What Is Minoxidil?

Oral minoxidil was first FDA-approved for hypertension (high blood pressure) in 1979 under the brand name Loniten by Upjohn Pharmaceutical Company. The oral dosage used to treat hypertension ranges from 10 mg to 40 mg per day. Dermatologists in the United States observed that their patients who were taking minoxidil for high blood pressure were also growing thicker and longer hair on their scalp, sideburn region, and other parts of the body (a term called hypertrichosis). With this knowledge, Dermatologists in the United States started compounding it by dissolving the blood pressure pill and applying it topically to balding men’s and women’s scalp throughout the 1980’s. This was considered off-label use since it was not FDA-approved to treat androgenetic alopecia.

Upjohn performed the very costly studies (hundreds of millions of dollars) to get 2% topical minoxidil (Rogaine) FDA-approved for androgenic alopecia in men in 1988. 2% minoxidil was approved for OTC sale in 1996. Upjohn then performed studies to get the 5% topical minoxidil FDA approved in 1997, and then for the OTC sale in 1998. 5% percent minoxidil foam was FDA approved for OTC use in men in 2006.

2% topical minoxidil was finally FDA approved for androgenetic alopecia in women in 1991, and the 5% Foam was FDA approved for women in 2014.

Upjohn never did comparative studies of oral minoxidil versus topical minoxidil in the treatment of androgenic alopecia. This would have been financial suicide. If the oral dose was shown to be more effective than the topical minoxidil, they would have never recouped their investment into getting the topical formulation FDA-approved.

Also Read: Finasteride for Hair Loss: A Guide by Dr. Paul J. McAndrews

How does Minoxidil Work?

Minoxidil must be broken down into its active metabolite minoxidil sulfate by the enzyme sulfotransferase to cause its effect for both hypertension and androgenetic alopecia.

The mechanism of action of minoxidil sulfate in treating hypertension is by being a potassium channel opener, creating a potent vasodilator. Minoxidil sulfate is an indiscriminate hyperkeratotic, which means it will try to get any hair follicle to grow a little bit thicker and longer.

You hear many doctors incorrectly pontificating that the mechanism of action in the treatment of androgenic alopecia is because of vasodilation, which increases blood flow to the hair follicles. This is completely incorrect. There are many vasodilators that are FDA-approved on the market that do NOT cause hair growth. 

The mechanism of action for minoxidil sulfate in treating androgenetic alopecia is still presently unclear. There is some thought that it works via expression of vascular endothelial growth factor (VEGF) and/or increasing prostaglandin E2 to cause lengthening of the growing phase (anagen) of the hair follicle and thickening of the hair shaft.

Also Read: Hair Growth Cycle: All You Need to Know

Minoxidil does not treat the hormonal cause of androgenetic alopecia. It is not an androgen modulator (ex: finasteride or dutasteride) or an anti-androgen (several in clinical studies).

Types of Minoxidil

Minoxidil is still the only FDA-approved topical treatment for androgenetic alopecia in both men and women. It may soon be joined by a few topical anti-androgens (see blog on Clascoterone and Pyrilutamide) that are close to being FDA-approved.

Topical minoxidil solution

Minoxidil (2%-5%) first got FDA-approved in a topical solution using propylene glycol to dissolve the minoxidil into a liquid. Higher strengths of minoxidil precipitate out of this solution, and it’s worthless. The 5% solution was shown to be more effective than the 2% solution.

Topical minoxidil foam

5% minoxidil foam subsequently got FDA approval, using glycerin to dissolve the minoxidil into solution. The minoxidil solution is absorbed through the skin slightly better than the foam. There were no comparative studies evaluating the efficacy of the 5% solution vs the 5% foam.

Low-dose oral minoxidil

Low-dose oral minoxidil is presently prescribed by many physicians “off-label” in both men and women to treat androgenetic alopecia. “Off-label” means it’s being used in the treatment of a disease that it’s not FDA-approved for. For example, topical minoxidil was used throughout the 1980s “off-label” to treat androgenic alopecia until it received FDA approval.

The smallest size tablet of oral minoxidil made is 2.5 mg. This 2.5 mg tablet of minoxidil is subtherapeutic for blood pressure (too low of a dose to decrease blood pressure); however, this dose definitely has the benefit of increasing hair shaft thickness and length. 

Also Read: Is Clascoterone the Miracle Cure for Hair Loss?

Efficacy of Oral Minoxidil vs Topical Minoxidil

The short answer is Oral Minoxidil is more effective than Topical Minoxidil. 

Oral Minoxidil is more effective for a few reasons:

• • Minoxidil must be broken down into its active metabolite, minoxidil sulfate, by the enzyme sulfotransferase to cause the beneficial effect of thicker and longer hair production by the hair follicle. Approximately 60% of patients do not have enough sulfotransferase in their scalp hair follicles to respond effectively to topical minoxidil. Therefore, they’re not converting enough active metabolite, minoxidil sulfate, for the beneficial effect in the hair follicle. There’s also some data to suggest this low enzyme activity is more prevalent in men. Oral minoxidil is converted into the active metabolite, minoxidil sulfate, in the liver, where there’s an abundance of the sulfotransferase enzyme.

• • Compliance is a big factor. Patients are more compliant with taking a medication orally than applying it topically.

• • The systemic distribution of minoxidil sulfate is more complete with oral administration. Topical administration has a tendency not to be applied to all the hair follicles prone to the influences of androgenetic alopecia.

Minoxidil for Men

Topical minoxidil solution and foam were FDA-approved in the treatment of androgenic alopecia, specifically in the vertex (crown) region in men. They did not do the studies in order to get FDA approval in the other areas (hairline, frontal forelock, mid-forelock, temporal points) affected by androgenetic alopecia. Therefore, they legally cannot say it works in other areas.

Minoxidil works the best in the vertex region of the scalp, and that is why they did the studies there to get FDA approval. It was FDA-approved to be applied twice a day. Minoxidil is an indiscriminate hypertrichotic that causes hair growth everywhere. As Dermatologists, we know it’s also a benefit in the other areas affected by androgenic alopecia.

It is of utmost importance that men experiencing androgenetic alopecia are realistic about their expectations and goals for the use of minoxidil. Being unrealistic about their goals is the single most common reason patients stop using minoxidil. Patients should think of androgenetic alopecia like they see tooth decay; both are an aging process that progressively gets worse as you get older. Toothpaste slows tooth decay; it does not fill in cavities. Men need to adjust their goals for minoxidil to be more realistic in that it will slow down or slightly reverse the progressive nature of androgenic alopecia.

Also Read: What Are the Best Medications for Hair Loss?

Minoxidil for Women

Topical minoxidil solution and foam were also FDA-approved in the treatment of androgenic alopecia, specifically in the vertex (crown) region in women. They did not do the studies in order to get FDA approval in the other areas (hairline, frontal forelock, mid-forelock, temporal points) affected by androgenetic alopecia. Therefore, they legally cannot say it works in other areas.

Minoxidil is an indiscriminate hypertrichotic that causes hair growth everywhere, so as Dermatologists we know it’s also a benefit in the other areas affected by androgenic alopecia.

Minoxidil works the best in the vertex region of the scalp, and that is why they did the studies there to get FDA approval. It was FDA approved for women to be applied twice a day with the 2% solution and applied once a day with the 5% foam.

It is of utmost importance that women experiencing androgenetic alopecia are realistic about their expectations and goals for the use of minoxidil. Being unrealistic about their goals is the single most common reasons patient stopped using minoxidil. Patients should think of androgenetic alopecia like they see tooth decay; both are an aging process that progressively gets worse as you get older. Toothpaste slows tooth decay; it does not fill in cavities. Women need to adjust their goals for minoxidil to be more realistic, in that it will slow down or slightly reverse the progressive nature of androgenic alopecia.

Minoxidil Shedding Phase

In the first few months of starting either topical or oral minoxidil, patients can experience an increase in shedding. The clinical term for this synchronization of the hair follicle to cause this increased shedding is “Telogen Effluvium”. I tell my patients there is nothing to worry about, and it is actually a good sign that the follicle is being stimulated by the minoxidil. Eventually, the shedding will slow down, and the follicles will produce another hair, which hopefully will be slightly thicker and grow slightly longer. There is no treatment, and this will self-correct over the next few months as you continue taking the minoxidil.

How Long Does Minoxidil Take to Work

1 – 3 Months

In the first several months of using minoxidil, there will be no visible benefits, and actually, you might see an increase in shedding, which is nothing to worry about.

4 – 6 Months

During this time, again, do not expect to see any visible benefits; however, the shedding should become less.

12 Months +

I tell my patients not to judge the results of minoxidil for at least a year. Again, it’s very important to set realistic expectations. I tell patients it’s not what you see, it’s what you’re not seeing. If they’re not seeing further progression of their androgenetic alopecia, that’s a huge benefit since the average patient’s hair density decreases by about 4% a year. Remember, the goal of toothpaste is to slow the progressive nature of tooth decay; the goal of the preventative medical therapies for androgenic alopecia is to slow the progressive nature of their hair loss.

It is important to consistently use minoxidil, just as it’s important we consistently brush our teeth. Toothpaste and minoxidil are both slowing the aging process if used consistently.

How to Use Minoxidil Correctly

Topical minoxidil is FDA-approved to be used twice a day in men, and only once a day in women. When minoxidil gets absorbed through the skin, it has a 22-hour half-life, so using it once a day is probably just as effective as twice a day.

Minoxidil doesn’t work if you do not use it consistently. One of the most common reasons people do not use topical minoxidil is lack of compliance: it’s too complicated or cumbersome to consistently use daily. Therefore, I tell my patients to make the application process as easy as possible to maintain a daily regimen.

Topical Minoxidil Application Process:

1. 1. Apply once a day
   2. Apply to all areas experiencing androgenetic alopecia (not just the vertex)
   3. It needs to get to the scalp and not onto the hair (unfortunately, the necessary evil is that it needs to get into the hair in order to get onto the scalp)
   4. Don’t worry about using too much – just apply a thin layer onto the balding scalp
   5. Don’t make it complicated – complicated regimens eventually are stopped secondary to the lack of compliance
   6. The foam is easier to use and less irritating

Oral Minoxidil Process:

1. 1. Swallow one pill a day with food or without food
   2. Leave it near your toothbrush, so when you brush your teeth in the morning or night, it reminds you to take it.

Side Effects and Safety

Feature	Topical Liquid (Oil)	Topical Foam
Skin Irritation	Itching, Flaking, and Redness  More irritating since it is dissolved in propylene glycol. Most people who get irritated or allergic to the topical solution, it’s usually due to the propylene glycol and not the minoxidil.	Less Itching, Flaking, & Redness The Topical Foam is dissolved in Glycerin, which is much less irritating
Drying Time	Greasier and stays wet for several minutes.	Dries quickly, and some people like it as a styling agent.
Application	Preferred more by women who do not want to get it in their long hair. Use a dropper to target the application to the scalp.	Easier to spread quickly to a large balding area, and some feel it helps style their hair.

Occasionally, patients complain of heart palpitations or dizziness with the topical formulations

Off-Label Oral Minoxidil

Occasional Complaints of:

• • Increased heart rate
  • Palpitations
  • Rash
  • Rare risk of Anasarca (swelling of extremities, around heart and lung)- potentially dangerous, and medications should be stopped ASAP

What Happens If You Stop Minoxidil?

If you stop brushing your teeth, you’ll lose the benefit of toothpaste in slowing tooth decay, since it is an aging process. Topical and oral minoxidil is treating the aging process; therefore, if you stop the medications, within a year, you will go back to how you would have been if you never took the medications. The longer you have been on minoxidil, the more significant the decline of density in areas that have the genetic predisposition for androgenetic alopecia will be in the year after stopping it.

Minoxidil vs Other Hair Loss Treatments

Finasteride & Dutasteride

Finasteride and Dutasteride are the most effective treatments for androgenetic alopecia in men. Their mechanism of action is that they competitively inhibit the enzyme, Type 2 Alpha-5-Reductase, which decreases the conversion of testosterone into DHT. DHT is known to cause miniaturization of the susceptible hair follicle predisposed to androgenic alopecia at a genetic time. 

Since the mechanism of action of Finasteride and Dutasteride is different than minoxidil, their combination use is synergistic.

Hair Transplant

Hair transplants and the preventative medical treatments of androgenic alopecia are accomplishing two different goals.

Androgenetic alopecia is an aging process, just like tooth decay is an aging process. Toothpaste and the dentist filling in the cavity accomplished two different goals. Toothpaste slows down tooth decay, not the dentist. A dentist fills in the cavity caused by tooth decay. Similarly, the medical preventative treatments slowed down the balding process of androgenetic alopecia, whereas a hair transplant surgeon just fills in a balding area left by the progressive nature of androgenic alopecia. The limitations of transplants are that there’s a fixed amount of good genetic hair that can be taken from the side and the back of the head to fill in these cavities. The hair transplant surgeon needs the help of preventative medical therapies in order to slow the progressive hair loss.

Also Read: Do Hair Transplants Really Work?

PRP

PRP stands for platelet rich plasma. This treatment involves the physician removing blood from a patient and spinning it down to get the platelet rich plasma (PRP), which is then injected back into the balding area of the patient. I believe the study designs used to evaluate PRP and the endpoints would never pass the scrutiny of the FDA approval process. I think there’s one absolute truth about PRP for the treatment of androgenic alopecia: it makes money for doctors. Even if there is some benefit of PRP, this treatment would have to be continued forever to maintain the benefit (similar to the continual use of toothpaste, blood-pressure meds, finasteride, and minoxidil in treating the aging process).

Who Is a Good Candidate for Minoxidil

The good candidate for minoxidil is:

• • Realistic about their expectations for minoxidil in slowing the progressive nature of androgenic alopecia 
  • Using it as soon as possible in the progressive course of androgenic alopecia. Similarly, the best time to start brushing your teeth is as soon as possible, given the progressive nature of tooth decay. We don’t wait till we have half our teeth left before we start finally brushing our teeth.

My Experience with Minoxidil 

As a Board -Certified Dermatologist that’s been formally trained in the science and art of hair restoration surgery, I am a very big advocate of the preventative medical treatments that slow the progressive nature of androgenic alopecia. Finasteride and dutasteride are presently the best treatments. However, since topical and oral minoxidil work on a totally different mechanism of action, adding them creates synergistic benefits. I like my patients on both medications if possible. In the proper hands, hair transplants should look completely natural. The big limitation to hair transplants is that there’s a fixed amount of good genetic hair that can be taken from the sides and the back of the head to transfer to the balding area. Unfortunately, most hair transplant surgeons are not formally trained in the pathophysiology of androgenic alopecia, so they solely rely on hair transplants to fill in the cavities, which creates unnatural results over the decades as the patient continues to bald (over-harvested donor areas become see-through and hair transplanted in the wrong area that becomes more and more unnatural as the patient ages).

The preventative medical therapies can slow the progressive nature of androgenic alopecia, which will create an environment where patients will not need anywhere close to the number of transplants to keep up with their hair loss. Hair transplant surgeons have a conflict of interest since we have a financial interest not to want you on the preventative medications. Hair transplant surgeons do more hair transplants on patients who are not on the preventative medical therapies. I highly encourage All my patients dealing with androgenetic alopecia to be on the preventative medical therapies.