In 1965, the pharmaceutical company Upjohn, which now is part of Pfizer, discovered that a derivative of piperidine-pyrimidine was a potent vasodilator in dogs. This ability to cause vasodilation, or opening up of the blood vessels, made it a lucrative addition to the arsenal of drugs used to treat hypertension. The plan was to use it to treat refractory hypertension, which is defined as blood pressure that had remained uncontrolled after three or more visits to a doctor within six months. So, it was marketed as a hypertensive treatment of last resort when all else failed. (Acelajado et al 2013). The drug developers gained a patent for this drug and called it Loniten.
However, researchers started noticing strange side effects once it was widely used. They began to see cases of hypertrichosis or Ambras syndrome or, to use a more politically incorrect name, werewolf syndrome (if there are any fans of Father Ted, they will know what this condition means….it was the episode when the jungle music priest came to replace Father Jack). This serendipitous discovery of hypertrichosis or the Ambras syndrome when using minoxidil (Zappacosta, A.R., 1980) opened the doors for more researchers to work on the elusive cure for “baldness”. Guinter Kahn and his colleague Paul J Grant started to work on testing subjects with a minoxidil 1% solution. In contrast, other physicians began prescribing Loniten “off-label” as a hair loss remedy.
Fortunately, the side effect of hypertrichosis caused hair growth, mainly on the head. In these cases, the side effect was warmly welcomed. However, in some instances, hair growth was triggered in other parts of the body, such as the arms, back, and chest. As a result of this unexpected side effect, researchers all over the world began experimenting with minoxidil and found that it demonstrated impressive hair growth, especially in conditions such as androgenetic alopecia (male pattern baldness) and alopecia areata.
The work of the researchers eventually bore fruit with the formulation of a topical minoxidil solution for treating androgenetic alopecia in men, with the licence later being extended to include women. Initially, a 2% minoxidil solution was marketed to stimulate hair regrowth in men in 1986 in the USA, with the 5% solution appearing in 1993 (Messenger & RUndegren, 2004). Finally, in 1986, the US FDA approved Rogaine topical lotion for treating genetic hair loss. In the UK, we know this product as Regaine, and eventually, both would move from the prescription-only status to the less restrictive over-the-counter form in 1995.
Once Rogaine’s patent expired, other cheaper generic and compounded versions entered the market. In the UK, Regina is available for hair loss for both men and women and is available in two different strengths: 2% and 5%, with the lower strength usually recommended for women.
The reason that a lower strength was initially recommended for women was that it was found that women were more susceptible to other side effects of minoxidil. These included a significant reduction in blood pressure, leading to other symptoms such as lightheadedness or dizziness. Other side effects that were experienced more so by women included allergic reactions such as dermatitis. It is interesting to note that women generally tend to have a more robust immune system than men. It seems that nature has decided that the female species is more valuable than the extra males and thus has given it a weaker immune system. It appears that nature somehow knew men would engage in risky activities to impress their friends on a Friday night and thus thought an efficient immune system would be wasted on them. However, there is no such thing as a free lunch; one consequence of this superior immune system is an increased risk of allergies and autoimmune conditions, which is when the immune system starts to attack the body when it has nothing to do,
For these reasons, women were recommended to use the 2% solution. Another unfortunate consequence of using minoxidil was that it could encourage facial hair growth, which would not be wanted in women if it ran down the temples. However, it was found that this problem usually resolved itself once the women stopped using the solution (Peluso, A.M., Misciali, C 1997). It was also found that facial hair growth in women occurred more frequently when the 5% solution was used. The development of a foam dispenser has made the application of minoxidil easier without any solution running down the sides of the temple. Also, unwanted hair growth can be mitigated by using a lower concentration of the minoxidil solution.
With regards to allergic dermatitis, which has previously been mentioned, this manifests itself as itching, burning, the appearance of papules or pustules, scalp tension, scalp pain, scaling or seborrheic dermatitis-like symptoms. However, the true allergy is usually associated with the propylene glycol in topical solution preparations. The propylene glycol content is more significant in the 5% solution than the 2% solution. Hence, switching to lower concentrations can sometimes alleviate the severity of the allergic response (Rogers, N.E. and Avram, M.R., 2008). The other way to mitigate the effects of propylene glycol allergy is to use the foam preparation. This is one of the reasons that we at APC Labs advocate using the foam solution; it’s easier to apply and causes less irritation. In other rare instances, there is an allergic reaction to the minoxidil.
A landmark study by Lucky et al. (2004) found that the use of the 5% solution produced better results than the 2% minoxidil solution in a cohort of women suffering from androgenetic alopecia or female-pattern hair loss. Both strengths were equally well tolerated, and as a result, minoxidil 5% foam became available for women’s use.
Minoxidil has become firmly established in treating hair loss and is included in many of the preparations we now prepare at APC Labs. If you do not see the strength you require or want to try a combination of hair loss ingredients that is not available on the market, please contact us, and we will see if we can formulate an original solution for you. This is because, at APC Labs, we know that everyone is different.
References:
Acelajado, M.C., Pisoni, R., Dudenbostel, T., Dell’Italia, L.J., Cartmill, F., Zhang, B., Cofield, S.S., Oparil, S. and Calhoun, D.A., 2012. Refractory hypertension: definition, prevalence, and patient characteristics. The Journal of Clinical Hypertension, 14(1), pp.7-12.
Messenger, A.G. and Rundegren, J., 2004. Minoxidil: mechanisms of action on hair growth. British Journal of Dermatology, 150(2), pp.186-194.
Peluso, A.M., Misciali, C., Vincenzi, C. and Tosti, A., 1997. Diffuse hypertrichosis during treatment with 5% topical minoxidil. British Journal of Dermatology, 136(1), pp.118-120.
Rogers, N.E. and Avram, M.R., 2008. Medical treatments for male and female pattern hair loss. Journal of the American Academy of Dermatology, 59(4), pp.547-566.
Zappacosta, A.R., 1980. Reversal of baldness in a patient receiving minoxidil for hypertension. The New England Journal of Medicine, 303(25), pp.1480-1481.
Written by Mr. Shazlee Ashan
BSc Pharmacy, MSc Endocrinology, PgDip Infectious Diseases, Ipresc
