Dr. Alan J. Bauman, MD, ABHRS, IAHRS, FISHRS
Before we get into topical dutasteride for hair loss, let’s look at the science behind the medication dutasteride due to its effects on androgens, its use in AGA androgenetic alopecia (MPHL male pattern hair loss or MPB male pattern baldness), how dutasteride as a hair loss treatment might help those with a balding crown area or a receding hairline, the pros and cons of using dutasteride orally or topically for thinning hair vs more traditional treatments like finasteride, and how topical dutasteride might fit in with your hair loss treatment stack.
Dutasteride belongs to a class of medications called 5AR 5-alpha-reductase inhibitors that can suppress the activity of the 5AR enzymes which convert testosterone to DHT dihydrotestosterone, the androgen primarily responsible in AGA androgenetic alopecia, aka MPB male pattern baldness. 5AR inhibitors can be used to treat male pattern hair loss as well as BPH Benign Prostatic Hypertrophy.
Dutasteride inhibits both the type 1 and type 2 5AR enzymes and is approved for the treatment of BPH benign prostatic hypertrophy, an enlarged prostate, at a daily dose of 0.5mg per day orally. Dutasteride has been approved in Japan and South Korea as a treatment for AGA Androgenetic Alopecia or MPHL male pattern hair loss. In the US, dutasteride is approved only for BPH benign prostatic hypertrophy but is often prescribed off-label for AGA.
AGA Androgenetic Alopecia aka hereditary MPHL Male Pattern Hair Loss is a genetic condition that affects tens of millions of American men causing them to lose hair in a readily recognizable pattern, starting typically with a receding hairline and thinning of density in the crown or “vertex” area of the scalp. Data reveals that twenty percent of men in their 20s will be noticing visible signs of hair loss, like a receding hairline. By age 50, nearly half of all men show some signs of AGA-related hair loss or male pattern baldness. AGA is an inherited chronic and progressive condition that can start anytime after puberty and progress slowly or quickly depending on your hair follicles’ own unique “sensitivity” to certain androgens or male hormones in your body.
The primary androgen known to promote AGA is a hormone called DHT dihydrotestosterone. It is your inherited sensitivity to DHT molecules at the cellular level within hair follicles, rather than the absolute level of DHT, that determines your “follicular fate” so to speak. Exposure to DHT over time, causes hair follicles to weaken, miniaturize and produce shorter, thinner, wispier hair over time with each successive growth cycle. This progressively recedes the hairline and diminishes the coverage of the scalp and can eventually lead to total and complete baldness over the frontal area and crown or vertex area. Some men lose more hair in front first, others see more balding in the crown initially.
The hair located around the sides and back of the scalp is considered to be resistant and relatively “immune” to DHT resulting in the traditional “monks ring” of hair that remains -- even with extensive male pattern baldness. [Note: these relatively permanent follicles located around the sides and the back of the scalp are often used as the Donor Area for hair transplantation to restore lasting coverage to the hairline or balding area.]
Because of DHT’s powerful negative effect on the follicles at risk, lowering serum DHT has been a mainstay of therapy for male pattern hair loss for decades. The first approved oral medication for AGA male pattern hair loss, Propecia (finasteride 1mg per day orally), was shown to effectively stop the progression of hair loss in 5 out of 6 men and trigger some regrowth in 2 out of 3 men by significantly suppressing serum DHT levels. Finasteride is an inhibitor of the type 2 5AR enzyme resulting in a significant reduction of DHT in the body.
Mild, temporary sexual side effects were reported in approximately 2-4% of those taking finasteride. [Kaufman 1998] In more recent years, topical application of finasteride has been used to treat hair loss on the scalp while minimizing the risk of sexual side effects by aiming to limit systemic absorption of the medication. [Lee 2018]
Dutasteride inhibits both the type 1 and type 2 5AR enzymes. Studies suggest that the 5AR inhibitor dutasteride is three times more powerful than finasteride in inhibiting type 2 5AR, and 100 times more powerful at inhibiting type 1 5AR [Clark 2004] reducing serum DHT significantly more than finasteride. At a dose of 0.5mg per day orally, dutasteride was able to lower serum DHT by an average of 90%, whereas finasteride lowered DHT by ~70%. [Clark 2004, Dallob 1994]
Dutasteride is not approved for hair loss in the US, but it has been approved in Japan since 2016 and South Korea since around 2010 as a treatment for AGA. In published scientific studies where oral dutasteride was used as a treatment for AGA, dutasteride was shown to improve hair counts, reduce hair loss, improve coverage of the scalp and significantly enhance patients’ quality of life and satisfaction. [Eun 2010, Stough 2007, Olsen, 2006]
Dutasteride, a 5-alpha-reductase inhibitor that was originally approved by the FDA for medical use in 2001 as a prostate medication, as previously mentioned, has been approved in South Korea and Japan for the treatment of androgenetic alopecia for years. In clinical studies, the oral version of dutasteride has been shown to regrow hair more rapidly and to a greater extent than the highest approved oral dose of finasteride.
The superiority of daily dutasteride 0.5mg to finasteride 1mg, with respect to hair density measurements and hair caliber, has been demonstrated in a global phase III clinical trial [Gubelin 2014] and supported by review articles [Zhou 2019, Arif 2017]. Recently, dutasteride was shown to be more potent than finasteride in modulating the expression of key hair growth genes (e.g. FGF7, IGF1, WNT5a) [Hatanaka 2021].
If you believe you have reached a “plateau” in hair growth or maintenance with finasteride use and looking for further improvement in hair growth, you may want to consider dutasteride. In peer-reviewed clinical trials, dutasteride has been shown to be a superior treatment for androgenetic alopecia [Shanshanwal 2017] and an effective alternative treatment for those who did not respond well to finasteride after six months of treatment. In this Korean study, after six months of oral dutasteride, improvements in global photography were seen in 77.4% of patients who had previously not responded well to oral finasteride. [Jung 2014]
Also, the authors noted that while it is possible that “slow responders” to finasteride would likely improve with continued treatment, dutasteride was shown to provide an incremental improvement in hair growth in these patients. They also note that it would be up to the patient and his physician to decide clinically whether to continue finasteride or switch to dutasteride in these cases where the response to finasteride was deemed to be muted or slow.
While finasteride is typically well-tolerated at the traditional dose of 1mg orally per day, finasteride-related sexual dysfunction including decreased libido, ejaculation disorder, erectile dysfunction has been reported in 1-4% of the patient population. [Kaufman 1998, McClellan 1999, Kawashima 2004, Kaufman 2002] Oral dutasteride, though also well-tolerated, has also been linked to sexual dysfunction. [Roehrborn 2004, Debruyme 2004, Bramson 1997]
Dutasteride-related sexual dysfunction occurred in 4.1% of the dutasteride group, which was reportedly similar to finasteride. One of the main concerns about side effects with dutasteride is the fact that its longer half-life may mean the side effects take longer to resolve once the medication has been discontinued than finasteride.
Both finasteride and dutasteride are 5AR 5-alpha reductase blocking agents each with a slightly different pharmacological action that results in decreased DHT production in the body. In recent years, topical finasteride has been an emerging therapy for male pattern hair loss due to the fact that there’s the potential for improving hair growth while also avoiding the systemic side effects of systemic oral finasteride. A recent review article that looked at the results from seven published randomized clinical trials supports the concept that topical finasteride can decrease hair loss, increase total and terminal hair counts, and results in positive hair growth assessment without “serious side effects.” [Lee 2018]
A study that compared serum finasteride levels in topical vs oral administration revealed that the finasteride levels found in the blood were well below the ability of the serum testing assay’s ability to detect and quantify compared to the orally administered finasteride. The fact that finasteride plasma rate and extent of absorption were much lower than with the oral tablets may be the reason that fewer side effects are seen with the topical application.
Pharmacokinetic studies revealed that topical finasteride resulted in a much smaller reduction of serum DHT than oral treatment, which may explain a decreased incidence of side effects. [Casarini 2014] In a follow-up study, finasteride plasma levels after a topical application regimen were revealed a negligible finasteride systemic exposure in the dosages tested. [Casarini 2016]
While it was shown that reduced systemic absorption results in a dramatically reduced side effect profile, additional studies are needed to fully elucidate the safety of topical finasteride.
Oral dutasteride has a proven track record of success when it comes to improving hair growth, hair density, and scalp coverage in AGA. In clinical trials, dutasteride performed better than finasteride in hair regrowth and lowering DHT. In addition, significant type 1 5AR activity has been identified in the scalp. [Bayne 1999] Multiple clinical studies report a significantly positive response from injectable dutasteride in the scalp using a mesotherapy approach.
While peer-reviewed published research on topical dutasteride has been minimal, there are a number of published clinical trial reports of the use of dutasteride on the scalp. Most of these studies are focused on the superficial injection of dutasteride into the scalp using a mesotherapy approach. If we look at these clinical trials we see improved hair counts, reduced hair loss, and improvements in scalp coverage with a good safety profile. [Reguero-Del Cura 2020]
Although there has been some discussion about topical dutasteride [https://www.hairlosscure2020.com/topical-dutasteride-for-hair-loss/], unfortunately, a lack of clinical trials and scientific studies regarding topical dutasteride has left us with more questions than answers regarding the ideal dose or concentration and frequency of use (twice daily, once daily, twice weekly, etc). The pharmacology and pharmacokinetics of dutasteride suggest that daily dosing may not be required. However, keep in mind the majority of studies on oral dutasteride and its effectiveness in BPH and AGA were done using daily dosing.
Unlike finasteride, which has a relatively short half-life (5-7 hours), dutasteride has a much longer half-life which increases with age: (approximately 170 hours in men aged 20 to 49 years, approximately 260 hours in men aged 50 to 69 years, and approximately 300 hours in men older than 70 years) which means once a steady-state has been developed in the body and tissues, infrequent dosing (every other day, twice a week, once a week, etc.) may be adequate.
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