- 1 How is the Success of Hair Loss Treatments Measured?
- 2 The Big Players: Finasteride, Dutasteride, Minoxidil, PRP, LLLT
- 3 Other Treatments
- 4 Notable Absences
- 5 Putting Everything Together: Best and Worst Treatments
- 6 Suggestions/Recommendations
- 7 Limitations of This Approach
The FDA approved minoxidil for male Androgenetic Alopecia (AGA) in 1988. That was a historical moment. Until then, many scientists believed treatment for hair loss to be impossible. Naturally, this breakthrough stimulated tremendous research into other treatments.
Since then, researchers have published thousands of research reports into various treatments. These range from:
- Medical devices
- Regenerative medicine (PRP)
Organizing and comparing this huge body of research to see what works best can be intimidating. Yet that is precisely what this article will do.
You will learn:
- The two ways of measuring hair growth efficacy
- Why objective hair counts are the best for comparison purposes.
- Which hair loss treatments are the most effective
- Which ones do not live up to expectations
- Recommendations and takeaways: which are the best treatments and which should be avoided.
- Limitations of this approach
How is the Success of Hair Loss Treatments Measured?
There are two ways to measure a hair loss treatment’s success.
The first is the so-called subjective assessment or global photography. This involves before and after photos of the patient’s entire head. Doctors take one photo at the start of treatment and one at the end.
One or more independent blinded dermatologists then assess each pair of photos. The dermatologists are independent because they did not participate in treating the patients. They are also blinded because they do not know which treatment each man received. This could have been active treatment vs placebo or active treatment 1 vs active treatment 2, etc.
The most common scale in subjective assessments is:
- 0 for no visible regrowth
- 1 for minimal, or barely visible regrowth
- 2 for moderate, or easily visible regrowth
- 3 for marked regrowth that is both easily visible and extensive.
The second method is objective hair counts or macro photography. Here researchers identify a small patch of the balding scalp. This is typically in the crown of the scalp and is 1 cm2 in size. After they identify the patch, researchers mark it with a semi-permanent tattoo.
Researchers use special cameras to take close-up photos of this area at the start and end of treatment. They then count the number of hairs in the sample, either manually or through special imaging software.
This allows researchers to identify exactly how many new hairs are growing in the sample.
Merits of the Two Methods
Both methods of assessment — subjective and assessment — are useful. Subjective assessments are particularly good in telling us if results are visible to the naked eye. After all, the patient is looking for a cosmetic improvement in the way he and others see his hair. In this sense, they are superior to zoomed-in hair counts.
Yet when it comes to comparing treatments, objective hair counts are more useful. They are the “gold standard” of hair loss research. All serious studies funded by large pharmaceutical companies use objective hair counts. Treatment results are collapsed into a single number: new hairs per cm2. This allows us to compare various treatments directly against each other.
The Big Players: Finasteride, Dutasteride, Minoxidil, PRP, LLLT
A recent 2020 review tried to determine the most and least effective hair loss treatments (1). The researchers were led by A.K. Gupta at the University of Toronto. The study reviewed all Randomized Clinical Trials (RCT) of AGA monotherapies. They left out studies that treated patients with combination treatments, and they only included studies that reported hair counts.
In the end, Gupta et al reviewed 30 studies on male AGA. These were published between 1986 and 2019. They had a combined total of 5679 subjects.
Compared to placebo, these were the average new hairs per cm2 for each of the treatments reviewed (from worst to best)
- Bimatoprost (Lumigan): 4.7
- Low-Level Light Therapy (LLLT): 20.7
- Platelet Rich Plasma (PRP) 33.6
The authors emphasized that more research is needed to confirm the apparent superiority of the newer treatments, LLLT and PRP. The evidence for PRP in particular was especially problematic. The best quality evidence was for 5% minoxidil.
The Gupta et. al. review did not study combination therapies. It also did not include studies that were not randomized controlled trials.
This strategy ensures only relatively high-quality research is included in the analysis. At the same time, it leaves many treatments out. Not just combination therapies (minoxidil fortified with finasteride), but also popular monotherapies like redensyl.
Using the Gupta et. al. review as the backbone, we will add more treatments to their list. These include combination treatments, as well as those with lower quality evidence. A number of statistical adjustments are necessary to keep these additional treatments in line with Gupta et. al.’s data. We keep these to a minimum.
Topical Minoxidil Fortified with Finasteride
Adding topical finasteride to a minoxidil solution gives superior regrowth. According to a 2020 meta-analysis, this treatment gives between 9.3 to 14.2 more hairs compared to 3% minoxidil monotherapy (2). The exact value depends on the statistical assumptions used. We will conservatively accept the lower value of 9.3 hairs. Adding it to an estimated 10.3 hairs/cm2 from minoxidil 3% monotherapy (calculated from Gupta et al), we get 19.3 new hairs/cm2.
Microneedling with Minoxidil
Adding microneedling sessions to an otherwise standard topical minoxidil treatment has become very popular in recent years. Typically the sessions are once a week.
The first study of this kind came from India in 2013. It reported 91.4 new hairs at an area of “1 cm diameter (3).” This is equivalent to 0.78 cm2, giving 117.2 hairs/cm2, an unbelievably high figure. The comparator treatment in this study was standard 5% minoxidil only. This group had 28.4 new hairs/cm2. This figure of 28.4 is 1.9 times higher than the 14.9 hairs/cm2 reported in Gupta et al. The discrepancy might reflect differences with the counting methodology or patient population. If we adjust the hair count for the microneedling/minoxidil group above by the same factor, we end up with 61.7 new hairs.
This figure is still astonishingly high. It is in line, however, with the global assessment of the blinded dermatologists. They noted visible improvement for 100% of patients in the microneedling group. 36% of these were given the highest rating (marked regrowth). Published before and after photos also suggest near-complete regrowth.
Another research team out of China reported similar results in two studies. Both studies compared, among others, a minoxidil 5% only and minoxidil/microneedling combination group (X, X).
In the first study, the 5% minoxidil group had 18.8 new hairs per cm2, compared to 38.3 for the combination group. In the second study, the 5% minoxidil group had 14.3 new hairs/cm2, essentially identical to Gupta et al. This compared to 39.8 hairs/cm2 for the combination group. An adjustment of the values seems unnecessary, given how close they are to Gupta et al.
The two Chinese studies together had an average regrowth rate of 39.1 hairs. They also had nearly the same number of patients as the Indian study. Treating the two combined Chinese studies and Indian study as two equal data points gives an average of 50.4 new hairs/cm2.
This is a naturally derived topical sold as a cosmetic to enhance hair growth. The only hair count data comes from a released document by the makers of Redensyl. According to this, Redensyl gives an average of 17 new hairs per cm2. The document is not peer-reviewed and makes some questionable assumptions.
Clascoterone is a topical antiandrogen medication (4). It is currently in early phase 3 research. Very likely, it will be the next FDA-approved medication against male AGA. The brand name will be Breezula. The only hair count data so far comes from a press release by Cassiopea, the makers of the drug (5). The strongest regrowth is observed with twice daily application, at 7.5%. Compared to placebo, clascoterone gave 14.3 new hairs/cm2.
Botulinum Toxin (Botox)
The aim of this treatment is to loosen the scalp muscles. This, in turn, is thought to stimulate blood flow and regenerate the hair follicles. Unfortunately, the first two studies that performed hair counts report them in terms of percentage increase, not absolute hair counts.
One study reported an 18% density increase and the other 10% (6). More useful data comes from the latest 2020 study from China (7). Patients were given a total of four botox sessions over 12 months. After 12 months, there was an average of 37.7 new hairs in a 2 cm2 area. Dividing this by two gives 18.9 hairs/cm2.
Botox Plus Finasteride
The same Chinese study also included men who were simultaneously treated with 4 botox sessions and daily oral finasteride 1mg. Treatment again lasted 12 months. After this time, there were 55.9 new hairs in a 2cm2 area. This gives 27.9 hairs/ cm2.
Ketoconazole Shampoo (Nizoral)
Ketoconazole is a powerful antifungal, also believed to have mild antiandrogenic properties. Nizoral is sold for dandruff but is widely used by men with AGA. It is believed to be effective in stopping hair loss. The most popular brand name is Nizoral.
The only study to report hair counts after 6-month Nizoral use compared it to 2% minoxidil (8). If we standardize the minoxidil results to Gupta et al’s value, we get a corrected value of 12.4 new hairs/cm2 for ketoconazole users.
Some AGA treatments are widely used. Unfortunately, they have no published efficacy data in terms of hair/cm2. The most important ones are:
- Oral finasteride with topical minoxidil. Surprisingly, there are no studies reporting hair counts after this combination treatment. We do know from subjective assessments that it is superior to either treatment on its own (9). Close to 95% of men on such a regimen will see at least some regrowth.
- Saw Palmetto. This is a very popular natural treatment for male AGA. Unfortunately, there are only a handful of studies, and none report hair counts (10). We therefore cannot compare it to other treatments.
- Castor oil. A widely used natural treatment for AGA, this is a low-cost vegetable oil. It is derived from the castor plant. There is no published research on its efficacy in male AGA.
- RU58841. Another popular treatment with the hair loss community. RU58841 was a once-promising hair loss treatment. Unfortunately, it never completed clinical research trials. Today, vendors sell it as a research chemical unapproved for human use. Men with AGA prepare their own solutions by purchasing raw powder and mixing it with a vehicle.
The company that held the rights to RU58841 conducted two trials in the early 2000s. They never published the results in full. It is therefore not possible to compare RU58841 to other treatments.
Putting Everything Together: Best and Worst Treatments
Now that we have reviewed the available data we can compile it in one table.
|Ketoconazole shampoo (Nizoral)||12.4||High|
|Minoxidil fortified with finasteride||19.3||High|
|Low Level Light Therapy (LLLT)||20.7||Low|
|Botox plus finasteride||27.9||Low|
|Platelet Rich Plasm (PRP)||33.6||Low|
|Minoxidil plus microneedling||50.4||High|
Table 1. All hair loss treatments with available data ranked from least to most effective
There are 14 treatments in the table. Values for seven of these were taken directly from Gupta et al. The other seven were added separately.
The third column is the plausibility of the hair counts values. It is a largely subjective measure. There are three possible values: high, medium, and low. For each treatment, we used the following criteria for plausibility:
- The quantity and quality of published research.
- These are adjusted by the value of the hair count. For example, bimatoprost claims only 4.7 hairs/cm2. This is very modest compared – for example – to LLLTs 20.7 hairs/cm. As a result, it is more plausible, even on the basis of weaker evidence.
- The presence or absence of photos. Studies that report good results should typically provide photographic evidence to support them.
- Agreement with investigator subjective assessments. If the hair counts increases are large, the improvement should also be visible to the naked eye.
- The popularity of the treatments (11). Successful treatments spread by word of mouth, even in the absence of scientific research. The opposite happens for unsuccessful treatments, even when the scientific reports are glowing.
- Anecdotal reports.
- Biological plausibility. Does the treatment make sense biologically?
- Conflicts of interest. For example, if a study on PRP is funded by a clinic offering PRP, this should be taken into account.
Starting from the weaker treatments, bimatoprost is an almost unknown topical unapproved for male AGA. It is also prohibitively expensive. Men with AGA will have no interest in it.
Minoxidil 2% / 5%
The next treatment is also one of the most popular on the list: minoxidil 2%. Unfortunately, it is inferior to more or less every other treatment on the market. The 5% solution offers far better regrowth and users should prefer it.
Clascoterone is a promising topical antiandrogen. It has just been FDA-approved against acne (12). Very likely it will be the next approved medication for male AGA. The hair count data for clascoterone is very limited. It comes directly from the manufacturer in the form of press releases. Having said that, the reported value of 14.3 new hairs/cm2 is more or less the same as 5% minoxidil. The drug is also a proven antiandrogen. This makes the reported value plausible.
As expected, oral finasteride is superior to minoxidil monotherapy, regardless of concentration. This agrees with studies that directly compared the two treatments (13).
The other systemic DHT blocker is dutasteride. This is more powerful and also slightly more effective than finasteride. Again, studies that directly compare the two treatments confirm dutasteride’s superiority (14).
In between finasteride and dutasteride lies Redensyl. This is a natural hair growth product. It is very hard to believe Redensyl has superior efficacy to oral finasteride. The evidence is weak and non-peer-reviewed. Redensyl has remained a marginal choice for men with AGA, even though it has been on the market for years.
Botox claims efficacy superior to finasteride, but not by much. At this point, there are several studies suggesting it is effective. Whether it really is superior to finasteride remains to be seen. It is also difficult to accept that combined with finasteride it can more or less double its strength. More research is needed to support this.
Topical Minoxidil Fortified with Finasteride
Topical minoxidil fortified with finasteride is superior to either topical finasteride or oral finasteride monotherapy. The two drugs have different mechanisms of action. They can therefore be expected to promote hair growth in a synergistic manner.
The results for the next two treatments are problematic in terms of plausibility.
Firstly, LLLT. This easily beats both finasteride and dutasteride in our table. Yet anecdotally, users report disappointing results. Another problem is the almost complete lack of photographic evidence to back up the reported results (15). Investigator assessments also often suggest no visible regrowth, in spite of impressive differences in macroscopic hair counts (16).
Then there is PRP. According to hair counts, this is the second most effective treatment. Its hair count figure is twice that of finasteride. If this were indeed the case, it should give at least some regrowth for the large majority of users. Yet users generally report disappointing results. The hair loss community views PRP with suspicion, especially considering the very high cost. The medical community itself is also split in terms of accepting PRP as a valid hair loss treatment. For these reasons, it is very difficult to accept the hair count value for PRP at face value.
By far the most effective treatment on the table is microneedling in combination with minoxidil. Fifty new hairs/cm2 is more than three times as effective as finasteride or 5% minoxidil. It is also roughly 2.5 times higher than the next most effective treatment with high plausibility: minoxidil fortified with finasteride. Yet in spite of their very high value, these figures are plausible.
They are reported independently by different research teams. The dermatologists’ subjective assessments are in agreement with the hair counts (visible improvement for nearly all patients). Photographic evidence is also provided. There can also be no significant conflict of interest on the part of researchers. A microneedling device costs next to nothing, and minoxidil is off patent. This is not the case with LLLT or PRP, where there are significant financial conflicts of interest.
Microneedling has also become very popular among men with AGA. Remarkable user photos suggesting near-complete regrowth are all over the internet. Taken together, these considerations suggest that this treatment’s seemingly outrageous efficacy is actually highly plausible.
In terms of efficacy, there is a clear winner. Microneedling in combination with topical minoxidil is by far the most effective treatment. It is multiple times more powerful than common monotherapies like finasteride or minoxidil. Almost all users see at least some regrowth. For many – around a third – this improvement will be dramatic. It is also a very low-cost treatment. Side effects are minimal, typically the mild topical reactions to minoxidil.
On the other hand, this treatment is quite demanding in terms of time. The application of minoxidil twice daily is an inconvenience. The weekly microneedling sessions will take up at least an hour (including preparation and cleaning afterwards).
For Ease of Use
In terms of ease of use, there are three winners: ketoconazole shampoo, finasteride, and dutasteride. All three will take up no additional time in the user’s daily routine. In the case of ketoconazole, the user simply replaces his supermarket shampoo with the Nizoral. Finasteride and dutasteride are once-daily pills. They also require no additional time. The difference between the three treatments is that ketoconazole shampoo has no significant side effects. Unfortunately, this is not the case for finasteride/dutasteride.
Minoxidil monotherapy seems like a poor choice, especially at the 2% strength. The 5% formulation is superior. Minoxidil fortified with finasteride gives even better results and avoids the side effects associated with oral finasteride.
Redensyl monotherapy is also ill-advised. Users could, however, find it beneficial as part of a combination treatment.
The newer, more expensive treatments in the form of LLLT and PRP are problematic.
LLLT involves a non-negligible cost in purchasing the appropriate device for home use. It is also the most demanding in terms of time. Treatments are typically several times a week and last a minimum of 15 minutes. It is difficult to justify this investment when there are more effective and plausible treatments that take less time.
PRP is one of the most expensive treatments on the table. For men where budget is not a problem, PRP makes sense as a treatment option. Sessions are spaced out once every few months. This means time investment is minimal. There are almost no side effects. At worst, the treatment will produce no results. For a minority of men, it could give satisfactory results as monotherapy. More realistically, it could boost the efficacy of other treatments in combination regimens.
Having said that, for the majority of men with AGA, budget is a consideration. In this case, PRP does not make sense. The same considerations apply to botox.
Limitations of This Approach
This paper exercise has severe limitations. These become apparent when we consider the ideal way of comparing all hair loss treatments. That would be one single study. It would be carried out by one research team, using one protocol. It would look like this:
A large interdisciplinary team of scientists with unlimited funds would recruit thousands of volunteers. All the volunteers would fulfill the same inclusion and exclusion criteria. Their baseline hair count would be recorded using a single set of criteria.
The volunteers would then be randomly assigned to one of the dozens of treatments. At the end of six or 12 months, their hair counts would again be carefully recorded. Blinded dermatologists would also subjectively assess the before and after photos of the entire head.
Such a study is practically impossible. It would be prohibitively complex and expensive. A handful of institutions and multinational companies would have the funds and logistics to carry it out. Yet none have the financial motivation to do so.
The only alternative is to piece together data from many different studies, which is what this article does. The problem, of course, is that crucial factors differ from study to study. These include the participants, the technicians, the methodology, the length of treatment, etc.
We also had to make decisions when selecting studies to include, such as whether to include studies with women and whether to include data from non-peer-reviewed sources.
Most treatments that work for women also tend to work for men. Yet the overlap is not perfect, and female hair loss is generally easier to treat. For this reason, we excluded studies with women completely. On the other hand, we included studies from non-peer-reviewed sources, like company press releases. The alternative was to simply leave out some treatments altogether.
A number of statistical decisions also have to be made when compiling all this data into one table. For example on adjusting the values that seem too high, weighing studies by sample size, etc. We described these decisions and the rationale behind them. We erred on the side of simplicity and kept in mind the general (non-academic) readership. Different writers would have probably made different decisions. These are largely subjective and justifiable either way.
For all these reasons, the present analysis leaves a lot to be desired. Readers should best view it as a general roadmap. The alternative to this analysis, however, is to simply not attempt any quantitative comparison whatsoever.