Endocrine and adrenergic pharmacological intervention in diseases of the prostate.

Abstract

The physiology of the male urogenital apparatus and reproductive function is critically dependent on a healthy prostate. Since growth and function of the prostate are governed by androgens, endocrine interventions with the synthesis, uptake, or metabolism of these hormones are major pharmacological/therapeutic strategies in prostate diseases, e.g. cancer of the prostate (CaP) and benign prostatic hyperplasia (BPH). Pharmacological interference with androgen metabolism is associated with inevitable adverse effects. Therefore, it is important that such treatment be exercised with caution and weighed against its potential effects on the symptoms and outcome of the disease. α-Adrenergic blockade is an alternative treatment in BPH since α1-adrenoceptors are localized in the prostate stromal structures and considered to mediate an increased infravesical obstruction. Cancer of the prostate (CaP) is the most common cancer in the western male population with the highest incidence in Nordic countries (115/100 000) and in the USA, particularly in black Americans [1]. The incidence increases with age. About 30 to 35% of Swedish men at the age of 50 years have microscopic adenocarcinoma whereas the corresponding figure is more than 50% at the age of 80 years [2]. It has been estimated that about 7% of Swedish men will develop clinical CaP before the age of 75 years [2]. The other major disease of the prostate is BPH which is a histopathological diagnosis leading to benign prostatic enlargement and finally to bladder outlet obstruction. For the sake of simplicity, the clinical syndrome will be referred to as BPH in the following review. BPH is symptomatic in more than 40% of the ageing male population [3]. Shown in Table 1 are some prevalence numbers for CaP and BPH. Table 1 Prevalence of diseases of the prostate in relation to age. Given this situation, it is not surprising that diseases of the prostate have attracted considerable interest from the scientific community and the public. Compared with men from western societies, oriental men like the Japanese have a low incidence of CaP [4]. The higher incidence in oriental men living in the US compared with men in their native countries indicates that environmental as well as genetic factors influence the prevalence of this disease in the population. For BPH, development of effective pharmacological intervention therapies as well as new physical treatment modalities have challenged the classical surgical approaches to cure the disease. Even though the efficacy of drugs may be limited compared to surgical and physical means of treatment, they are often preferred because of the much lower complication risks [5]. A comparison of pharmacological and non-pharmacological treatments in terms of efficacy and complication risks is depicted in Figure 1. Figure 1 Efficacy of treatment methods for BPH in relation to risk of complications. Arbitrary dimensions on Y- and X-axes. TUMT=transurethral microwave treatment; TUNA=transurethral needle ablation; TUIP=transurethral incision of the prostate; TURP=transurethral ... The scope of this article is to describe the current possibilities and ideas for pharmacological intervention strategies, and to discuss their limitations and basis for further development of more advanced treatment programs.