Testosterone use and shorter electrocardiographic QT interval duration in men living with and without HIV.

OBJECTIVES: Testosterone usage (T-use) may alter risk factors for sudden cardiac death in men living with HIV (MLWH). Electrocardiographic QT interval prolongation, which could potentiate ventricular arrhythmias, has previously been associated with HIV infection and, separately, with low testosterone levels. We investigated whether T-use shortens the QT interval duration in MLWH and HIV-uninfected men. METHODS: We utilized data from the Multicenter AIDS Cohort Study, a prospective, longitudinal study of HIV infection among men who have sex with men. Multivariable linear regression analyses were used to evaluate associations between T-use and corrected QT interval (QTc) duration. RESULTS: Testosterone usage was more common in MLWH compared with HIV-uninfected men (19% vs. 9%). In a multivariable regression analysis, T-use was associated with a 5.7 ms shorter QT interval [95% confidence interval (CI): -9.5 to -1.9; P = 0.003). Furthermore, stronger associations were observed for prolonged duration of T-use and recent timing of T-use. CONCLUSIONS: This study is the first known analysis of T-use and QTc interval in MLWH. Overall, our data demonstrate that recent T-use is associated with a shorter QTc interval. Increased T-use duration above a threshold of ≥ 50% of visits in the preceding 5 years was associated with a shorter QTc interval while lesser T-use duration was not.

To T or not to T: Differences in Testosterone Use and Discontinuation by HIV Serostatus among Men who Have Sex with Men.

OBJECTIVES: The aim of the study was to characterize contemporary patterns and correlates of testosterone therapy (TTh) use and discontinuation by HIV serostatus among men in the Multicenter AIDS Cohort Study (MACS). METHODS: Self-reported testosterone use data were collected semiannually from 2400 (1286 HIV-infected and 1114 HIV-uninfected) men who have sex with men. Multivariable Poisson regression was used to estimate prevalence ratios for TTh use and predictors of TTh discontinuation (2012-2015). RESULTS: Use was higher among HIV-infected compared with HIV-uninfected men in all age strata, with an age-adjusted prevalence of 17% vs. 5%, respectively (adjusted prevalence ratio 3.7; P < 0.001). Correlates of use in the multivariable model were similar by HIV serostatus: white race, the Los Angeles (LA) site, more than one recent sexual partner, non-smoking status, and higher American Heart Association/American College of Cardiology (AHA/ACC) cardiovascular disease (CVD) risk score category (approximately 70% of testosterone users were in the high-risk category). Compared with HIV-uninfected men, HIV-infected men more frequently reported building muscle mass as a motivation for testosterone use. The TTh discontinuation rate was 20.9/100 person-years [95% confidence interval (CI) 17.3, 25.0/100 person-years]. Relative to HIV-uninfected men, HIV-infected men were half as likely to discontinue (adjusted incidence rate ratio 0.4; P < 0.001). Discontinuation was 40% higher in the period after the US Food and Drug Administration (FDA) safety communication for testosterone in 2014, independent of co-factors (P = 0.06). CONCLUSIONS: Given the high prevalence of both TTh use and CVD risk among HIV-infected men, the benefits and risks of TTh should be examined in future studies of aging HIV-infected men and monitored routinely in clinical practice.

Pre-diabetes and serum sex steroid hormones among US men.

Several studies demonstrate a link between diabetes and sex steroid hormones, but the link with pre-diabetes remains elusive. In this study, we hypothesize that pre-diabetes, which is characterised by having impaired fasting glucose and/or impaired glucose tolerance and/or impaired HbA1C, may influence circulating sex steroid hormone concentrations in men. Thus, we investigated whether serum sex steroid hormone concentrations differ between men with and without pre-diabetes. We analyzed data for 1139 men who were aged 20+ years when they participated in the Third National Health and Nutrition Examination Survey. We calculated adjusted geometric mean serum concentrations of total and estimated free testosterone, androstanediol glucuronide, total and estimated free estradiol, and sex hormone-binding globulin (SHBG) in men with and without pre-diabetes. Logistic regression was used to calculate adjusted odds ratios (OR) of lower concentrations of androgens and SHBG, and higher concentrations of estradiol by prediabetes status. Adjusting for age and race/ethnicity, total testosterone concentration was lower among men with (geometric mean: 4.68 ng/mL) than without (5.36 ng/mL, p = 0.01) pre-diabetes. SHBG concentration was also lower in men with (31.67 nmol/L) than without (36.16 nmol/L; p = 0.01) pre-diabetes. Concentrations of the other hormones did not differ between men with and without pre-diabetes. After adjusting for demographic and lifestyle factors, pre-diabetic men had a higher odds of lower testosterone (OR: 2.58; 95% CI: 1.54-4.29), higher free estradiol level (OR: 1.59; 95% CI: 1.14-2.22), and lower SHBG level (OR: 2.27; 95% CI: 1.32-3.92) compared to men without pre-diabetes. These associations were attenuated after adjusting for adiposity (testosterone OR: 1.76; 95% CI 0.95-3.27, free estradiol OR: 1.29, 95% CI: 0.88-1.88, SHBG OR: 1.71; 95% CI 0.88-3.30). Our findings suggest that men with pre-diabetes have lower circulating total testosterone and SHBG and higher free estradiol levels.

Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk.

CONTEXT: Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. OBJECTIVE: The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. DESIGN: This was a cross-sectional case control study. SETTING: The study was conducted at a clinical research center. PARTICIPANTS: Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. INTERVENTIONS: Blood samples and anthropometric measures were obtained. MAIN OUTCOME MEASURES: LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. RESULTS: Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T. CONCLUSION: Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance.

Racial variation in sex steroid hormone concentration in black and white men: a meta-analysis.

Sex steroid hormones are associated with chronic diseases and mortality with risk associations that differ between racial and ethnic groups. However, it is currently unclear whether sex steroid hormone levels differ between black and white men. The aim of this study was to assess racial variation in circulating testosterone, free testosterone, sex hormone-binding globulin (SHBG) and estradiol levels in men. We searched PubMed for articles comparing circulating hormones in black and white men. A meta-analysis was performed using weighted mean differences (WMD) to compare hormones levels between black and white men. Fifteen eligible studies were identified; three did not report adjusted means. After age adjustment, free testosterone levels were significantly higher in black than in white men (WMD = 4.07 pg/mL, 95% CI 1.26, 6.88). Depending on the free testosterone concentration in white men, this WMD translates into a racial difference ranging from 2.5 to 4.9%. Total testosterone (WMD = 0.10 ng/mL, 95% CI -0.02, 0.22), estradiol (WMD = 0.67 pg/mL, 95% CI -0.04, 1.38) and SHBG (WMD = -0.45 nmol/L, 95% CI -1.75, 0.85) concentrations did not differ comparing blacks with whites. After adjustment for age, black men have a modestly but significantly 2.5 to 4.9% higher free testosterone level than white men. Based on previous studies on effects of sex steroid hormones on risk of chronic diseases or mortality, this modest difference is unlikely to explain racial differences in disease risk.

Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.

CONTEXT: In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion. OBJECTIVE: The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD. DESIGN: This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1-29)NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone. MAIN OUTCOME MEASURE: Peak GH area under the receiver operating characteristic curve after macimorelin was measured. RESULTS: Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 ± 5.69 and 17.71 ± 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with 82% sensitivity, 92% specificity, and 13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = -0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported. CONCLUSION: Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.

Low free testosterone in HIV-infected men is not associated with subclinical cardiovascular disease.

OBJECTIVES: Low testosterone (T) is associated with cardiovascular disease (CVD) and increased mortality in the general population; however, the impact of T on subclinical CVD in HIV disease is unknown. This study examined the relationships among free testosterone (FT), subclinical CVD, and HIV disease. METHODS: This was a cross-sectional analysis in 322 HIV-uninfected and 534 HIV-infected men in the Multicenter AIDS Cohort Study. Main outcomes were coronary artery calcification presence, defined as a coronary artery calcium (CAC) score >10 (CAC score was the geometric mean of the Agatston scores of two computed tomography replicates), and far wall common carotid intima-media thickness (IMT)/carotid lesion presence by B-mode ultrasound. RESULTS: Compared with the HIV-uninfected men in our sample, HIV-infected men were younger, with lower body mass index (BMI) and more often Black. HIV-infected men had lower FT (age-adjusted FT 88.7 ng/dL vs. 101.7 ng/dL in HIV-uninfected men; P=0.0004); however, FT was not associated with CAC, log carotid IMT, or the presence of carotid lesions. HIV status was not associated with CAC presence or log carotid IMT, but was associated with carotid lesion presence (adjusted odds ratio 1.69; 95% confidence interval 1.06, 2.71) in HIV-infected men compared with HIV-uninfected men. CONCLUSIONS: Compared with HIV-uninfected men, HIV-infected men had lower FT, as well as more prevalent carotid lesions. In both groups, FT was not associated with CAC presence, log carotid IMT, or carotid lesion presence, suggesting that FT does not influence subclinical CVD in this population of men with and at risk for HIV infection.

Association of baseline sex hormone levels with baseline and longitudinal changes in waist-to-hip ratio: Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Waist-to-hip ratio (WHR) is strongly associated with prevalent atherosclerosis. We analyzed the associations of baseline serum levels of testosterone (T), estradiol (E2), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA) with WHR in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. SUBJECTS: Baseline data was available for 3144 men and 2038 postmenopausal women, who were non-users of hormone therapy, who were 45-84 years of age, and of White, Chinese, Black or Hispanic racial/ethnic groups. Of these, 2708 men and 1678 women also had longitudinal measurements of WHR measured at the second and/or the third study visits (median follow-up 578 days and 1135 days, respectively). RESULTS: In cross-sectional analyses adjusted for age, race and cardiovascular disease risk factors, T was negatively associated with baseline WHR in men, whereas in both sexes, E2 was positively associated and SHBG was negatively associated with WHR (all P<0.001). In longitudinal analyses, further adjusted for follow-up time and baseline WHR, baseline T was negatively associated with WHR at follow-up (P=0.001) in men, whereas in both sexes, E2 was positively associated (P=0.004) and SHBG was negatively associated with WHR (P<0.001). The longitudinal association of E2, but not T, was independent of SHBG. In cross-sectional or longitudinal analyses, there were no associations between DHEA and WHR in either men or women. CONCLUSION: Sex hormones are associated with WHR at baseline and also during follow-up above and beyond their baseline association. Future research is needed to determine if manipulation of hormones is associated with changes in central obesity.

Hip bone geometry in HIV/HCV-co-infected men and healthy controls.

UNLABELLED: People with both HIV and hepatitis C are more likely than those with HIV alone to have wrist, hip, and spine fractures. We compared hip strength between HIV/HCV-co-infected men and healthy men and found that HIV/HCV-co-infected men had decreased hip strength due to lower lean body mass. INTRODUCTION: Hepatitis C co-infection is a risk factor for fragility fracture among HIV-infected populations. Whether bone strength is compromised in HIV/HCV-co-infected patients is unknown. METHODS: We compared dual-energy x-ray absorptiometry (DXA)-derived hip geometry, a measure of bone strength, in 88 HIV/HCV-co-infected men from the Johns Hopkins HIV Clinic to 289 men of similar age and race and without HIV or HCV from the Boston Area Community Health Survey/Bone Survey. Hip geometry was assessed at the narrow neck, intertrochanter, and shaft using hip structural analysis. Lean body mass (LBM), total fat mass (FM), and fat mass ratio (FMR) were measured by whole-body DXA. Linear regression was used to identify body composition parameters that accounted for differences in bone strength between cohorts. RESULTS: HIV/HCV-co-infected men had lower BMI, LBM, and FM and higher FMR compared to controls (all p < 0.05). At the narrow neck, significant differences were observed between HIV/HCV-co-infected men and controls in bone mineral density, cross-sectional area, section modulus, buckling ratio, and centroid position. After adjustment for race, age, smoking status, height, and weight, only buckling ratio and centroid position remained significantly different between cohorts (all p < 0.05). Substituting LBM, FM, and FMR for weight in the multivariate model revealed that differences in LBM, but not FM or FMR, accounted for differences in all narrow neck parameters between cohorts, except buckling ratio and centroid position. CONCLUSION: HIV/HCV-co-infected men have compromised hip strength at the narrow neck compared to uninfected controls, which is attributable in large part to lower lean body mass.

Effect of high-dose isoflavones on cognition, quality of life, androgens, and lipoprotein in post-menopausal women.

CONTEXT: Recent interventional studies indicate that post-menopausal hormone replacement therapy is associated with an increased risk of cardiovascular mortality and breast cancer. Isoflavones, a class of plant estrogens, have structural similarities to estradiol. Hence, isoflavones may exert beneficial estrogenic health effects in postmenopausal women with fewer adverse effects. OBJECTIVE: To evaluate the effect of high-dose isoflavones on self-reported quality of life (QOL), cognition, lipoproteins and androgen status in post-menopausal women. DESIGN AND SUBJECTS: Double-blind, randomized, placebo-controlled, 12-week trial of 93 healthy, ambulatory, post-menopausal women (mean age 56 yr). The study was conducted at a tertiary care center in the United States. INTERVENTION: Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). Both soy and the placebo were provided in the form of a powder to be mixed with beverages. MAIN OUTCOME MEASURES: QOL was judged by the Menopause-specific Quality of Life (MENQOL) questionnaire while cognitive function was assessed with standard instruments. Total, free, and bioavailable testosterone, gonadotropins, SHBG, and fasting lipids were measured. RESULTS: Eighty-four women (90%) completed the study (active=38, placebo=46). There was a significant improvement in all 4 QOL subscales (vasomotor, psychosexual, physical, and sexual) among the women taking isoflavones, while no changes were seen in the placebo group. No significant changes in cognition, serum androgens or plasma lipids were seen within any of the groups. However, at the end of the study, a group-by-time interaction was observed such that total testosterone and HDL levels were significantly lower in the isoflavones compared to placebo groups. CONCLUSION: High-dose isoflavones is associated with improved QOL among women who have become menopausal recently. Hence, the timing of isoflavone supplementation with regards to the onset of menopause appears to be important. The use of isoflavones, as an alternative to estrogen therapy, may be potentially useful and seemingly safe in this group of women who are looking for relief from menopausal symptoms.

Longitudinal changes in serum lipids among HIV-infected men on highly active antiretroviral therapy.

OBJECTIVE: The aim of the study was to describe longitudinal changes in serum lipids among HIV-infected men receiving highly active antiretroviral therapy (HAART) with long-term follow-up. METHODS: A total of 304 HIV-infected men who initiated HAART and who had serum lipid measurements prior to and for up to 7 years after HAART initiation were identified from the Multicenter AIDS Cohort Study (MACS). Mean levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were examined at biannual time-points. RESULTS: Significant lipid changes were seen within 0.5 years of HAART initiation but increases in TC (+1.09 mmol/L), LDL-C (+0.57 mmol/L), HDL-C (+0.16 mmol/L) and non-HDL-C (+0.91 mmol/L) reached peak levels 2-3 years after HAART initiation. Declines in serum TC, LDL-C and non-HDL-C in subsequent years occurred concurrently with a substantial increase in use of lipid-lowering medications (from 1% usage pre-HAART to 43% 6-7 years after HAART initiation) but the proportion of men who either were treated with cholesterol-lowering medication or had elevated cholesterol levels (>5.18 mmol/L) did not change during the 2-7-year interval after HAART. Mean HDL-C also decreased after 2-3 years and was low (<1.04 mmol/L) in 55% of HIV-infected men 6-7 years after HAART initiation. CONCLUSIONS: Atherogenic serum lipids increased early after the initiation of HAART, peaked at 2-3 years and remained high or required treatment thereafter. Low HDL-C levels persisted in the majority of men. The long-term effects of lipid abnormalities on cardiovascular risk and the effectiveness and toxicity of prolonged use of lipid-lowering medications in combination with HAART are not known.

Alternative therapies for osteoporosis.

A variety of common complementary and alternative medicine therapies are now being examined for effectiveness in the management of osteoporosis. Short-term studies in postmenopausal women show beneficial effects of soy isoflavone supplementation on bone density, but its long-term effects require clarification. Prospective controlled trials have shown that physical training can increase bone density to varying degrees. Other therapies that have been examined include herbal formulae, essential fatty acids and vitamins A, C, and K, but few data regarding their effectiveness, mechanisms and safety have been published. Further randomized controlled trials are needed.

Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy.

Sex steroids are known to modulate serum lipoproteins. Studies have suggested that serum testosterone levels are associated with a beneficial lipid profile. Androgen deprivation therapy (ADT) is employed in the treatment of recurrent and metastatic prostate cancer (PCa), resulting in profound hypogonadism. As male hypogonadism unfavorably influences lipid profile and men with PCa have high cardiovascular mortality, we evaluated the effects of long-term ADT on fasting lipids. This Cross-sectional study was conducted in a university-based research institution. We evaluated 44 men, 16 undergoing ADT for at least 12 months before the study (ADT group), 14 age-matched eugonadal men with non-metastatic PCa who were status post prostatectomy and/or radiotherapy and not on ADT (non-ADT group) and 14 age-matched eugonadal controls (Control group). None of the men had known history of diabetes or dyslipidemia. Mean age was similar in the three groups (P = 0.37). Serum total (P < 0.01) and free (P < 0.01) testosterone levels were lower in the ADT group compared to the other groups. Men on ADT had higher body mass index (BMI) compared to the other groups (P < 0.01). Men in the ADT group had significantly higher levels of total cholesterol compared to the other two groups (P = 0.03). After adjustment for BMI, men on ADT continued to have significantly higher fasting levels of total cholesterol (P = 0.02), LDL cholesterol (P = 0.04) and non-HDL cholesterol (P = 0.03) compared to the control group. No significant differences were seen in the levels of other lipoproteins between the three groups. These data show that men undergoing long-term ADT have higher total and LDL cholesterol than age-matched controls. Long-term prospective studies are needed to determine the time of onset of changes in these lipoproteins while on ADT and the influence of these changes on cardiovascular mortality.

The effect of simvastatin on triglyceride-rich lipoproteins in patients with type 2 diabetic dyslipidemia: a SILHOUETTE trial sub-study.

OBJECTIVE: To determine if simvastatin effectively decreases the elevated levels of triglyceride (TG), TG-rich lipoproteins, and small, dense LDL particles, which are characteristic of diabetic dyslipidemia. RESEARCH DESIGN AND METHODS: We conducted a prespecified analysis from a double-blind, placebo-controlled, randomized, 6-week crossover trial in patients with type 2 diabetes and low HDL-C (< 40 mg/dL). Each patient was randomized to 1 of 6 possible treatment arms; each patient received simvastatin 80 mg, simvastatin 40 mg, and placebo over 3 periods. We used the validated vertical auto profile (VAP) method to directly assess TG-rich lipoproteins and LDL subclasses. We assessed the efficacy of simvastatin to improve the lipoprotein profile in adult men (71%) and women (29%) (n = 151) with stable type 2 diabetes (HbA1C < 9%), LDL-C > 100 mg/dL, HDL-C < 40 mg/dL, and fasting TG level > 150 and < 700 mg/dL (median = 273 mg/dL). MAIN OUTCOME MEASURES: Percentage change from baseline in IDL and VLDL (TG-rich lipoproteins), LDL subclasses, and additional lipoproteins at the end of each 6-week treatment interval; percentage of patients who reached NCEP ATP III non-HDL goal of < 130 mg/dL by the end of each 6-week period. RESULTS: Both simvastatin 80 mg and 40 mg significantly reduced VLDL-C, VLDL3, and IDL, as well as the four LDL subclasses measured with VAP, compared with placebo. Simvastatin 80 mg, compared with simvastatin 40 mg, provided additional efficacy. With simvastatin 80 mg, 77.2% of patients not at their non-HDL-C goal of < 130 mg/dL at study baseline reached goal, compared with 65.7% following simvastatin 40 mg treatment, and 2.2% following placebo. CONCLUSIONS: Treatment with simvastatin effectively reduced the elevated levels of TG-rich lipoproteins and improved LDL composition in patients with type 2 diabetes. A large percentage of these patients attained the NCEP ATP III non-HDL-C goal of < 130 mg/dL, which demonstrates the improvement of the atherogenic profile in these patients.

Body shape and composition in HIV-infected women: an urban cohort.

OBJECTIVES: Alterations in body shape and composition are associated with HIV/AIDS. Wasting remains prevalent; increasingly, lipodystrophy is reported. Obesity is also epidemic in the USA. In this study, we sought to characterize the body changes reported by women attending a US urban clinic, and to evaluate contributing factors using inexpensive methods that are readily available in clinical practice. METHODS: In an urban Maryland clinic, a cross-section of HIV-infected women were evaluated by self report, anthropomorphic measurements, bioelectric impedance analysis (BIA) and chart review; they were categorized as no change, lipodystrophy, weight loss/wasting or weight gain/obesity. RESULTS: One hundred and sixty-one women were evaluated: 144 (89%) were African-American; 100 (62%) had used intravenous drugs and 40 (25%) were actively injecting drugs, while 39 (24%) smoked crack. Ninety-five (59%) were on highly active antiretroviral therapy (HAART) for a median period of 11.7 months [interquartile range (IQR)=4.5-24.2]. Since starting current HAART or in the previous year, 12 (7.4%) reported lipodystrophy changes, 85 (52.8%) weight gain, 27 (16.8%) overall weight loss, and 37 (23.0%) no change. Lipodystrophy was associated with higher CD4 percentage (P=0.03), lower frequency of crack use (P=0.04) and higher educational level (P=0.03). Weight loss correlated with longer duration of infection (P=0.01), select BIA results and increased rate of crack use (P=0.005). Weight gain was associated with higher fat mass (P=0.005), higher peak viral load (P=0.02), and lower rate of intravenous drug use (P=0.03). CONCLUSIONS: Self-reported changes in body shape were common. Obesity and complications of illicit drug use were more prevalent than lipodystrophy in this inner-city population of HIV-positive women.

Short-term pharmacokinetic comparison of a novel testosterone buccal system and a testosterone gel in testosterone deficient men.

OBJECTIVE: The primary objective of the study was to compare the percentage of men with mean serum total T (C(ave(0-24))) within normal range during the 24-h pharmacokinetic (PK) sampling period on Days 14 and 15. METHODS: Treatment with a new testosterone (T) buccal system, (Striant), 30 mg twice daily was compared to a transdermal gel delivery system, (T-gel) [AndroGel 5 g containing 1% (50 mg) T] daily for 14 days in T-deficient men. Safety parameters included laboratory assessments and collection of adverse events. Patients were otherwise healthy T-deficient men with total T

Role of testosterone in maintaining lean body mass and bone density in HIV-infected patients.

Low testosterone levels are common in both men and women with human immunodeficiency virus (HIV) infection and may contribute to loss of lean body mass and AIDS wasting. Causes of low testosterone levels are complex and may include chronic illness, HIV infection and its complications, medications used to treat HIV and opportunistic diseases, and normal aging-related declines. In the majority of studies addressing the use of testosterone treatment in HIV-infected patients, testosterone has been found to help prevent loss of lean body and muscle mass. Whether the combination of exercise and testosterone is more effective in preventing loss of lean body mass than either therapy alone is not yet clear and warrants further study. In addition to its effects on body composition, testosterone treatment results in improved mood and libido in HIV-infected women and increased bone mineral density in HIV-infected men. Testosterone may thus make a valuable contribution to the treatment of HIV-infected individuals. International Journal of Impotence Research (2003) 15, Suppl 4, S21-S25. doi:10.1038/sj.ijir.3901032

Clinical review 138: Anabolic-androgenic steroid therapy in the treatment of chronic diseases.

The purpose of this study was to review the preclinical and clinical literature relevant to the efficacy and safety of anabolic androgen steroid therapy for palliative treatment of severe weight loss associated with chronic diseases. Data sources were published literature identified from the Medline database from January 1966 to December 2000, bibliographic references, and textbooks. Reports from preclinical and clinical trials were selected. Study designs and results were extracted from trial reports. Statistical evaluation or meta-analysis of combined results was not attempted. Androgenic anabolic steroids (AAS) are widely prescribed for the treatment of male hypogonadism; however, they may play a significant role in the treatment of other conditions as well, such as cachexia associated with human immunodeficiency virus, cancer, burns, renal and hepatic failure, and anemia associated with leukemia or kidney failure. A review of the anabolic effects of androgens and their efficacy in the treatment of these conditions is provided. In addition, the numerous and sometimes serious side effects that have been known to occur with androgen use are reviewed. Although the threat of various side effects is present, AAS therapy appears to have a favorable anabolic effect on patients with chronic diseases and muscle catabolism. We recommend that AAS can be used for the treatment of patients with acquired immunodeficiency syndrome wasting and in severely catabolic patients with severe burns. Preliminary data in renal failure-associated wasting are also positive. Advantages and disadvantages should be weighed carefully when comparing AAS therapy to other weight-gaining measures. Although a conservative approach to the use of AAS in patients with chronic diseases is still recommended, the utility of AAS therapy in the attenuation of severe weight loss associated with disease states such as cancer, postoperative recovery, and wasting due to pulmonary and hepatic disease should be more thoroughly investigated.

Post-menopausal hormone therapy and concentrations of protein C and antithrombin in elderly women.

The effects of post-menopausal hormone therapy (HRT) on blood coagulation in elderly women are not well defined. We studied associations of HRT use with levels of natural anticoagulant proteins in a cross-sectional study of 3393 women > or = 65 years of age participating in the Cardiovascular Health Study. Protein C antigen and antithrombin were measured in all users (n = 230 unopposed oestrogen; 60 oestrogen/progestin) and a comparison group of 196 age- and race-matched non-users. Compared with non-users, oestrogen use was associated with higher protein C (4.80 vs. 4.30 microg/ml, P < 0.01). Results were similar for oestrogen/progestin (P > 0.05). In both user groups, antithrombin was lower than in non-users (109% for each vs. 115% in non-users, P < 0.001). Adjustment for factors related to prescription of HRT and to anticoagulant protein levels had little impact on the results. For antithrombin, associations with HRT were larger for thinner Caucasian women and black women. Venous thrombosis from HRT may be mediated partly by alterations in antithrombin, but not protein C concentrations. This study extends previous observations to older women, the group at highest risk of venous thromboembolism. Studies of HRT-induced alterations in anticoagulant function in relation to the occurrence of thrombosis with HRT are required.