Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma

被引:66
作者
Caruso, Donatella [1 ]
Abbiati, Federico [1 ]
Giatti, Silvia [1 ]
Romano, Simone [1 ]
Fusco, Letizia [2 ,3 ]
Cavaletti, Guido [2 ,3 ]
Melcangi, Roberto Cosimo [1 ]
机构
[1] Univ Milan, Ctr Excellence Neurodegenerat Dis, Dept Pharmacol & Biomol Sci, Milan, Italy
[2] Univ Milano Bicocca, Dept Surg & Translat Med, Monza, Italy
[3] S Gerardo Hosp, Dept Neurol, Monza, Italy
关键词
Progesterone; Testosterone; Metabolites; 5; alpha-Reductase; Depression; Liquid chromatography-tandem mass spectrometry; BENIGN PROSTATIC HYPERPLASIA; MAJOR DEPRESSION; NERVOUS-SYSTEM; ANDROGENETIC ALOPECIA; TESTOSTERONE LEVELS; FEMALE RATS; OLDER MEN; NEUROGENESIS; ALLOPREGNANOLONE; NEUROSTEROIDS;
D O I
10.1016/j.jsbmb.2014.03.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Observations performed in a subset of patients treated for male pattern hair loss indicate that persistent sexual side effects as well as anxious/depressive symptomatology have been reported even after discontinuation of finasteride treatment. Due to the capability of finasteride to block the metabolism of progesterone (PROG) and/or testosterone (T) we have evaluated, by liquid chromatography-tandem mass spectrometry, the levels of several neuroactive steroids in paired plasma and cerebrospinal fluid (CSF) samples obtained from post-finasteride patients and in healthy controls. At the examination, post-finasteride patients reported muscular stiffness, cramps, tremors and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Although severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in CSF showed a decrease of PROG and its metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), associated with an increase of its precursor pregnenolone (PREG). Altered levels were also observed for T and its metabolites. Thus, a significant decrease of dihydrotestosterone (DHT) associated with an increase of T as well as of 3 alpha-diol was detected. Changes in neuroactive steroid levels also occurred in plasma. An increase of PREG, T, 3 alpha-diol, 3 beta-diol and 17 beta-estradiol was associated with decreased levels of DHP and THP. The present observations show that altered levels of neuroactive steroids, associated with depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment. This article is part of a Special Issue entitled 'Sex steroids and brain disorders'. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:74 / 79
页数:6
相关论文
共 47 条
[1]   Depression circumstantially related to the administration of finasteride for androgenetic alopecia [J].
Altomare, G ;
Capella, GL .
JOURNAL OF DERMATOLOGY, 2002, 29 (10) :665-669
[2]   Isoallopregnanolone; an antagonist to the anaesthetic effect of allopregnanolone in male rats [J].
Bäckström, T ;
Wahlström, G ;
Wahlström, K ;
Zhu, D ;
Wang, MD .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2005, 512 (01) :15-21
[3]   ANXIOLYTIC EFFECTS OF 3A-HYDROXY-5A[BETA]-PREGNAN-20-ONE - ENDOGENOUS METABOLITES OF PROGESTERONE THAT ARE ACTIVE AT THE GABA-A RECEPTOR [J].
BITRAN, D ;
HILVERS, RJ ;
KELLOGG, CK .
BRAIN RESEARCH, 1991, 561 (01) :157-161
[4]  
Brinton Roberta Diaz, 2006, Current Alzheimer Research, V3, P185
[5]   EFFICACY, TOLERABILITY, AND EFFECT ON HEALTH-RELATED QUALITY-OF-LIFE OF FINASTERIDE VERSUS PLACEBO IN MEN WITH SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA - A COMMUNITY-BASED STUDY [J].
BYRNES, CA ;
MORTON, AS ;
LISS, CL ;
LIPPERT, MC ;
GILLENWATER, JY .
CLINICAL THERAPEUTICS, 1995, 17 (05) :956-969
[6]   Effect of Short-and Long-Term Gonadectomy on Neuroactive Steroid Levels in the Central and Peripheral Nervous System of Male and Female Rats [J].
Caruso, D. ;
Pesaresi, M. ;
Maschi, O. ;
Giatti, S. ;
Garcia-Segura, L. M. ;
Melcangi, R. C. .
JOURNAL OF NEUROENDOCRINOLOGY, 2010, 22 (11) :1137-1147
[7]   Comparison of plasma and cerebrospinal fluid levels of neuroactive steroids with their brain, spinal cord and peripheral nerve levels in male and female rats [J].
Caruso, Donatella ;
Pesaresi, Marzia ;
Abbiati, Federico ;
Calabrese, Donato ;
Giatti, Silvia ;
Miguel Garcia-Segura, Luis ;
Melcangi, Roberto Cosimo .
PSYCHONEUROENDOCRINOLOGY, 2013, 38 (10) :2278-2290
[8]  
Duskova M, 2009, Prague Med Rep, V110, P222
[9]   A new look at the 5α-reductase inhibitor finasteride [J].
Finn, Deborah A. ;
Beadles-Bohling, Amy S. ;
Beckley, Ethan H. ;
Ford, Matthew M. ;
Gililland, Katherine R. ;
Gorin-Meyer, Rebecca E. ;
Wiren, Kristine M. .
CNS DRUG REVIEWS, 2006, 12 (01) :53-76
[10]   Sex, Hormones and Neurogenesis in the Hippocampus: Hormonal Modulation of Neurogenesis and Potential Functional Implications [J].
Galea, L. A. M. ;
Wainwright, S. R. ;
Roes, M. M. ;
Duarte-Guterman, P. ;
Chow, C. ;
Hamson, D. K. .
JOURNAL OF NEUROENDOCRINOLOGY, 2013, 25 (11) :1039-1061