Androgenetic alopecia (AGA) is a non-scarring disease with a progressive thinning of the
scalp hair that follows a characteristic pattern. AGA, the most common form of hair loss
in men, involves the progressive loss of visible pigmented terminal hair on the scalp in
response to circulating androgens. AGA is an autosomal disorder that begins in puberty in
genetically predisposed individuals. Thinning usually begins between the age of 12 and 40
years in both sexes, and at least 50% of the men by the age of 50 and 50% of women by 60
years are more affected. The pathogenesis of androgenetic alopecia involves both genetic
and hormonal factors. The hair follicles are genetically targeted for androgen
stimulation leading to follicular miniaturization and replacement of large pigmented
hairs (terminal hairs) with shorter, thinner depigmented hairs (vellus hairs) in affected
areas. Environmental factors, the nutritional influences, metabolic syndrome, smoking,
and UV radiation, also play a role in the pathogenesis of AGA. Recent histological
studies illustrated perifollicular inflammation in the upper third of the hair follicles,
suggesting that inflammation plays a pathogenic role in AGA, although clinically, AGA is
considered a non-inflammatory disease. Oxidative stress and inflammation are closely
linked in biological systems. The enhanced hair loss in androgenetic alopecia was linked
to several factors that increase cellular oxidative stress, including metabolic syndrome,
alcohol consumption, smoking, and UV radiation. AGA patients were found to suffer from
oxidative stress as evidenced by the decreased total antioxidant activity as well as
increased malondialdehyde levels. Erdogan et al.investigated the oxidative stress in
early-onset androgenetic alopecia and found that the total oxidant levels and oxidative
stress index are higher in younger patients with early-onset AGA. Molecular studies of
the paracrine mediators around the dermal papilla cells have shed light on the role
played by ROS in bald scalp. Prostaglandin D2 (PGD2) was found to be elevated in the bald
scalp of AGA patients and negatively affected the growth of human hair. PGD2 was found to
enhance the capacity of human keratinocytes to convert the weak androgen,
androstenedione, to testosterone through the involvement of the ROS cellular signaling
axis. The ROS scavenger, N-acetyl-cysteine, blocked the enhanced testosterone production
by PGD2. Transforming growth factor-beta (TGF-β) is another key promotor of hair follicle
apoptosis. TGF-β was found to be androgen-inducible via the induction of ROS and its
induction was significantly suppressed by the ROS-scavenger, N-acetyl cysteine in the
hair follicle dermal papilla cells. Treatment of cases of androgenetic alopecia comprises
a therapeutic challenge. AGA is neither life-threatening nor does it lead to pain;
however, it leads to a significant emotional burden and is considered as a
therapeutically frustrating disorder to the patients. The therapeutic approach to the
patient with androgenetic alopecia should be global: combined treatments may obtain
improvements in hair density, reduction of miniaturization and hair loss. Minoxidil 2% or
5% solution is the most frequently used drug for topical application. In men with AGA, 5%
topical minoxidil was clearly superior to 2% topical minoxidil in increasing hair
regrowth.
Men who used 5% topical minoxidil also had an earlier response to treatment than those
who used 2% topical minoxidil. Psychosocial perceptions of hair loss in men with AGA were
also improved. Finasteride, a selective inhibitor of 5α- reductase of type II reduces the
conversion of testosterone into DHT, was approved by FDA in 1997 in a dosage of 1 mg/day
as a systemic therapy in adult men with mild to moderate AGA. N-acetylcysteine (NAC) has
been widely used as an antioxidant in vivo and in vitro. N-Acetylcysteine may act as a
precursor of glutathione facilitating its biosynthesis. Glutathione will then serve as a
protective agent and detoxify reactive species both enzymatically and non-enzymatically.
It is possible that N-acetylcysteine could scavenge the active oxygen species directly by
non-enzymatic reduction. By replenishing glutathione, NAC can prevent paracetamol
toxicity. NAC is traditionally used as a hepatoprotective agent for the treatment of
paracetamol toxicity. Its mucolytic and anti-inflammatory actions allow its successful
use in chronic bronchopulmonary disease. Dermatologically, NAC in a dose ranging from
1200 mg/day up to 2400 mg/day constitutes an effective treatment of trichotillomania
owing to its glutamate modulating action via the reduction of oxidative stress and
normalization of glutaminergic transmission. It is generally well tolerated with a high
safety profile, mild gastrointestinal symptoms like vomiting and diarrhea are the most
common side effects. Given that oxidative stress emerges as a new component in the
multifactorial milieu of the aetiopathogenesis of AGA; the proved high oxidative stress
index in patients with early-onset androgenetic alopecia; the established in vitro
efficacy of ROSscavenger, N-acetyl cysteine, in blocking ROS and subsequently the
inhibitory paracrine mediators (PGD2 & TGF-β) of the hair follicle dermal papilla in the
bald scalp; together with the high safety profile and tolerability of NAC, the
investigators thought to investigate the efficacy and tolerability of NAC as a single
therapy and in combination with minoxidil for treatment of the early-onset androgenetic
alopecia in men.
