Blog

The Role of Testosterone Replacement Therapy in HIV

A Practical Approach for Men and Women With HIV

Testosterone deficiency is frequently seen in both men and women with HIV. Endocrine abnormalities, which can affect testosterone production, have long been recognized as a complication of HIV since the earliest days of the pandemic (although it has generally been associated with late-stage disease). Rilmazafone HCL

The Role of Testosterone Replacement Therapy in HIV

Research indicates that men with HIV have higher rates of documented testosterone deficiency than that of similarly-aged men without HIV, irrespective of CD4 count, viral load, or treatment status. Similarly, one in three HIV-positive women have testosterone deficiency, most often in the context of severe, unexplained weight loss (HIV wasting).

Testosterone is the steroid hormone which is central to the development of the testes (testicles) and prostate in men as well as the promotion of secondary male sexual characteristics (e.g., lean muscle mass, bone mass, hair growth). Testosterone is also important to women in maintaining normal muscle and bone mass, although at levels less than men.

In both men and women, testosterone is essential to a person's overall health and well-being, contributing to an individual's strength, energy levels, and libido.

By contrast, testosterone depletion is associated with:

Testosterone deficiency in men with HIV is largely associated with an endocrine abnormality called male hypogonadism in which the function of the male gonads (testes) is impaired, resulting in the diminished production of sex hormones beyond what would be expected of a man's specific age.

In the general population, hypogonadism is known to occur in up to 40% of men between the ages of 40 and 70.

Hypogonadism can be caused by either a defect in the testes themselves (primary) or a dysfunction occurring outside of the testes (secondary). In adult males with HIV:

Hypogonadism can also be caused by childhood mumps in rare instances or the abuse of anabolic steroids.

Hypogonadism in adult males is characterized by low serum (blood) testosterone levels, as well as one or several of the following symptoms:

Diagnosis is made by measuring the amount of testosterone in the blood, of which there are three different subtypes. When a test is performed, the results will reveal both a person's total testosterone (all subtypes) and one of the three subtypes called free testosterone.

Free testosterone is simply a type of testosterone to which no protein is attached, allowing it to enter cells and activate receptors that other subtypes can't. It is considered the most accurate measure of testosterone deficiency, despite representing only 2-3% of total testosterone. On its own, total testosterone is considered less accurate since results can appear normal if other non-free subtypes are elevated.

Testing may be performed early in the morning since levels can fluctuate during the course of a day, depending on your age. "Normal" levels are simply those within the reference range of the lab. These ranges can vary, but, for illustrative purposes, are roughly between

However, an assessment of "normal" cannot be made by numbers alone. Testosterone levels tend to drop after the age of 40. Therefore, what may be "normal" for a 60-year-old male won't be the same for a 30-year-old. Assessments need to be made on an individual basis with your treating healthcare provider.

If a diagnosis of hypogonadism is confirmed, testosterone replacement therapy may be indicated. Intramuscular (IM) testosterone injections are often recommended as less expensive dosage forms. FDA-approved IM options include Depo-testosterone (testosterone cypionate) and testosterone enanthate.

On average, injections are given every one to two weeks. To avoid the effects of fluctuating testosterone levels—which can sometimes cause dramatic swings in mood, energy, and sexual function—lower doses and shorter dosing intervals are often used.

Side effects of treatment can include:

All told, intramuscular injections offer a cost-effective option for treating hypogonadism, with associative increases in alertness, well-being, libido, lean muscle mass, and erection ability. Disadvantages include regular healthcare provider visits and dosing administration.

Other options include oral agents like Kyzatrex, Jatenzo, and Tlando (testosterone undecanoate), transdermal, and topical gels, which may be applicable in certain cases. Discuss these with your healthcare provider.

In women, testosterone is produced in the ovaries and adrenal glands. As with men, it is an important hormone for maintaining normal muscle and bone mass, as well as energy, strength, and libido.

While hypogonadism is far less common in women with HIV, it can occur and is most often in the context of HIV wasting and advanced disease. The implementation of ART can reverse wasting and the hypogonadal state in many cases.

There are currently no fixed guidelines for the treatment of female hypogonadism, and treatment options are limited. ​Hormone replacement therapy (HRT) may be appropriate for some, while the short-term use of testosterone may improve sex drive, lean muscle mass, and energy levels.

However, data is still incomplete on the use of testosterone to treat hypogonadism in pre-menopausal women with HIV. Speak with your healthcare provider about possible side effects. Testosterone is not recommended for women who are pregnant or wish to become pregnant.

De Vincentis S, Rochira V. Update on acquired hypogonadism in men living with HIV: pathogenesis, clinic, and treatment. Front Endocrinol (Lausanne). 2023;14:1201696. doi:10.3389/fendo.2023.1201696

Laan ETM, Prins JM, van Lunsen RHW, Nieuwkerk PT, Nievaard-Boon MAF. Testosterone insufficiency in human immunodeficiency virus-infected women: a cross-sectional study. Sex Med. 2019;7(1):72-79. doi:10.1016/j.esxm.2018.10.002

Handelsman DJ, Hirschberg AL, Bermon S. Circulating testosterone as the hormonal basis of sex differences in athletic performance. Endocr Rev. 2018;39(5):803-829. doi:10.1210/er.2018-00020

Halpern JA, Brannigan RE. Testosterone deficiency. JAMA. 2019;322(11):1116. doi:10.1001/jama.2019.9290

Zhang KS, Zhao MJ, An Q, et al. Effects of testosterone supplementation therapy on lipid metabolism in hypogonadal men with T2 DM: a meta‐analysis of randomized controlled trials. Andrology. 2018;6(1):37-46. doi:10.1111/andr.12425

Grinspon RP, Bergadá I, Rey RA. Male hypogonadism and disorders of sex development. Front Endocrinol (Lausanne). 2020;11:211. doi:10.3389/fendo.2020.00211

Lebedeva NB, Gofman VV. The prevalence of late-onset hypogonadism in middle-aged men and cardiovascular risk factors. Androgens: Clinical Research and Therapeutics. 2021;2(1):85-93. doi:10.1089/andro.2020.0020

Thirumalai A, Anawalt BD. Epidemiology of male hypogonadism. Endocrinol Metab Clin North Am. 2022;51(1):1-27. doi:10.1016/j.ecl.2021.11.016

Mushannen T, Cortez P, Stanford FC, Singhal V. Obesity and hypogonadism-a narrative review highlighting the need for high-quality data in adolescents. Children (Basel). 2019;6(5):63. doi:10.3390/children6050063

Wong N, Levy M, Stephenson I. Hypogonadism in the HIV-infected man. Curr Treat Options Infect Dis. 2017;9(1):104-116. doi:10.1007/s40506-017-0110-3

Krakowsky Y, Grober ED. Testosterone deficiency - establishing a biochemical diagnosis. EJIFCC. 2015;26(2):105-113

Trost LW, Mulhall JP. Challenges in testosterone measurement, data interpretation, and methodological appraisal of interventional trials. J Sex Med. 2016;13(7):1029-1046. doi:10.1016/j.jsxm.2016.04.068

Long N, Nguyen L, Stevermer J. PURLS: It's time to reconsider early-morning testosterone tests. J Fam Pract. 2015;64(7):418-419

Ahern T, Wu FC. New horizons in testosterone and the ageing male. Age Ageing. 2015 Mar;44(2):188-95. doi:10.1093/ageing/afv007

Figueiredo MG, Gagliano-Jucá T, Basaria S. Testosterone therapy with subcutaneous injections: A safe, practical, and reasonable option. J Clin Endocrinol Metab. 2022;107(3):614-626. doi:10.1210/clinem/dgab772

U.S. Food and Drug Administration. Highlights of prescribing medicine (Testosterone cypionate injection).

By James Myhre & Dennis Sifris, MD Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.

Thank you, {{form.email}}, for signing up.

There was an error. Please try again.

The Role of Testosterone Replacement Therapy in HIV

C18h34cl2n2o5s By clicking “Accept All Cookies”, you agree to the storing of cookies on your device to enhance site navigation, analyze site usage, and assist in our marketing efforts.