Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know?

  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},
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… 

Negative Impact of Testosterone Deficiency and 5α-Reductase Inhibitors Therapy on Metabolic and Sexual Function in Men.

  • A. Traish
  • Medicine, Biology
    Advances in experimental medicine and biology
  • 2017
There are areas of controversies, including whether age-related androgen deficiency (functional hypogonadism) merits treatment and whether T therapy provided real proven benefits, and considerable debate exists with respect to the potential and purported cardiovascular risks of treating TD with exogenous T.

Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm

  • A. Traish
  • Medicine, Biology
    The world journal of men's health
  • 2020
It is suggested that long-term use of finasteride and dutasteride may be associated with health risks including NAFLD, IR, T2DM, dry eye disease and potential kidney disease and this treatment may result in development of non-alcoholic fatty liver diseases (NAFLD), insulin resistance (IR), type 2 diabetes (T2DM),dry eye disease, potential kidney dysfunction, and metabolic dysfunctions.

Exploring the neural mechanisms of finasteride: a proteomic analysis in the nucleus accumbens

Post-finasteride syndrome: An emerging clinical problem

Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels

The preponderance of available clinical data indicates that modest elevations in circulating levels of DHT in response to androgen therapy should not be of concern in clinical practice.

Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain

It is suggested that finasteride treatment may have broad consequences for brain function as well as changes in neuroactive steroid levels, steroid receptors, and GABA-A receptor subunits.

Post-finasteride syndrome☆☆☆

The postfinasteride syndrome; an overview

It is argued that finasteride adverse effects occurring during Finasteride administration should be delineated from postfinasteride side effects (encountered after treatment cessation), suggesting the need to be addressed separately within a therapeutic perspective.



Steroid 5α-reductase as a novel therapeutic target for schizophrenia and other neuropsychiatric disorders.

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

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

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.

  • A. Traish
  • Biology, Medicine
    Endocrine 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

  • E. Stoner
  • Medicine, Biology
    The Journal of Steroid Biochemistry and Molecular Biology
  • 1990

Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR.

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

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.

  • E. Stoner
  • Medicine, Biology
    The 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

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

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.