Testosterone patches can increase muscle strength in HIV-positive women with low body weight, according to a study published in the April 26th edition of the Archives of Internal Medicine.
Numerous studies in men and a few in women (many by the same Massachusetts General Hospital/Harvard Medical School research team that conducted the present study) have demonstrated that individuals with HIV often have below-normal testosterone levels (hypogonadism). Low testosterone is more common in people with advanced HIV disease and wasting. Research in men has shown that supplemental testosterone at physiological doses -- enough to bring levels within the normal range -- is an effective therapy for treating overall body wasting, as well as the mixed peripheral wasting and central fat accumulation often seen in people with lipodystrophy. Testosterone therapy can also reduce fatigue, relieve depression, and restore lost libido.
Although testosterone is usually considered a male hormone, women also produce a small amount. A few small studies have shown that physiological testosterone therapy produces weight gain in HIV-infected women. The hormone must be administered cautiously to women, however, since it can cause undesired masculinising effects such as excessive hair growth (hirsutism), voice hoarseness, and clitoral enlargement. (For this reason, some physicians prefer to treat women with synthetic androgens such as oxandrolone or nandrolone decanoate, which may provide the muscle-building benefits of testosterone with fewer masculinising effects.)
This study included 57 HIV-infected women aged 18-45 (mean 38) recruited between 1998 and 2001; 56% were white, 18% were African American, 16% were Hispanic, and 10% were classified as “other”. All women had lost 10% or more of their pre-illness body weight (average loss of 18.7%) or weighed less than 90% of the ideal weight for women their age; the mean body mass index was 20.6. The group as a whole had a mean CD4 count of 317 cells/mm3 and an average viral load of nearly 16,000 copies/ml. Although most were on antiretroviral therapy (93% NRTIs; 74% PIs; 53% NNRTIs), only 25% had an undetectable viral load.
At baseline, the subjects had demonstrated reduced muscle function and free testosterone levels below the midpoint of the normal range for women, approximately 1.1 to 6.3pg/ml. (Free testosterone refers to bioavailable testosterone that is not bound to proteins in the blood.)
Participants were randomly assigned to use 4mg transdermal testosterone patches (estimated to deliver about 150µg per day) or placebo patches applied twice weekly for six months.
Women who used testosterone patches achieved significantly increased blood concentrations of total and free testosterone, bringing levels into the upper half or slightly above the normal range for most subjects. The treatment group had an average increase in total testosterone of 37ng/dl, compared with an average decrease of 2ng/dl in the placebo group (p<.001 and="" change.="" changes="" corresponding="" did="" for="" free="" hormones="" levels="" not="" oestrogen="" of="" other="" testosterone="" the="" were="">
Women who received testosterone experienced significantly improved muscle strength as determined by the amount of force they could exert in tests of shoulder, elbow, and knee flexion, and knee extension. A trend toward improvement was seen in shoulder extension; elbow extension, ankle dorsiflexion, and grip strength did not change. Muscle strength did not increase in the placebo group, and for some muscle groups it decreased. In addition, women in the treatment group were able to walk longer distances in six minutes, while the distance walked in the placebo arm decreased.
The treated women also showed a trend toward increased muscle mass (a gain of 1.4 kg with testosterone vs 0.3 kg with placebo), although the change did not reach statistical significance (p= 0.08). In contrast to some previous testosterone studies, total weight did not increase, nor were significant changes in either total body fat or abdominal fat.
The testosterone patch was well tolerated and did not produce hirsutism, voice deepening, menstrual irregularities, or other signs of masculinisation. Further, testosterone did not adversely affect glucose or lipid metabolism or liver function - side effects sometimes seen with higher doses of testosterone.
“Testosterone administration is well-tolerated and increases muscle strength in low-weight HIV-infected women,” the researchers concluded. “Testosterone administration may be a useful adjunctive therapy to maintain muscle function in symptomatic HIV-infected women.”
While severe AIDS-related wasting is uncommon today among HIV-infected individuals receiving combination antiretroviral therapy, there remains considerable concern about muscle and fat wasting associated with use of HAART. Testosterone (and synthetic androgens) appears to be an effective therapy for lipodystrophy in men, but further research is needed for women.
Reference
Dolan S et al. Effects of testosterone administration in human immunodeficiency virus–infected women with low weight: a randomised placebo-controlled study. Arch Intern Med 164: 897-904, 2004.