Int J Cancer. 2006 Dec 22; [Epub ahead of print]

Bertelsen L, Mellemkjaer L, Frederiksen K, Kjaer SK, Brinton LA, Sakoda LC, van Valkengoed I, Olsen JH.

Although several risk factors are common to endometriosis and breast cancer, the results of observational studies of an association have so far been inconsistent. We evaluated the relationship between endometriosis and breast cancer on the basis of data on selected cancers and medical histories from the Danish nationwide cancer and hospital registries used in a large case-cohort study. A total of 114,327 women were included in the study of whom 1,978 women had received a diagnosis of endometriosis and 16,983 had had a diagnosis of breast cancer between 1978 and 1998. Of the women with endometriosis, 236 subsequently received a diagnosis of breast cancer. The crude overall rate ratio for breast cancer after endometriosis was 1.00 and after adjustment for reproductive factors, calendar-period, bilateral oophorectomy and benign breast disease, the rate ratio was 0.97 (95% confidence interval, 0.85-1.11). The risk for breast cancer increased with age at diagnosis of endometriosis, so that women in whom endometriosis was diagnosed at a young age (approximately <40 years) had a reduced risk for breast cancer and women in whom endometriosis was diagnosed at older ages (approximately >/=40 years) tended to have an increased risk for breast cancer. The reduced risks observed among young women may reflect their exposure to drugs with antiestrogenic effects. The increased risk associated with endometriosis among postmenopausal women may be due to common risk factors between postmenopausal endometriosis and breast cancer or an altered endogenous estrogen.

Breast Cancer Res Treat. 2006 Dec 23; [Epub ahead of print]

Altiok N, Koyuturk M, Altiok S.

Estrogen is known to stimulate breast cancer development in humans. Ironically, high doses of estrogen can induce regression of hormone-dependent breast cancer in postmenopausal women. The mechanism by which estrogen induces tumour regression in breast cancer is still unknown. We found that under low growth-stimulated conditions, high concentrations of 17-beta-estradiol (estradiol) induces apoptosis and concomitantly increases phosphorylation of c-jun in estrogen receptor (ER)-positive breast cancer cell line, MCF-7, but not in ER-negative breast cancer cell line MDA-MB 231 suggesting an ER-mediated event. Interestingly, when the c-jun NH(2)-terminal kinase (JNK) signalling pathway was disrupted by the JNK inhibitor SP600125, the ability of estradiol to inhibit the growth of MCF-7 cells and to induce apoptosis was completely blocked. These data suggest that JNK plays a central role in mediating the anticancer effect of high concentrations of estradiol in MCF-7 cells. Our data showing the apoptotic effect of estradiol in low growth-stimulated conditions suggest potential implications for the pharmacological control of breast cancer with high dose estrogen in postmenopausal women. Furthermore, our results indicate that augmenting JNK activity could be an efficient novel approach for treating breast cancer.

Wien Klin Wochenschr. 2006 Dec;118(23-24):728-37.

Strohle A, Waldmann A, Wolters M, Hahn A.

INTRODUCTION: As shown in the first part of this article, consuming high amounts of fruits, vegetables, whole grains and nuts can lower the risk for several chronic diseases. However, the relevance of animal foods consumed within a vegetarian diet is less well-known. MATERIALS AND METHODS: We followed a nutritive and a metabolic-epidemiological approach to obtain dietary recommendations. A MEDLINE-research was performed for all animal food groups relevant with a vegetarian diet (key words: "eggs", "milk", "dietary pattern" "vegetarian diet", "cancer", "cardiovascular disease", "diabetes mellitus", "osteoporosis", "vitamin D", "vitamin B(12)", "iron", "iodine"). All relevant food groups were characterized regarding their nutrient content and rated with respect to the available metabolic-epidemiological evidence. RESULTS: Based on the evidence criteria of the WHO/FAO, colorectal cancer risk reduction by a high intake of milk and milk products is assessed as probable, while a higher risk of prostate and ovarial carcinomas is also probable. The evidence of a risk-increasing effect of eggs relating to cardiovascular disease, colorectal cancer and breast cancer is assessed as probable. As the data of prospective cohort studies suggest, a prudent diet pattern characterized high in fruits, vegetables, whole grains and nuts is associated with a lower risk of coronary heart disease and diabetes mellitus type 2. In contrast, there is no overall association between prudent diet pattern and risk of breast cancer or colorectal cancer. The critical key nutrients for vegetarians are vitamin D and B12, iodine and iron. CONCLUSION: For the first time evidence based dietary recommendations were provided for persons on a vegetarian diet in the D-A-CH-region.

Endocr J. 2006 Dec 21; [Epub ahead of print]

Majima T, Komatsu Y, Fukao A, Nakao K.

No consensus has been reached on whether the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have beneficial effects on bone health. The purpose of our study was to evaluate the effects of atorvastatin on bone metabolism by means of measuring bone turnover markers in male patients with hypercholesterolemia both at diagnosis and prospectively after 3 months of treatment. Twenty-two Japanese male patients (mean age 62.36+/-10.1 years) with untreated hypercholesterolaemeia were selected for this study. After 3-months treatment of atorvastatin, total cholesterol and low density lipoprotein cholesterol significantly decreased as expected (p<0.001 for both parameters). Bone-specific alkaline phosphatase (BAP) did not change significantly (p=0.444). However, serum N-terminal telopeptide of type I collagen (NTx) significantly decreased by -19.86+/-26.4% (p=0.020). In addition, DeltaNTx during the course of this study was negatively correlated with NTx at baseline (r=-0.645, p=0.0008). Although there was a tendency of positive correlations of DeltaNTx with Deltatotal cholesterol, Deltatriglycerides, and Deltalow density lipoprotein cholesterol, and of negative correlations of DeltaNTx and DeltaBAP with Deltahigh density lipoprotein cholesterol, none of them reached statistical significance. Our findings suggest that atorvastatin may have potentially beneficial effects on bone metabolism in patients with hypercholesterolemia mostly by reducing bone resorption rather than by stimulating bone formation. Further studies with more patients and longer duration are warranted to evaluate its effects, if any, on prevention of osteoporosis and subsequent fractures.

Maturitas. 2006 Dec 18; [Epub ahead of print

Nir Y, Huang MI, Schnyer R, Chen B, Manber R.

OBJECTIVE: To determine whether individually tailored acupuncture is an effective treatment option for reducing postmenopausal hot flashes and improving quality of life. METHODS: In a randomized, placebo-controlled pilot study, 29 postmenopausal participants averaging at least seven moderate to severe hot flashes per 24h, with a baseline estradiol concentration of less than 50pg/mL and a normal TSH level, were randomized to receive 7 weeks (nine treatment sessions) of either active acupuncture or placebo acupuncture (placebo needles that did not penetrate the skin at sham acupuncture points). Participants recorded hot flashes in logs that were reported daily. Global indices of the severity and frequency of hot flashes were derived from the participants' daily logs. RESULTS: Participants receiving the active treatment had a greater reduction in hot flash severity (24.5+/-30.7%) compared to those receiving placebo (4.4+/-17.1%, P=0.042). Within group repeated measures analyses of variance revealed a significant reduction in hot flash severity in the active (P=0.042), but not in the placebo treatment group (P=0.15). Although there was no significant group difference in the reduction of hot flash frequency between the active (42.4+/-32.2%) and placebo groups (32.0+/-26.5%; P>/=0.352), within group repeated measures analyses of variance revealed that the reduction was statistically significant in both groups (P</=0.001). CONCLUSIONS: Standardized, individually tailored acupuncture treatment was associated with significantly greater decrease in the severity, but not the frequency, of hot flashes, in symptomatic postmenopausal women when compared to placebo acupuncture of equal duration. Future, larger scale, studies are needed.

Br J Nutr. 2006 Dec;96(6):993-6.

Tonstad S, Klemsdal TO, Landaas S, Hoieggen A.

Observational data have suggested that increased water intake decreases the risk of CHD. A postulated mechanism is that increased water ingestion reduces blood viscosity. The aim of the present study was to assess the effect of increased fluid intake on blood viscosity. Men (n 67) and postmenopausal women (n 27) with one or more risk factors for CVD who reported intake of </=0.5 litres water daily were randomised to a control group (n 31), an intervention group (n 32) that increased their daily water intake by 1 litre/d and an intervention group (n 31) that ingested 1 litre blueberry juice/d. All were encouraged to continue their usual diet and lifestyle. Whole-blood viscosity and blood and urine chemistries were measured by standard techniques after 2 and 4 weeks. Urine volume increased (by a median of 872 and 725 ml in the water and blueberry juice groups, respectively, v. 10 ml in the control group; P</=0.002), confirming the subjects' adherence to the protocol. Urine osmolality and urinary levels of Na, K and creatinine decreased in the water and blueberry juice groups v. the controls (P<0.05). No change was seen in whole-blood viscosity or in levels of fibrinogen, total protein, lipids, glucose, insulin, C-peptide or other chemistry and haematology variables. In conclusion, a postulated protective effect of increased water or fluid intake is not explained by a change in blood viscosity and increased fluid intake does not influence CVD risk factors in the short term.

J Bone Miner Res. 2006 Dec 20; [Epub ahead of print

Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD.

Microabstract We assessed the role of low areal bone mineral density (aBMD) and impaired architecture - assessed by a HR-pQCT system- in a case-control study of postmenopausal women with fractures. Vertebral and nonvertebral fractures are associated with low volumetric bone density and architectural alterations of trabecular and cortical bone, independently of aBMD assessed by DXA.

Br J Cancer. 2006 Dec 19; [Epub ahead of print]

Danforth KN, Tworoger SS, Hecht JL, Rosner BA, Colditz GA, Hankinson SE.

The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk is unclear, particularly for specific hormone formulations, but recent studies suggest that there is a positive association. We conducted a prospective observational study with 82 905 postmenopausal women, including 389 ovarian cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users of PMH, both current and past users of >/=5 years had a significantly elevated risk of ovarian cancer (RR=1.41, 95% confidence interval (CI) 1.07-1.86 and relative risk (RR)=1.52, 95% CI 1.01-2.27, respectively). Examined by hormone type in continuous years, use of unopposed estrogen was associated with a significant increase in the risk of epithelial ovarian cancer (P for trend <0.001; RR for 5-year increment of use=1.25, 95% CI 1.12-1.38). Use of estrogen plus progestin (RR for 5-year increment of use=1.04, 95% CI 0.82-1.32) was not significantly associated with ovarian cancer risk. Generally, results were similar for serous tumours (RR for 5-year increment of unopposed estrogen use=1.23, 95% CI 1.07-1.40) and slightly stronger for endometrioid tumours (RR for 5-year increment of unopposed estrogen use=1.53, 95% CI 1.20-1.94). Recency of use was not significantly associated with ovarian cancer risk, but statistical power was limited here.

Ann Pharmacother. 2006 Dec 19; [Epub ahead of print]

Halil M, Cankurtaran M, Yavuz BB, Ulger Z, Piskinpasa S, Gedik A, Haznedaroglu IC, Kirazli S, Ariogul S.

BACKGROUND: Strontium ranelate offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal osteoporosis. However, there are some data revealing an association between strontium ranelate treatment and increased incidence of venous thromboembolism (VTE), suggesting possible adverse prothrombotic effects of the drug. OBJECTIVE: To assess the effect of strontium ranelate treatment on primary hemostasis, secondary hemostasis, and the natural anticoagulant defense system, together with prothrombotic markers, in elderly women with osteoporosis. METHODS: This study was designed in a prospective manner. Thirty-five elderly women diagnosed with osteoporosis were included. During a 2 month treatment period, participants received strontium ranelate 2 g. Platelet Function Analyzer-100 (PFA-100) in vitro bleeding time was performed to depict primary hemostasis. Secondary hemostatic parameters including prothrombin time, international normalized ratio, activated partial thromboplastin time, anti-cardiolipine immuno-globulin (Ig) M and IgG, antiphospholipid IgM and IgG, protein C, protein S, anti-thrombin III, lupus anticoagulant, fibrinogen, thrombin, activated protein C resistance, and plasma levels of D-dimer were assessed. These parameters were tested before and after 2 month treatment with strontium ranelate. RESULTS: Mean +/- SD age of the patients was 72.82 +/- 5.69 years. After 60 days of treatment, there was no statistically significant prolongation in PFA-100 in vitro bleeding time and no statistically significant change in the critical hemostatic parameters in patients receiving strontium ranelate that led to discontinuation of the treatment. None of the subjects developed clinical VTE during the 2 month period of strontium ranelate treatment. CONCLUSIONS: The hemostatic safety of strontium ranelate in the elderly population with osteoporosis was shown over 2 months of treatment; however, its long-term hemostatic safety should be evaluated further.

J Br Menopause Soc. 2006 Dec;12(4):164-71.

Brown TJ.

The objective of this systematic review was to determine the effect on long-term health outcomes of lifestyle interventions designed to produce weight loss in postmenopausal women. A systematic search of the MEDLINE, EMBASE, PsychINFO and CINAHL databases retrieved four randomized controlled trials (RCTs) and one controlled clinical trial (CCT) of at least 24 weeks' duration as well as one systematic review. The majority of the studies recruited from the community, had samples with similar baseline characteristics and assessed completers only. Drop-out rates varied from 2.5% to 16%. All active-treatment arms demonstrated significant improvements in weight and body composition from baseline. Significant effects between treatment groups were shown only in intervention versus control studies. Significant weight loss was not accompanied by beneficial changes in cardiovascular risk factors in the majority of studies. None of the studies of weight loss reported disease outcomes. Weight loss in active-treatment arms varied from 1.5 kg to 9 kg over 6-12 months. The study that produced the greatest weight loss demonstrated improvements in risk factors and it may be that only this one study produced sufficient weight loss to do so. Many of the studies were probably underpowered and too short in duration to detect change in risk factors. Lifestyle interventions do produce weight loss in overweight postmenopausal women and have the potential to improve disease outcomes associated with overweight.

J Br Menopause Soc. 2006 Dec;12(4):153-7

Mokate T, Wright C, Mander T.

Hysterectomy is one of the most common major gynaecological operations performed in the UK and the USA. Its impact on sexual function is a major cause of preoperative anxiety. Unfortunately, this anxiety is seldom articulated by patients, nor recognized and discussed by clinicians. Reports about the impact of hysterectomy on sexual function have been conflicting, partly due to the use of different and often unsatisfactory parameters to assess sexual function. The aim of this review is to assess the current evidence about the effect of hysterectomy on sexual function. Female sexual function is governed by psychological, social and physiological factors. A new model of 'the sexual response cycle', comprising physical, emotional and cognitive feedback, helps explain the sexual difficulties that arise before and after hysterectomy. Evidence is lacking for sexual dysfunction caused by the disruption of local nerve and blood supply, or by changing anatomical relationships. Removal of the ovaries at hysterectomy is associated with no change or even an improvement in sexual function, particularly in women on hormone replacement therapy. Thus, overall, hysterectomy improves sexual function, regardless of surgical method or removal of the cervix. This is probably due to the amelioration of the symptoms that have previously had a negative effect on sexual function.

J Br Menopause Soc. 2006 Dec;12(4):143-8

Ireland K, Child T.

Polycystic ovary syndrome (PCOS) is a common syndrome among young women. It is associated with fertility problems, clinical manifestations of hyperandrogenism and metabolic disturbance, particularly insulin resistance. The long-term consequences of PCOS have not been fully determined, but there is an increased risk of progression to diabetes and an increase in cardiovascular risk factors. The extent to which PCOS is present in postmenopausal women and the degree to which it increases various risk factors in addition to the known risk of the postmenopausal period are not yet known. This paper reviews the pathophysiology of PCOS and its long-term consequences and considers the evidence to date that is applicable to the postmenopausal woman.

Coron Artery Dis. 2007 Feb;18(1):9-13.

Montalcini T, Gorgone G, Gazzaruso C, Sesti G, Perticone F, Pujia A.

OBJECTIVE: It is well known that coronary heart disease incidence increases in women after menopause. This phenomenon was related to reduced levels of female sex hormones. Estrogen decline, however, is not the only hormonal change during the postmenopausal period and estrogen administration did not protect women from cardiovascular disease. Therefore, it is justified to explore other hormonal changes. The role of androgens is still controversial. The aim of the present study was to investigate the relationship between endogenous sex hormones and endothelial function, measuring the brachial artery flow-mediated dilation. METHODS AND RESULTS: Sixty postmenopausal women were consecutively enrolled and underwent a clinical and biochemical examination. Brachial artery flow-mediated dilation was also evaluated by ultrasound. After correction for confounding variables, testosterone was positively correlated to flow-mediated dilation (beta=0.277, P=0.03). Indeed, women in the lowest testosterone tertile had a flow-mediated dilation smaller than that in the highest tertile (P=0.02). CONCLUSIONS: This result could suggest that the development of cardiovascular disease after menopause is due not only to estrogen decline but also to androgen decline. More studies are needed to evaluate the role of androgen replacement therapy on postmenopausal women with low level of this hormone.

Semana del 5 al 12 de Diciembre de 2006

Dr. Juan Enrique Blümel

Osteoporos Int. 2006 Dec 7

How to select the doses of vitamin D in the management of osteoporosis.

Bischoff-Ferrari HA.

Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Switzerland.

The dose of vitamin D in the management of osteoporosis should be no less than 700-800 IU per day. An optimal dose of vitamin D should raise serum concentrations of 25(OH)D to the desirable range of at least 75 nmol/l. Higher intermittent oral doses of vitamin D may overcome low adherence. Vitamin D supplementation in the management of osteoporosis holds a significant public health potential because of its low cost, excellent tolerability, and combined musculo-skeletal benefits. Fall and fracture prevention with vitamin D is especially appealing in the treatment of older individuals at risk for fall-related fractures. However, bone density, strength, and function benefits with vitamin D include active and inactive subgroups of community-dwelling older men and women. Based on a recent expert panel and supportive evidence presented in this review, serum concentrations of at least 75 nmol/l 25(OH)D will be referred to as desirable. Today, desirable serum 25(OH)D levels of at least 75 nmol/l may only be reached in about one third of US older individuals and even fewer European older individuals. Two main factors discussed in this review may help public health efforts to ensure desirable vitamin D levels for fall and fracture prevention, including (1) a sufficient dose of vitamin D and (2) improved adherence to supplementation.

JAMA. 2006 Dec 6;296(21):2601-10

A 55-year-old woman with osteopenia.

Cummings SR.

University of California, San Francisco, USA. scummings@sfcc-cpmc.net

About half of postmenopausal women have a bone density T score at the femoral neck between -1.0 and -2.5. Bone density in this range was termed "osteopenia" by a World Health Organization working group. Osteopenia is not a disease and the label can cause unnecessary anxiety. Osteopenia encompasses a wide range of fracture risks; an individual patient's risk can be estimated from her age, bone mineral density, and clinical risk factors. Regardless of bone mineral density, regular exercise and adherence with vitamin D and calcium intake may reduce the risk of hip fracture. Osteopenia by itself is not an indication for treatment. Decisions about pharmacological treatment to prevent fractures should be based on the patient's risk of fractures, evidence about the efficacy and nonskeletal effects of the specific treatment, and the patient's preferences.

Menopause. 2006 Dec 5; [Epub ahead of print]

Vasomotor symptoms among Japanese-American and European-American women living in Hilo, Hawaii.

Sievert LL, Morrison L, Brown DE, Reza AM.

From the 1Department of Anthropology, University of Massachusetts at Amherst, Amherst, MA

OBJECTIVE:: The Hilo Women's Health Survey was designed and administered to gather baseline data on women's health in Hilo, HI. This randomized, cross-sectional study allowed for a focus on ethnic differences in symptom reporting. The results presented here focus on hot flash and night sweat experience among Japanese-American and European-American women. DESIGN:: Survey packets were mailed to street addresses associated with parcel numbers pulled randomly from Hilo tax maps. Of the 6,401 survey packets delivered to households, 1,824 questionnaires were completed and returned. The results reported here are based on 869 women aged 40 to 60, of whom 249 described themselves to be 100% Japanese and 203 described themselves to be 100% European-American. Logistic regression analyses were used to examine whether the relationship between ethnicity and vasomotor symptoms persisted after controlling for other variables. RESULTS:: European-American participants were more likely to have ever experienced a hot flash as compared with Japanese-American participants (72% vs 53%, P < 0.01). During the 2 weeks before the survey, European-American participants were more likely to have experienced hot flashes (P < 0.05) and night sweats (P < 0.01). In logistic regression analyses, after controlling for age, body mass index, menopause status, level of education, financial comfort, smoking habits, alcohol intake, exercise, use of hormone therapy, and soy intake, European-American women were still significantly more likely to have experienced hot flashes (odds ratio = 1.858) and night sweats (odds ratio = 2.672). CONCLUSIONS:: The results, based on self-reporting of menopausal symptoms, indicate that Japanese-American women report fewer hot flashes and night sweats than European-American women. Japanese-American women reported a higher intake of soy, but soy intake was not associated with fewer vasomotor symptoms.

J Orthop Surg. 2006 Oct 7;1(1):7

Direct effects of caffeine on osteoblastic cells metabolism: the possible causal effect of caffeine on the formation of osteoporosis.

Tsuang YH, Sun JS, Chen LT, Sun SC, Chen SC.

Department of Orthopedic Surgery, Taipei City Hospital, Taipei, Taiwan, ROC. jssun@ym.edu.tw.

BACKGROUND: Caffeine consumption has been reported to decrease bone mineral density (BMD), increase the risk of hip fracture, and negatively influence calcium retention. In this study, we investigated the influence of caffeine on the osteoblasts behaviour. METHOD: Osteoblasts derived from newborn Wistar-rat calvaria was used in this study. The effects of various concentrations of caffeine on bone cell activities were evaluated by using MTT assay. Alkaline phosphatase (ALP) staining, von Kossa staining and biochemical parameters including ALP, lactate dehydrogenase (LDH), prostaglandin E2 (PGE2) and total protein were performed at day 1, 3, and 7. DNA degradation analysis under the caffeine influence was also performed. RESULTS AND DISCUSSION: The results showed that the viability of the osteoblasts, the formation of ALP positive staining colonies and mineralization nodules formation in the osteoblasts cultures decreased significantly in the presence of 10 mM caffeine. The intracellular LDH, ALP and PGE2 content decreased significantly, the LDH and PGE2 secreted into the medium increased significantly. The activation of an irreversible commitment to cell death by caffeine was clearly demonstrated by DNA ladder staining. CONCLUSION: In summary, our results suggest that caffeine has potential deleterious effect on the osteoblasts viability, which may enhance the rate of osteoblasts apoptosis.

Gynecol Endocrinol. 2006 Nov;22(11):636-45

Development of low-dose reproductive hormone therapies in China.

Ge Q, Tian Q, Tseng H, Naftolin F.

Division of Reproductive Endocrinology, Chinese Academy of Medical Sciences, Beijing, China.

A historical account is presented of the development of sex hormone treatment from its beginning at the Peking Union Medical College to its present-day generalization throughout China. The general theme of this work has been to test low-dose hormone regimens. Notable successes include low-dose oral contraception and menopausal hormone treatment. In support of the latter, we present a new clinical study of the effects of low-dose, intermittent, patient-metered hormone replacement therapy (HRT), which shows decreased menopausal symptoms, maintenance of bone health and height, and improved cardiovascular status compared with untreated controls. Cardiovascular testing, included carotid artery ultrasound scanning and computed tomographic coronary angiography, supports a cardioprotective effect of long-term (up to 31 years) low-dose HRT that is begun during the menopausal transition. These results highlight the urgent need for larger, prospective trials of long-term low-dose HRT started during the perimenopausal period.

AIDS Res Hum Retroviruses. 2006 Nov;22(11):1131-41

Modulation of osteoclastogenesis induced by nucleoside reverse transcriptase inhibitors.

Pan G, Kilby M, McDonald JM.

Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294.

Osteopenia is a common and debilitating side-effect of HAART, yet little is known concerning the effects of HAART on bone metabolism. We reported previously that zidovudine (AZT) stimulates osteoclastogenesis in vitro and causes osteopenia in mice. Here, we confirmed that the AZT-induced osteoclastogenesis is dependent on RANKL in that osteoclastogenesis is blocked by osteoprotegestin. Alendronate, which is used for the treatment of osteopenia and osteoporosis, failed to inhibit AZT-induced osteoclastogenesis in vitro. Osteoclastogenesis in vitro was not affected by tumor necrosis factor-alpha. Two other NRTI drugs, ddl and 3TC, also induced osteoclastogenesis in vitro and induced osteopenia in mice. The osteopenia was associated with an elevation of parameters of osteoclasts, but not with osteoblasts. Combinations of the NRTIs did not result in additive or synergistic effects in vitro or in vivo. Finally, AZT induced osteoclastogenesis of human osteoclast precursors in a RANKL-dependent manner. This in vitro osteoclastogenesis assay using human peripheral blood mononuclear cells could be useful in evaluating bone turnover and the risk of developing osteopenia in AIDS patients on HAART.

Gynecol Endocrinol. 2006 Nov;22(11):646-650

Short-term effects of a combination of isoflavones, lignans and Cimicifuga racemosa on climacteric-related symptoms in postmenopausal women: A double-blind, randomized, placebo-controlled trial.

Sammartino A, Tommaselli GA, Gargano V, di Carlo C, Attianese W, Nappi C.

Department of Obstetrics and Gynecology, University of Naples 'Federico II', Naples, Italy.

The present study aimed to evaluate the short-term effects of a combination of isoflavones, lignans and Cimicifuga racemosa on acute climacteric-related symptoms in postmenopausal women in a double-blind, randomized, placebo-controlled trial performed at the menopause clinic of our department. Eighty healthy postmenopausal women were randomly assigned to two treatment groups - one receiving the combination (group A, n = 40), the other receiving calcium supplements (group B, n = 40) - for three cycles of 28 days. Climacteric-related symptoms were evaluated by the Kupperman index (KI) at baseline and after the three cycles of treatment. At baseline no significant difference was detected in KI between groups A and B; however, after three cycles of treatment, KI was significantly (p < 0.05) lower in group A compared with baseline and with group B. We conclude that the administration of a combination of isoflavones, lignans and C. racemosa already reduces acute climacteric symptoms in postmenopausal women after 3 months of treatment. This prompt effect is probably due to the different pharmacokinetic properties of isoflavones and lignans; isoflavones are absorbed faster than lignans, while lignans are removed later. The combination of these molecules can guarantee a better reduction of postmenopausal symptoms over a 24-h period.

J Psychol. 2006 Nov;140(6):533-47

The relationship between menopausal status, phase of menstrual cycle, and replacement estrogen on cognition in healthy women without dementia.

Lokken KL, Ferraro FR.

Department of Psychology, Box 8380, University of North Dakota, Grand Forks, ND 58202-8380, USA.

The authors examined the effect of menopausal status on several aspects of cognition in 4 groups of women (young premenopausal women, middle-aged premenopausal women, naturally postmenopausal women not using hormone therapy, and postmenopausal women using hormone replacement therapy). Participants (N = 48) completed questionnaires designed to assess psychological and physical health. The authors administered a test battery consisting of 10 neuropsychological tests to assess cognitive functioning. Using multivariate analyses of covariance with age as the covariate, the authors found a significant main effect of menopausal status on attention and complex processing abilities. Postmenopausal women using hormone replacement therapy significantly outperformed postmenopausal women not using hormone therapy on the Trail Making Test, Part B of the Halstead-Reitan (R. M. Reitan, 1958). This effect was significant even when the authors controlled for the effects of age, vocabulary levels, and education. Results are consistent with previous findings and may provide further evidence for an ameliorative effect of estrogen replacement therapy on specific cognitive functions.

Nat Clin Pract Endocrinol Metab. 2006 Dec;2(12):670-680

Drug Insight: existing and emerging therapies for osteoporosis.

Mulder JE, Kolatkar NS, Leboff MS.

Harvard Medical School, Boston, MA, USA.

Osteoporosis is a major public health problem that is characterized by microarchitectural deterioration, low bone mass, and increased risk of fractures. Currently, many women and men affected with this disease are not diagnosed or treated. As osteoporosis is often clinically silent, risk-factor assessment and measurement of BMD are needed to identify those who may benefit from osteoporosis therapy. Although adequate daily intake of calcium and vitamin D, and regular weight-bearing exercise are important for skeletal health, they are not adequate treatments for individuals with osteoporosis. Therapies approved for treatment and/or prevention of osteoporosis in the United States include oral bisphosphonates (alendronate, ibandronate and risedronate), calcitonin, estrogens, teriparatide (parathyroid hormone fragment [1-34]), and raloxifene. For most patients, oral bisphosphonates are the treatment of choice, given the large-scale randomized-trial data demonstrating efficacy in fracture reduction, although bisphosphonates that reduce spine and nonspine fractures (e.g. alendronate and risedronate) are preferred. For high-risk patients (those with very low bone density, or with fractures), teriparatide therapy for 2 years should be considered. The treatment paradigm for osteoporosis will evolve further as promising new treatments progress through clinical development.

Clin Calcium. 2006 Dec;16(12):2005-10

Do hip protectors decrease the risk of hip fracture in elderly ?

Koike T.

Osaka City University Medical School, Department of Rheumatosurgery.

Efforts aimed at preventing hip fractures include lifestyle advice for high-risk elderly, interventions to reduce the risk of falls and medication for osteoporosis. Alternative approach is the use of hip protectors. Hip protectors have pads designed to cover the greater trochanter and attenuate or disperse the force of a fall sufficiently to prevent a hip fracture. There are 14 randomized controlled trials (RCTs) included in the Cochrane systematic review until 2005. All RCTs were classified into three groups by the type of randomization ; cluster randomized in institutions, individually randomized in institutions and individually randomized in community. There is little evidence to support the use of hip protectors outside the nursing home setting. Further research is required, primarily to produce a device that provide higher compliance, and which will then need to be tested in another RCT

Metabolism. 2006 Dec;55(12):1630-1636

Leptin and adiponectin levels in middle-aged postmenopausal women: associations with lifestyle habits, hormones, and inflammatory markers-a cross-sectional study.

Rolland YM, Perry HM 3rd, Patrick P, Banks WA, Morley JE.

Geriatric Research, Education and Clinical Center, St Louis VA Medical Center, Saint Louis, MO 63104, USA; Inserm, U558, F-31073 Toulouse, France; Univ Toulouse III, Toulouse, F-31062 France; CHU Toulouse Hopital Casselardit, Service de Medecine interne et gerontologie clinique, Toulouse, France.

To investigate the relationships between blood levels of leptin or adiponectin and lifestyle habits, hormones, and inflammatory markers, we measured parameters of alcohol intake, smoking, physical activity, and blood levels of leptin, adiponectin, testosterone, estrone, estradiol, cortisol, dihydroepiandrostenedione, luteinizing hormone, thyroxin, C-reactive protein (CRP), and interleukin 6 and interleukin 2 receptor in 76 healthy middle-aged postmenopausal women. Anthropometric measures and body composition (evaluated by dual-energy x-ray absorptiometry) and lipid profiles were also assessed. By simple regression, leptin correlated positively with fat and lean masses, glucose, triglycerides, low-density lipoprotein cholesterol, and total cholesterol, and negatively with high-density lipoprotein cholesterol. Adioponectin correlated negatively with fat and lean masses and low-density lipoprotein cholesterol, and positively with high-density lipoprotein cholesterol. Leptin concentration was correlated inversely with adiponectin (r = -0.26, P < .05) and positively with CRP (r = 0.56, P < .01). Adiponectin concentration was negatively correlated with time since last alcoholic drink (r = -0.24, P < .05) and CRP (r = -0.27, P < .05) and positively with testosterone level (r = 0.23, P < .05). By multiple regression analysis, leptin concentration was predicted by age (P < .05), testosterone (P < .05), adiponectin (P < .05), CRP (P < .01), and interleukin 6 receptor (P < .01). Adiponectin concentration was predicted by the time since last alcoholic drink (P < .05), testosterone (P < .05), leptin (P < .05), and C-reactive protein (P = .05). Similar results were found when leptin or adiponectin concentration was adjusted for fat mass. These results suggested that levels of leptin and adiponectin in middle-aged postmenopausal women are partially determined by sexual hormones and inflammatory marker levels, and both predicted one another. Moreover, adiponectin level may be modulated by alcohol intake.

Trends Mol Med. 2006 Nov 30; [Epub ahead of print

FSH and bone - important physiology or not?

Prior JC.

Endocrinology and Metabolism, Centre for Menstrual Cycle and Ovulation Research, University of British Columbia, Vancouver Coastal Health Research Institute, Vancouver V5Z 1M9, Canada.

For many years, osteoporosis in women was equated with estrogen deficiency. The recent articles by Zaidi and colleagues offer a new challenge to the estrogen-deficiency-osteoporosis hypothesis by showing that follicle-stimulating hormone (FSH) stimulates osteoclastic bone resorption perhaps through tumor necrosis factor-alpha (TNF-alpha). These authors, however, neglected to mention bone abnormalities and high testosterone levels that were previously shown in FSH-receptor knockout and other modified mice. It is also possible that they have overemphasized potential relationships of these new data with human bone loss. Despite these fascinating data, the paradigm of FSH causing hypogonadal bone loss is not yet ready to displace the estrogen-deficiency-osteoporosis paradigm, although that model already faces considerable challenge.

Med Pregl. 2006 Jul-Aug;59(7-8):335-41

Endothelial dysfunction: mechanisms of development and therapeutic options

Pesic S, Radenkovic M, Grbovic L.

Institut za farmakologiju sa toksikologijom, Medicinski fakultet, Nis. srdjan@medfak.ni.ac.yu

INTRODUCTION: Vascular endothelial cells play a key role in cardiovascular regulation by producing a number of potent vasoactive agents, including the vasodilator molecule nitric oxide (NO) and the vasoconstrictor peptide endothelin (ET). ENDOTHELIAL DYSFUNCTION: Endothelial dysfunction is recognized as the initial step in the atherosclerotic process. Impairment of NO synthesis, or increased inactivation of NO by superoxide radicals, may account for the increased periferal vascular tone, as well as contribute to the clinical consequences of different pathophysiological conditions which include vascular hypertrophy, increased platelet and monocyte adhesion to the endothelium, atherosclerosis, myocardial infarction and stroke. To date, most interventions attempting to improve endothelial dysfunction have targeted one or more of the numerous risk factors that can cause endothelial damage: hypertension (ACE inhibitors and calcium antagonists), hypercholesterolemia (lipid-lowering agents), cigarette smoking (cessation), sedentary lifestyle (increased physical activity), menopause (estrogen replacement therapy), and diabetes mellitus (control of metabolic abnormalities). Several pharmacologic agents have been suggested to achieve vascular protection through mechanisms that go beyond their primary therapeutic actions (ACE-and HMG-CoA reductase inhibitors). Beneficial changes to the endothelium might result from promotion of vasorelaxation, inhibition of vasoconstriction, reduction in the production of free radicals, or other mechanisms that protect the endothelium from injury. CONCLUSION: This study deals with the results of many experimental and clinical investigations. The possibility of using different classes of drugs was also established, including ACE inhibitors, Ca-antagonists, AT and endothelin receptor antagonists, direct activator of adenyl cyclase, statins, antioxidants, L-arginine, phosphodiesterase inhibitors, beta-blockers and organic nitrates.