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DHT in the scalp provides patients with improved hairline rejuvenation.
Greater improvements have been noted with long-term therapy, and as with
minoxidil, reversal of results can occur if treatment is stopped. Usually,
providers will assess the efficacy of this medication after at least 1year of
therapy [42].
Finasteride has some side effects and can impact laboratory results in
men, although it is generally considered safe. The most common adverse
impact on male patients is the development or worsening of erectile
dysfunction, which may not be reversible after treatment is discontinued.
The hormonal alterations can lead to lower levels of prostate-specific
antigen in men, and providers should be aware of this impact when
interpreting laboratory results. Elevation of certain liver enzymes is another
adverse effect, although this tends to occur with very high doses and longer
duration of therapy [42, 44].
2.4.2 Off-Label Pharmaceutical Treatments
Dutasteride is a more potent 5-alpha reductase inhibitor, usually prescribed
for the treatment of benign prostatic hyperplasia (BPH). In previous studies,
Dutasteride was shown to be more effective than Finasteride at a two-fold
decreased concentration [45]; additional data show similar efficacy [46].
Anti-androgenic therapy can be used off-label for hairline rejuvenation,
including Ketoconazole (anti-fungal medication), Zinc-containing shampoo,
and spironolactone, the latter of which is the most used for this indication.
Ketoconazole and zinc shampoo both help to reduce inflammation,
seborrheic dermatitis, and dandruff through similar MOAs. Improvements
to female pattern hair loss are noted when Ketoconazole is used at a 2%
concentration in shampoo formulations. Spironolactone inhibits ovarian
production of androgen and acts as a competitive inhibitor at the androgen
receptor. A little less than half of patients taking 200 mg of spironolactone
once daily note improvements in hair regrowth after 1year of therapy [47,
48].
Prostaglandin F2 analogues (latanoprost, bitamoprost) are not
commonly used but have the potential to improve hair density. Application
of topical solutions to small areas of the scalp show documented
improvements in hair density [49]. Progesterone derivatives such as
cyproterone acetate bind to androgen receptors and reduce testosterone
levels via reduced production of follicle-stimulating hormone (FSH) and
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leutenizing hormone (LH). The results with cyproterone acetate are
comparable to spironolactone [48].
2.4.3 Minimally Invasive Aesthetic Procedures
Microneedling is a procedure performed by aestheticians or aesthetic
surgeons, using a rolling device with fine needles along the hairline (as
shown in the right image). The damage induced by these needles to the
outer skin layers is thought to contribute to wound healing and stimulate
hair growth. Many patients experience minimal side effects, including
pinpoint bleeding at the site of needle entry or minor inflammation. When
used with pharmaceutical therapy (described above in detail), it is a
promising adjuvant in the rejuvenation of the hairline [50] (Figs. 5 and 6).
Fig. 5 A microneedling device (yellow) and application of treatment (red lines) are shown in the
right image [51]
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Fig. 6 Before (right) and after (left): The appearance of a female patient’s hairline before (right) and
after (left) microneedling in conjunction with additional treatments, showing a notable improvement
in hair density towards the frontal scalp [51]
Purified platelet-rich plasma (PRP) is shown to stimulate hair growth.
PRP is collected from the patient’s own blood sample, using centrifugation
techniques. The alpha-granules contained in platelets release cytokines,
including platelet-derived growth factor (PDGF), transforming growth
factor (TGF), vascular endothelial growth factor (VEGF), and interleukin 1
(IL-1), which contribute to increased stem cell signaling [49]. Cytokine
stimulation promotes angiogenesis and increases to the number of follicular
bulges and dermal papilla cells.
Once-monthly injections of PRP should be administered near the
hairline for at least 3months, followed by additional treatment 6months
later. After the first 6months, yearly supplemental injections are shown to
be beneficial for long-term aesthetic improvement. Studies assessing the
efficacy show promising results regarding hair growth and increased hair
follicle/shaft size. There is significant variation of these results, indicating a
need for additional trials with larger sample sizes. The complications of
PRP injections are similar to the previously mentioned adverse effects
discussed with microneedling [52].
Low-level laser therapy (LLLT), also referred to as low-intensity light
therapy, acts to stimulate cellular tissue activity. Wavelengths within the
range of 600–950 nm (red or infrared light) are well utilized to stimulate
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hair growth for both men and women diagnosed with androgenic alopecia
(AGA). Stimulation of anagen reentry and increased proliferation rate with
LLLT counteract the reduction of proliferative activity in hair follicles and
miniaturization of hair with AGA. Devices such as the HairMax laser comb
help to improve both precision and penetration of light on the scalp. There
is promising evidence in the literature to suggest its benefit when used
concurrently with pharmaceutical therapy (minoxidil, finasteride) and
surgical follicular transplantation [50].
3 Topical Therapy and Skin Resurfacing
3.1 Review of Relevant Anatomy
The skin is broadly composed of three layers, including superficial
epidermis, underlying dermis, and deep subcutaneous fat. Five layers are
contained within the epidermis, characterized by their cell composition and
thickness. The deepest layer is made up of proliferative cells, which are
pushed out to the surface and undergo maturation [53, 54]. Keratinocytes
are most prevalent, although there are epidermal Langerhans cells (antigenpresenting), melanocytes, and sensory structures present as well [53, 54].
Sun exposure and UVR increases melanogenesis, inducing melanocyte
recruitment and melanosome transfer into keratinocytes. The chief
regulatory pathway involves binding of ACTH and MSH-α, which bind to
melanocortin receptor MC1-R [53–55].
The dermis contains cells surrounded by an extracellular matrix (ECM),
the latter of which is comprised of collagen and elastin protein fibers. Cells
in the dermis include fibroblasts (progenitors), dermal dendrocytes, and
mast cells (immune function) [53, 54]. Intrinsic aging occurs naturally as a
result of disorganized elastin formation and is attributed in part to decreased
fibulin-5 (stimulates production of elastic fibers) [56, 57]. Additionally, the
breakdown of oligosaccharides reduce the skin’s ability to retain water
molecules [58].
Photoaging (extrinsic aging) induces “solar elastosis” through the
activation of membrane metalloproteases (MMPs), which break down
organized elastin [58]. Collagen is similarly damaged by MMPs, which are
activated by reactive oxygen species (ROS) resultant of aging or increased
exposure to toxins/UVR. In addition, ROS inhibits TGF-β, reducing
synthesis of new collagen molecules [59] (Fig. 7).
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Fig. 7 The anatomical arrangement of epidermal and dermal tissues and their constituents are
illustrated above [60]
3.2 Patient-Applied Topical Therapy
Topical skin treatments are used primarily to slow and reduce the aesthetic
changes related to aging. These include sunscreen, antioxidants, retinoids,
and exfoliative agents/Alpha hydroxy acids (AHAs).
Sunscreen is the least invasive option to reduce the effects of aging on
the skin, and it does not require any prescriptions or medical intervention. It
is estimated that UVR exposure is responsible for 80% of age-related skin
changes [61]. Previous studies have highlighted the efficacy of sun
protection in reducing the prospective effects of aging resulting from UV
exposure [62].
There are many chemical formulations available, although the most
effective contain titanium dioxide and zinc oxide. These molecules allow
for better broad-spectrum protection while reducing the risk of allergic
reactions common with organic formulations. For the best results, patients
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should apply 30 min before UV exposure and reapply as recommended
(indicated on product packaging) [63, 64].
Antioxidants and retinoids can be used with sunscreen to further protect
and restore skin. Antioxidants work by neutralizing previously formed ROS
in the skin, acting to reduce MMP-induced damage [65]. Retinoids are
effective at increasing glycosaminoglycan deposition, dermal collagen
content, and epidermal thickness.
Vitamin C is used to increase collagen production and cell turnover,
while vitamin E helps to neutralize ROS. Both vitamins may be combined
with ferulic acid to stabilize the formula. Topical antioxidant therapy should
be used as part of the daily skincare regimen, and the ideal concentration
should be high enough to improve the skin without irritation. If the patient
uses alpha hydroxy acid treatments, they should be informed of its
destabilizing effect on Vitamin C and avoid simultaneous application [66–
68].
There are two main formulations of topical retinoids, available over the
counter (retinol) or prescribed (Tretinoin, Retinaldehyde). Tretinoin is
readily absorbed and utilized by the skin, unlike Retinol, which is a
precursor and must be converted after absorption [68]. As a result, the
overall efficacy of OTC Retinol is 20-fold lower compared with
prescription formulations. Despite the advantage of dose-dependent skin
rejuvenation with Tretinoin, many patients experience redness and irritation
from higher and frequent doses. If this occurs, physicians can reduce the
dosage or instruct patients to apply less frequently [69].
Alpha hydroxy acids (AHAs) such as glycolic, lactic, or citric acid work
to chemically exfoliate the skin and reduce cohesion of epithelial cells.
Improved collagen density and elastin integrity has been documented with
use of AHA, along with dose-dependent improvement of skin texture and
reduction of rhytids (wrinkles). Since AHAs are dose dependent, patients
should use the highest tolerable concentration. Their use is contraindicated
with antioxidants (namely vitamin C), as AHA can reduce their efficacy
[71] (Fig. 8).
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Fig. 8 Topical retinoids are additionally utilized in the treatment of acne scarring, the results of
which are indicated by the green circles, compared with untreated scars (red circles) [70]
3.3 Skin Resurfacing with Chemical Peels
Chemical peels are a more invasive option for skin resurfacing, and they are
relatively cost-effective compared with other techniques. The level of skin
resurfacing can be adapted to each patient’s skin quality. Individuals who
are at higher risk of pigmentary abnormalities are not indicated for chemical
peel treatments, although some skilled providers can safely perform
rejuvenation if great caution is exercised. With patients that have a past
medical history significant for herpes simplex infection, antiviral therapy is
administered prior to the procedure and should be continued for 10days
following application of the chemical peel [72, 73].
Patients are instructed to use Tretinoin and glycolic acid as tolerated for
4–6weeks before treatment, to increase the rate and uniformity of
reepithelialization. These pretreatments are discontinued 1week prior to
chemical peel application to reduce the risk of inflammation. Directly
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before the procedure, the skin will be prepared with acetone or isopropyl
alcohol to reduce oil and produce an even surface [74].
Initial application of chemical solutions commonly utilizes gauze or
cotton-tipped applicators, and the edges should be gently blended into the
untreated surrounding skin [75]. Any orifices (eyes, mouth, alar groove)
should be avoided, as this can cause severe erosion and resultant
complications [76]. The provider should observe the skin color after
application to ensure sufficient treatment without excessive abrasion. Pink
frosty skin indicates penetration to the epidermis, and this frosty layer
appears whitish-pink once the papillary dermis is reached. Deeper
treatments that penetrate to the reticular dermis induce a solid white
appearance when complete [74].
After medium or deep chemical peel resurfacing, patients require at
least 3–5days of rest and recovery, which can impact work or home
activities. These individuals should apply petroleum-based moisturizers
regularly as a protective barrier to maintain skin hydration. Sunscreen
application is not recommended for at least 2weeks following deeper peels,
but all individuals should avoid sunlight and UV exposure regardless of
treatment depth [74]. Complications include hyperpigmentation and
milia/acne, which can be corrected with timely initiation of hydroquinone
and topical tretinoin respectively [77]. For individuals with a history of
herpes simplex infection, excessive redness and irritation should be treated
with fluconazole to reduce the risk of yeast infection [75] (Fig. 9).
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Fig. 9 Photos taken before (left) and after (right) combination treatment with multiple superficial
chemical peels, which show an improvement in skin complexion with reduced dark spots [78]
3.4 Laser Skin Resurfacing
Laser therapy is well utilized in some patients to reduce wrinkles,
pigmentation, and irregular skin tone. Unlike chemical peels, laser
treatment can reduce vascular lesions (telangiectasias, cutaneous angiomas)
and individual pigmentary lesions. Lasers can be generally classified as
ablative or nonablative, either targeting small columns of tissue
(fractionated) or the entire tissue (nonfractionated) [79].
Ablative laser therapy works by targeting a specific molecule
(chromophore), such as water, melanin, or oxyhemoglobin molecules in the
skin, and vaporizing the treated areas. This method produces more dramatic
results, although there are additional risks and longer recovery time [75].
Carbon dioxide laser therapy is notable for the long recovery period (up to
6months) and increased risk of hypopigmentation. Erbium:YAG laser
treatments are less damaging, although the rejuvenation is often not as
obvious [80]. Nonablative lasers generate thermal energy to induce damage
to the dermis while maintaining the integrity of the epidermis. This method
involves the use of intense pulsed light (IPL), pulsed dye lasers, or
neodymium:YAG lasers [79].
Fractionated therapy can penetrate columns of cutaneous tissue without
damaging the entire dermis, giving it the advantage of deeper rejuvenation
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with shorter recovery. Additional treatments with fractionated laser therapy
may be required to achieve desired results, as the tissue is not damaged in
its entirety. Ablative nonfractionated laser therapy can produce the most
dramatic effects, while the results of nonablative fractionated therapy are
more discreet. Moderate rejuvenation is accomplished with ablative
fractionated or nonablative nonfractionated lasers [77] (Fig. 10).
Fig. 10 The patient shown has resultant full-thickness cutaneous damage after one fractional laser
resurfacing treatment (middle image), which can take up to 6months to heal completely in some
patients. More invasive treatments often require fewer subsequent treatments to achieve the desired
result [81]
In general, the pretreatment used with chemical peel rejuvenation is also
indicated with laser resurfacing [247]. Topical anesthetics are well utilized
with superficial therapy, but deeper treatments require IV sedation, nerve
blocks, or general anesthesia. After the procedure, occlusive or petrolatum
dressings are applied to the skin surface and should be kept on until
epithelialization is complete. At that point, patients should begin using
nonocclusive moisturizers and sunblock, exercising caution with additional
skincare products to avoid irritation [73, 82].
Erythema is expected throughout the healing process, and some patients
may experience increased acne/milia after using occlusive dressings. Both
side effects often resolve as healing progresses. Irreversible
hypopigmentation may occur, although it can be camouflaged in some cases
by reducing adjacent pigmentation with additional treatment.
Hyperpigmentation is another frequently encountered complication which
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