Why is hair loss from various causes still not cured, and what mechanisms are used to treat hereditary hair loss?

Hereditary hair loss is caused by the conversion of testosterone to DHT, which leads to thinning and hair loss. Minoxidil and Propecia are medications that inhibit this process, but early detection and consistent treatment are key.

 

Despite thousands of years of medical advances, hair loss is still incurable. There are many factors that contribute to hair loss. In addition to genetics and stress, other factors that can contribute to hair loss include diabetes, smoking, metabolic changes due to crash diets, and poor habits such as excessive exposure to hot air or over-combing. As there are many different causes, there are also many different types of hair loss and treatments, but there is currently no cure for hair loss. However, in the case of hereditary hair loss, the mechanisms are well understood and can be treated with medication in the early and middle stages. Therefore, we will focus on hereditary hair loss that can be treated with modern medical technology.
First, we need to recognize that hair loss is a disease, not just a symptom. A disease is a condition in which an organism”s physical functions are abnormal. In a broader sense, stress or genetics can also be considered diseases. However, the line between a symptom and a disease, which is caused by the expression of genes, can be problematic, and in this case, social factors play a big role. If society views a symptom as a disease, then it is a disease, and if not, then it is simply a phenomenon caused by gene expression. It’s unclear exactly how it would have been perceived in older times, but at least in the modern world, medications are taken to treat hair loss, and it’s treated as a stressful disease for patients. In fact, South Korea’s National Health Insurance Service recognizes hair loss as a disease and includes it on its list of medical conditions.
Hereditary hair loss is also commonly referred to as hereditary androgenetic alopecia. The term androgen refers to any substance that exhibits the behavior of male hormones. However, when it comes to hair loss, we usually talk about two main ones: testosterone and dihydrotestosterone, or DHT. But let’s start by explaining how male hormones, which are known to be involved in the development of secondary sex characteristics, can cause hair loss.
Testosterone, a male hormone produced primarily by the testes in men and the ovaries and adrenal cortex in women, travels to the hair follicles. Before it reaches the hair follicle, about 5% of the total amount is converted to DHT by an enzyme called type 2 5-alpha-reductase. In the hair follicle, testosterone and DHT coexist together. The problem is that DHT binds to the androgen receptor in the hair follicle many times more strongly than testosterone. When DHT binds to the receptors, instead of producing hair growth factors, it produces cell suicide factors such as DKK-1 and TGF-beta, which destroy proteins in their own and neighboring cells and accelerate the hair’s degeneration. This causes hair to become thinner, weaker, and more prone to shedding, which is commonly referred to as hair loss. In short, hair thinning occurs because DHT binds to the receptor instead of testosterone. In other words, if you have a normal amount of reductase in your body, the steady production of DHT will cause hair loss.
It’s important to note that different people lose hair at different rates due to their unique genes. People with hereditary hair loss have a shorter time before their hair becomes weak and thinner because they have factors expressed from birth that negatively affect hair formation. Mechanistically, hair is regulated by testosterone, 5-alpha-reductase, androgen receptors, hair growth factors, and apoptotic factors. In other words, people with the hair loss gene have more genes that produce 5-alpha-reductase than other people, more genes that produce androgen receptors that can bind DHT than other people, and more genes that produce apoptotic factors than hair growth factors. Hair loss caused by inheriting these genes is called hereditary hair loss (androgenetic alopecia).
To stop hereditary hair loss, you might think that you could reduce the amount of testosterone, reduce the amount of 5-alpha-reductase, or inhibit androgen receptor binding. However, it’s not that easy, and while there are 66 types of medications for male pattern baldness distributed and produced in Korea, only two are officially FDA-approved to treat hereditary hair loss. One is the minoxidil class of medications, and the other is Propecia.
The first, minoxidil, was originally developed in the 1950s by a pharmaceutical company called Upjohn to treat stomach ulcers. However, it didn’t work on stomach ulcers, but instead was approved by the FDA in 1979 under the name Loniten because of its ability to dilate blood vessels. However, patients who took the drug experienced a side effect called hirsutism, so it was used to treat hair loss and was approved by the FDA in 1988 as a treatment for hair loss. It’s not known exactly why minoxidil causes hirsutism, but it’s thought that increased blood flow to the hair follicles increases nutrients to the hair, allowing more hair to grow. The drug is available in pill form and as a direct application to the head, and it takes as little as six months of consistent use to see results in thinning hair. However, because it works to dilate blood vessels, it should not be taken by people with low blood pressure, and side effects can include heart palpitations and nervousness.
Second, Propecia (finasteride) was originally developed as a treatment for BPH, but it was found to be effective in treating hair loss and is now used as a hair loss medication. The mechanism of Propecia is relatively well understood. It works by inhibiting the amount of 5-alpha-reductase, which reduces the amount of DHT and thus slows hair loss. Similar to minoxidil, Propecia was first used to treat BPH, but was approved by the FDA for male pattern baldness in 1997 after the mechanism of hereditary hair loss was discovered. A patient with 5-alpha-reductase deficiency provided a major clue to the invention of Propecia.
In a small village in the Dominican Republic, many DHT-deficient newborns were born with 5-alpha-reductase deficiency due to incest. Without DHT, these children fail to achieve primary sexual characteristics, and it’s not until secondary sexual characteristics that testosterone explodes and masculinizes the genitals. With this in mind, efforts began to identify drugs that reduce 5-alpha-reductase. Later, it was realized that 5-alpha-reductase plays an important role in the mechanism of hereditary hair loss. However, since the drug was originally developed to treat prostate enlargement, it can have side effects such as decreased libido due to increased female hormones. It has also been linked to an increased risk of male birth defects in pregnant women, so it should not be taken by pregnant women.
In addition to the medications mentioned above, there are a number of other treatments available, including anti-androgen medications such as spironolactone, which blocks androgen receptor binding; the dutasteride class of medications, which inhibits both type 1 enzymes as well as type 2 5-alpha-reductase; and physical methods such as hair transplantation, although these are only approved or used in some areas due to a lack of information on the extent of side effects or exact efficacy. However, it’s important to remember that early detection and consistent treatment is the most effective treatment for hair loss.