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Summary: Background: Cancer-induced muscle wasting begins early in the course of a patient's malignant disease, resulting in declining physical function and other detrimental clinical consequences. This randomised, double-blind, placebo-controlled phase 2 trial assessed the efficacy and safety of enobosarm, a selective androgen receptor modulator, in patients with cancer. Methods: We enrolled male (>45 years) and female (postmenopausal) patients with cancer who were not obese and who had at least 2% weight loss in the previous 6 months. Participants were randomly assigned (1:1:1 ratio, by computer generated list, block size three, stratified by cancer type) to receive once-daily oral enobosarm 1 mg, 3 mg, or placebo for up to 113 days at US and Argentinian oncology clinics. The sponsor, study personnel, and participants were masked to assignment. The primary endpoint was change in total lean body mass from baseline, assessed by dual-energy x-ray absorptiometry. Efficacy analyses were done only in patients who had a baseline and an on-treatment assessment in the protocol-specified window of within 10 days before baseline or first study drug, and within 10 days of day 113 or end of study (evaluable efficacy population). Adverse events and other safety measurements were assessed in the intention-to-treat (safety) population. This trial is registered with ClinicalTrials.gov, number NCT00467844. Findings: Enrolment started on July 3, 2007, and the last patient completed the trial on Aug 1, 2008. 159 patients were analysed for safety (placebo, n=52; enobosarm 1 mg, n=53; enobosarm 3 mg, n=54). The evaluable efficacy population included 100 participants (placebo, n=34; enobosarm 1 mg, n=32; enobosarm 3 mg, n=34). Compared with baseline, significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups (enobosarm 1 mg median 1·5 kg, range −2·1 to 12·6, p=0·0012; enodosarm 3 mg 1·0 kg, −4·8 to 11·5, p=0·046). Change in total lean body mass within the placebo group (median 0·02 kg, range −5·8 to 6·7) was not significant (p=0·88). The most common serious adverse events were malignant neoplasm progression (eight of 52 [15%] with placebo vs five of 53 [9%] with enobosarm 1 mg vs seven of 54 [13%] with enobosarm 3 mg), pneumonia (two [4%] vs two [4%] vs three [6%]), and febrile neutropenia (three [6%vs one [2%] vs none). None of these events were deemed related to study drug. Interpretation: Cancer cachexia is an unmet medical need and our data suggest that use of enobosarm might lead to improvements in lean body mass, without the toxic effects associated with androgens and progestational agents. Funding: GTx. [ABSTRACT FROM AUTHOR]

Summary: Background: Osteoporosis is common in advanced COPD and worsens rapidly after transplantation, potentially impairing quality of life. Increased high density lipoprotein cholesterol (HDLc) has been observed in COPD and linked with osteoporosis in the general population. This association has not been previously examined in COPD. Methods: We reviewed the records of 245 COPD patients referred for lung transplant evaluation. Osteoporosis was defined by either dual energy X-ray absorptiometry scan or use of osteoporosis medications. The presence or absence of osteoporosis could be ascertained in 152 subjects. Cholesterol values and other clinical variables were assessed for their association with osteoporosis. Results: Clinical factors associated with osteoporosis included lower BMI [OR 0.81, 95% CI 0.73–0.90], higher HDLc [OR 1.04, 95% CI 1.02 to 1.07], and worse lung function. HDLc was an independent predictor of OP and demonstrated an inverse linear correlation with T-scores (r = −0.21, p = 0.05), which was stronger amongst males (r = −0.45, p = 0.004). Conclusion: In COPD patients referred for lung transplantation, osteoporosis is highly prevalent. Raised HDLc levels are common in this group and are independently associated with OP. [Copyright &y& Elsevier]

Abstract: A reduced concentration of serum testosterone resulting in male hypogonadism is a well described endocrine abnormality associated with classical signs and symptoms. This manuscript presents one such patient. However, low serum testosterone is being recognized more commonly associated with aging and chronic disease. It is in this situation in which the signs and symptoms of male hypogonadism can be subtle and non-specific. This manuscript reviews examples of such situations and highlights our need to have a reliable and accurate measure of serum testosterone. Both clinicians and researchers need better assays to better understand basic mechanisms, diagnose, treat, and monitor men with testosterone deficiency. [Copyright &y& Elsevier]

Abstract: Background: Most studies of hypothalamic-pituitary-gonadal (HPG) function in illicit drug users either focus on men or do not consider the impact of HIV. Objective: This study investigated the relationships between cocaine and/or opiate use, HIV status, and HPG function in both men and women. Methods: Men and women between 18 and 50 years of age were stratified by sex, drug use, and HIV status. Information on demographics, HIV disease and treatment, and illicit drug use patterns was collected. To determine potential effects on HPG function, free testosterone (free T), estradiol, and gonadotropin concentrations were measured. Results: In a total of 197 men and women, free T concentrations were lower in men who used cocaine and/or opiates and in women infected with HIV Gonadotropin concentrations were elevated in seropositive men only. In women who received highly active antiretroviral therapy, HIV infection and illicit drug use had an additive or synergistic impact on free T concentrations. Conclusions: Our data reveal the importance of considering the independent effects of illicit drug use and HIV status for both men and women, so that risks may be identified and potential treatments designed for HPG dysfunction in these groups. [Copyright &y& Elsevier]

Recently, interest has grown in the use of androgen replacement therapy for postmenopausal women. Androgen replacement in women improves libido, bone density, and body composition. The adverse effects, like hirsutism, are generally mild, and the safety profile of transdermal testosterone replacement is more favorable than that of other modes of androgen therapy. Further studies may help to determine the effect of lipid changes on cardiac outcomes. We believe that long-term studies are necessary to observe the potential effect of androgen replacement on cardiovascular mortality, breast and endometrial tissues, and mood and anger before this therapy can be used routinely in women. [ABSTRACT FROM AUTHOR]

Presents a randomized, multicenter, double-blind parallel-group study to evaluate the lipid-altering efficacy and safety of simvastatin 80/mg/day. Administration of a lipid-lowering diet and simvastatin to hypercholesterolemic patients in the United States; National Cholesterol Education Program low-density lipoprotein (LDL) cholesterol criteria for pharmacologic treatment.

The relation between insulin resistance (IR) and coronary artery disease in patients with human immunodeficiency virus (HIV) infection remains incompletely defined. Fasting serum insulin and glucose measurements from 448 HIV-infected and 306 uninfected men enrolled in the Multicenter AIDS Cohort Study were collected at semiannual visits from 2003 to 2013 and used to compute the homeostatic model assessment of IR (HOMA-IR). Coronary computed tomographic angiography (CTA) was performed at the end of the study period to characterize coronary pathology. Associations between HOMA-IR (categorized into tertiles and assessed near the time of the CTA and over the 10-year study period) and the prevalence of coronary plaque or stenosis ≥50% were assessed with multivariate logistic regression. HOMA-IR was higher in HIV-infected men than HIV-uninfected men when measured near the time of CTA (3.2 vs 2.7, p = 0.002) and when averaged over the study period (3.4 vs 3.0, p <0.001). The prevalence of coronary stenosis ≥50% was similar between both groups (17% vs 15%, p = 0.41). Both measurements of HOMA-IR were associated with greater odds of coronary stenosis ≥50% in models comparing men with values in the highest versus the lowest tertiles, although the effect of mean HOMA-IR was stronger than the single measurement of HOMA-IR before CTA (odds ratio 2.46, 95% CI 1.95 to 3.11, vs odds ratio 1.43, 1.20 to 1.70). This effect was not significantly modified by HIV serostatus. In conclusion, IR over nearly a decade was greater in HIV-infected men than HIV-uninfected men, and in both groups, was associated with significant coronary artery stenosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hypogonadism is common with opiate-like drug use and may contribute to cognitive abnormalities. With the increasing epidemic of HIV and substance use (SU) worldwide, it is important to understand the impact of these conditions on cognition, which may affect quality of life and possibly decrease adherence to treatment. We hypothesized that men with SU, by virtue of hypogonadism secondary to HIV and/or SU, may demonstrate impaired cognition. Methods: We recruited men aged 18–50 from a population of low income, inner-city individuals. Details of HIV and SU status, serum blood levels of total testosterone (TT), free testosterone (FT) and estradiol (E2) were assessed. All subjects were administered ten neuropsychological tests. Results: Our sample consisted of 68 men (mean age: 43.2 years (SD 5.8), African Americans: 86.6%). The recruited population was primarily from low socioeconomic status and unemployed. The mean level of TT was 553.9ng/dL (SD 262.0), the mean level of FT was 69.5pg/mL (SD 34.8), mean E2 was 3.2pg/mL (SD 4.4). We found that 30.9% were hypogonadal and it was associated with higher SU. We observed some relationships between sex hormones and cognitive domains, however, after adjustment for age, drug use category, education, depression, HIV, there was no statistically significant correlation between cognitive performance and sex hormone levels. Conclusions: In this cross-sectional study of men with a high prevalence of SU and hypogonadism, endogenous levels of TT, FT or E2 were not related to cognitive performance. Other factors need to be identified which may contribute to poor cognitive function in the setting of SU. [Copyright &y& Elsevier]

Summary: Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender. [Copyright &y& Elsevier]

Up to 75% of hip fracture patients never recover to their pre-fracture functional status. Supervised exercise that includes strength training can improve functional recovery after hip fracture. The role of testosterone replacement for augmenting the effects of exercise in older women after hip fracture is unknown. The Starting Testosterone and Exercise after Hip Injury (STEP-HI) Study is a 6-month Phase 3 multicenter randomized placebo-controlled trial designed to compare supervised exercise (EX) plus 1% testosterone topical gel, with EX plus placebo gel, and with enhanced usual care (EUC). Female hip fracture patients age ≥ 65 years are being recruited from clinical centers across the United States. Participants are community dwelling and enrolled within 24 weeks after surgical repair of the fracture. The EX intervention is a center-based program of progressive resistance training. The EUC group receives a home exercise program and health education. Participants receive dietary counseling, calcium and vitamin D. The primary outcome is the Six Minute Walk Distance. Secondary outcomes include physical performance measures, self-reported function and quality of life, and dual energy x-ray absorptiometry measures of body composition and bone mineral density. Enrollment, interventions, and follow-up are ongoing. We describe the impact of the coronavirus disease 2019 pandemic on the trial, including modifications made to allow continuation of the interventions and outcome data collection using remote video and audio technology. Results from the STEP-HI study are expected to have important clinical and public health implications for management of the growing population of hip fracture patients. • Hip fractures in older women are a major public health problem of increasing magnitude. • Most patients do not reach their pre-fracture mobility status after successful surgical repair of a hip fracture. • Exercise can improve physical function after hip fracture surgery. • Testosterone replacement can augment the effects of exercise but its efficacy is unknown in older women with hip fracture. • Topical testosterone plus high-intensity exercise may improve strength and physical function in women after hip fracture. • RRe Results of the STEP-HI study may help to guide decisions on therapies to improve outcomes after hip fracture in older women. [ABSTRACT FROM AUTHOR]