Intermittent androgen replacement for intense hypogonadism symptoms in castrated patients

Abstract

Objectives: For locally advanced prostate cancer management, medical androgen deprivation and surgical castration are alternatives. These hormonal treatments may cause a myriad of side effects, such as osteoporosis with increased risk of fractures, anemia, behavioral changes and lack of sexual interest. We evaluated the feasibility of intermittent androgen replacement in surgically castrated patients with significant side effects. Methods: Five patients with advanced prostate cancer, ranging from 71 to 77 years of age (mean age ¼ 74 years), surgically castrated for at least 3 years, with important symptoms of hypoandrogenism received testosterone replacement. They were followed with PSA and testosterone measurement every other month and bone scans every 6 months. Results: For the first year all patients improved significantly, none of them showed PSA increase over 10 ng/ml. There was no evidence of local recurrence or distant disease. After 18 months, only one patient (20%) had a significant PSA increase, controlled by androgen withdrawal. No side effects or metastasis were observed. Conclusions: Hormonal replacement in patients that underwent castration seems to be feasible in improving intense symptoms associated to androgen deprivation. After 18 months, no evidence of recurrence was noted. It is an experimental alternative for highly symptomatic patients, but the short follow-up and the small number of patients cannot allow for definitive conclusions and should be studied further.

Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review

“…[65][66][67][68] There was no evidence of prostate cancer recurrence in these men over periods of 0.5-12 years. The prospective case series included five men who had subcapsular orchiectomy to treat advanced prostatic carcinoma; these men had PSA increases while undergoing testosterone therapy for up to 2.5 years.…”

“…[65][66][67][68] Further, men with high-grade PIN treated with testosterone did not have a greater increase in PSA or a significantly elevated risk of prostate cancer than testosterone-treated men without PIN. 54 Testosterone therapy did not cause a sudden progression to prostate cancer in men with PIN.…”

“…The prospective case series included five men who had subcapsular orchiectomy to treat advanced prostatic carcinoma; these men had PSA increases while undergoing testosterone therapy for up to 2.5 years. 65 One retrospective , mean TT increased to 21.7 ± 8.6 at 6 months and stayed at that level until 3 years in TTD group and did not change from baseline of 12.8 in PBO group Mean PSA increased from 1.6±1.0 at baseline to 2.2±1.8 (Po0.001) in TTD group and from 1.7 ± 1.1 to 1.9 ± 1.4 in PBO group 1 TTD group 1 (details not supplied)…”

“…Further, data from the four studies of men who received testosterone therapy over periods of up to 12 years after treatment for prostate cancer provide no evidence that testosterone therapy increased the risk of cancer recurrence or metastasis. [65][66][67][68] This review was designed to provide information to help answer the specific question about whether prostate cancer risks are increased by testosterone therapy for hypogonadism. The review included studies of adult men of any age with hypogonadism of any etiology, regardless whether the studies were placebo-controlled and randomized or involved men with previous prostate cancer.…”

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

“…Several studies have shown that ART of hypogonadal patients with localized prostate cancer treated with radical prostatectomy or ADT has no adverse effect on prostate cancer progression (Kaufman and Graydon, 2004;Agarwal and Oefelein, 2005;Ferreira et al, 2006;Khera et al, 2009). Fowler and Whimore, (1981) observed that out of 52 metastatic prostate cancer patients who received ART, 45 exhibited increased cancer progression that could be reversed by androgen withdrawal, whereas 7 experienced symptomatic benefits.…”