Does Hypogonadism Correlate with HIV in Men?

What is the relationship between HIV infected men who suffer with hypogonadism?

For those men who are suffering from HIV, be it under treatment or not, they all share low natural testosterone levels.

We know that having a higher level of natural testosterone can improve life quality, affecting such parameters as:

  • Bone density
  • Muscle mass
  • Fat distrbution
  • Lipolysis process
  • Energy
  • Cognitive health
  • Libido
  • Cardiovascular health

It can also cause a loss of hair, reduced sleep quality, reduced testicle size and puffy nipples (gynaecomastia).

Therefore, it is imperative that options for treatment for the HIV infected man are discussed and implemented.

  • [Raffi F, Brisseau JM, Planchon B, et al. Endocrine function in HIV infected patients: a prospective study. AIDS. 1991;5:729–733. doi: 10.1097/00002030-199106000-00013.]

Correlation

There has been a connection observed between low test levels and HIV within infected men for some time now.

This is more evident in men suffering from advanced immunosuppression.

Tests have seen a slight raise in natural T levels when men are treated with anti-retroviral therapy (ART).

However, low test levels ares still an concurrent issue for those infected men.

  • [Wunder DM, Bersinger NA, Fux CA, et al. Hypogonadism in HIV-1 infected men is common and does not resolve during antiretroviral therapy. Antivir Ther. 2007;12:261–265.]

How does testosterone work?

Testosterone is the male sex hormone which is produced in the testes by Leydig cells by the stimulation of the luteinising hormone.

This stimulation produces the secretion of testosterone.

When a man suffers from low test (hypogonadism) this is due to the testes being unable to produce sufficient levels of testosterone along with a failure to produce enough sperm.

Hypogonadism can be confirmed by measuring the serum total testosterone during the morning hours of 8 and 10, this is because test concentrations peak in the morning.

  • [Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab. 1983;56:1278. doi: 10.1210/jcem-56-6-1278.]

To confirm hyogonadism status, there must be two low testosterone measurements taken and concluded.

There are two forms of testosterone which circulates:

  • sex hormone-binding globulin
  • free testosterone.

If there is any abnormal activity with the sex hormone-binding globulin, this can then have an influence over the total testosterone results.

This is due to low sex hormone-binding globulin will result in a low testosterone level.

On the flip of a coin, if sex hormone-binding globulin is at a healthy level, it can make total test levels appear in the normal range, regardless of free testosterone levels reading significantly lower and actually causing hypogonadism.

Sex hormone-binding globulin concentrations can provide different readings and abnormalities can be thrown up for a variety of causes.

These can be due to:

  • Ageing
  • Hypothroydism (causing the metabolism to run slow)
  • Increased estroegn
  • Liver disease and cirrhosis
  • HIV
  • Obesity
  • Type 2 diabetes
  • Anabolic steroid use
  • Kidney damage

Those men who are infected with HIV will show an elevated level of sex hormone-binding globulin, this could actually provide a ‘false’ reading of total testosterone levels when the free testosterone is low.

If sex hormone-binding globulin levels are low for the HIV infected man on treatment, this is most likely due to obesity, diabetes or insulin resistance.

Reducing weight in the patient can reverse the abnormal reading.

  • [Dobs A. Role of testosterone in maintaining lean body mass and bone density in HIV-infected patients. Int J Impot Res. 2003;15(Suppl 4):S21–S25. doi: 10.1038/sj.ijir.3901032.]

Hypogonadism and HIV

What has been established is that the occurrence of hypogonadism is prevalent in men who are also infected with HIV, in fact, up to 70% were showing results of low serum testosterone levels.

They were also experiencing weight loss, low CD4 count ans AIDS wasting.

Further associated illnesses suppressed the secretion from gonadotrope cells, as a result, the low testosterone concentrations in AIDS could be the result of inflammation and disease.

Even 30% of men who are receiving anti-retroviral therapy, which can help alleviate low test levels, suffer from low serum testosterone levels.

The accompanying factors are:

  • strength reduction
  • depression
  • muscle degeneration

A study in New York involving men with HIV viruses in the blood that here not controlled has a strong link to abnormally low testosterone as well as obesity and chronic hepatitis C virus infection.

  • [Reitschel P, Corcoran C, Stanley T, et al. Prevalence of hypogonadism among men with weight loss related to HIV infection who were receiving highly active antiretroviral therapy. Clin Infect Dis. 2000;11:1120–1244.]

Moreover, there is a strong correlation between ill health and hypogonadism in HIV infected men.

As the testosterone levels drop, the risk of accompanying potential fatal illnesses along with other disease, inflammation and infections rise significantly.

There appears to be a multi-risk factor issue which promotes and nurtures the reduction of low testosterone in HIV infected men.

This is most likely related to a number of co-occurring disease and disorders such as inflammation, hepatitus C, recreational drug use, anti-retroviral therapy and the change of body composition.

  • [Rochira V, Diazzi C, Santi D, et al. Low testosterone is associated with poor health status in men with HIV infection: retrospective study. Andrology. 2015;3:298–308. doi: 10.1111/andr.310]

Studies highlighting the effects of hypogonadism

Studies have unearthed a number of results that correlate with the findings and theories previously discussed.

One patient who was a 57 year old male with HIV complained of fatigue, low libido and impotency.

He had type 2 diabetes, pulmonary tuberculosis and a low CD4 count. Physically he was of sound condition.

He was diagnosed with hypogonadism and received treatment, of which his symptoms cleared.

Another study involving a 51 year old male with controlled HIV was suffering from tuberculosis over a number of sites.

He also suffered from positive rheumatoid arthritis and described fatigue, continued lethargy and a reduction of muscle strength.

Once placed on a course of testosterone treatment, his symptoms resolved.

Each patient had HIV and low concentrations of total testosterone.

These examples illustrate how low testosterone in HIV infected men can also effect other co-morbidities, and how treating the hypogonadism can then alleviate those other associated illnesses.

Therefore, as soon as a man has confirmation from tests that he has hypogonadism, testosterone treatment should be considered and applied.

  • [Asboe D, Aitken C, Boffito M, et al. British HIV Association guidelines for the routine investigation and monitoring of adult HIV-1-infected individuals. HIV Medicine. 2011;13:1–44. doi: 10.1111/j.1468-1293.2011.00971.x.]

The treatment should then improve any co-existing symptoms of illness, plus reduce the risk of other ailments that are associated with low test levels such as osteoporosis, depression, muscle wastage, fat distribution and a loss of libido.

  • [Grinspoon S, Corcoran C, Askari H, et al. Effects of androgen administration in men with the AIDS wasting syndrome: a randomised, double-blind, placebo-controlled trial. Ann Intern Med. 1998;128:18–26. doi: 10.7326/0003-4819-129-1-199807010-00005.]

Conclusion

There has been a continued review of testosterone treatment for HIV infected men and the results have always correlated with an increase of lean muscle mass and lean overall body mass.

Not only that, there were other key improvements across endpoints such as mood, strength, fatigue and overall general quality of life.

  • [Knapp PE, Storer TW, Herbst KL, et al. Effects of supraphysiological dose of testosterone on physical function, muscle performance, mood and fatigue in HIV associated weight loss. Am J Phys. 2008;294:1135–1143.]

Traditionally, low testosterone levels and HIV are often overlooked, however, these results from numerous studies add weight to the requirement of further investigation, and where necessary testosterone treatment applied.

  • [Grinspoon S, Corcoran C, Stanley T, et al. Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men. J Clin Endocr Metab. 2000;85:60–65.]

 

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