Androgenetic alopecia

 Androgenetic alopecia (AGA) a non-scarring alopecia. 

 It is an extremely common disorder affecting both men and women. 

 The incidence of AGA is generally considered greater in males than females. 

 Onset is mostly prior to age 40 years, although many of the patients (both male and female) show evidence of the disorder by age 30 years. 

 The incidence of androgenetic alopecia increases greatly in women following menopause. 

Pathophysiology 

 A process called “Miniaturization” occurs in which large, thick, pigmented terminal hairs turn into thinner, shorter, smooth, non-pigmented vellus hairs in the involved areas gradually. The resulted hair is called “miniaturized hair”. 

 There is a reduction in the terminal-to-vellus hair ratio. 

 Anagen phase shortens with the telogen phase remaining constant. As a result, more hairs are in the telogen phase, and the patient may notice an increase in hair shedding. 

Causes 

 AGA involves both genetic and hormonal factors. 

 A major determinant of AGA is intracellular androgen metabolism, which involves: 

 5 α-reductase 

 Cytochrome P450 aromatase 

 Androgen receptor proteins. 

Other important factors may remain to be discovered. 

 Variances in levels of these androgen-metabolizing enzymes and androgen receptor proteins help explain the differences between balding and non-balding scalp at various ages and the different clinical patterns and severities between men and women. 

5 α-reductase isoenzymes 

 They reduce testosterone (T) to dihydrotestosterone (DHT). 

 DHT levels are increased in balding scalp when compared to non-balding scalp. 

 Women have 3.0–3.5 times less 5 α-reductase (I and II) than men and this may explain why female AGA is usually less severe than male AGA. 

Cytochrome P450 aromatase 

 The cytochrome P450 aromatase enzyme has a protective effect on hair follicles. 

 They convert T to estradiol and estrone, therefore decreasing the conversion of T to DHT. 

 Aromatase is significantly higher in the hair follicles of women. There is 6 times more aromatase in the frontal follicles of women than in those of men and that is why women with AGA usually retain their frontal hairline and have less hair loss than men with AGA. 

Androgen receptor proteins (ARP) 

 Binding of androgens to ARP results in the transformation of terminal to miniaturized hair follicles on the scalp in AGA. 

 Androgen receptor proteins (ARP) are found in the outer root sheath and dermal papilla fibroblasts of scalp hair follicles. 

 The receptor levels were found to be 30% greater in balding frontal hair follicles than in non-balding occipital follicles in both men and women with AGA. 

 The total receptor content is 40% less in women than in men. 

Symptoms 

 The onset of androgenetic alopecia is gradual. 

 Hair loss is patterned, following Norwood/Hamilton pattern in males and Ludwig pattern in women. 

 A hair pull test is usually negative, although there may be a mild increase in telogen hairs, though only in involved areas of the scalp. 

 Miniaturized vellus-like hairs can usually be seen with contrast paper placed over a part. 

 Women usually retain their frontal hairline and hair thinning is mostly on the crown. 

 These patterns are not restrictive, and some women can present with the Norwood-Hamilton pattern and some men with the Ludwig pattern. 

Treatment 

General considerations 

 These treatments are most effective when started early. 

 Medical treatments will only be effective if there is sufficient hair to keep, with at least miniaturized hairs to convert into terminal hair. 

 For those with more advanced hair loss, surgery may be the only options. 

 Micrografting produces a more natural appearance than the old technique of transplanting plugs. 

Medications 

 AGA medications can be classified according to their mode of action into: 

 Hormone modifiers, act by blocking either 5areductase or androgen receptor proteins. 

 Biologic response modifiers, have a non-hormonal effect. The aim of all these agents is to: 

 Prevent the transfer into catagen then telogen. 

 Maintain a longer anagen state, so that miniaturization will be delayed or prevented. 

 Nurture hair growth and inhibit factors that have a negative effect on hair growth. 

 The only 2 FDA approved drugs for the treatment of AGA are Minoxidil and Finasteride. 

 For men, treatment options include Minoxidil, finasteride. 

 For women, treatment options include Minoxidil, spironolactone and Cyproterone acetate. 

Minoxidil

 The 2% solution was approved for women and the 5% solution was approved for men.

 Both solutions are OTC products.

 Its mechanism of action is unknown but it appears to lengthen the duration of the anagen phase, and it may increase the blood supply to the follicle.

 Response is better with those who have a recent onset of AGA and small areas of hair loss.

 Regrowth is not noted for at least 4 months but it should be used for one full year before its efficacy is assessed.

 Continuing topical treatment with the drug is necessary indefinitely  because discontinuation of treatment produces a rapid reversion to the pretreatment balding pattern.

 The increase in effectiveness of the 5% solution was not evident for women in the FDA-controlled studies. In addition, the occurrence of facial hair growth appears to be increased with the use of the higher-concentration formulation.

 One milliliter of Minoxidil solution must be used twice daily, every day in order to be effective.

Twenty-five drops (1 ml) must be applied directly on to a dry scalp and then slightly spread with the fingers.

 No more than 2 ml should be applied every day, regardless of the extent of the affected area.

 The scalp applicator is more preferred than the spray applicator, since most of the sprayed solution will be applied on the hairs, where it is ineffective and thus wasted.

 Should be used with caution in patients with cardiovascular disease.

 Minoxidil should not be used by pregnant or nursing women. Minoxidil is secreted in human milk.

 Topical Minoxidil solution is very safe, and side effects are mainly dermatologic.

 The most frequent side effect are irritant contact dermatitis and facial hypertrichosis.

 If patients experience an irritant contact dermatitis due to the 5% solution, they should stop the treatment until all symptoms have resolved. If they again develop dermatitis on the second trial, the concentration should be lowered to 2%. If the same problem persists, then treatment may have to be discontinued altogether.

 Facial Hypertrichosis may occur in 3–5% of women, and is usually not a problem in men.

 Hypertrichosis is totally reversible upon discontinuation of the drug.

 Those patients who are affected and continue with the treatment usually notice a decrease in and even a disappearance of the facial hair within a year.

 Thorough hand washing after each use may minimize irritation and possibly Hypertrichosis in other body areas.

Finasteride

 In 1997 the FDA approved finasteride for use at a dose of 1 mg/day in men with AGA.

 Finasteride is a 5-alpha reductase type 2 inhibitor that has been shown to diminish the progression of AGA in males who are treated and in many patients, it has stimulated new regrowth.

 The drug cannot be used by women because it can produce ambiguous genitalia in a developing male fetus and no beneficial effect of the medication in treating AGA in postmenopausal females.

 Propecia™ 1 mg is to be taken every day, on a regular schedule, with or without food.

 Finasteride must be continued indefinitely  because discontinuation results in gradual progression of the disorder.

 Finasteride is metabolized in the liver, and therefore caution should be taken in patients with liver function abnormalities while dosage does not need to be adjusted in case of renal insufficiency.

 No drug interactions have been reported because Finasteride does not affect the cytochrome P450 metabolizing enzyme system.

 Finasteride is well tolerated, and side effects occur in less than 2% of patients.

 Side-effects include decreased libido,erectile dysfunction and decreased ejaculate volume.

 Side effects will subside spontaneously in 58% of those who decide to continue the treatment, and are reversible upon cessation of treatment.

 Exposure to semen of men who are taking finasteride does not pose a risk to a pregnant woman’s male fetus.

Other drugs

 Some drugs are not approved by the FDA but are potentially helpful medications:

 Androgen suppressants or antagonists (e.g., spironolactone, oral contraceptives).

 Dutasteride

o Topical latanoprost 0.1%,

Patient Education

 The key features to distinguish between are prevention and regrowth.

 In patients with early stages , It is important to emphasize that regrowth can be difficult to perceive and only stabilization may be detected.

 In Patients with more advanced balding. It is important to keep the expectations of this group low, emphasizing prevention and minimizing expectations of regrowth.