What does the research say about androgen use and cerebrovascular events?

M. Reza Sadaie, Mehdi Farhoudi, Masumeh Zamanlu, Nasser Aghamohammadzadeh, Atieh Amouzegar, Robert E. Rosenbaum, Gary A. Thomas

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Many studies have investigated the benefits of androgen therapy and neurosteroids in aging men, while concerns remain about the potential associations of exogenous steroids and incidents of cerebrovascular events and ischemic stroke (IS). Testosterone is neuroprotective, neurotrophic and a potent stimulator of neuroplasticity. These benefits are mediated primarily through conversion of a small amount of testosterone to estradiol by the catalytic activity of estrogen synthetase (aromatase cytochrome P450 enzyme). New studies suggest that abnormal serum levels of the nonaromatized potent metabolite of testosterone, either high or low dihydrotestosterone (DHT), is a risk factor for stroke. Associations between pharmacologic androgen use and the incidence of IS are questionable, because a significant portion of testosterone is converted to DHT. There is also insufficient evidence to reject a causal relationship between the pro-testosterone adrenal androgens and incidence of IS. Moreover, vascular intima-media thickness, which is a predictor of stroke and myocardial symptoms, has correlations with sex hormones. Current diagnostic and treatment criteria for androgen therapy for cerebrovascular complications are unclear. Confounding variables, including genetic and metabolic alterations of the key enzymes of steroidogenesis, ought to be considered. Information extracted from pharmacogenetic testing may aid in expounding the protective–destructive properties of neurosteroids, as well as the prognosis of androgen therapy, in particular their cerebrovascular outcomes. This investigative review article addresses relevant findings of the clinical and experimental investigations of androgen therapy, emphasizes the significance of genetic testing of androgen responsiveness towards individualized therapy in post-IS injuries as well as identifying pertinent questions.

Original languageEnglish (US)
Pages (from-to)439-455
Number of pages17
JournalTherapeutic Advances in Drug Safety
Volume9
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Androgens
Stroke
Testosterone
Research
Aromatase
Dihydrotestosterone
Cytochrome P-450 Enzyme System
Neurotransmitter Agents
Therapeutics
Tunica Intima
Tunica Media
Neuronal Plasticity
Confounding Factors (Epidemiology)
Incidence
Gonadal Steroid Hormones
Genetic Testing
Estradiol
Steroids
Wounds and Injuries
Enzymes

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

Sadaie, M. R., Farhoudi, M., Zamanlu, M., Aghamohammadzadeh, N., Amouzegar, A., Rosenbaum, R. E., & Thomas, G. A. (2018). What does the research say about androgen use and cerebrovascular events? Therapeutic Advances in Drug Safety, 9(8), 439-455. https://doi.org/10.1177/2042098618773318
Sadaie, M. Reza ; Farhoudi, Mehdi ; Zamanlu, Masumeh ; Aghamohammadzadeh, Nasser ; Amouzegar, Atieh ; Rosenbaum, Robert E. ; Thomas, Gary A. / What does the research say about androgen use and cerebrovascular events?. In: Therapeutic Advances in Drug Safety. 2018 ; Vol. 9, No. 8. pp. 439-455.
@article{ba3dc4a6b38d46099a4dfc0deaba920c,
title = "What does the research say about androgen use and cerebrovascular events?",
abstract = "Many studies have investigated the benefits of androgen therapy and neurosteroids in aging men, while concerns remain about the potential associations of exogenous steroids and incidents of cerebrovascular events and ischemic stroke (IS). Testosterone is neuroprotective, neurotrophic and a potent stimulator of neuroplasticity. These benefits are mediated primarily through conversion of a small amount of testosterone to estradiol by the catalytic activity of estrogen synthetase (aromatase cytochrome P450 enzyme). New studies suggest that abnormal serum levels of the nonaromatized potent metabolite of testosterone, either high or low dihydrotestosterone (DHT), is a risk factor for stroke. Associations between pharmacologic androgen use and the incidence of IS are questionable, because a significant portion of testosterone is converted to DHT. There is also insufficient evidence to reject a causal relationship between the pro-testosterone adrenal androgens and incidence of IS. Moreover, vascular intima-media thickness, which is a predictor of stroke and myocardial symptoms, has correlations with sex hormones. Current diagnostic and treatment criteria for androgen therapy for cerebrovascular complications are unclear. Confounding variables, including genetic and metabolic alterations of the key enzymes of steroidogenesis, ought to be considered. Information extracted from pharmacogenetic testing may aid in expounding the protective–destructive properties of neurosteroids, as well as the prognosis of androgen therapy, in particular their cerebrovascular outcomes. This investigative review article addresses relevant findings of the clinical and experimental investigations of androgen therapy, emphasizes the significance of genetic testing of androgen responsiveness towards individualized therapy in post-IS injuries as well as identifying pertinent questions.",
author = "Sadaie, {M. Reza} and Mehdi Farhoudi and Masumeh Zamanlu and Nasser Aghamohammadzadeh and Atieh Amouzegar and Rosenbaum, {Robert E.} and Thomas, {Gary A.}",
year = "2018",
month = "8",
day = "1",
doi = "10.1177/2042098618773318",
language = "English (US)",
volume = "9",
pages = "439--455",
journal = "Therapeutic Advances in Drug Safety",
issn = "2042-0986",
publisher = "SAGE Publications Ltd",
number = "8",

}

Sadaie, MR, Farhoudi, M, Zamanlu, M, Aghamohammadzadeh, N, Amouzegar, A, Rosenbaum, RE & Thomas, GA 2018, 'What does the research say about androgen use and cerebrovascular events?', Therapeutic Advances in Drug Safety, vol. 9, no. 8, pp. 439-455. https://doi.org/10.1177/2042098618773318

What does the research say about androgen use and cerebrovascular events? / Sadaie, M. Reza; Farhoudi, Mehdi; Zamanlu, Masumeh; Aghamohammadzadeh, Nasser; Amouzegar, Atieh; Rosenbaum, Robert E.; Thomas, Gary A.

In: Therapeutic Advances in Drug Safety, Vol. 9, No. 8, 01.08.2018, p. 439-455.

Research output: Contribution to journalReview article

TY - JOUR

T1 - What does the research say about androgen use and cerebrovascular events?

AU - Sadaie, M. Reza

AU - Farhoudi, Mehdi

AU - Zamanlu, Masumeh

AU - Aghamohammadzadeh, Nasser

AU - Amouzegar, Atieh

AU - Rosenbaum, Robert E.

AU - Thomas, Gary A.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Many studies have investigated the benefits of androgen therapy and neurosteroids in aging men, while concerns remain about the potential associations of exogenous steroids and incidents of cerebrovascular events and ischemic stroke (IS). Testosterone is neuroprotective, neurotrophic and a potent stimulator of neuroplasticity. These benefits are mediated primarily through conversion of a small amount of testosterone to estradiol by the catalytic activity of estrogen synthetase (aromatase cytochrome P450 enzyme). New studies suggest that abnormal serum levels of the nonaromatized potent metabolite of testosterone, either high or low dihydrotestosterone (DHT), is a risk factor for stroke. Associations between pharmacologic androgen use and the incidence of IS are questionable, because a significant portion of testosterone is converted to DHT. There is also insufficient evidence to reject a causal relationship between the pro-testosterone adrenal androgens and incidence of IS. Moreover, vascular intima-media thickness, which is a predictor of stroke and myocardial symptoms, has correlations with sex hormones. Current diagnostic and treatment criteria for androgen therapy for cerebrovascular complications are unclear. Confounding variables, including genetic and metabolic alterations of the key enzymes of steroidogenesis, ought to be considered. Information extracted from pharmacogenetic testing may aid in expounding the protective–destructive properties of neurosteroids, as well as the prognosis of androgen therapy, in particular their cerebrovascular outcomes. This investigative review article addresses relevant findings of the clinical and experimental investigations of androgen therapy, emphasizes the significance of genetic testing of androgen responsiveness towards individualized therapy in post-IS injuries as well as identifying pertinent questions.

AB - Many studies have investigated the benefits of androgen therapy and neurosteroids in aging men, while concerns remain about the potential associations of exogenous steroids and incidents of cerebrovascular events and ischemic stroke (IS). Testosterone is neuroprotective, neurotrophic and a potent stimulator of neuroplasticity. These benefits are mediated primarily through conversion of a small amount of testosterone to estradiol by the catalytic activity of estrogen synthetase (aromatase cytochrome P450 enzyme). New studies suggest that abnormal serum levels of the nonaromatized potent metabolite of testosterone, either high or low dihydrotestosterone (DHT), is a risk factor for stroke. Associations between pharmacologic androgen use and the incidence of IS are questionable, because a significant portion of testosterone is converted to DHT. There is also insufficient evidence to reject a causal relationship between the pro-testosterone adrenal androgens and incidence of IS. Moreover, vascular intima-media thickness, which is a predictor of stroke and myocardial symptoms, has correlations with sex hormones. Current diagnostic and treatment criteria for androgen therapy for cerebrovascular complications are unclear. Confounding variables, including genetic and metabolic alterations of the key enzymes of steroidogenesis, ought to be considered. Information extracted from pharmacogenetic testing may aid in expounding the protective–destructive properties of neurosteroids, as well as the prognosis of androgen therapy, in particular their cerebrovascular outcomes. This investigative review article addresses relevant findings of the clinical and experimental investigations of androgen therapy, emphasizes the significance of genetic testing of androgen responsiveness towards individualized therapy in post-IS injuries as well as identifying pertinent questions.

UR - http://www.scopus.com/inward/record.url?scp=85046643500&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046643500&partnerID=8YFLogxK

U2 - 10.1177/2042098618773318

DO - 10.1177/2042098618773318

M3 - Review article

C2 - 30364888

AN - SCOPUS:85046643500

VL - 9

SP - 439

EP - 455

JO - Therapeutic Advances in Drug Safety

JF - Therapeutic Advances in Drug Safety

SN - 2042-0986

IS - 8

ER -

Sadaie MR, Farhoudi M, Zamanlu M, Aghamohammadzadeh N, Amouzegar A, Rosenbaum RE et al. What does the research say about androgen use and cerebrovascular events? Therapeutic Advances in Drug Safety. 2018 Aug 1;9(8):439-455. https://doi.org/10.1177/2042098618773318