Controversies in the treatment of androgenetic alopecia: The history of finasteride

1 | HISTORY

In 1992 the U.S. FDA approved Proscar (finasteride 5 mg daily) for the

treatment of benign prostatic hyperplasia (BPH). A 4-year placebocontrolled

study of 3,040 men suffering from BPH (the Proscar Long

Term Efficacy and Safety Study [PLESS]) was conducted (US FDA,

2011). About 1,524 subjects were administered Proscar and 1,516

subjects were administered a placebo. During the first year, decreased

libido was reported in 6.4% of subjects in the Proscar group versus

3.4% observed in the placebo group. Erectile dysfunction was

reported in 8.1% of subjects in the Proscar group versus 3.7% in the

placebo group. However, in the second year of the study there was

no significant difference in the rate of sexual adverse events between

the Proscar and placebo groups. Decreased libido was reported in

2.6% of subjects in the Proscar group versus 2.6% in the placebo

group (p = 1.00). Erectile dysfunction was reported in 5.1% if subjects

in the Proscar group versus 5.1% in the placebo group (p = 1.00)

(US FDA, 2011).

As early as 1942, James Hamilton observed that low testosterone

due to castration prevented the development of AGA in males

(Hamilton, 1942). Additional evidence for hormonal involvement in

the development of AGA came from a group suffering from congenital

5-alpha reductase deficiency. In this group, males failed to develop

AGA (Imperato-McGinley, Guerrero, Gautier, & Peterson, 1974). Subsequently,

scientists at Merck, Inc. developed a lower dosage oral

finasteride for the treatment of AGA. In 1997, the U.S. FDA approved

Propecia (finasteride 1 mg daily) for the treatment of AGA.

In three 12 months clinical studies, 945 subjects were administered

Propecia and 934 subjects were administered a placebo. During

the first year, decreased libido was reported in 1.8% of subjects in the

Propecia group versus 1.3% in the placebo group. Erectile dysfunction

was reported in 1.3% of subjects in the Propecia group versus 0.7% in

the placebo group. In the fifth year of treatment the rate of adverse

events decreased to less than 0.3% in all groups (US FDA, 2011).

Additionally, men that discontinued therapy had no further sexual

adverse events. A recent study by Gupta et al. examined finasteride

adverse events from 2004–2015 using the Food and Drug Administration

Adverse Event Reporting System (FAERS) database. Similarly,

they concluded that occurrence sexual adverse events from finasteride

are rare (Gupta, Carviel, MacLeod, & Shear, 2017).

In 2011 the U.S. FDA conducted a post marketing evaluation of

reported cases of persistent sexual dysfunction after finasteride discontinuation.

About 2,527 cases of Propecia related adverse events

were identified from December 19, 1997 to April 14, 2011. Of the

2,527 cases, the U.S. FDA identified 59 reported cases of sexual dysfunction

that lasted three or more months after finasteride discontinuation.

In 20 of these cases (34%) sexual dysfunction persisted for 1–2

years and in 7 of the cases (12%) sexual dysfunction persisted for

three or more years (US FDA, 2011). It was noted that in some of the

cases subjects had low testosterone values. Subsequently, the FDA

has required Merck to revise the Propecia label to disclose the post

marketing sexual adverse events. Shortly after Merck revised its label,

thousands (or perhaps hundreds of thousands) of websites claim that

Propecia and finasteride cause erectile dysfunction and loss of libido.

In addition, dozens of lawsuits and support group websites were

formed. As of the writing of this chapter, a Google search (www.

google.com) yielded the following number of results (Table 1).

2 | CLINICAL PRACTICE

2.1 | Aging in males

Lower testosterone is associated with erectile dysfunction, decreased

libido, and depression (Wu, 2010). It is widely recognized that males

experience a gradual decline in testosterone concentration starting as

early as their third decade (Dimopoulou et al., 2016); however, erectile

dysfunction can afflict men of all ages. In a study of 27,839 men from

eight countries, Rosen et al. (2004) observed a prevalence of erectile

dysfunction of 11% in men between the ages of 30 and 39, and 8% in

men between the ages of 20 and 29. Different methodologies are

often used to diagnose erectile dysfunction (Nguyen, Gabrielson, &

Hellstrom, 2017) and these varied methodologies can produce different

prevalence rates. Nevertheless, it is evident that the rate of sexual

adverse events in patients treated with finasteride is consistent with

the prevalence of erectile dysfunction in the general population. Additionally,

the age of onset for hormonal changes that manifest as sexual

dysfunction often coincide with the age of onset for the development

of AGA. As such, subjects experiencing AGA may be more likely to

experience sexual dysfunction; hence, it may be difficult to attribute

the development of sexual dysfunction to finasteride use alone.

2.2 | Other drugs

It is important to note that several widely used drugs elicit sexual dysfunction.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin

norepinephrine reuptake inhibitors (SNRIs) are well known for their

sexual side effects. In his review, Rothschild (2000) concluded that

antidepressants may cause sexual adverse events in up to 40% of

patients. Higgins, Nash, and Lynch (2010) literature review concludes

that incidence of sexual adverse events among SSRIs users is greater

than 50%. In contrast, the long-term rate of sexual adverse events

among patients using finasteride is less than 1%.

RECOMENDATIONS [sic]

All drugs carry a risk of adverse events. As clinicians, when prescribing drugs, we strike a balance between the risk of developing adverse events and the benefit of the treatment. While some drugs such as finasteride are effective in the treatment of the underlying disease, the controversy surrounding the risk of adverse events clouds patient’s willingness to use the drug. This is a dilemma frequently faced by pediatricians when attempting to immunize children. Pediatricians attempt to overcome the resistance to immunization by educating parents with evidence from controlled studies. While physicians should avoid controversial topics, finasteride is unfortunately the only U.S. FDA approved drug with significant efficacy in arresting the progress of AGA. The other common alternative, minoxidil, has relatively low efficacy; less than 40% of patients regrow hair following 16 weeks of daily application of 5% minoxidil (Olsen et al., 2007). Prior to prescribing finasteride, physicians should adequately educate patients and thoroughly assess their current sexual and psychological well-being. To that end we have developed the following short workup questionnaire:

• Do you experience any symptoms of sexual or erectile dysfunction?

• Do you experience nocturnal erection three or more times per week?

• How often do you have sex?

• Are you using any anti-depressants?

• Do you suffer from hypertension?

• Do you suffer from diabetes?

• Do you have a history of depression?

Together these questions help assess the risk a patient has or is likely to develop sexual dysfunction. Patients that are not suffering from sexual dysfunction or are less likely to develop sexual dysfunction, are good candidates for finasteride. In patients that are candidates for finasteride, it would be appropriate to explain the evidence from the controlled studies presented on the finasteride FDA label. It is ultimately up to the patient to decide if the relatively low risk of sexual dysfunction outweighs the benefit of finasteride in the treatment of AGA, but the evidence speaks for itself.

Goren Andy1 | McCoy John1 | Situm Mirna2 | Dhurat Rachita3 | Krychman Michael1 | Kovacevic Maja2 | Sharma Aseem3 | Bolanca Zeljana2

1Applied Biology, Inc., Irvine, California

2Department of Dermatology and

Venereology, University Hospital Center

Sestre Milosrdnice, Zagreb, Croatia

3Department of Dermatology, LTM Medical

College & Hospital Sion, Mumbai, India

Correspondence

Maja Kovacevic, MD, Department of

Dermatology and Venereology, University

Hospital Center Sestre Milosrdnice,

Vinogradska cesta 29, Zagreb, Croatia.

1 Like

This was a good post. I agree with you. Why withdrawn?

I don’t get it.

How is sexual (dys)function prior to taking finasteride supposed to predict an adverse reaction?
That’s like saying a person is at a higher risk of developing hypertension from taking a specific drug based on that person already having hypertension.

At least this questionnaire might show evidence of the changes in sexual function before/during/after.

1 Like

This questionnaire will definitely highlight the sexual problems this drug causes.
As to people missing out on stopping there hair loss in it’s tracks due to negative feedback surrounding side effects of finasteride well that’s laughable as in my opinion the lucky guys are the ones that don’t take this drug in the first place why risk a lifetime of problems all to save your hair .
Vanity leads to insanity when this drug leaves you with persistent long term side effects life will never be the same again and you will still lose your hair along with your manhood .
Finasteride is dangerous my advice to anyone is don’t take the gamble.

1 Like

This reads to me like the hair loss industry trying to manage the larger number of men declining finasteride due to their increased awareness of their long term side effects. To equate hair loss with a disease and then to imply that those who turn away from the most effective current treatment for hair loss are akin to parents refusing to have their children vaccinated suggests that they are continuing to peddle their misinformation under their abusive power as care givers. To even suggest that hair loss is a disease state and that declining finasteride is as a result of misinformation is so much more b.s. That they then present themselves as the harbingers of truth in that they can somehow properly inform and assess risk will only falsely reassure any man. I have only briefly read the above and not had a proper look at the link, but at first glance it feels like a guide to continue to deceive and increase sales and makes me just a little angry. This to me is the evil in men.

6 Likes

Totally agree, @Scotsman. I want to like that post twice. This is absolute garbage. It is also implying data that doesn’t exist and then asserting this survey would somehow help based on that, which it won’t in any way. Either irresponsibly ignorant or muddying the waters by design. Disgusting either way.

5 Likes

@Scotsman @axolotl @Dubya_B Yep, I’m with you guys. I had zero sexual problems before propecia. I would’ve passed that test with flying colors only to be disappointed and have my life ruined just a short time later.

4 Likes

Love the username Alteredlife
Let’s hope this survey backfires on them and the sexual dysfunction lack of libido etc etc complaints come in thick and fast as we know they sure will do.
I would have walked straight through any test prior to Finasteride but now I doubt i would get off first base due what this drug did to me and Im left with the life altering circumstances im in with no one to turn to as GPs are so useless with these problems it’s pointless talking to them yet the media the medical world and all of us have pointed the complications that we face yet we are ignored and left to ponder amongst ourselves waiting for the answers looking for the reasons as to why this drug affected us this way.

3 Likes

Read these reviews im sure we can all see the sexual problems are coming to light

WOW! There are only 3 positive reviews out of the first 20.

“Hop on finasteride and don’t think about the side effects!”

^Worst advice ever.

Yes and to think they are actually selling the poison , Not exactly good for business feedback like that …
More importantly it shows the true picture of finasteride users experiences.

1 Like

Hop on finasteride if you want to be chemically castrated…

1 Like

I edited the original post to include the rest of the article.

I went and left my own review. I didn’t even have to sign up. You guys ought to do the same if you haven’t already.

2 Likes

Absolutely right! Every single member of this forum should report their experience on this and other drug review pages. We need to educate the world on how many cases there are. Many people, including myself, took fin thinking side effects were super rare. Now I believe they are the rule, not the exception. It’s just that they’re easier to notice in some people.

So leave a damn review!