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Hormone replacement therapy (HRT) is not recommended for treating learning and memory decline in menopausal women because it exerts adverse effects by activating classic estrogen receptors ERa and ERp. The membrane estrogen receptor G protein-coupled receptor 30 (GPR30) has been reported to be involved in memory modulation; however, the underlying mechanisms are poorly understood. Here, we found that GPR30 deletion in astrocytes, but not in neurons, impaired learning and memory in female mice. Astrocytic GPR30 depletion induced A1 phenotype transition, impairing neuronal function. Further exploration revealed that Praja1 (PJA1), a RING ubiquitin ligase, mediated the effects of astrocytic GPR30 on learning and memory by binding to Serpina3n, which is a molecular marker of neuroinflammation in astrocytes. GPR30 positively modulated PJA1 expression through the CREB signaling pathway in cultured murine and human astrocytes. Additionally, the mRNA levels of GPR30 and PJA1 were reduced in exosomes isolated from postmenopausal women while Serpina3n levels were increased in the plasma. Together, our findings suggest a key role for astrocytic GPR30 in the learning and memory abilities of female mice and identify GPR30/PJA1/Serpina3n as potential therapeutic targets for learning and memory loss in peri- and postmenopausal women., Introduction The process of learning and memory is how people acquire, encode, store, retain and later retrieve information in the brain. For perimenopausal women, learning and memory abilities decline rapidly [...]

Purpose To provide a practical overview of the management of the potential organ donor in the intensive care unit. Methods Seven areas of donor management were considered for this review: hemodynamic management; fluids and electrolytes; respiratory management; endocrine management; temperature management; anaemia and coagulation; infection management. For each subchapter, a narrative review was conducted. Results and conclusions Most elements in the current recommendations and guidelines are based on pathophysiological reasoning, epidemiological observations, or extrapolations from general ICU management strategies, and not on evidence from randomized controlled trials. The cardiorespiratory management of brain-dead donors is very similar to the management of critically ill patients, and the same applies to the management of anaemia and coagulation. Central diabetes insipidus is of particular concern, and should be diagnosed based on clinical criteria. Depending on the degree of vasopressor dependency, it can be treated with intermittent desmopressin or continuous vasopressin, intravenously. Temperature management of the donor is an area of uncertainty, but it appears reasonable to strive for a core temperature of > 35 °C. The indications and controversies regarding endocrine therapies, in particular thyroid hormone replacement therapy, and corticosteroid therapy, are discussed. The potential donor should be assessed clinically for infections, and screening tests for specific infections are an essential part of donor management. Although the rate of infection transmission from donor to receptor is low, certain infections are still a formal contraindication to organ donation. However, new antiviral drugs and strategies now allow organ donation from certain infected donors to be done safely., Author(s): Geert Meyfroidt [sup.1], Jan Gunst [sup.1], Ignacio Martin-Loeches [sup.2], Martin Smith [sup.3], Chiara Robba [sup.4], Fabio Silvio Taccone [sup.5], Giuseppe Citerio [sup.6] [sup.7] Author Affiliations: (1) 0000 0004 0626 [...]

High-dose (HD) IL-2 therapy in patients with cancer increases the general population of Tregs, which are positive for CD4, CD25, and the Treg-specific marker Foxp3. It is unknown whether specific subsets of Tregs are activated and expanded during HD IL-2 therapy or whether activation of any particular Treg subset correlates with clinical outcome. Here, we evaluated Treg population subsets that were induced in patients with melanoma following HD IL-2 therapy. We identified a Treg population that was positive for CD4, CD25, Foxp3, and the inducible T cell costimulator (ICOS). This Treg population increased more than any other lymphocyte subset during HD IL-2 therapy and had an activated Treg phenotype, as indicated by high levels of CD39, CD73, and TGF-β. [ICOS.sup.+] Tregs were the most proliferative lymphocyte population in the blood after IL-2 therapy. Patients with melanoma with enhanced expansion of [ICOS.sup.+] Tregs in blood following the first cycle of HD IL-2 therapy had worse clinical outcomes than patients with fewer [ICOS.sup.+] Tregs. However, there was no difference in total Treg expansion between HD IL-2 responders and nonresponders. These data suggest that increased expansion of the [ICOS.sup.+] Treg population following the first cycle of HD IL-2 therapy may be predictive of clinical outcome., Introduction High-dose (HD) bolus IL-2 therapy is currently one of the most potent forms of immunotherapy and was approved by the FDA as a single-agent cytokine therapy for metastatic melanoma [...]

Objectives. We investigated whether there were socioeconomic and racial/ ethnic disparities in recent reported declines in overall US breast cancer incidence rates attributed to post-2002 declines in hormone therapy use following publication of the Women's Health Initiative study. Methods. We analyzed 1992-2005 US breast cancer incidence data from the US Surveillance, Epidemiology and End Result (SEER) 13 Registries Database, stratified by race/ethnicity, county income level, age, and estrogen receptor (ER) status. Results. As we hypothesized, between 1992 and 2005, the temporal pattern of rising and then falling US breast cancer incidence rates occurred only among White non-Hispanic women who lived in high-income counties, were aged 50 years and older, and had ER-positive tumors. No such trends were evident-regardless of county income level, ER status, or age--among Black non-Hispanic, Asian/Pacific Islander, Hispanic, or--where numbers were sufficient to conduct meaningful analyses--American Indian/Alaska Native women. Conclusions. The recent decline in US breast cancer incidence was not equally beneficial to all women, but instead mirrored the social patterning of hormone therapy use. Joint information on socioeconomic resources and race/ethnicity is vital for correctly understanding disease distribution, including that of breast cancer. (Am J Public Health. 2010;100:S132-S139. doi: 10.2105/AJPH.2009. 181628)

Xu HL, Vetri F, Lee HK, Ye S, Paisansathan C, Mao L, Tan F, Pelligrino DA. Estrogen replacement therapy in diabetic ovariectomized female rats potentiates postischemic leukocyte adhesion in cerebral venules via a RAGE-related process. Am J Physiol Heart Circ Physiol 297: H2059-H2067, 2009. First published October 9, 2009; doi: 10.1152/ajpheart.00445.2009.--In this study, we tested the hypothesis that the documented transformation of 17[beta]-estradiol ([E.sub.2]) from a counterinflammatory hormone in nondiabetic (ND) rats to a proinflammatory agent in rats with diabetes mellitus (DM) is due to an enhanced contribution from the receptor for advanced glycation end products (RAGE). Rhodamine 6G-labeled leukocytes were observed through a closed cranial window in rats. In vivo pial venular leukocyte adherence and infiltration were measured over 10 h reperfusion after transient forebrain ischemia in DM (streptozotocin) versus ND intact, ovariectomized (OVX), and [E.sub.2]-replaced (for 7-10 days) OVX (OVE) females. The role of RAGE was examined in two ways: 1) RAGE knockdown via topical application of RAGE antisense versus missense oligodeoxynucleotide or 2) intracerebroventricular injection of the RAGE decoy inhibitor, soluble RAGE. Among diabetic rats, the lowest levels of cortical RAGE mRNA and immunoreactivity of the RAGE ligand, AGE, were seen in OVX females, with significantly higher levels exhibited in intact and OVE females. However, results from the analysis of cortical RAGE protein only partially tracked those findings. When comparing ND to DM rats, cortical AGE immunoreactivity was significantly lower in OVE and intact females but similar in OVX rats. In DM rats, the level of postischemic leukocyte adhesion and infiltration (highest to lowest) was OVE > intact >> untreated OVX. In NDs, adhesion was highest in the untreated OVX group. Leukocyte extravasation was observed at >6 h postischemia but only in diabetic OVE and intact females and in ND OVX (untreated) rats. Pretreatment with RAGE antisense-oligode-oxynucleotide or soluble RAGE attenuated postischemic leukocyte adhesion and prevented infiltration but only in the diabetic OVE and intact groups. These results indicate that the exacerbation of postischemic leukocyte adhesion by chronic [E.sub.2] replacement therapy in diabetic OVX females involves a RAGE-related mechanism. Targeting RAGE may restore the neuroprotective effect of [E.sub.2] replacement therapy in diabetic females. transient forebrain ischemia; neutrophil; inflammation; diabetes mellitus doi: 10.1152/ajpheart.00445.2009

After randomized trials failed to support the use of hormone replacement therapy (HRT) for preventing cardiovascular disease (CVD), HRT use for postmenopausal women declined. Our analysis of 1999-2000 and 2003-2004 National Health and Nutrition Surveys (NHANES) shows that HRT use decreased 19% (from 27.6 to 8.4%; P

The study attempts to evaluate the increased risk of different kinds of hormone therapy leading to ovarian cancer. The results confirmed thehypothesis that such kinds of therapy did lead to an increased risk of ovarian cancer.

Background: The use of menopausal hormone therapy (HT) has significantly declined since the release of the Women's Health Initiative findings, but to what extent physicians' and women's concerns about breast cancer contributed to this change is unknown. Our study explored physicians' and women's beliefs about hormone therapy and breast cancer risk. Methods: We conducted qualitative in-depth interviews with 22 primary care physicians and 45 female patients at two large integrated health care delivery systems in Washington State and Massachusetts. Results: Concerns about breast cancer risk weighed into the decision-making process for physicians and women in initiating and continuing hormone therapy. For women, control of menopausal symptoms was important and possibly outweighed their concerns about the potential risks of breast cancer. Though concerned about its association with increasing breast cancer risk, physicians were willing to consider hormone therapy to manage women's menopausal symptoms but were frustrated about the lack of available non-hormone therapy alternatives. Most physicians and some women were aware of the Women's Health Initiative, and its findings appeared to influence their beliefs about hormone therapy and breast cancer risk, though doubts remained among both groups about the study findings and implications. Conclusions: Our qualitative study suggests that after the Women's Health Initiative, concerns about breast cancer risk weighed into decisions to initiate and continue hormone therapy for both physicians and women, but menopausal symptoms often directed use. KEYWORDS breast cancer, hormone therapy, qualitative

Chronically decerebrate (CD) rats, in which the forebrain and its descending projections are completely neurally isolated from hindbrain and rostral projections, gain substantial amounts of body fat, lose lean tissue, and have low circulating testosterone concentrations. We tested whether testosterone replacement would normalize body composition of male CD rats. Five groups of rats were used: CD placebo, CD testosterone, control placebo, castrate placebo, and castrate testosterone. Testosterone replacement was initiated at the first stage of CD surgery in both CDs and castrate controls. The second stage of CD surgery occurred 8 days later, and the study ended 15 days later. Testosterone implants produced 10-fold normal circulating concentrations. Food intake was fixed for all rats by tube feeding. CD rats had substantially more body fat and less lean tissue than neurally intact rats. Testosterone replacement did not affect adiposity of CD rats but did increase carcass water content. Energy expenditure of CD rats was significantly lower than that of control placebo and castrated rats. Testosterone lowered respiratory equivalency ratio and ameliorated a fall in energy expenditure late in the intermeal interval in CD rats. Castration increased, and testosterone decreased luteinizing hormone (LH) and follicle stimulating hormone (FSH) in neurally intact controls. LH was undetectable, and FSH was equivalent to neurally intact controls in CD rats, and neither was affected by testosterone. Collectively, low testosterone did not explain obesity or decreased lean body mass of CD rats, although CD rats exhibited abnormal levels of circulating reproductive hormones and disrupted testosterone negative feedback. caudal brainstem; white adipose tissue; energy expenditure; body composition

Leptin replacement rescues the phenotype of morbid obesity and hypogonadism in leptin-deficient adults. However, leptin's effects on insulin resistance are not well understood. Our objective was to evaluate the effects of leptin on insulin resistance. Three leptin-deficient adults (male, 32 yr old, BMI 23.5 kg/[m.sup.2]; female, 42 yr old, BMI 25.1 kg/[m.sup.2]; female, 46 yr old, BMI 31.7 kg/[m.sup.2]) with a missense mutation of the leptin gene were evaluated during treatment with recombinant methionyl human leptin (r-metHuLeptin). Insulin resistance was determined by euglycemic hyperinsulinemic clamps and by oral glucose tolerance tests (OGTTs), whereas patients were on r-metHuLeptin and after treatment was interrupted for 2-4 wk in the 4th, 5th, and 6th years of treatment. At baseline, all patients had normal insulin levels, C-peptide, and homeostatic model assessment of insulin resistance index, except for one female diagnosed with type 2 diabetes. The glucose infusion rate was significantly lower with r-metHuLeptin (12.03 [+ or -] 3.27 vs. 8.16 [+ or -] 2.77 mg x [kg.sup.-1] x [min.sup.-1], P = 0.0016) but did not differ in the 4th, 5th, and 6th years of treatment when all results were analyzed by a mixed model [F(1,4) = 0.57 and P = 0.5951]. The female patient with type 2 diabetes became euglycemic after treatment with r-metHuLeptin and subsequent weight loss. The OGTT suggested that two patients showed decreased insulin resistance while off treatment. During an off-leptin OGTT, one of the patients developed a moderate hypoglycemic reaction attributed to increased posthepatic insulin delivery and sensitivity. We conclude that, in leptin-deficient adults, the interruption of r-metHuLeptin decreases insulin resistance in the context of rapid weight gain. Our results suggest that hyperleptinemia may contribute to mediate the increased insulin resistance of obesity. recombinant methionyl human leptin; euglycemic hyperinsulinemic clamp; homeostatic model assessment

A study was conducted to determine the efficacy and safety of testosterone as a form of treatment for low libido in postmenopausal women not taking estrogen. Results indicated that testosterone treatment was effective in a modest and meaningful improvement in sexual function among postmenopausal women not taking estrogen.

The study, known as the Long-Term Intervention on Fractures with Tibolone (LIFT) examines if tibolone treatment reduces the risk of vertebral fracture and modifies the risk of nonvertebral fracture, breast cancer, and cardiovascular disease in older women with osteoporosis. Results show tibolone reduced the risk of fracture and breast cancer but increased the risk of stroke.

Byline: Rebecca E. Greene, PharmD, BCOP (South Texas Veterans Health Care System, San Antonio, Texas, Rebecca.greene@va.gov); Vivian Tsang, PharmD (South Texas Veterans Health Care System, San Antonio, Texas) Keywords: Breast [...]

Erectile dysfunction is the inability of a man to attain and maintain penile erection for sufficient time during sexual intercourse. The factors and the cures associated with the problem are explained.

Androgen-deprivation therapy (ADT) via either surgical or chemical castration is the standard treatment for advanced prostate cancer (PCa). In North America, it is estimated that more than 40,000 men start ADT each year. The side effects of this treatment are extensive and include gynecomastia, erectile dysfunction, and reduced libido. These changes strongly challenge patients' self-identity and sexuality. The historical term for a man who has been castrated is 'eunuch', now a pejorative term implying overall social and sexual impotence. In this paper, we review key historical features of eunuch social performance and sexuality from a variety of cultures in order to assess the validity of contemporary stereotypes of the androgen-deprived male. Data were taken from secondary sources on the history of Byzantium, Roman Antiquity, Early Islamic societies, the Ottoman Empire, Chinese Dynasties, and the Italian Castrati period. This cross-cultural survey shows that castrated men consistently held powerful social positions that yielded great political influence. Many eunuchs were recognized for their loyalty, managerial style, wisdom, and pedagogical skills. Furthermore, rather than being consistently asexual and celibate, they were often sexually active. In certain cultures, they were objects of sexual desire for males, or females, or both. Collectively, the historical accounts suggest that, given the right cultural setting and individual motivation, androgen deprivation may actually enhance rather than hinder both social and sexual performance. We conclude that eunuch history contradicts the presumption that androgen deprivation necessarily leads to social and sexual impotence. The capabilities and accomplishments of eunuchs in the past gives patients on ADT grounds for viewing themselves in a positive light, where they are neither socially impotent nor sexually chaste. Keywords: Castration; Eunuchs; Androgen deprivation; Prostate cancer; Sexuality; History

The Women's Health Initiative studies were begun in 1997, in large part the result of women's health activists who for 40 years questioned the safety of hormone use at menopause and criticized the menopause as disease ideology. The studies were prematurely discontinued when investigators found that heretofore acclaimed benefits of hormone use were not supported. Risks to health such as stroke, breast cancer, and thrombophlebitis were found. A feeling of vindication was experienced by feminists but was quickly replaced by cautious optimism as strategies to continue hormone use were published and quality of life issues tied to symptom management emerged. The focus of this article is a review of the hormone story, a discussion of the implications of the Women's Health Initiative results, and strategies for resolution of the continuing hormone dilemma. Keywords Menopause * Women's health initiative * Hormone replacement

Research on the effect of hormone replacement therapy (HRT) on memory in mid-aged women is equivocal although findings indicate that oestrogen may enhance verbal memory. Mood may mediate the relationship between HRT and memory. This study examined the effect of HRT on mood and everyday memory in two samples of women between ages 40 and 60 years. In the cross-sectional comparison (N = 124), HRT users performed significantly better on tests of everyday and verbal memory. A within-woman comparison of 17 women showed that everyday memory, working memory, and delayed verbal memory improved after 3 months of HRT use. The improvement in memory was not mediated by mood. These results suggest that any effect of HRT on mood may be short-term but that some aspects of everyday memory are enhanced, particularly verbal memory. The development of the everyday memory construct and future investigation are discussed. KEYWORDS. Menopause, HRT, everyday memory, verbal memory

The purpose of the study was to examine the factors associated with hormone therapy (HT) use among women with mobility impairments. A non-probability sample of 188 menopausal women (average age = 53 years) from 38 states was recruited in 2004 for the study. Twenty-two percent of participants were currently taking HT; 33% were past users. Using multinomial logistic regression, this study found that those most likely to be taking HT now or in the past were older women, knowledgeable about HT, had had a hysterectomy, had bone loss, and had their provider's encouragement. Implications for health care providers are discussed. KEYWORDS. Hormone therapy, mobility impairment, women's health

We tested the hypothesis that long-term growth hormone (GH) replacement in aged rats would preserve diastolic function and attenuate left ventricular remodeling associated with normal aging. Male Brown Norway x F344 rats were randomized to receive twice daily injections of porcine GH (200 [micro]g/injection, subcutaneous) or saline from 24 to 30 months of age. Adult rats (6- to 9-months old) received saline injections throughout the study. Thirty-month-old, saline-treated rats exhibited low levels of insulin-like growth factor 1 (IGF-1), impaired diastolic left ventricular filling (Doppler), increased cardiac angiotensin II (Ang II), reduced plasma Ang II, and increased cardiac collagen. GH administration in old rats restored IGF-1 and diastolic indices to values comparable to those of adults. These effects were associated with reduced cardiac Ang II and attenuations in cardiac collagen. Age-related decreases in GH and IGF-1 may contribute to the decline in diastolic function of aging, in part through alterations in renin-angiotensin system-mediated ventricular remodeling.

Background. The purpose of our study was to assess the early effects of a potent anabolic androgen on muscle mass and strength, lower extremity power, and functional performance in older men. Methods. Thirty-two men 72 [+ or -] 6 years of age were randomized to receive oxandrolone (10 mg twice daily) or matching placebo in a 2:1 manner for 12 weeks. Total and appendicular lean body mass (LBM) were assessed by dual-energy x-ray absorptiometry (DEXA). Lower extremity muscle volume was determined by magnetic resonance imaging to validate DEXA changes. Results. Total LBM increased by 2.7 [+ or -] 1.6 kg after 6 weeks with oxandrolone (p < .00l), which was greater (p < .001) than the decline in LBM (-0.5 [+ or -] 0.9 kg) with placebo. Appendicular LBM increased by 1.2 [+ or -] 0.9 kg after just 6 weeks with oxandrolone (p < .001), which was greater (p < .001) than the decline in LBM (-0.4 [+ or -] 0.5 kg) with placebo. These changes were >90% of the gains in total and appendicular LBM (3.0 [+ or -] 1.5 kg and 1.3 [+ or -] 0.9 kg, respectively) after 12 weeks. Total thigh and hamstring muscle volume increased by 111 [+ or -] 29 [mm.sup.3] (p = .001) and 75 [+ or -] 18 [mm.sup.3] (p .001), respectively, after 12 weeks. Maximal strength increased for the leg press 6.3 [+ or -] 5.6% (p = .003), leg curl 6.7 [+ or -] 8.6% (p = .01), chest press 6.9 [+ or -] 6.5% (p = .001), and latissimus pull-down 4.8 [+ or -] 6.3% (p = .009) with oxandrolone after 6 weeks; these increases were different than those with placebo (p < .001) and were 93%, 96%, 74%, and 94% of the respective gains at week 12. There were no improvements in functional measures. Conclusion. Treatment with a potent anabolic androgen may produce significant increases in muscle mass and strength after only 6 weeks in healthy older men. However, such treatment did not improve leg muscle power or walking speed.

For many years, hormone replacement therapy (HRT) was considered the gold standard for the symptomatic treatment of menopause. Clinical trials have found that HRT reduces the symptoms of hot flashes and sweating, while also decreasing vaginal dryness and urinary tract infections. HRT has also been shown to be protective against colon cancer (37%) and hip fractures (34%). However, recent findings from the Women's Health Initiative (WHI) have revealed that long-term HRT may actually lead to an increase in heart disease (29%), breast cancer (26%) and other adverse events, such as stroke (41%). Consequently, many women in the United States and abroad are actively looking for alternative treatments for menopause, including botanical dietary supplements. Key words: endometrial hyperplasia, isoflavones, menopause, soy

Currently, there is widespread controversy regarding the risks and benefits of hormone therapy for women over 50. The history of hormone therapy provides an excellent example of how different constituencies with competing objectives can produce health practices and policies of questionable benefit. We examine this history from the perspectives of women who now live longer, expecting higher quality of life throughout their later years, healthcare providers who are influenced by the real and perceived needs of their patients as well as information provided by drug manufacturers, the pharmaceutical industry which seeks to identify and promote drugs that offer the most promise for both patients and shareholders, and medical researchers--including the National Institutes of Health and the Federal Drug Administration.

The study regarding whether conjugated equine estrogen (CEE) alters global cognitive function in older women are determined and its effect with CEE plus medroxyprogestrone acetate (CEE plus MPA) are compared. For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women and lower cognitive function at initiation of treatment.

Postmenopausal women who use hormone therapy are known to have less incidence of fracture compared to those women who do not. The study of postmenopausal UK women, investigates the effect of various patterns of hormone therapy use, on the incidence of fracture.

Postmenopausal women who use hormone therapy are known to have less incidence of fracture compared to those women who do not. The study of postmenopausal UK women, investigates the effect of various patterns of hormone therapy use, on the incidence of fracture.

Byline: Ailsa Welch (1), Joanna Camus (1), Nichola Dalzell (2), Suzy Oakes (1), Jonathan Reeve (2), K. T. Khaw (3) Keywords: BMI; Broadband ultrasound attenuation; Calcaneous; CUBA; Fractures; Heel sonometry; Hormone replacement therapy; Osteoporosis; Quantitative ultrasound; Smoking Abstract: Osteoporotic fractures have substantial clinical and public health impact. Bone quality is an important determinant of fracture risk. Quantitative ultrasound (QUS) of bone measured as broadband ultrasound attenuation (BUA) has been shown to predict fracture risk. However, there have been very few large population studies, particularly in men. We investigated the correlates of calcaneal BUA using a CUBA clinical machine in 15,668 middle and older aged men and women (42--82 years) from the UK, EPIC-Norfolk cohort. At all ages mean BUA was significantly greater in men than women (men, 90.1+-17.6 women 72.1+-16.5). The age-related decline in BUA was five times greater in women than men (-0.77 vs. -0.15 dB/MHz per year). Pre- and post-menopausal bone loss was 0.39 and 0.85 dB/MHz per year, respectively. In univariate regression BUA increased with weight and height by 0.45 dB/MHz per kg and 0.68 per cm in women and 0.24 dB/MHz per kg and 0.33 per cm in men. BUA increased with body mass index (BMI) by 0.84 dB/MHz per kg/m.sup.2 in women and 0.55 in men. However, weight was twice as influential as height in men and seven times as great in women. Age, weight and height explained 27% of the variance of BUA in women, but only 3% in men. Adjusted BUA was significantly lower in men and women with an existing history of any hip, wrist or spinal fracture both overall and when analysed for specific site. Figures were: all fractures 66.8 vs. 72.5 dB/MHz (P&lt 0.001), women 84.1 vs. 90.5 (P&lt 0.001), men hip fractures 61.9 vs. 72.2 dB/MHz (P&lt 0.001), women 81.5 vs. 90.2 (P&lt 0.001), men wrist fractures 66.6 vs. 72.5 dB/MHz (P&lt 0.001), women 81.5 vs. 90.2 (P&lt 0.001), men spinal fractures 68.1 vs. 72.1 dB/MHz (P&lt 0.01), women 85.1 vs. 90.2 (P&lt 0.01), men. These differences equate to reductions of 14, 9 and 6% and 10, 7 and 6% for fractures of the hip, wrist and spine in the BUA of women and men, respectively. Thus, despite the overall gender difference in BUA the relative magnitude of a previous history of fracture was equally important in both men and women. Adjusted BUA was also lower in those with previous history of osteoporosis. In women currently taking hormone replacement therapy (HRT) the adjusted BUA was 5 dB/MHz or one-third of an SD greater than in those who did not. The BUA of those with a current smoking habit was 1.7% lower in women and 3.2% lower in men. Overall, there are substantial sex differences in the relationship of the physical and osteoporotic risk factors associated with BUA. A better understanding of these determinants of heel ultrasound may provide insights into how some of the sex differences in bone health can be explained and bone loss in later life minimised. Author Affiliation: (1) Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK (2) Department of Medicine, Strangeways Research Laboratory, University of Cambridge, Cambridge, CB1 8RN, UK (3) Clinical Gerontology Unit, University of Cambridge, Cambridge, CB2 2QQ, UK Article History: Registration Date: 01/01/2003 Received Date: 19/09/2002 Accepted Date: 25/02/2003 Online Date: 27/01/2004

Byline: A. Sawicki (1,2), A. Regula (1), K. Godwod (3), A. Debinski (1) Keywords: Bone mineral density; Calcium intake; Osteoporosis; Peptic ulcer; Risk factors; Women Abstract: Introduction: Low dietary intake and decreased absorption of calcium are known as important risk factors of osteoporosis. Peptic ulcer disease may be accompanied by dietary restrictions influencing negatively calcium intake. Inflammation of gastric and duodenal mucosa as well as alkali used may significantly decrease calcium absorption. Additionally, bone metabolism may be changed by inflammatory mediators released as a result of mucosal inflammation. Aims: Comparison of bone mineral density and calcium dietary intake in women with and without (control group) peptic ulcer disease. Methods: Two hundred and sixty-three women were studied: 143 (mean age 60.3 years) with peptic ulcer disease diagnosed by endoscopy and/or upper gastrointestinal X-ray, and 120 (mean age 58.4 years) as controls. History of alimentary tract diseases and presence of risk factors of osteoporosis, as well as history of hormone replacement therapy, were collected based on specially designed questionnaires. Women with present risk factors of secondary osteoporosis and with previously diagnosed osteoporosis were excluded. The calcium dietary intake was determined using a standard questionnaire assessing milk and milk products intake as well as calcium supplementation when used. Bone mineral density of the lumbar spine and femoral bone was determined by DXA. Results: Women with peptic ulcer disease not using hormone replacement therapy had lower bone mineral density in all studied regions as compared to control group without peptic ulcer disease. In the subgroup not using hormone replacement therapy all studied values differed significantly. In the smaller subgroup of women using hormone replacement therapy not all values were statistically significant. There was no statistical significance between studied groups in dietary calcium intake as milk, milk products, and calcium supplements. Conclusions: Calcium intake in women with ulcer disease is similar to healthy subjects. Peptic ulcer disease is an independent risk factor for osteoporosis in women. Author Affiliation: (1) Mineral Metabolism and Bone Diseases Unit, National Food and Nutrition Institute, Powsinska Street 61/63, 02-903, Warsaw, Poland (2) Polish Academy of Sciences Medical Research Center, Warsaw, Poland (3) Institute of Physics, Polish Academy of Science, Warsaw, Poland Article History: Received Date: 13/11/2002 Accepted Date: 30/06/2003 Online Date: 03/10/2003

Byline: Robert S. Weinstein (1), A. Michael Parfitt (1), Robert Marcus (2,5), Maria Greenwald (3), Gerald Crans (4), Douglas B. Muchmore (4) Keywords: Activation frequency; Bone formation; Bone histomorphometry; Cancellous bone; Endocortical bone; SERM Abstract: Raloxifene, a nonsteroidal selective estrogen receptor modulator (SERM), increases bone mineral density (BMD), decreases biochemical markers of bone turnover, and prevents incident vertebral fractures in postmenopausal women, while sparing the breast and endometrium from the undesirable stimulation caused by estrogen. How the long-term beneficial effects of raloxifene on bone turnover, as assessed by bone histomorphometry, compare with hormone replacement therapy (HRT) and placebo are not known. We studied 66 healthy postmenopausal women (age 55 to 75 years, mean 63 years) who were randomized to either raloxifene 150 mg/day, HRT (Premarin 0.625 mg/day, and Provera 2.5 mg/day), or placebo for 1 year. All women received 1--1.5 g of calcium/day. Following double tetracycline labeling, transiliac bone biopsies were obtained at baseline and 1 year and analyzed for changes in histologic indexes of bone remodeling on the cancellous surface as well as at the endocortical subdivision of the endosteal envelope, the location of the greatest fraction of postmenopausal bone loss. BMD and biochemical markers of bone turnover were also determined at baseline and 1 year. Four paired biopsies were obtained in the HRT group, six in the raloxifene group, and five in the placebo group. The frequency of remodeling events on cancellous bone and rate of bone formation in both cancellous and endocortical bone increased in the placebo group, while these measurements decreased in both drug treatment groups. Using analysis of mean percentage changes, when compared with the placebo group, these changes were significantly different for both raloxifene and HRT treatment groups (p&lt 0.02). In all subjects, the bone was lamellar with discrete tetracycline labels and there was no evidence of marrow fibrosis or abnormal bone cells. BMD increased from baseline at the lumbar spine (p&lt 0.05 in the HRT group) and in the total body (p&lt 0.05 for both raloxifene and HRT). Compared with that of the raloxifene group, the increase in BMD was greater in the HRT group at the lumbar spine but not in the total body. Serum bone alkaline phosphatase, serum osteocalcin, and urine C-terminal cross-linking telopeptide of type I collagen significantly decreased (p&lt 0.05) in both active treatment groups, changes significantly different from those seen with placebo. Overall, these results support the hypothesis that raloxifene preserves bone mass by reducing the elevated bone turnover found in postmenopausal women receiving placebo, by mechanisms similar to those operative in postmenopausal women receiving HRT. Author Affiliation: (1) Center for Osteoporosis and Metabolic Bone Diseases, Division of Endocrinology and Metabolism, Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, 4301 W. Markham St., Slot 587, Little Rock, AR 72205, USA (2) VA Medical Center, Palo Alto, California, USA (3) Osteoporosis Medical Center, Palm Desert, California, USA (4) Eli Lilly and Company, Indianapolis, Indiana, USA (5) Eli Lilly and Company, Indianapolis, Indiana, USA Article History: Received Date: 28/10/2002 Accepted Date: 05/03/2003 Online Date: 28/08/2003

Byline: Alexandra Papaioannou (1,8), George Ioannidis (1), Jonathan D. Adachi (1), Rolf J. Sebaldt (2), Nicole Ferko (3), Mark Puglia (1), Jacques Brown (4), Alan Tenenhouse (2), Wojciech P. Olszynski (5), Pauline Boulos (1), David A. Hanley (6), Robert Josse (7), Timothy M. Murray (7), Annie Petrie (2), Charlie H. Goldsmith (2) Keywords: Adherence; Bisphosphonates; Hormone replacement therapy; Osteoporosis Abstract: Therapies for osteoporosis must be taken for at least 1 year to be effective. The purpose of this study was to determine the difference in adherence to etidronate, alendronate and hormone replacement therapy in a group of patients seen at our tertiary care centres. The Canadian Database of Osteoporosis and Osteopenia (CANDOO), a prospective observational database designed to capture clinical data, was searched for patients who started therapy following entry into CANDOO. There were 1196 initiating etidronate, 477 alendronate and 294 hormone replacement therapy women and men aged (mean, SD) 65.8 (8.7) years in the study. A Cox proportional hazards regression model was used to assess differences between treatment groups in the time to discontinuation of therapy. Several potential covariates such as anthropometry, medications, illnesses, fractures and lifestyle factors were entered into the model. A forward selection technique was used to generate the final model. Hazard ratios and 95% confidence intervals (CI) were calculated. Adjusted results indicated that alendronate-treated patients were more likely to discontinue therapy as compared with etidronate-treated patients (1.404 95% CI: 1.150, 1.714). After 1 year, 90.3% of patients were still taking etidronate compared with 77.6% for alendronate. No statistically significant differences were found between hormone replacement therapy and etidronate users (0.971 95% CI: 0.862, 1.093) and hormone replacement therapy and alendronate users (0.824 95% CI: 0.624, 1.088) after controlling for potential covariates. After 1 year, 80.1% of patients were still taking hormone replacement therapy, which decreased to 44.5% after 6 years. Increasing age and presence of incident non-vertebral fractures were found to be independent predictors of adherence. In conclusion, alendronate users were more likely to discontinue therapy than etidronate users over the follow-up period. Potential barriers to long-term patient adherence to osteoporosis therapies need to be evaluated. Author Affiliation: (1) Department of Medicine, McMaster University, Hamilton, Ontario, Canada (2) Department of Clinical Epidemiology and Biostatistics,St Joseph's Health Care, McMaster University, Hamilton, Ontario, Canada (3) Clinical Health Sciences (Health Research Methodology Programme), McMaster University, Hamilton, Ontario, Canada (4) Centre Hospitalier de l'Universite Laval, Ste-Foy, Quebec, Canada (5) Department of Medicine, University of Saskatchewan, Saskatoon, Saskatechewan, Canada (6) Department of Medicine, University of Calgary, Calgary, Alberta, Canada (7) University of Toronto, Toronto, Ontario, Canada (8) Geriatric Medicine , Hamilton Health Sciences, Chedoke Site, Wilcox Building, 2nd Floor, Sanatorium Road, Hamilton, Ontario, L8N 3Z5, Canada Article History: Received Date: 25/11/2002 Accepted Date: 03/03/2003 Online Date: 11/09/2003

Hormone replacement therapy can strengthen bones and reduce the risk of bone fractures in postmenopausal women, according to a study of 16,608 women. Three years of treatment increased bone density in the hip by an average of four percent and reduced the risk of bone fracture by 24%. Hormone replacement therapy had no beneficial effect on other health outcomes.