Author: Atharva Tilewale
What is Androgenic Alopecia?
Androgenetic alopecia (AGA), also known as male pattern baldness or female pattern hair loss, is a medical condition characterised by gradual thinning of the hair and ultimately hair loss in a specific pattern. Androgenetic alopecia (AGA) in men typically begins with a receding hairline and thinning at the crown, progressing to partial or complete baldness. Women with Androgenetic alopecia (AGA) typically have diffuse thinning across the crown of the scalp, while the frontal hairline is usually intact. The primary cause of Androgenetic alopecia (AGA) is thought to be a combination of genetic and hormonal factors. Androgens, specifically dihydrotestosterone (DHT), play an important role in the development of AGA. DHT binds to androgen receptors in hair follicles, causing them to miniaturise and produce increasingly finer and shorter hairs until they stop growing altogether.
AGA can have a significant impact on the self-esteem and quality of life of those affected. While there is no cure for AGA, there are several treatments available to slow hair loss and promote hair regrowth, including medications like finasteride and minoxidil, as well as procedures like hair transplantation.
Pathogenesis of Androgenetic alopecia
Androgenetic alopecia (AGA) causes hair follicles to shrink gradually due to changes in the hair cycle, resulting in vellus transformation of terminal hair follicles. Anagen, the active growth phase of the hair cycle, typically lasts between two and seven years.
The process begins with a brief regression (catagen) lasting one to two weeks, followed by a resting phase (telogen) lasting five to six weeks to approximately 100 days. During the catagen phase, follicular keratinocytes undergo apoptosis, pigment production stops, and dermal papillae condensate. The outcome is an upward movement of dermal papillae. During the telogen phase, hair shafts mature into club (vellus) hair. After combing and washing, the hair sheds and returns to the anagen phase.
In AGA, the anagen phase gradually decreases while the telogen phase increases. The duration of the anagen phase affects hair length, resulting in shorter hair, miniaturization, and eventual baldness.
What causes androgenic alopecia?
androgenic alopecia (AGA) is caused due to increased levels of DHT in the body. DHT is produced by the reduction of testosterone by the enzyme 5α-reductase (5AR). 5AR converts steroids with a 3-oxo-Δ4 structure could be converted to their corresponding 3-oxo-5α steroids. It converts testosterone, and progesterone into 5α-dihydrotestosterone (DHT) and 5α-dihydroprogesterone respectively. This reaction is catalysed by the cofactor NADPH which acts as a hydride donor. Compared with testosterone, DHT has a 2–5 greater affinity for ligand binding sites, thereby prolonging AR-mediated DHT signalling. This attacks hair follicles and causes them to miniaturize and produce increasingly finer and shorter hairs until they stop growing altogether.
What is Treatment androgenic alopecia?
Several factors influence treatment choice for androgenetic alopecia (AGA), including efficacy, ease of use, associated risks, and affordability. The European Dermatology Forum (EDF) has developed a comprehensive evidence-based S3 guideline for the treatment of AGA. This guideline considers a variety of factors, including the clinical efficacy of treatments, their feasibility in real-world settings, potential side effects, and the economic implications of various interventions. By taking these factors into account, healthcare professionals can make more informed decisions and tailor treatment plans to patients’ specific needs and preferences with AGA.
- Minoxidil
Minoxidil’s mechanism of action remains unclear. Minoxidil is converted to minoxidil sulphate, which activates ATP-sensitive potassium channels in cell membranes, resulting in a vasodilatory effect. Minoxidil may promote hair growth through various mechanisms, including increased expression of VEGF mRNA in the dermal papillae, activation of cytoprotective prostaglandin synthase-1, and increased expression of HGF mRNA.
Applying a 2% or 5% minoxidil solution, 1 ml twice daily, can prevent and improve AGA in males over 18 years old. The 5% solution is more effective, and the standard formulation (with propylene glycol) is preferred due to insufficient evidence for other preparations, such as foam or higher concentrations. Assess treatment response after six months. There is insufficient evidence to recommend using a 5% minoxidil solution over a 2% solution for female patients. Patients should be aware of telogen shedding, which typically occurs in the first 8 weeks of therapy.
Side effects: Hypertrichosis is the most commonly reported side effect of topical minoxidil. Contact dermatitis can be both irritant and allergic. The 5% solution is more likely to cause irritation due to its higher propylene glycol content.
- 5α-reductase inhibitors
The enzyme 5-alpha-reductase converts testosterone to its active form, dihydrotestosterone (DHT). Inherited sensitivity of hair follicles to DHT is one of the etiological factors in AGA. There are two types of 5-alpha-reductase in humans. Type I occurs primarily in the liver, skin, and scalp, while type II is found in the prostate, genitourinary tract, and hair follicles. Finasteride, a type II 5-alpha-reductase inhibitor, and dutasteride, an inhibitor of both type I and type II 5-alpha-reductase, are used to treat AGA.
Finasteride was initially approved to treat benign prostatic hyperplasia (BPH) but was later discovered to be effective in treating AGA. It inhibits the type II isoform of 5-alpha-reductase, the enzyme that converts testosterone to DHT in hair follicles. Finasteride reduces DHT levels, which slows down the miniaturization of hair follicles, promoting hair growth and preventing further hair loss. Finasteride is usually taken orally in the form of a tablet.
Dutasteride, on the other hand, inhibits both type I and type II isoforms of 5-alpha-reductase, resulting in a more complete suppression of DHT production than finasteride. Although dutasteride has not been approved by regulatory agencies for the treatment of AGA, some studies have found it to be more effective than finasteride in promoting hair regrowth. However, dutasteride is associated with a higher risk of side effects, including sexual dysfunction, than finasteride.
Dutasteride is 100 times more effective than finasteride at inhibiting the type I isoenzyme of 5- reductase and three times more effective at inhibiting the type II isoenzyme, which accounts for its greater potency. Additionally, only the type II isoenzyme is inhibited by finasteride. The half-life of dutasteride is longer than finasteride (5 weeks as opposed to 6 hours).
Both finasteride and dutasteride are generally well-tolerated medications for treating androgenetic alopecia (AGA). Studies comparing the two drugs have found no statistically significant difference in the occurrence of sexual dysfunction, including changes in libido, erectile dysfunction, and ejaculatory problems. Concerns regarding the long-term use of dutasteride and its potential impact on prostate cancer progression have been raised. However, a meta-analysis found insufficient evidence to support this association, contradicting earlier reports. Additionally, a study suggested that dutasteride may be better tolerated with fewer adverse events over a four-year period.
Furthermore, it’s noted that adverse effects of 5-alpha-reductase inhibitors (5αRIs), such as finasteride and dutasteride, tend to diminish with continued treatment over time. This suggests that any side effects experienced are often transient and may improve with ongoing medication use.
- Hormonal treatment
Hormonal therapy, such as anti-androgens, has not proven effective in treating male AGA.
Cyproterone acetate appears to be the only evidence-based treatment option for female patients with clinical and biochemical evidence of hyperandrogenism. Cyproterone acetate (25-50 mg per day, days 1-10) is typically prescribed alongside an oral contraceptive, such as estradiol.[69,75] Alfatradiol, a topical estrogen, helps slow or stabilise hair loss. However, studies on its use in AGA have yielded conflicting results.
Conclusion
Androgenetic alopecia (AGA) is a common dermatological complaint that patients seeking treatment. AGA can cause significant psychological distress for affected patients. Dermatologists should understand how to diagnose and treat AGA. Although treatment options for AGA are limited, ongoing research is shedding light on its pathogenesis and leading to the development of new therapies.
References
- Kaliyadan F, Nambiar A, Vijayaraghavan S. Androgenetic alopecia: An update. Indian J Dermatol Venereol Leprol. 2013;79:613-25.
- Mysore V, Shashikumar B. Guidelines on the use of finasteride in androgenetic alopecia. Indian J Dermatol Venereol Leprol. 2016.
- Loughlin K. The clinical applications of five-alpha reductase inhibitors. Can J Urol. 2021;28(2):10584-10588.
- Han Y, Zhuang Q, Sun B, et al. Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism. Nat Commun. 2021;12:449. doi:10.1038/s41467-020-20675-2.
- Srivilai J, Minale G, Scholfield C, Ingkaninan K. Discovery of natural steroid 5 alpha-reductase inhibitors. doi:10.1089/adt.2018.870.
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