Androgens in Health and Disease.pdf - E Library

328 Matsumoto
such as hepatic cirrhosis (16). Careful examination usually reveals some gynecomastia
and increased amounts subcutaneous fat tissue of the chest in hypogonadal men prior to
initiation of androgen therapy. Furthermore, small amounts of palpable breast tissue
(usually ≤ 2 cm) are commonly detectable in eugonadal men. Therefore, it is important
to do a careful breast examination prior to and during T therapy.
Testosterone-replacement therapy in hypogonadal men increases prostate size to volumes
that are similar to those of age-matched eugonadal men, but it does not cause
excessive stimulation of prostate growth and enlargement (80,81). There is no evidence
that androgen-replacement therapy worsens symptoms, urine flow, or urinary retention
associated with benign prostatic hyperplasia (BPH) that may require invasive intervention,
such as transurethral resection of the prostate (TURP). However, long-term controlled
studies have not been performed to evaluate these issues in the population of men
over age 45 yr who are at increased risk for developing clinically significant BPH. Therefore,
caution should be exercised when treating middle-aged to older men, especially
those with moderate to severe symptoms of BPH prior to T treatment, and monitoring of
symptoms should be performed (82). Symptoms of BPH should be assessed (e.g., using
the American Urological Association Symptom Index or International Prostate Symptom
Score) prior to and during T replacement in these men. Low-dose T supplementation and/
or concomitant therapy for BPH (e.g., α-adrenergic receptor antagonists, 5α-reductase
inhibitors, or bladder outlet procedures) should be considered in patients with moderate
to severe symptoms.
There is no evidence that T treatment causes prostate cancer. However, in middleaged
to older hypogonadal men, the most concerning potential long-term risk of
T-replacement therapy is stimulation of growth of previously unrecognized localized or
metastatic prostate cancer or, in older men particularly, growth of pre-existing subclinical
(microscopic) prostate cancer into clinically apparent and significant disease (7).
Although there is evidence that T treatment will stimulate the growth of metastatic and
locally invasive prostate cancer, the effect of T on subclinical prostate cancer is not
known. Long-term, prospective, controlled trials are needed to determine whether
T therapy will stimulate growth and progression of subclinical microscopic prostate
cancer into clinically evident and significant disease.
Serum PSA levels are reduced in hypogonadal men and increased to levels observed
in age-matched eugonadal men with androgen replacement (80). Whether an individual
physician monitors PSA levels before and during T replacement therapy in an older
hypogondal men depends, to some extent, on whether they feel PSA screening in
eugonadal men is justified (7,83). The practice of yearly PSA screening in eugonadal
men over the age of 45 yr is controversial and its utility has not been demonstrated
convincingly. Increasingly however, it is becoming a standard of care in many communities,
and many patients are demanding PSA screening. An argument raised for more
intensive PSA monitoring during T treatment in older hypogonadal men is that a potentially
disease-modifying therapeutic intervention is being initiated, often with a T formulation
that produces transient supraphysiological T levels (T esters). Therefore, for
clinical and medical legal reasons, more careful monitoring of PSA levels is prudent. An
argument against more intensive PSA monitoring is that abnormal PSA levels that
trigger a prostate biopsy are more likely to occur in older hypogonadal men on T treatment
and, therefore, there is an increased likelihood of detecting subclinical prostate
cancer for which treatment is unclear. Even if subclinical prostate cancer discovered on