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 lack of male pattern baldness. These observations and findings ultimately led to the development of finasteride.
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 was approved 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 be used 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 found in sebaceous glands, sweat glands, dermal papillae cells, and epidermal and follicular keratinocytes. Type II is found in the outer root sheaths of hair follicles, the epididymis, vas deferens, seminal vesicles, and prostate.
Finasteride has been shown 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 reduced risk of urinary retention and delayed the need for surgical intervention.
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 steady state. Upon discontinuation of finasteride, DHT levels return to normal within 14 days. In patients being treated for benign prostate hyperplasia, prostate volume returns to baseline within three months; patients being treated 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.
Common adverse effects associated with finasteride include loss of libido, erectile dysfunction (2% to 4%), decreased ejaculatory volume, and gynecomastia. It has also been associated with orthostatic hypotension. This can be additive in patients who are taking concomitant alpha blockers. Finasteride has been reported to cause orthostatic hypotension in approximately 9% of users as monotherapy, and as high as 18% with combined therapy. Therefore, appropriate patient counseling should be undertaken.
Post-finasteride syndrome (PFS) has recently been reported. This refers to the continuation of adverse effects despite 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 from the urologic and dermatologic practitioners that utilize the medication (in different doses and for different indications). Thus far there is minimal data to support the association of permanent infertility with use of low dose 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 be impacted by 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 been linked to symptoms of dizziness, weakness, dyspnea, rhinitis, and skin rash.
No specific laboratory monitoring guidelines exist for finasteride. However, prostate-specific antigen is assessed in men with benign prostate hyperplasia and surveillance for prostate cancer. Due to the decrease in prostatic volume at the 5-mg dose, there is an expected decrease in serum prostate-specific antigen levels. Therefore, it is recommended to obtain baseline prostate-specific antigen levels before initiating therapy. Practitioners should be cognizant of serum prostate-specific antigen values in patients using finasteride. Serum labs values are often multiplied by 2 to estimate a more accurate approximation of levels.
There has been some controversy regarding the role of finasteride in the development of prostate cancer. The Prostate Cancer Prevention Trial (PCPT) was a landmark study that compared daily finasteride to placebo therapy in over 18,000 men aged 55 and older who were followed for seven years. The study ultimately concluded that finasteride was associated with a 25% reduction in the prevalence of prostate cancer. However, it was also associated with an increased rate of detection of high-grade prostate cancer. The FDA eventually placed a black box warning on the medication safety label, resulting in a negative impact on prescribing patterns of the drug. There is a considerable consensus in the field that the increased rate of high-grade cancer in the PCPT may be the result of confounding factors and detection bias. However, it cannot be excluded with certainty.
The American Society of Clinical Oncology (ASCO) and American Urological Association (AUA) released a joint statement in 2008 and developed a clinical practice guideline to assist physicians and patients with making informed decisions after reviewing the risks and benefits of the medication.
The AUA supports the use of finasteride as a treatment option for men with benign prostate hyperplasia and shared decision-making.
Overdoses of finasteride resulting in clinically significant toxicity have not been reported. However, overdoses are expected to be an extension of previously reported adverse drug effects, including orthostatic hypotension.
Finasteride is an FDA-approved pharmacologic agent for the treatment of benign prostate hyperplasia and androgenic alopecia (male pattern hair loss) in men. The drug is also sometimes used to treat hyperandrogenism and hirsutism. Healthcare workers including nurse practitioners who prescribe this medication should screen all males for prostate cancer while on this agent,
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