Finasteride Topical Solution - What is the Perfect Dose?

Oral Finasteride is a well-established and effective treatment for men with androgenic alopecia (AGA), but oral dosing comes with some risky side effects. The side effects that may be experienced from oral Finasteride include:

• Reduced sperm count

• Reduction in libido

• Erectile dysfunction

• Depression

• Breast tenderness

 

Topical finasteride offers men a way to regrow their hair by targeting receptors localised to the scalp and may help avoid the systemic side effects listed above when done correctly.

This article will aim to explore:

• The history of Finasteride,

• How much oral finasteride lowers blood DHT,

• Finasteride 1mg tablet vs topical finasteride,

• What is the ideal dose of topical Finasteride for men; and 

• How topical finasteride can go systemic.

 

 

What is Finasteride?

Finasteride is a competitive inhibitor of the type II 5-alpha-reductase isoenzyme. This inhibits the conversion of testosterone to dihydrotestosterone (DHT). DHT is the most potent androgen and is considered a pure androgen. Unlike other androgens, DHT cannot be converted back into oestrogen.

Research shows Finasteride reduces prostatic DHT levels by up to 90% and serum DHT levels by a staggering 70% just by inhibiting the 5-alpha-reductase enzyme. This is where side effects can occur if finasteride leaks into the bloodstream. Its potent effects on prostatic DHT levels make it the drug of choice for treating prostate enlargement in men. The DHT-lowering effects of Finasteride are also dose-dependent (this means a small increase can produce a big change).

 

"If you inhibit the conversion of testosterone to dihydrotestosterone, then men would have more testosterone, so isn't this a good thing?"

 

It's not quite so simple. Compared to testosterone, DHT has approximately twice the binding affinity for the androgen receptor and a dissociation rate about 5 times slower (meaning it hangs around for much longer). DHT plays a critical role in male sexual development, and its role differs as males progress through adult life.

Low serum DHT levels have been associated with reduced libido, depression, weight gain and lethargy. In a perfect world, you want a nice balance of testosterone and dihydrotestosterone.

 

How much serum DHT is affected by oral finasteride?

Drake and Hordinsky et al showed that serum DHT levels are significantly reduced even with low-dose oral Finasteride. A study conducted in 249 men with androgenetic alopecia included scalp biopsies before and after receiving 0.01mg, 0.05 mg, 0.2mg, 1mg, and 5 mg of oral finasteride or placebo daily for 42 days. The results showed scalp DHT levels declined by 13.0% with placebo and by 14.9%, 61.6%, 56.5%, 64.1%, and 69.4% with 0.01mg, 0.05 mg, 0.2mg, 1mg, and 5 mg doses of finasteride, respectively.

Key takeaway: Men who took a 1mg finasteride tablet daily experienced a 71% reduction in blood DHT levels (Figure 2).

 

 

Oral finasteride 1mg vs topical finasteride solution. 

If I am taking 1mg oral finasteride, what is the topical equivalent?

The 2021 study by Piraccini et al. (published in the Journal of the European Academy of Dermatology and Venereology) found that 0.25% topical finasteride was as effective as 1mg oral finasteride in treating male pattern hair loss (AGA) over 24 weeks, while causing a smaller reduction in blood DHT level (Figure 3). The study, involving 458 patients, showed similar, significant improvements in hair count. 

Key takeaway: Men who used 0.25% topical finasteride daily experienced a 34.5% drop in DHT levels versus a 55% reduction with 1mg oral finasteride. Similar improvements in hair count were seen in both groups.

 

 

Does that mean I should start with 0.25% finasteride topical solution if I want to switch from finasteride 1mg oral tablet?

Not so fast. A small reduction in blood DHT may cause side effects in some but not in others (this is also seen in practice). This is also noted in the study (the keyword is "less likelihood"):

 

"As maximum plasma finasteride concentrations were >100 times lower, and reduction from baseline in mean serum DHT concentration was lower (34.5 vs. 55.6%), with topical vs. oral finasteride, there is less likelihood of systemic adverse reactions of a sexual nature related to a decrease in DHT with topical finasteride."

 

Key takeaway: A lower likelihood of side effects does not always mean no side effects, so it is best to start low and increase as needed, with personalisation. 

 

 

Is there a safe dose that doesn't affect blood DHT levels?

It is important to note that a small reduction in DHT level does not automatically equal side effects. The threshold at which side effects can occur varies from person to person (think of it like a pain threshold). If you want the safest, no reduction zone, then read on.

The first study on topical finasteride was conducted by Mazarella et al. in 1997 as a single-blind, placebo-controlled trial that enrolled 28 males and 24 females with AGA and lasted 16 months. The Subjects were randomly split into two groups:

• Group 1 - Received 1.0 mL topical Finasteride 0.005% solution twice daily

• Group 2 - Received 1.0ml placebo twice daily

Blood samples showed no significant differences in plasma levels of total testosterone, free testosterone, or DHT between the groups.

At sixteen months, the researchers observed a significant decrease in hair loss in Group 1 compared with the placebo group.

 

Key takeaway: This study lasted 1.5 years, with 1 mL of 0.005% finasteride twice daily (total daily exposure = 0.01%). Understandably, most men don't want to wait that long to see cosmetic improvements.

 

What is the ideal dose of topical Finasteride for men?

We know from the studies above that 0.25% reduces serum DHT by 34.5%, whereas 0.01% has no effect. This leads to the conclusion that the ideal dose for most men is somewhere in between ...

Setting aside any cognitive biases, the large multi-centre study published by Piraccini et al also demonstrated two interesting points:

• The range that showed an improvement in hair count with the least impact on serum DHT was 0.114mg to 0.912mg.
• Spray pumps have a higher margin for error.

 

Key takeaway: the ideal dose for each individual should be personalised, and the results from the studies should be used as a guide only.

 

How does topical Finasteride get into the bloodstream?

Systemic exposure to topical Finasteride can occur due to:

• Drawing too much into the dropper. Finasteride has a dose-dependent response curve, so a little extra Finasteride can produce a big response.

• The strength/dose is too high for the individual,

• The formulation. Alcoholic and hydroalcoholic formulations have been found to improve the absorption of Finasteride compared to Liposomal and aqueous (water) formulations. It is thought that alcohol disrupts the surface of the skin, allowing better drug penetration.

• Application device - In the most recent study conducted, a topical spray was used containing Finasteride 2.275mg/ml but only 50 µL of solution was delivered due to air dispersion. If the same person applied the exact same dose in a topical solution, the systemic exposure would increase significantly due to the absence of air dispersion.

Finally,

• The frequency - twice daily application has shown to have a larger impact on serum DHT and therefore daily application is preferred.

 

 

 

 

 

 

 

 

Author: Helen Huynh B.Pharm MPS

 

References:

1) Mazzarella GF, Loconsole GF, Cammisa GA, Mastrolonardo GM, Vena G. Topical finasteride in the treatment of androgenic alopecia. Preliminary evaluations after a 16-month therapy course. J of Derm Tr. 1997;8(3):189–92. DOI: 10.3109/09546639709160517.

2) Caserini M, Radicioni M, Leuratti C, et al. A novel finasteride 0.25% topical solution for androgenetic alopecia: pharmacokinetics and effects on plasma androgen levels in healthy male volunteers. Int J Clin Pharmacol Ther. 2014;52(10):842–9

3) Tabbakhian M, Tavakoli N, Jaafari MR, Daneshamouz S. Enhancement of follicular delivery of finasteride by liposomes and niosomes 1. In vitro permeation and in vivo deposition studies using hamster flank and ear models. Int. J Pharm 2006. October 12; 323(1–2):1–10

4) Pirracini, B et al. Efficacy and safety of topical finasteride spray solution for male androgenetic alopecia: a phase III, randomized, controlled clinical trial. J Eur Acad Dermatol Venereol. 2021;Feb;36(2):286-294.

5) Drake L, Hordinsky M et al. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J of American Dermatology. 1999 Oct;41(4):550-4.