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An Investigation into Effectiveness of Current and Future Treatments for Hair Loss
Androgenetic alopecia, also known as male/female pattern baldness, is a form of hair loss that is very common and is characterised by a ‘non-scarring progressive miniaturization of the hair follicle’ in predisposed men and women with a pattern distribution. In men, the hairline typically recedes in a distinctive ‘M’ shape and hair often thins at the crown (the top of the head), usually leading to partially or total baldness. The Norwood Scale is used to determine what stage of hair loss you may be in. In women, hair becomes thinner all over the head but rarely leads to total baldness.
Androgenetic alopecia is the form of hair loss that is most prevalent in men, and becomes increasingly common with age, affecting about 80% of men over their life-time. In females, the reported occurrences of female androgenetic alopecia differs a lot, due to the varying thresholds for diagnosing hair loss and the assessment methods are very subjective. A group study of 377 white women referred to a general dermatology clinic in England with symptoms unrelated to their hair, found that female pattern hair loss was present in 6% of women younger than 50 years of age, rising to 38% of women 70 years of age or older which could link female pattern baldness to the menopause.
The gene that researchers believe play a role in androgenetic alopecia, is the AR gene which provides instructions for making androgen receptors. These receptors allow the body to react properly to dihydrotestosterone and other androgens. A change in this gene can lead to increased activity of androgen receptors. The hormone androgens are important in normal male puberty as well as other key functions in male and female, like regulating hair growth and sex drive. However, it remains uncertain to scientists how changes in the AR gene increase the risk of hair loss in men and women. Dihydrotestosterone (DHT) is a product when 5α-reductase catalyses testosterone. DHT causes shrinkage in these delicate follicles making hair shorter and wispier.
There are three major stages of the hair growth cycle are: anagen (the period of active growth), catagen (the period of cessation of the growth and regression), telogen (the period of relative inactivity and the event of the old hair fibre shedding). Up to 90% of someone’s hairs are going to anagen, pushing hair up by 1 cm per month, and can last 2 – 7 years depending on the person. Signals within the skin indicate to hair follicles to begin a new stage, catagen, when hair follicles shrink to a fraction of their size and last 2-3 weeks and ends with the blood supply to the follicle being cut off. Then the telogen phase starts and 200 hairs can be lost in a day. A new cycle starts when the follicle begins growing a new hair. Increased levels of androgens in hair follicles can lead to a shorter cycle of hair growth and the growth of shorter and thinner strands of hair4.
This leads to my inquiry into the different types of treatments of androgenetic hair loss. I will look at how each treatment works chemically and physically and research the efficacy of the treatments through analysing past clinical trials whilst looking into the side effects that may occur with each treatment.
The first FDA approved medication for hair loss was minoxidil, commonly known by its trade name Rogaine. It is a chemical called 6-piperidin-1-ylpyrimidine-2,4-diamine 3-oxide and it acts as an antihypertensive vasodilator. Minoxidil gets converted by sulphotransferase enzymes into minoxidil sulphate which allows it to open plasma membrane adenosine triphosphate sensitive potassium channels. By opening these channels, the smooth muscle on arterioles relax which decreases blood pressure. This increase in blood flow can directly stimulate hair follicle cells and force them ‘from their resting phase into their active growing phase’. Minoxidil encourages hair regrowth in four keyways: reversing follicle miniaturization; increasing blood flow around follicles; stimulating follicle movement to growth phase and extending the growth phase of follicles. Minoxidil is recommended to be applied twice a day or 14 times a week
Due to the chemical nature of the treatment, there are some adverse effects when in use. In a clinical trial, ‘an increased occurrence of pruritus and local irritation was observed with 5% topical minoxidil compared with 2% topical minoxidil’. Some rarer side effects that have been recorded is facial hair growth, acne at site of application, breast tenderness and nausea; these side effects typically worry women more which is why minoxidil is normally given to women at a lower dosage which also lowers the effectiveness of the treatment. Additional side effects of facial swelling, dizziness, difficulty breathing and inflammation at root of hair are signs of an allergic reaction to the drug. With topical solution of minoxidil there is the chance that too much medicine can be absorbed into the body through the scalp which can cause blurred vision, chest pain (irregular/fast heartbeat), numbness and rapid weight gain. Minoxidil can also be taken orally at a lower dose for those who have not responded to the topical treatment. The risk of side effects is reduced by using a low dose however there are still some undesirable effects which include pericarditis, low blood pressure, increased body hair growth, blood test abnormalities and the effects that occur with topical minoxidil.
A clinical trial 8 shows that between 5% Minoxidil topical and 2% Minoxidil topical, the 5% solution was superior as it increase hair growth by 45% more than the 2% solution at week 48. There was a significant increase in nonvellus hair count and patient and investigation rating of scalp coverage with the 5% topical minoxidil. With the 5% solution there was also an earlier response to the treatment compared to the 2% solution and the placebo. Furthermore, patient questionnaire on hair growth, global benefit and quality of life results show that 5% topical minoxidil also ‘improved patients’ psychosocial perceptions’ of hair loss.
Minoxidil can be applied topically as a cream or taken orally and in a recent clinical trial they have compared to the two methods in a ‘24-week, randomized, open, comparative study’. The trial was between 1mg Oral Minoxidil and 5% Topical solution. The results concluded that at the end of twenty-four weeks, 62% of women taking minoxidil orally improved compared to 42% of women applying minoxidil topically. After the 24 weeks, total hair density increase by 12% when taking oral minoxidil compared to 7.2% in women applying topical minoxidil. Scalp pruritus affected 19% of participants in topical minoxidil group and pretibial edema (ankle swelling) occurred in 4% of the oral Minoxidil group. Both groups, oral Minoxidil and topical Minoxidil, experienced hypertrichosis (excessive hair growth) 27% versus 4% respectively which some people managed by waxing. The mean heart rate of the oral Minoxidil group increased by 6.5% when no change was recorded with the topical Minoxidil group. The journal’s conclusion was that ‘oral Minoxidil can be considered an option for female pattern hair loss patients with poor compliance to topical Minoxidil’.
Finasteride is the other prescription-only drug that is approved by the FDA for treating androgenetic alopecia in men only. It is a synthetic 4-azasteriod compound which inhibits the steroid 5α-reductase. Reduced levels of 5α-reductase means less testosterone would be converted into DHT which is the androgen responsible follicle miniaturisation. Women, especially pregnant women, shouldn’t take Finasteride as can result in risk of pregnancy as the drug’s purpose is to hinder the conversion of testosterone into DHT which can cause a male foetus to have underdeveloped or abnormal genitalia. Finasteride, which is usually an oral drug, needs to be taken 7 times a week.
Finasteride’s chemical structure resembles a hormone and also inhibits a key male hormone, testosterone, which could be why there are so many sexual disfunctions as side effects when taking finasteride. Common side effects include the loss of libido and impotence. In a clinical trial  in 1999, out of 1879 patients with androgenetic alopecia, 7.7% of finasteride recipients had treatment related adverse effects; 3.8% were sexual disorders however these undesirable effects were resolved in many men who continued the treatment and in all men who discontinued the medicine after experiencing these effects. Additionally, Finasteride had no major effects on non-scalp body hair unlike minoxidil.
The final FDA cleared item are the HairMax Laser devices. On the HairMax website, it states that the gadget is ‘indicated to treat Androgenetic Alopecia, and promote hair growth in males who have Norwood Hamilton Classifications of IIa to V and in females who have Ludwig (Savin) I-4, II-1, II-2, or frontal patterns of hair loss and who both have Fitzpatrick Skin Types I to IV’. They use Medical Grade laser diodes which produce a near-infrared wavelength (655nM +/-10nM) light and operates over the process of photo biostilmulation. The devices use low level laser light energy to increase the growth factors for hair follicles like oxygen and also stimulates the hair follicles in catagen and telogen phase to be replaced by a new hair in the active anagen phase. One characteristic indicator of androgenetic alopecia is the weakening root and miniaturisation of hair follicles causing ‘vellus hair’ (thin, slight coloured and barely noticeable hair) to develop into terminal hair and become thicker. However, when there is a dead root, the HairMax devices cannot help. The HairMax Laser comb is recommended to use at least 3 times a week to be effective.
There isn’t a primary chemical source in the laser treatment so fewer adverse effects have been noted. In the 2014 clinical trial involving 269 people, side effects from the laser-comb included dry skin (5.1%), pruritus – itchy skin – (2.5%), ‘scalp tenderness (1.3 %), irritation (1.3 %), and a warm sensation at the site (1.3 %)’. There are reports from HairMax users that their scalp feels tight which has been explained by HairMax is due to the increased in blood flow and this sensation will eventually go as you get familiar to it if you keep on using the product.
In 2009 HairMax issued a clinical trial that was ‘randomized, double blind, sham device-controlled, multicentre trial’ which lead to it’s first FDA clearance.
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