Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know?
@article{Traish2015AdverseEO, title={Adverse effects of 5$\alpha$-reductase inhibitors: What do we know, don’t know, and need to know?}, author={Abdulmaged M. Traish and Roberto Cosimo Melcangi and Marco Bortolato and Luis Miguel Garcia-Segura and Michael Zitzmann}, journal={Reviews in Endocrine and Metabolic Disorders}, year={2015}, volume={16}, pages={177-198} }
Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions. One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5α-reductase (5α-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events. Indeed, both 5α-R inhibition and supplementation of 5…
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References
SHOWING 1-10 OF 222 REFERENCES
Steroid 5α-reductase as a novel therapeutic target for schizophrenia and other neuropsychiatric disorders.
- Biology, PsychologyCurrent pharmaceutical design
- 2011
The enzyme steroid 5α reductase (S5α R) catalyzes the conversion of Δ⁴-3-ketosteroid precursors--such as testosterone, progesterone and androstenedione--into their 5α-reduced metabolites. Although…
5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis
- Biology, MedicineHormone molecular biology and clinical investigation
- 2014
The hypothesis that inhibition of 5α-reductases by finasteride and dutasteride alters not only steroid metabolism but also interferes with the downstream actions and signaling of these hormones is advanced.
Antipsychotic-Like Properties of 5-α-Reductase Inhibitors
- Biology, PsychologyNeuropsychopharmacology
- 2008
The results suggest that 5AR inhibitors elicit antipsychotic-like effects in animals and may be proposed as a putative novel target in the management of psychotic disorders.
5α-reductases in human physiology: an unfolding story.
- Biology, MedicineEndocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
- 2012
There is an urgent need to better understand the function of 5 α-reductases and the role of neuroactive steroids in human physiology in order to minimize the potential adverse side effects of inhibitors targeting 5α- reductases to treat benign prostatic hyperplasia and androgenic alopecia.
The clinical development of a 5α-reductase inhibitor, finasteride
- Medicine, BiologyThe Journal of Steroid Biochemistry and Molecular Biology
- 1990
Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR.
- Biology, ChemistryThe Journal of pharmacology and experimental therapeutics
- 1997
Results from single-dose evaluations in man indicate that GG745 has a terminal half-life of approximately 240 hr, and single doses of >10 mg decreased DHT levels significantly more than did single 5-mg doses of finasteride, which support the hypothesis that a molecule (GG745) that effectively inhibits both 5alpha-reductases will lower serum DHT Levels significantly more.
5α-Reductase Type 1 Modulates Insulin Sensitivity in Men
- Medicine, BiologyThe Journal of clinical endocrinology and metabolism
- 2014
Dutasteride and finasteride had similar effects on steroid profiles, with reduced urinary androgen and glucocorticoid metabolites and reduced circulating DHT but no change in plasma or salivary cortisol, and mRNA for 5 αR1 but not 5αR2 was detected in human adipose tissue.
The clinical development of a 5 alpha-reductase inhibitor, finasteride.
- Medicine, BiologyThe Journal of steroid biochemistry and molecular biology
- 1990
Selective inhibition of 5 alpha-reductase by finasteride may provide a novel approach to BPH therapy by reducing prostate size without affecting T-dependent processes such as fertility, muscle strength, and libido.
The 5 Alpha-Reductase Isozyme Family: A Review of Basic Biology and Their Role in Human Diseases
- Biology, MedicineAdvances in urology
- 2012
This review describes the basic biochemical properties, functions, tissue distribution, chromosomal location, and clinical significance of the 5 alpha-reductase isozyme family.
The Dark Side of 5α-Reductase Inhibitors' Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression
- MedicineKorean journal of urology
- 2014
Considerable evidence exists from preclinical and clinical studies, which point to significant and serious adverse effects of 5α-RIs, finasteride and dutasteride, on sexual health, vascular health, psychological health and the overall quality of life, which need to be aware of.