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Endogenous androgen levels and well-being: differences between premenopausal and postmenopausal women.

OBJECTIVE: We investigated whether there is a relationship between androgens levels and well-being in pre- and postmenopausal women. DESIGN: We randomly recruited 1423 women aged 18 to 75 years from the community via the electoral roll. Each provided a morning blood sample and completed the Psychological General Well Being Index questionnaire on the same day. Women were excluded if they took medication for any psychiatric illness, had abnormal thyroid function, or had documented polycystic ovarian syndrome. Analysis was by linear regression for well-being, including demographic and lifestyle variables as well as serum levels of androgens. RESULTS: We included 1224 women in the analysis. Being partnered was positively associated with well-being in premenopausal women. In postmenopausal women, well-being was positively related to age and exercising, whereas smoking, obesity, and postmenopausal hormone therapy use were each negatively associated with well-being. None of the measured androgens (total and free testosterone, dehydroepiandrosterone sulfate, and androstenedione) made an independent contribution to well-being in postmenopausal women (n = 603). However, for premenopausal women (n = 621), levels of dehydroepiandrosterone sulfate were independently and positively associated with the domain score for vitality. CONCLUSIONS: Our findings do not support an important independent role for androgens as determinants of well-being in postmenopausal women. That dehydroepiandrosterone sulfate alone is associated with greater vitality in premenopausal women is of interest but requires further evaluation as an a priori hypothesis in another study.

Adolescent↗

Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society.

OBJECTIVE: To update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2002 regarding the management of osteoporosis in postmenopausal women. DESIGN: NAMS followed the general principles established for evidence-based guidelines to create this updated document. A panel of clinicians and researchers expert in the field of metabolic bone diseases and/or women's health were enlisted to review the 2002 NAMS position statement, compile supporting statements, and reach consensus on recommendations. The panel's recommendations were reviewed and approved by the NAMS Board of Trustees. RESULTS: Osteoporosis, whose prevalence is especially high among elderly postmenopausal women, increases the risk of fractures. Hip and spine fractures are associated with particularly high morbidity and mortality in this population. Given the health implications of osteoporotic fractures, the primary goal of osteoporosis therapy is to prevent fractures, which is accomplished by slowing or stopping bone loss, maintaining bone strength, and minimizing or eliminating factors that may contribute to fractures. The evaluation of postmenopausal women for osteoporosis risk requires a medical history, physical examination, and diagnostic tests. Major risk factors for postmenopausal osteoporosis (as defined by bone mineral density) include advanced age, genetics, lifestyle factors (such as low calcium and vitamin D intake, smoking), thinness, and menopause status. The most common risk factors for osteoporotic fracture are advanced age, low bone mineral density, and previous fracture as an adult. Management focuses first on nonpharmacologic measures, such as a balanced diet, adequate calcium and vitamin D intake, adequate exercise, smoking cessation, avoidance of excessive alcohol intake, and fall prevention. If pharmacologic therapy is indicated, government-approved options are bisphosphonates, a selective estrogen-receptor modulator, parathyroid hormone, estrogens, and calcitonin. CONCLUSIONS: Management strategies for postmenopausal women involve identifying those at risk of low bone density and fracture, followed by instituting measures that focus on reducing modifiable risk factors through lifestyle changes and, if indicated, pharmacologic therapy.

Evidence-Based Medicine↗

Serum leptin levels and body composition in postmenopausal women treated with tibolone and raloxifene.

OBJECTIVE: To compare body composition and serum leptin levels in untreated postmenopausal women and postmenopausal women treated with tibolone or raloxifene. DESIGN: This was a prospective, randomized, controlled study. Sixty-eight postmenopausal women were randomized to receive either no treatment (group A, n = 21) or tibolone 2.5 mg/day (group B; n = 23) or raloxifene 60 mg/day (group C; n = 24). All women underwent height, weight, body mass index evaluation and dual energy x-ray absorptiometry determination of body composition at the beginning of the study and after 12 months. Serum leptin levels were determined at the beginning of the study and after 1, 3, 6, and 12 months in all groups. RESULTS: Women in group A showed no significant changes in both fat and lean mass of arms and legs, whereas a significant increase in trunk fat mass, total fat mass, total percentage of body fat, and trunk percentage of fat was detected 1 year after the beginning of the study. After 12 months, the total percentage of fat mass was significantly higher in group A compared with group B, and the trunk percentage of fat mass was significantly higher in group A compared with groups. In subjects in groups B and C, after 1 year, fat mass, both total and at all areas evaluated, did not show any significant change compared with baseline values. In subjects in group B, total lean and lean mass of the trunk and legs increased significantly at the end of the study, whereas no significant changes were observed in lean mass, total and at all areas evaluated in subjects in group C. After 12 months, total lean mass and lean mass of the legs were significantly higher in group B compared with the other groups. In group A, serum leptin levels were significantly increased at the end of the study compared with baseline values. Leptin concentrations were significantly higher in group A compared with groups B and C after 6 and 12 months. No significant change in serum leptin levels in subjects in groups B and C was detected throughout the study. Serum leptin levels showed a positive, significant correlation with all body composition parameters and body mass index in all groups at the beginning and at the end of the study. CONCLUSIONS: The present study confirms that postmenopausal hypoestrogenism leads to increased fat content and serum leptin levels. Raloxifene and tibolone seem to prevent postmenopausal body composition changes without significant modifications of serum leptin levels.

Absorptiometry, Photon↗

Effects of estrogen-progestin therapy on serum levels of RANKL, osteoprotegerin, osteocalcin, leptin, and ghrelin in postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate the effects of estrogen-progestin therapy on serum levels of receptor-activating nuclear factor kappabeta ligand (RANKL), osteoprotegerin, osteocalcin, leptin, and ghrelin in a cross-sectional study of 99 healthy postmenopausal women conducted at the Menopause Clinic of our department. DESIGN: In this cross-sectional, observational study, 99 participants were divided into two groups. Group A was composed of 77 postmenopausal women who had never received estrogen-progestin therapy, and group B was composed of 22 postmenopausal women who had received transdermal 17beta-estradiol at a dose of 50 microg/day in a continuous regimen for at least 24 months and nomegestrol at a dose of 5 mg/day for 12 days/month in a sequential regimen. All participants underwent blood sampling in the morning and quantitative ultrasound bone-densitometry measurement of the proximal phalanges of the dominant hand. RESULTS: T score and amplitude-dependent speed of sound were significantly higher in group B than in group A. No significant differences in RANKL, osteoprotegerin, and osteocalcin were observed between the two groups. Serum leptin levels were significantly lower in group B than in group A, whereas ghrelin was significantly higher in group B than in group A. CONCLUSIONS: The data gathered in this preliminary study indicate that estrogen-progestin therapy may protect against postmenopausal bone loss, but this protective effect does not seem to be exerted through action on the RANK-RANKL-osteoprotegerin system. Similarly, although several reports suggest that leptin and ghrelin are involved in bone metabolism, we could not detect any important correlation of these two hormones with bone metabolism or bone status in treated and untreated postmenopausal women. Because of the limited number of treated participants and the study design, the results of this preliminary study must be confirmed in larger, prospective, longitudinal studies.

Administration, Cutaneous↗

Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide.

OBJECTIVE: Drospirenone (DRSP), a spironolactone analog with aldosterone antagonist activity, is a novel progestogen developed for use as hormone therapy in postmenopausal women in combination with 17beta-estradiol (E2). DRSP/E2 lowers blood pressure when used alone in hypertensive postmenopausal women or when administered concomitantly with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. DRSP/E2 has not been studied in combination with the widely prescribed hydrochlorothiazide (HCTZ). We investigated the effects of 3 mg DRSP/1 mg E2 versus placebo on blood pressure and potassium balance when added to existing therapy with 25 mg HCTZ in postmenopausal women with established stage I hypertension. DESIGN: This was a single-center, double-blind, randomized, placebo-controlled, two-treatment, two 4-week treatment period crossover study in 36 postmenopausal women with stage I hypertension maintained on 25 mg HCTZ. The endpoint was a change from baseline in systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring. Safety monitoring included serum potassium (mEq/L) and adverse events. RESULTS: Mean systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring were reduced significantly, by -7.2 and -4.5 mm Hg, respectively, with DRSP/E2 as compared with placebo. The decrease in potassium with HCTZ was 0.2 mEq/L less with DRSP/E2 than placebo, suggesting a potassium-sparing effect. The most frequently observed adverse events with DRSP/E2 were vaginal bleeding and breast tenderness, which were attributable to the hormone therapy. CONCLUSIONS: DRSP/E2 substantially lowers systolic and diastolic blood pressure when added to existing antihypertensive therapy with HCTZ in hypertensive postmenopausal women. In addition, DRSP/E2 has a potassium-sparing effect that counteracts HCTZ-induced potassium loss.

Aged↗

Frequency of spontaneously occurring postmenopausal bleeding in the general population.

BACKGROUND: To determine the frequency of spontaneously occurring postmenopausal bleeding in the population, a prospective observational population study was undertaken. METHODS: Out of a population-based sample of 2000 Danish women aged 45-54 years, 1616 women responded to an initial questionnaire. Of these, 1059 women with natural gynecologic functions were eligible for the diary study, and of these, 951 (89.8%) women completed 1 year of daily recording of bleeding, medication relevant to bleeding, and medical consultations for gynecologic matters. Of the 951 women, 271 were postmenopausal. MAIN OUTCOME MEASURES: Occurrence of spontaneous postmenopausal bleeding including strength and length of each bleeding. RESULTS: Of 271 postmenopausal women, 29 (10.7%, 95% confidence interval 7.3-15.0%) recorded spontaneous postmenopausal bleeding. The incidence of women with bleeding was strongly correlated with time since menopause (P = 0.0001), with an estimated incidence of 409/1000 (218/1000-771/1000) person-years immediately after the first 12 months of amenorrhea following the menopause falling to 42/1000 (17/1000-102/1000) more than 3 years after menopause. CONCLUSIONS: This study indicates that recurrence of bleeding is very common in the time immediately after the 12 months of amenorrhea after what is currently defined as the final menstrual period, declining to low frequencies more than 3 years after the final menstrual period.

Female↗

Pharmacokinetics and systemic endocrine effects of the phyto-oestrogen 8-prenylnaringenin after single oral doses to postmenopausal women.

AIMS: Pre-clinical data suggest that the racemic phyto-oestrogen 8-prenylnaringenin (8-PN) may have beneficial effects in postmenopausal women and may become an alternative to classical hormone replacement therapy (HRT) treatment regimes. The aim of this study was to investigate the pharmacokinetics, endocrine effects and tolerability of chemically synthesized 8-PN in postmenopausal women. METHODS: The study was performed using a randomized, double-blind, placebo-controlled, dose-escalation design with three groups of eight healthy postmenopausal women. In each group six subjects received 8-PN and two subjects placebo. 8-PN was given orally in doses of 50, 250 or 750 mg. Drug concentrations in serum, urine and faeces were measured up to 48 h and follicle-stimulating hormone/luteinizing hormone (LH) concentrations up to 24 h. RESULTS: All treatments were well tolerated and associated with a low incidence of (drug unrelated) adverse events. Serum concentrations of free 8-PN showed rapid drug absorption and secondary peaks suggestive of marked enterohepatic recirculation. Independent of the treatment group, approximately 30% of the dose was recovered in excreta as free compound or conjugates over the 48-h observation period. The first C(max) and AUC(0-48 h) showed dose linearity with ratios of 1 : 4.5 : 13.6 (C(max)) and 1 : 5.2 : 17.1 (AUC). The750- mg dose decreased LH concentrations by 16.7% (95% confidence interval 0.5, 30.2). CONCLUSION: Single oral doses of up to 750 mg 8-PN were well tolerated by postmenopausal women. The pharmacokinetic profile of 8-PN was characterized by rapid and probably complete enteral absorption, high metabolic stability, pronounced enterohepatic recirculation and tight dose linearity. The decrease in LH serum concentrations found after the highest dose demonstrates the ability of 8-PN to exert systemic endocrine effects in postmenopausal women.

Administration, Oral↗

Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing's syndrome.

OBJECTIVE: Cushing's syndrome (CS) is a well recognized cause of bone loss. Although many previous studies have shown decreased bone mineral density (BMD) in the lumbar spina and proximal femur of patients with endogenous CS, so far, the data estimating BMD in their peripheral skeleton are sparse. The aim of the present study was to evaluate BMD in the forearm and heel of women with newly diagnosed CS and to investigate its possible correlation with serum osteocalcin (BGP) and 24-hour urinary free cortisol levels (UFC). PATIENTS AND METHODS: BMD in the forearm (distal and ultradistal area) of 29 (13 premenopausal and 16 postmenopausal) women with newly diagnosed CS (18 with pituitary adenoma, 10 with adrenal tumor and 1 with ectopic) was measured by dual x-ray absorptiometry (DEXA) and was compared with BMD of 29 age, body mass index (BMI)- and oestrogen status matched healthy controls. Furthermore, in 18 (9 premenopausal and 9 postmenopausal) of the above patients (14 with pituitary adenoma, 5 with adrenal tumor and 1 with ectopic) broadband ultrasound attenuation (BUA) by quantitative ultrasound (QUS) of the heel was estimated and 18 age-, BMI- and oestrogen status matched healthy women served as controls. In all the patients serum BGP and UFC were measured at the time of diagnosis of CS. RESULTS: Compared to their matched controls, BMD in the forearm and BUA values in the heel did not differ in the premenopausal women with CS, while in the postmenopausal group BMD in the forearm was decreased (P < 0.05) but not BUA. Apart from a weak negative correlation between serum BGP and BMD in the ultradistal site of the forearm in premenopausal women (P = 0.05), serum BGP and UFC did not show significant correlation with BMD or BUA. CONCLUSIONS: BMD in the forearm is reduced only in postmenopausal women with newly diagnosed endogenous CS, while BUA in the heel is unaffected in both pre- and postmenopausal patients. Moreover, serum BGP and UFC do not seem to be relevant markers for assessing bone loss in the peripheral skeleton at the time of diagnosis of hypercortisolemia.

Absorptiometry, Photon↗

Effects of oestradiol and oestroprogestin on erythrocyte antioxidative enzyme system activity in postmenopausal women.

OBJECTIVE: Data concerning the relationship between sex steroid hormones and the cellular antioxidative enzyme system are controversial. We investigated the effects of oestradiol deficiency after menopause and the influence of transdermal oestradiol therapy (ET) and hormonal (oestradiol plus medroxyprogesterone) replacement therapy (HT) on erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). GSH and selenium (Se) concentrations were also estimated. Serum lipid peroxide (LPO) levels were measured as an indicator of free-radical production and lipid peroxidation. PATIENTS: The study group consisted of 80 postmenopausal women, divided into two subgroups: 26 women with surgically induced menopause (ET1) and 54 women with physiological menopause (HT1). Forty premenopausal healthy volunteers were controls (C group). RESULTS: LPO was higher in postmenopausal women and decreased after both ET and HT. GSH-Px and GSH were lower in the postmenopausal groups but increased significantly after both types of therapy. Se concentrations did not differ significantly among the groups. CAT activities were similar in all groups and decreased after ET and HT. SOD activities in postmenopausal women were similar to those in the C group and did not change significantly after treatment. CONCLUSIONS: The administration of natural oestrogens to postmenopausal women diminishes oxidative stress and increases antioxidative cell potency.

Antioxidants↗

Dietary macro- and micronutrient intakes of nonsupplemented pre- and postmenopausal women with a perspective on menopause-associated diseases.

OBJECTIVES: To assess the dietary intakes and diet quality of menopausal women relative to premenopausal women, and to determine whether their diets are compatible with reducing risks of cardiovascular disease (CVD) and osteoporosis. DESIGN: Cross-sectional study using 3-day food records and anthropometric measurements. Subjects Thirty apparently healthy, nonoestrogen using and nonsupplemented women menopausal since 3-5 years and 30 well-matched premenopausal women. Outcome measures Nutrient intakes, diet nutrient density, body mass index (BMI), waist circumference, waist-to-hip ratio and serum oestradiol. RESULTS: Energy intake and body weight of pre- and postmenopausal women were comparable. Their BMI, waist circumference and waist-to-hip ratios were within healthy ranges. The diet of postmenopausal women was compatible (less total lipids and saturated fatty acids; more fibres, antioxidant vitamins and potassium) with North American nutritional recommendations linked to cardiovascular health. Their dietary iron intakes exceeded their reduced physiological need, which may jeopardize their cardiovascular system. Their calcium and vitamin D intakes were far below recommendations for healthy bones. Five other nutrients were also suboptimal. Phosphorus intake (high in both groups) correlated with dietary proteins, sulphur amino acids and calcium. CONCLUSIONS: The diet of the postmenopausal women studied were more compatible with national nutritional recommendations than that of premenopausal controls. However, these postmenopausal women, not taking hormone replacement therapy (HRT) and having inadequate dietary calcium and vitamin D intakes, may be at increased risk of osteoporotic fracture later in life. More studies on CVD risk inherent to body iron accumulation involving a large number of postmenopausal women are warranted before planning public health measures regarding dietary iron intake.

Adult↗

Does beclomethasone dipropionate suppress dehydroepiandrosterone sulphate in postmenopausal women?

BACKGROUND: Patients with chronic obstructive airways disease and asthma are at special risk of developing osteoporosis. Previous research has indicated that adrenal androgen levels in postmenopausal women are suppressed by short term high dose inhaled corticosteroids. Such an effect, if sustained, may be a causative factor for long term bone loss. We tested the hypothesis that postmenopausal women receiving > or = 1 mg/day inhaled beclomethasone dipropionate, long term, have suppressed dehydroepiandrosterone sulphate levels when compared to postmenopausal controls. METHODS: As part of a larger study, we studied 36 postmenopausal subjects, recruited from regional pharmacies and a hospital chest clinic, who had been receiving treatment for asthma. Subjects were selected if they were receiving > or = 1 mg/day inhaled beclomethasone dipropionate (n = 27) or receiving no beclomethasone dipropionate (n = 9). The two groups were compared for dehydroepiandrosterone sulphate levels, age and potential confounders. RESULTS: Mean dehydroepiandrosterone sulphate levels were 35% lower in the high dose beclomethasone dipropionate group than the control group (p < 0.01). CONCLUSIONS: This is the first report of suppression of dehydroepiandrosterone sulphate in postmenopausal women receiving long term inhaled beclomethasone dipropionate. Further research is needed to clarify whether or not there is any associated clinically important adverse effect on bone density.

Age Distribution↗

Dyslipoproteinaemia in postmenopausal women with a history of eclampsia.

OBJECTIVE: To test the hypothesis that postmenopausal women with a history of eclampsia manifest a more high risk lipid profile than postmenopausal women with a history of normal pregnancy. SETTING: The Department of Obstetrics and Gynaecology, National University Hospital, Reykjavik, Iceland, and the Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA. PARTICIPANTS: Thirty Icelandic women with a history of eclampsia, aged between 50 and 67 years at the time of re-examination (cases) were individually matched for current age, and for age and parity at index pregnancy, to 30 unrelated Icelandic women with a history of normal pregnancy (controls). METHODS: The participating women completed a health and family history questionnaire and underwent a physical examination. Fasting plasma low density lipoprotein diameter, serum lipids, insulin, and glucose were measured. RESULTS: Mean low density lipoprotein size was significantly smaller and apolipoprotein B concentration was higher in women with prior eclampsia. The percentage of cases receiving blood pressure medication (33%) was significantly greater than controls (6.7%). Thirteen cases had had hypertensive complications in at least one other pregnancy (recurrent subgroup); postmenopausally, these women displayed significantly increased diastolic blood pressures, smaller-sized low density lipoprotein, increased apolipoprotein B, decreased high density lipoprotein2 (HDL2) cholesterol, and increased total cholesterol: HDL cholesterol ratio compared with their controls. Fourteen cases were normotensive in all other pregnancies (nonrecurrent); these showed no differences from their controls. CONCLUSIONS: Dyslipoproteinaemia is more prevalent among postmenopausal women with prior eclampsia, especially with recurrent hypertension in pregnancy, than in postmenopausal women with prior normal pregnancies.

Aged↗

Moderate alcohol consumption and estrogen levels in postmenopausal women: a review.

This report reviews the literature to evaluate association between moderate alcohol consumption and estrogen levels in healthy postmenopausal women. Of the eight studies available in literature on postmenopausal women who were not on estrogen therapy, two analyzed urine samples and six analyzed blood samples for estrogen levels. Of the two urine sample studies, only one reported positive association (p < 0.05) between alcohol consumption and estrogen (estrone and estradiol) levels that increased by 16 to 20%. Of the six blood sample studies, only two--one in American women and one in European women--reported significant increases (p < 0.05) in estradiol levels in response to alcohol consumption. In the American women study, estradiol levels increased only with wine and not with beer or whiskey. In the European women study, estradiol levels increased in Danish and Portuguese women, but not in Spanish women. Thus, further studies are required to establish correlation between moderate alcohol consumption and estrogen levels in postmenopausal women. Of the two studies on postmenopausal women who were on estrogen replacement therapy, one administered estradiol through transdermal patch (0.15 mg) and one orally (1 mg/day). In both studies, blood estradiol levels were measured after administering a single dose of ethanol orally (0.7-0.75 g/kg of body weight). Estradiol levels were increased by 22 and 300% in the transdermal patch and oral studies, respectively. These results suggest that alcohol consumption may increase blood estradiol levels in postmenopausal women who are on estrogen replacement therapy, and this may increase the risk of breast cancer.

Alcohol Drinking↗

Hormone replacement therapy does not affect the 24-hour heart rate variability in postmenopausal women: results of a randomized, placebo-controlled trial with two regimens.

Postmenopausal women are at greater risk of coronary heart disease. The results of previous studies of the effects of hormone replacement therapy (HRT) on cardiac autonomic modulation in postmenopausal women have been contradictory. This study examined whether continuous treatment for 3 months with estradiol alone (ERT) or with estradiol plus norethisterone (HRT), increases 24-hour heart rate variability (HRV) in postmenopausal women. In this double-blind, placebo-controlled trial, 40 healthy postmenopausal women, 46-63 years of age, were randomly assigned to (1) continuous 2 mg of estradiol plus 1 mg of norethisterone acetate daily (HRT, n = 13), or (2) 2 mg of estradiol daily (ERT, n = 14), or (3) placebo (n = 13). Before and after 3 months of therapy, blood estradiol concentrations were measured and 24-hour electrocardiograms recorded for evaluation of 24-hour time-domain indices of HRV, and indices derived from the three-dimensional return map. Both hormone replacement regimens significantly increased blood estradiol concentrations, while no change occurred in the placebo group. In the three treatment groups, multiple 24-hour time-domain indices of HRV and indices derived from the three-dimensional return map remained unchanged. In healthy postmenopausal women, HRT with estradiol or estradiol and norethisterone for 3 months did not modify cardiac autonomic activity evaluated by 24-hour indices of HRV. These findings are consistent with a lack of protective cardiovascular effect of HRT described in recent large randomized trials.

Circadian Rhythm↗

An approach to postmenopausal osteoporosis treatment: a case study review.

PURPOSE: To review and discuss the clinical evaluation and therapeutic options for a postmenopausal woman with osteoporosis. DATA SOURCES: Review of scientific literature, practice guidelines, and a case study. CONCLUSIONS: To prevent and treat postmenopausal osteoporosis, women should be encouraged to perform weight-bearing exercise, to not smoke, and to optimize calcium and vitamin D intake through diet and supplements. Drug regimens are effective and well tolerated in postmenopausal women with osteoporosis. IMPLICATIONS FOR PRACTICE: Drugs currently approved by the U.S. Food and Drug Administration for the treatment of postmenopausal osteoporosis include the bisphosphonates risedronate and alendronate; the selective estrogen receptor modulator, raloxifene; and intranasal calcitonin-salmon spray. Bisphosphonates have demonstrated the most impressive fracture risk reduction in prospective clinical trials of women with postmenopausal osteoporosis. Risedronate has consistently demonstrated significant reductions in vertebral fracture risk at 1 year and in vertebral and nonvertebral fracture risk at 3 years. Alendronate has demonstrated significant reductions in vertebral and nonvertebral fracture risk after 3 years.

Aged↗

Relation of common allelic variation at vitamin D receptor locus to bone mineral density and postmenopausal bone loss: cross sectional and longitudinal population study.

OBJECTIVE: To determine whether common allelic variation at the vitamin D receptor locus is related to bone mineral density and postmenopausal bone loss. DESIGN: Cross sectional and longitudinal population study. SETTING: Outpatient clinic in research centre. SUBJECTS: 599 healthy women aged 27 to 72 and 125 women with low bone mass aged 55-77 had bone mineral density measured once in the cross sectional study. 136 women aged 45-54 were followed up for 18 years in the longitudinal study. MAIN OUTCOME MEASURES: Bone mineral density measured at the lumbar spine, hip, and forearm and rate of bone loss at different times over 18 years in relation to vitamin D receptor genotype as defined by the endonucleases ApaI, EsmI, and TaqI. RESULTS: Vitamin D receptor genotype was not related to bone mineral density at any site. The maximum difference between homozygotes was 1.3% (P = 0.33, n = 723). Women with low bone mineral density had almost the same genotype frequencies as the women with normal bone mineral densities. Vitamin D receptor genotype was not related to early postmenopausal bone loss from age 51 to 53 (mean (SD) total loss at the lower forearm -3.6% (3.6%)), late postmenopausal bone loss from age 63 to 69 (at the hip-6.2% (8.7%)), or to long term postmenopausal loss from age 51 to 69 (at the lower forearm-24.5% (11.4%)). CONCLUSION: Common allelic variation at the vitamin D receptor locus as defined by the endonucleases ApaI, EsmI, and TaqI is related neither to bone mineral density nor to the rate of bone loss in healthy postmenopausal Danish women.

Adult↗

Proliferative activity in postmenopausal endometrium: the lurking potential for giving rise to an endometrial adenocarcinoma.

AIMS: To investigate proliferation in disease free postmenopausal endometrium and that harbouring endometrial adenocarcinoma-is there a dynamic, yet lurking, potential for atrophic endometrium to give rise to endometrial adenocarcinoma? MATERIAL/METHODS: The study comprised 84 disease free endometria from asymptomatic postmenopausal women who had undergone hysterectomy for prolapse, and 50 endometrioid cell type endometrial adenocarcinomas with adjacent uninvolved postmenopausal endometrium. The non-neoplastic tissues were separated histologically into active, inactive, and mixed forms, although only the first two categories were studied immunohistochemically for oestrogen and progesterone receptors (ERs, PRs), epidermal growth factor receptor (EGFR), Ki-67, and angiogenic activity. RESULTS: All postmenopausal endometria were atrophic, but only 42 were inactive; of the remaining samples, 22 were weakly proliferative and 20 were mixed active and inactive. In contrast, the non-neoplastic component of 43 of the 50 endometrial adenocarcinomas examined was of the active form; four specimens were of the pure and 39 of the mixed form. Interestingly, high ER and PR expression was seen in active and inactive endometria, but only the former were EGFR positive and had high proliferative (Ki-67) and angiogenic activity. A similar trend was also shown by the non-neoplastic atrophic endometrium adjacent to endometrial adenocarcinoma. CONCLUSIONS: At least half of the disease free postmenopausal atrophic endometria show a weak proliferative pattern, either diffuse or focal, probably as a response to continuous low level oestrogenic stimulation. These tissues have a latent, although very small, carcinogenic potential, as demonstrated by the immunohistochemical profile and their frequent association with adjacent endometrial adenocarcinoma.

Adenocarcinoma↗

Plasma C-reactive protein is not elevated in physically active postmenopausal women taking hormone replacement therapy.

We tested the hypothesis that hormone replacement therapy (HRT)-related increases in C-reactive protein (CRP) would either be blunted or absent in postmenopausal women who regularly perform endurance exercise. Plasma CRP is an independent predictor of future cardiovascular events in healthy men and women. Oral HRT increases plasma CRP concentrations in postmenopausal women. Regular aerobic exercise reduces the risk of cardiovascular events and is associated with lower CRP concentrations in adults. To date, no study has evaluated the influence of habitual physical activity on the elevation of CRP associated with HRT. Plasma CRP concentrations were measured in 114 postmenopausal women: 39 physically active (endurance trained) and 75 sedentary postmenopausal subjects. Sixty-five women were users of HRT (22 physically active and 43 sedentary), and 49 were nonusers (17 physically active and 32 sedentary). CRP levels were approximately 75% higher (P < 0.01) in the sedentary users vs. nonusers of HRT (1.9 +/- 1.8 vs. 1.1 +/- 1.0 mg/l). In contrast, there was no difference in CRP levels between the physically active users and nonusers of HRT (0.6 +/- 0.4 vs. 0.4 +/- 0.2 mg/l; P = 0.61). Regardless of HRT status, CRP concentrations were approximately 65% lower in the physically active compared with sedentary women. In conclusion, physically active postmenopausal women exhibit lower plasma CRP concentrations compared with sedentary controls. Importantly, the HRT-related elevation in plasma CRP levels observed in sedentary women is absent in women who engage in regular endurance exercise. These data suggest that habitual physical activity may prevent the elevation in CRP concentrations due to HRT.

Aged↗