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PubMed1997

Controversies surrounding estrogen use in postmenopausal women.

OBJECTIVE: To provide an overview of controversies regarding the use of estrogen in postmenopausal women. DATA SOURCES: A MEDLINE search was conducted to identify pertinent literature published since 1990. Recently published textbooks devoted to the subjects of menopause and women's health were also reviewed, particularly their bibliographies. The bibliographies of selected review articles were also reviewed. STUDY SELECTION: Due to the vast amount of literature, only the most relevant published studies were reviewed. Review articles and book chapters authored by researchers of international reputation were also reviewed. DATA EXTRACTION: Identified studies from the primary literature and selected reviews were carefully reviewed. Information regarding the use of estrogen in postmenopausal women was extracted. Particular attention was given to areas of controversy commonly dealt with in the lay media. DATA SYNTHESIS: The number of postmenopausal women in the US will approach 60 million in the next decade. Despite numerous potential benefits, many women elect to not take estrogen due to fear of cancer or poor understanding of the long-term consequences of menopause and the beneficial effects of estrogen replacement therapy. Many women rely on the news media for information about hormone therapy and subsequently become confused regarding the benefits and risks. Estrogen relieves climacteric symptoms such as hot flushes and symptoms related to genitourinary tissue atrophy. Outcomes from controlled clinical trials are lacking, but numerous epidemiologic studies document clinically significant decreases in cardiovascular disease and osteoporotic morbidity and mortality. Unopposed estrogen increases the risk for endometrial cancer, but addition of a progestin for at least 10 days per cycle effectively reduces this risk to that of women who do not take estrogen. The association between postmenopausal estrogen use and breast cancer remains controversial, despite the results of numerous observational studies. This uncertainty regarding estrogen replacement and breast cancer risk can actually be reassuring when placed in proper perspective. CONCLUSIONS: Until some of the controversies surrounding postmenopausal hormone use are resolved, an objective discussion with a knowledgeable healthcare professional regarding the potential benefits and risks will help women make informed decisions regarding estrogen replacement therapy in the postmenopausal years.

Aged↗

PubMed2004

A randomized placebo-controlled trial of short-term graded transdermal estradiol in healthy gonadotropin-releasing hormone agonist-suppressed pre- and postmenopausal women: effects on serum markers of bone turnover, insulin-like growth factor-I, and osteoclastogenic mediators.

The acute effects of estradiol on procollagen type 1 formation in pre- and postmenopausal women are controversial. Twenty-three premenopausal women and 13 postmenopausal women received two consecutive im injections of 3.75 mg leuprolide acetate 3 wk apart to block endogenous ovarian steroidogenesis. Transdermal estradiol therapy commenced on the night of the second leuprolide injection in all subjects, except five pre- and two postmenopausal women who were randomized to receive placebo patches. Estradiol therapy was applied incrementally, with each dose of 0.05, 0.10, 0.15, and 0.20 mg/d administered for 4 consecutive days, to mimic the estradiol changes typifying the follicular phase of the menstrual cycle. Blood aminoterminal propeptide of type I procollagen (PINP), intact osteocalcin (OC), carboxyterminal telopeptide of type I collagen (CTx), IGF-I, and estradiol were measured before and at the end of each estradiol increment. Potential mediators such as osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) were also measured. Despite comparable increases in serum estradiol, PINP increased more in postmenopausal compared with premenopausal women (between-group P = 0.03) and occurred at a time when CTx and OC did not change. CTx and IGF-I changed minimally and inconsistently, whereas OC, RANKL, and osteoprotegerin were stable. Repeated measures linear regression disclosed a significant negative association between increases in estradiol and PINP in premenopausal women (P = 0.0006) only. This suggests that lower dose estradiol should greatly increase PINP. Analogous regressions also showed significant negative relationships between changes in estradiol and RANKL in both pre- (P = 0.04) and postmenopausal (P = 0.002) women. Changes in serum markers of bone formation (PINP or OC) did not correlate with those of IGF-I. We conclude that lower dose estradiol rapidly increases osteoblastic collagen synthesis in women at a time when collagen degradation is stable and that this response differs between pre- and postmenopausal women. The effect of estradiol on bone formation does not appear to be mediated by IGF-I. In contrast, RANKL is likely to mediate the effect of estradiol on osteoclastogenesis.

Administration, Cutaneous↗

PubMed1990

Postmenopausal hypertrophy of neurons expressing the estrogen receptor gene in the human hypothalamus.

Computer microscopy and in situ hybridization were used to investigate neuronal hypertrophy in the infundibular nucleus of postmenopausal women. In the first experiment, hypothalami from premenopausal (n = 3) and postmenopausal (n = 3) women were formalin fixed, paraffin embedded, serially sectioned, and stained with cresyl violet. Soma areas of more than 3500 neurons were digitized using an image-combining computer microscope. The mean cross-sectional area of infundibular neurons in the postmenopausal women was 30% greater than that in premenopausal women, with no change in cell density. The mean cross-sectional area of mammillary neurons was unchanged, indicating that the infundibular neuronal hypertrophy was not an artifact of tissue processing. In the second experiment, hypothalami from premenopausal (n = 3) and postmenopausal (n = 2) women were frozen, serially sectioned, and incubated with a 48-base synthetic cDNA probe complementary to estrogen receptor (ER) mRNA. Adjacent sections were incubated with a cDNA probe complementary to GnRH mRNA. Morphometric analysis revealed that the mean cross-sectional area of infundibular neurons expressing the ER gene in the postmenopausal women was twice as large as the mean area in premenopausal hypothalami. The hypertrophied neurons did not contain GnRH mRNA. Finally, analysis of the infundibular nucleus from an oophorectomized 38-yr-old woman also revealed hypertrophied neurons containing ER mRNA. These data support the hypothesis that hypertrophy of infundibular neurons in postmenopausal women is secondary to loss of the inhibitory feedback of ovarian steroids.

Adult↗

PubMed2006

Clinical significance of cytologic diagnosis of atypical squamous cells, cannot exclude high grade, in perimenopausal and postmenopausal women.

We used cytohistologic correlation to determine the clinical significance of atypical squamous cells, cannot exclude high grade (ASC-H) in perimenopausal and postmenopausal women. A computer search identified 250 Papanicolaou smears from women older than 45 years with a diagnosis of ASC- H. Cases were considered perimenopausal (45 to < 55 years; 150 cases) and postmenopausal ((3)55 years; 100 cases). No follow-up data were available for 33 cases, which were excluded. The remaining 217 cases (perimenopausal, 127; postmenopausal, 90) had surgical or cytologic follow-up. Results of follow-up colposcopic biopsy were available for 176 (81.1%) and cytology for 41 (18.9%) women. Follow-up results were as follows: perimenopausal women, negative, 50 (39.4%); mild dysplasia (low-grade squamous intraepithelial lesion [LSIL]), 46 (36.2%); high-grade dysplasia (high-grade SIL [HSIL]); 28 (22.0%); and ASC of undetermined significance (ASC-US), 3 (2.4%); postmenopausal women, negative, 52 (58%); LSIL, 31 (34%); HSIL, 5 (6%); and ASC-US, 2 (2%). The diagnosis of ASC-H in postmenopausal women usually is associated with LSIL or a negative diagnosis on follow-up, suggesting a less aggressive surveillance and treatment regimen is needed for postmenopausal women with ASC-H.

Aged↗

PubMed1985

Effects of alcohol on endocrine function in postmenopausal women: a review.

The rationale for evaluating potential endocrine effects of alcoholic beverage use or misuse in postmenopausal women is presented. Drinking prevalence data in postmenopausal women as well as the relevance of determining to what degree alcoholic beverage consumption may play a role in the risk of various diseases in these women via modulation of endocrine status in general and estrogenization in particular are included. Both human and animal studies relevant to alcoholic beverage consumption effects on endocrine function in females are reviewed. Data obtained in young women or animals that may be applicable to postmenopausal women are evaluated and data on these women are examined. There exists a paucity of definitive data concerning endocrine effects of alcohol in postmenopausal women. In an effort to foster and facilitate future studies that will be scientifically well founded and designed, aspects of normal postmenopausal endocrine function are described. Potential sites and mechanisms by which alcohol might be postulated to affect the endocrine status of postmenopausal women are reviewed.

Adrenal Glands↗

PubMed1989

Effects of repetitive administration of growth hormone-releasing hormone on growth hormone secretion, insulin-like growth factor I, and bone metabolism in postmenopausal women.

This study sought to determine whether GH response to synthetic GHRH was impaired in 13 postmenopausal (55-71 years) as compared with that in 8 eugonadal women and whether IGF-I and bone metabolism were consequently depressed. Thereafter, the effects of daily iv injections of 80-micrograms GHRH-44 for 8 days were studied in the same postmenopausal group. In addition to significantly higher basal IGF-I and osteocalcin levels (P less than 0.005) in eugonadal as compared with the postmenopausal women, the administration of one GHRH-44 injection resulted in significantly higher 120-min postinjection GH maximum peak and cumulative responses in the former group as well (P less than 0.005). Highly significant correlations were observed between 17 beta-estradiol plasma levels and either GH maximum peak or cumulative responses to GHRH-44 when both groups were pooled together, but not when considered independently. In postmenopausal women, a correlation was found between both age and duration of menopause and GH responses. Repeated GHRH-44 injections in postmenopausal women induced a significant increase in GH response (P less than 0.001) as well as in IGF-I levels from day 4 to 8. No phospho-calcium parameters were modified except for a significant rise in osteocalcin from day 2 to 8. These data indicate an age-related loss of sensitivity of somatotrope cells to GHRH-44 in postmenopausal women, partly corrected by repeated daily GHRH-44 injections. As a consequence of the GHRH-induced increase in GH secretion, IGF-I was also enhanced and may be responsible for a stimulatory effect on bone formation, as shown by the osteocalcin increase, uncoupled from bone resorption.

Adult↗

PubMed2000

Glycaemic control and hormone replacement therapy: implications of the Postmenopausal Estrogen/Progestogen Intervention (PEPI) study.

Despite evidence that supports the beneficial effects of postmenopausal hormone replacement therapy (HRT), concerns remain about its possible adverse effects. However, entry into the postmenopausal state is associated with many characteristics of the insulin resistance syndrome, including increased cardiovascular morbidity and mortality, accretion of generalised and visceral adiposity and insulin resistance. Studies carried out in postmenopausal women have revealed that an increase in visceral obesity is associated with an increase in androgenicity that, in turn, is associated with type 2 (non-insulin-dependent) diabetes mellitus. Short term studies of HRT containing conjugated estrogens (CEE) and medroxyprogesterone (MPA) have shown prevention of the accretion of visceral fat. However, longer term studies using other techniques suggest that these effects may be evanescent. A few trials suggest that oral estrogen therapy reduces postmenopausal insulin resistance, as suggested by reductions in fasting insulin and glucose levels and an increase in glucose metabolism rates, whereas most studies do not show an adverse effect upon carbohydrate metabolism. MPA may decrease these beneficial effects. Transdermal estrogen is essentially neutral with regard to insulin sensitivity and oral estradiol (17beta-estradiol) may also be neutral or enhance sensitivity. Different progestogens vary in their effects upon carbohydrate metabolism. The Postmenopausal Estrogen/Progestogen Intervention (PEPI) Study was a prospective, 3-year, randomised trial in 875 women that compared placebo, unopposed CEE, CEE plus continuous MPA, CEE plus cyclical MPA, and CEE plus cyclical micronised progesterone. Fasting insulin and glucose levels decreased significantly by 16.1% and 0.122 mmol/L, respectively, in all drug treatment groups. However, after a 75g glucose load, glucose levels at 2 hours increased by 0.33 mmol/L in the active treatment groups without a corresponding increase in insulin levels. No beneficial effects on waist/hip ratio could be demonstrated. Data from the PEPI trial also suggested that the maximum benefit regarding carbohydrate metabolism was achieved in patients who were the most hyperglycaemic and hyperinsulinaemic at the start of therapy. It can be concluded, therefore, that HRT has few, if any, harmful effects on carbohydrate metabolism and that it may be of benefit in women in modifying the long term complications of the postmenopausal state.

Aged↗

PubMed2001

Estradiol and norgestimate: a review of their combined use as hormone replacement therapy in postmenopausal women.

The focus of this review is hormone replacement therapy (HRT) with continuous administration of micronised, oral 17beta-estradiol 1 mg/day (herein referred to as continuous estradiol) plus micronised, oral norgestimate 90 microg/day administered for 3 days then withdrawn for 3 days in a 6-day repeating sequence (herein referred to as intermittent norgestimate). According to data from randomised, comparative trials of 1 year's duration, continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day relieves climacteric symptoms (vasomotor symptoms and vulvovaginal atrophy) in postmenopausal women. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day appeared as effective as estradiol 1 mg/day alone or continuous estradiol 2 mg/day plus continuous norethisterone acetate 1 mg/day in the treatment of postmenopausal women with vasomotor symptoms. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was as effective as continuous estradiol 1 mg/day in causing the maturation of vaginal epithelial cells. In a randomised, double-blind study, bone mineral density (BMD) increased to a significantly greater extent and the rate of bone turnover was slower in postmenopausal women treated with continuous oral estradiol 1 mg/day plus intermittent norgestimate 90 microg/day than in placebo-treated patients. Two randomised, double-blind studies indicated that the addition of norgestimate 90 microg/day to continuous estradiol 1 mg/day did not attenuate the beneficial effects of estradiol on lipid parameters. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was associated with increases in mean serum high density lipoprotein (HDL)-cholesterol levels and decreases in total cholesterol, low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels, compared with baseline. There was no statistically significant increase in triglyceride levels. In comparative trials, continuous oral estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was well tolerated. Headache, breast pain or discomfort, abdominal pain or discomfort, uterine bleeding, dysmenorrhoea, oedema, nausea and depression were the most commonly reported adverse events. Continuous estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was associated with a favourable uterine bleeding profile that improved over time. In a randomised trial, 80% of women were free from bleeding (irrespective of spotting) during month 12 of treatment. Norgestimate 90 microg/day was effective in protecting postmenopausal women against induction of endometrial hyperplasia by continuous estradiol 1 mg/day. In conclusion, data from a limited number of randomised studies indicate that HRT with continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day is effective in relieving climacteric symptoms, increasing BMD and slowing the rate of bone turnover in postmenopausal women. This HRT regimen is well tolerated and is associated with a similar incidence of adverse events to that reported in recipients of continuous estradiol 1 mg/day. The norgestimate component of the regimen provides good endometrial protection and is associated with a favourable bleeding profile. Long-term studies investigating the associated risk of breast cancer and thromboembolic events in recipients of continuous estradiol plus intermittent norgestimate are needed. In the meantime, continuous oral estradiol plus intermittent oral norgestimate can be regarded as an effective new option for HRT in postmenopausal women.

Contraceptives, Oral, Synthetic↗

PubMed2004

Transdermal 17-beta-estradiol and risk of developing type 2 diabetes in a population of healthy, nonobese postmenopausal women.

OBJECTIVE: Various observational and randomized studies have demonstrated a reduction in the incidence of type 2 diabetes in postmenopausal women who received estrogen orally. No studies have been performed on the incidence of type 2 diabetes in postmenopausal women treated with transdermal 17-beta-estradiol. The purpose of our study was to assess the influence of transdermal 17-beta-estradiol on the incidence of type 2 diabetes in a population of healthy, nonobese postmenopausal women. RESEARCH DESIGN AND METHODS: Between January 1998 and December 2002, 673 healthy, nonobese postmenopausal women (mean age 54 +/- 5 years) were enrolled: 144 (21.4%) of these took transdermal 17-beta-estradiol and 529 (78.6%) had never taken hormones during their postmenopausal period. Final elaboration of the data took place in July 2003, with a mean follow-up of 3.7 +/- 0.7 years (ranging from 0.5 to 5 years). RESULTS: Type 2 diabetes developed in 60 patients during the follow-up period, which is the equivalent of 22 cases per 1,000 women-years. In the "hormones nonusers" group, diabetes developed in 10% (54 of 529 women; equivalent of 26.5 cases/1,000 women-years), whereas in the "hormones users" group, diabetes developed in 4.16% (6 of 144 women; equivalent of 12.1 cases/1,000 women-years). Transdermal 17-beta-estradiol emerged as a treatment that significantly reduced the risk of developing diabetes (RR 2.19, 95% CI 1.79-3.56; P=0.006). CONCLUSIONS: Our results suggest a significant reduction in the incidence of type 2 diabetes in our population of nonobese, healthy postmenopausal women who used transdermal 17-beta-estradiol. This could suggest that, in some women, the estrogen deficiency that occurs after menopause could represent a fundamental step in the process of diabetogenesis.

Administration, Cutaneous↗

PubMed1978

Ultrastructural features in normal and hyperplastic postmenopausal endometrium.

Seven samples of postmenopausal endometrium were studied by electron microscopy. Four samples were diagnosed as adenomatous hyperplasia (2 of which were atypical) and 3 as normal postmenopausal endometrium. The most striking ultrastructural features of hyperplastic endometrium were: numerous nucleoli, deep nuclear membrane infoldings, increased nucleocytoplasmic ratio, prominent and enlarged RER closely associated with mitochondria and nuclear membrane, abundant free ribosomes and marked network microfilaments. In the case of atypical adenomatous hyperplasia, the protruded intraglandular proliferating epithelial cells exhibited more atypical features than the epithelial cells of the glandular lining, suggesting a more advanced degree of anaplastic change. The characteristic features of the normal postmenopausal endometrium were: paucity and random distribution of the cytoplasmic organelles, the presence of large cytoplasmic vacuoles and short, blunt microvilli. Secretory vacuoles opening into the lumen of the gland were found in one case of cystic atrophy of a normal postmenopausal endometrium. Collagenization was found in the stroma of both groups, although predominantly in the normal postmenopausal endometrium. In 2 cases of adenomatous hyperplasia stromal cells with vacular cytoplasm were found. The significance of these findings, as related to their importance as precursor stages of endometrial cancer (in the cases of adenomatous and atypical adenomatous hyperplasia); as involutional manifestations (in the cases of normal postmenopausal endometrium); and as related to the absence of cyclic activity (in both groups) is briefly discussed.

Cell Nucleus↗

PubMed1993

Immunohistochemical localization of pituitary gonadotropins and estrogen in human postmenopausal ovaries.

Immunohistochemical localization of pituitary gonadotropins (FSH, LH) and estrogen was investigated in 17 ovaries from ten postmenopausal women. Positive immunostaining for 17 beta-estradiol was demonstrated in the cortical stroma of 14 postmenopausal ovaries. Positive immunostaining for FSH was localized in the cortical stroma of 12 postmenopausal ovaries, and positive immunostaining for LH was also localized in 12 ovaries. Immunohistochemical localization for pituitary gonadotropins (FSH and/or LH) and 17 beta-estradiol was identified in the same hypertrophic cortical stroma of 13 postmenopausal ovaries. The ultrastructural study suggested steroidogenic activity in the cortical stromal cells of the postmenopausal ovary. In addition, peripheral and ovarian venous concentrations of 17 beta-estradiol were measured in 13 postmenopausal subjects, and significant concentration gradient for serum 17 beta-estradiol was noted. The ovarian/peripheral concentration gradient for 17 beta-estradiol had a tendency to be higher in the subjects with positive immunostaining for 17 beta-estradiol compared with that in the subjects with negative immunostaining. The present results suggest that the human ovary secretes estrogen in response to pituitary gonadotropins even after the menopause.

Aged↗

PubMed2004

Should postmenopausal hormone therapy be used to prevent osteoporosis?

OBJECTIVE: To discuss the risks and benefits of hormone therapy for the prevention of postmenopausal osteoporosis. DATA SOURCES: A MEDLINE search was conducted to identify articles that are pertinent to the risks and benefits of hormone therapy for the prevention of postmenopausal osteoporosis. Additional references were obtained from the bibliographies of these articles. STUDY SELECTION: Human studies that present efficacy and safety data for the effects of postmenopausal hormone therapy. DATA EXTRACTION: Analysis of studies to determine the benefits of hormone therapy on bone (in terms of bone mineral density or fracture risk) and risks of hormone therapy in postmenopausal women. DATA SYNTHESIS: Studies were analyzed to determine the risk-benefit profile of hormone therapy for the prevention of postmenopausal osteoporosis. This information was synthesized to help practitioners make decisions regarding the role of postmenopausal hormone therapy in the prevention of osteoporosis. CONCLUSION: Given the risks of hormone therapy, some of which are associated with increased duration of use, hormone therapy cannot be routinely recommended for the sole purpose of preventing osteoporosis. Many alternative therapies exist that may offer patients a better benefit versus risk ratio.

Journal Article↗

PubMed2004

[Depression-anxiety and disability in the premenopausal and postmenopausal period].

OBJECTIVE: The aim of the study is to compare levels of depression-anxiety and disability in premenopausal and postmenopausal women. METHOD: The study was carried out with women between 45-55 years of age, living in the service area of a Mother-Child Health and Family Planning Center. Women who did not have a menstruation at least for one year were accepted as postmenopausal. The premenopausal group was consisted of women having menstruation. Hospital Anxiety and Depression Scale (HAD) and Brief Disability Questionnaire (BDQ) were applied to the women. RESULTS: Four hundred and ninety four women were recruited to the study. There were 214 women in the premenopausal period and 280 women in the postmenopausal period. In premenopausal women the level of education was higher and smoking was more prevalent; whereas in postmenopausal women the prevalence rates of being housewife and having continuous drug therapy due to chronic physical diseases were higher. In postmenopausal women, levels of depression and disability were significantly higher. In this group, the predictive factors for having a high HAD score were disability, education having a previous psychiatric disorder having drug therapy due to chronic physical diseases, diabetes mellitus, low level, menopause before the age of 40, not having any counselling for menopause, and not having routine laboratory tests. Having a previous psychiatric disorder and not having any counselling were also predicting disability. None of the variables predicted a high HAD score psychiatric disorder and not having any counselling were also predicting disability and disability in the premenopausal women. CONCLUSION: The postmenopausal period seems to predispose women to depressive symptoms and disability compared to the premenopausal period.

Depressive Disorder↗

PubMed2002

Baseline BMD and bone loss at distal radius measured by peripheral quantitative computed tomography in peri- and postmenopausal Hong Kong Chinese women.

The current study was designed to investigate the rate of bone loss in distal radius and its association with baseline volumetric bone mineral density (BMD) and years since menopause (YSM) in peri- and postmenopausal women using precise and multislice peripheral quantitative computed tomography (pQCT; Densiscan 2000). Two hundred and five healthy Hong Kong Chinese perimenopausal ( n = 26) and postmenopausal ( n = 179) women within 10 years of the onset of menopause were recruited. Anthropometric parameters and menstrual status were also measured. The linear regression model derived from the baseline volumetric BMD revealed a significant and slightly better correlation with YSM than age, with a YSM-related annual decline of 2.56%, 1.82% and 0.65% in trabecular BMD (tBMD), integral BMD (iBMD) and cortical BMD (cBMD), respectively. Follow-up measurements after a time interval of 12 months showed that the rate of bone loss was higher than the annual decline in BMD calculated from the baseline BMD, with decreases of 2.89%, 2.16% 0.91% in tBMD, iBMD and cBMD, respectively. Baseline BMD was associated with age or YSM ( r ranges from -0.283 to -0.502; p<0.001 in all cases), but no relationship was found between annual rate of bone loss and age or YSM. The rate of bone loss did not correlate with baseline volumetric BMD values or YSM after dividing the subjects into fast bone losers (with annual tBMD loss > or =3%), normal bone losers (with annual tBMD loss > or = 1% but <3%) or slow bone losers (with annual tBMD loss <1%). The rate of bone loss was greater in both trabecular and cortical bone of postmenopausal women within the first 3 menopausal years but was only significant in the iBMD as compared with perimenopausal and postmenopausal women over 7 years after onset of menopause. The percentage distribution of slow and fast bone losers was not found to be associated with YSM. As a total of only 4 fracture cases were documented, the study could not provide conclusive information on whether perimenopausal and early postmenopausal baseline volumetric BMD or rate of bone loss determines the development of osteoporosis or fracture occurrence.

Adult↗

PubMed2006

Increased prevalence of peripheral arterial disease in osteoporotic postmenopausal women.

The aim of this study was to investigate the prevalence and correlates of peripheral arterial disease (PAD) in a population of osteoporotic postmenopausal women. The presence of PAD was assessed by ankle brachial index (ABI) in 345 ambulatory osteoporotic postmenopausal women, and in 360 community-based, age- and race-matched postmenopausal women with normal bone mineral density (BMD) (control group). PAD was detected in 63/345 (18.2%) osteoporotic women and in 14/360 (3.8%) control subjects (P < 0.0001). The mean ABI values were significantly lower in the osteoporosis group than in the control group (0.98 +/- 0.09 vs. 1.04 +/- 0.06, P < 0.0001). No difference in cardiovascular risk factors was observed between osteoporotic patients and controls, or between osteoporotic patients with and without PAD. Osteoporotic patients with PAD had lower femoral neck BMD T scores than those without PAD (-4.2 +/- 0.7 vs. -2.3 +/- 0.7, P < 0.0001). Only 4 PAD patients (5.1%) had intermittent claudication. In multivariate logistic regression analysis, factors independently associated with PAD within osteoporotic patients were lower femoral neck BMD T score (odds ratio (OR) = 0.20, 95% confidence interval (CI), 0.05-0.70, P = 0.01) and systolic blood pressure (OR = 1.02, 95% CI, 1.00-1.03, P = 0.01). This study shows for the first time an increased prevalence of PAD among osteoporotic postmenopausal women, with a lower femoral neck BMD T score being a significant independent predictor. The findings suggest that vascular status evaluation should be done in osteoporotic postmenopausal women in order to identify candidate patients for preventive and therapeutic cardiovascular interventions.

Age Factors↗

PubMed2004

Raloxifene is not associated with biologically relevant changes in hot flushes in postmenopausal women for whom therapy is appropriate.

OBJECTIVES: Raloxifene is approved for the treatment and prevention of postmenopausal osteoporosis. Previous studies have described a raloxifene-associated increase in hot flushes, reported as adverse events. This study was undertaken to provide a detailed evaluation of the potential of raloxifene to induce or exacerbate hot flushes in postmenopausal women. STUDY DESIGN: In this double-blind, placebo-controlled, parallel group multicenter study, 487 postmenopausal women were randomized to receive 8 months of treatment with either raloxifene (RLX) at the recommended dose of 60 mg/day, or by slow-dose escalation for the first 2 months, followed by the standard dose for the rest of the study (SDE), or placebo (PL). The frequency, duration, intensity, severity, and impact of hot flushes were measured. RESULTS: With 3-5 hot flushes per week, the mean number at baseline was low. During treatment, it increased by <1 hot flush/week in both active treatment groups and decreased by <1 hot flush/week with PL. The high proportion ( approximately 60%) of asymptomatic patients at baseline had increased further by the end of treatment in all groups. The proportion of women whose pre-existing hot flushes abated during treatment was significantly greater with SDE (P=.005) and PL (P=.050), but not with RLX, when compared with the proportion with treatment-emergent flushes. There were no statistically significant between-group differences in the distribution of the number of hot flushes after 2 months of treatment. At end point, there were no significant differences between SDE and either RLX or PL, but the difference between RLX and PL was statistically significant (P=.035). There were no significant between-group differences in the hot flush impact scores, in treatment satisfaction, and in the proportion of patients requesting symptomatic treatment to alleviate hot flushes. CONCLUSION: In a postmenopausal population meeting the criteria for the prescription of RLX, the overall effect of the drug on hot flushes is low. Previous studies using adverse event reports have overestimated the importance of hot flushes in postmenopausal women during treatment with RLX. Slow-dose escalation seems to decrease the number of symptomatic patients further and may be a useful strategy in women reporting flushes when starting RLX.

Aged↗

PubMed1993

Tamoxifen reduces bone turnover and prevents lumbar spine and proximal femoral bone loss in early postmenopausal women.

Although widely used for its anti-estrogen properties tamoxifen has estrogen like effects on a number of tissues including bone and liver. Previous studies suggest a preservation of lumbar spine density in postmenopausal women but the effect on the hip had not been addressed. To determine whether tamoxifen prevents bone loss in the early postmenopausal period bone mineral density at the lumbar spine and femoral neck was measured using dual energy X-ray absorptiometry at presentation and 6 monthly thereafter for 1 year in a prospective controlled study. Also indices of bone turnover, serum osteocalcin and urinary hydroxyproline excretion, were assessed. Fifteen early postmenopausal women with Stage I or II breast cancer treated with tamoxifen and 21 normal postmenopausal women were studied. Sex hormone binding globulin and antithrombin III levels in serum were also measured as indices of the hepatic estrogenic activity. Tamoxifen (20 mg daily) prevented bone loss at the femoral neck and lumbar spine. Median rates of change in bone mineral density (%/year) for the tamoxifen group were +0.09%/year in the lumbar spine and 1.4%/year in the femoral neck compared with -2.3%/year and -1.8%/year for the control group (P = 0.04 and 0.03, respectively). Tamoxifen resulted in a significant decrease in both serum osteocalcin and urinary hydroxyproline by 6 months of treatment and this effect persisted for the 12 months of observation. An increase in sex hormone binding globulin and a decline in antithrombin III levels was also observed. These data indicate that, in recently, postmenopausal women tamoxifen prevented bone loss at both the lumbar spine and femur and reduced bone turnover.

Absorptiometry, Photon↗

PubMed2005

Coexistence of osteoporosis and cardiovascular disease risk factors in apparently healthy, untreated postmenopausal women.

This study aimed to determine whether apparently healthy, untreated postmenopausal women at risk of osteoporosis relative to nonmenopausal women are concomitantly at risk of cardiovascular disease (CVD) in terms of various aspects of lifestyle, personality, body shape and composition, and blood chemistry. Two homogeneous groups of 30 women having reached menopause for 3-5 years and 30 nonmenopausal controls, all non-estrogen users without apparent CVD risk factors, were compared in a cross-sectional design. Data related to physical activity, dietary intakes, personality type, anthropometry, and skinfold-thickness were collected. Plasma insulin-like growth factor (IGF-1) and serum lipids were measured and used as biochemical predictors of osteoporosis and CVD, respectively. Compared to nonmenopausal controls, postmenopausal women were at greater risk of bone loss given their lower plasma IGF-1, lower physical activity level, and even given their higher serum lipids, as recent literature suggests. Moreover, their dietary calcium intake fulfilled only 70% of the current recommendation, which may reduce protection against osteoporosis and CVD (particularly hypertension) as well. The two groups did not differ regarding energy intake, body weight and frame size, body mass index (BMI), waist circumference, and waist-hip ratio (WHR). However, postmenopausal subjects had more adipose tissue and differed in terms of lifestyle factors (lower dietary lipids and greater alcohol consumption). While neither group was at particular risk of CVD according to waist circumference, WHR, and serum triglycerides, postmenopausal women were at risk according to percent body adiposity and serum cholesterol. This study shows that several risk factors for osteoporosis and CVD can coexist in apparently healthy postmenopausal women after a few years of natural menopause. It emphasizes the need for a timely screening that would stress both heart and bone risk factors.

Adipose Tissue↗