Do Integrase Inhibitors Affect Testosterone Levels in Men?

March/April 2017

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Lower-than-normal levels of testosterone in men are associated with the following problems:

  • decreased interest in sex
  • erectile dysfunction
  • reduced muscle mass and strength
  • thinning bones
  • fatigue
  • in some cases, depression

Decreased testosterone levels occur as all men age.

In the time before potent HIV treatment (ART) became available, researchers found low testosterone levels in some men with HIV. In such cases this problem may have arisen for several reasons, including the following:

  • unintentional and severe weight loss (due to HIV disease)
  • HIV-related inflammation and injury to the body's hormonal networks
  • the development of life-threatening infections and prolonged and intense regimens of antibiotics, antifungals and antivirals needed to treat and later prevent infections from recurring

However, lower-than-normal levels of testosterone also have been found among HIV-positive men in the subsequent era who were using ART and never developed AIDS.

The reasons for this are not clear but may be related to dysfunction in the body's production of some hormones, including testosterone, perhaps arising directly or indirectly from HIV infection.

Decreased testosterone levels have also been linked to the following:

  • excessive intake of alcohol
  • injecting street drugs
  • hepatitis C virus infection

Measuring Testosterone

There are antibodies in the blood that bind to hormones such as testosterone. The unbound (or "free") testosterone is what is available for use by the body's cells. Therefore, when assessing testosterone levels, endocrinologists usually ask the laboratory to measure the amount of free testosterone in the blood. Hormone levels in the body usually vary by time of day (because of internal 24-hour cellular clocks). Researchers who study testosterone recommend that measurements of free testosterone be done early in the morning.

Researchers in Paris and elsewhere in France have conducted a study with 113 HIV-positive men, all less than 50 years old, who did not have AIDS and who were taking ART and who had a viral load less than 50 copies/mL. The researchers published their findings in the January 28, 2017 issue of the journal AIDS. They found that about 12% of the men had lower-than-normal levels of testosterone (measured as free testosterone) -- less than 70 pg/mL. This rate of low testosterone (called hypogonadism) is double the rate that would be seen in HIV-negative men of a similar range in age.

The researchers stated that they found a link between the use of integrase inhibitors and the presence of low testosterone. We caution readers that due to the study's design and other issues, such a conclusion must be treated very cautiously, and we explain why the researchers may have inadvertently arrived at such a conclusion.

Study Details

The average profile of the men when they were recruited for this study was as follows:

  • age -- 41 years
  • CD4+ count -- 627 cells/mm3
  • estimated duration of HIV infection -- six years

Bear in mind that blood and other tests were done largely at one point in time. We will return to this aspect of the study later.

Results -- Testosterone

  • Levels of antibodies that bind to testosterone were elevated in 48% of participants.
  • Lower-than normal levels of testosterone were found in 12% of men.
  • Men who had low testosterone levels were more likely to have had HIV longer than men with normal testosterone levels.
  • Some men with low testosterone levels also had thinner-than-normal bone density.
  • Having a percentage of body fat greater than 19% was associated with decreased testosterone levels (excess belly fat can convert some of the body's testosterone into estrogen).

Erectile Dysfunction

Men with low testosterone were more likely to have ED. However, even among men with normal levels of testosterone, 54% had ED. Men with ED had been using ART longer (76 months) than men without ED (44 months).

Specific Anti-HIV Drugs

The researchers stated that they found a relationship between the use of integrase inhibitors for more than two years and the presence of hypogonadism. Note that only 14 men were using integrase inhibitors in this study. We urge readers to treat this finding with caution due to a number of factors, including the nature of the study, which is explained below.

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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.

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