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Biomedical subjects

S Grinspoon

Publications and source records attributed to S Grinspoon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of total body potassium with other techniques for measuring lean body mass in men and women with AIDS wasting.

BACKGROUND: Lean body mass is an important predictor of survival and functional status in patients with AIDS wasting. The bias between different techniques for assessing body composition in AIDS wasting is not known. DESIGN: We compared total body potassium (TBK) with fat-free mass (FFM) determined by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and skinfold-thickness measurement (SKF) in 132 patients (63 men, 69 women) with AIDS wasting (weight < 90% of ideal body weight, or weight loss > 10% of original, or both). None of the subjects exhibited clinical lipodystrophy. Comparisons were made by using different BIA equations. RESULTS: Lean body mass determined by DXA was highly correlated with TBK in men (r = 0.79, P: < 0.0001) and women (r = 0.84, P: < 0.0001). FFM(BIA) and FFM(DXA) were significantly different (P: < 0.01 in men and P: < 0.0001 in women). The difference between FFM(DXA) and FFM(BIA) was significantly greater with greater weight and body fat, particularly in HIV-infected women (r = -0.39, P: = 0.001 for weight; r = -0.60, P: < 0.0001 for fat). The comparability of FFM and fat mass determined by DXA and BIA was dependent on the specific BIA equation used. Among men, no single BIA equation was more highly predictive of fat mass and FFM in comparison with DXA. CONCLUSIONS: The differences between DXA, BIA, and SKF in the determination of fat mass and FFM are significant in patients with AIDS wasting. BIA overestimates FFM compared with DXA in those with greater body fat. Standard BIA equations may not accurately estimate FFM and fat mass in men and women with AIDS wasting.

Absorptiometry, Photon↗
PubMed2000

Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men.

Hypogonadism is prevalent among human immunodeficiency virus-infected men, in whom significantly reduced quality of life and mood disturbances have been reported. Previous studies have not investigated the relationship between depression score and gonadal function among such patients. We first compared depression scores in hypogonadal (n = 52) and eugonadal (n = 10) patients with acquired immunodeficiency syndrome (AIDS) wasting, matched for weight and disease status, and then investigated the effects of testosterone administration on depression score in a randomized, double-blind, placebo-controlled study among the group of hypogonadal men with AIDS wasting. The primary end point in all comparisons was the Beck Depression Inventory. Hypogonadal patients demonstrated significantly increased scores on the Beck inventory compared with eugonadal-, age-, weight-, and disease status-matched subjects (15.5+/-1.1 vs. 10.6+/-1.4 mean +/- SEM, P = 0.02). Among the combined hypogonadal and eugonadal subjects, a significant inverse correlation was seen between the Beck score and both free (r = 0.41, P<0.01) and total serum testosterone levels (r = -0.43, P<0.001). The relationship between the Beck score and testosterone levels remained highly significant, controlling for weight, viral load, CD4 count, and antidepressant use (P<0.01 for free testosterone, P<0.001 for total testosterone). Furthermore, when subjects were divided into two groups, based on a Beck score greater than 18 or less than or equal to 18, serum total and free testosterone levels were significantly lower in the subjects with a Beck score greater than 18, whereas there were no differences in weight, viral load, CD4 count, or Karnofsky status. End of study data were available in 39 patients who completed the randomized, placebo-controlled study. Beck score decreased significantly only in the subjects receiving testosterone (-5.8+/-1.3, P< 0.001), but not in subjects randomized to placebo (-2.7+/-1.3, P> 0.05). In a regression analysis, the change in Beck score was related significantly to change in weight (P<0.01). These data demonstrate increased depression score in association with hypogonadism in men with AIDS wasting, independent of weight, virologic status, and other disease factors. In such patients, administration of testosterone results in a significant improvement in depression inventory score. This effect may be a direct effect of testosterone or related to positive effects of testosterone on weight and/or other anthropometric indices. Additional studies are needed to assess the effects of testosterone on clinical depression indices in human immunodeficiency virus-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Fasting hyperinsulinemia in human immunodeficiency virus-infected men: relationship to body composition, gonadal function, and protease inhibitor use.

Fat redistribution in the setting of protease inhibitor use is increasingly common and is associated with insulin resistance in human immunodeficiency virus (HIV)-infected patients. However, little is known regarding the factors that may contribute to abnormal insulin regulation in this population. We assessed fasting insulin levels in HIV-infected men and determined the relationship among insulin, body composition, endogenous gonadal steroid concentrations, and antiviral therapy in this population. We also determined the effects of exogenous testosterone administration using the homeostatic model for insulin resistance (HOMA IR) in hypogonadal HIV-infected men with the acquired immunodeficiency syndrome wasting syndrome. Fifty HIV-infected men with acquired immunodeficiency syndrome wasting were compared with 20 age- and body mass index (BMI)-matched healthy control subjects. Insulin concentrations were significantly increased in HIV-infected patients compared to those in control patients (16.6+/-1.8 vs. 10.4+/-0.8 microU/mL; P<0.05) and were increased in nucleoside reverse transcriptase (NRTI)-treated patients who did not receive a protease inhibitor (PI; 21.7+/-4.3 vs. 10.4+/-0.8 microU/mL; P<0.05). Insulin concentrations and HOMA IR were inversely correlated with the serum free testosterone concentration (r = -0.36; P = 0.01 for insulin level; r = -0.30; P = 0.03 for HOMA), but not to body composition parameters, age, or BMI. In a multivariate regression analysis, free testosterone (P = 0.05), BMI (P<0.01), and lean body mass (P = 0.04) were significant. Lower lean body mass and higher BMI predicted increased insulin resistance. The HIV-infected patients demonstrated an increased trunk fat to total fat ratio (0.49+/-0.02 vs. 0.45+/-0.02; P<0.05) and an increased trunk fat to extremity fat ratio (1.27+/-0.09 vs. 0.95+/-0.06, P = 0.01), but a reduced extremity fat to total fat ratio (0.44+/-0.01 vs. 0.49 + 0.01; P = 0.02) and reduced overall total body fat (13.8+/-0.7 vs. 17.2+/-0.9 kg; P<0.01) compared to the control subjects. Increased truncal fat and reduced extremity fat were seen among NRTI-treated patients, but this pattern was most severe among patients receiving combined NRTI and PI therapy [trunk fat to extremity ratio, 1.47+/-0.15 vs. 0.95+/-0.06 (P<0.01); extremity fat to total fat ratio, 0.40+/-0.02 vs. 0.49+/-0.01 (P<0.05)]. Insulin responses to testosterone administration were investigated among 52 HIV-infected men with hypogonadism and wasting (weight <90% ideal body weight and/or weight loss >10%) randomized to either testosterone (300 mg, im, every 3 weeks) or placebo for 6 months. Testosterone administration reduced HOMA IR in the HIV-infected men (-0.6+/-0.7 vs. +1.41+/-0.8, testosterone vs. placebo, P = 0.05) in association with increased lean body mass (P = 0.02). These data demonstrate significant hyperinsulinemia in HIV-infected patients, which can occur in the absence of PI use. In NRTI-treated patients not receiving PI, a precursor phenotype is apparent, with increased truncal fat, reduced extremity fat, and increased insulin concentrations. This phenotype is exaggerated in patients receiving PI therapy, with further increased truncal fat and reduced extremity fat, although hyperinsulinemia per se is not worse. Endogenous gonadal steroid levels are inversely related to hyperinsulinemia in HIV-infected men, but reduced lean body mass and increased weight are the primary independent predictors of hyperinsulinemia. Indexes of insulin sensitivity improve in response to physiological androgen administration among hypogonadal HIV-infected patients, and this change is again related primarily to increased lean body mass in response to testosterone administration.

Adipose Tissue↗
PubMed2000

Hyperandrogenemia in human immunodeficiency virus-infected women with the lipodystrophy syndrome.

A novel lipodystrophy syndrome characterized by insulin resistance, hypertriglyceridemia, and fat redistribution has recently been described in human immunodeficiency virus (HIV)-infected men and women. Women with the HIV lipodystrophy syndrome exhibit a marked increase in waist-to-hip ratio and truncal adiposity; however, it is unknown whether androgen levels are increased in these patients. In this study, we assessed androgen levels in female patients with clinical lipodystrophy based on evidence of significant fat redistribution in the trunk, extremities, neck and/or face (LIPO: n = 9; age, 35.7+/-1.7 yr; BMI, 24.7+/-0.8 kg/m2) in comparison with age- and BMI-matched nonlipodystrophic HIV-infected females (NONLIPO: n = 14; age, 37.6+/-1.1 yr; BMI, 23.4+/-0.6 kg/m2) and healthy non-HIV-infected control subjects (C: n = 16; age, 35.8+/-0.9 yr; BMI, 23.1+/-0.4 kg/m2). Fasting insulin, lipid levels, virologic parameters, and regional body composition using dual energy x-ray absorptiometry were also assessed. Total testosterone [ LIPO, 33+/-6 ng/dL (1.1+/-0.2 nmol/L); NONLIPO, 17+/-2 ng/dL (0.6+/-0.1 nmol/L); C, 23+/-2 ng/dL (0.8+/-0.1 nmol/L); P < 0.05 LIPO vs. C and LIPO vs. NONLIPO] and free testosterone determined by equilibrium dialysis [LIPO, 4.5+/-0.9 pg/mL (16+/-3 pmol/L); NONLIPO, 1.7+/-0.2 pg/mL (6+/-1 pmol/L); C, 2.4+/-0.2 pg/mL (8+/-1 pmol/L); P < 0.05 LIPO vs. C and LIPO vs. NONLIPO] were increased in the lipodystrophic patients. Sex hormone-binding globulin levels were not significantly different between LIPO and C, but were significantly lower in the LIPO vs. NONLIPO patients (LIPO 84+/-7 vs. NONLIPO 149+/-17 nmol/L, P < 0.05). The LH/FSH ratio was significantly increased in the LIPO group compared with the NONLIPO and C subjects (LIPO, 2.0+/-0.6; NONLIPO, 1.1+/-0.1; C, 0.8+/-0.1; P < 0.05 LIPO vs. NONLIPO and LIPO vs. C). Body fat distribution was significantly different between LIPO and C subjects. Trunk to extremity fat ratio (1.46+/-0.17 vs. 0.75+/-0.05, LIPO vs. C, P < 0.05) was increased and extremity to total fat ratio decreased (0.40+/-0.03 vs. 0.55+/-0.01, LIPO vs. C, P < 0.05). In contrast, fat distribution was not different in the NONLIPO group vs. control subjects. Among the HIV-infected patients, free testosterone correlated with percent truncal fat (trunk fat/trunk mass) (r = 0.43, P = 0.04). These data suggest that hyperandrogenemia is another potentially important feature of the HIV-lipodystrophy syndrome in women. Additional studies are necessary to determine the clinical significance of increased androgen levels and the relationship of hyperandrogenism to fat redistribution and insulin resistance in this population of patients.

Adult↗
PubMed1999

Long-term mortality after transsphenoidal surgery for Cushing disease.

BACKGROUND: Untreated Cushing disease historically has a high mortality rate, but the long-term survival of patients with Cushing disease after transsphenoidal surgery has not been reported. OBJECTIVE: To determine long-term mortality rate in patients who are treated for Cushing disease with current management techniques. DESIGN: Retrospective case series. SETTING: Tertiary care center. PATIENTS: 161 patients (32 men and 129 women; mean age, 38 years) who were treated for Cushing disease between 1978 and 1996. INTERVENTION: Transsphenoidal adenomectomy and as-needed adjunctive therapy. MEASUREMENT: Record review with follow-up interview. RESULTS: The cure rate for patients with microadenomas who had no previous therapy was 90% (123 of 137). No perioperative deaths occurred (0 of 193 procedures [95% CI, 0.0% to 1.9%]). Follow-up data (mean, 8.7 years) were obtained for 99% of patients (159 of 161). Six patients died. The 5- and 10-year survival rates were 99% (CI, 97% to 100%) and 93% (CI, 88% to 99%), respectively. Survival was similar to that seen in an age- and sex-matched sample that was based on U.S. population data (standardized mortality ratio, 0.98 [CI, 0.44 to 2.2]; P > 0.2). CONCLUSION: Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder.

Adenoma↗
PubMed1999

Sustained anabolic effects of long-term androgen administration in men with AIDS wasting.

Fifty-one human immunodeficiency virus-positive men with hypogonadism and wasting were randomized to receive testosterone enanthate, 300 mg i.m. every 3 weeks, or placebo for 6 months, followed by open-label testosterone administration for 6 months. Subjects initially randomized to placebo gained lean body mass (LBM) only after crossover to testosterone administration (mean change +/- standard error of the mean, -0.6 +/- 0.7 kg [months 0-6] vs. 1.9 +/- 0.7 kg [months 6-12]; P = .03). In contrast, subjects initially randomized to testosterone continued to gain LBM during open-label administration (2.0 +/- 0.7 kg [months 0-6] vs. 1.6 +/- 0.6 kg [months 6-12]; P = .62) and had gained more LBM at 1 year than did subjects receiving testosterone for only the final 6 months of the study (3.7 +/- 0.8 kg vs. 1.0 +/- 1.0 kg; P = .05). Testosterone administration results in sustained increases in LBM during 1 year of therapy in hypogonadal men with AIDS wasting.

Cross-Over Studies↗
PubMed1999

Quantitative assessment of cross-sectional muscle area, functional status, and muscle strength in men with the acquired immunodeficiency syndrome wasting syndrome.

The acquired immunodeficiency syndrome wasting syndrome (AWS) in men is characterized by the loss of lean body mass out of proportion to weight. Although the wasting syndrome has been thought to contribute to reduced functional capacity, the relationships among lean body mass, muscle size, functional status, and regional muscle strength have not previously been investigated in this population. In this study, 24 eugonadal men with the AWS (weight <90% of the ideal body weight or weight loss >10% from preillness maximum) underwent determination of body composition by dual energy x-ray absorptiometry (DXA), 40K isotope analysis, urinary creatinine excretion, and quantitative computed tomographic analysis of cross-sectional muscle areas of the midarm and thigh. Overall exercise functional capacity was evaluated using the 6-min walk test, and performance of upper and lower extremities was determined with the quantitative muscle function test. Subjects were 37 +/- 1 yr of age and weighed 95.5 +/- 3.0% of ideal body weight, with a body mass index of 21.9 +/- 0.7 kg/m2 and an average weight loss of 15 +/- 1%. The mean CD4 count among the subjects was 354 +/- 70 cells/mm3, and viral load was 58,561 +/- 32,205 copies. Sixty-two percent of subjects were receiving protease inhibitor therapy. The subjects demonstrated 90% of the expected muscle mass by the creatinine height index method. Overall performance status on the Karnofsky scale was highly correlated to weight (r = 0.51; P = 0.018; by body mass index), lean body mass (r = 0.46; P = 0.036; by DXA), and body cell mass (r = 0.47; P = 0.037; by 40K isotope analysis). Cross-sectional muscle area of the upper extremity was the best predictor (P < 0.001) of Karnofsky score, accounting for 52% of the variability in a stepwise regression analysis. Upper body muscle strength was most significantly predicted by lean body mass (by DXA; r2 = 0.78; P < 0.0001), whereas lower body strength and performance on the 6-min walk test were best predicted by lower extremity cross-sectional muscle area (r2 = 0.70; P < 0.0001 and r2 = 0.26; P = 0.030, respectively). These data demonstrate that cross-sectional muscle area is highly predictive of functional status and muscle strength in men with the AWS.

Adult↗
PubMed1999

The effects of anorexia nervosa on bone metabolism in female adolescents.

Osteopenia is a frequent, often persistent, complication of anorexia nervosa (AN) in adolescent girls and occurs during a critical time in bone development. Little is known about bone metabolism in this patient population. Therefore, we measured bone density (BMD) and body composition by dual energy x-ray absorptiometry, nutritional status, bone turnover, calcium, and hormonal status in 19 adolescent girls with AN (mean +/- SEM, 16.0+/-0.4 yr) and 19 bone age-matched controls. The mean duration of AN was 19+/-5 months. Spinal (L1-L4) osteopenia was common in AN. Lumbar anterioposterior BMD was more than 1 SD below the mean in 42% of patients, and lateral spine BMD was more than 1 SD below in 63% of patients compared with controls. Lean body mass significantly predicted lumbar bone mineral content (r = 0.75; P < 0.0001) in controls only. In AN, duration of illness was the most significant predictor of spinal BMD (lumbar: r = -0.44; P = 0.06; lateral: r = -0.59; P = 0.008). AN adolescents with mature BA (15 yr and greater) were hypogonadal [estradiol, 16.2+/-1.9 vs. 23.3+/-1.6 pg/mL (P = 0.01); free testosterone, 0.70+/-0.17 vs. 1.36+/-0.14 pg/mL (P = 0.01)] although dehydroepiandrosterone sulfate and urinary free cortisol levels did not differ. Leptin levels were reduced in AN (2.9+/-2.1 vs. 16.5+/-1.8 ng/mL; P < 0.0001). Insulin-like growth factor I (IGF-I) was reduced in AN to 50% of control levels (219+/-41 vs. 511+/-35 ng/mL; P < 0.0001) and correlated with all measures of nutritional status, particularly leptin (r = 0.80; P < 0.0001). Surrogate markers of bone formation, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP), were significantly (P = 0.02) reduced in AN vs. controls (OC, 39.1+/-6.4 vs. 59.2+/-5.2 ng/mL; BSAP, 27.9+/-4.0 vs. 40.6+/-3.4 U/L). The majority of the variation in bone formation in AN was due to IGF-I levels (OC: r2 = 0.72; P = 0.002; BSAP: r2 = 0.53; P = 0.01) in stepwise regression analyses. Bone resorption was comparable in patients and controls. These data demonstrate that bone formation is reduced and uncoupled to bone resorption in mature adolescents with AN in association with low bone density. Lean body mass was a significant predictor of BMD in controls, but not AN patients. The major correlate of bone formation in AN was the nutritionally dependent bone trophic factor, IGF-I. Reduced IGF-I during the critical period of bone mineral accumulation may be an important factor in the development of osteopenia in adolescents with AN.

Absorptiometry, Photon↗
PubMed1999

Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women.

A novel lipodystrophy syndrome (characterized by insulin resistance, hypertriglyceridemia, and fat redistribution) has recently been described in human immunodeficiency virus (HIV)-infected patients. However, investigation of the lipodystrophy syndrome has generally been limited to men; and a comprehensive evaluation of insulin, lipids, and regional body composition has not been performed in the expanding population of HIV-infected women. In this study, we assessed fasting insulin, lipid levels, virologic parameters, and regional body composition, using dual-energy x-ray absorptiometry, in a cohort of 75 HIV-infected women (age, 25-46 yr), in comparison with 30 healthy weight-matched premenopausal control subjects. HIV-infected women demonstrated significant truncal adiposity (38.5 +/- 0.9 vs. 34.9 +/- 1.3%, P < 0.05) hyperinsulinemia (15.9 +/- 1.5 vs. 7.5 +/- 0.6 microU/mL, P < 0.001) and an increased insulin-to-glucose ratio (0.2 +/- 0.02 vs. 0.1 +/- 0.03, P < 0.001), compared with control subjects. Insulin and the insulin-to-glucose ratio were increased, even among HIV-infected patients with low body weight (<90% of ideal body weight) (insulin, 13.3 +/- 2.8 microU/mL, P < 0.01 vs. control; insulin/glucose, 0.2 +/- 0.04, P < 0.01 vs. control). Insulin and the insulin-to-glucose ratio were most significantly elevated among patients with increased truncal adiposity (insulin, 28.2 +/- 3.2 microU/mL, P < 0.001 vs. control; insulin/ glucose, 0.32 +/- 0.04, P < 0.001 vs. control). In contrast, no differences in insulin were seen in relation to protease inhibitor (PI) use. Similarly, HIV-infected women also demonstrated significant hypertriglyceridemia (144 +/- 15 vs. 66 +/- 23 mg/dL, P < 0.01 vs. controls), which was present even among low-weight patients (148 +/- 32 mg/dL, P < 0.001 vs. control) but was not related to truncal adiposity or PI usage. These data demonstrate significant hyperinsulinemia and truncal adiposity in HIV-infected women. Our data suggest that these metabolic abnormalities occur at baseline in HIV-infected women, independent of PI use. However, these data do not rule out a direct effect of PI therapy on fat metabolism or indirect effects of PI therapy to further worsen glucose and lipid homeostasis in association with weight gain and disease recovery.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Severity of osteopenia in estrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea.

Reduced bone density is observed in over half of women with anorexia nervosa (AN), in whom the risk of fracture is significantly increased even at a young age. It is unknown to what extent low bone density in AN differs from other conditions of premenopausal osteoporosis and is related to estrogen deficiency and/or other factors, such as nutritional status. We therefore investigated bone loss in nutritionally replete and nutritionally deplete amenorrheic women by comparing patients with AN (n = 30) to age-matched subjects with hypothalamic amenorrhea (HA; n = 19) in whom duration of amenorrhea, prior estrogen use, and age of menarche were comparable. Healthy, age-matched, eumenorrheic women were studied as a control group (NL; n = 30). Weight and nutritionally dependent factors including (body mass index, 20.7 +/- 0.3 vs. 16.7 +/- 0.3 kg/m2; P < 0.0001), insulin-like growth factor I (270 +/- 18 vs. 203 +/- 17 ng/mL; P < 0.01), percent body fat (26% vs. 19%; P < 0.0001), and lean body mass (38.7 +/- 1.1 vs. 34.3 +/- 0.8, P < 0.01) were significantly different between the HA and AN groups, respectively. The bone densities of the anterior-posterior (AP) spine, total hip, and total body measured by dual energy x-ray absortiometry were reduced in both amenorrheic groups compared to those in control subjects, but were significantly lower in women with AN than in those with HA. The t scores for AP spine and hip were -1.80 +/- 0.15 (AN), -0.80 +/- 0.22 (HA), and 0.28 +/- 0.19 SD (NL) for the AP spine and -1.62 +/- 0.17 (AN), -0.51 +/- 0.21 (HA), and 0.25 +/- 0.16 (NL) for the total hip, respectively (P < 0.01 for all comparisons). Among the amenorrheic subjects, duration of amenorrhea, age of menarche, and N-telopeptide were inversely correlated with bone density at all sites, whereas body mass index, insulin-like growth factor I, lean body mass, and fat intake were positively correlated with bone density at all sites measured. In multivariate regression analyses, bone density was most significantly related to lean body mass (P = 0.05 and P = 0.03 for the spine and hip, respectively), but not to the duration of amenorrhea or other indexes of estrogen status among patients with AN. In contrast, bone density of the lumbar spine was significantly related to weight and duration of amenorrhea among patients with HA. These data demonstrate that the severity of osteopenia in AN is greater than that in patients with HA and is critically dependent upon nutritional factors in addition to the degree or duration of estrogen deficiency itself. Lean body mass, independent of the duration or severity of estrogen deficiency, is an important predictor of bone loss among women with AN.

Absorptiometry, Photon↗
PubMed1998

Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Development of successful anabolic strategies to reverse the loss of lean body mass is of critical importance to increase survival in men with the AIDS wasting syndrome. Hypogonadism, an acquired endocrine deficiency state characterized by loss of testosterone, occurs in more than half of all men with advanced HIV disease. It is unknown whether testosterone deficiency contributes to the profound catabolic state and loss of lean body mass associated with the AIDS wasting syndrome. OBJECTIVE: To investigate the effects of physiologic testosterone administration on body composition, exercise functional capacity, and quality of life in androgen-deficient men with the AIDS wasting syndrome. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University medical center. PATIENTS: 51 HIV-positive men (age 42 +/- 8 years) with wasting (body weight < 90% of ideal body weight or weight loss > 10% of baseline weight) and a free testosterone level less than 42 pmol/L (normal range for men 18 to 49 years of age, 42 to 121 pmol/L [12.0 to 35.0 pg/mL]). INTERVENTION: Patients were randomly assigned to receive testosterone enanthate, 300 mg, or placebo intramuscularly every 3 weeks for 6 months. MEASUREMENTS: Change in fat-free mass was the primary end point. Secondary clinical end points were weight, lean body mass, muscle mass, exercise functional capacity, and change in perceived quality of life. Virologic variables were assessed by CD4 count and viral load. RESULTS: Compared with patients who received placebo, testosterone-treated patients gained fat-free mass (-0.6 kg and 2.0 kg; P = 0.036), lean body mass (0.0 kg and 1.9 kg; P = 0.041), and muscle mass (-0.8 kg and 2.4 kg; P = 0.005). The changes in weight, fat mass, total-body water content, and exercise functional capacity did not significantly differ between the groups. Patients who received testosterone reported benefit from the treatment (P = 0.036), feeling better (P = 0.033), improved quality of life (P = 0.040), and improved appearance (P = 0.021). Testosterone was well tolerated in all patients. CONCLUSIONS: Physiologic testosterone administration increases lean body mass and improves quality of life among androgen-deficient men with the AIDS wasting syndrome.

Adolescent↗
PubMed1998

Determinants of increased energy expenditure in HIV-infected women.

BACKGROUND: Little is known about sex-specific effects of HIV infection on energy expenditure. OBJECTIVE: We investigated the determinants of energy expenditure in HIV-infected women. DESIGN: Resting energy expenditure (REE), body composition, and hormonal and nutritional indexes were compared in 33 ambulatory, premenopausal HIV-infected women and 26 weight-matched, healthy premenopausal control subjects. REE was determined by indirect calorimetry and body composition by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis, and skinfold-thickness analysis. Hormonal indexes included leptin, testosterone, estradiol, and insulin-like growth factor I. RESULTS: HIV-infected subjects had a higher REE than control subjects [6794 +/- 1374 compared with 6011 +/- 607 kJ/d (1624 +/- 329 compared with 1437 +/- 145 kcal/d), P = 0.0096]. On average, REE was 119 +/- 23% of Harris-Benedict predictions in HIV-infected subjects compared with 102 +/- 9% for control subjects (P = 0.0007). In HIV-infected subjects, REE was highly correlated with fat-free mass (FFM) by DXA (R = 0.641, P < 0.001), but not with weight or disease status. The slope of the regression equation for REE and FFM was significantly greater (P = 0.027, analysis of covariance) for HIV-infected subjects [REE (kJ/d) = 203.5 (kg FFM) - 1237] than for control subjects [REE (kJ/d) = 77.4 (kg FFM) + 2923]. In a stepwise regression analysis, FFM was the most significant variable (P = 0.005), followed by free testosterone (P = 0.029), which together explained 49% of the variation in REE. The final equation was REE (kJ/d) = 230.8 (kg FFM) + 395.9 (free testosterone, pmol/L) - 3304. CONCLUSIONS: Energy expenditure was higher in HIV-infected women than in control women. FFM is the primary determinant of REE in HIV-infected women, but energy expenditure is greater per kg FFM in HIV-infected subjects than in control subjects, which may contribute to the wasting syndrome.

Absorptiometry, Photon↗
PubMed1998

Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly.

To analyze the long term outcome after multimodality therapy for acromegaly, a retrospective review was performed on 162 patients who underwent transsphenoidal surgery at Massachusetts General Hospital between 1978 and 1996. The surgical cure rate for microadenomas was 91%, that for macroadenomas was 48%, and it was 57% overall. The surgical cure rate was significantly dependent on tumor size, but was not dependent on age or sex. An improvement in the surgical cure rate was noted over the course of the review, from 45% before 1987 to 73% since 1991. Long term follow-up was obtained in 99% of U.S. residents (149 of 151), with a mean follow-up period of 7.8 yr. Adjuvant radiation and/or pharmacological therapy was given to 61 patients. Of the entire group, 83% (124 of 149) were in biochemical remission as determined by normalization of serum insulin-like growth factor I levels or by GH suppression after oral glucose tolerance testing at last contact or at death. The recurrence rate was 6% at 10 yr and 10% at 15 yr after surgery in those patients who initially met the criteria for surgical cure. The 10-yr survival rate was 88%, and there were 12 deaths at postoperative intervals of 2-12 yr, with the most common cause of death being cardiovascular disease. A Cox proportional hazards model showed that patient-years with persistent disease carried a 3.5-fold [95% confidence interval (CI), 1.0-12; P = 0.02] relative mortality risk compared to those patient-years in remission. A Poisson person-years regression analysis showed no significant difference in survival between those 86 patients cured at operation and an age- and sex-matched sample from the U.S. population [standardized mortality ratio (SMR), 0.84; 95% CI, 0.3-2.2; P = 0.35]. A similar analysis on the entire group of 149 patients showed no significant difference in survival from that in a control sample (SMR, 1.16; 95% CI, 0.66-2.0; P = 0.3). Mortality risk for patient-years with persistent active disease after unsuccessful treatment vs. that in the U.S. population sample remained increased (SMR, 1.8; 95% CI, 0.9-3.6; P = .05). This analysis suggests that the decreased survival previously reported to be associated with acromegaly can be normalized by successful surgical and adjunctive therapy.

Acromegaly↗
PubMed1998

Effects of androgen administration on the growth hormone-insulin-like growth factor I axis in men with acquired immunodeficiency syndrome wasting.

It is unknown whether hypogonadism contributes to decreased insulin-like growth factor I (IGF-I) production and/or how testosterone administration may effect the GH-IGF-I axis in human immunodeficiency virus (HIV)-infected men with the acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS). In this study, we investigate the GH-IGF-I axis in men with the AWS and determine the effects of testosterone on GH secretory dynamics, pulse characteristics determined from overnight frequent sampling, arginine stimulation, and total and free IGF-I levels. Baseline GH-IGF-I parameters in hypogonadal men with AWS (n=51) were compared before testosterone administration (300 mg, im, every 3 weeks vs. placebo for 6 months) with cross-sectional data obtained in two age-matched control groups: eugonadal men with AIDS wasting (n=10) and healthy age-matched normal men (n=15). The changes in GH-IGF-I parameters were then compared prospectively in testosterone- and placebo-treated patients. Mean overnight GH levels [1.8+/-0.3 and 2.4+/-0.3 vs. 0.90+/-0.1 microg/L (P=0.04 and P=0.003 vs. healthy controls)] and pulse frequency [0.35+/-0.06 and 0.37+/-0.02 vs. 0.22+/-0.03 pulses/h (P=0.06 and P=0.002 vs. healthy controls)] were comparably elevated in the eugonadal and hypogonadal HIV-positive groups, respectively, compared to those in the healthy control group. No significant differences in pulse amplitude, interpulse interval, or maximal GH stimulation to arginine administration (0.5 g/kg, i.v.) were seen between either the eugonadal and hypogonadal HIV-positive or healthy control patients. In contrast, IGF-I levels were comparably decreased in both HIV-positive groups compared to the healthy control group [143+/-16 and 165+/-14 vs. 216+/-14 microg/L (P=0.004 and P=0.02 vs. healthy controls)]. At baseline, before treatment with testosterone, overnight GH levels were inversely correlated with IGF-I (r=-0.42; P=0.003), percent ideal body weight (r=-0.36; P=0.012), albumin (r=-0.37; P=0.012), and fat mass (r=-0.52; P=0.0002), whereas IGF-I levels correlated with free testosterone (r=0.35; P=0.011) and caloric intake (r=0.32; P= 0.023) in the hypogonadal HIV-positive men. In a stepwise regression model, albumin (P=0.003) and testosterone (P=0.011) were the only significant predictors of GH [mean GH (microg/L)=-1.82 x albumin (g/dL) + 0.003 x total testosterone (microg/L) + 6.5], accounting for 49% of the variation in GH. Mean overnight GH levels decreased significantly in the testosterone-treated patients compared to those in the placebo-treated hypogonadal patients (0.9+/-0.3 vs. 0.2+/-0.4 microg/L; P=0.020). In contrast, no differences in IGF-I or free IGF-I were observed in response to testosterone administration. The decrement in mean overnight GH in response to testosterone treatment was inversely associated with increased fat-free mass (r=-0.49; P= 0.024), which was the only significant variable in a stepwise regression model for change in GH [change in mean GH (microg/L)=-0.197 x kg fat-free mass - 0.53] and accounted for 27% of the variation in the change in GH. In this study, we demonstrate increased basal GH secretion and pulse frequency in association with reduced IGF-I concentrations, consistent with GH resistance, among both hypogonadal and eugonadal men with AIDS wasting. Testosterone administration decreases GH in hypogonadal men with AIDS wasting. The change in GH is best predicted by and is inversely related to the magnitude of the change in lean body mass in response to testosterone administration. These data demonstrate that among hypogonadal men with the AWS, testosterone administration has a significant effect on the GH axis.

Adult↗
PubMed1998

Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study.

Although human immunodeficiency virus (HIV) disease is increasing rapidly among women, no prior studies have investigated gender-based therapeutic strategies for the treatment of acquired immunodeficiency syndrome (AIDS) and its complications in this population. Markedly decreased serum androgen levels have been demonstrated in women with AIDS and may be a contributing factor to the wasting syndrome in this population. To assess the effects of androgen replacement therapy in women with AIDS wasting, we conducted a randomized, placebo-controlled, pilot study of transdermal testosterone administration. The primary aim of the study was to determine efficacy in terms of the change in serum testosterone levels, safety parameters and tolerability. A secondary aim of the study was to investigate testosterone effects on weight, body composition, quality of life, and functional indexes. Fifty-three ambulatory women with the AIDS wasting syndrome defined as weight less than 90% of ideal body weight or weight loss of more than 10% of the preillness maximum, free of new opportunistic infection within 6 weeks of study initiation, and with screening serum levels of free testosterone less than the mean of the normal reference range (< 3 pg/mL) were enrolled in the study. Subjects were age 37 +/- 1 yr old (mean +/- SEM), weighed 92 +/- 2% of ideal body weight, and had lost 17 +/- 1% of their maximum weight. CD4 count was 324 +/- 36 cells/mm3, and viral burden was 102,382 +/- 28,580 copies. Subjects were randomized into three treatment groups, in which two placebo patches (PP), one active/one placebo patch (AP group), or two active patches (AA group) were applied twice weekly to the abdomen for 12 weeks. The expected nominal delivery rates of testosterone were 150 and 300 microg/day, respectively, for the AP and AA groups. Forty-five subjects completed the study (PP group, n = 13; AP group, n = 14; AA group, n = 18). Two additional subjects from the PP group and two from the AP group were included in the intent to treat analysis. Serum free testosterone levels increased significantly from 1.2 +/- 0.2 to 5.9 +/- 0.8 pg/mL (AP) and from 1.9 +/- 0.4 to 12.4 +/- 1.6 pg/mL (AA) in response to testosterone administration (P < 0.0001 for comparison of AA vs. PP and AP vs. PP; normal range, 1.3-6.8 pg/mL). Testosterone administration was generally well tolerated locally and systemically, with no adverse trends in hirsutism scores, lipid profiles, or liver function tests. Weight increased significantly in the AP group (1.9 +/- 0.7 kg) vs. the PP group (0.6 +/- 0.8 kg; P = 0.043), but did not increase significantly in the AA group (0.9 +/- 0.4 kg; P = 0.263 vs. PP, by mixed effects model assessing the interaction of time and treatment on all available data, one-tailed test). Improved social functioning (P = 0.024, by one-tailed test) and a trend toward improved pain score (P = 0.059) were observed in the AP vs. the PP-treated patients (RAND 36-Item Health Survey questionnaire). Five of six previously amenorrheic patients in the AP group had spontaneous resumption of menses compared to only one of four amenorrheic patients in the AA group (P = 0.045 for comparison of actual number of periods during the study). This study is the first investigation of testosterone administration in women with AIDS wasting. We demonstrate a novel method to augment testosterone levels in such patients that is safe and well tolerated during short term administration. At the lower of the two doses administered in this study, testosterone therapy was associated with positive trends in weight gain and quality of life. Higher, more supraphysiological, dosing was not associated with positive trends in weight or overall well-being. These data suggest that testosterone administration may improve the status of women with AIDS wasting. Further studies are needed to assess the effects of testosterone on weight in HIV-infected women and to define the optimal therapeutic window for test

Administration, Cutaneous↗