Inhibition of 5α-reductase also reduces epididymal weight, and decreases motility and normal morphology of spermatozoa in the epididymis.Neurosteroids like 3α-androstanediol (derived from DHT) and allopregnanolone (derived from progesterone) activate the GABAA receptor in the brain; because finasteride prevents the formation of neurosteroids, it functions as a neurosteroidogenesis inhibitor and may contribute to a reduction of GABAA activity. Reduction of GABAA receptor activation by these neurosteroids has been implicated in depression, anxiety, and sexual dysfunction.In accordance with finasteride being a potent 5α-reductase inhibitor but a weak inhibitor of 5β-reductase, the medication decreases circulating levels of 5α-reduced steroids like allopregnanolone but does not reduce concentrations of 5β-reduced steroids like pregnanolone. Pregnanolone acts as a potent GABAA receptor positive allosteric modulator similarly to allopregnanolone. Pharmacokinetics
The mean oral bioavailability of finasteride is approximately 65%. The absorption of finasteride is not affected by food. At steady-state with 1 mg/day finasteride, mean peak concentrations of finasteride were 9.2 ng/mL (25 nmol/L). Conversely, following a single 5 mg dose of finasteride, mean peak levels of finasteride were 37 ng/mL (99 nmol/L), and plasma concentrations increased by 47 to 54% following 2.5 weeks of continued daily administration. The volume of distribution of finasteride is 76 L. Its plasma protein binding is 90%. The drug has been found to cross the blood–brain barrier, whereas levels in semen were found to be undetectable.Finasteride is extensively metabolized in the liver, first by hydroxylation via CYP3A4 and then by aldehyde dehydrogenase. It has two major metabolites, which are the tert-butyl side chain monohydroxylated and monocarboxylic acid metabolites.
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Finasteride for BPH
The most common adverse sexual effects of finasteride for BPH are: trouble getting or keeping an erection, decrease in sex drive, decreased volume of ejaculate and ejaculation disorders. : 16 A 2010 Cochrane review found that men taking finasteride for BPH (with a mean age of 62.4) are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder for the first year of treatment. The rates became indistinguishable from placebo after 2–4 years and these side effects usually got better over time. Long-term
Finasteride may cause persistent adverse sexual, neurological and physical effects in a subset of men. A 2019 metastudy surveyed the literature on the reversibility of finasterides side effects. It identified three studies which demonstrated full reversibility of side effects and eleven that describe patients with irreversible adverse events. The findings were most convincing in a retrospective review of about 12,000 patients that 1.4% of the cohort developed persistent ED (ED lasting longer than 90 days post-withdrawal). Post-finasteride syndrome
Men in the U.S. and Canada concerned about persistent sexual side effects "coined the phrase post-finasteride syndrome, which they say is characterized by sexual, neurological, hormonal and psychological side effects that can persist in men who have taken finasteride for hair loss or an enlarged prostate". As of 2016, Merck was a defendant in approximately 1,370 product liability lawsuits which had been filed by customers alleging they have experienced persistent sexual side effects following cessation of treatment with finasteride.A 2019 editorial in The BMJ called post finasteride syndrome "ill defined and controversial".