Finasteride

Finasteride is a synthetic 5-alpha-reductase inhibitor, an inhibitor of the enzyme that converts

testosterone to dihydrotestosterone (DHT). Finasteride is approved for the treatment of benign prostatic
hyperplasia (BPH) and male pattern baldness (MPB).

Benign prostatic hyperplasia

For the treatment of BPH, aka enlarged prostate. The approved dose is 5 mg once a day for 6 months or
more. Finasteride may improve the symptoms associated with BPH such as difficulty urinating, getting up
during the night to urinate, hesitation at the start of urination, and decreased urinary flow.

Adverse effects

Side effects of finasteride include impotence (1.1% to 18.5%), abnormal ejaculation (7.2%), decreased
ejaculatory volume (0.9% to 2.8%), abnormal sexual function (2.5%), gynecomastia (2.2%), erectile
dysfunction (1.3%), ejaculation disorder (1.2%) and testicular pain. Merck added depression as a side
effect of finasteride.[6]

Mechanism of action

Finasteride is an inhibitor of 5-alpha reductase. By blocking 5-alpha reductase, finasteride blocks the
conversion of testosterone into the more powerful androgen DHT. In the prostate, inhibition of 5-alpha
reductase leads to a reduction of prostate volume, which improves the symptoms of benign prostatic
hyperplasia (BPH) and reduces the risk of prostate cancer.

History

In 1974, Julianne Imperato-McGinley of Cornell Medical College in New York attended a conference on
birth defects. She reported on a group of hermaphroditic children in the Caribbean who appeared sexually
ambiguous at birth, and were initially raised as girls, but then grew external male genitalia and other
masculine characteristic post-onset of puberty. Her research group found that these children shared a
genetic mutation, causing deficiency of the 5-alpha reductase enzyme and male hormone
dihydrotestosterone (DHT), which was found to have been the etiology behind abnormalities in male
sexual development. Upon maturation, these individuals were observed to have smaller prostates which
were underdeveloped, and were also observed to lack incidence of male pattern baldness.

In 1975, copies of Imperato-McGinley's presentation were seen by P. Roy Vagelos, who was then serving
as Merck's basic-research chief. He was intrigued by the notion that decreased levels of DHT led to the
development of smaller prostates. Dr. Vagelos then sought to create a drug which could mimic the
condition found in the pseudo-hermaphroditic children in order to treat older men who were suffering
from benign prostatic hyperplasia.

In 1992, finasteride (5 mg) was approved by the U.S. Food and Drug Administration (FDA) for treatment
of benign prostatic hyperplasia (BPH), which Merck marketed under the brand name Proscar.
In 1997, Merck was successful in obtaining FDA approval for a second indication of finasteride (1 mg)
for treatment of male pattern baldness (MPB), which was marketed under the brand name Propecia.