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MELCANGI 2014 Altered Levels of Neuroactive Steroids in Cerebrospinal Fluid and Plasm of PFS Patients Journal of Steroid Biochemistry and Molecular Biolo.pdf


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ARTICLE IN PRESS

SBMB-4178; No. of Pages 6

Journal of Steroid Biochemistry & Molecular Biology xxx (2014) xxx–xxx

Contents lists available at ScienceDirect

Journal of Steroid Biochemistry and Molecular Biology
journal homepage: www.elsevier.com/locate/jsbmb

Review

Patients treated for male pattern hair with finasteride show, after
discontinuation of the drug, altered levels of neuroactive steroids in
cerebrospinal fluid and plasma
Donatella Caruso a , Federico Abbiati a , Silvia Giatti a , Simone Romano a , Letizia Fusco b,c ,
Guido Cavaletti b,c , Roberto Cosimo Melcangi a,∗
a
Department of Pharmacological and Biomolecular Sciences – Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano,
Milano, Italy
b
Department of Surgery and Translational Medicine, University of Milan-Bicocca, Monza, Italy
c
Department of Neurology, S. Gerardo Hospital, Monza, Italy

a r t i c l e

i n f o

Article history:
Received 27 January 2014
Received in revised form 28 March 2014
Accepted 31 March 2014
Available online xxx
Keywords:
Progesterone
Testosterone
Metabolites
5␣-Reductase
Depression
Liquid chromatography–tandem mass
spectrometry

a b s t r a c t
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, postfinasteride 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␣-diol was detected. Changes in neuroactive steroid levels also occurred in plasma. An
increase of PREG, T, 3␣-diol, 3␤-diol and 17␤-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’.
© 2014 Elsevier Ltd. All rights reserved.

Contents
1.
2.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1.
Study design and sample preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.
Quantitative analysis of neuroactive steroids by LC–MS/MS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.
Calibration curves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4.
Instrumental conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5.
Statistical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abbreviations: 3␣-diol, 5␣-androstane-3␣,17␤-diol; 3␤-diol, 5␣-androstane-3␤,17␤-diol; 17␤-E, 17␤-estradiol; AR, androgen receptor; CSF, cerebrospinal fluid; DHEA,
dehydroepiandrosterone; DHP, dihydroprogesterone; DHT, dihydrotestosterone; IS, internal standards; LC-MS/MS, liquid chromatography tandem mass spectrometry; PREG,
pregnenolone; PROG, progesterone; T, testosterone; THP, tetrahydroprogesterone.
∗ Corresponding author. Tel.: +39 02 50318238; fax: +39 02 50318204.
E-mail address: roberto.melcangi@unimi.it (R.C. Melcangi).
http://dx.doi.org/10.1016/j.jsbmb.2014.03.012
0960-0760/© 2014 Elsevier Ltd. All rights reserved.

Please cite this article in press as: D. Caruso, et al., Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma, J. Steroid Biochem. Mol. Biol. (2014),
http://dx.doi.org/10.1016/j.jsbmb.2014.03.012