Although hair loss disorders are not considered life-threatening, to assume that they are not life altering is a disservice to patients across the world. There is a profound social and psychological impact that is undeniable and which unquestionably decreases their quality of life and overall state of well-being. The rapid search for effective Hair Loss treatments for hair loss fuels a multi-billion dollar industry and is characterized by an urgency that demonstrates the deep-seeded need for a viable solution. However, the solution has been more elusive than initially hoped and more research will need to be conducted. In the meantime, let us take a deeper look at the available treatments and therapies for male hair loss.
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INTRODUCING THE PROBLEM: ANDROGENIC ALOPECIA HAIRLOSS
The common baldness, or male pattern baldness as it is also known, is, in fact, a symptom of a condition termed Androgenic Alopecia. Androgenic Alopecia is without question the most common type of hair loss in men. In fact, it is estimated that an alarming 50% of men experience it to some degree by the time they turn 40 years old. This condition follows a defined pattern in all individuals whose genes predispose them to it.
In men suffering from this type of hair loss, the large terminal hairs of the scalp are shed and replaced by small vellus hairs. There are three main areas of the scalp that are affected by this phenomenon; these are the mid-frontal scalp, the vertex scalp or crown, and the temples. All the hairs in the affected area will be involved in what has been observed as systematic miniaturization of the hair follicle. In fact, it is believed by a large segment of the medical community that the total number of hair follicles decreases significantly over time during the advancement of androgenic alopecia.
Although the biological mechanisms that lead to the development of a case of androgenic alopecia have not been entirely mapped, it has been known for some time now that there exists a very strong concordance of the degree to which fathers and sons go bald over time. This interrelationship means that there is little doubt as to the role inherited genes play. These genes, however, remain unidentified despite our best efforts. Nevertheless, we have identified a strong relationship between androgen metabolism and hair growth and loss.
Polymorphism of an Androgen receptor gene has been determined to have an association with Androgenic alopecia. However, because the Androgen receptor gene lies on the X chromosome, we can deduce that other autosomal genes contribute to the expression of the phenotype. It was also observed that castrated males do not develop any form of androgenic alopecia; which confirms that androgen metabolism is largely at play.
TESTOSTERONE AND HAIR LOSS IN MEN
The sex hormone testosterone is the main free circulating androgenic hormone in males. It has been established that hair growth, for the most part, is mediated by a powerful testosterone metabolite known as 5-alpha-dihydrotestosterone. This metabolite is orders of magnitude more sensitive to the androgen receptor, and as such, patients with androgen insensitivity do not go bald. Once this mechanism of action begins to take hold, a male will experience a gradual hair loss, which if left untreated will progress inexorably until it leads to a completely hairless scalp.
In a healthy adult male’s scalp, we find compound follicles with up to five terminal hairs growing out of a single skin pore. In a balding male, the scalp presents less terminal hairs and a significantly higher number of vellus hairs spread out over a greater number of pores. This transition event is what leads to a noticeable reduction in the volume of the hair. This apparent thinning of the hairs gradually turns into full out baldness once all the follicles have become miniaturized. A close examination of the scalp to accurately measure a possible reduction in the number of total terminal hairs per follicular complex can be used to effectively predict the appearance of androgenic alopecia.
The pathophysiology of the process suggests that in any predisposed hair follicle, it is the testosterone metabolite dihydrotestosterone or DHT, that binds to the androgen receptor in the follicular complex and this in turns activates the genetic pathways which lead to the gradual deterioration of the follicles.
Dihydrotestosterone metabolism is quite complex, but it can be summarized like so.
The enzymatic 5-alpha-reductase conversion of peripheral testosterone into dihydrotestosterone prevents free testosterone from synthesizing into estradiol in the hair follicles. Estradiol promotes follicle health and integrity and as such a reduction in estradiol levels compounds the catabolic nature of DHT.
Interestingly enough, and further evidence of the role of androgen receptors in the development of male pattern hair loss is the fact that individuals presenting reduced levels of 5-alpha-reductase develop significantly lower rates of baldness.
FOLLICULAR STRUCTURE AND GROWTH CYCLES
Before we begin to discuss the state and method of action of the current male hair loss treatment options, let’s take a moment to study the physiological mechanisms of hair growth. If we aim to revert hair loss, we must first understand how it grew in the first place.
Hair growth is derived out of a complex interplay between specific dermal structures.
The hair follicle is the most dynamic of these structures. It is found deep in the dermis and is made up of specialized cells, each with distinctly unique roles to initiate. Inside the hair follicle, an intricate metabolic process involving several hormones, peptides, and immune organelles, stimulate and regulate the growth of hair.
At the base of the hair follicle, we find the dermal papilla. The papilla is a cluster of mesenchyme cells that are involved in the production of the fibrous structures which will make up the hair shaft. At the same time, the hair shaft and all surrounding root sheaths are derived from epithelial cells.
These structures take form during embryonic formation and remain active throughout most of the individual’s lifetime. However, the nature of each follicle’s function changes over time. For example, an unsolved paradox exists in the fact that androgenic response causes lighter hairs to thicken and darken during puberty, yet the same response causes the exact opposite effect later in life.
The entire follicle will also undergo a sort of structural remodel on a cyclic nature to dictate hair growth. This cycle, known as the follicular growth cycle, consists of phases of growth, regression, rest, and shedding.
ANAGEN: This is the growth phase of the cycle. This is the phase where a physical elongation of individual strands can be measured. The anagen process begins inside the papilla where specialized cells divide and transform into the fibrous hair. Growth is fed by follicle itself, and this phase can last up to six years. Almost all hairs on the head at any one time are on the anagen phase.
CATAGEN: Catagen is the regressive or transitional phase. Curiously, during the catagenic phase, much of the follicular structure undergoes pre-programed apoptosis, or cell death, in order to reduce its size as it enters the next phase. This phase can last up to two weeks and terminates once the hair has been cut off from the nourishment of the papilla. During Catagen there is no active growth.
TELOGEN: This is the resting phase where the follicle will go dormant for up to four months. Around 15 percent of the hairs on the scalp are in the resting phase at any one time.
A regenerative follicular process signals the onset of the next anagen in the cycle. During the earliest moments of the anagen, stem cells form a new follicular structure, as well as a hair shaft and inner root sheath. The length of the shaft depends entirely on the size of the follicle and the duration of the anagen phase. Early anagen also sees a wild proliferation of melanocytes to produce pigmentation for the hair.
HOW HAIR CYCLE DYNAMICS ENABLE TREATMENT FOR HAIR LOSS
Because hair is lost and then regained in a cyclical pattern in which follicular cells undergo repeating phases of growth, involution, rest, and regeneration, we have been able to identify various molecular signals and pathways that regulate growth. These molecular actions are composed of growth factors, androgenic receptors, and cytokines. The role these signals play has been established and purported by clinical evidence, especially that of testosterone and its conversion into dihydrotestosterone by 5-alpha-reductase. A couple of therapeutic methods based on this interaction have been tested and approved for human use by the U.S. Food and Drug Administration.
The main goal of these therapeutic approaches is to increase hair coverage of the scalp and to prevent further loss of hair. The two approved drugs that have been developed for this purpose are Finasteride and Minoxidil.
FINASTERIDE: Finasteride therapies are based on the drugs ability to actively inhibit the synthesis of type 2 5-alpha-reductase which has as a consequence a marked reduction in the active conversion of testosterone into dihydrotestosterone. The idea to use the effects of finasteride to treat male hair loss was born out of the realization that males with a congenital deficiency in the production of enzymatic 5-alpha-reductase do not present any cases of androgenic alopecia.
A dose of 1 mg per day of finasteride can effectively lower blood serum levels of dihydrotestosterone up to 60%. In various randomized and double-blind, studies with placebo control, men with moderate to severe cases of thinning hair, finasteride significantly improved the total hair count and area coverage of the men after one year of treatment. During these tests, some men were switched from the placebo group to the finasteride group and vice versa. The men who were switched from the drug to the placebo control group experienced a reversal of the growth gained during the previous year of the study. Although it does take the scalp some time to get used to and can cause minor itchy scalp spots.
In the case of the men who were switched from the placebo group to the group receiving finasteride, new hair growth was observed. Increased scalp coverage was observed in two-thirds of the finasteride group, and it was determined that the net gain of hair growth is arrived at after one year of treatment; however, continued treatment can potentially increase the length and diameter of the hairs.
It is important to note that the gradual deterioration of follicular integrity occurs over many years, and therefore, any reversal of the process should be expected to take just as long. Finasteride does not provide an immediate solution to male hair loss, but it does provide consistently positive results.
How to take finasteride: Finasteride needs to be taken consistently for months before a patient can positively determine the success or failure of the therapy. Finasteride is metabolized quickly, and thus even a brief interruption to the treatment will adversely impact the potential hair growth and loss reversal. It is important to remember that growth occasioned by finasteride therapy is gradual patience is needed to find success. Take one 1 mg tablet each day, preferably at the same time each day. The tablet should be swallowed whole with a cup of water. Finasteride can be taken with or without food. If you skip a dose, take the tablet as soon as you remember, but never take two tablets at the same time. In case it is time for your next dose simply leave out the missed dose.
Side effects include: an increased risk for prostate cancer due to a decrease in the Prostate Specific Antigen PSA, diminished libido, Increase in breast size, and skin irritation. Patients with decreased liver function should take precaution as finasteride is metabolized in the liver. All known side effects are reversible and require cessation of the therapy.
MINOXIDIL: Minoxidil is the second drug approved by the Food and Drug Administration for the treatment of male hair loss. Minoxidil is a curious drug; it is a Potassium-channel opener and vasodilator medication that was developed for the treatment of severe hypertension. The mechanisms behind minoxidil’s effect on hair growth do not appear to be related to vasodilation or hypertension, but its follicle stimulating effects are so potent that when added straight to a culture of hair follicles, their survival is increased. Minoxidil is highly effective in stimulating hair growth after it has been arrested by androgenic alopecia and other health conditions.
The first studies into its efficacy regarding hair growth occurred in the decade of the 80s. A 12-month long placebo controlled study of almost 3000 men with mild to moderate vertex hair thinning was conducted. In all cases, minoxidil significantly improved hair count and shaft diameter. The initial testing was conducted using a 2% solution, but by the turn of the millennium, a more concentrated minoxidil solution was tested. A 5% solution was administered twice daily in another placebo-controlled study. 5% percent minoxidil solution was almost 50% more effective than the previously approved 2% solution.
Yet another long-term study was conducted where hair clippings from patients being treated with the two minoxidil solutions were weighted. After 96 weeks of treatment, the doses were stopped, and patients were monitored for another 24 week period. The results were as expected; both minoxidil solutions were significantly more effective than placebo in generating and stimulating follicular integrity and hair growth.
Another curious fact about minoxidil therapy is that the drug causes a surge of growth in miniaturized follicles and still the hairs fall out. In fact, patients undergoing minoxidil therapy are warned to expect a period of increased shedding 10 to 12 weeks into the therapy.
How to take minoxidil: One ml of minoxidil topical solution is to be applied twice daily directly to the scalp and massaged light with a finger. Spray application is discouraged because most of the medicine ends up being absorbed by the hairs instead of the scalp where it induces the most rapid effect. Hair and scalp should be completely dry before applying minoxidil. Shampooing is discouraged for up to 4 hours after treating your scalp with minoxidil solutions. Contact with skin should be kept to a minimum and immediately after usage hands need to be thoroughly washed.
Side effects include: Minoxidil is well tolerated by most healthy individuals; however, various adverse side effects may arise with continued use. Most of the side effects that develop due to minoxidil therapy are dermatologic and include irritation of the eyes, irritation, and inflammation of the treated area. Though rarely reported, more severe side effects include difficulty breathing, swelling of the face, chest pains, heart palpitations, headache, and dizziness. Some patients also experience the appearance of dandruff and contact dermatitis. No alteration to either systolic or diastolic blood pressure has been reported in patients undergoing minoxidil therapy. At the highest dosage of the 5% solution, no hemodynamic changes occur.
TREATMENTS ON THE HAIR LOSS HORIZON
The effective treatment of male hair loss has been significantly advanced by the introduction to the market of the drugs Finasteride and Minoxidil. The mechanism of action caused by finasteride is well understood. Finasteride is a potent inhibitor of the enzyme 5-alpha-reductase which is one of the main factors that act upon the follicular hair cycle to degrade follicular integrity and cause loss of hair in men. Funnily enough, the mechanism of action generated by Minoxidil regarding the stimulation of follicular growth is unknown.
Thankfully we can rest assured that research is being done every single day to produce more viable, effective, and accessible treatments for balding men. Presently one of the most exciting fields of study is that of molecular biology. Biologists worldwide are actively attempting to identify all genes involved in the activation of androgenic alopecia and other hair loss disorders. With the aid of powerful microarray technologies, and the recent accessibility of the human genome sequence these avenues of research might eventually lead to substantial advancements in the therapeutic treatment of male hair loss.
Geneticists are busy working with spliced human, primate, and mice genetic models for androgenic alopecia. Potential treatments would look to modulate inflammatory response and cytokine activation near the follicle. Another potential therapy approach would be to identify antigenic receptors in the follicle and induce a tolerance to increased T-cell populations. Ideally, although further down the road, the goal is recreated brand new follicles at sites of deterioration.
Currently, biologists are also investigating the possible interaction of follicle precursors, or placodes and powerful signaling molecules called SHH and platelet-derived-growth-factor-A or PDGF-A. This interaction is responsible for the formation of clusters of dermal condensates that eventually transform under the dermis into the papilla. It has been established that mutations in these type of signaling molecules are responsible for wavy hair, and therefore integral to the proper formation of the hair follicle. The WNT, BMP, LEF1, FOXN1, and HOXC13 signaling molecules act as genetic transcription factors that regulate hair shaft differentiation. It has also been established that SHH in conjunction with a form of the Beta-catenin of the epidermis stimulates the generation of an additional hair follicle.
All of this genetic knowledge is still in its earliest development, but the discovery of their active mechanisms of action and the interactions with one another present exciting future possibilities for the eventual development of effective gene therapies aimed at reversing the loss of hair in men around the world.
BACK TO HAIR LOSS BASICS
As always we must remind our readers that the human body is a highly complex piece of “machinery”, and therefore what might initially seem unrelated to the development of hair loss and androgenic alopecia, ends up being extremely important.
There are several seemingly unrelated factors that can contribute to an excessive hair loss in men, but one of the most frequently overlook is an inadequate diet and poor nutrition. Nutritional deficiencies can at best generate a decrease in the amount of natural nourishment that the hair follicle receives. A malnourished hair follicle will end up deteriorating and eventually lead to loss of hair. The evidence was accrued from clinical studies in energy-protein actuation, malnutrition, starvation, and eating disorders. Otherwise healthy individuals present significant amounts of hair shedding and outright hair loss when persistent nutritional factors come into play.
For decades the medical world has known about the importance of the role played by Iron in non-anemic patients that are deficient in serum ferritin. Evidence suggests that increasing a patient’s serum ferritin levels by including higher doses of nutritional iron into their diet, significantly improves the rate at which hair is lost. Why would iron affect hair loss? Perhaps it comes down to the essential role of iron in the blood. Iron’s primary role in blood is to efficiently transport oxygen to and remove carbon-dioxide products from healthy tissues such as the hair follicle. Oxidative damage might be at play here.
The essential amino acid L-lysine is another important nutritional factor that has been linked in various studies as having a direct relationship to hair loss in men. Biotin, or vitamin b7, is also linked to increased hair loss when patients present measurable deficiencies; perhaps because Vitamin B7 acts as a potent cofactor of enzymatic action during the catalysis of essential metabolic byproducts and the synthesis of certain fatty acids.
ARE THERE BEST FOODS TO HELP OUR HAIR GROWTH?
Whatever the case may be, we must recognize that because of the follicular growth cycle, these cells have a rather high turnover and this
requires a steady flow of nutrients. A caloric deficit or nutritional deprivation of such components such as proteins, minerals, fatty acids, and vitamins might potentially lead to structural abnormalities of the hair follicle and eventual hair loss. Often the importance of the nutritional element in follicular health is overlooked, especially in developed countries where malnutrition is not as prevalent. However, it is important that we adhere to established nutritional guidelines and ensure proper intake of all necessary nutrients.
So to avoid any possible complications make sure to include the following Hair-growing foods and do everything possible to avoid the possibility of hair loss.
- Foods rich in iron: red meats, green leafy vegetables, lentils, chickpeas, seafood, peas and whole grains, spirulina, liver, grass-fed beef, dark chocolate, raisins.
- Foods rich in antioxidants: red fruits, citrus fruits, tomatoes, kiwi, lean meats, bluefish, carrots, cabbage, and broccoli, purple, red, and blue grapes, blueberries, nuts, sweet potatoes.
- Foods rich in folic acid: spinach, asparagus, legumes, chicken liver, beef liver, egg, strawberry, banana, papaya, and cereals.
- Foods rich in vitamin A, B, C, and E.
- Foods rich in L-lysine: Beef, parmesan cheese, turkey breast, chicken wings, pork, soybeans, tofu, salmon, Pollock, sea bass, shrimp, lobster, mussels, cuttlefish, chia seeds, pistachio nuts, almonds, eggs, white beans, lentils, split peas, and chick peas.
To Sum it ALL up…
The biggest problem of hair loss in men is much more complicated than one might initially think. Nevertheless, recent advances in the medical understanding of the biological mechanisms that regulate hair follicle biology and hair growth have proven once again that the fight is not yet lost; and more effective solutions are right over the horizon.
I hope I helped guys.
John and Medical Team 🙂
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- Cotsarelis, George, and Sarah E. Millar. “Towards a molecular understanding of hair loss and its treatment.” Trends in molecular medicine 7.7 (2001): 293-301.
- Price, Vera H. “Treatment of hair loss.” New England Journal of Medicine 341.13 (1999): 964-973.
- Hoffmann, R. “Male androgenetic alopecia.” Clinical and experimental dermatology 27.5 (2002): 373-382.
- Rathnayake, Deepani, and Rodney Sinclair. “Male androgenetic alopecia.” Expert opinion on pharmacotherapy 11.8 (2010): 1295-1304.