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The Influence of Androgen Deprivation Therapy on Dihydrotestosterone Levels in the Prostatic Tissue of Patients with Prostate Cancer

¹ Division of Urology, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata; and ² Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo, Japan

Purpose: The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue is not clearly known. Changes in dihydrotestosterone levels in the prostatic tissue during androgen deprivation therapy in the same patients have not been reported. We analyzed dihydrotestosterone levels in prostatic tissue before and after androgen deprivation therapy.

Experimental Design: A total of 103 patients who were suspected of having prostate cancer underwent prostatic biopsy. Sixty-nine patients were diagnosed as having prostate cancer whereas the remaining 34 were negative. Serum samples were collected before biopsy or prostatectomy. Dihydrotestosterone levels in prostatic tissue and serum were analyzed using liquid chromatography/electrospray ionization-mass spectrometry after polar derivatization. In 30 of the patients with prostate cancer, dihydrotestosterone levels in prostatic tissue were determined by performing rebiopsy or with prostate tissues excised after 6 months on androgen deprivation therapy with castration and flutamide.

Results: Dihydrotestosterone levels in prostate tissue after androgen deprivation therapy remained at 25% of the amount measured before androgen deprivation therapy. Dihydrotestosterone levels in serum decreased to 7.5% after androgen deprivation therapy. The level of dihydrotestosterone in prostatic tissue before androgen deprivation therapy was not correlated with the serum level of testosterone. Serum levels of adrenal androgens were reduced to 60% after androgen deprivation therapy.

Conclusions: The source of dihydrotestosterone in prostatic tissue after androgen deprivation therapy involves intracrine production within the prostate, converting adrenal androgens to dihydrotestosterone. Dihydrotestosterone still remaining in prostate tissue after androgen deprivation therapy may require new therapies such as treatment with a combination of 5-reductase inhibitors and antiandrogens, as well as castration.

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