A French study of men living with well-controlled HIV identified risk factors for low testosterone. It found that being aged over 43, use of efavirenz as treatment, having a higher percentage of body fat or a nadir CD4 count of less than 200 were all linked to lower levels of testosterone. Using these risk factors, it may be possible to improve early diagnosis of low testosterone and provide replacement treatment, to avoid problems with bones, mental health and sex.
Prior to the use of widespread effective antiretroviral treatment, low testosterone – otherwise known as hypogonadism – was the most common endocrine problem in people living with HIV. Testosterone is a sex hormone produced by the testicles, which is important for development of male characteristics and encourages bone growth, muscle growth and sperm production. Low testosterone can cause a decrease in bone density, sexual dysfunction, decreased muscle mass and depression, so can have a huge impact on a person’s quality of life.
In previous studies, low testosterone levels were strongly associated with people who had advanced HIV. Estimates of the prevalence of low testosterone have ranged from 9% to 70% of people living with HIV. Dr Marie Lachâtre and her colleagues have conducted the first published research on low testosterone levels in men who have never had an AIDS-defining illness, to see if there was still a problem, despite viral suppression and antiretroviral treatment.
The research published in AIDS was conducted from January 2013 until June 2016 in France. In total, 231 men living with HIV who were mostly in their late thirties or forties and were on HIV treatment with a suppressed viral load were recruited. Two early morning blood samples were collected, eight days apart, to measure average free testosterone levels (not bound to any other protein in the blood) and overall testosterone levels. Early morning samples are best, as levels change throughout the day. Men with previous opportunistic infections, liver or kidney problems and those on treatment involving testosterone, sex hormones or anabolic steroids were all excluded.
Free testosterone levels of less than 70 indicate low functioning testicles (hypogonadism). In people living with HIV, measurement of free testosterone levels is preferable to total testosterone levels due to the increase of another hormone (sex hormone binging globulin), which makes total testosterone less accurate. Other sex hormones were measured to confirm the reason for low testosterone. Low testosterone can be either a failure of the testicles to make testosterone (primary hypogonadism) or the brain not sending signals to the testicles to make testosterone (secondary hypogonadism). Participant demographics were recorded, as were other factors, such as erectile function, quality of life, depression, bone health and weight.
Overall, 20 (8.7%) of the men were found to have low testosterone, which is twice the rate in the general population of the same age. All 20 had secondary hypogonadism, in which a problem with the signalling from the brain is the cause of low testosterone. Risk factors identified for low testosterone included being over the median of 43 years old, having a lowest ever CD4 count of less than 200, using a treatment regimen including efavirenz and having a total fat percentage greater than 19%. The total fat percentage compares the level of fat in the body to overall weight, with the expected value for men being around 15%, but much higher for women. Increased fatty tissue encourages testosterone to be converted to oestrogen. The researchers hypothesised that efavirenz may also increase testosterone conversion into oestrogen, which lowers testosterone levels and causes the growth of breast tissue. They also suggested that the increase in low testosterone amongst men living with HIV was due to the early ageing effect of HIV.
When measuring both erectile dysfunction and worsening of quality of life, 55% participants reported these issues. One third of participants had symptoms of depression and 18% a diagnosis of osteoporosis. However, it is important to note that there was no significant link between any of these symptoms and low testosterone levels in this study, possibly due to the small size of the study.
Screening could be targeted at the higher risk groups for low testosterone such as those who use efaverinz, have a total body fat of at least 19% or who are aged over 43. Taking an early morning free testosterone sample in these groups could enable earlier detection of low testosterone levels. In turn this could lead to faster access to treatment with replacement testosterone and an improved quality of life.
Lachâtre M et al. Hypogonadism: a neglected comorbidity in young and middle-aged HIV-positive men on effective combination antiretroviral therapy. AIDS 36: 1061-1071, 2022 (open access).