LAUSR

The human fetus is initially capable of differentiating both to female or male fenotype irrespective of the genotype. Subsequent development of sexual characteristics in both genders is highly dependent on the proper, timely and balanced secretion of sex steroids. A remnant of this peculiar phenomenon is underlying the observations made by Alfthan and Holsti in their article dating from the early issues of SJU [1]. In their paper, they examined prevention of gynecomastia by roentgen irradiation in men who were treated with estrogen to treat their prostate cancer. High levels of parenteral estrogen not only caused suppression of gonadotropin release from the pituitary and subsequent castrate levels of testosterone, but also secondary indirect feminizing effects such as gynecomastia. In their prospective study, Alfthan and Holsti elegantly demonstrate the powerful effect of local irradiation in preventing hyperplasia of the male mammary glandular tissue. However, the secondary effects of estrogen in the male were not entirely unwanted: estrogens are trophic on the bone and prevent climacteric symptoms otherwise common among castrates. Estrogen treatment for prostate cancer as a means of ADT is nowadays rare, but the advantageous effects of estrogens particularly on the bone are still of interest [2,3]. Furthermore, combining estrogen therapy with novel therapies in treating castration-resistant prostate cancer is showing promise [3]. At present, a shifted balance between androgen and estrogen action is still seen in different conditions: Pure antiandrogens such as bicalutamide exert their anti-androgenic effect at their main target tissue, the prostate. However, when used as monotherapy they also block the negative androgen feedback on the hypothalamic and pituitary level resulting in increased LH and subsequently testosterone production. Abundance of testosterone in turn results in increased estrogen turnover by aromatase action resulting in gynecomastia and analogously to protection of bone mass. The recently developed antiandrogens such as enzalutamide share the endocrine effects of bicalutamide and when used as monotherapy their use also warrants prophylactic irradiation of mammary tissue [5]. In addition to hormonal manipulations for prostate cancer, a shift of hormonal balance may be a contributing factor to changes seen in the normal aging of males, but these changes are subtle and not well understood [6,7]. As a part of metabolic syndrome, accumulation of body fat contributes to increased aromatization of testosterone to estrogen, which is mainly responsible for negative feedback in the pituitary level, also in the male. This results in decreased testosterone production which further contributes to the vicious circle seen in obesity [8]. The paper by Alfthan and Holsti exemplifies one aspect of how the interplay of sex steroids can affect various organ systems. However, our understanding of this complex system is still incomplete. Understanding of the male endocrinology gives us urologists a unique position in the study of male hormonal changes seen during normal aging and sickness.