Effects of androgen deficiency and replacement on prostate zonal volumes

BACKGROUND AND OBJECTIVES Androgens play a key role In prostate development and disease. However the effects of androgen deficiency and replacement on the prostate during mid-life are not well understood, and there is no info rmation on their effects on prostate zonal volumes. This study aimed to def ine the effects of androgen deficiency and androgen replacement therapy on prostate zonal volumes (central, peripheral & total) using planimetric pros tate ultrasound with particular emphasis on the central zone of the prostat e, the most hormonally sensitive and fastest growing region of the prostate and the zone where nodular benign prostate hyperplasia originates. PATIENTS AND MEASUREMENTS Central and total prostate volume were measured d irectly, and peripheral prostate volume calculated, by a single observer us ing transrectal ultrasound in 71 hypogonadal men (aged 40 +/- 2, range 18-7 8 years) who were compared with individually age-matched health controls wi thout prostate or gonadal disease. Among the men with androgen deficiency, 17 men had untreated androgen deficiency (never treated or no treatment for at least 6 months) and 54 men were receiving long-term androgen replacemen t therapy (median 32 months, 93% greater than or equal to 6 months) with te stosterone implants (n = 27), testosterone ester injections (n = 24) or oth er testosterone treatment (n = 3). RESULTS Compared with individually age-matched controls, untreated androgen deficient men (n = 17) had reduced central (4.0 +/- 0.5 vs. 6.2 +/- 0.5 ml , P < 0.001) and total (23.4 +/- 2.6 vs. 29.2 +/- 1.6 ml, P < 0.001) prosta te volumes whereas the reduction in peripheral prostate volume (19.4 +/- 1. 2 vs. 23.0 +/- 1.3 ml, P = 0.15) was not statistically significant. Men wit h treated androgen deficiency (n = 54) also still had significantly reduced central (4.8 +/- 0.4 vs. 6.8 +/- 0 4, P < 0.001), peripheral prostate volu me (19.6 +/- 0.8 vs. 21.6 +/- 0.7 ml, P = 0.06) and total (24.4 +/- 1.1 vs. 28.4 +/- 1.0 ml, P = 0.008) despite prolonged restoration of physiological testosterone concentrations. Neither modality of testosterone treatment no r type of hypogonadism influenced prostate zonal volumes before or after tr eatment. In contrast, central, peripheral and total prostate volume increas ed with age among healthy controls and men with androgen deficiency regardl ess of androgen replacement therapy. Plasma PSA concentrations were reduced in men with untreated androgen deficiency and were similar to age-matched controls in men with treated androgen deficiency. CONCLUSIONS We conclude that, during mid-life, chronic androgen deficiency due to hypogonadism is associated with reduced central, peripheral and tota l prostate volumes. Reduced prostate volumes persist even during long-term maintenance of effective androgen replacement therapy with physiological te stosterone concentrations until the fourth decade of life. After that, pros tate volumes increase with age regardless of androgen deficiency or replace ment. These findings suggest: that, during mid-life, age is a more importan t determinant of prostate growth than ambient testosterone concentrations m aintained in the physiological range. The persistently subnormal prostate v olumes despite adequate androgen replacement therapy may explain the appare nt paucity of cases of overt prostate disease among testosterone-treated an drogen deficient men who retain protection against prostate disease despite physiological androgen replacement therapy.