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 information on their effects on prostate zonal volumes. This study aimed to define the effects of androgen deficiency and androgen replacement therapy on prostate zonal volumes (central, peripheral & total) using planimetric prostate ultrasound with particular emphasis on the central zone of the prostate, 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 directly, and peripheral prostate volume calculated, by a single observer using transrectal ultrasound in 71 hypogonadal men (aged 40 ± 2, range 18–78 years) who were compared with individually age‐matched health controls without 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 replacement therapy (median 32 months, 93% ≥ 6 months) with testosterone implants ( n  = 27), testosterone ester injections ( n  = 24) or other 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) prostate volumes whereas the reduction in peripheral prostate volume (19·4 ± 2·1 vs. 23·0 ± 1·3 ml, P  = 0·15) was not statistically significant. Men with 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 volume (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 nor type of hypogonadism influenced prostate zonal volumes before or after treatment. In contrast, central, peripheral and total prostate volume increased with age among healthy controls and men with androgen deficiency regardless 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 total prostate volumes. Reduced prostate volumes persist even during long‐term maintenance of effective androgen replacement therapy with physiological testosterone concentrations until the fourth decade of life. After that, prostate volumes increase with age regardless of androgen deficiency or replacement. These findings suggest that, during mid‐life, age is a more important determinant of prostate growth than ambient testosterone concentrations maintained in the physiological range. The persistently subnormal prostate volumes despite adequate androgen replacement therapy may explain the apparent paucity of cases of overt prostate disease among testosterone‐treated androgen deficient men who retain protection against prostate disease despite physiological androgen replacement therapy.