In 1947, James Hamilton of Yale University published an article on male hormone stimulation as a prerequisite to common baldness after examining 104 men with testicular insufficiency. In 1974, Julianne Imperato-McGinley, of Cornell University, published reports on Caribbean children that had a mutation leading to deficiencies in 5-alpha-reductase and dihydrotestosterone. When these male children matured, they had smaller prostate sizes and a lack of male pattern baldness. These observations and findings ultimately led to the development of finasteride.[1][2][3]

Finasteride is an FDA-approved pharmacologic agent for the treatment of benign prostate hyperplasia and androgenic alopecia (male pattern hair loss) in men. Finasteride was first used in 1992 to treat benign prostate hyperplasia at a dose of 5 mg. In 1998, it received approval to treat male pattern hair loss at a dose of 1 mg. Finasteride has also been used to treat signs of hyperandrogenism, such as hirsutism, and may find use in transgender women in combination with estrogen for its anti-androgen properties.

Finasteride is a competitive inhibitor of types II and III 5-alpha-reductase isoenzyme, resulting in inhibition of the conversion of testosterone to dihydrotestosterone (DHT). Finasteride has minimal selectivity for the type I 5-alpha-reductase enzyme. The type I 5-alpha-reductase isomer is present in sebaceous glands, sweat glands, dermal papillae cells, and epidermal and follicular keratinocytes. Type II is in the outer root sheaths of hair follicles, the epididymis, vas deferens, seminal vesicles, and prostate.[4][5][6]

Research has shown finasteride to reduce prostatic DHT levels by upwards of 90% and serum DHT levels by upwards of 70%. However, increasing the dose does not necessarily result in greater serum reduction. Dutasteride, in comparison, inhibits all three 5-alpha-reductase isoenzymes leading to a 99% reduction in serum DHT levels. In the treatment of androgenic alopecia where finasteride does not lead to a 100% reduction in DHT, hair loss is slowed but not completely halted. In the treatment of benign prostate hyperplasia, long-term use of finasteride has been associated with a reduction in prostatic volume, thereby providing relief from bothersome urinary symptoms attributed to an enlarged gland. Previously published literature has demonstrated a reduced risk of urinary retention and delayed the need for surgical intervention.

Pharmacokinetics 

The bioavailability of finasteride is approximately 65% and is not affected by food. Finasteride is approximately 90% protein bound with a volume of distribution of 76 L at a steady state. Upon discontinuation of finasteride, DHT levels return to normal within 14 days. In patients treated for benign prostate hyperplasia, the prostate volume returns to baseline within three months; patients receiving treatment for androgenic alopecia have a reversal of hair count within 12 months.

Finasteride undergoes extensive metabolism in the liver (hepatic metabolism) via the cytochrome P450 enzyme system, specifically CYP3A4, into two active metabolites with less than 20% of the activity of finasteride. Finasteride has a half-life of elimination from the serum of 5 to 6 hours, with a range of 3 to 16 hours. In elderly patients (greater than 70 years of age), the half-life can be prolonged to 8 hours. In comparison to dutasteride, the half-life of finasteride is markedly shorter. Dutasteride has a half-life of 4 to 5 weeks. 

Finasteride is eliminated as metabolites, 57% in the feces, and 39% in the urine.

Finasteride is available as a 1 mg tablet or a 5 mg tablet for oral use. Each dose has a different indication. As much as six months of continued treatment may be necessary to assess the benefit in treatment.

Recommended Dosages

• Benign prostatic hyperplasia: 5 mg once daily (as a single agent or combined with an alpha-blocker).
• Androgenic alopecia (male pattern baldness): 1 mg once daily.
• Hirsutism (female, idiopathic, and related to polycystic ovary syndrome): 5 mg once daily or 2.5 mg once daily; this is an off-label use.

Common adverse effects associated with finasteride include loss of libido, erectile dysfunction (2% to 4%), decreased ejaculatory volume, and gynecomastia. It also correlates with orthostatic hypotension. This adverse event can be additive in patients who are taking concomitant alpha-blockers. Finasteride reportedly causes orthostatic hypotension in approximately 9% of users as monotherapy and as high as 18% with combined therapy. Therefore, appropriate patient counseling is necessary.

Post-finasteride syndrome (PFS) has been a recently reported issue. This term refers to the continuation of adverse effects despite the discontinuation of therapy. Further investigational studies to better understand post-finasteride syndrome are currently underway.

The impact of finasteride on fertility has also been examined by the urologic and dermatologic practitioners that utilize the medication (in different doses and for various indications). Thus far, there is minimal data to support the association of permanent infertility with the use of a low dose of 1 mg finasteride. The effects of low dose finasteride on fertility appear to be reversible as various studies have demonstrated improved fertility and sperm parameters in those who discontinued therapy. However, fertility may suffer a negative impact from the use of the higher 5-mg dose. Not all users experience issues with fertility, and many users of the medication are still able to conceive. 

Additionally, finasteride has correlations to symptoms of dizziness, weakness, dyspnea, rhinitis, and skin rash.

• Finasteride is contraindicated in those with hypersensitivity to any component of the formulation. 
• Finasteride is contraindicated in children.
• Furthermore, finasteride is contraindicated in pregnant women or women of childbearing age.
• Pregnant women should avoid contact with tablets that have been crushed or broken as animal reproduction studies resulted in an abnormality of external male genitalia. If used for the off-label management of hirsutism in female patients with polycystic ovary syndrome, adequate contraception is the recommendation from the American College of Gynecology.
• Blood donation is contraindicated in those currently taking finasteride and for up to 6 months following the last dose of finasteride.