French study finds testosterone deficiency more common in men with HIV than in HIV-negative men

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CATIE News 03082022
  • Testosterone deficiency was common in men with HIV before effective HIV treatment (ART) became available
  • A study in France of more than 200 men on ART assessed them for testosterone deficiency
  • 9% of these men were deficient—double the proportion seen in a study of HIV-negative men

Testosterone

The hormone testosterone plays an important role in the body, contributing to muscle strength, energy, mood, bone health and sexual function. Historically, HIV infection was associated with testosterone deficiency that could be at times severe. Today, with the widespread use of HIV treatment (ART) and a return to health for many ART users, HIV likely has a less drastic impact on testosterone levels.

A French study

Researchers in France analyzed blood samples from men with HIV who were using ART and who had undetectable viral loads. They found that about 9% of the men had testosterone deficiency. This proportion of HIV-positive men with testosterone deficiency was twice that seen in a study of men without HIV in the U.S. This finding from France is similar to results from a recent German study that compared testosterone levels in men with and without HIV. The French researchers made recommendations for doctors about screening HIV-positive men for this deficiency.

Study details

Researchers in France interviewed participants, gave them validated surveys to assess depression and quality of life, performed physical exams and collected blood samples for analysis. The men also underwent low-dose X-ray scans to determine body composition.

Importantly, blood samples were drawn between 7 am and 9 am (testosterone levels tend to peak early in the morning). All blood samples were assessed for testosterone at one laboratory, minimizing the chances for variation if multiple laboratories were used.

The average profile of participants upon study entry was as follows:

  • age – 43 years
  • 78% were gay, bisexual or other men who have sex with men
  • duration of HIV infection – 9 years
  • duration of suppressed HIV – 3 years
  • CD4+ cell count – 630 cells/mm3
  • all participants were taking ART and had an undetectable viral load

About testosterone forms

Most testosterone in circulation in the body is bound to a protein called SHBG (sex hormone binding globulin). This testosterone is called bound testosterone and is not available for use by the body. However, a small proportion of testosterone in the body (between 1% and 4%) is not bound; this is called free testosterone and is the testosterone that is available for use by the body.

Results

A total of 20 men (9%) had free testosterone levels less than 70 pg/mL, indicating deficiency.

The researchers stated that this proportion was double that seen in HIV-negative men of similar age in one U.S. study.

Participants with testosterone deficiency were more likely to have the following characteristics:

  • be older than 43 years
  • have a total body fat percentage greater than 19%
  • taking the drug efavirenz

Other findings

More than 50% (133) of men in the study reported erectile dysfunction and a deterioration in their quality of life. One-third of the men in the study had depression.

All participants with testosterone deficiency were referred to hormone specialists to initiate discussion about testosterone supplementation.

Limits to ART

Although multiple studies project that many ART users will have near-normal life expectancy, ART cannot resolve every issue. For instance, despite the use of ART, excessive levels of immune activation and inflammation occur. The cause of this excess immune activation and inflammation in people with HIV is not clear. Over the long term, it is plausible that such chronic immune activation and inflammation could contribute to the slow degradation of organs such as the brain, heart, liver, lungs, kidneys and pancreas. It is plausible that excess immune activation and inflammation could also contribute to deficiencies of hormones, such as growth hormone and testosterone.

Bear in mind

Ideally, the present study could have been larger and could have also enrolled a group of HIV-negative French men of similar age, body mass index and other factors for comparison. However, such a study would have been much more expensive and time consuming. Funds for HIV research are limited and other issues have a higher priority.

Although the present study suggested that as a group HIV-positive men were at heightened risk for testosterone deficiency, other factors could have influenced this finding. For instance, men with HIV in the present study might have had more risk factors (such as excess body fat, older age, and so on) for testosterone deficiency that were unrelated to HIV itself. It is also possible that some men in the study were taking medicines—anti-anxiety drugs, antidepressants, drugs for high blood pressure, opioids—that could have affected testosterone levels. However, there was no apparent assessment of non-HIV-related medicines and their potential impact on testosterone.

In studies of HIV-negative men, researchers have found that testosterone deficiency may be related to a wide range of factors, such as older age, insufficient sleep, nutrient deficiencies, excess body fat, stress, hepatitis C virus infection and more complex medical issues. Thus, when trying to find the cause of testosterone deficiency, consultation with a doctor is important.

For the future

Given their findings, the French researchers encourage doctors caring for men with HIV to assess their patients for the factors found in the present study—age older than 43, fat percent greater than 19% and use of efavirenz—and, if the factors are present, to screen them for testosterone deficiency.

The present study was done between 2013 and mid-2016. In the meantime, leading HIV treatment guidelines have changed and the use of efavirenz has declined. A study on testosterone deficiency in the current decade may be useful because of the changes in the use of ART regimens driven by treatment guidelines. Also, a larger study could assess the impact of other factors that might have contributed to testosterone deficiency.

—Sean R. Hosein

REFERENCES:

  1. Lachatre M, Pasquet A, Ajana F, et al. Hypogonadism: a neglected comorbidity in young and middle-aged HIV-positive men on effective cART. AIDS. 2022; in press.
  2. Wrzosek M, Woźniak J, Włodarek D. The causes of adverse changes of testosterone levels in men. Expert Review in Endocrinology and Metabolism. 2020 Sep;15(5):355-362.  
  3. Bhasin S, Jameson JL. Chapter 384. Disorders of the testes and male reproductive system. In: Jameson JL, Fauci AS, Kasper DL, Huser SL, Longo DL, Loscalzo, eds. Harrison’s Principles of Internal Medicine. 20th ed. New York: McGraw-Hill; 2018.
  4. Raffi F, Brisseau JM, Planchon B, et al. Endocrine function in 98 HIV-infected patients: a prospective study. AIDS. 1991 Jun;5(6):729-33.  
  5. Rodrigues Dos Santos M, Bhasin S. Benefits and risks of testosterone treatment in men with age-related decline in testosterone. Annual Review of Medicine. 2021 Jan 27; 72:75-91.  
  6. Maggio M, Basaria S, Ble A, et al. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. Journal of Clinical Endocrinology and Metabolism. 2006 Jan;91(1):345-7.  
  7. Sherman BT, Hu X, Singh K, et al. Genome-wide association study of high-sensitivity C-reactive protein, D-dimer, and interleukin-6 levels in multiethnic HIV+ cohorts. AIDS. 2021 Feb 2;35(2):193-204.  
  8. Taylor BS, So-Armah K, Tate JP, et al. HIV and obesity comorbidity increase interleukin 6 but not soluble CD14 or D-dimer. JAIDS. 2017 Aug 15;75(5):500-508.  
  9. Medzhitov R. The spectrum of inflammatory responses. Science. 2021 Nov 26;374(6571):1070-1075. 
  10. Meizlish ML, Franklin RA, Zhou X, et al. Tissue homeostasis and inflammation. Annual Review of Immunology. 2021 Apr 26; 39:557-581. 
  11. Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nature Medicine. 2019 Dec;25(12):1822-1832.
  12. Contrepois K, Wu S, Moneghetti KJ, et al. Molecular choreography of acute exercise. Cell. 2020 May 28;181(5):1112-1130.
  13. Marcus JL, Leyden WA, Alexeeff SE, et al. Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV Infection, 2000-2016. JAMA Network Open. 2020 Jun 1;3(6):e207954.
  14. Patterson S, Cescon A, Samji H, et al. Life expectancy of HIV-positive individuals on combination antiretroviral therapy in Canada. BMC Infectious Diseases. 2015 Jul 17; 15:274.  
  15. Pezzaioli LC, Porcelli T, Delbarba A, et al. Impact of hypogonadism on bone mineral density and vertebral fractures in HIV-infected men. Journal of Endocrinological Investigation. 2022 Feb;45(2):433-443.
  16. Wehbeh L, Dobs AS. Opioids and the Hypothalamic-Pituitary-Gonadal (HPG) Axis. Journal of Clinical Endocrinology and Metabolism. 2020 Sep 1;105(9):dgaa417.  
  17. Postel N, Wolf E, Balogh A, et al. Functional hypogonadism and testosterone deficiency in aging males with and without HIV infection. Experimental and Clinical Endocrinology and Diabetes. 2021 Nov;129(11):798-802.  
  18. Munkboel CH, Larsen LW, Weisser JJ, et al. Sertraline suppresses testis and adrenal steroid production and steroidogenic gene expression while increasing LH in plasma of male rats resulting in compensatory hypogonadism. Toxicological Sciences. 2018 Jun 1;163(2):609-619.
  19. Raittinen PVH, Syvälä H, Tammela TLJ, et al. Atorvastatin induces adrenal androgen downshift in men with prostate cancer: A post hoc analysis of a pilot adaptive randomised clinical trial. EBioMedicine. 2021 Jun; 68:103432. 
  20. Terentes-Printzios D, Ioakeimidis N, Rokkas K, et al. Interactions between erectile dysfunction, cardiovascular disease and cardiovascular drugs. Nature Reviews Cardiology. 2022 Jan;19(1):59-74.  
  21. De Vincentis S, Decaroli MC, Fanelli F, et al. Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV. European Journal of Endocrinology. 2021 Jan;184(1):107-122.  
  22. Price JC, Wang R, Seaberg EC, et al. Sex hormone-binding globulin levels are inversely associated with nonalcoholic fatty liver disease in HIV-infected and -uninfected men. Open Forum Infectious Diseases. 2019 Nov 6;6(12): ofz468.  
  23. Melo BP, Guariglia DA, Pedro RE, et al. Combined exercise modulates cortisol, testosterone, and immunoglobulin A levels in individuals living with HIV/AIDS. Journal of Physical Activity and Health. 2019 Nov 1;16(11):993-999.  
  24. Chaudhury CS, Mee T, Chairez C, et al. Testosterone in men with chronic hepatitis C infection and after hepatitis C viral clearance. Clinical Infectious Diseases. 2019 Aug 1;69(4):571-576.
  25. Falutz J. Growth hormone and HIV infection: contribution to disease manifestations and clinical implications. Best Practice and Research: Clinical Endocrinology & Metabolism. 2011 Jun;25(3):517-29.