Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study

Abstract

SUMMARYMen with human immunodeficiency virus (HIV) infection are often hypogonadal and develop several HIV-associated nonacquired immunodeficiency syndrome (AIDS) (HANA) conditions that impair overall health status. No studies explored the relationship between health status and serum testosterone (T) in HIV-infected men. This study aims to investigate the association between total serum T and HANA, multimorbidity, and frailty in a large cohort of 1359 HIV-infected men and to explore the relationship between patients' overall health status and serum T. Among biochemical and hormonal measurement performed the main are serum total T, free triiodothyronine (fT3), and luteinizing hormone. Other outcome measurements include anthropometry, assessment of comorbidities and disabilities, overall health status defined as the number of HANA and by the 38-item multimorbidity frailty index, anthropometry, and bone mineral density. The cumulative relative risk of comorbidities is increased in HIV-infected men with hypogonadism (p < 0.001) and hypogonadism is associated with several comorbidities. The prevalence of hypogonadism increases progressively with the increase of the number of comorbidities. Frailty index is inversely related to serum total T (age-adjusted r = 0.298, r 2 = 0.089, p < 0.0001). Serum fT3 levels are significantly lower in hypogonadal than eugonadal men (p = 0.022). This suggests that low serum T could be considered a sensitive marker of frailty and poor health status and that the latter might induce hypogonadism. The more HIV-infected men are frail the more they are hypogonadal. This suggests that hypogonadism might be a naturally occurring condition in unhealthy HIV-infected men and raises concern about the safety of T treatment. In conclusion, low serum T is associated with multimorbidity, HANA, and frailty in HIV-infected men and this association seems to be bidirectional. Given the wide attitude to offer T treatment to HIV-infected men, caution is needed when prescribing T to HIV-infected male patients, especially if the patient is unhealthy or frail.

Hypogonadotropic hypogonadism in human immunodeficiency virus infected men: uncommonly low testosterone levels

“…The pathogenesis of hypogonadotropic hypogonadism in HIV-infected men is multifactorial and androgen deficiency is more often a consequence of secondary hypogonadism than primary hypogonadism (2,3,4,5,7,8); causes of hypogonadotropic hypogonadism in HIVinfected men include undernutrition, severe illness, drugs (psychotropics, opiates, megestrol acetate or steroids), pituitary dysfunction (tumor, hyperprolactinemia), an AIDS-related lesion (very rarely), the HIV virus replication and co-morbid conditions, such as antibody to hepatitis C virus seropositivity and injection drug use (2,3,4,5). Also, HAART, particularly protease inhibitor therapy has been associated with sexual dysfunction in men, but the causal nature of this relation has not been clearly established as many of these patients have normal testosterone levels and some studies have demonstrated that initiation of HAART, including protease inhibitor, can restore testosterone levels to normal (2,3,6).…”

“…Since HIV therapy is now initiated at earlier stages of HIV infection than in the past, the prevalence of hypogonadism is lower, being present in about 20% of men who receive HAART (4,5). Hypogonadism in HIV-infected men presents similarly to androgen deficiency in the general population and is characterized by loss of facial and body hair, decreased muscle mass and strength, high percentage of body fat, low libido, erectile dysfunction, testicular atrophy, infertility and sometimes gynecomastia (2,3,6,7,8,9,10). Depression, fatigue, low energy, poor concentration, mild anemia and low bone mineral density with osteoporotic fractures may also occur (2,3,6,7,8,9,10).…”

“…However, the cutoff used for the general population is commonly used in HIV-infected men: a clinical suspicion of hypogonadism is confirmed with a low serum total testosterone level (generally <300 ng/mL) in two different samples in the morning (8:00 h) (1, 2, 3, 4, 5, 6, 7). As sexual hormonebinding globulin (SHBG) is more frequently increased in HIV-infected men, levels of free testosterone should be measured because total testosterone levels may be normal in an HIV-infected male, but free testosterone levels may be low (2,3,6).…”

“…The other hormones that reflect the anterior pituitary function (adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), insulin growth factor-1 (IGF-1), thyroid-stimulating hormone (TSH) and free T4 (FT 4 )) should also be measured (2,3). Besides, a pituitary magnetic resonance imaging (MRI) must be carried out in patients with confirmed hypogonadotropic hypogonadism, to rule out a pituitary or hypothalamic lesion (2, 3).…”

Aging and sex hormones in males

“…40 With this in view, a considerable quote of LOH are not consistent with a clinical condition of hypogonadism, but represents an epiphenomenon of a poor health status, which is a common condition in the elderly. 38,40 With this in view, hypogonadism could be considered as a functional, adaptive mechanism enrolled in presence of a condition of poor health status, 40,50,165,166 as it happens in case of acute, severe illness.…”