Semana del 25 al 31 de Julio de 2006

Dr. Juan Enrique Blümel

J Thromb Haemost. 2006 Jul 26; [Epub ahead of print]

Hormonal factors and risk of recurrent venous thrombosis: the prevention of recurrent venous thromboembolism trial.

Cushman M, Glynn RJ, Goldhaber SZ, Moll S, Bauer KA, Deitcher S, Shrivastava S, Ridker PM.

Department of Medicine, University of Vermont, Burlington, VT, USA.

Background: In some but not all studies, men with venous thrombosis had a higher risk of recurrence than women. Information on women with initial hormone-related thrombosis is scant. Objective: We assessed the incidence of recurrent thrombosis by gender, and among women using exogenous hormones or pregnant/postpartum at the time of index thrombosis. Patients/Methods: 508 men and women with one or more previous venous thrombosis episodes were observed while participating in a randomized trial of low-intensity warfarin or placebo for 2.1 years. Index thrombosis events during treatment with postmenopausal hormones, oral contraceptives or during pregnancy or the puerperium were considered hormone-related events. Results: Among 268 men the 3-year probability of recurrent thrombosis was 18.4% (95% CI 12.3-24.4). Among 109 women without hormone-related thrombosis, the rate was 15.0% (95% CI 6.3-23.8). Among 129 women with hormone-related thrombosis, the rate was 5.0% (95% CI 1.1-8.9). Adjusting for other risk factors and treatment assignment, women had a 39% lower thrombosis recurrence risk than men: hazard ratio (HR) 0.61 (95% CI 0.34-1.08). Women with hormone-related thrombosis had a 58% lower risk than men: HR 0.42 (95% CI 0.19-0.97); and a 46% lower recurrence risk than other women; HR 0.54 (95% CI 0.19-1.54). Women without hormone-related index events had a recurrence rate similar to men; HR 0.83 (95% CI 0.42-1.66). Conclusions: In this trial population, women had a lower risk of recurrent venous thrombosis than men. This difference was explained by a low risk of recurrence among women with hormone-related index thrombosis.

J Clin Endocrinol Metab. 2006 Jul 25; [Epub ahead of print]

Effect of raloxifene on bone mineral density in premenopausal women at increased risk of breast cancer.

Eng-Wong J, Reynolds JC, Venzon D, Liewehr D, Gantz S, Danforth D, Liu ET, Chow C, Zujewski J.

Medical Oncology Clinical Research Unit, National Cancer Institute, Clinical Center, NIH, Bethesda, MD, Genome Institute of Singapore, Singapore, Surgical Oncology Branch, National Cancer Institute.

Context: Raloxifene is a promising breast cancer prevention agent in postmenopausal women at increased risk for breast cancer. The effects of raloxifene in premenopausal women are unknown. Objective: We evaluated the effect of raloxifene in premenopausal women at increased risk for breast cancer on bone mineral density (BMD). Design: Phase II clinical trial. Setting: This study was conducted at an academic medical center. Participants: 37 premenopausal women at increased risk for breast cancer enrolled on the trial. 30 subjects began treatment and 27 were evaluable. Intervention: Raloxifene (60 mg daily) and calcium (1200 mg daily) were given for 2 yr. Subjects were followed off medications for 1 yr. Main Outcome Measure: The primary endpoint was the intrasubject percent change in BMD at one year measured by DEXA. Results: The mean baseline lumbar spine density was 1.027 g/cm(2). Lumbar spine density decreased 2.3% at one year (p-value <0.00001) and 3.5% (p-value <0.00001) at two years. Percent change from year 2 to 3 was +1.4%. The mean baseline total hip bone density was 0.905 g/cm(2). Total hip density decreased 0.3% at 1 yr and 1.0% at 2 yr (p-value 0.033). Percent change from year 2 to year 3 was +1.7%. Conclusions: Raloxifene use is associated with a decrease in BMD in premenopausal women at increased risk for breast cancer. The clinical significance of this decrease is unknown and is attenuated with stopping raloxifene.

Arch Intern Med. 2006 Jul 24;166(14):1483-9

Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women.

Tamimi RM, Hankinson SE, Chen WY, Rosner B, Colditz GA.

Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA USA.

BACKGROUND: The role of androgens in breast cancer etiology has been unclear. Epidemiologic studies suggest that endogenous testosterone levels are positively associated with breast cancer risk in postmenopausal women. Given the increasing trend in the use of hormone therapies containing androgens, we evaluated the relation between the use of estrogen and testosterone therapies and breast cancer. METHODS: We conducted a prospective cohort study in the Nurses' Health Study from 1978 to 2002 to assess the risk of breast cancer associated with different types of postmenopausal hormone (PMH) formulations containing testosterone. During 24 years of follow-up (1 359 323 person-years), 4610 incident cases of invasive breast cancer were identified among postmenopausal women. Information on menopausal status, PMH use, and breast cancer diagnosis was updated every 2 years through questionnaires. RESULTS: Among women with a natural menopause, the risk of breast cancer was nearly 2.5-fold greater among current users of estrogen plus testosterone therapies (multivariate relative risk, 2.48; 95% confidence interval, 1.53-4.04) than among never users of PMHs. This analysis showed that risk of breast cancer associated with current use of estrogen and testosterone therapy was significantly greater compared with estrogen-only therapy (P for heterogeneity, .007) and marginally greater than estrogen and progesterone therapy (P for heterogeneity, .11). Women receiving PMHs with testosterone had a 17.2% (95% confidence interval, 6.7%-28.7%) increased risk of breast cancer per year of use. CONCLUSION: Consistent with the elevation in risk for endogenous testosterone levels, women using estrogen and testosterone therapies have a significantly increased risk of invasive breast cancer.

Arch Intern Med. 2006 Jul 24;166(14):1453-65

Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review.

Nedrow A, Miller J, Walker M, Nygren P, Huffman LH, Nelson HD.

Department of Medical Informatics, Oregon Evidence-Based Practice Center, Portland, OR, USA.

BACKGROUND: Nearly half of adults in the United States use complementary and alternative therapies each year for a variety of reasons. These therapies are increasingly popular among women seeking alternatives to treatment with estrogen for managing menopausal symptoms. The objective of this review was to assess the effectiveness of complementary and alternative therapies in the management of menopausal symptoms. DATA SOURCES: MEDLINE, PsychINFO, Cochrane Library database, MANTIS, and AMED. STUDY SELECTION: Full-text, English-language, randomized controlled trials and meta-analyses comparing a complementary or alternative therapy with placebo or control for treatment of menopausal symptoms. DATA EXTRACTION: All eligible trials were reviewed, abstracted into evidence tables, and rated for quality. DATA SYNTHESIS: Seventy randomized controlled trials met inclusion criteria. Forty-eight studies of phytoestrogens and other biologically based agents showed mixed results. Smaller numbers of studies using mind-body, energy, manipulative, and body-based therapies and whole medical systems showed little benefit in treating menopausal symptoms. CONCLUSIONS: Although individual trials suggest benefits from certain therapies, data are insufficient to support the effectiveness of any complementary and alternative therapy in this review for the management of menopausal symptoms. Many of these potential therapies warrant further study in trials with rigorous scientific designs to determine benefit and safety.

Gynecol Endocrinol. 2006 Jul;22(7):381-387

Effects of oral continuous 17beta-estradiol plus norethisterone acetate replacement therapy on abdominal subcutaneous fat, serum leptin levels and body composition.

Y Ksel H, Odabasi AR, Demircan S, Karul A, Kozaci LD, Koseoglu K, Kizilkaya K, Basak O.

Department of Obstetrics and Gynecology, Adnan Menderes University, Faculty of Medicine, Aydin, Turkey.

Aim. To evaluate the effects of oral continuous 17beta-estradiol plus norethisterone acetate (E2/NETA) replacement therapy on abdominal subcutaneous fat, serum leptin level (SLL) and body composition in postmenopausal women.Materials and methods. A 6-month, prospective, randomized, double-blind and placebo-controlled study was conducted. Forty-three healthy naturally postmenopausal women aged 43-65 years were randomly assigned to receive E2/NETA (2 mg E2 plus 1 mg NETA, n = 22) or placebo (n = 21). Fasting SLL by enzyme-linked immunosorbent assay, subcutaneous abdominal fat thickness (STh) by ultrasound and the anthropometric indices of body weight (BW), body mass index (BMI), waist and hip circumference (WC, HC) and waist-to-hip ratio (WHR) were recorded at the beginning and the end of the study.Results. After 6 months of therapy, BW and SLL increased in the placebo group (p = 0.043 and 0.033, respectively). WC, HC and STh decreased significantly in the E2/NETA group (p = 0.002, 0.006 and 0.000, respectively) and they were also significantly lower in women receiving E2/NETA than in women taking placebo (p = 0.000, 0.034 and 0.000, respectively). At baseline, SLL and STh were positively correlated with all anthropometric indices except WHR.Conclusion. Oral continuous combined regimen of E2/NETA significantly reduced central fat accumulation as assessed by WC and STh, and attenuated the increase in SLL. The observed changes in SLL were highly and positively related to changes in STh. The oral continuous combined E2/NETA regimen appears to have protective effects on cardiovascular function and probably on metabolic diseases by its slimming effect upon WC in postmenopausal women.

Osteoporos Int. 2006 Jul 28; [Epub ahead of print]

Vitamin D and intact PTH status in patients with hip fracture.

Sakuma M, Endo N, Oinuma T, Hayami T, Endo E, Yazawa T, Watanabe K, Watanabe S.

Division of Rehabilitation Medicine, Niigata University Niigata, 951-8510, Japan.

The prevalence of hypovitaminosis D in patients with acute hip fracture was examined in a population on Sado Island in Japan. There were 85 cases of hip fracture among this population in 2004, giving an overall incidence of hip fracture of 121.4 per 100,000 population per year. This study included 50 of the 85 cases, and these cases were defined as the hip fracture group. Patients older than 70 years without established osteoporosis who were admitted to the hospital on the island during almost the same period for treatment of an orthopedic condition other than a hip fracture were defined as the control group. MATERIALS AND METHODS: The levels of serum 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (intact PTH), alkaline phosphatase (ALP), albumin, and the number of remaining teeth were examined in each group. In the hip fracture group, serum calcium, serum phosphorus, urine N-terminal cross-linking telopeptide of type I collagen (NTx), bone mineral density (BMD) of the nonfractured hip, the presence of a vertebral fracture on X-ray, severity of dementia, and physical activity level were also examined. RESULTS: Both the serum 25-OHD and serum albumin levels were significantly lower in patients with hip fracture than in controls, and the intact PTH level was significantly higher in patients with hip fracture. The number of remaining teeth was correlated with age, and was also significantly correlated with 25-OHD. In the hip fracture group, 62% of the subjects had hypovitaminosis D (25-OHD <20 ng/ml) and one-fifth of cases with hypovitaminosis D showed elevated PTH levels (>65 pg/ml). On the other hand, in the control group, hypovitaminosis D occurred in 18.9% of the subjects, and only one case showed elevated PTH. The serum 25-OHD level showed a decrease as the severity of dementia progressed and the activity level decreased. CONCLUSION: Our results indicate that about two-thirds (62%) of hip fracture patients had vitamin D insufficiency, suggesting that this condition may be closely associated with hip fracture in elderly people. Therefore, the serum 25-OHD level may be a useful index for the risk of hip fracture in elderly people.

Biofactors. 2005;25(1-4):61-6

Effects of menopause and hormone replacement therapy on serum levels of coenzyme Q_{10} and other lipid-soluble antioxidants.

Palan PR, Connell K, Ramirez E, Inegbenijie C, Gavara RY, Ouseph JA, Mikhail MS.

Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, USA.

The present study examines the influence of menopause and hormone replacement therapy (HRT) on serum levels of coenzyme Q_{10} and other lipid-soluble antioxidants in normal women. Serum levels of coenzyme Q_{10}, alpha-tocopherol, gamma-tocopherol, beta-carotene and lycopene in 50 premenopausal women (not using oral contraceptives), 33 healthy postmenopausal and 15 postmenopausal women on HRT ("Prempo"; combination of 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone acetate) were measured by high-pressure liquid chromatography. Lipid profiles were also analyzed. Significantly higher serum coenzyme Q_{10} and alpha-tocopherol levels were detected in postmenopausal compared with premenopausal women (P<0.05, and < 0.001); whereas, in postmenopausal subjects on HRT, we detected a significant decrease in coenzyme Q_{10} and gamma-tocopherol levels (P<0.001, and < 0.05) and increased alpha-tocopherol levels (P<0.05). Serum levels of beta-carotene, lycopene, LDL, HDL, cholesterol and triglyceride were comparable among the study groups. Coenzyme Q_{10} is postulated to be involved in preventing cardiovascular disease (CVD) because of its bioenergetics role in the mitochondrial respiratory chain and its antioxidant properties at the mitochondrial and extramitochondrial levels. The decrease in serum concentrations of coenzyme Q_{10}, produced by HRT, may promote oxygen free radical-induced membrane damage and may, thus alter cardiovascular risk in postmenopausal women. HRT-induced reductions in lipid-soluble antioxidant(s) levels, and its potential consequences on CVD, needs to be further investigated.

Arthritis Rheum. 2006 Jul 26;54(8):2441-2451 [Epub ahead of print]

Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: Implications of the time of initiation.

Oestergaard S, Sondergaard BC, Hoegh-Andersen P, Henriksen K, Qvist P, Christiansen C, Tanko LB et als

Nordic Bioscience, Herlev, Denmark.

OBJECTIVE: To investigate how the time of initiation influences the effects of estrogen therapy on type II collagen (CII) turnover and the structural integrity of articular cartilage in ovariectomized rats and to determine whether estrogen exerts direct effects on the catabolic function of chondrocytes ex vivo. METHODS: A total of 46 Sprague-Dawley rats were distributed into 1 of the following treatment groups: 1) ovariectomy, 2) ovariectomy plus early estrogen therapy, 3) ovariectomy plus delayed estrogen therapy, or 4) sham operation. Cartilage turnover was estimated by measuring the serum levels of C-telopeptide of type II collagen (CTX-II). Cartilage lesions at week 9 were quantified using a published scoring technique. The presence of the CTX-II epitope in articular cartilage was assessed by immunohistochemistry. The effects of estrogen (1-100 nM) on chondrocytes were investigated in bovine cartilage explants subjected to catabolic cytokines (tumor necrosis factor alpha [TNFalpha] and oncostatin M [OSM]). RESULTS: In ovariectomized rats, estrogen therapy evoked significant decreases in serum CTX-II independently of the time of initiation; yet, delayed initiation resulted in diminished efficacy in terms of preventing cartilage lesions. CTX-II fragments were present in articular cartilage, colocalizing with early lesions at the cartilage surface. In untreated animals, the early relative increases in serum CTX-II were proportional to the severity of cartilage lesions at week 9 (r = 0.73, P < 0.01). Estrogen significantly and dose-dependently countered CTX-II release from TNFalpha plus OSM-stimulated cartilage explants ex vivo. CONCLUSION: Our results suggest that estrogen counters the acceleration of CII degradation and related structural alterations, and these benefits can be maximized by early initiation after menopause. The protective effect of estrogen seems to involve direct inhibition of the catabolic function of chondrocytes.

Public Health. 2006 Jul 24; [Epub ahead of print]

Preferred skeletal site for osteoporosis screening in high-risk populations.

Moayyeri A, Soltani A, Bahrami H, Sadatsafavi M, Jalili M, Larijani B.

Endocrinology and Metabolism Research Centre, Tehran University of Medical Sciences, Iran; Research Development Centre, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

OBJECTIVES: The current World Health Organization (WHO) definition of osteoporosis, which is based on densitometry of lumbar and femoral regions, is extensively used for decision-making in clinical practice. Discordance in diagnosis of osteoporosis using this definition is a known phenomenon. The aim of this study was to evaluate the impact of such discordance and to assess the diagnostic value of using one skeletal site for screening purposes as opposed to the two sites required in the WHO criteria. STUDY DESIGN: Data was collected from 4188 individuals (3848 female); mean age=53.4 years (standard deviation 11.8) referred to a community-based outpatient osteoporosis testing centre in Tehran, Iran. METHODS: Dual-energy X-ray absorptiometry (DXA) was performed on L1-L4 lumbar spine and total hip for all cases. The DXA results were categorized according to WHO criteria. Sensitivity for each site was calculated as number of cases with T-score <-2.5 at that site divided by the total number of cases with T-score <-2.5 at any site. RESULTS: Prevalence of osteoporosis diagnosis using lumbar DXA, femoral DXA, and WHO criteria (either of the sites) were 24.7%, 12.4%, and 27.8%, respectively. Sensitivity of lumbar DXA for diagnosis of osteoporosis (88.9%) was significantly higher than femoral DXA (44.6%, P<0.001); but this difference became non-significant for men 60 and women 70 (P=0.615 and P=0.077, respectively). Agreement of the procedures in different sites (kappa) was 0.40 (0.37 to 0.43). When proximal femur was considered as the reference, positive likelihood ratios of lumbar DXA to detect cases were 4.7 and 2.0 in younger and older groups, respectively. CONCLUSIONS: Concerning the high rate of discordance and low agreement between DXA results, the data obtained from each anatomical site cannot predict the condition of the other site. However, if use of a single assessment is intended for screening programs, public health authorities can develop different strategies for different age groups of their population. We propose lumbar DXA for the younger group (men <60 and women <70) and femoral densitometry for the older.

Gynecol Endocrinol. 2006 Jul;22(7):369-75

The European Menopause Survey 2005: Women's perceptions on the menopause and postmenopausal hormone therapy.

Genazzani AR, Schneider HP, Panay N, Nijland EA.

Department of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.

Objectives. To identify and describe current women's thoughts about the menopause, hormone treatment (HT) and perceptions about breast cancer.Methods. Between December 2004 and January 2005, 4201 postmenopausal women in seven European countries were interviewed via a standardized computer-aided telephone interview protocol.Results. Almost all women reported to have experienced climacteric symptoms, and 63% of the women rated them as being severe. Only 52% of women were aware of the benefits of HT for relief of climacteric symptoms. Although 84% felt that severe symptoms should be treated, only 40% had used HT at some point in time. Thirty-four percent of the women preferring treatment with natural products did so because of the risk of breast cancer associated with HT. HT was recognized by 59% of the women as one of the most important contributors to an increased breast cancer risk. Most women received their information about HT and breast cancer risk from the media.Conclusions. This European survey reveals that the majority of women experience climacteric symptoms but that their decision whether or not to use HT is highly dependent on their concern about breast cancer risk. An increase in knowledge of the benefits and risks of HT is required for women to make appropriate decisions about hormone use.

Obesity (Silver Spring). 2006 Jun;14(6):1046-55

Changes in Intra-abdominal Fat in Early Postmenopausal Women: Effects of Hormone Use.

Gower BA, Munoz J, Desmond R, Hilario-Hailey T, Jiao X.

University of Alabama at Birmingham, Department of Nutrition Sciences, University Boulevard. USA.

OBJECTIVE: Intra-abdominal fat (IAF) accumulates with age, is greater among postmenopausal vs. premenopausal women, and is linked to risk for both type 2 diabetes and cardiovascular disease. Whether hormone replacement therapy (HRT) prevents or attenuates changes in IAF and related risk factors is not clear. The objectives of this observational study were to 1) determine whether HRT attenuated the expected age-related increase in IAF and 2) identify the independent effects of HRT and fat distribution on changes in disease risk factors. RESEARCH METHODS AND PROCEDURES: Subjects were early postmenopausal white women 45 to 55 years of age. Women either used HRT at the time of enrollment (n = 33) or did not (n = 17). Subjects were evaluated at baseline and 2 years for body composition (DXA), body fat distribution (computed tomography), insulin sensitivity (Si; minimal model), and serum lipids. RESULTS: IAF increased significantly over 2 years, and this increase was not attenuated by HRT. HRT users had less IAF throughout the study. HRT users showed an increase in Si, whereas non-users showed a decrease. Superficial subcutaneous adipose tissue was significantly and independently related to total cholesterol, whereas IAF was related to high-density lipoprotein cholesterol, triglycerides, and Si. DISCUSSION: HRT users had less IAF at baseline and throughout the study. Whether HRT altered the relationship between total body fat and IAF or whether differences between groups existed before the study should be addressed through a randomized, interventional study design. HRT had a significant effect on Si; IAF and superficial subcutaneous adipose tissue were significant determinants of disease risk factors.

J Med Assoc Thai. 2005 Nov;88 Suppl 3:S71-6

The comparative study of bone mineral density between premenopausal women receiving long term suppressive doses of levothyroxine for well-differentiated thyroid cancer with healthy premenopausal women.

Sajjinanont T, Rajchadara S, Sriassawaamorn N, Panichkul S.

Division of Nuclear Medicine, Department of Radiology, Phramongkutklao Hospital, Bangkok, Thiland.

OBJECTIVE: To compare bone mineral density (BMD) of lumbar spines (LS) and femoral neck (FN) by Dual energy X-ray absorptiometry (DEXA) in premenopausal well-differentiated thyroid carcinoma women S/P total or near total thyroidectomy with a control group and the effect of Levothyroxine (LT4) to BMD between short term and long term treatment. MATERIAL AND METHOD: DEXA were performed at LS (L1-L4) and FN in 22 premenopausal thyroid carcinoma women S/P total or near total thyroidectomy followed by 1-131 ablation and long term suppressive dose LT4 and 22 healthy premenopausal women. RESULTS: Mean BMD of LS and FN were not significantly different between thyroid cancer group and control (LS 1.023 +/- 0.088 VS 0.980 +/- 0.075 g/cm2, p > 0.05, FN 0.800 +/- 0.068 VS 0.770 +/ - 0.061 g/cm2, p > 0.05). Period of time taking suppressive doses LT4 was divided into 3 groups (2-5 6-10 yrs and 11-14 yrs). Mean LS BMD +/- S.D of 2-5 yrs, 6-10 yrs and 11-14 yrs therapy are 1.042 +/- 0.135, 1.004 +/- 0.044 and 1.042 +/- 0.055 respectively (p > 0.05). Mean FN BMD +/- S.D of 2-5 yrs, 6-10 yrs and 11-14 yrs therapy are 0.808 +/- 0.084, 0.781 +/- 0.067 and 0.816 +/- 0.013 respectively (p > 0.05). CONCLUSION: The suppressive doses LT was not the risk factor of osteoporosis. Although, there was no 4 statistically significant difference of BMD between short and long-term suppressive doses LT groups, the present sample size was not enough to conclude that long-term suppressive doses LT did not decrease BMD.

J Med Assoc Thai. 2005 Jun;88 Suppl 1:S12-20.

Comparing the effect of short term post meals and bedtime calcium supplementation on the C-terminal telopeptide crosslinks and PTH levels in postmenopausal osteopenic women.

Chuengsamarn S, Suwanwalaikorn S.

Division of Endocrinology, Faculty of Medicine, Srinakharinwirot University, Thailand.

Calcium supplement for postmenopausal osteopenic women can significantly reduce bone loss and the risk of fractures. However, the optimal time for calcium supplementation remains controversial. Objective: The aim of the present study was to compare the effect of twice daily post meals and bedtime calcium supplementation for a two week periods, on C-terminal telopeptide crosslinks and PTH levels in postmenopausal osteopenic women. Design: A randomized double blind placebo-control, crossover design, was carried out on 3 consecutive periods 3 of a 2-week treatment regimen. In the first period, all the subjects randomly received either two calcium carbonate tablets (Chalk Cap all subjects randomly received either two calcium 334 mg per tab) or placebo at bedtime with one tablet of calcium tablet or placebo after breakfast and dinner for two weeks. In the second period, subjects received only placebo tablets after the meals and at bedtime for 2 weeks. In the third period subjects received either calcium carbonate or placebo for another two weeks. The C-terminal telopeptide crosslinks were measured at 8.00 am and serum PTH were sampled at 8 time points (12.00 am, 2.00 am, 4.00 am, 6.00 am, 8.00 am, 9.00 am, 5.00 pm, and 7.00 pm respectively by the end of each study at the first and third period. Results: The present study showed thirty-six postmenopausal subjects (mean age 63.9 + 3.66 years) participated in the present study. The mean T-score BMD of the spine and hip were -2.96 + 0.87 and -2.96 + 0.77 gm/cm2. C-terminal telopeptide crosslinks levels of the bedtime supplementation were significantly lower than the post meal supplementation (0.228 + 0.002 ng/ml vs 0.313 + 0.003 ng/ml, p < 0.001). The mean night time serum PTH level during the bedtime was significantly lower than the post meal period. (25.17 + 2.31 pg/ml vs 31.930 + 2.677 pg/ml, p < 0.001). No differences in the post meal PTH level between two periods were observed Conclusion: The bedtime calcium supplementation appeared to reduce the bone resorption marker and night time serum PTH levels greater than the post meal calcium supplementation in this short term period study. However, long term comparison may be needed.

LA RECURRENCIA DE TROMBOSIS VENOSA ASOCIADA A ESTADOS “HORMONALES” ES MENOR, COMPARADO CON HOMBRES O CON MUJERES SIN ACO, EMBARAZO NI TERAPIA HORMONAL.

En un estudio de seguimiento de terapia anticoagulante oral por trombosis venosas, investigadores de Vermont encuentran que los hombres recaen en un 18,4% y las mujeres en un 15%, pero cuando segregan a las mujeres que presentaron su primera trombosis estando embarazada o bajo terapias hormonales por ACO o posmenopausia, la tasa de recaída es menos de la mitad. Se tendería a pensar que el arbitrario estado “hormonal” es una variable evitable, y por ende su supresión explicaría la menor incidencia futura, sin embargo, el estudio es de muy difícil interpretación, la población bastante heterogénea y está expuesto a sesgos de diversa índole.

LA PROBABILIDAD DE OSTEOPOROSIS DE CADERA EN MUJERES ASIÁTICAS URBANAS ES CUATRO VECES MAYOR QUE EN MUJERES SUBURBANAS. Este hallazgo correlaciona con un mayor grado de hiperparatiroidismo secundario e hipovitaminosis D en mujeres urbanas. Pueden influir: el estilo de vida con menor exposición a la intemperie, mayor sedentariedad o menor ingestión de lácteos,

MUJERES CON ALTO RIESGO DE CÁNCER DE MAMA TRATADAS CON RALOXIFENO PIERDEN MASA OSEA.

En columna lumbar pierden 2,3% a un año y 3,5% a dos años. Un año después de suspender la terapia han recuperado +1,4%. En cadera hay una evolución proporcionalmente similar. Esta pérdida no es sorprendente puesto que el grupo está compuesto por mujeres en edad entre 23 y 47 años, con producción estrogénica ovárica comprobada, en quienes el raloxifeno actúa atenuando la acción de los estrógenos endógenos. El estudio STAR, recientemente publicado, fue realizado en posmenopáusicas, donde la actividad agonista estrogénica de raloxifeno sobre hueso, siendo de baja potencia, es relativamente mayor que la conferida por el estado posmenopáusic. Raloxifeno n huso de psomenopáusicas es similar a tamoxifeno, el que a su vez es mejor que placebo según otros estudios.

LA COMBINACIÓN DE TESTOSTERONA Y ESTRÓGENOS AUMENTA LEVEMENTE EL RIESGO DE CÁNCER INVASIVO DE MAMA EN EL ESTUDIO DE LAS ENFERMERAS.

Comparado con placebo, la revisión retrospectiva de los datos prospectivamente acumulados en 24 años de seguimiento en el estudio de las enfermeras, el uso de estrógenos solo tuvo un apenas significativo mayor riesgo anual de presentar cáncer de mama OR 1.02 (IC 1.01-1.03), pero el uso combinado de estrógenos y testosterona fue algo mayor OR 1.10 (1.03-1.16). La testosterona sola tuvo una tendencia aún mayor pero no alcanzó significación estadística. Estos datos indican que la testosterona puede tener un impacto desfavorable. En relación a los estrógenos, estos datos están presentados de manera tendenciosa puesto que el informe original de Chen (Arch Intern Med. 2006;166:1027-1032) comunica que los estrógenos sin progesterona no se asocian con riesgo significatívo sino hasta terapias de mas de 15 años de duración, o mas de 20 años si se evalúan solo las que inician después de los cincuenta años de edad.

POBRE EVIDENCIA EN TERAPIAS ALTERNATIVAS PARA LA MENOPAUSIA

Un análisis de evidencia publicado en Arch Intern Med. 2006 Jul, indica que la mitad de las mujeres que consultan por síntomas asociados a la menopausia recurren a terapias alternativas, tendencia claramente marcada desde el anuncio del primer brazo del estudio WHI. Un estudio mostró que el 70% de las mujeres que usaban terapias alternativas, no lo comunicaban a sus médicos. El Institudo de Salud Nacional Norteamericano gasta mas de 200 millones de dólares anuales en investigación en terapias alternativas pero el público gasta mucho mas en productos que carecen de estudios de eficacia y de efectos secundarios.

Los investigadores eligieron 183 artículos médicos de un total de 1432 estudios sobre terapias alternativas, de los cuales solo 48 se refieren a terapias biológicas: 31 a fitoestrógenos y el resto a otros fármacos.

ESTRADIOL + NETA ORAL CONTINUO DISMINUYE EL DIÁMETRO DE CINTURA.

Un estudio Turco, en Gynecol Endocrinol de julio 2006 encuentra reducción del diámetro de cintura y de la relación cintura cadera entre otros parámetros antropométricos asociados al riesgo cardiovascular por reisstencia a la insulina.

Otro artículo en Obesity de junio de 2006, (Gower et al.) se suma a muchos otros que demuestran que la terapia hormonal aumenta la sensibilidad la insulina y se asocia a menor cantidad de grasa intra abdominal. Sin embargo, este estudio de Birmingham, es observacional y muy pequeño y sus conclusiones sirven tan solo como estudio piloto.

DEXA PARECE SER MEJOR EN COLUMNA PARA IDENTIFICAR OSTEOPOROSIS EN GENTE JOVEN, EN CAMBIO CADERA SERÍA EL SITIO ADECUADO EN LOS MAYORES.

Esta es una antigua recomendación que provenía del simple análisis de densitometrías de columna, que muestran aumento espúreo a medida que avanza la edad, cuando la paciente va desarrollando espondiloartrosis. Un estudio Iraní publicado en Public Health de julio, evalúa la concordancia entre la densitometría obtenida en columna, cadera y los criterios WHO. Concluyen que la medición densitométrica de un sitio no expresa correctamente el estado del otro y dexa es el doble mas eficiente en detectar osteoporosis en columna en su grupo de estudio (entre 42 y 64 años de edad aproximadamente). La explicación mas obvia es que la osteoporosis de columna precede a la de cadera.

LOS PACIENTES CON FRACTURA DE CADERA TIENEN MENORES NIVELES DE VITAMINA-D Y MAYORES DE PARATHORMONA.

La tasa de fractura de cadera en la isla de Sado, en Japón es de 0,12% de la población total anual. Es una comunidad bastante cerrada. De un total de 85 fracturas ocurridas en un año en toda la isla, compararon 50 casos con pacientes de similar edad (mayores de 70 años). El grupo con fracturas tiene tres veces mas insuficiencia de vitamina D, la cual es mas baja en pacientes con mayor deterioro mental. En efecto, hay hipovitaminosis en el 62% de las fracturadas y en el 18,9% de las controles. La parathormona por su parte, que sube en respuesta a la menor absorción intestinal de calcio en la carencia de vitamina D, llega a sobrepasar los valores máximos normales de 65 pg/ml, hasta en un quinto de las pacientes con hipovitaminosis-D, pero solo en un caso en el grupo control. Esta especificidad mostrada por la PTH en sangre, induce a los autores a proponer a esta hormona como marcador de riesgo de fractura de cadera en ancianos.

Cabe comentar, que de acuerdo a las recomendaciones de la NOF (National Osteoporosis Foundation) de los EEUU, la paciente de 70 años por el solo mérito de la edad, ya tiene riesgo suficiente como para indicar tratamiento, incluyendo calcio y vitamina D con lo que se evita el hiperparatiroidismo secundario. Con esto, en nuestra opinión, no es costoefectivo medir PTH en sospechas de déficit de vitamina D.

LA TH CON ECE 0,625+AMP 2,5 BAJA NIVELES DE COENZIMO Q10, GAMA-TOCOFEROLES Y AUMENTA ALFATOCOFEROLES

Este es un muy pequeño estudio publicado en una poco conocida revista Biofactors por Palan et al. Que consiste en 15 casos tratados con el equivalente a PrempakR y 33 controles, que entre otras cosas encuentra similares niveles de colesterol HDL, LDL y triglicéridos en ambos grupos. Lamentablemente no es mas que una buena intención de evaluar el impacto de la TH sobre niveles de antioxidantes, ya que el estudio carece de poder estadístico y no refleja los efectos conocidos del fármaco sobre lípidos.

LA TERAPIA CON ESTRÓGENOS REDUCE EL CATABOLISMO DE COLAGENO ARTICULAR TIPO II EN RATAS CASTRADAS.

Oestergaard et al, en un estudio patrocinado por nuestro conocido Dr. Claus Christensen, encuentra correlación entre marcadores de remodelación cartilaginosa (C-telopéptido de colágeno tipo II) y la magnitud de lesiones artrósicas en ratas ovariectomizadas. El estrógeno redujo los índices de recambio cartilaginoso de una manera similar a como lo hace en hueso, independiente del tiempo de inicio, pero como hubo mas lesiones a mayor duración del estado hipogonadal, la terapia sería mas efectiva mientras mas precoz.

LA ENCUESTA TELEFÓNICA EUROPEA DE MENOPAUSIA EN 2005 REVELA DISTINTA ACTITUD FRENTE A HORMONAS PARA TRATAR SINTOMAS DEL CLIMATERIO COMPARADA CON CHILENAS

La publicación es del Prof. Andrea Genazzani y el Prof. Hermann Schneider entre otros, su grupo de estudio 4201 posmenopáusicas de siete países. En dos meses aplican un cuestionario telefónico, terminando en enero de 2005.

Casi todas refieren haber tenido síntomas climatéricos, calificados como severos en el 63%, pero solo el 52% estuvo consciente de los beneficios de una terapia. Aunque el 84% cree que hay tratamiento disponible, solo el 40% ha utilizado TH alguna vez.

34% de las mujeres prefieren tratamientos “naturales” por creer que son alternativa segura contra el riesgo de cáncer de mama, que asocian con la HT. Un 59% de las mujeres cree que la TH es uno de los contribuyentes mas importantes para el aumento del cáncer de mama. La mayoría se forma su opinión a partir de los medios de comunicación.

A muchos nos parece que esta encuesta coincide con lo observado en los niveles medio de la estratificación socioeconómica hacia arriba, en nuestra práctica diaria, aunque sondeos nacionales han mostrado una menor relevancia para el argumento cáncer.

CARBONATO DE CALCIO DESPUES DE COMIDA O AL ACOSTARSE.

Un estudio tailandés de mujeres entre 60 y 67 años compara marcadores de resorción ósea y niveles de PTH después de administrar carbonato de calcio antes de acostarse o después de comida. Tal como es de esperar, la dosis de calcio nocturna reduce mas la PTH y el C-telopéptido que marca la resorción de colágena ósea. Hay que recordar que el efecto esperado cambia según la sal cálcica que se utiliza. Citrato, ftalato o gluconolactato no interactúan de manera adversa con la comida como lo hacen los carbonatos y acetatos, los cuales no solo se absorben menos, son también quelantes.

Semana del 4 al 11de Julio de 2006

Dr. Juan Enrique Blümel

J Bone Miner Res. 2006 Jul;21(7):1106-12.

Effects of 3- and 5-year treatment with risedronate on bone mineralization density distribution in triple biopsies of the iliac crest in postmenopausal women.

Zoehrer R, Roschger P, Paschalis EP, Hofstaetter JG, Durchschlag E, Fratzl P, Phipps R, Klaushofer K.

Long-term effects of risedronate on bone mineralization density distribution in triple transiliac crest biopsies of osteoporotic women were evaluated. In this double-blinded study, 3- and 5-year treatment with risedronate increased the degree and homogeneity of mineralization without producing hypermineralization. These changes at the material level of bone could contribute to risedronate's antifracture efficacy. Introduction: Risedronate, a nitrogen-containing bisphosphonate, is widely used in the treatment of osteoporosis. It reduces bone turnover, increases BMD, and decreases fracture risk. To date, there are no data available on the long-term effects of risedronate on bone mineralization density distribution (BMDD) in humans. Materials and Methods: Osteoporotic women enrolled in the VERT-NA trial received either risedronate (5 mg/day, orally) or placebo for up to 5 years. All subjects received calcium and vitamin D supplementation if deficient at baseline. Triple iliac crest biopsies were collected from a subset of these subjects at baseline and 3 and 5 years. BMDD was measured in these biopsies using quantitative backscattered electron imaging, and the data were also compared with a normal reference group. Results: At baseline, both risedronate and placebo groups had a lower degree and a greater heterogeneity of mineralization as well as an increase in low mineralized bone compared with the normal reference group. The degree of mineralization increased significantly in the risedronate as well as in the placebo group after 3- and 5-year treatment compared with baseline. However, the degree of mineralization did not exceed that of normal. Three-year treatment with risedronate significantly increased the homogeneity of mineralization and slightly decreased low mineralized bone compared with placebo. Surprisingly with 5-year risedronate treatment, heterogeneity of mineralization increased compared with 3-year treatment, which might indicate an increase in newly formed bone. Conclusions: Long-term treatment with risedronate affects the homogeneity and degree of mineralization without inducing hypermineralization of the bone matrix. These changes at the material level of the bone matrix may contribute to risedronate's antifracture efficacy in osteoporotic patients.

Am J Hypertens. 2006 Jul;19(7):744-749

Different Effects of Transdermal and Oral Hormone Replacement Therapy on the Renin-Angiotensin System, Plasma Bradykinin Level, and Blood Pressure of Normotensive Postmenopausal Women.

Ichikawa J, Sumino H, Ichikawa S, Ozaki M.

Department of Anesthesiology, Tokyo Women's Medical University, Tokyo, Japan.

BACKGROUND: This study compared the efficacy of transdermally administered estradiol with that of orally administered conjugated equine estrogens (CEE) on the renin-angiotensin system, plasma bradykinin level, and blood pressure (BP) in normotensive postmenopausal women (PMW). METHODS: A total of 38 normotensive PMW were randomly assigned to two groups. The transdermal hormone replacement therapy (HRT) group consisted of 19 women treated with a continuous transdermal estradiol patch (36 mug/day) plus cyclic oral medroxyprogesterone acetate (MPA; 2.5 mg/day for 12 days) for 12 months. The oral HRT group consisted of 19 women who received continuous oral CEE (0.625 mg/day) plus cyclic oral MPA (2.5 mg/day for 12 days) for 12 months. Plasma renin activity (PRA), serum angiotensin-converting enzyme (ACE) activity, plasma angiotensin (Ang) I, Ang II, and bradykinin concentrations, and BP were measured before and 12 months after the start of HRT. RESULTS: Transdermal HRT significantly decreased both diastolic and mean BP and concomitantly reduced bradykinin levels (all P < .05). However, no significant changes in PRA, ACE activity, Ang I, or Ang II levels were observed. The BP remained unchanged in the oral HRT group, but the PRA, Ang I, Ang II, and bradykinin levels had significantly increased and ACE activity had significantly decreased (all P < .05) at 12 months after the start of HRT. CONCLUSIONS: Transdermal HRT decreased BP in normotensive PMW without influencing Ang II, whereas oral HRT increased Ang II without altering BP. Transdermal HRT may be more beneficial than oral HRT with regard to BP and Ang II levels.

Phys Ther. 2006 Jul;86(7):912-23.

Effect of brisk walking in 1 or 2 daily bouts and moderate resistance training on lower-extremity muscle strength, balance, and walking performance in women who recently went through menopause: a randomized, controlled trial.

Asikainen TM, Suni JH, Pasanen ME, Oja P, Rinne MB, Miilunpalo SI, Nygard CH, Vuori IM.

Satakunta Central Hospital, Sairaalantie 3, FIN-28500 Pori, Finland. tm.asikainen@sci.fi.

BACKGROUND AND PURPOSE: Menopause may induce a phase of rapid decreases in bone mineral density, aerobic fitness, muscle strength, and balance, especially in sedentary women. The purpose of this study was to examine the effects and feasibility of an exercise program of 1 or 2 bouts of walking and resistance training on lower-extremity muscle strength (the force-generating capacity of muscle), balance, and walking performance in women who recently went through menopause. SUBJECTS AND METHODS: The subjects were 134 women who recently went through menopause. The study was a 15-week, randomized, controlled trial with continuous and fractionated exercise groups. The outcomes assessed were lower-extremity muscle strength, balance, and walking time over 2 km. Feasibility was assessed by questionnaires, interviews, and training logs. RESULTS: One hundred twenty-eight women completed the study. Adherence to the study protocol was 92%. Both continuous and fractionated exercise groups improved equally in lower-extremity muscle strength and walking time but not in balance. Almost 70% of the subjects considered the program to be feasible. Two daily walking sessions caused fewer lower-extremity problems than did continuous walking. DISCUSSION AND CONCLUSION: Brisk walking combined with moderate resistance training is feasible and effective. Fractionating the walking into 2 daily sessions is more feasible than continuous walking.

Nestle Nutr Workshop Ser Clin Perform Programme. 2006;11:31-42.

Pharmacological and Surgical Intervention for the Prevention of Diabetes.

Chiasson JL.

Research Group on Diabetes and Metabolic Regulation, Research Center, Centre hospitalier de l'Université Montreal, Que, Canada.

The increasing prevalence of diabetes is reaching epidemic proportion worldwide. Because of the associated morbidity and mortality, it is exerting major pressure on the healthcare system. With a better understanding of the pathophysiology of type-2 diabetes, the concept of primary prevention has emerged. A number of studies have confirmed that intensive lifestyle modification was very effective in the prevention of diabetes in the impaired glucose tolerance (IGT) population. However, maintaining long-term lifestyle modification is a major challenge. It is, therefore, important to have other strategies, either pharmacological or surgical, that can be used as an adjunct or alternative to lifestyle modification. The Chinese study showed that metformin and acarbose could reduce the risk of diabetes by 65 and 83%, respectively, in IGT subjects. The efficacy of metformin was confirmed by the Diabetes Prevention Program (31% risk reduction) and that of acarbose by the STOP-NIDDM trial (36% risk reduction) in a similar high-risk population. The TRIPOD study showed that troglitazone could reduce the risk of diabetes by 55% in Hispanic women with a history of gestational diabetes. And more recently, the XENDOS study showed that orlistat could reduced the risk of diabetes by 37% in obese subjects when used as an adjunct to an intensive lifestyle program. Three studies have suggested that bariatric surgery in morbidly obese subjects could reduce the risk of diabetes to near zero. Furthermore, a number of studies have examined the effect of a renin angiotensin aldosterone system inhibitor, as well as statin and hormone replacement therapy on the prevention of type-2 diabetes in high-risk subjects as secondary outcomes and have suggested that they could be of potential benefit. The accumulating evidence is now overwhelming. Yes, diabetes can be prevented or delayed in high-risk populations. With this new information, we need to design new strategies to screen high-risk populations and to implement the new treatments that have proven effective in the prevention of type-2 diabetes.

Can Fam Physician. 2006 Jun;52:743-7

Premenopausal women and low bone density.

Khan A.

Division of Endocrinology, McMaster University, Hamilton, Ont. avkhan@aol.com

OBJECTIVE: To review the evidence and provide an approach to management of low bone density among premenopausal women. QUALITY OF EVIDENCE MEDLINE: was searched from January 1990 to November 2004 and articles graded by level of evidence (I to III). Diagnosis and management recommendations were based on evidence from randomized controlled trials and expert consensus. MAIN MESSAGE: Bone mineral density (BMD) testing among premenopausal women should be completed only in the presence of approved indications. Current evidence does not support screening for osteoporosis among premenopausal women. Low BMD in premenopausal women is associated with a lower fracture risk than seen in postmenopausal women. In the absence of fragility fractures, low BMD might reflect low peak bone mass based on genetic predisposition, environment, and lifestyle factors. Clinical evaluation enables distinction between low peak bone mass and a systemic disorder resulting in low BMD and skeletal fragility. Common causes of low bone density among premenopausal women include ovulatory disturbances and low body weight. CONCLUSION: Bone mineral density alone is insufficient for diagnosis of osteoporosis among premenopausal women in the absence of fragility fractures. Antiresorptive therapy has been evaluated and shown to benefit premenopausal women using glucocorticoid therapy or those with primary hyperparathyroidism.

J Natl Cancer Inst. 2006 Jul 5;98(13):920-31.

Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC).

Pischon T, Lahmann PH, Boeing H, Friedenreich C, Norat T, Tjonneland A, Halkjaer J, et als.

Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. pischon@mail.dife.de

BACKGROUND: Body weight and body mass index (BMI) are positively related to risk of colon cancer in men, whereas weak or no associations exist in women. This discrepancy may be related to differences in fat distribution between sexes or to the use of hormone replacement therapy (HRT) in women. METHODS: We used multivariable adjusted Cox proportional hazards models to examine the association between anthropometric measures and risks of colon and rectal cancer among 368 277 men and women who were free of cancer at baseline from nine countries of the European Prospective Investigation Into Cancer and Nutrition. All statistical tests were two-sided. RESULTS: During 6.1 years of follow-up, we identified 984 and 586 patients with colon and rectal cancer, respectively. Body weight and BMI were statistically significantly associated with colon cancer risk in men (highest versus lowest quintile of BMI, relative risk [RR] = 1.55, 95% confidence interval [CI] = 1.12 to 2.15; P(trend) = .006) but not in women. In contrast, comparisons of the highest to the lowest quintile showed that several anthropometric measures, including waist circumference (men, RR = 1.39, 95% CI = 1.01 to 1.93; P(trend) = .001; women, RR = 1.48, 95% CI = 1.08 to 2.03; P(trend) = .008), waist-to-hip ratio (WHR; men, RR = 1.51, 95% CI = 1.06 to 2.15; P(trend) = .006; women, RR = 1.52, 95% CI = 1.12 to 2.05; P(trend) = .002), and height (men, RR = 1.40, 95% CI = 0.99 to 1.98; P(trend) = .04; women, RR = 1.79, 95% CI = 1.30 to 2.46; P(trend)<.001) were related to colon cancer risk in both sexes. The estimated absolute risk of developing colon cancer within 5 years was 203 and 131 cases per 100,000 men and 129 and 86 cases per 100,000 women in the highest and lowest quintiles of WHR, respectively. Upon further stratification, no association of waist circumference and WHR with risk of colon cancer was observed among postmenopausal women who used HRT. None of the anthropometric measures was statistically significantly related to rectal cancer. CONCLUSIONS: Waist circumference and WHR, indicators of abdominal obesity, were strongly associated with colon cancer risk in men and women in this population. The association of abdominal obesity with colon cancer risk may vary depending on HRT use in postmenopausal women; however, these findings require confirmation in future studies.

Int J Obes (Lond). 2006 Jul 4; [Epub ahead of print]

Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones.

Laughlin GA, Barrett-Connor E, May S.

Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA, USA.

Objective:To assess the sex-specific association of adiponectin with multiple factors thought to influence its levels, with a special emphasis on endogenous sex hormones.Design and methods:A cross-sectional study of determinants of serum adiponectin in 873 men and 673 postmenopausal women, ages 50-92. Factors evaluated include age, body size, fat distribution, lifestyle (exercise, smoking, alcohol intake), insulin resistance, renal function and endogenous sex hormone levels (total and bioavailable testosterone and estradiol).Results:Median serum adiponectin was 50% higher in women than men (P<0.001). In unadjusted analyses, adiponectin was positively related to age, alcohol intake, high-density lipoprotein (HDL) and testosterone, and negatively related to waist girth, body mass index, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), triglycerides and bioavailable estradiol in both sexes (all P<0.01). Adiponectin was positively related to blood urea nitrogen, a measure of renal function, in men only (P<0.001). Sex-specific multivariate linear regressions adjusting for HDL and triglycerides showed that only age, HOMA-IR and sex hormones independently predicted circulating adiponectin for both men and women. Higher levels of endogenous testosterone and lower bioavailable estradiol concentrations each predicted higher adiponectin; this was true for both sexes, and was not explained by differences in age, adiposity, alcohol intake, insulin resistance or lipoprotein levels.Conclusions:The association of adiponectin with the factors studied here is strikingly similar for men and women. Sex differences in circulating adiponectin levels in older adults cannot be explained by sex hormone regulation.

CMAJ. 2006 Jul 4;175(1):52-9.

Parathyroid hormone for the treatment of osteoporosis: a systematic review.

Cranney A, Papaioannou A, Zytaruk N, Hanley D, Adachi J, Goltzman D, Murray T, Hodsman A.

Department of Medicine, University of Ottawa, Ottawa, Ont.

BACKGROUND: Human parathyroid hormone (hPTH)(1-34) was approved in 2004 for the treatment of severe osteoporosis. Members of the Osteoporosis Canada clinical guidelines committee conducted a systematic review of randomized controlled trials (RCTs) to assess the efficacy and safety of hPTH for fracture prevention in postmenopausal women and men with osteoporosis. METHODS: We searched MEDLINE, EMBASE, HTA, Current Contents and the Cochrane Controlled Trials Registry for published data from 1966 to February 2005. A systematic literature search for RCTs was conducted using the Cochrane Collaborative approach. We identified 12 trials that randomly assigned patients either to hPTH or placebo or to hPTH or an active comparator and were at least 1 year in duration. Outcomes included change in bone mineral density (BMD), fractures, back pain and adverse events. Two independent reviewers abstracted data on study characteristics and outcomes. RESULTS: hPTH(1-34) significantly increases lumbar spine BMD, with smaller increases at the femoral neck and total hip. hPTH(1-84) significantly increases lumbar spine BMD. The data show a significant reduction in both vertebral and nonvertebral fractures with hPTH(1-34) in postmenopausal women with previous vertebral fractures. There were no data on fractures comparing the approved dose of hPTH(1-34) with active comparators. INTERPRETATION: There is Level I evidence that hPTH(1-34) significantly increases BMD at all skeletal sites except the radius and significantly reduces the risk of new vertebral and nonvertebral fractures in postmenopausal women with prior fractures.

Clin Endocrinol (Oxf). 2006 Jul 1;65(1):40-4.

Effects of HRT on liver enzyme levels in women with type 2 diabetes: a randomized placebo-controlled trial.

McKenzie J, Fisher BM, Jaap AJ, Stanley A, Paterson K, Sattar N.

Department of Medicine, Glasgow Royal Infirmary University NHS Trust, Glasgow, Scotland, UK.

Background Increasingly strong links are being recognized between diabetes, insulin resistance and liver fat accumulation [e.g. nonalcoholic fatty liver disease (NAFLD)]. Recent data indicating that hormone replacement therapy (HRT) may lessen diabetes risk is intriguing but explanatory mechanisms are unclear. Objective Post hoc investigation of the possibility that HRT may favourably influence liver enzyme levels commonly elevated in patients with diabetes. We examined liver function test data from a 6-month trial of a low-dose continuous combined HRT (1 mg 17beta oestradiol and 0.5 mg norethisterone acetate). Design Double-blind, randomized placebo-controlled. Patients Fifty women with type 2 diabetes. Measurements Liver enzyme levels (AST, ALT, gamma-glutamylytransferase [GGT], and alkaline phosphatase [ALP]). Results Forty-five women completed the study with 19/22 in the active group demonstrating compliance as measured by sex hormone changes. Relative to placebo recipients (n = 23), women randomized and compliant to HRT demonstrated significant reductions in ALT [-14 (-23 to -6) U/l, P = 0.002], AST [-9.2 (-14 to -5) U/l, P < 0.001] and ALP [-60.8 (-80 to -42) U/l, P < 0.001]. Circulating concentrations in GGT were also significantly reduced (P = 0.035). All changes were significant using an intention-to-treat analysis. Conclusion HRT containing low-dose oestradiol and norethisterone reduces serum concentrations of liver function enzymes, potentially due to a lowering of liver fat accumulation. Better understanding of mechanisms by which this HRT improves liver function tests could help the design of new therapies to treat individuals with NAFLD.

J Sex Res. 2006 Feb;43(1):68-75.

Dysfunctional sexual beliefs as vulnerability factors to sexual dysfunction.

Nobre PJ, Pinto-Gouveia J.

Universidade de Tras-os-Montes e Alto Douro, Portugal. pedro.j.nobre@clix.pt

The differences on sexual beliefs presented by men and women with sexual dysfunction and their sexually functional counterparts were investigated. A total of 488 participants (160 females and 232 males without sexual problems and 47 females and 49 males with a DSM-IV diagnosis of sexual dysfunction) answered the Sexual Dysfunctional Beliefs Questionnaire. Findings showed that, although effects have only reached statistical significance for the female group, both dysfunctional men and women endorsed more sexual dysfunctional beliefs than functional. Women presented significantly more age related beliefs (after menopause women loose their sexual desire, as women age, the pleasure they get from sex decreases) and body image beliefs (women who are not physically attractive cannot be sexually satisfied). Additionally, sexually dysfunctional males presented higher scores (not statistically significant) on 'macho' belief (a real man has sexual intercourse very often) and the beliefs about women satisfaction (the quality of the erection is what most satisfies women). Overall, findings support the idea that sexual beliefs may play a role as vulnerability factors for sexual dysfunction.

J Bone Miner Metab. 2006;24(4):291-9

Immobilization decreases duodenal calcium absorption through a 1,25-dihydroxyvitamin D-dependent pathway.

Sato T, Yamamoto H, Sawada N, Nashiki K, Tsuji M, Nikawa T, Arai H, Morita K, Taketani Y, Takeda E.

Department of Clinical Nutrition, The University of Tokushima Graduate School, Japan.

Immobilization induces significant and progressive bone loss, with an increase in urinary excretion and a decrease in intestinal absorption of calcium. These actions lead to negative calcium balance and the development of disuse osteoporosis. The aims of this study were to evaluate the molecular mechanisms of decreased intestinal calcium absorption and to determine the effect of dietary 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and a high-calcium diet on bone loss due to immobilization. The immobilized rat model was developed in the Bollman cage III to induce systemic disuse osteoporosis in the animals. There was a significant decrease in lumbar bone mineral density (BMD) and intestinal calcium absorption in the immobilized group compared with the controls. Serum 25-hydroxyvitamin D concentration did not change, but 1,25(OH)(2)D concentration decreased significantly. The mRNA levels of renal 25-hydoxyvitamin D 24-hydroxylase (24OHase) increased, whereas those of renal 25-hydroxyvitamin D 1-alpha hydroxylase (1alpha-hydroxylase), duodenal transient receptor potential cation channel, subfamily V, member 6 (TRPV6), TRPV5, and calbindin-D9k were all decreased. A high-calcium diet did not prevent the reduction in lumbar BMD or affect the mRNA expression of proteins related to calcium transport. Dietary administration of 1,25(OH)(2)D increased the intestinal calcium absorption that had been downregulated by immobilization. TRPV6, TRPV5, and calbindin-D9k mRNA levels were also upregulated, resulting in prevention of the reduction in lumbar BMD. Therefore, it is concluded that dietary 1,25(OH)(2)D prevented decreases in intestinal calcium absorption and simultaneously prevented bone loss in immobilized rats. However, it remains unclear that calcium absorption and expression of calcium transport proteins are essential for the regulation of lumbar BMD.

Obstet Gynecol. 2006 Jul;108(1):41-48

Gabapentin, Estrogen, and Placebo for Treating Hot Flushes: A Randomized Controlled Trial.

Reddy SY, Warner H, Guttuso T Jr, Messing S, Digrazio W, Thornburg L, Guzick DS.

Department of Obstetrics and Gynecology, University of Rochester, Buffalo, New York.

OBJECTIVE: To compare the efficacy of gabapentin, estrogen, and placebo in the treatment of hot flushes. METHODS: We performed a randomized, double-blind, placebo-controlled trial of 60 postmenopausal women to assess the efficacy of estrogen and gabapentin in the treatment of moderate-to-severe hot flushes. Participants were randomly assigned to receive either 0.625 mg/d of conjugated estrogens (n = 20), placebo (n = 20), or gabapentin titrated to 2,400 mg/d (n = 20) for 12 weeks. Participants recorded frequency and severity of baseline hot flushes on a hot flush diary for 2 weeks before randomization and for 12 weeks after randomization. The primary outcome measure was the weekly hot flush composite score, which takes into account both severity and frequency of hot flushes. Secondary outcome measures were differences in pre- and posttreatment scores pertaining to depression (Zung Depression Scale) and other climacteric symptoms (Greene Climacteric Scale). RESULTS: Intention-to-treat analysis showed that the reduction in the hot flush composite score for both estrogen (72%, P = .016) and gabapentin (71%, P = .004) was greater than the reduction associated with placebo (54%) at the conclusion of the 12th week. The extent of reduction in hot flush composite score, however, was not significantly different between estrogen and gabapentin (P = .63). No differences were seen between groups in the Zung Depression Scale, or in any of the Greene Climacteric subscales except for the Somatic Symptom cluster, which was significantly greater in the gabapentin arm than in the placebo arm. Despite a lack of group differences in adverse events, the Headache, Dizziness, and Disorientation cluster appeared with greater frequency in the gabapentin group. Estimation of the number needed to harm in this cluster suggests that these symptoms may occur with every fourth patient treated with gabapentin. CONCLUSION: Despite the small scale of this study, gabapentin appears to be as effective as estrogen in the treatment of postmenopausal hot flushes.

Sleep Med. 2006 Jun 30; [Epub ahead of print

Sleep deprivation and hormone therapy in postmenopausal women.

Kalleinen N, Polo O, Himanen SL, Joutsen A, Urrila AS, Polo-Kantola P.

Sleep Research Unit, Department of Physiology, University of Turku, Dentalia, Turku, Finland.

BACKGROUND AND PURPOSE: Sleep complaints increase after menopause, but literature on the effect of postmenopausal hormone therapy (HT) on sleep is controversial. The purpose of this study was to determine the effect of ageing and HT on sleep quality, assessed using polysomnography, and on the accuracy of the subjective estimation of sleep quality in women before and after sleep deprivation. PATIENTS AND METHODS: Twenty postmenopausal women (aged 58-72 years) were recruited: 10 HT-users and 10 non-HT-users. Eleven young women (aged 20-26 years) served as controls. Polysomnography and subjective sleep quality were measured on four consecutive nights: adaptation, baseline, 40-h sleep deprivation and recovery. RESULTS: Although the postmenopausal women slept worse than the controls at baseline, and in particular during the recovery night, their recovery response to sleep deprivation was well preserved. At baseline, HT-users had a shorter latency to rapid eye movement (REM) (P=0.043), with fewer awakenings from slow wave sleep (SWS) (P=0.029) but more from REM (P=0.033) than non-HT-users. During recovery, the HT-users had more stage 2 sleep (P=0.048) and less slow wave activity (SWA) in the first non-rapid eye movement (NREM) sleep episode (P=0.021) than the non-HT-users. The poor correlation between subjective and objective sleep quality at baseline became significant during recovery. CONCLUSIONS: Although sleep in postmenopausal women was worse than in young controls, the recovery response following sleep deprivation was relatively well preserved. HT offered no significant advantage to sleep at baseline and slightly weakened the recovery response to prolonged wakefulness.

Maturitas. 2006 Jun 29; [Epub ahead of print]

Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin.

Anderson GL, Chlebowski RT, Rossouw JE, Rodabough RJ, McTiernan A, Margolis KL, et als.

WHI Clinical Coordinating Center, Public Health Sciences Division, Seattle, WA 98109-1024, United States.

OBJECTIVES: To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E+P) in the Women's Health Initiative (WHI) randomized trial. METHODS: Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E+P over an average 5.6 years of follow-up. RESULTS: Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E+P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E+P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p=0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p=0.01) and among never users (p=0.02) but not among prior users (p=0.10). The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p=0.08) or recency of prior use (p=0.17). Prior hormone use significantly increased the E+P hazard ratio for larger, more advanced tumors. CONCLUSION: A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.