madman
Super Moderator
7.1 Introduction
Historically, testosterone (T) was thought to be involved in negative prostate events such as the growth of benign or malignant prostate tissue. This notion stems from the seminal 1941 article by Huggins and Hodges, which demonstrated that in men with metastatic prostate cancer (CaP), surgical castration led to a reduction in acid phosphatase levels, while administration of exogenous T led to an increase in these levels [1]. Our understanding has been further expanded with the concept of the saturation model, which suggests that above a certain T threshold, the androgen receptors are maximally stimulated and, thus, further increases in T levels have no additional effects on prostate cells [2]. However, at lower levels of T, prostate cells do respond to increased T levels, and changes in prostate tissue may occur. While the exact T saturation threshold in humans is not known, animal studies suggest that this is near-castrate levels and is at sub-physiologic levels in humans [2]. More recent data suggests that this total testosterone (TT) threshold is <250 ng/dL (8.67 nmol/L), although there is interindividual variability [3]. This chapter focuses on the effects of T on prostate tissues.
7.2 Prostate-Specific Antigen (PSA) Changes
In summary, the above data are inconclusive and somewhat contradictory. Results seem to suggest a possible effect of TTH on increasing PSA, although the overall effect is likely minor and appears to be more prominent among men with lower baseline TT levels. Larger, adequately powered series dedicated to specifically evaluating changes in PSA is required to definitively address whether TTH truly increases PSA, particularly in men with normal baseline TT levels.
7.3 Prostate Volume Changes
These findings are consistent with the previously described saturation model, in that, at lower baseline TT levels (i.e., below the saturation point), increases in TT result in concomitant increases in prostate volume.
7.4 Lower Urinary Tract Symptoms (LUTS)
Thus, these studies all suggest no role of T in LUTS.
7.5 Prostate Cancer (CaP) Development
In addition to the lack of evidence that TTH increases the risk for prostate cancer (among men with T levels above the saturation level), there are also data that indicate that increased T levels are not associated with higher grades of prostate cancer.
Overall results suggest that TTH is not a risk factor for CaP and T deficiency is associated with more aggressive cancer.
7.6 Conclusion
In summary, the role of T and prostate events, such as increased PSA, prostate volume, LUTS, or CaP, is variably defined, with relatively limited, short-term studies with small patient numbers available. Overall, there is a minor association with PSA levels and T in most men. As explained by the saturation model, PSA and T levels are most strongly correlated at T levels below the saturation threshold. Beyond the saturation point, the correlation between T and PSA is less pronounced and remains debatable. Similarly, the prostate volume does not correlate with T levels beyond the saturation point, and there are no data to suggest an association between LUTS and T levels. With regard to CaP, the literature does not support a link between TTH and CaP risk, particularly among men with baseline levels beyond the saturation point. In contrast, TD seems to be associated with a higher risk of CaP and higher grade and/ or pathologic features compared to men with normal T. Thus, the currently available data suggest that TTH does not increase the risk for prostate cancer among men who do not have any evidence for existing prostate cancer.
Historically, testosterone (T) was thought to be involved in negative prostate events such as the growth of benign or malignant prostate tissue. This notion stems from the seminal 1941 article by Huggins and Hodges, which demonstrated that in men with metastatic prostate cancer (CaP), surgical castration led to a reduction in acid phosphatase levels, while administration of exogenous T led to an increase in these levels [1]. Our understanding has been further expanded with the concept of the saturation model, which suggests that above a certain T threshold, the androgen receptors are maximally stimulated and, thus, further increases in T levels have no additional effects on prostate cells [2]. However, at lower levels of T, prostate cells do respond to increased T levels, and changes in prostate tissue may occur. While the exact T saturation threshold in humans is not known, animal studies suggest that this is near-castrate levels and is at sub-physiologic levels in humans [2]. More recent data suggests that this total testosterone (TT) threshold is <250 ng/dL (8.67 nmol/L), although there is interindividual variability [3]. This chapter focuses on the effects of T on prostate tissues.
7.2 Prostate-Specific Antigen (PSA) Changes
In summary, the above data are inconclusive and somewhat contradictory. Results seem to suggest a possible effect of TTH on increasing PSA, although the overall effect is likely minor and appears to be more prominent among men with lower baseline TT levels. Larger, adequately powered series dedicated to specifically evaluating changes in PSA is required to definitively address whether TTH truly increases PSA, particularly in men with normal baseline TT levels.
7.3 Prostate Volume Changes
These findings are consistent with the previously described saturation model, in that, at lower baseline TT levels (i.e., below the saturation point), increases in TT result in concomitant increases in prostate volume.
7.4 Lower Urinary Tract Symptoms (LUTS)
Thus, these studies all suggest no role of T in LUTS.
7.5 Prostate Cancer (CaP) Development
In addition to the lack of evidence that TTH increases the risk for prostate cancer (among men with T levels above the saturation level), there are also data that indicate that increased T levels are not associated with higher grades of prostate cancer.
Overall results suggest that TTH is not a risk factor for CaP and T deficiency is associated with more aggressive cancer.
7.6 Conclusion
In summary, the role of T and prostate events, such as increased PSA, prostate volume, LUTS, or CaP, is variably defined, with relatively limited, short-term studies with small patient numbers available. Overall, there is a minor association with PSA levels and T in most men. As explained by the saturation model, PSA and T levels are most strongly correlated at T levels below the saturation threshold. Beyond the saturation point, the correlation between T and PSA is less pronounced and remains debatable. Similarly, the prostate volume does not correlate with T levels beyond the saturation point, and there are no data to suggest an association between LUTS and T levels. With regard to CaP, the literature does not support a link between TTH and CaP risk, particularly among men with baseline levels beyond the saturation point. In contrast, TD seems to be associated with a higher risk of CaP and higher grade and/ or pathologic features compared to men with normal T. Thus, the currently available data suggest that TTH does not increase the risk for prostate cancer among men who do not have any evidence for existing prostate cancer.
