One of the major concerns for the prescription of medications containing testosterone (T) in the aging men with T deficiency (TD) is prostate disorders (such as benign prostatic hyperplasia, BPH) and their related symptoms (lower urinary tract symptoms, LUTS). This is because prostate is an androgen-responsive gland; however, the androgen dependence of prostate growth, well demonstrated in earlier phases of life, has no clear evidence in late adulthood and senescence. In fact, after the age of 40 years, BPH becomes increasingly more prevalent. On the other hand, in men older than 40 year, a progressive decline in T is observed. These epidemiological data are a starting point for questioning a putative detrimental role of T on the prostate health in the ageing man.
In addition, even the administration of supraphysiological doses of T in adult healthy men with or without dutasteride did not result in a significant change in prostate volume over 20 weeks of treatment. Based on this evidence, it is not surprising that epidemiological studies failed to demonstrate that BPH is associated with higher serum T. Conversely, there is even an evidence of a negative relationship between T and BPH. In a derivative study of the Prostate Cancer Prevention Trial, involving 1417 men free from BPH, lower total T at baseline predicted the occurrence of BPH over 7 years of follow-up. Similarly, low T was found as a predictor of worsening in LUTS in the Florey Adelaide Male Ageing Study and in the Rancho Bernardo Study, lasting 5 years and 20 years, respectively.,
TD in midlife and senescence is a relatively common finding, with a prevalence of about 15% in the general population. Metabolic conditions included in the construct of metabolic syndrome (MetS) are common causes of TD in adulthood, and, among men with MetS, the prevalence of low T is at least doubled. Interestingly, in men with MetS, the prevalence of BPH is also increased. Evidence from epidemiological studies of a mutual association among MetS, low T, and BPH is a sound basis for hypothesizing that these three conditions are part of a single clinical picture. Amounting evidence in support to this hypothesis is provided by experimental preclinical studies.
It is important to underline that, before being a hyperplastic condition, BPH is an inflammatory disease with peculiar features. Within prostate tissue, consequent to proinflammatory stimuli whose nature is still only partially known, a progressive shift from acute to chronic histopathological characteristics of inflammation is documented. Prostatic chronic inflammation occurring in BPH is characterized by the secretion of interleukins (IL), such as IL-4, IL-13, IL-17, and IL-15, typical of a Th2 or Th17 immune response. In addition, besides specialized immunocompetent cells, prostatic stromal cells have the potential to become antigen-presenting cells (APC), and, accordingly, it has been demonstrated that they are able to activate CD4+ T lymphocytes. In turn, the activated lymphocytes secrete cytokines and growth factors, which self-maintain the inflammatory process and favor the proliferation of stromal cells leading to BPH.