This blog post explores why hair loss is difficult to cure due to various causes, and specifically examines the mechanisms behind treating hereditary hair loss.
Despite thousands of years of steady medical advancement, hair loss remains incurable. Multiple factors contribute to this condition. Primarily, these can be divided into genetic factors and stress-related factors. Beyond these, other causes include diabetes, smoking, metabolic changes from drastic dieting, and poor habits like excessive heat exposure or vigorous brushing, all of which can worsen overall health and lead to hair loss. Given the diverse causes, there are various types of hair loss and treatment methods, but currently, almost no form of hair loss can be completely cured. However, for hereditary hair loss, where the mechanism is well-studied, a cure is possible through medication in the early and middle stages. Therefore, we will focus primarily on hereditary hair loss, which can be cured with modern medical technology.
First, it is essential to recognize that hair loss is not merely a symptom but a disease. A disease refers to a state where an organism’s physical functions become abnormal. Broadly speaking, stress or genetic factors can also be considered diseases. This raises the question of where to draw the line between phenomena caused by gene expression being classified as symptoms versus diseases, a distinction heavily influenced by social factors. If society views such symptoms as a disease, then it is a disease; if not, it is merely a phenomenon caused by gene expression. While it is unclear how it was perceived in the past, at least in modern society, medications are taken to treat hair loss, and it is treated as a disease that causes stress to patients. In fact, the National Health Insurance Service of Korea recognizes hair loss as a disease and includes it in its list of medical treatment surveys.
Hereditary hair loss is often called hereditary androgenetic alopecia. Androgen refers to any substance exhibiting the action of male hormones. However, in relation to hair loss, testosterone and dihydrotestosterone (DHT) are typically the two main substances discussed. So, let’s first explain how male hormones, known to be involved in the development of secondary sexual characteristics, cause the disease of hair loss.
Testosterone, a male hormone primarily produced in the testes of males and the ovaries and adrenal cortex of females, travels to the hair follicles. Before reaching the hair follicles, approximately 5% of this testosterone encounters an enzyme called type 2 5-alpha-reductase and is converted into DHT. Both testosterone and DHT coexist within the hair follicles. The problem is that DHT binds to the androgen receptors located in the hair follicles several times more potently than testosterone. When DHT binds to the receptor, instead of producing hair growth factors, it triggers the production of cell suicide factors like DKK-1 and TGF-beta. These factors destroy the proteins in the hair follicle and surrounding cells, accelerating the hair’s telogen (resting) phase. This leads to hair becoming thinner, weaker, and more prone to falling out—a condition commonly known as hair loss. To summarize simply, DHT binds to receptors instead of testosterone, causing hair to thin. In other words, if the reductase enzyme is normally present in our bodies, DHT is continuously produced, leading to progressive hair loss.
The crucial point here is that the rate of hair loss progression varies among individuals due to their unique genetic makeup. Individuals with hereditary hair loss experience a shorter timeframe for hair weakening and thinning because factors negatively impacting hair formation manifest from birth. Examining the mechanism, hair regulation involves testosterone, 5-alpha reductase, androgen receptors, hair growth factors, and cell suicide factors. Specifically, individuals with the hair loss gene possess genes that produce more 5-alpha-reductase than others, genes that produce more androgen receptors capable of binding DHT than others, and genes that produce relatively more cell suicide factors than hair growth factors. Hair loss resulting from the inheritance of these genes is called hereditary hair loss (male pattern baldness).
Therefore, to prevent hereditary hair loss, one might consider methods to reduce testosterone levels, decrease 5-alpha-reductase activity, or inhibit androgen receptor binding. However, this has proven challenging. While 66 types of male pattern hair loss medications are distributed and produced domestically, only two drug therapies for treating hereditary hair loss have received official FDA approval. One is the minoxidil class of treatments, and the other is Propecia.
First, the minoxidil class of treatments was originally developed in the 1950s by the pharmaceutical company Upjohn as a drug to treat peptic ulcers. However, it proved ineffective for ulcers. Instead, it demonstrated an exceptional ability to dilate blood vessels, leading to its FDA approval in 1979 under the name ‘Loniten’. However, patients taking this medication experienced a side effect called hypertrichosis. This effect was then utilized for hair loss treatment, leading to FDA approval as a hair loss treatment in 1988. While the exact reason minoxidil causes hypertrichosis remains unclear, it is believed that increased blood flow to the hair follicles enhances nutrient delivery to the hair, enabling more hair growth. This medication is available as a topical solution applied directly to the scalp and as an oral tablet. Consistent use for at least six months is required to see the effect of thickening thinning hair. However, because it dilates blood vessels, it cannot be used by patients with low blood pressure and may cause side effects such as heart palpitations or persistent nervousness.
Second, Propecia (finasteride) was originally developed as a treatment for benign prostatic hyperplasia (BPH). Its effectiveness in treating hair loss was later confirmed, leading to its use as a hair loss medication. The mechanism of Propecia is relatively well understood. This drug inhibits the amount of 5-alpha-reductase, thereby reducing DHT levels and slowing hair loss. Similar to minoxidil, Propecia was initially used as a treatment for benign prostatic hyperplasia. After the mechanism of hereditary hair loss was elucidated, the FDA approved it for male pattern baldness in 1997. The invention of Propecia was significantly aided by insights from patients with 5-alpha reductase deficiency.
In a small village in the Dominican Republic, many newborns lacked DHT due to a deficiency in 5-alpha-reductase caused by inbreeding. Children without DHT failed to undergo primary sexual development. Only during secondary sexual development did testosterone surge dramatically, leading to the masculinization of their genitals. Building on this observation, efforts began to identify drugs that reduce 5-alpha-reductase activity. Subsequently, as 5-alpha-reductase was identified as a key player in the mechanism of hereditary hair loss, this led to the development of hair loss treatments. However, since the drug was originally developed to treat benign prostatic hyperplasia, it can have side effects such as decreased libido due to increased female hormone levels. Furthermore, pregnant women should not take this medication as it increases the risk of male birth defects.
Beyond the drugs mentioned above, anti-androgen medications like spironolactone, which blocks androgen receptor binding, dutasteride-type drugs that inhibit both type 1 and type 2 5-alpha-reductase enzymes, and physical methods like hair transplantation. However, due to insufficient information on the extent of side effects or precise efficacy, they are only approved or used in certain regions. Nevertheless, it is crucial to remember that early detection and consistent treatment remain the most effective hair loss therapy, surpassing any drug treatment.
