Extensive Alteration of Androgen Precursor Levels after Castration in Prostate Cancer Patients and Their Association with Active Androgen Level.

Dihydrotesterone (DHT) and testosterone are thought to be major contributors of prostate cancer progression and resistance. We studied the modulation of 15 circulating steroids by castration and their association with DHT and testosterone levels.

A total of 116 serum samples were collected from 99 prostate cancer patients and categorized as eugonadal, castration-sensitive (CSPC), castration-resistant (CRPC) or CRPC under abiraterone acetate. Serum levels of 15 steroids were measured using mass spectrometry and compared between groups using ANOVA. Intrapatient association of steroid levels and the androgens testosterone and DHT were assessed using Pearson correlation and linear regression.

Testosterone, DHT, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androsterone, androstenediol, estrone, estrone-sulfate, estradiol, androsterone/3α-diol-3/3α-diol-17-glucuronide levels were significantly decreased in CSPC (castrated) compared to eugonadal patients. Testosterone levels were strongly associated with multiple steroids under eugonadal conditions, whereas they were weakly affected by precursor steroids in castrated patients. By contrast, DHT levels under androgen deprivation therapy (ADT) were associated with testosterone and the backdoor pathway metabolite androsterone. In CRPC patients, levels of androstenedione were significantly associated with testosterone level, while testosterone was the only steroid associated with DHT levels.

ADT significantly reduces the levels of 13 circulating steroids. Upon ADT initiation, the backdoor pathway metabolite androsterone are strongly associated with DHT levels. Under CRPC conditions, androstenedione was significantly associated with testosterone levels suggesting the presence of tumor-related circulating androgens in these patients. These results provide further rationale to intensify treatments with androgen receptor axis signalling pathway inhibitors in patients with prostate cancer.

The Journal of urology. 2022 Sep 14 [Epub ahead of print]

Mélanie Rouleau, Bertrand Neveu, Patrick Caron, Fannie Morin, Paul Toren, Louis Lacombe, Véronique Turcotte, Éric Lévesque, Chantal Guillemette, And Frédéric Pouliot

Division of Urology, Department of Surgery and Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, QC, Canada., Pharmacy Faculty, Université Laval and CHU de Québec-Université Laval, Québec, QC, Canada., Medicine Faculty, Université Laval and CHU de Québec-Université Laval, Québec, QC, Canada.

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