From Hypertension to Hair Growth: The Unexpected Story of Minoxidil

Minoxidil is one of the most well-known treatments for hair loss today, but its origins have nothing to do with dermatology. In fact, it was first developed to treat a completely different condition: severe hypertension. Its transformation into a hair growth treatment was a surprising accident—one that changed the way we approach hair loss forever. This is the fascinating journey of Minoxidil, from a blood pressure pill to a staple in hair regrowth solutions.

In the 1950s, researchers at the Upjohn Company (now part of Pfizer) were searching for new ways to treat high blood pressure. They developed a powerful vasodilator—Minoxidil—that worked by relaxing and widening blood vessels, allowing blood to flow more easily. By 1979, the U.S. Food and Drug Administration (FDA) approved Minoxidil as an oral medication under the brand name Loniten, intended for patients with severe, treatment-resistant hypertension.

But doctors and patients began noticing something unusual. Many people taking Minoxidil started growing excessive hair—not just on their heads, but on their arms, hands, and even foreheads. This unexpected side effect, known as hypertrichosis, sparked curiosity among researchers: Could this drug help people struggling with hair loss?

The Birth of a Hair Loss Treatment

Scientists quickly began exploring whether Minoxidil could be applied directly to the scalp to promote hair growth, without affecting blood pressure. By the 1980s, clinical trials confirmed that topical Minoxidil was effective for male pattern baldness. In 1988, the FDA approved it under the brand name Rogaine, making it the first medically approved treatment for androgenetic alopecia. Initially, Minoxidil was only available with a prescription, and only in a 2% concentration. But as research progressed, stronger formulations (like the 5% solution) were developed. In 1996, Minoxidil was approved for over-the-counter sale, making it accessible to millions worldwide.

Even though Minoxidil has been around for decades, scientists are still unraveling exactly how it stimulates hair growth. What we do know is that it works through several mechanisms:

Improves blood circulation: Minoxidil widens blood vessels, allowing more oxygen and nutrients to reach the hair follicles. This helps hair grow better and longer.

Elongates the hair growth phase: Minoxidil works primarily by prolonging the anagen phase, meaning that hair keeps growing longer before entering the shedding phase. It also helps "weak" follicles start producing thicker, healthier hair again.

Activates certain cells in the follicle: Minoxidil influences structures called potassium channels, which help the follicle cells function better and continue producing hair.

Stimulates substances that promote growth: Minoxidil is believed to increase the production of a molecule called PGE2, which is linked to healthy hair growth and follicle strength.

Evita que los folículos se encojan: En la calvicie, los folículos pilosos se vuelven más pequeños con el tiempo hasta que dejan de producir pelo. Minoxidil puede frenar este proceso, ayudando a que los folículos sigan activos.

note: One key discovery was that Minoxidil is actually a prodrug, meaning it needs to be converted into its active form (minoxidil sulfate) by enzymes in the scalp.

Note: Minoxidil, in its raw state, is not fully active on its own. It is what is called a "prodrug," meaning it needs to be transformed into another substance within the body to take effect. When you apply Minoxidil to your scalp, your body does not use it directly. First, enzymes called sulfotransferases convert it into its active form: minoxidil sulfate. This is the version that actually stimulates hair follicles and promotes hair growth. The problem is that not everyone has the same amount or activity of these enzymes in their scalp. Some people produce more minoxidil sulfate and therefore see better results. Others, with lower enzyme activity, convert less Minoxidil into its active form, which reduces its effectiveness. This discovery has led to research into ways to improve absorption or better activate Minoxidil in people who do not respond well to it.

Expanding Use: Minoxidil for Women and Oral Treatments

Initially, studies on Minoxidil focused on male pattern baldness. However, as more people used it, reports began to emerge about its effectiveness in women with hair loss. This led to specific clinical research into its use in female pattern baldness.

In 1998, after several clinical trials, the FDA approved 2% Minoxidil as the first topical treatment for hair loss in women. Although studies showed it was effective in slowing hair loss and stimulating growth, the results were most noticeable in the early stages of alopecia.

As research progressed, different concentrations and formulations were compared.In microneedling, studies showed that **5% Minoxidil foam **had superior efficacy in women without significantly increasing adverse effects. This led to the approval of this version specifically formulated for female use.

More recently, oral Minoxidil has gained popularity as an alternative option for those who do not respond well to topical treatment. Clinical research has evaluated low-dose oral Minoxidil (LDOM), showing that it may be more effective in certain patients, as it avoids absorption problems in the scalp and acts systemically. However, this approach also presents additional risks, such as fluid retention and hair growth in unwanted areas (hypertrichosis).**

Minoxidil is widely available over-the-counter in many countries, typically in 2% and 5% concentrations. Some key aspects of its commercial access include regulatory differences between countries, the availability of various formulations such as liquid, foam, and oral options, and the presence of both brand-name and generic versions that affect pricing and accessibility. Online pharmacies have made Minoxidil even more widely available, but regulations vary regarding higher concentrations and oral prescriptions.

Research and Studies on Minoxidil

Since its discovery, Minoxidil has been the subject of numerous investigations that have allowed its efficacy and application to be optimized in hair loss. In the 1980s, the first clinical trials confirmed its effectiveness in men with androgenetic alopecia. A study by Orentreich et al. (1984) demonstrated that topical application of 2% Minoxidil could stimulate hair growth in patients with male pattern baldness, leading to its approval by the FDA in 1988.

In the 1990s, research focused on dosage optimization. A study by Olsen et al. (1990) compared the efficacy of 2% and 5% Minoxidil, showing that the higher concentration provided significantly greater hair growth, leading to the marketing of the 5% version by Upjohn (now part of Pfizer) in 1997. Beginning in the 2000s, studies began to include women with hair loss. Olsen et al. (2002) published a clinical trial in the Journal of the American Academy of Dermatology showing that 2% Minoxidil was effective in women with androgenetic alopecia, leading to its approval for this group. In 2014, the FDA approved a 5% foam version specifically for women, based on internal studies by Johnson & Johnson.

In the 2010s, research explored new delivery methods. A study by Ramos et al. (2017) evaluated the effectiveness of low-dose oral Minoxidil (LDOM), concluding that it was a viable alternative for patients who did not respond well to the topical version. Its combination with tretinoin, an agent that improves skin penetration, was also investigated, with promising results in the absorption and efficacy of the treatment.

More recent research has sought to improve the absorption of Minoxidil. A trial by Fabbrocini et al. (2020) analyzed the use of microneedling, a technique that increases the penetration of the drug into the scalp, and found that combined with 5% Minoxidil, it doubled the hair growth rate compared to the use of Minoxidil alone. Other recent studies explore nanoencapsulation, a technology that could allow for a more controlled release of the drug, optimizing its effectiveness and reducing side effects.

In addition, genetic research is examining specific markers that could predict individual response to Minoxidil. A study by Suchonwanit et al. (2021) suggests that certain variations in genes related to enzymatic activity in the scalp could influence the effectiveness of the treatment, opening the door to personalized therapies in the future.

The Future of Minoxidil: What's Next?

Despite being on the market for over 40 years, Minoxidil remains one of the most widely used and studied treatments for hair loss. Research continues with the goal of improving its efficacy, reducing side effects, and making its application more convenient. One of the most promising approaches is personalizing the treatment based on the enzymatic activity of the scalp. Since Minoxidil needs to be converted into its active form (minoxidil sulfate) by the enzyme SULT1A1, some studies have looked at the possibility of genetic testing to predict who will respond best to the treatment. Research such as that of Gupta et al. (2019) has pointed out that certain biomarkers can correlate with the efficacy of Minoxidil, opening the door to individualized treatments.

Another field of study focuses on improving its absorption through advanced delivery systems. Nanoencapsulation has emerged as an alternative for a controlled and more efficient release of the drug, avoiding the evaporation of the vehicle in traditional solutions. Recent studies have shown that the use of lipid nanoparticles could increase the bioavailability of the drug and reduce the need for frequent applications.

Similarly, microneedling has been the subject of multiple clinical trials in recent years, confirming its ability to enhance the effects of Minoxidil by facilitating its penetration into the scalp. A meta-analysis published in Dermatologic Therapy in 2022 concluded that the combination of Minoxidil with microneedling not only accelerates the response to treatment, but also improves hair density in patients with resistant androgenic alopecia.

The combination of Minoxidil with other treatments has also been widely investigated.

Tretinoin, a vitamin A derivative known for its exfoliating action, has been shown to increase the absorption of Minoxidil by improving cell renewal in the scalp. A study published in the International Journal of Trichology in 2016 found that co-application of 5% Minoxidil with 0.025% tretinoin produced better results in hair growth compared to Minoxidil alone. On the other hand, the use of antiandrogens such as finasteride and dutasteride, which block the action of dihydrotestosterone (DHT), has been explored as a complementary approach, especially in cases of severe alopecia.

Studies have also begun to evaluate the potential of anti-inflammatory agents to reduce irritation associated with Minoxidil use and improve hair follicle health. Recent research has looked at the effect of certain flavonoids and antioxidants in combination with Minoxidil, suggesting that they may mitigate scalp inflammation and prolong the hair growth phase.

Experiences and Community Discussion: How Do People Respond to Minoxidil?

Minoxidil use remains a widely discussed topic in online forums and communities, where users share their experiences with different formulations and dosages. One of the most recurrent themes is concern about dependence on the treatment: many wonder whether hair follicles treated with Minoxidil become dependent on the drug for continued growth. Some users report that after discontinuing use, treated hair quickly re-miniaturizes, while others mention more gradual hair loss.

Another common discussion revolves around variations in the effectiveness of different brands and formulations. Recently, there have been debates about whether certain batches of Kirkland Minoxidil have reduced efficacy, with users noting that the new packaging could be related to changes in formulation. Additionally, there are those who seek to optimize their treatment by choosing between liquid and foam versions, evaluating which offers better absorption and fewer side effects.

Note: Low-dose oral Minoxidil (LDOM) has also gained popularity, with users sharing testimonials about its effectiveness and adverse effects. While some have noticed significant hair growth without the irritation of topical Minoxidil, others report side effects such as fluid retention or hypertrichosis in unwanted areas.

These discussions reflect the variable nature of response to Minoxidil and the importance of considering individual factors, such as scalp enzyme activity and personal tolerance, when choosing the best treatment strategy.

sources

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Olsen, E.A., et al. (2002). A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men. Journal of the American Academy of Dermatology, 47(3), 377-385. PUBMED.NCBI.NLM.NIH.GOV

Rossi, A., Cantisani, C., Melis, L., Iorio, A., Scali, E., & Calvieri, S. (2012). Minoxidil use in dermatology, side effects and recent patents. Recent Patents on Inflammation & Allergy Drug Discovery, 6(2), 130-136. PMC.NCBI.NLM.NIH.GOV

Dhurat, R., & Sukesh, M. (2013). A randomized evaluator blinded study of effect of microneedling in androgenetic alopecia: A pilot study. International Journal of Trichology, 5(1), 6-11. PMC.NCBI.NLM.NIH.GOV

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Mexican Social Security Institute. (2012). Clinical Practice Guide: Diagnosis and Treatment of Androgenetic Alopecia in the First Level of Care. Retrieved from https://www.imss.gob.mx/sites/all/statics/guiasclinicas/566GER.pdf IMSS.GOB.MX

Sinclair, R. (2018). Oral minoxidil in the treatment of hair disorders: A review. Dermatologic Clinics, 36(2), 197-203. ESPANOL.MEDSCAPE.COM

Ramos, P. M., & Miot, H. A. (2015). Female pattern hair loss: a clinical and pathophysiological review. Anais Brasileiros de Dermatologia, 90(4), 529-543. SEME.ORG

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