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Clinical Studies |
Neuroendocrine (S.G., C.C., B.M.K.B., E.W., A.K.) Infectious Disease (N.B., H.M.H.) Departments and the General Clinical Research Center (J.H., E.J.A), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Address all correspondence and requests for reprints to: Steven Grinspoon, M.D., Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114.
The acquired immunodeficiency syndrome (AIDS) wasting syndrome is a devastating complication of human immunodeficiency virus (HIV) infection characterized by progressive weight loss and severe inanition. In men, the wasting syndrome is characterized by a disproportionate decrease in lean body mass and relative fat sparing. In contrast, relatively little is known about the gender-specific changes in body composition that characterize AIDS wasting in women.
Three groups of women were studied to determine body composition and hormonal changes with respect to stage of wasting [nonwasting (NW; weight >90% ideal body weight; weight loss <10% of preillness maximum; n = 12), early wasting (EW; weight >90% ideal body weight; weight loss >10% of preillness maximum; n = 10), and late wasting (LW; weight <90%; n = 9)] and compared with a control group of 12, healthy, age-matched women. Weight loss averaged 6 ± 6% (NW), 15 ± 6% (EW), and 20 ± 8% (LW) in the three groups. Lean, fat, and muscle masses were determined by dual energy x-ray absorptiometry and urinary creatinine excretion.
Subjects were 36 ± 5 yr of age (mean ± SD) with a CD4 cell count of 379 ± 239 cells/mm3. The body mass index was 24.4 ± 2.6 kg/m2 (NW), 22.2 ± 1.2 kg/m2 (EW), 18.2 ± 2.0 kg/m2 (LW), and 24.3 ± 2.6 kg/m2 (controls; P < 0.01, NW vs. EW; P < 0.0001, NW vs. LW). Lean body mass indexed for height was 15.7 ± 2.4 kg/m2 (NW), 14.8 ± 2.0 kg/m2 (EW), and 13.7 ± 1.2 kg/m2 (LW) and was decreased significantly only in the LW group (P < 0.05 vs. NW). Muscle mass was 96% (NW), 94% (EW), and 78% (LW) of that predicted for height (P < 0.05, NW vs. LW). In contrast, fat mass indexed for height was decreased significantly among patients in both the EW and LW groups [8.7 ± 1.9 kg/m2 (NW), 6.5 ± 1.9 kg/m2 (EW), and 3.7 ± 1.4 kg/m2 (LW); P < 0.05, NW vs. EW; P < 0.001, NW vs. LW). Expressed as a percentage of the value in nonwasting HIV-positive controls (NW), the relative loss of fat was greater than the loss of lean mass with progressive degrees of wasting [EW, 25% vs. 6% (fat vs. lean); LW, 58% vs. 13%].
The prevalence of amenorrhea was 20% among study subjects [17% (NW), 10% (EW), and 38% (LW)]. The percent predicted muscle mass was significantly lower in subjects with amenorrhea (74 ± 8%) compared to that in eumenorrheic HIV-positive subjects (94 ± 4%; P < 0.05). Estradiol levels were lower among subjects with amenorrhea (17.6 ± 21.8 pg/mL) compared to eumenorrheic HIV-positive (48.9 ± 33.6 pg/mL) and control (68.3 ± 47.6 pg/mL) subjects and did not correlate with body composition. Mean free testosterone, but not total testosterone, levels were decreased in subjects with EW and LW compared to those in age-matched healthy controls, but not compared with those in NW [0.9 ± 0.6 ng/dL (NW), 0.7 ± 0.4 ng/dL (EW), 0.6 ± 0.3 ng/dL (LW), and 2.0 ± 2.4 ng/dL (controls); P < 0.05, EW vs. controls and LW vs. controls] and correlated with muscle mass (r = 0.37; P < 0.05). The percentages of women with free testosterone levels below the age-adjusted normal range were 33% (NW), 50% (EW), and 66% (LW). Dehydroepiandrosterone sulfate levels were also low in the subjects with LW compared to those in the control group [98 ± 85 µg/dL (NW), 102 ± 53 µg/dL (EW), 55 ± 46 µg/dL (LW), and 132 ± 68 µg/dL (controls); P < 0.05 LW vs. controls] and were correlated highly with free testosterone levels (r = 0.73; P < 0.00001) and also with muscle mass (r = 0.48; P < 0.01).
These data demonstrate that women lose significant lean body and muscle mass in the late stages of wasting. However, in contrast to men, women exhibit a progressive and disproportionate decrease in body fat relative to lean body mass at all stages of wasting, consistent with gender-specific effects in body composition in AIDS wasting. In addition, these data demonstrate that androgen deficiency is common in women with AIDS wasting and may contribute to decreased muscle mass in this population.
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