1974: Influential paper on “male pseudohermaphrodites” is published in Science
1987: Merck announces clinical trials of a 5-alpha reductase inhibitor for reducing size of an enlarged prostate
1992: Merck’s application for Proscar approved by FDA
1997: Merck’s application for Propecia approved by FDA
2000: A report of continuing sexual dysfunction after stopping finasteride appears online
2007: A physician describes “Post Propecia Syndrome” at a medical conference
2008: “Persistence of erectile dysfunction” added to Propecia label in Europe
2010: First medical paper on persistent sexual adverse effects is published online
2012: Sexual dysfunction after discontinuation added to Propecia label in U.S.
2018: Most plaintiffs in Propecia litigation in U.S. accept settlement
2022: FDA requires addition of suicidal ideation & behavior to Propecia label; French regulator ANSM requires addition of red boxed warning to finasteride packaging
2023: UK drugs regulator MHRA launches safety review; Health Canada finds “possible link” to risks of suicidal ideation and self-injury; red boxed warning rolled out in France.
A study by James B. Hamilton reports a lack of baldness in testosterone-deficient men, suggesting androgens contribute to balding.
Man & Woman, Boy & Girl, a book on sex and gender development by John Money & Anke Ehrhardt, is published. The authors’ influential views set the context for Dr. Julianne Imperato-McGinley’s investigations of ‘male pseudohermaphrodites’ in Dominican Republic (see 1974).
A paper in Science reports on guevedoces, people of atypical sexual development in a remote village in the Dominican Republic. At birth, these individuals appeared to be female or had ambiguous genitalia. At puberty they developed male characteristics; however, in adulthood they had small prostates and their hairlines did not recede. These findings later prompted Merck to develop finasteride, branded as Proscar, to treat benign prostatic hyperplasia (BPH, or enlarged prostate). (Source: Imperato-McGinley et al, 1974. See also: How was finasteride invented? and 5-alpha reductase deficiency from MedlinePlus)
Brooks et al. of Merck Research Laboratories report a new 5ɑ-reductase inhibitor, MK-4, noting that this drug class might be useful for treating “BPH, prostatic carcinoma, acne, hirsutism, male-pattern baldness, and, possibly, androgen-responsive breast carcinoma.”
April 28: At Merck’s annual meeting, Chairman Roy Vagelos announces that MK-906, a 5ɑ-reductase inhibitor, is being tested in patients with enlarged prostates. (MK-906 would later be named finasteride.)
Elizabeth Stoner of Merck Sharpe & Dohme Research publishes The clinical development of finasteride summarizing development of the drug for the treatment of benign prostatic hyperplasia.
June: U. S. Food and Drug Administration (FDA) approves Merck’s Proscar (finasteride 5 mg/day) for treatment of benign prostatic hyperplasia (BPH).
October: The Prostate Cancer Prevention Trial (PCPT) is launched, with a National Cancer Institute grant of $73 million to the Southwest Oncology Group. 18,882 men would be enrolled in the study over the first three years. (Source: National Cancer Institute)
Roy Vagelos, MD retires as CEO and Chairman of Merck & Co. (Source: Stanford Report)
April: Phase 2 study of finasteride for hair loss (Study 047) concludes. (Source: Drug approval packet, part 1, p. 13)
June: Ray Gilmartin joins Merck as President and Chief Executive Officer. (Source: UPI)
August: In a internal Merck report, Dr. Martin Malkin outlines a strategy for bringing finasteride for hair loss to the market in the “most rapid registration possible.” Although Phase III clinical studies have not begun, the report recommends describing the medication as “well-tolerated” with “mild” adverse reactions that are “not any different from patients in the placebo group.”
December: Merck begins its Phase 3 pivotal trial of Propecia in the United States. (Source: Drug approval packet, part 1, p. 32)
May: Phase 3 one-year pivotal trial of Propecia in the U.S. (Study 087) concludes.
October: It is reported that Merck has hired the Young & Rubicam agency for the marketing of Propecia. (Source: WSJ)
November: Merck is granted patent 5,571,817 for treating androgenetic alopecia (AGA, or male pattern hair loss) with finasteride.
December: FDA approves Merck’s application for Propecia (finasteride 1 mg/day) for treatment of male pattern hair loss.
December: Merck launches propecia.com website (Source: Internet Archive; site content not available as of 2022)
Mid-year (estimated): Merck 4-year extension study of Propecia concludes.
September 24: A user posts to the Usenet group alt.baldspot:
I, like quite a few others, have suffered sexual side effects from the drug finasteride (Propecia, Proscar). In particular, we have difficulty obtaining erections, even after we have discontinued the drug. I my case, I had difficulty with erections soon after I started Propecia in early 1998. Over the course of two years I started and stopped the drug three times at various dosage levels. I have now been off the drug permanently for four months and I still have difficulty obtaining an erection.Source: UsenetArchives.com (Archived)
April: Merck submits Supplemental New Drug Application to FDA incorporating 5-year extension study results.
A revised Propecia consumer label states that sexual adverse effects occurred in less than 2% of men, and “went away in men who stopped taking PROPECIA. They also disappeared in most men who continued taking PROPECIA.” The previous label had stated “went away in all men” but this revision removed the word “all.”
May: In an email, Dr. Eugene Shippen writes:
I have become aware of a growing number of young men who started to take Propecia for male pattern baldness [who] develop full symptoms of hypogonadism: decreased libido, sexual dysfunction, ED, fatigue, gynecomastia and depression… What is really troubling is the lack of response to T replacement, clomiphene stimulation, HCG injections. There may be significant increase in T after various methods of increasing it, but the response in all areas seems to be lacking entirely!Source: HairLossTalk Forums
June: The Prostate Cancer Prevention Trial (PCPT) is concluded. (Source: National Cancer Institute)
May: Ray Gilmartin retires as President, CEO and Chairman of Merck (Source: Internet Archive)
PropeciaHelp support site is launched. An FAQ notes: “As membership for the Yahoo group grew to 1000+ people over 3 years, it was decided that a newer, easier-to-use forum was needed…” (Sources: About Propeciahelp and FAQ)
November: The Swedish Medical Products Agency requests from Merck a complete listing of the outcome “in terms of reversibility” of all adverse event cases related to the male reproductive system. Over the next two years, Merck will continue to correspond with the Swedish agency about persistent sexual dysfunction and other classes of adverse events associated with Propecia. (Sources: see The Merck files, part 2)
April: At an anti-aging medicine conference in Orlando, Florida, Dr. Eugene Shippen delivers a workshop which includes “The Proscar/Propecia problem: ‘Rare’ but dangerous reactions of 5 alpha reductase inhibitors – the ‘Post Propecia Syndrome‘.” (Source: Master Series Workshop program, 15th Annual World Congress on Anti-Aging Medicine…)
June: Merck adds to the Propecia product monograph in Europe: “Persistence of erectile dysfunction after discontinuation of treatment with PROPECIA has been reported in post-marketing use.” (Source: Merck Risk Management Plan, p. 61)
February: Merck releases an internal Risk Management Plan identifying the following as ‘Important Potential Risks’: Persistence of Erectile Dysfunction, Male Infertility and Depressive Disorders. (Source: Merck Risk Management Plan, p. 55)
December 1: An advisory committee convened by FDA meets to consider finasteride and dutasteride as treatments for the prevention of prostate cancer. The committee votes against approving either drug for this indication. Archived materials
February: Merck reports $447 million in annual revenue from Propecia in the prior year—the peak amount in the life of the drug, which would be matched the following year. (See Merck’s Propecia business)
February: Two men file a lawsuit against Merck in the U.S. District Court of New Jersey, alleging negligence and failure to warn about serious sexual dysfunction from taking Propecia (Case 3:11-cv-00641; see also Litigation history).
March: Depression is added as an adverse event in the Postmarketing Experience section of the drug label in the United States.
September: A research seminar on post-finasteride syndrome is held in Trieste, Italy. Participants include Michael Irwig and Roberto Melcangi who went on to publish numerous papers on the topic. (Source: Post Finasteride Syndrome blog [Italian])
November: The product monograph for Propecia in Canada is updated to warn that sexual dysfunction could persist after discontinuation of treatment. (Source: Miller v. Merck Frosst Canada Ltd., 2013)
February: Merck takes down Propecia.com website (Source: Examiner.com via archive.org)
April 11: FDA releases a revised Propecia label. The Postmarketing Experience section has new warnings about sexual adverse effects, noting that some can continue after stopping the medication. FDA announces it “has notified healthcare professionals who would normally prescribe finasteride products—dermatologists, family practice professionals, internists and urologists—about FDA’s review of postmarketing reports and the label changes.” (Source: FDA release: Questions and Answers: Finasteride Label Changes)
The Post-Finasteride Syndrome Foundation (PFS Foundation) is founded in New Jersey by John Santmann.
Michael Irwig publishes an article on depressive symptoms and suicidal thoughts among former users of finasteride.
Jul: The term “post-finasteride syndrome” appears in the medical literature for the first time, in Ganzer et al, 2015 (first published online June 13, 2014).
Mar: Kelly Pfaff files a lawsuit against Merck concerning her husband’s health problems and death by suicide after using finasteride. (Source: Reuters)
PFS Foundation files a Citizen Petition with FDA to remove finasteride for hair loss from the market or add a black box warning to the drug label.
Telepharmacy Hims is founded. The company sells finasteride for hair loss using online marketing and telemedicine consultations with doctors.
An article in Urology discloses that Kevin T. McVary, MD was retained by Merck as an expert in Propecia litigation. Learn more
Most of the ~1,100 plaintiffs who sued Merck over adverse effects of Propecia accept a settlement offer from the company. (Sources: Reuters | Motion and Memorandum for Approval of Settlement Plan)
Telepharmacy Keeps, selling finasteride and other hair loss treatments, accepts $15 million in financing from two venture capital firms. (Source: TechCrunch)
Jun: A study reports penile vascular abnormalities in 68% of young men with persistent adverse effects after using finasteride or dutasteride as a treatment for hair loss.
Nov: A study of suicidality and psychological adverse events of finasteride is published in JAMA Dermatology.
Dec: PFS Foundation files supplements to a 2017 Citizen Petition to FDA to remove finasteride from the market or add a black box warning to the label.
Feb: PropeciaHelp launches PFSNetwork.org, a community to raise awareness and understanding of ‘post-finasteride syndrome’.
Jul: A study reporting altered gene expression in PFS patients is published in the Journal of Sexual Medicine: Howell S, et al. Differential gene expression in post-finasteride syndrome patients.
Oct: In Post-Finasteride Syndrome Foundation v. FDA, Judge Howell grants FDA’s motion to stay proceedings until June 15, 2022.
Nov: PFS Network announces a study of epigenetic changes associated with post-finasteride syndrome, to be carried out by the Institute for Human Genetics at University Medical Center Schleswig-Holstein. (Source: PFS Network)
Jun 8: FDA publishes a response to the 2017 Citizen Petition of the Post-Finasteride Syndrome Foundation, noting: “We are requiring the addition of suicidal ideation and behavior to the list of nervous system/psychiatric reactions in the ADVERSE REACTIONS (Postmarketing Experience) section of the Propecia labeling.” (Sources: FDA response (see p. 43) | Reuters story)
Jun 9: The Post-Finasteride Syndrome Foundation withdraws its lawsuit against FDA regarding the Citizen Petition. (Source: Public Citizen)
Jul 6: France’s national drug regulator ANSM releases an information kit & video to inform patients about the risks of finasteride. (Source: ANSM announcement; see also translated excerpts on Twitter)
Aug: Organon updates Propecia Prescribing Information to meet FDA’s requirements in its letter dated June 8, 2022. Changes include adding “suicidal ideation and behavior” to the Adverse Reactions: Postmarketing Experience section. Patient Information is not updated to include this adverse reaction. (Source: Propecia Prescribing Information at Organon website)
Aug 10: The New York Post publishes the first article on lasting harms of finasteride in a high-circulation U.S. newspaper: Propecia users claim drug causes memory loss, ED, suicidal thoughts.
Jan 19: Health Canada publishes a safety review which found a “possible link between the use of finasteride and the risks of suicidal ideation and self-injury.” Agency plans to update product safety information and inform health professionals.
Jan 31: Organon, the marketer of Propecia, takes the drug off the market in France, but the drug remains available in generic form. (Source: ANSM announcement)
Mar 4: The Daily Mail reports that the UK’s Medicines and Healthcare Products Agency (MHRA) will launch a safety review of finasteride.
May 24: French regulator ANSM announces that since April 28, red boxed warnings have been progressively added to packaging of finasteride 1 mg. The warning states “unwanted sexual and/or psychiatric effects can arise during and after treatment” and includes a QR code linking to an information packet.