5-ARIs: finasteride and dutasteride
Clinically reviewed by
Finasteride and dutasteride are considered the most clinically effective medications for male pattern hair loss. The two make up an exclusive class of drugs called 5-alpha reductase inhibitors (5-ARIs) and each work in a similar way to target a primary cause of hair loss in men.
We’ve put together an overview of clinical data, drug facts and other topical information to help you be proactive, ask questions and select the most suitable treatment for your hair loss.
Discovery and drug development
A medical phenomenon discovered in the mid-1970s spurred the development of finasteride and dutasteride. Individuals with this genetic condition – coined 5-alpha reductase deficiency – have extremely low levels of the male sex hormone, dihydrotestosterone (DHT).
The discovery of this genetic condition informed a more cohesive understanding of 5-AR, testosterone and DHT in relation to prostate health. Finasteride was developed to alleviate symptoms associated with BPH by actually mimicking the effects of 5-AR deficiency.
In early clinical trials, improvements to hair count and quality were observed as a common side effect. Soon afterwards, a reduced oral dosage of finasteride was approved as a treatment for AGA specifically (FDA).
Dutasteride was developed shortly after, with a 0.5 mg/day oral dosage being indicated as a treatment for BPH in 2001 (FDA).
Are finasteride and dutasteride a good option for hair loss?
5-ARIs are the most clinically effective medications used to treat male pattern hair loss. Finasteride and dutasteride literally get to the root of androgenetic hair loss by reducing DHT at the scalp (Hu et al. 2015).
Minoxidil (the active pharmaceutical ingredient in Rogaine™) is another type of drug commonly used to treat hair loss. While it can be effective, minoxidil doesn’t specifically target DHT, the condition’s root cause.
How do finasteride and dutasteride target hair loss?
Elevated DHT within the scalp is often to blame for premature hair loss in men and women. DHT binds to androgen receptors (AR) in the hair follicle. When DHT levels become elevated, the likelihood of DHT binding to AR increases. This can negatively impact the hair growth cycle, resulting in follicle miniaturization, stunted growth and irreversible follicle death if left untreated.
5-ARIs are competitive enzyme inhibitors. Alternatively known as DHT-blockers, these drugs slow the production of DHT by interfering with its synthesis.
Finasteride and dutasteride mimic the usual target of 5-AR, testosterone, binding to a specific location on the enzyme called the active site. Once the drug and enzyme are bound, there’s effectively no way for testosterone to attach itself to the enzyme. DHT can’t be produced once the drug and enzyme are bound.
How are finasteride and dutasteride different?
There are three distinct, or isoforms, of the 5-α reductase enzyme. Two of these isoforms play an important role in DHT synthesis: type I and type II (Kinter and Aneker 2021). Finasteride targets type II 5-α reductase only. Dutasteride inhibits both type I and type II isoforms of this enzyme.
How effective is finasteride in treating hair loss?
In most cases, oral and topical forms of finasteride can treat AGA with success by targeting a leading cause of hair loss: elevated DHT at the scalp. A 5 mg/day oral dose of finasteride was found to reduce serum DHT up to 69% from baseline, in one clinical study.
A recently-published, large-scale literature review surveyed clinical data on finasteride in the treatment of male pattern hair loss. Gupta et al. (2021) established that both topical and oral finasteride can improve hair quality and generate new hair growth in most men with AGA.
Similar conclusions were made by Suchonwanit et al. (2020), in another literature review on finasteride that leaned into topical formulations, specifically. The research team compared the results of 28 studies on topical finasteride for AGA, concluding that topical finasteride can stimulate hair growth akin to an oral treatment regimen, with a more favourable side effect profile.
How effective is dutasteride in treating hair loss?
Dutasteride has demonstrated a greater inhibition of type II 5-α reductase than finasteride, as well as inhibition of type I 5-α reductase (Hu et al. 2015). The drug’s broader action has been credited for the success reported in clinical trials, compared to finasteride. For this reason, it’s been suggested as a potential alternative therapy for men with AGA who have not responded to treatment with finasteride.
In one clinical trial, men with BPH were administered a 0.5 mg/day oral dosage of dutasteride to treat symptoms of prostate enlargement (Rittmaster et al., 2008). Within 4 months of starting treatment, most men experienced an average 90% reduction of serum DHT, the amount in circulation.
Shanshanwal & Dhurat (2017) compared the clinical efficacy of 5-ARIs for male pattern hair loss, specifically. The research team noted a ‘significant improvement’ in hair growth with dutasteride versus. finasteride. Results were observed to be dependent on dosage, which highlights the importance of optimal dosing to strike a balance between efficacy and potential adverse effects.
Is finasteride legal?
In 1992, finasteride was endorsed by the FDA to treat prostate enlargement at a dosage of 5mg/day, taken in pill or tablet form (FDA). In 1998, the drug was approved to treat male pattern hair loss at a 1mg/day oral dosage. This lower dosage is marketed under the brand name Propecia™ but is also available in generic form.
Finasteride is currently indicated as a treatment for hair loss at 1 mg/day taken orally.
Given the potential for sexual and other adverse effects when taken orally, topical finasteride formulations for AGA have been developed to improve drug action at the scalp and reduce the impact on DHT levels in circulation. Topical finasteride can only be obtained by prescription from a compounding pharmacy.
The concentration of compounded topical finasteride varies by formulation. Most formulations contain 0.1-1% finasteride. But a select few are designed to deliver a significantly greater concentration of the active ingredient to hair follicles.
XYON’s Topical Finasteride, with SiloxysSystem™ Gel uses timed-release technology to prolong the delivery of finasteride into the skin. This prescription medication can be compounded at up to 2.5% finasteride.
Is dutasteride legal?
In North America, dutasteride is approved by the FDA to treat BPH at a 0.5mg/day oral dosage. It was marketed under the brand name Avodart™ in 2011, although the FDA patent expired in November 2015.
Dutasteride is currently not FDA-approved for the treatment of male pattern hair loss at an oral dosage or in a topical formulation.
Dutasteride has demonstrated clinical efficacy in treating AGA, making the drug an exciting prospect for topical formulations in development. However, topicals containing this active pharmaceutical ingredient (API) can be more challenging to develop, given dutasteride’s extended half-life and solubility of the drug in different carriers.
What side effects are associated with finasteride and dutasteride?
While 5-ARIs typically treat male pattern hair loss with the highest level of success, drugs in this class have been scrutinized for their risks of adverse drug reactions. For some individuals, sexual side effects associated with finasteride and dutasteride can be cause for alarm, although most individuals do not experience lasting side effects with topical treatment (Gupta et al. 2021).
Finasteride and dutasteride have a similar side effect profile. However, dutasteride’s broader action on 5-α reductase isoforms might carry a greater risk of sexual side effects than finasteride when delivered orally, given its more pronounced effect on DHT levels in the circulation.
The most common sexual side effects of finasteride and dutasteride include:
- Lowered libido
- Difficulty ejaculating
- Erectile dysfunction
- Decreased sperm counts
Other adverse drug reactions have been noted, including the growth of male breast tissue, acute reactions to some topical formulations such as skin irritation, burning or rashes. Some individuals may develop a condition known as post-finasteride syndrome, experiencing side effects of finasteride or dutasteride even after discontinuing treatment.
Note: 5-ARI drugs are currently not permitted for use in women and can be harmful to unborn children (FDA).
Why do finasteride and dutasteride carry a risk of side effects?
The sexual side effects associated with 5-ARIs occur when DHT levels in circulation are impacted. Administered orally, finasteride and dutasteride generally carry a greater risk of long-term side effects than topical forms of both drugs. When more of the active ingredient is in circulation throughout the body, there’s a greater chance that the drug effect will be systemic, or more widespread.
Note: Systemic reduction of DHT concentrations is not needed to effectively target male pattern hair loss, which is why topical formulations can be effective.
5-AR: not just responsible for DHT
The 5-α reductase enzyme catalyzes several chemical reactions and contributes to the production of various steroid by-products, in addition to DHT. Although the most is known about 5-α reductase action on testosterone, this enzyme also targets hormones including aldosterone, cortisol, progesterone and corticosterone (Paba et al. 2011). The hormonal by-products of 5-α reductase reactions are important to various biological processes such as sexual development, metabolism and emotional regulation (Wu et al. 2017).
Some of the side effects associated with finasteride and dutasteride might be attributed to inhibition of other reactions synthesized by the 5-AR enzyme. Further research is required to determine the impact of 5-ARI drugs on other chemical reactions within the body and how they may be tied to certain adverse reactions to finasteride or dutasteride.
Dutasteride and finasteride have both been used to target androgenetic hair loss, with success. Both can reduce levels of DHT at the scalp to target androgenetic hair loss by reducing the ‘attack’ of DHT on the hair follicle.
Oral and topical finasteride can be obtained with a physician’s prescription to treat hair loss in men. While it’s more novel, dutasteride can be an effective alternative for those who haven’t achieved optimal results with finasteride. Consult with a XYON specialist dermatologist to discuss your treatment options.
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