Reduced testosterone levels in HIV-positive women
Polly Clayden, HIV i-Base
A paper from Massachusetts General and Harvard Medical School published in Clinical Infectious Diseases investigates the relationship between reduced androgen levels and antiretroviral regimen amongst HIV-positive women with low weight or weight loss.
Research into sex-specific and hormonal factors in women either with or without HIV is scarce. There are data from the pre-HAART era to suggest that women with HIV have reduced androgen levels and more recently that reduced levels in this population may be caused by altered androgen metabolism. In contrast to androgen deficiency in men, androgen deficiency in women and in turn the contribution this may make to their general health and well being, particularly with respect to weight loss, fatigue and decreased functional status has not been well characterised.
This study investigates hormone levels in 69 HIV-positive women participants with AIDS wasting syndrome screened for a testosterone intervention study with 25 age, ethnicity and BMI-matched uninfected women as control subjects. Women were excluded from screening if they had used growth hormone, systemic corticosteroids, megastrol acetate, estrogens, androgens or any hormonal products that could affect androgen levels up to three months before entering the study or if they had switched their antiretroviral regimen up to six weeks before.
Participants were asked their pre-illness maximum weight and were stratified according to their current menstrual status and their height and weight measured. Antiretroviral history was also obtained from HIV-positive women.
Serum samples were obtained during visits scheduled independently to the menstrual cycle and time of day and free testosterone levels determined. All samples obtained from the same subject were tested in duplicate.
The normal range for total testosterone concentration in adult women is 10-55ng/dL (0.4-1.9nM). The normal ranges for total testosterone (n=215) and free testosterone (n=141) were determined for healthy subjects tested during the course of the day and also with regard to menstrual cycle. Testosterone levels were compared among HIV-positive women by menstrual status – eumenorrheic (normal menstrual function) or not and by weight loss of >10% from pre-illness maximum and antiretroviral regimen.
HIV-positive women had low weights, with a BMI of 21.0+- 3.0kg/m2. Subjects had lost a mean of –17.6%+-9.7% from their pre-illness maximum and more HIV-positive women had a BMI of <205kg/m2. Seventy five percent of HIV-positive subjects were using antiretroviral therapy and 49% were using HAART (triple therapy including two nucleosides and either a PI or NNRTI).
Total and free testosterone levels were reduced in the HIV women compared to the controls. Free testosterone levels were less than the normal range in 49% of HIV-positive subjects but only in 8% of control subjects, but only 26% of HIV-positive women had total testosterone levels that were less than the normal range.
Free testosterone levels were compared by disease and menstrual status and by various weight and antiretroviral regimen variables in the HIV-positive women and significant differences in free testosterone levels were seen in the comparison arm by percentage of weight loss.
Fifty-eight percent of the patients with weight loss of >10% versus 24% of subjects with weight loss of <10% of body weight had a free testosterone level that was less than the normal range. Free testosterone levels were significantly higher in eumenorrheic subjects. But no differences in free testosterone levels were seen in comparisons by antiretroviral use or by HIV disease status.
The investigators also found that among HIV-positive women free testosterone levels correlated with age, length of HIV infection and percentage of change in weight but not weight itself. They also reported that among the eumenorrheic group (n=39) greater numbers of women had low free testosterone levels in the follicular phase (the first seven days of cycle n=14, 71.4% had levels below the normal range) than in other phases of the cycle.
The investigators report: “Our data demonstrate severely reduced testosterone levels in HIV-infected women with weight loss of >10% of pre-illness maximum weight. In contrast, other weight parameters, including historical low weight and percentage of ideal body weight, as well as use of antiretroviral medication, did not contribute significantly to testosterone levels in this population. Menstrual status did appear to correlate with serum free testosterone levels but did not remain a significant predictor in multivariate modeling.”
They also noted: “In this study, we demonstrated the relationship between weight loss and androgen levels in HIV-infected women. A large percentage of HIV-infected women with significant weight loss have reduced androgen levels, even in the era of HAART. Determination of the functional consequences of androgen deficiency and the role of physiological androgen replacement will be important in this population.”
Huang JS, Wilkie SJ, Dolan S et al Reduced testosterone levels in Human Immunodeficiency Virus-infected women with weight loss and low weight. Clinical infectious diseases 2003;36:499-506.