Finasteride: The First 5α‐Reductase Inhibitor

  title={Finasteride: The First 5$\alpha$‐Reductase Inhibitor},
  author={S L Sudduth and Michael J. Koronkowski},
  journal={Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy},
Finasteride is a synthetic 4‐azasteroid that is a specific competitive inhibitor of 5α‐reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone (DHT). It has no binding affinity for androgen receptor sites and itself possesses no androgenic, antiandrogenic, or other steroid hormone‐related properties. It is well absorbed after oral administration, with absolute bioavailability in humans of 63% (range 34–108%). The mean time to maximum concentration is 1–2 hours, and… 
A new look at the 5alpha-reductase inhibitor finasteride.
The data suggest that endogenous neuroactive steroid levels may be inversely related to symptoms of premenstrual and postpartum dysphoric disorder, catamenial epilepsy, depression, and alcohol withdrawal.
PHARMACODYNAMICS AND PHARMACOKINETICS 5 á-Reductase Isozyme Sensitivity to Finasteride : Species Differences
The data suggest that endogenous neuroactive steroid levels may be inversely related to brain function and behavior, and finasteride, which inhibits both isoforms of 5á-reductase in rodents, has been used as a tool to manipulate neuroactive steroids levels and determine the impact on behavior.
The influence of low dose finasteride, a type II 5α-reductase inhibitor, on circulating neuroactive steroids
The decrease of 5α-reduced steroids, especially of allopregnanediol, dihydrotestosterone, and pregnenolone, is probably one of the factors responsible for the increased occurrence of depression in men treated with finasteride, even at low doses.
Comparison of cyproterone acetate plus ethinyl estradiol and finasteride in the treatment of hirsutism
CPA+E appears to be more effective than 5α-reductase inhibitor finasteride in long-term treatment of hirsute women, and Diane® is also a cost-effective drug.
Pharmacokinetics and pharmacodynamics of TF-505, a novel nonsteroidal 5alpha-reductase inhibitor, in normal subjects treated with single or multiple doses.
TF-505 was well tolerated in healthy male volunteers and the predicted effect curves matched the observed data when the indirect response model was applied to the time course of the suppressant effect of TF-505 on plasma DHT concentrations after both the single and multiple studies.
Finasteride‐induced depression: new insights into possible pathomechanisms
A recent study reported that finasteride treatment inhibits hippocampal neurogenesis in mice, which could be of possible relevance for the pathophysiology of affective disorders.
5&agr;-Reductase inhibitors in androgenetic alopecia
Sexual side-effects are uncommon and resolve spontaneously in most patients even without discontinuing therapy, and although patients treated with 5&agr;RIs have an increased incidence of sexual adverse events, these events decrease if discontinued or over time with continued therapy.
Down-regulation of prostate-specific antigen expression by finasteride through inhibition of complex formation between androgen receptor and steroid receptor-binding consensus in the promoter of the PSA gene in LNCaP cells.
The data indicate that inhibition of complex formation between SRBC and nuclear proteins due to the remarkable decrease in the level of androgen receptor plays a key role in the down-regulation of PSA gene expression by finasteride in LNCaP cells.
Biochemical roles of testosterone and epitestosterone to 5 alpha-reductase as indicators of male-pattern baldness.
Findings demonstrate that analysis of terminal hair may not only provide a basis for predicting baldness when the subject is still young, but also for preventing and treating male-pattern baldness by controlling the steroid hormone balance.


The clinical development of a 5α-reductase inhibitor, finasteride
  • E. Stoner
  • Medicine, Biology
    The Journal of Steroid Biochemistry and Molecular Biology
  • 1990
Hormonal effects of an orally active 4‐azasteroid inhibitor of 5α‐reductase in humans
It is concluded that MK‐906 is a highly effective 5α‐reductase inhibitor in vivo, and both hepatic and extrasplanchnic 5α-reductases are inhibited.
Effects of finasteride (MK-906), a 5 alpha-reductase inhibitor, on circulating androgens in male volunteers.
Finasteride is well tolerated by normal volunteers and results in significant suppression of serum DHT at all doses tested, and the T/DHT ratio increased with all doses and returned to baseline when drug was discontinued.
Effect of MK-906, a specific 5 alpha-reductase inhibitor, on serum androgens and androgen conjugates in normal men.
While all three steroids appeared to be good markers of systemic 5 alpha-reductase inhibition, further research will be needed to determine which steroid best reflects tissue DHT levels in patients receiving these inhibitors.
One‐Year Experience in the Treatment of Benign Prostatic Hyperplasia with Finasteride
It is concluded that finasteride has the potential to be an effective chronic therapy for benign prostatic hyperplasia and can reduce prostate size and improve maximum urinary flow with no loss of efficacy after 1 year of treatment.
Species Differences in Prostatic Steroid 5α-Reductases of Rat, Dog, and Human
The conversion of testosterone to 5a-dihydrotestosterone by prostate particulates from rats, dogs, and humans was investigated, and significant species differences were found with their pH profiles,
Effect of castration, DES, flutamide, and the 5α‐reductase inhibitor, MK‐906, on the growth of the dunning rat prostatic carcinoma, R‐3327
The failure of MK‐906 to influence tumor growth in the TP‐treated castrates strongly suggests that the R‐3327 tumor can respond to testosterone directly, and is unlikely to be affected by a pure 5α‐reductase inhibitor such as MK‐ 906.
Disposition and pharmacokinetics of [14C]finasteride after oral administration in humans.
The disposition of [14C]finasteride, a competitive inhibitor of steroid 5 alpha-reductase, was investigated after oral administration of 38.1 mg of drug in six healthy volunteers and concluded that in humans, finasteride is extensively metabolized through oxidative pathways.