Absence of polycystic ovary syndrome features in human immunodeficiency virus-infected women despite significant hyperinsulinemia and truncal adiposity.

CONTEXT: HIV-infected women increasingly demonstrate insulin resistance and fat redistribution characterized by relative truncal adiposity. It is unknown whether insulin resistance and truncal adiposity are associated with features of the polycystic ovary syndrome in this population. OBJECTIVE: The objective of the study was to characterize ovarian morphology and reproductive indices in a large cohort of HIV-infected women in comparison with healthy age- and body mass index-matched control subjects. SETTING: The study was conducted at an academic medical center. SUBJECTS: Eighty-eight HIV-infected women were compared with 94 age- and body mass index-matched healthy control subjects. MAIN OUTCOME MEASURES: Androgen, SHBG, and gonadotropin levels and ovarian morphology were measured. RESULTS: HIV-infected subjects demonstrated increased visceral adipose tissue (VAT) (101 +/- 6 vs. 71 +/- 5 cm2; P < 0.0001), increased VAT to s.c. adipose tissue ratio, and a trend toward decreased abdominal s.c. adipose tissue. Fasting insulin (12 +/- 1 vs. 6 +/- 1 microIU/ml; P < 0.001) and 2-h glucose (124 +/- 4 vs. 106 +/- 4 mg/dl; P = 0.001) were also significantly increased in the HIV-infected women, compared with control subjects, respectively. Despite significant hyperinsulinemia and visceral adiposity, HIV-infected women did not demonstrate irregular menses or an increased number of small ovarian follicles (8.0 +/- 0.9 vs. 8.5 +/- 0.7 follicles; P = 0.65, HIV-infected vs. controls). Rather, SHBG (124 +/- 10 vs. 84 +/- 4 nmol/liter; P < 0.001) was increased significantly in HIV-infected women, and free testosterone by equilibrium dialysis was significantly reduced (2.2 +/- 0.2 vs. 2.7 +/- 0.2 pg/ml; P = 0.04), as was LH to FSH ratio (0.62 +/- 0.05 vs. 0.83 +/- 0.07; P = 0.03). Menstrual function, androgen levels, and ovarian morphology by ultrasonography were not different between HIV-infected women and healthy controls. CONCLUSIONS: These data demonstrate that among HIV-infected subjects with severe abdominal fat accumulation and hyperinsulinemia, common features of polycystic ovary syndrome are not seen.

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 exercise training and metformin on body composition and cardiovascular indices in HIV-infected patients.

OBJECTIVE: To determine whether exercise training in combination with metformin improves cardiovascular risk indices and insulin in comparison to metformin alone among HIV-infected patients. METHODS AND DESIGN: We conducted a prospective, randomized, 3-month study of HIV patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution. Subjects received metformin alone or metformin and exercise training consisting of 1 h of aerobic and resistance training three times a week. Cardiovascular parameters, including blood pressure and endurance during sub-maximal stress testing, body composition, strength, insulin and other biochemical parameters were determined. RESULTS: Thirty-seven patients were randomized and 25 subjects completed the study. Subjects receiving exercise training and metformin demonstrated significant decreases in median waist-to-hip ratio [-0.02 (-0.06, -0.01) (median (interquartile range) versus -0.01 (0.03, 0.02), P = 0.026], resting systolic [-12 (-20, -4) versus 0 (-11, 11), P = 0.012] and diastolic blood pressures [-10 (-14, -8) versus 0 (-7, 8), P = 0.001], increased thigh muscle cross-sectional area [3 (-3, 12) versus -7 (-11, 0), P = 0.015], and improved exercise time [3 (0, 4) versus 0 (-1, 1), P = 0.045] compared with subjects receiving metformin alone. Fasting insulin and insulin area under the curve decreased significantly more in the exercise and metformin group (P < 0.05). Lipids and resting lactate did not change significantly between treatment groups. CONCLUSIONS: These data demonstrate that exercise training in combination with metformin significantly improves cardiovascular and biochemical parameters more than metformin alone in HIV-infected patients with fat redistribution and hyperinsulinemia. Combined treatment was safe, well tolerated and may be a useful strategy to decrease cardiovascular risk in this population.

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.