Minoxidil is probably the most popular hair loss treatment in the world. It’s one of only two treatments for androgenetic alopecia that have FDA approval, and it has decades of evidence behind it. Yet despite all of this, the overall response rate for topical minoxidil sits at only around 30 to 40%. That means somewhere between half and two-thirds of people who use topical minoxidil don’t see meaningful results. So if you’ve been applying minoxidil consistently for months without results, you might be a non-responder. In this article, we explore the science behind why minoxidil does and doesn’t work for everyone. We’ll also review what you can do to improve your chances of it working, and the alternatives if you’re a non-responder.
How Does Minoxidil Actually Work?
To understand why minoxidil fails for some people, it helps to understand how it works. Minoxidil was originally developed in the 1970s as a treatment for severe high blood pressure. It’s a vasodilator, which means it relaxes blood vessels and improves blood flow. Doctors noticed that patients taking it were experiencing increased hair growth as a side effect. Off the back of this, topical formulations then became available for treating hair loss.
Minoxidil promotes hair growth through several mechanisms. It shortens the telogen (resting) phase of the hair growth cycle and prolongs the anagen (active growth) phase. This encourages dormant follicles to re-enter active growth and allows existing hairs to grow for longer. Minoxidil also improves blood flow to the follicle, which helps deliver more oxygen and nutrients. The end result is that, when it works, it produces thicker and denser hair over time.
Why Doesn’t Minoxidil Work for Everyone?
Topical minoxidil works for some people and not others. The reason is that minoxidil itself is not the active compound. It is a prodrug, which means it needs to be converted into its active form before it can do anything useful. That active form is called minoxidil sulfate. The conversion is carried out by an enzyme called sulfotransferase, specifically the SULT1A1 isoform. This enzyme is found in the outer root layer of hair follicles. When you apply topical minoxidil to your scalp, it penetrates the skin and reaches the follicle, where SULT1A1 converts it into minoxidil sulfate. It is this active metabolite that then stimulates the follicle.
The problem is that SULT1A1 enzyme activity varies enormously between individuals. Some people have high levels of sulfotransferase in their follicles and convert minoxidil efficiently. Others have low levels and can’t perform this conversion at an adequate rate, regardless of how much minoxidil they apply. In fact, in one study of 120 patients attending a hair loss clinic, roughly 49% had low levels of sulfotransferase. Although this is a very small study, the figure aligns closely with the known non-response rate to topical minoxidil.
Is It Possible to Predict Who Will Respond to Topical Minoxidil?
For years, there was no way to know in advance whether topical minoxidil would work for you. The standard approach was to commit to 6 months of daily use and see what happened. However, this is slowly starting to change. A landmark study by Goren et al developed an enzymatic assay to measure SULT1A1 activity in plucked hair follicles. The test predicted minoxidil response with 95% sensitivity and 73% specificity, which means it was very good at identifying who would not respond.
Commercial versions of this test are now available in some countries. They involve plucking a small number of hairs, sending them to a lab and receiving a result within a few weeks. However, it is not clear how sensitive or reliable the test is. So it remains a useful guide for planning rather than a definitive way to choose treatment. The test isn’t yet widely available in the UK, though a small number of private hair clinics offer it.
For most doctors, the more practical approach is to address hair loss through multiple pathways from the outset. This gives you the best chance of a good outcome without needing to test enzyme activity first. An example would be to combine minoxidil with tretinoin and a DHT blocker.
Can Anything Boost Sulfotransferase Activity?
Your SULT1A1 activity level is largely down to your genetics. People with certain variants of the SULT1A1 gene have higher enzyme activity and tend to respond well to minoxidil. Those with other variants have lower activity and are more likely to be non-responders. This is why two people with the same type and severity of hair loss can get completely different results. They might use the exact same product in the exact same way. Obviously, there’s not much you can do to alter your genes. However, there are several ways to boost sulfotransferase activity in the scalp, which can improve your response to minoxidil:
- Tretinoin: this topical retinoid enhances minoxidil absorption and increases the expression of sulfotransferase in the follicles. In one study, topical tretinoin applied over just 5 days converted 43% of predicted non-responders into responders. This is one of the key reasons why tretinoin is increasingly combined with minoxidil in compounded hair loss treatments.
- Microneedling: there is some evidence that regular microneedling at 1.5mm depth may increase sulfotransferase activity and response to minoxidil. This is on top of the benefits of microneedling for hair growth, which include stimulating blood supply at the follicles.
- Enzyme boosters: some evidence suggests that applying SULT1A1 enzyme boosters can significantly increase hair growth and response to minoxidil in non-responders. This is still early-stage research, but it points to a promising direction for future treatments.
On the other side, certain compounds can actually inhibit sulfotransferase activity and so may make minoxidil less effective. Salicylic acid is a known inhibitor of sulfotransferase enzymes in the liver. Based on data from small studies, there is reason to suspect it may have a similar effect in the scalp. Although more research is needed, it’s worth keeping in mind if you take regular aspirin or use scalp products containing salicylic acid.
What Should You Do If Minoxidil Isn’t Working?
If you’ve been using topical minoxidil consistently for 6 months or more with no visible improvement, it is reasonable to try and adjust course. Several treatments may help if minoxidil isn’t working for you, including the following:
- Tretinoin: adding tretinoin to topical minoxidil can boost sulfotransferase activity and improve absorption. This is one of the simplest ways to potentially improve your response. Compounded formulations that combine minoxidil with tretinoin are available by prescription.
- DHT blocker: combining minoxidil with a DHT blocker addresses androgenetic hair loss from a completely different pathway. This can significantly improve overall results.
- Microneedling: this is a useful adjunct treatment that can boost sulfotransferase activity, improve topical absorption and activate wound-healing pathways that stimulate follicular stem cells.
- Oral minoxidil: for people who don’t respond to topical minoxidil, switching to oral minoxidil bypasses the scalp enzyme pathway. That’s because oral minoxidil is converted into minoxidil sulfate in the liver, where sulfotransferase activity is much higher. However, it is available by prescription only after medical assessment, and it needs monitoring due to its cardiovascular side effect profile.
- Supporting actives: adding ingredients like caffeine and melatonin can complement minoxidil by targeting additional pathways, helping with follicle stimulation, antioxidant protection and DHT inhibition.
- Health MOT: it’s also worth making sure there’s no underlying or co-existing cause of your hair loss. Blood tests for thyroid function, iron, ferritin, vitamin D and zinc are all useful if you haven’t already had them.
Why Else Might Minoxidil Not Be Working?
Sulfotransferase activity is the main biological reason for non-response. However, it’s not the only reason minoxidil might not be working for you. There are several other factors worth considering:
- Wrong diagnosis: minoxidil works best for androgenetic alopecia. It might not help if your hair loss is caused by something else entirely, like telogen effluvium, an autoimmune condition, thyroid dysfunction, iron deficiency or a medication side effect.
- Insufficient duration: like all hair growth treatments, minoxidil takes time to work. You typically need to use it consistently for at least 3 to 6 months before you can assess whether it’s working. Many people give up too early, especially after the initial shedding phase (sometimes called the “dread shed”), which can be alarming. However, it usually indicates the treatment is having an effect on the hair cycle.
- Incorrect application: for topical minoxidil to work, it needs to reach the scalp, not just coat the hair. It should be applied directly to dry scalp skin, ideally at night, and left on for at least 4 hours before washing. Applying it to wet hair, or not using enough product, can reduce its effectiveness.
- Advanced miniaturisation: minoxidil is most effective in the earlier stages of androgenetic hair loss, when follicles are still capable of producing meaningful hair. Once follicular miniaturisation has progressed beyond a certain point, the follicle effectively shuts down. At this stage, most hair regrowth treatments can’t help, which is why early intervention is key.
- Not addressing DHT: minoxidil is a growth stimulant and doesn’t block DHT, the primary hormonal driver of pattern hair loss. If you use minoxidil alone without addressing the DHT component, the hormone keeps damaging your follicles whilst you’re trying to stimulate them. Combining minoxidil with a DHT blocker like finasteride, dutasteride or spironolactone addresses hair loss from both angles and is generally more effective than either treatment alone.
Topical minoxidil is a highly effective and accessible treatment, but it doesn’t work for everyone. Your genetics determine how well you respond to it. Although there’s nothing you can do to change this, there are strategies that can improve your response rate. These range from combining minoxidil with tretinoin and microneedling, to switching to oral formulations. You can also build multi-treatment plans that address hair loss from several directions at once. So if topical minoxidil alone isn’t working for you, there are still plenty of options. It’s best to start with a medical assessment to properly diagnose your hair loss and build a treatment plan around your needs.
At City Skin Clinic, we offer personalised hair loss treatments for women and men in the UK through our online clinic. Our doctors create custom hair growth treatments using actives such as minoxidil, finasteride, dutasteride, spironolactone, melatonin, caffeine and tretinoin where appropriate. To start your personalised plan, book a virtual video consultation or use our online consultation form. The journey towards great skin and hair starts here.
This article is intended for general informational purposes only and is not a substitute for medical advice, diagnosis or treatment. Always consult a qualified medical provider for any health concerns or questions you might have.
