling for the Ki67 antigen. Other measures included progesterone
receptor expression and endometrial thickness (as surrogate markers of systemic
estrogen exposure) and urinary estrogen metabolite profile. All CEE doses were
given at the human equivalent of 0.625 mg/day (n = 281), whereas E2 was given
at the human equivalent of 1.0 mg/day or less (n = 131). RESULTS:: Oral CEE
resulted in a modest overall increase in breast epithelial proliferation of 75%
that reached significance at P < 0.05 compared with placebo in one of four
parallel-arm studies. In contrast, oral E2 resulted in a more substantial
increase in breast epithelial proliferation of 259% (all studies) to 330%
(parallel-arm studies only) that reached significance at P <
Menopause Int. 2008
Jun;14(2):70-7.
A 10-year follow-up of the effect of continuous-combined hormone
replacement therapy and its discontinuation on bone in postmenopausal women.
Heikkinen
J, Vaheri R, Haapalahti
J, Timonen U.
Orion Pharma, PO Box 65, 02101 Espoo, Finland.
raija.vaheri@orionpharma.com.
OBJECTIVE: To establish the
effect on bone mineral density of long-term (nine years) continuous-combined
hormone replacement therapy (ccHRT) with estradiol valerate/
medroxyprogesterone acetate (E(2)V/MPA) and follow-up one year after
discontinuation of ccHRT. STUDY DESIGN: A total of 279 women were treated with
daily dosages of E(2)V + MPA: 1 mg + 2.5 mg (n = 69), 1 mg + 5 mg (n = 70) or 2
mg + 5 mg (n = 140) (Indivina((R)), Orion Pharma,
Maturitas. 2008 May 28. [Epub
ahead of print]
Risk factors for onset of menopausal symptoms Results from a large
cohort study.
Sabia S, Fournier A, Mesrine S, Boutron-Ruault
MC, Clavel-Chapelon
F.
INSERM, Institut National de
OBJECTIVES: Menopause, the
permanent cessation of ovarian activity, is part of normal aging, resulting in
climacteric symptoms for most women, particularly in Western countries. The
objective of the present study was to analyse risk factors for onset of
menopausal symptoms. METHODS: Analyses were based on the 28,118 women
participating in the French E3N cohort study who reached menopause between 1990
and 2000. Questionnaires were sent every 2 years, and specifically enquired
about use of hormonal treatments, reproductive factors, smoking status,
anthropometric measurements, dietary habits and personal medical history,
including onset of menopausal symptoms. Hazard ratios were computed from
multivariable Cox proportional hazard models with age as the time-scale.
RESULTS: The risk of onset of menopausal symptoms was negatively associated
with education level and with some hormonal and reproductive factors (usual
duration of menstrual cycles, parity and current use of oral contraceptives). A
decrease in risk was found in those with underweight, overweight and obesity,
but only in post-menopause. The risk was positively associated with smoking and
alcohol consumption; it was also positively related to certain frequent medical
conditions (depression, migraine, benign thyroid disease, atopy), possibly due
to underlying common mechanisms such as the influence of vaso-active
substances. Among dietary factors, rapidly absorbed sugars and snacking were
positively associated with the risk of onset of menopausal symptoms.
CONCLUSIONS: Onset of menopausal symptoms seems to be affected by various
reproductive, hormonal and environmental factors. Some of them are modifiable,
which may allow suggesting recommendations.
Med J Aust. 2008 Jun
2;188(11):641-4.
Decrease in breast cancer incidence following a rapid fall in use of
hormone replacement therapy in
Canfell K, Banks E, Moa AM, Beral V.
Cancer Epidemiology Research
Unit, The Cancer Council NSW,
OBJECTIVE: To determine if the
recent rapid fall in use of hormone replacement therapy (HRT) in Australia has
been followed by a reduction in breast cancer incidence among women aged 50
years or older, but not among younger women. DESIGN AND SETTING: Analysis of
trends in annual prescribing of HRT, using Pharmaceutical Benefits Scheme data,
and in annual age-standardised breast cancer incidence rates in Australian
women for the period 1996-2003. RESULTS: In
Arthritis Rheum. 2008 May
31;58(6):1687-1695. [Epub ahead of print]
Effects of long-term strontium ranelate treatment on the risk of
nonvertebral and vertebral fractures in postmenopausal osteoporosis: Results of
a five-year, randomized, placebo-controlled trial.
Reginster
JY, Felsenberg
D, Boonen S, Diez-Perez
A, Rizzoli R, Brandi ML, Spector TD, et al.
OBJECTIVE: This study was
undertaken to assess the effect of strontium ranelate on nonvertebral and
vertebral fractures in postmenopausal women with osteoporosis in a 5-year,
double-blind, placebo-controlled trial. METHODS: A total of 5,091
postmenopausal women with osteoporosis were randomized to receive either
strontium ranelate at 2 gm/day or placebo for 5 years. The main efficacy
criterion was the incidence of nonvertebral fractures. In addition, incidence
of hip fractures was assessed, by post hoc analysis, in the subset of 1,128
patients who were at high risk of fractures (age 74 years or older with lumbar
spine and femoral neck bone mineral density T scores -2.4 or less). The
incidence of new vertebral fractures was assessed, using the semiquantitative
method described by Genant, in the 3,646 patients in whom spinal radiography (a
nonmandatory procedure) was performed during the course of the study. Fracture
data were analyzed using the Kaplan-Meier survival method. RESULTS: Of the
5,091 patients, 2,714 (53%) completed the study up to 5 years. The risk of
nonvertebral fracture was reduced by 15% in the strontium ranelate group
compared with the placebo group (relative risk 0.85 [95% confidence interval
0.73-0.99]). The risk of hip fracture was decreased by 43% (relative risk 0.57
[95% confidence interval 0.33-0.97]), and the risk of vertebral fracture was
decreased by 24% (relative risk 0.76 [95% CI 0.65-0.88]) in the strontium
ranelate group. After 5 years, the safety profile of strontium ranelate
remained unchanged compared with the 3-year findings. CONCLUSION: Our findings
indicate that treatment of postmenopausal osteoporosis with strontium ranelate
results in a sustained reduction in the incidence of osteoporotic nonvertebral
fractures, including hip fractures, and vertebral fractures over 5 years.
Semana
del 27de Mayo al 3 de Junio 2008
Am J Obstet Gynecol. 2008 May 27. [Epub
ahead of print]
Metabolic syndrome in postmenopausal women: the influence of oral or
transdermal estradiol on inflammation and coagulation markers.
Chu MC, Cushman M, Solomon R, Lobo RA.
Departments of Obstetrics and
Gynecology,
OBJECTIVE: The objective of
the study was to determine whether the route of administration of estrogen
therapy in women with metabolic syndrome (MBS) influences inflammation and
coagulation parameters. STUDY DESIGN: Fifty symptomatic postmenopausal women
with MBS were randomized to receive 1 mg oral estradiol (oE(2)) or 0.05 mg
transdermal E(2) (tE(2)) for 3 months. Measurements were compared with those of
20 healthy premenopausal women and 74 normal postmenopausal women. RESULTS:
Compared with both control groups, women with MBS had significantly higher
levels of certain inflammation and coagulation markers, which cannot be
accounted for based on weight alone. After oE(2), antithrombin III decreased
from 104% to 96% (P < .01), the metalloproteinase-9/ tissue inhibitor of
metalloproteinase-1 ratio increased (P < .02), and E-selectin decreased from
60 +/- 4.4 to 55 +/- 4.6 ng/mL (P < .05). With tE(2), there were no major
changes noted. CONCLUSION: Postmenopausal women with MBS have higher levels of
certain coagulation and inflammation markers and different responses to oral compared
with transdermal estradiol.
Breast Cancer Res Treat. 2008 May 29. [Epub
ahead of print]
Circulating steroid hormone concentrations in postmenopausal women in
relation to body size and composition.
Baglietto
L, English DR, Hopper JL, Macinnis
RJ, Morris HA, Tilley WD, Krishnan K, Giles GG.
Cancer Epidemiology Centre,
The Cancer Council Victoria,
Steroid hormones are
associated with the risk of postmenopausal breast cancer and evidence suggests
that increased concentrations of oestrogens from peripheral aromatisation in
adipose tissue partly explains the association between body mass index (BMI)
and risk of postmenopausal breast cancer. This study examined the associations
between circulating concentrations of steroid hormones and anthropometric
measurements in a sample of naturally postmenopausal women from the Melbourne
Collaborative Cohort Study, not using hormone replacement therapy. We measured
plasma concentration of total oestradiol, oestrone sulphate,
dehydroepiandrosterone sulphate, androstenedione, testosterone and sex hormone
binding globulin (SHBG) and calculated concentration of free oestradiol. Body
measurements included height, weight, BMI, waist circumference, fat mass and
fat-free mass, the last two estimated by bioelectrical impedance analysis. BMI
was positively associated with both oestrogens and androgens and negatively
with SHBG. Fat mass was the principal measure responsible for the association
observed between body size and total oestradiol. The associations between
oestrone sulphate and androgens and body size were mainly with waist
circumference. The associations between oestrogens and body size were close to
null for the first 6 years since menopause and became positive thereafter. Our
results are compatible with the hypothesis that after the menopause excess fat
mass increases oestrogen concentrations through the peripheral aromatisation of
androgens in adipose tissue. This effect requires around 6 years to be
detectable by way of circulating steroid hormone levels.
Endocr Relat Cancer. 2008
Jun;15(2):485-497.
Endogenous sex hormones and endometrial cancer risk in women in the
European Prospective Investigation into Cancer and Nutrition (EPIC).
Allen NE, Key TJ, Dossus L, Rinaldi S, Cust A, Lukanova A, et al
Cancer Research
Epidemiological data show that
reproductive and hormonal factors are involved in the etiology of endometrial
cancer, but there is little data on the association with endogenous sex hormone
levels. We analyzed the association between prediagnostic serum concentrations
of sex steroids and endometrial cancer risk in the European Prospective
Investigation into Cancer and Nutrition using a nested case-control design of
247 incident endometrial cancer cases and 481 controls, matched on center,
menopausal status, age, variables relating to blood collection, and, for
premenopausal women, phase of menstrual cycle. Using conditional regression
analysis, endometrial cancer risk among postmenopausal women was positively
associated with increasing levels of total testosterone, free testosterone,
estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the
highest versus lowest tertile were 2.66 (95% confidence interval (CI)
1.50-4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI
1.20-3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98-2.82; P=0.001) for
free estradiol. For total and free testosterone, ORs for the highest versus
lowest tertile were 1.44 (95% CI 0.88-2.36; P=0.05) and 2.05 (95% CI 1.23-3.42;
P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were
not associated with risk. Sex hormone-binding globulin was significantly
inversely associated with risk (OR for the highest versus lowest tertile was
0.57, 95% CI 0.34-0.95; P=0.004). In premenopausal women, serum sex hormone
concentrations were not clearly associated with endometrial cancer risk, but
numbers were too small to draw firm conclusions. In conclusion, relatively high
blood concentrations of estrogens and free testosterone are associated with an
increased endometrial cancer risk in postmenopausal women.
Arch Intern Med. 2008 May
26;168(10):1070-6.
Treatment of symptomatic androgen deficiency: results from the
Hall SA, Araujo AB, Esche GR, Williams
RE, Clark RV, Travison
TG, McKinlay
JB.
BACKGROUND: Despite the aging
of the
Pharmacotherapy. 2008
Jun;28(6):712-8.
Absorption, bioavailability, and partner transfer of estradiol from a
topical emulsion.
1 Esprit Pharma,
Abstract Study Objective. To
investigate the systemic absorption of estradiol in partners of postmenopausal
women after making skin-to-skin contact with the application sites of estradiol
topical emulsion. Design. Open-label, nonrandomized clinical study. Setting.
Clinical study unit. Subjects. Fourteen postmenopausal women and their male
partners (mean +/- SD age 57.6 +/- 8.7 and 49.1 +/- 13.3 yrs, respectively).
Intervention. Women applied 1.74 g/day of estradiol topical emulsion (containing
2.5 mg estradiol/g) to each leg on 2 consecutive days. Their male partners were
exposed to the application sites by mean of vigorous skin-to-skin contact at 2
and 8 hours after application. Measurements and Main Results. Serum
concentrations of estradiol, estrone, and estrone sulfate were measured in the
female subjects and their male partners. The mean +/- SD estradiol level in the
women at baseline was 2.9 +/- 1.5 pg/ml. Their average concentration
(C(average)) increased from 15.3 +/- 14.8 pg/ml on the first day of treatment
to 27.6 +/- 22.7 pg/ml on the second day. Among male partners, C(average) for
serum estradiol increased from 17.0 +/- 4.3 pg/ml at baseline to 21.0 +/- 4.4
pg/ml on the second exposure day. Their geometric mean fold ratio for the area
under the serum concentration-time curve from 0-24 hours was 1.25 (baseline vs
after second exposure, p<0.0001). Conclusions. Estradiol was transferred to
male partners by means of vigorous skin-to-skin contact at application sites.
Although the increase in postexposure levels of estradiol was statistically
significant, all levels were still below the upper limit of the normal range
for men (45 pg/ml).
Metabolism. 2008 Jun;57(6):838-44.
Does insulin resistance, visceral adiposity, or a sex hormone alteration
underlie the metabolic syndrome? Studies in women.
Phillips
GB, Jing T, Heymsfield
SB.
Department of Medicine,
Columbia University College of Physicians and Surgeons, St Luke's-Roosevelt
Hospital Center, New York, NY 10019, USA.
Insulin resistance, obesity, and
a sex hormone alteration have each been suggested as the underlying link for
the constellation of risk factors for myocardial infarction (MI) commonly
referred to as the metabolic syndrome or the insulin resistance syndrome. In an
attempt to identify in women which of these variables is the most likely link,
insulin, adiposity variables, sex hormones, and risk factors for MI were
measured and their relationships analyzed statistically in 58 premenopausal and
20 postmenopausal healthy women. On controlling for age, visceral adipose
tissue (VAT) correlated more strongly with risk factors for MI, insulin, and
free testosterone (FT) than did total adipose tissue or subcutaneous adipose
tissue. VAT, therefore, was used as the adiposity variable for further data
analysis. Waist circumference was a better surrogate of VAT than was waist-hip
ratio, which was a poor surrogate of VAT. VAT correlated positively with
insulin, FT, triglyceride, and glucose, and negatively with high-density
lipoprotein and sex hormone-binding globulin. On controlling for age, FT and
insulin correlated with risk factors for MI and with each other, but on
controlling for age and VAT, all of their correlations lost statistical
significance except for FT-triglyceride and FT-insulin in the postmenopausal
women. In conclusion, VAT accumulation in women, independently of other
measures of adiposity, may largely explain the correlations of insulin,
obesity, and sex hormones with risk factors for MI and may be the immediate
underlying factor that links risk factors for MI to form the metabolic
syndrome. Insulin resistance, which has been generally accepted to be the
underlying factor, may be a component of the syndrome rather than its
underlying link. We hypothesize that in women FT may effect preferential VAT
accumulation and induce insulin resistance directly, as well as via VAT
accumulation, so that a sex hormone alteration may underlie VAT accumulation
and thus ultimately underlie the metabolic syndrome (with insulin resistance as
a component).