Increased cardiovascular disease risk indices in HIV-infected women.

Little is known regarding cardiovascular disease risk indices in HIV-infected women. This study investigated cardiovascular disease risk indices in 100 consecutively recruited HIV-infected women and 75 healthy female control subjects. Subjects were recruited from hospital- and community-based health care providers. C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, lipid, and glucose levels were the main outcome measures. CT scan, dual-energy x-ray absorptiometry (DXA), and anthropometry were used to assess body composition. Although similar in age, weight, and racial composition, HIV-infected women demonstrated higher CRP (4.6 +/- 0.7 vs. 2.3 +/- 0.4 mg/L, P = 0.007), IL-6 (2.7 +/- 0.2 vs. 1.8 +/- 0.1 pg/mL, P = 0.02), triglyceride (1.84 +/- 0.21 vs. 0.85 +/- 0.05 mM, P = 0.0002), 2-hour glucose after oral glucose challenge (6.88 +/- 0.22 vs. 5.72 +/- 0.17 mM, P = 0.0003), and fasting insulin (81 +/- 8 vs. 45 +/- 2 pM, P = 0.0002) and lower high-density lipoprotein cholesterol (1.17 +/- 0.03 vs. 1.45 +/- 0.05 mM, P < 0.0001) and adiponectin (5.4 +/- 0.3 vs. 7.6 +/- 0.5 mg/L, P = 0.0001) levels compared with the control population. HIV-infected women had more abdominal visceral fat and less extremity fat by CT and DXA scan and demonstrated a higher waist-to-hip ratio (WHR) than the control population. Within the HIV group, CRP and other indices were significantly related to body composition in stepwise regression models. Among all subjects, WHR, but not HIV status, was significantly related to CRP and other cardiovascular disease risk indices. HIV-infected women demonstrate significantly increased risk factors for cardiovascular disease in association with abnormal fat distribution.

Effects of testosterone administration on growth hormone pulse dynamics in human immunodeficiency virus-infected women.

The effects of testosterone administration on the GH axis in androgen-deficient HIV-infected women are unknown. In this study, we determined the effects of transdermal testosterone administration on GH secretory dynamics and pulse characteristics in this population. GH-IGF-I parameters were determined in response to testosterone (4.1 mg/patch, twice a week; estimated delivery rate, 150 microg/d) vs. placebo over 6 months in 31 HIV-infected women. IGF-I increased significantly in the testosterone-treated compared with the placebo-treated patients [37 (-4, 73) vs. -30 (-98, 39) ng/ml, P = 0.01; 4.8 (-0.5, 9.6) vs. -3.9 (-12.8, 5.1) nmol/liter]. GH pulse frequency increased significantly in the testosterone-treated compared with the placebo-treated subjects [1.0 (1.0, 2.0) vs. 0.0 (-0.5, 1.5) peaks per 12 h, respectively; P = 0.02]. Before testosterone administration, overnight GH pulse amplitude was significantly related to IGF-I in univariate (r = 0.41, P = 0.03) and multivariate regression analysis; however, free testosterone, estradiol, and body mass index were not significantly correlated with baseline IGF-I. In contrast, after 6 months of treatment with testosterone, the change in IGF-I was significantly correlated to the change in free testosterone in univariate (r = 0.40, P = 0.04) and multivariate regression analysis. For each 1.0 pg/ml (3.5 pmol/liter) increase in free testosterone, IGF-I increased 19 ng/ml (2.5 nmol/liter), controlling for estradiol, body mass index, and GH pulse parameters (r(2) = 0.64). We demonstrate that IGF-I increases in response to physiologic, transdermal testosterone in HIV-infected women. The mechanism of this effect is unknown, but may involve a direct effect of testosterone on IGF-I, independent of changes in GH pulse dynamics.

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.

Reduced bone density in HIV-infected women.

OBJECTIVES: Although bone density has been previously investigated in HIV-infected men, little is known regarding bone density in HIV-infected women. METHODS AND DESIGN: Bone density was measured by dual-energy X-ray absorptiometry in 84 ambulatory, HIV-infected females and 63 healthy female control subjects similar in age (41 +/-1 versus 41+/- 1 years, P = 0.83), body mass index (26.0 +/- 0.6 versus 27.0 +/- 0.5 kg/m, P = 0.44) and racial background (% non-Caucasian, 61 versus 51%; P = 0.24, HIV-infected versus control). RESULTS: Lumbar spine (1.02+/- 0.02 versus 1.07 +/- 0.02 g/cm, P = 0.03) and total hip (0.93 +/-0.01 versus 0.99 +/- 0.01 g/cm, P = 0.004) bone density were reduced in HIV-infected compared with control subjects. Osteopenia was demonstrated in 54 versus 30% (P = 0.004) of HIV-infected versus control subjects and was 2.5 times more likely in a multivariate model accounting for age, race, menstrual function and body mass index. Urinary N-telopeptides of type 1 collagen (NTx) (39.6 +/- 3.5 versus 29.9 +/- 2.0 nM/mM urine creatinine, P = 0.03) and osteoprotegerin (4.76 +/- 0.23 versus 3.39 +/- 0.17 pmol/l, P < or = 0.0001) were increased in HIV-infected compared with control subjects. Among the HIV-infected women, bone density correlated with weight (r = 0.41, P < 0.001) and inversely with urinary NTx (r = -0.28, P = 0.01). Bone density did not differ by current or past protease inhibitor, nucleoside reverse trancriptase inhibitor, or non-nucleoside reverse transcriptase inhibitor exposure. CONCLUSIONS: HIV-infected women demonstrate reduced bone density. Altered nutritional status, hormonal function and body composition may contribute to lower bone density in HIV-infected women. Consideration should be given to testing bone density in HIV-infected women with risk factors for osteopenia.

Reduced testosterone levels in human immunodeficiency virus-infected women with weight loss and low weight.

Risk factors for hypoandrogenemia among low-weight, human immunodeficiency virus (HIV)-infected patients are not known. Testosterone levels of 69 HIV-infected women with low weight and weight loss were compared with levels for 25 healthy, age- and body mass index-matched control subjects. HIV-infected subjects were of low weight, with a mean (+/- standard deviation) weight loss of -17.6% +/- 9.7% from preillness maximum, and 42% of HIV-infected subjects had a body mass index of <20 kg/m(2). Forty-nine percent of the HIV-infected population versus 8% of the control population exhibited low free testosterone levels (P<.001). Among HIV-infected women, when we controlled for chronic hepatitis status, age, and time of blood sampling, weight loss of >10% of maximum weight was a significant predictor of low free testosterone levels. Free testosterone levels did not differ by drug class or antiretroviral regimen. In conclusion, decreased androgen levels are common among HIV-infected women reporting significant weight loss, independent of exposure to antiretroviral medications.