A randomized, placebo-controlled trial of nandrolone decanoate in human immunodeficiency virus-infected men with mild to moderate weight loss with recombinant human growth hormone as active reference treatment

OBJECTIVE: We compared the effectiveness of a biweekly regimen of 150 mg nandrolone with placebo in HIV-infected men with mild to moderate weight loss and contrasted its effects against a Food and Drug Administration-approved regimen of recombinant human (rh)GH. METHODS: In this placebo-controlled, randomized, 12-wk trial, placebo and nandrolone (150 mg im biweekly) were administered double blind, and rhGH (6 mg sc daily) was administered in an open-label manner. Participants were HIV-infected men with 5-15% weight loss over 6 months and on stable antiretroviral therapy for more than 12 wk. Lean body mass (LBM), muscle performance, physical function, endurance, hormone levels, insulin sensitivity, sexual function, quality of life, and appetite were assessed at baseline and after 12 wk. RESULTS: Nandrolone administration was associated with a greater increase in LBM (+1.6 +/- 0.3 kg) by dual-energy x-ray absorptiometry scan than placebo (+0.4 +/- 0.3 kg; P < 0.05); however, the change in LBMs with nandrolone was not significantly different from rhGH (+2.5 +/- 0.3 kg). Nandrolone administration was also associated with significantly greater gains in fat-free mass (+1.6 +/- 0.3 kg), body cell mass (+1.0 +/- 0.2 kg), and intracellular water (+0.9 +/- 0.2 kg) than placebo; these changes in the nandrolone group were not significantly different from the rhGH group. rhGH administration was associated with greater loss of whole body fat mass and higher frequency of drug-related adverse effects and treatment discontinuations than nandrolone and placebo and a greater increase in extracellular water than nandrolone. Nandrolone treatment was associated with greater improvements in perception of health than rhGH and sexual function than placebo. The cachexia/anorexia scores, health care resource use, and insulin sensitivity did not significantly change. CONCLUSION: We conclude that nandrolone is superior to placebo and not significantly different from a Food and Drug Administration-approved regimen of rhGH in improving lean body mass in HIV-infected men with mild to moderate weight loss.     

Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis

Many HIV patients develop weight loss, which increases morbidity and mortality. We aimed to assess the effects of testosterone therapy on lean body mass, total body weight, over-all exercise functional capacity, and perceived quality of life in patients with HIV wasting syndrome and its adverse effects. We systematically reviewed randomised, placebo-controlled trials that compared the effects of testosterone therapy with placebo in HIV patients with wasting. Eight trials met the inclusion criteria and 417 randomised patients were included. Only six trials used lean-body mass, fat-free mass, or body-cell mass as outcome measures. The meta-analysis of the six trials showed a difference in the lean body mass between the testosterone group and placebo group of 1.22 kg (95% CI 0.23-2.22) for the random effect model and 0.51 kg (0.09-0.93) for fixed effect. However, the difference was much greater in the three trials that used the intramuscular route-3.34 kg in the post-hoc analysis. All eight trials included total body weight as an outcome measure, the meta-analysis of which showed a difference of 1.04 kg (-0.01-2.10) between testosterone group and placebo group by random effect and 0.63 kg (-0.01-1.28) for fixed effect models. Over-all, the incidence of adverse effects is similar in both groups. Testosterone therapy has been shown in this review to increase lean body mass more than placebo. The increase is even greater if the therapy is given intramuscularly. There is also a small positive effect in total body weight. The study is, however, limited by the small numbers and heterogeneity of the population, which potentially introduced bias into the methods and results. Testosterone therapy may be considered in patients with HIV wasting syndrome to reverse muscle loss, but there is a concern about the adverse metabolic effects of long-term testosterone administration and long-term follow-up for these patients is needed.     

Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment

Long-term glucocorticoid therapy in men is associated with loss of bone and muscle mass as well as a decrease in serum testosterone. We tested the effect of two androgens, testosterone and its minimally aromatizable analog nandrolone, on muscle mass (dual x-ray absorptiometry), muscle strength (knee flexion and extension by isokinetic dynamometry), bone mineral density (BMD), and quality of life (Qualeffo-41 questionnaire) in 51 men on a mean daily prednisone dose of 12.6 +/- 2.2 mg. Men were randomized, double blind, to testosterone (200 mg mixed esters), nandrolone decanoate (200 mg), or placebo given every fortnight by im injection for 12 months. At 12 months, both androgens increased muscle mass (mean change from baseline +3.5%, +5.8%, and -0.9% in testosterone, nandrolone, and placebo groups, respectively, P < 0.0001) and muscle strength (P < 0.05). Lumbar spine BMD increased significantly only in men treated with testosterone (4.7 +/- 1.1%, P < 0.01). There was no significant change in hip or total body BMD. Testosterone, but not nandrolone or placebo, improved overall quality of life (P < 0.001). These results suggest that androgen therapy may have a role in ameliorating adverse effects of glucocorticoid therapy such as muscle and bone loss and aromatization is necessary for androgen action on bone but not on muscle.     

Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: a randomized, double-blind, placebo-controlled, multicenter trial

BACKGROUND: Weight loss is associated with accelerated mortality and disease progression in patients with human immunodeficiency virus (HIV) infection. Although studies have examined a variety of anabolic therapies in HIV-infected men, the safety and efficacy of such treatments in women have not been adequately studied. METHODS: In this randomized, double-blind, placebo-controlled, multicenter, phase I/II study, 38 HIV-infected women with documented weight loss of 5% or greater in the preceding year or a body mass index of less than 20 kg/m(2) were randomized to receive nandrolone decanoate (100 mg) or an equivalent volume of placebo every other week by intramuscular injection. Subjects received blinded treatment for 12 weeks, followed by open-label therapy for 12 weeks. Lean body mass and fat (bioelectrical impedance analysis) and weight were measured at baseline and at weeks 6, 12, 18, and 24. Biochemical assessments of safety (hematologic analyses, liver function tests, and sex hormone measurements) were performed at these same time points. Clinical signs and symptoms were monitored biweekly. RESULTS: Subjects randomized to receive nandrolone had significant increases in weight and lean body mass during blinded treatment (4.6 kg [9.0%] and 3.5 kg [8.6%], respectively; P<.001 vs baseline and placebo in each case). Fat mass did not change statistically significantly in either group. Although there were no statistically significant differences between groups in biochemical measures, the number of grade 3 or greater toxicities, or reports of virilizing effects, a full assessment of safety cannot be made in a trial of this size. CONCLUSION: Nandrolone decanoate therapy may prove to be generally safe and beneficial in reversing weight loss and lean tissue loss in women with HIV infection and other chronic catabolic diseases.     

Anabolic steroids in COPD: a review and preliminary results of a randomized trial

Patients with severe chronic obstructive pulmonary disease (COPD) commonly develop weight loss, muscle wasting, and consequently poor survival. Nutritional supplementation and anabolic steroids increase lean body mass, improve muscle strength, and survival in patients enrolled in comprehensive rehabilitation programs. Whether anabolic steroids are effective outside an intensive rehabilitation program is not known. We conducted a prospective, double-blind, placebo-controlled, 16-week trial to study the benefits of anabolic steroids in patients with severe COPD who did not participate in a structured rehabilitation program. Biweekly intramuscular injections of either the drug (nandrolone decanoate) or placebo were administered. Sixteen patients with severe COPD were randomized to either placebo or nandrolone decanoate. The placebo group weighed 55.32 +/- 11.33 kg at baseline and 54.15 +/- 10.80 kg at 16 weeks; the treatment group weighed 68.80 +/- 6.58 at baseline and 67.92 +/- 6.73 at 16 weeks. Lean body mass remained unchanged, 71 +/- 6 vs. 71 +/- 7 kg in placebo group and 67 +/- 7 vs. 67 +/- 7 in treatment group, at baseline and 16 weeks respectively. The distance walked on 6 min was unchanged at baseline, 8 weeks, and 16 weeks in placebo (291.17 +/- 134.83, 282.42 +/- 115.39, 286.00 +/- 82.63 m) and treatment groups (336.13 +/- 127.59, 364.83 +/- 146.99, 327.00 +/- 173.73 m). No improvement occurred in forced expiratory volume in one second, forced vital capacity, maximal inspiratory pressure, maximal expiratory pressure, VO(2) max or 6-min walk distance or health related quality of life. Administration of anabolic steroids (nandrolone decanoate) outside a dedicated rehabilitation program did not lead to either weight gain, improvement in physiological function, or better quality of life in patients with severe COPD.     

Monitoring changes in fat-free mass in HIV-positive men with hypotestosteronemia and AIDS wasting syndrome treated with gonadal hormone replacement therapy

OBJECTIVE: To compare methods for assessing changes in body composition during gonadal hormone replacement therapy in a group of HIV-positive men with AIDS wasting syndrome. DESIGN: The study included a 21-day, double-blind, randomized, placebo-controlled inpatient intervention and a 12-week open-label intervention. The inpatient intervention included 18 men who were confined to a metabolic ward. Days 1-7 comprised weight stabilization and body composition measures followed by 14 days of nandrolone decanoate at either 65 or 195 mg weekly, or placebo, and repeat testing. The open-label intervention comprised 12 weeks of 200 mg nandrolone decanoate fortnightly with measurements of fat-free mass at 6 and 12 weeks. METHODS: The inpatient intervention measured nitrogen balance from 24 h urine and fecal collections and fat-free mass by dual energy x-ray absorptiometry (DEXA), bioimpedance spectroscopy (BIS) and D2O dilution. Nitrogen balance was calculated as the difference between dietary intake and urinary and fecal nitrogen excretion. Nitrogen was converted to fat-free mass using the constant of 32.5 g. Repeated measures analysis of variance was used to determine which methods were significantly different from the reference nitrogen balance technique. RESULTS: Nitrogen accretion of lean tissue was 0.55 and 0.85 kg weekly for low and high-dose groups, respectively. Estimated nitrogen retention during the open-label study was 0.42 kg weekly. Body weight increased with the estimated lean tissue accretion. DEXA, BIS and D2O methods demonstrated improvements in fat-free mass, although the BIS estimate of fat-free mass most closely matched the results of the nitrogen retention method. CONCLUSION: DEXA, BIS and D2O techniques demonstrated increases in fat-free mass. The BIS method is less costly, more convenient to use, and had results that more closely matched those from nitrogen balance and retention methods. BIS may be the preferred method to monitor changes in fat-free mass in AIDS patients and patients with malnutrition.     

The use of a transscrotal testosterone delivery system in the treatment of patients with weight loss related to human immunodeficiency virus infection.

PURPOSE: Weight loss is a strong predictor of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. Men with acquired immunodeficiency syndrome (AIDS) lose body cell mass. Hypogonadism is also common. This study tested the efficacy of a testosterone transscrotal patch (6 mg/day) in improving body cell mass and treating hypogonadism in these patients. SUBJECTS AND METHODS: This multicenter, randomized, double-blinded, placebo-controlled trial was conducted from August 1995 to October 1996 in 133 men, 18 years of age and older, who had AIDS, 5% to 20% weight loss, and either a low morning serum total testosterone level (<400 ng/dL) or a low free testosterone level (<16 pg/mL). Outcomes included weight, body cell mass as measured using bioelectrical impedance analysis, quality of life, and morning measurements of serum testosterone and dihydrotestosterone levels, lymphocyte subsets, and HIV quantification. RESULTS: There were no significant differences in baseline weight, CD4 cell counts, or HIV serum viral quantification between treatment arms. Morning total and free testosterone levels increased in those treated with testosterone, but not with placebo. Following 12 weeks of treatment there were no differences (testosterone-placebo) in mean weight change (-0.3 kg [95% confidence interval (CI): -1.4 to 0.8]) or body cell mass (-0.2 kg [95% CI: -1.0 to 0.6]) in the two groups. There were also no changes in quality of life in either group. CONCLUSION: Hypogonadal men with AIDS and weight loss can achieve adequate morning serum sex hormone levels using a transscrotal testosterone patch. However, this system of replacement does not improve weight, body cell mass, or quality of life.     

Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss

The objective of this study was to determine whether physiological testosterone replacement increases fat-free mass (FFM) and muscle strength and contributes to weight maintenance in HIV-infected women with relative androgen deficiency and weight loss. Fifty-two HIV-infected, medically stable women, 18-50 yr of age, with more than 5% weight loss over 6 months and testosterone levels below 33 ng/dl were randomized into this double-blind, placebo-controlled trial of 24-wk duration. Subjects in the testosterone group applied testosterone patches twice weekly to achieve a nominal delivery of 300 mug testosterone over 24 h. Data were evaluable for 44 women. Serum average total and peak testosterone levels increased significantly in the testosterone group, but did not change in the placebo group. However, there were no significant changes in FFM (testosterone, 0.7 +/- 0.4 kg; placebo, 0.3 +/- 0.4 kg), fat mass (testosterone, 0.3 +/- 0.7 kg; placebo, 0.6 +/- 0.7 kg), or body weight (testosterone, 1.0 +/- 0.9 kg; placebo, 0.9 +/- 0.8 kg) between the two treatment groups. There were no significant changes in leg press strength, leg power, or muscle fatigability in either group. Changes in quality of life, sexual function, cognitive function, and Karnofsky performance scores did not differ significantly between the two groups. High-density lipoprotein cholesterol levels decreased significantly in the testosterone group. The patches were well tolerated. We conclude that physiological testosterone replacement was safe and effective in raising testosterone levels into the mid to high normal range, but did not significantly increase FFM, body weight, or muscle performance in HIV-infected women with low testosterone levels and mild weight loss. Additional studies are needed to fully explore the role of androgens in the regulation of body composition in women.     

Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus

This nonplacebo-controlled, open label, randomized study was conducted to test the hypotheses that pharmacological doses of nandrolone decanoate would increase lean body tissue, muscle mass, and strength in immunodeficient human immunodeficiency virus-infected men, and that these effects would be enhanced with progressive resistance training (PRT). Thirty human immunodeficiency virus-positive men with fewer than 400 CD4 lymphocytes/mm3 were randomly assigned to receive weekly injections of nandrolone alone or in combination with supervised PRT at 80% of the one-repetition maximum three times weekly for 12 weeks. Total body weight increased significantly in both groups (3.2 +/- 2.7 and 4.0 +/- 2.0 kg, respectively; P < 0.001), with increases due primarily to augmentation of lean tissue. Lean body mass determined by dual energy x-ray absorptiometry increased significantly more in the PRT group (3.9 +/- 2.3 vs. 5.2 +/- 5.7 kg, respectively; P = 0.03). Body cell mass by bioelectrical impedance analysis increased significantly (P < 0.001) in both groups (2.6 +/- 1.0 vs. 2.9 +/- 0.8 kg), but to a similar magnitude (P = NS). Significant increases in cross-sectional area by magnetic resonance imaging of total thigh muscles (1538 +/- 767 and 1480 +/- 532 mm2), quadriceps (705 +/- 365 and 717 +/- 288 mm2), and hamstrings (842 +/- 409 and 771 +/- 295 mm2) occurred with both treatment strategies (P < 0.001 for the three muscle areas); these increases were similar in both groups (P = NS). By the one-repetition method, strength increased in both upper and lower body exercises, with gains ranging from 10.3-31% in the nandrolone group and from 14.4-53.0% in the PRT group (P < 0.006 with one exception). Gains in strength were of significantly greater magnitude in the PRT group (P < or = 0.005 for all comparisons), even after correction for lean body mass. Thus, pharmacological doses of nandrolone decanoate yielded significant gains in total weight, lean body mass, body cell mass, muscle size, and strength. The increases in lean body mass and muscular strength were significantly augmented with PRT.     

Front Cover

Aim

Use of sodium-glucose co-transporter-2 inhibitors (SGLT2is) for glycaemic control is increasing in individuals with type 2 diabetes (T2D) for their additional benefits on heart failure and chronic kidney disease. However, SGLT2is generally reduce body weight, which might promote sarcopenia in older individuals. We evaluated the effects of the SGLT2i empagliflozin on muscle mass and strength in addition to glucose control in elderly adults with T2D.

Materials and Methods

Individuals with T2D aged ≥65 years with body mass index ≥22 kg/m² and glycated haemoglobin (HbA1c) 7.0%-10.0% were randomized 1:1 to once-daily empagliflozin 10 mg or placebo for 52 weeks. The primary endpoint was change from baseline in HbA1c at week 52. Secondary endpoints included changes from baseline in muscle mass and strength.

Results

Of the 129 individuals randomized, 72.4% were men, mean age 74.1 years, body mass index 25.6 kg/m² and HbA1c 7.6%. The placebo-adjusted mean change from baseline in HbA1c at week 52 with empagliflozin was −0.57% [95% confidence interval (CI) −0.78, −0.36]. Change in body weight was −3.26 kg and −0.90 kg with empagliflozin and placebo, respectively (placebo-adjusted difference: −2.37 kg; 95% CI −3.07, −1.68). Placebo-adjusted change in muscle mass was −0.61 kg (95% CI −1.61, 0.39), fat mass −1.84 kg (95% CI −2.65, −1.04) and grip strength −0.3 kg (95% CI −1.1, 0.5).

Conclusions

Empagliflozin improved glucose control and reduced body weight without compromising muscle mass or strength in elderly adults with T2D in this trial.     

Motivational interviewing to improve weight loss in overweight and/or obese patients: a systematic review and meta‐analysis of randomized controlled trials

Motivational interviewing, a directive, patient‐centred counselling approach focused on exploring and resolving ambivalence, has emerged as an effective therapeutic approach within the addictions field. However, the effectiveness of motivational interviewing in weight‐loss interventions is unclear. Electronic databases were systematically searched for randomized controlled trials evaluating behaviour change interventions using motivational interviewing in overweight or obese adults. Standardized mean difference (SMD) for change in body mass, reported as either body mass index (BMI; kg m^?2) or body weight (kg), was the primary outcome, with weighted mean difference (WMD) for change in body weight and BMI as secondary outcomes. The search strategy yielded 3540 citations and of the 101 potentially relevant studies, 12 met the inclusion criteria and 11 were included for meta‐analysis. Motivational interviewing was associated with a greater reduction in body mass compared to controls (SMD = ?0.51 [95% CI ?1.04, 0.01]). There was a significant reduction in body weight (kg) for those in the intervention group compared with those in the control group (WMD = ?1.47 kg [95% CI ?2.05, ?0.88]). For the BMI outcome, the WMD was ?0.25 kg m^?2 (95% CI ?0.50, 0.01). Motivational interviewing appears to enhance weight loss in overweight and obese patients.     

Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes

Aim: To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [haemoglobin A_1c (HbA_1c) 7–11%] on metformin monotherapy. Methods: Patients (n = 273) on metformin (≥1500 mg/day) were randomized to receive the addition of once‐daily placebo, sitagliptin 100 mg or rosiglitazone 8 mg in a 1 : 1 : 1 ratio for 18 weeks. The efficacy analysis was based on the all‐patients‐treated population using an analysis of co‐variance with change in HbA_1c from baseline as the primary endpoint. Results: The mean baseline HbA_1c was 7.7% for the entire cohort. After 18 weeks, both active add‐on therapies led to greater improvements in HbA_1c from baseline: ?0.73% for sitagliptin (p < 0.001 vs. placebo) and ?0.79% for rosiglitazone compared with ?0.22% for placebo. No difference was observed between the sitagliptin and rosiglitazone treatments (0.06% [95% confidence interval (CI): ?0.14 to 0.25]). The proportion of patients achieving an HbA_1c < 7% was greater with sitagliptin (55%) and rosiglitazone (63%) compared with placebo (38%). Body weight increased from baseline with rosiglitazone (1.5 kg) compared with body weight reduction with sitagliptin (?0.4 kg) and placebo (?0.8 kg). The difference in body weight between the sitagliptin and rosiglitazone groups was 1.9 kg (95% CI: 1.3–2.5). In a prespecified analysis, the proportion of patients experiencing a greater than 3‐kg increase in body weight was 21% in the rosiglitazone group compared with 2% in both the sitagliptin and placebo groups. Both active treatments were generally well tolerated, with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo. Conclusions: In this 18‐week study, the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Treatment with sitagliptin produced similar reductions in HbA_1c compared with the addition of rosiglitazone.     

Effect of orlistat treatment on body composition and resting energy expenditure during a two-year weight-reduction programme in obese Finns

OBJECTIVE: To examine the effect of orlistat (Xenical) treatment on body composition and resting energy expenditure (REE) during a 2 y weight-reduction programme in obese Finns. SUBJECTS: Of initially 96 obese subjects who participated in the weight-reduction programme, those 72 subjects (13 men, 59 women, body mass index (BMI) 35.9 +/- 3.9 kg/m2, age 43.4 +/- 6.0 y, mean +/- s.d.) with the complete set of data for 2 y were included in the study. DESIGN: After a 4-week lead-in period, subjects were randomized with either orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a mildly hypoenergetic balanced diet for 1 y. This was followed by 1 y double-blind period with the subjects within each treatment group re-assigned to receive orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a weight maintenance diet. MEASUREMENTS: Body composition and REE were measured after an overnight fast by a bioelectrical impedance method and indirect calorimeter, respectively. The measurements were performed at the beginning and at 3, 6, 12 and 24 months. RESULTS: During the first year, the orlistat-treated group had greater reduction of body weight and fat mass but not of fat-free mass or REE as compared to placebo. During the second year, orlistat treatment was associated with smaller regain of body weight and fat mass with no significant differences in the changes of fat-free mass or REE as compared to placebo. CONCLUSION: In addition to better weight loss and maintenance of reduced weight, orlistat treatment is associated with beneficial changes in body composition but with no excess decrease in resting energy expenditure as compared to that achieved during placebo with a dietary therapy alone.     

Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors

Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo, although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients. At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy. Therapy for hypertension continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly greater weight loss compared with placebo: 4.5 kg with sibutramine compared with 0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their body weight compared with six patients (8.3%) treated with placebo; 19 patients (13.1%) treated with sibutramine lost > or = 10% of their body weight compared with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both comparisons). Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment. After 52 weeks, the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF; P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo). The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points. Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated withdrawals from the study due to protocol-defined changes in BP were not statistically different between the two treatment groups. Greater favourable changes in lipid profile, serum glucose, and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group. Sibutramine was well tolerated. This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor, with or without concomitant thiazide diuretic therapy, sibutramine safely and effectively achieves weight loss without compromising good BP control.     

A systematic review on use of Chinese medicine and acupuncture for treatment of obesity

Obesity is a major health hazard and despite lifestyle modification, many patients frequently regain any lost body weight. The use of western anti‐obesity drugs has been limited by side effects including mood changes, suicidal thoughts, and gastrointestinal or cardiovascular complications. The effectiveness and safety of traditional Chinese medicine including Chinese herbal medicine (CHM) and acupuncture provide an alternative established therapy for this medical challenge. In this systematic review, we used standard methodologies to search, review, analyse and synthesize published data on the efficacy, safety and relapse of weight regain associated with use of CHM and acupuncture. We also examined the rationale, mechanisms and potential utility of these therapies. A total of 12 electronic databases, including Chinese, English, Korean and Japanese, were searched up to 28 February 2010. Randomized controlled trials (RCTs) for CHM and/or acupuncture with comparative controls were considered. We used the Jadad scale to assess methodological qualities, the random effect model in the pooled analysis of therapeutic efficacy to adjust for heterogeneity and funnel plots to explore publication bias. After screening 2,545 potential articles from the electronic databases, we identified 96 RCTs; comprising of 49 trials on CHM treatment, 44 trials on acupuncture treatment and 3 trials on combined therapy for appraisal. There were 4,861 subjects in the treatment groups and 3,821 in the control groups, with treatment duration ranging from 2 weeks to 4 months. Of the 77 publications written in Chinese, 75 had a Jadad score <3, while 16 of the 19 English publications had a Jadad score of >3. Efficacy was defined as body weight reduction ≥2 kg or body mass index (BMI) reduction ≥0.5 kg/m². Compared with placebo or lifestyle modification, CHM and acupuncture exhibited respective ‘risk ratio’ (RR) of 1.84 (95% CI: 1.37–2.46) and 2.14 (95% CI: 1.58–2.90) in favour of body weight reduction, with a mean difference in body weight reduction of 4.03 kg (95% CI: 2.22–5.85) and 2.76 kg (95% CI: 1.61–3.83) and a mean difference in BMI reduction of 1.32 kg m^–2 (95% CI: 0.78–1.85) and 2.02 kg m^–2 (95% CI: 0.94–3.10), respectively. Compared with the pharmacological treatments of sibutramine, fenfluramine or orlistat, CHM and acupuncture exhibited an RR of 1.11 (95% CI: 0.96–1.28) and 1.14 (95% CI: 1.03–1.25) in body weight reduction, mean difference in body weight reduction of 0.08 kg (95% CI: ?0.58 to 0.74) and 0.65 kg (95% CI: ?0.61 to 1.91), and mean difference in BMI reduction of 0.18 kg m^–2 (95% CI: ?0.39 to 0.75) and 0.83 kg m^–2 (95% CI: 0.29–1.37), respectively. There were fewer reports of adverse effects and relapses of weight regain in CHM intervention studies conducted in China than studies conducted outside China. CHM and acupuncture were more effective than placebo or lifestyle modification in reducing body weight. They had a similar efficacy as the Western anti‐obesity drugs but with fewer reported adverse effects. However, these conclusions were limited by small sample size and low quality of methodologies.     

A clinical trial of the use of sibutramine for the treatment of patients suffering essential obesity

OBJECTIVE: To evaluate the safety and efficacy of Sibutramine 10 mg per os, once a day in obese patients over a period of 6 months. DESIGN: A monocenter, double-blind, placebo-controlled, parallel, prospective clinical trial. SUBJECTS: 109 male and female obese patients (BMI>30 kg/m2) from 16 to 65 y entered the trial. MEASUREMENTS: Body weight, body mass index (BMI), waist and waist/hip ratio, medical history, assessment of hunger, satiety and diet compliance, standard laboratory assessments, blood pressure, heart rate and ECG. RESULTS: 40 out of 55 patients in the Sibutramine group and 44 out of 54 patients in the placebo group completed the trial. Using the method of last observation carried forward (LOCF), the weight loss in the Sibutramine group was 7.52 kg (95% confidence intervals (95% CI) 6.15; 8.9) and that in the placebo group was 3.56 kg (95% CI 2.41; 4.7). The BMI loss was 3.14 kg/m2 (95% CI 2.58; 3.69) in the Sibutramine group and 1.46 kg/m2 (95% CI 0.99; 1.93) in the placebo group. The waist reduction was 12. 51 cm (95% CI 9.25; 15.77) in the Sibutramine group and 3.26 cm (95% CI 1.38; 5.14) in the placebo group (P<0.05 by paired Student's t-test for all the intragroup comparisons). 32 Sibutramine patients had 45 adverse events, the most frequent adverse events in the Sibutramine group being dry mouth (n=19), increase in blood pressure (n=5), constipation (n=5) and tachycardia (n=5); 23 placebo patients had 29 adverse events, mainly increase in blood pressure (n=11) and dry mouth (n=10). Two Sibutramine patients withdrew from the trial due to adverse events. CONCLUSION: Sibutramine induces significant loss of body weight, BMI and waist, but does not significantly affect cardiovascular function. Sibutramine was well tolerated by most of the patients.     

The effect of tibolone on fat mass, fat-free mass, and total body water in postmenopausal women

Changes in body composition occur around the menopausal transition. The major characteristics are a decline in fat-free mass and an increase in body fat as a percentage of body weight. These alterations might be affected by age only or by menopause-related changes in hormone concentration. In this study the effects of tibolone, a tissue-specific compound with favorable effects on bone, vagina, and climacteric symptoms, were determined on body composition using bioelectrical impedance analysis. The focus was especially on fat mass, fat-free mass, and total body water in a group of 85 healthy women (mean +/- SD age, 54.2 +/- 4.7 yr), between 1-15 yr postmenopausal. Participants were randomly assigned to either tibolone (2.5 mg; n = 42) or identically appearing placebo tablets (n = 43) daily for 12 months. All analyses were based on the intent to treat group and last visit. Compared with placebo, tibolone significantly increased fat-free mass by 0.85 kg (P = 0.003) and total body water by 0.78 liter (P = 0.001). No significant difference was observed on the fat mass parameter (P = 0.16). From these results it can be concluded that tibolone may counteract the postmenopausal changes in body composition.     

Efficacy and safety of lorcaserin in obese adults: a meta‐analysis of 1‐year randomized controlled trials (RCTs) and narrative review on short‐term RCTs

Lorcaserin is a new anti‐obesity drug recently approved by US Food and Drug Administration. We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) to evaluate the association of lorcaserin therapy with weight loss and adverse events in obese adults (18–65 years old). Weight loss of 3.23 kg (95% confidence interval [CI]: 2.70, 3.75) and body mass index reduction of 1.16 kg m^?2 (95% CI: 0.98, 1.34) was observed compared with placebo in RCTs of 1 year duration. The use of lorcaserin for 8 and 12 weeks reduced weight of 1.60 kg (95% CI: 0.34, 2.86) and 2.9 kg (95% CI: 2.2, 3.5), respectively. In comparison to placebo, lorcaserin decreased waist circumference, blood pressure, total cholesterol, low‐density lipoprotein‐cholesterol and triglycerides, however did not statistically affect heart rate or high‐density lipoprotein‐cholesterol. Headache, nausea and dizziness were found to be significantly higher in the patients receiving lorcaserin than patients receiving placebo, whereas diarrhoea is no more likely than in patients receiving placebo. In conclusion, lorcaserin achieves modest weight loss and appears to be well tolerated. Clinical and pharmacovigilance studies with longer study duration are needed to inform of the long‐term efficacy and safety of lorcaserin.     

History of weight and obesity through life and risk of benign prostatic hyperplasia

OBJECTIVE: The relation of anthropometric measures, diabetes, hypertension and hyperlipidemia with benign prostatic hyperplasia (BPH) risk was investigated. DESIGN: Hospital-based case-control study. SUBJECTS: Cases were 1369 men with histologically confirmed BPH, and controls were 1451 men below 75 y, admitted to hospital for acute non-neoplastic diseases. MEASUREMENTS: Using a structured questionnaire, trained interviewers collected information on self-reported height and weight, and measured waist and hip circumference of patients. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models. RESULTS: Compared to the corresponding lowest quartile, the OR for the highest one were 0.76 (95% CI 0.59-0.98) for body weight, 0.71 (95% CI 0.54-0.94) for waist-to-hip ratio and 0.87 (95% CI 0.70-1.09) for body mass index (BMI, kg/m(2)). Compared to a lowest lifelong BMI <20.7 kg/m(2), the OR was 1.56 (95% CI 1.25-1.95) for a lowest lifelong BMI > or =23.7 kg/m(2). The OR was 0.74 (95% CI 0.60-0.93) for a lifelong increase of BMI > or =6.1 kg/m(2), compared to <1.6 kg/m(2). No association emerged for history of diabetes, hypertension and hyperlipidemia. CONCLUSIONS: Overweight was modestly, inversely related to BPH. The hypothesis of reduced testosterone levels in obese individuals may explain the different BPH risk and need to be tested.     

Effects of testosterone administration in human immunodeficiency virus-infected women with low weight: a randomized placebo-controlled study

BACKGROUND: The prevalence of human immunodeficiency virus (HIV) disease is increasing among women, many of whom remain symptomatic with low weight and poor functional status. Although androgen levels may often be reduced in such patients, the safety, tolerability, and efficacy of testosterone administration in this population remains unknown. METHODS: A total of 57 HIV-infected women with free testosterone levels less than the median of the reference range and weight less than 90% of ideal body weight or weight loss greater than 10% were randomly assigned to receive transdermal testosterone (4 mg/patch) twice weekly or placebo for 6 months. Muscle mass was assessed by urinary creatinine excretion. Muscle function was assessed by the Tufts Quantitative Muscle Function Test. Treatment effect at 6 months was determined by analysis of covariance. Results are mean +/- SEM unless otherwise specified. RESULTS: At baseline, subjects were low weight (body mass index [calculated as weight in kilograms divided by the square of height in meters] 20.6 +/- 0.4), with significant weight loss from pre-illness maximum weight (18.7% +/- 1.2%), and demonstrated reduced muscle function (upper and lower extremity muscle strength, 83% and 67%, respectively, of predicted range). Testosterone treatment resulted in significant increases in testosterone levels vs placebo (total testosterone: 37 +/- 5 vs -2 +/- 2 ng/dL [1.3 +/- 0.2 vs -0.1 +/- 0.1 nmol/L] [P<.001]; free testosterone: 3.7 +/- 0.5 vs -0.4 +/- 0.3 pg/mL [12.8 +/- 1.7 vs -1.4 vs 1.0 pmol/L] [P<.001]) and was well tolerated, without adverse effects on immune function, lipid and glucose levels, liver function, or body composition or the adverse effect of hirsutism. Muscle mass tended to increase (1.4 +/- 0.6 vs 0.3 +/- 0.8 kg; P =.08), and shoulder flexion (0.4 +/- 0.3 vs -0.5 +/- 0.3 kg; P =.02), elbow flexion (0.3 +/- 0.4 vs -0.7 +/- 0.4 kg; P =.04), knee extension (0.2 +/- 1.0 vs -1.7 +/- 1.3 kg; P =.02), and knee flexion (0.7 +/- 0.5 vs 0.3 +/- 0.7 kg; P =.04) increased in the testosterone-treated compared with the placebo-treated subjects. CONCLUSIONS: Testosterone administration is well-tolerated and increases muscle strength in low-weight HIV-infected women. Testosterone administration may be a useful adjunctive therapy to maintain muscle function in symptomatic HIV-infected women.