Fwd: CATIE News - Testosterone increase may depend on medications used

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In a message dated 6/7/2007 10:13:33 A.M. Central Daylight Time, info@... writes:

CATIE News - Testosterone increase may depend on medications used

Before highly active antiretroviral therapy (HAART) became available, several studies in high-income countries with people with HIV/AIDS (PHAs) suggested that less-than-normal levels of testosterone may occur. This can result in thinning bones, reduced sex drive and difficulty maintaining or increasing muscle mass. Some men may also become depressed when a testosterone deficiency occurs.

After PHAs begin taking HAART, production of HIV falls and the body begins to repair the damage done by years of unrelenting HIV infection. As a result, improvements in health start to occur. Researchers with the United States AIDS Clinical Trials Group (ACTG) were curious as to what happens to testosterone levels when PHAs use HAART. Exploring this idea is important because currently, at least in most high-income countries, comprehensive health care and treatment is widely available. Provided that PHAs are aware of their HIV infection and engaged in their health care, they should not be severely ill—as was often the case before the advent of HAART, particularly for people with AIDS. Severely ill PHAs, including those suffering from the wasting syndrome, tended to have low testosterone levels.

Assessing testosteroneMany studies assess testosterone levels in the blood by reporting “total testosterone.†This is important to note because testosterone in the blood is found in two forms, as follows:

* free testosterone—this is the amount of testosterone that is available or free for use by the body

* bound testosterone—this means that testosterone is bound to a protein called SHBG (serum hormone binding globulin). This protein captures testosterone and makes it unavailable for use.

When assessing testosterone levels, tests that can be ordered include “total†testosterone and “free†testosterone. Total testosterone does not distinguish between free testosterone and bound testosterone.

The ACTG team decided to focus its research on free testosterone and conducted a study called A5005s. This was a sub-study of a larger clinical trial called ACTG 384. In that larger trial, PHAs were enrolled in the late 1990s to study the effects of different combinations of anti-HIV medications.

Overall, study A5005s found that testosterone deficiency was relatively uncommon before starting HAART—occurring in about 6% of men. After HAART was initiated, testosterone levels rose. However, the increase differed depending on the study regimens.

Study detailsACTG 384 was a large study that enrolled 940 PHAs. It was designed to assess the effectiveness of different drug regimens for the treatment of HIV infection. Study A5005s, a sub-study of some PHAs who were enrolled in the larger study, is the focus of our report.

Enrollment in the sub-study occurred between 1998 and 1999, and participants were monitored until 2001. Unfortunately, only a relatively small number of women volunteered for this study. As a result, no meaningful interpretation of their results could be made, so the research team focused its analysis on 213 men on whom they collected data.

Here is the average profile of the male participants in study A5005s before they began to take HAART:

* age – 37 years* CD4+ cell count – 263 cells* viral load – 160,000 copies* free testosterone level – 92 picograms/mL (pg/mL)* about 7% had previously engaged in injecting drugs

Upon entering the study, no participant was taking hormone-replacement therapy.

Participants were randomly assigned to one of the following six regimens:

* AZT (zidovudine, Retrovir) + 3TC (lamivudine, Epivir) + efavirenz (Sustiva, Stocrin)* AZT + 3TC + nelfinavir (Viracept)* ddI (didanosine, Videx) + d4T (stavudine, Zerit) + efavirenz* ddI + d4T + nelfinavir* ddI + d4T + efavirenz + nelfinavir* AZT + 3TC + efavirenz + nelfinavir

The study also assessed body composition, focusing on changes in fat and muscle. This was done using a relatively simple technique called BIA (bio-electrical impedance analysis), during which a very small, painless electric current is run through the body. The amount of resistance to the current helps researchers to assess the amount of water, fat, bone and muscle in the body. Although BIA is not as accurate as other tests such as low-dose X-rays (DEXA) or MRI (magnetic resonance imaging), it is much cheaper.

Results—testosterone levelsAccording to the study team, the expected range for free testosterone levels in adult men is between 50 and 210 pg/mL. In this study, the average level of free testosterone before participants took HAART was 92 pg/mL, which suggests that testosterone deficiency was uncommon. Indeed, only 6% of men had less-than-normal levels of free testosterone.

The researchers compared total testosterone levels with free testosterone and found that total testosterone was often inadequate in correctly estimating the amount of testosterone available for use.

Factors that were associated with having a testosterone deficiency at the start of this study included the following:

* having a low CD4+ cell count (suggesting poorer overall health)* being older (testosterone levels decline with age)* being overweight

Several months after starting HAART, on average, testosterone levels began to rise significantly compared to pre-study values. But participants on some regimens were more likely to have larger increases in testosterone levels than those on other regimens. For instance, after one year, participants who received AZT + 3TC were more likely to have greater increases in testosterone (31 pg/mL) than participants who received ddI + d4T (2 pg/mL).

Participants who received efavirenz were also more likely to have significantly increased testosterone levels (30 pg/mL) after one year than those who received nelfinavir (minus 3 pg/mL).

Results—changes in body compositionAccording to the study team, increases in muscle mass were greater over time among participants who received AZT + 3TC than among those who received ddI + d4T. And muscle mass increased to a greater extent among men who received efavirenz than those who received nelfinavir.

Points to considerThe findings from this study may be reflective of testosterone levels in men in the HAART era. Indeed, studies conducted before the availability of HAART suggested that testosterone deficiency may have been more common. Perhaps this was the case because more people were ill, had lower CD4+ counts or experienced unintentional weight loss.

The researchers encourage physicians to request that their laboratories measure free testosterone levels when assessing their HIV positive patients for hormone-related health concerns.

Finally, it is important to note that the results seen in this study occurred with the specific regimens used. Other regimens might have different effects on testosterone levels and these will need to be tested in the future, on men as well as women.

— R. Hosein

REFERENCE:

Dubé MP, RA, Mulligan K, et al. Effects of potent antiretroviral therapy on free testosterone levels and fat-free mass in men in a prospective, randomized trial: A5005s, a substudy of AIDS Clinical Trials Group Study 384. Clinical Infectious Diseases 2007 July 1; in press.

****************************************************CATIE-News Subscription Information================================= CATIE-News is a moderated mailing list operated by the Canadian AIDS Treatment Information Exchange to distribute information about the treatment of HIV/AIDS and related infections in Canada. To see a directory of archived messages, visit CATIE's Web site at http://www.catie.ca/catienews.nsf To subscribe to the list, visit https://www.catie.ca/mailing.nsf/subscribe To cancel your subscription to the list, visit https://www.catie.ca/mailing.nsf/Unsubscribe For assistance with your subscription from a real human being, please send a message to web@... CATIE-News is written by Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto. Your comments are welcome. Permission to Reproduce:This document is copyrighted by the Canadian AIDS Treatment Information Exchange (CATIE). All CATIE materials may be reprinted and/or distributed without prior permission. However, reprints may not be edited and must include the following text: From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca For permission to edit any CATIE material for further publication, please send an e-mail to info@... If you are changing your e-mail address, please be sure to inform us of this change so that we can update your records and ensure that you continue to receive the latest treatment information. E-mail us at info@...

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CATIE News - Testosterone increase may depend on medications used

Before highly active antiretroviral therapy (HAART) became available, several studies in high-income countries with people with HIV/AIDS (PHAs) suggested that less-than-normal levels of testosterone may occur. This can result in thinning bones, reduced sex drive and difficulty maintaining or increasing muscle mass. Some men may also become depressed when a testosterone deficiency occurs.

After PHAs begin taking HAART, production of HIV falls and the body begins to repair the damage done by years of unrelenting HIV infection. As a result, improvements in health start to occur. Researchers with the United States AIDS Clinical Trials Group (ACTG) were curious as to what happens to testosterone levels when PHAs use HAART. Exploring this idea is important because currently, at least in most high-income countries, comprehensive health care and treatment is widely available. Provided that PHAs are aware of their HIV infection and engaged in their health care, they should not be severely ill—as was often the case before the advent of HAART, particularly for people with AIDS. Severely ill PHAs, including those suffering from the wasting syndrome, tended to have low testosterone levels.

Assessing testosteroneMany studies assess testosterone levels in the blood by reporting “total testosterone.” This is important to note because testosterone in the blood is found in two forms, as follows:

* free testosterone—this is the amount of testosterone that is available or free for use by the body

* bound testosterone—this means that testosterone is bound to a protein called SHBG (serum hormone binding globulin). This protein captures testosterone and makes it unavailable for use.

When assessing testosterone levels, tests that can be ordered include “total” testosterone and “free” testosterone. Total testosterone does not distinguish between free testosterone and bound testosterone.

The ACTG team decided to focus its research on free testosterone and conducted a study called A5005s. This was a sub-study of a larger clinical trial called ACTG 384. In that larger trial, PHAs were enrolled in the late 1990s to study the effects of different combinations of anti-HIV medications.

Overall, study A5005s found that testosterone deficiency was relatively uncommon before starting HAART—occurring in about 6% of men. After HAART was initiated, testosterone levels rose. However, the increase differed depending on the study regimens.

Study detailsACTG 384 was a large study that enrolled 940 PHAs. It was designed to assess the effectiveness of different drug regimens for the treatment of HIV infection. Study A5005s, a sub-study of some PHAs who were enrolled in the larger study, is the focus of our report.

Enrollment in the sub-study occurred between 1998 and 1999, and participants were monitored until 2001. Unfortunately, only a relatively small number of women volunteered for this study. As a result, no meaningful interpretation of their results could be made, so the research team focused its analysis on 213 men on whom they collected data.

Here is the average profile of the male participants in study A5005s before they began to take HAART:

* age – 37 years* CD4+ cell count – 263 cells* viral load – 160,000 copies* free testosterone level – 92 picograms/mL (pg/mL)* about 7% had previously engaged in injecting drugs

Upon entering the study, no participant was taking hormone-replacement therapy.

Participants were randomly assigned to one of the following six regimens:

* AZT (zidovudine, Retrovir) + 3TC (lamivudine, Epivir) + efavirenz (Sustiva, Stocrin)* AZT + 3TC + nelfinavir (Viracept)* ddI (didanosine, Videx) + d4T (stavudine, Zerit) + efavirenz* ddI + d4T + nelfinavir* ddI + d4T + efavirenz + nelfinavir* AZT + 3TC + efavirenz + nelfinavir

The study also assessed body composition, focusing on changes in fat and muscle. This was done using a relatively simple technique called BIA (bio-electrical impedance analysis), during which a very small, painless electric current is run through the body. The amount of resistance to the current helps researchers to assess the amount of water, fat, bone and muscle in the body. Although BIA is not as accurate as other tests such as low-dose X-rays (DEXA) or MRI (magnetic resonance imaging), it is much cheaper.

Results—testosterone levelsAccording to the study team, the expected range for free testosterone levels in adult men is between 50 and 210 pg/mL. In this study, the average level of free testosterone before participants took HAART was 92 pg/mL, which suggests that testosterone deficiency was uncommon. Indeed, only 6% of men had less-than-normal levels of free testosterone.

The researchers compared total testosterone levels with free testosterone and found that total testosterone was often inadequate in correctly estimating the amount of testosterone available for use.

Factors that were associated with having a testosterone deficiency at the start of this study included the following:

* having a low CD4+ cell count (suggesting poorer overall health)* being older (testosterone levels decline with age)* being overweight

Several months after starting HAART, on average, testosterone levels began to rise significantly compared to pre-study values. But participants on some regimens were more likely to have larger increases in testosterone levels than those on other regimens. For instance, after one year, participants who received AZT + 3TC were more likely to have greater increases in testosterone (31 pg/mL) than participants who received ddI + d4T (2 pg/mL).

Participants who received efavirenz were also more likely to have significantly increased testosterone levels (30 pg/mL) after one year than those who received nelfinavir (minus 3 pg/mL).

Results—changes in body compositionAccording to the study team, increases in muscle mass were greater over time among participants who received AZT + 3TC than among those who received ddI + d4T. And muscle mass increased to a greater extent among men who received efavirenz than those who received nelfinavir.

Points to considerThe findings from this study may be reflective of testosterone levels in men in the HAART era. Indeed, studies conducted before the availability of HAART suggested that testosterone deficiency may have been more common. Perhaps this was the case because more people were ill, had lower CD4+ counts or experienced unintentional weight loss.

The researchers encourage physicians to request that their laboratories measure free testosterone levels when assessing their HIV positive patients for hormone-related health concerns.

Finally, it is important to note that the results seen in this study occurred with the specific regimens used. Other regimens might have different effects on testosterone levels and these will need to be tested in the future, on men as well as women.

— R. Hosein

REFERENCE:

Dubé MP, RA, Mulligan K, et al. Effects of potent antiretroviral therapy on free testosterone levels and fat-free mass in men in a prospective, randomized trial: A5005s, a substudy of AIDS Clinical Trials Group Study 384. Clinical Infectious Diseases 2007 July 1; in press.

****************************************************CATIE-News Subscription Information================================= CATIE-News is a moderated mailing list operated by the Canadian AIDS Treatment Information Exchange to distribute information about the treatment of HIV/AIDS and related infections in Canada. To see a directory of archived messages, visit CATIE's Web site at http://www.catie.ca/catienews.nsf To subscribe to the list, visit https://www.catie.ca/mailing.nsf/subscribe To cancel your subscription to the list, visit https://www.catie.ca/mailing.nsf/Unsubscribe For assistance with your subscription from a real human being, please send a message to web@... CATIE-News is written by Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto. Your comments are welcome. Permission to Reproduce:This document is copyrighted by the Canadian AIDS Treatment Information Exchange (CATIE). All CATIE materials may be reprinted and/or distributed without prior permission. However, reprints may not be edited and must include the following text: From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca For permission to edit any CATIE material for further publication, please send an e-mail to info@... If you are changing your e-mail address, please be sure to inform us of this change so that we can update your records and ensure that you continue to receive the latest treatment information. E-mail us at info@...