Monitoring urinary testosterone and epitestosterone levels, and their ratio, in Korean chemical castration subjects using liquid chromatography–tandem mass spectrometry

Abstract

In Europe, chemical castration has been adopted as a treatment for paraphilia since the 1930s. Among the various chemical castration agents, luteinizing hormone-releasing hormone (LHRH) agonists are now used widely because of their effectiveness and safety. In South Korea, a legislation of chemical castration to control the sexual impulses of sexual offenders was enforced in July 2011. Most of these subjects are treated with leuprorelin acetate, an LHRH agonist, for chemical castration. Despite this, there are few studies that address the long-term influence of LHRH agonists on testosterone (T) and epitestosterone (E) levels in chemical castration subjects. In order to analyze the urinary levels of T in chemical castration subjects, whose T levels are extremely low, we developed and validated an analytical method for the detection of both T and E in human urine using a liquid chromatography-tandem mass spectrometry (LC–MS/MS) system. The urine samples were hydrolyzed, extracted, and analyzed by LC–MS/MS with electrospray ionization in the positive-ion mode. The limits of detection were 0.02 ng/mL and the limits of quantitation were 0.05 ng/mL, which provided great sensitivity. The established method was applied to urine samples from chemical castration subjects and healthy male volunteers. The chemical castration subjects showed significantly lower urinary T levels than the control subjects. In addition, the urinary E levels were also lower in the chemical castration subjects; however, the T/E ratios were constant and did not show a notable decrease because of the simultaneous decrease in both urinary T and E. The urinary T levels and T/E ratio did not exceed the doping control criteria for exogenous T ingestion for any subject. This study shows the trend of urinary T and E levels in long-term treated chemical castration subjects by establishing a highly sensitive LC–MS/MS method, that provides useful information for monitoring chemical castration.

Annual banned‐substance review: Analytical approaches in human sports drug testing 2019/2020

“…Another aspect that potentially contributes to unusual elimination characteristics of transdermally administered testosterone is hypogonadism as reported by Iannone et al 72 In a single‐dose application study (40‐mg testosterone) comparing late‐onset hypogonadal (LOH) patients with non‐LOH patients, different characteristics of excretion pathways were observed with a more pronounced production and excretion of T sulfate and EpiT sulfate in non‐LOH patients, which further seconds the momentum of strengthening the role of steroidal sulfo‐conjugates in routine doping controls, potentially also in the context of therapeutic regimens applied, for example, to address sexual impulses 73 …”

“…Via positive ESI, the effluent was directed into a QqQ-based MS, operated in MRM mode to target dutasteride, 4 0 -hydroxy-and 6βhydroxydutasteride by means of diagnostic precursor/product ion pairs. With LODs between 0.1 and 0.4 ng/ml, the administration of 0.5 mg of dutasteride was traceable for at least 3-4 days.Another aspect that potentially contributes to unusual elimination characteristics of transdermally administered testosterone is hypogonadism as reported by Iannone et al72 In a single-dose application study (40-mg testosterone) comparing late-onset hypogonadal (LOH) patients with non-LOH patients, different characteristics of excretion pathways were observed with a more pronounced production and excretion of T sulfate and EpiT sulfate in non-LOH patients, which further seconds the momentum of strengthening the role of steroidal sulfo-conjugates in routine doping controls, potentially also in the context of therapeutic regimens applied, for example, to address sexual impulses 73. The information contained in urinary steroid sulfate concentrations was highlighted in different studies, one of which focused on population-based reference ranges computed from six endogenous AAS sulfo-conjugates acquired by means of LC-HRMS (in addition to commonly determined steroid profile parameters) 74.…”

The Curcumin Derivative, H10, Suppresses Hormone-Dependent Prostate Cancer by Inhibiting 17β-Hydroxysteroid Dehydrogenase Type 3

“…At present, there are multiple treatment strategies for hormone-dependent prostate cancer, including orchidectomy and the administration of androgen receptor (AR) blockers, luteinizing hormone-releasing hormone (LHRH) agonists, and 5a-reductase inhibitors (Estevez et al, 2016;Fang and Zhou, 2019). However, the widely used chemical castration strategy with the depot LHRH agonist failed to achieve castration levels for T in nearly 20% of men (Sim et al, 2019). Despite the impressive clinical activity of the second-generation antiandrogens, including enzalutamide and ARN-509, acquired resistance invariably develops in patients with prostate cancer (Rice et al, 2019).…”