Updated Review of the Hair Loss and Prostate Drug Finasteride (PROPECIA, PROSCAR)

In the 1990s, the Food and Drug Administration (FDA) approved two doses of finasteride — an oral prescription drug that belongs to a drug class called 5-alpha reductase inhibitors, which inhibit the formation of a potent form of testosterone — for use in men only. The high (5-milligram [mg]) dose, which is sold under the brand name PROSCAR, is approved for use as a stand-alone drug to control symptomatic benign prostatic hyperplasia or enlargement (BPH) and also for use in combination with the alpha-blocker doxazosin (CARDURA) to reduce the risk of symptomatic progression of this condition.[1]

The low (1-mg) dose form of finasteride, which is sold under the brand name PROPECIA, is approved for male pattern hair loss.[2] Neither dosage form of the drug has been approved for use in women or children. Both dosage forms are taken once daily.

For many years, Public Citizen’s Health Research Group has classified both finasteride products as Do Not Use[3] because their benefits do not outweigh their adverse effects. Yet the drug continues to be among the top 100 most commonly prescribed medications in the U.S.[4]

Small benefits

The main clinical trials that supported the initial approval of finasteride showed that the drug improved some symptoms of BPH (mainly resulting in increased urine output) compared with a placebo. A 1993 review by the independent French drug safety journal Prescrire International characterized these benefits as “slow” and as being of “mild clinical efficacy.”[5] The review also noted a lack of long-term clinical trials, at that time, comparing finasteride with alpha-blockers (such as doxazosin), which are the first-line drugs for BPH.

A 2010 review by Cochrane (a nonprofit organization that specializes in analyzing evidence from multiple studies) concluded that doxazosin improves BPH symptoms better than finasteride in the short and long term.[6] Notably, doxazosin (and other alpha-blockers) improve BPH symptoms immediately by relaxing the smooth muscles in the bladder and prostate, whereas finasteride generally takes six to 12 months before it improves BPH symptoms.[7]

A 2003 trial with an average follow-up of 4.5 years found that taking either doxazosin or finasteride, as well as taking both of them together (in combination), improves BPH symptoms, but only their combination decreased clinical progression of the disorder.[8] The 2010 Cochrane review also showed that combining doxazosin and finasteride improves urinary symptoms better than doxazosin alone in men with medium or large prostates but does not do so in those with small prostates.[9] However, the review found that this combination is associated with more adverse effects than is taking doxazosin alone.

Likewise, the clinical trials that supported the approval of finasteride for male pattern hair loss showed that the drug increased hair growth in one-half of the male subjects with mild-to-moderate degrees of male pattern baldness after one year of treatment.[10] However, any hair that grew due to finasteride use was shed after the drug was discontinued.

Multiple, serious risks

Finasteride is associated with serious adverse effects that were not known until several years after the drug was approved, requiring the addition of multiple warnings to the drug’s labeling over the years.

A large, federally funded clinical trial, called the Prostate Cancer Prevention Trial, found that finasteride increases the risk of high-grade prostate cancer (although the drug reduced the risk of overall prostate cancer) compared with placebo.[11] Therefore, an editorial that accompanied a 2003 New England Journal of Medicine (NEJM) article that summarized the results from that trial argued that finasteride should not be used for prostate cancer prevention.[12] The results of this trial also led the FDA to require that a warning be added to the labeling of all finasteride products regarding this increased risk of high-grade prostate cancer among users of the drug.[13]

An 18-year follow-up of the Prostate Cancer Prevention Trial that was published in the NEJM also found an increased risk of high-grade prostate cancer but no difference in survival between finasteride users and those who received a placebo.[14] However, a 2019 analysis of large population-based data from the Department of Veterans Affairs showed that finasteride was associated with delayed prostate cancer diagnosis and worsened prostate cancer outcomes among men who took the drug at least one year before being diagnosed with prostate cancer.[15]

Evidence from the Prostate Cancer Prevention Trial and other postmarketing studies also links finasteride to sexual adverse effects including decreased libido, erectile dysfunction, infertility and reduced ejaculate volume.[16] Postmarketing studies show that these sexual adverse effects persist in some patients after finasteride is discontinued.[17],[18]

An analysis that linked data from the Prostate Cancer Prevention Trial with Medicare claim data showed a 10% increase in depression-related claims among finasteride users, compared with those who received a placebo.[19]

Recent evidence from postmarketing and population-based studies has linked finasteride to suicidal thoughts (ideation),[20],[21],[22] which prompted French drug regulators to require this adverse effect to be added to finasteride labeling in early 2018.[23] In contrast, the FDA has not, at press time, taken a similar action to warn U.S. consumers about this risk.

Finasteride also has been linked to additional neuropsychiatric adverse effects that are not yet included on its labeling, including anxiety, decreased concentration, memory problems and slowed thought processes.[24] These adverse effects possibly occur because the drug has negative effects on the levels of multiple hormones in the brain, including those derived from progesterone and cortisol, which influence mood and memory.

Additionally, finasteride can cause other physical adverse effects, including hearing impairment, male breast enlargement (gynecomastia), metabolic problems, muscle weakness and skin rash.[25]

Persistence of a combination of the mental, neurological, physical and sexual adverse effects among patients who have taken finasteride is known as post-finasteride syndrome.[26] Although this condition is still not recognized as an official medical condition, it is an area of ongoing research.

Other adverse effects of finasteride include angioedema (a potentially life-threatening allergic reaction that can cause swelling in the skin, lips, mouth and throat),[27] male breast cancer and chronic fatigue.[28],[29] Importantly, finasteride causes abnormalities in the external genitalia of male fetuses of pregnant women who are exposed to the drug.[30]

Although it has been over two decades since the approval of finasteride, its long-term safety profile remains incomplete and more research is needed to understand its effects.[31] Presently, the drug’s benefits for symptomatic BPH and male-pattern hair loss still do not outweigh its multiple risks. Therefore, we continue to recommend against its use.

What You Can Do

Do not take finasteride for any purpose. If you are a man with minimal BPH symptoms, no treatment is necessary, no matter the size of your prostate gland. If you have bothersome BPH symptoms, then an alpha-blocker, such as doxazosin, alfuzosin (UROXATRAL) or terazosin (generic only), is your safest choice, even if your prostate is very enlarged. If you are currently taking finasteride for BPH, consult your doctor about switching to an alpha-blocker. Surgical procedures are also an option if you have severe symptomatic BPH.

Do not take finasteride for hair loss. A safer drug option for both male- and female-pattern hair loss is the topical over-the-counter drug minoxidil (ROGAINE, THEROXIDIL).

Report all serious adverse events related to finasteride or any other medications to the FDA’s MedWatch adverse event reporting program by visiting http://www.fda.gov/MedWatch or by calling 800-FDA-1088.
 

References

[1] Merck Sharp & Dohme Corp. Label: finasteride (PROSCAR). September 2013. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020180s044lbl.pdf. Accessed November 4, 2019.

[2] Merck Sharp & Dohme Corp. Label: finasteride (PROPECIA). January 2014. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020788s024lbl.pdf. Accessed November 4, 2019.

[3] Do Not Use finasteride (PROSCAR, PROPECIA) for preventing prostate cancer. Worst Pills, Best Pills News. August 2003. /newsletters/view/231. Accessed October 28, 2019.

[4] Symphony Health. Top 200 drugs – 2016. https://symphonyhealth.com/wp-content/uploads/2017/04/Top-200-Drug-List-2016.pdf. Accessed October 28, 2019.

[5] Finasteride tablets. Prescrire Int. 1993;2(7):99-101.

[6] Tacklind J, Ha F, Macdonald R, et al. Finasteride for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2010;6(10):CD006015.

[7] Cunningham GR, Kadmon D. Medical treatment of benign prostatic cancer. UpToDate. September 2019. https://www.uptodate.com/contents/medical-treatment-of-benign-prostatic-hyperplasia. Accessed October 28, 2019.

[8] McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;49(25):2387-2398.

[9] Tacklind J, Ha F, Macdonald R, et al. Finasteride for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2010;6(10):CD006015.

[10] Merck Sharp & Dohme Corp. Label: finasteride (PROPECIA). January 2014. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020788s024lbl.pdf. Accessed November 4, 2019.

[11] Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215-224.

[12] Scardino PT. The prevention of prostate cancer – The dilemma continues. N Engl J Med. 2003;349(3):297-299.

[13] Food and Drug Administration. FDA drug safety communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer. June 9, 2011. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-5-alpha-reductase-inhibitors-5-aris-may-increase-risk-more-serious. Accessed October 28, 2019.

[14] Thompson IMJ, Goodman PJ, Tangen CM, et al. Long-term survival of participants in the prostate cancer prevention trial. N Engl J Med. 2013;369(7):603-610.

[15] Sarkar RR, Parsons JK, Bryant AK, et al. Association of treatment with 5α-reductase inhibitors with time to diagnosis and mortality in prostate cancer. JAMA Intern Med. 2019;179(6):812-819.

[16] Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215-224.

[17] Irwig MS, Kolukula S. Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med. 2011;8(6):1747-1753.

[18] Institute for Safe Medication Practices. QuarterWatch™ (2012—Quarter 2) signals for finasteride, methylphenidate patches, and anticoagulants. January 10, 2013. https://www.ismp.org/resources/quarterwatchtm-2012-quarter-2-signals-finasteride-methylphenidate-patches-and. Accessed October 28, 2019.

[19] Unger J, Till C, Thompson IMJ, et al. Long-term consequences of finasteride vs placebo in the prostate cancer prevention trial. J Natl Cancer Inst. 2016;108(12):djw168.

[20] Gupta MA, Vujcic B, Gupta AK. Suicidal behaviors (suicidal ideation, suicide attempt and completed suicide) in patients treated with finasteride for hair loss: Results from the U.S. FDA Adverse Event Reporting System (FAERS) database. J Am Acad Dermatol. 2018;79(3 Supplement 1):AB274.

[21] Welk B, McArthur E, Ordon M, et al. Association of suicidality and depression with 5α-reductase inhibitors. JAMA Intern Med. 2017;177(5):683-691.

[22] Irwig MS. Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects. J Clin Psychiatry. 2012;73(9):1220-1223.

[23] Finasteride in alopecia: a disproportionate risk of depression or suicidal thoughts. Prescrire Int. 2018;27(196):214.

[24] Fertig R, Shapiro J, Bergfeld W, Tosti A. Investigation of the plausibility of 5-alpha-reductase inhibitor syndrome. Ski Appendage Disord. 2017;2(3-4):120-129.

[25] Gray SL, Semla TP. Post-finasteride syndrome. BMJ. 2019;366(August 9):l5047.

[26] Post-Finasteride Syndrome Foundation. About post-finasteride syndrome. https://www.pfsfoundation.org/about-pfs-post-finasteride-syndrome/. Accessed October 28, 2019.

[27] Food and Drug Administration. Letter to Merck Sharpe & Dohme Corp. re. supplemental approval NDA 020180/S-044 requiring labeling changes for finasteride (PROSCAR). March 11, 2014. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/020180Orig1s044ltr.pdf. Accessed October 28, 2019.

[28] Food and Drug Administration. Letter to Merck Sharp & Dohme Corp. re. supplemental approval NDA 020180/S-037 requiring labeling changes for finasteride (PROSCAR). October 4, 2010. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/020180s037ltr.pdf. Accessed October 28, 2019.

[29] Almohanna HM, Perper M, Tosti A. Safety concerns when using novel medications to treat alopecia. Expert Opin Drug Saf. 2018;17(11):1115-1128.

[30] Merck Sharp & Dohme Corp. Label: finasteride (PROSCAR). September 2013. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020180s044lbl.pdf. Accessed November 4, 2019.

[31] Gray SL, Semla TP. Post-finasteride syndrome. BMJ. 2019;366(August 9):l5047.