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Updates in management of aga.pptx

1- Hormone Antagonists, Hormone Receptor Modulators
2- Wnt/β-catenin Activation
3- Ant-infammatory, Antioxidant and Antimicrobial Agents
4- Stem Cell-Based Therapies
5- Stimulation of ECM components
6- Direct Stimulation of Stem Cells and Dpcs
7- Nutritional and antioxidant therapy
8- Miscellaneous And Emerging Options

Therapeutic recommendation for
minoxidil
• Topical Minoxidil 2–5% solution 1 mL twice daily is
recommended to improve AGA in male patients above
18 years with mild to moderate AGA (Hamilton-
Norwood IIv-V).
• 5% solution or foam for greater efficacy.
• NO recommendation for the 5% minoxidil foam instead
of the 5% solution at the present time.

minoxidil
• The response to ttt should be assessed at 6 months, if
successful, ttt needs to be continued to maintain efficacy.
• For greater efficacy: combination of oral finasteride 1 mg,
1/d and topical Minoxidil 2–5% solution, 2/d.
• Cannot make a recommendation for combination therapy
of topical minoxidil with topical 5a-reductase or azelaic
acid and betamethasone valerate at the present time.

minoxidil
• Topical Minoxidil 2% solution 1 mL 2/d or 5% minoxidil topical foam
1/d is recommended to improve AGA in female patients above 18 y.
• NO recommendation for the 5% minoxidil foam once daily instead of
the 2% solution twice daily at the present time.
• The response to ttt assessed at 6 months, if successful, ttt continued.
• Cannot make a recommendation for combination therapy of topical
minoxidil with red ginseng, azelaic acid and betamethasone or oral
nutritional supplements at the present time

A- Topical 5 AR Inhibitors
B- Oral 5AR inhibition
C- Botanical 5AR inhibitors
D- Oral anti-androgens and
estrogens for FPHL
Hormone Antagonists, Hormone Receptor
Modulators

A- Topical 5 AR Inhibition
• Some efficacy as oral formulation + minimal risk of
side effects
• Topical Finasteride: Efficacy established in increasing
hair density
• Can be used in maintaining hair density after
successful treatment with oral finasteride

B- Oral 5AR inhibition
Finastride
Dutasteride

Finasteride
• Mechanism of action:
– Selective inhibitor of 5 α-reductase type-2.
– DHT level lowered but not plasma testosterone level.
• Uses:
– BPH.
– FDA approved for male androgenetic alopecia (1 mg/d).
– Hirsutism.

Finasteride
• Finasteride evaluated in women with FPHL.
• No clinical improvement in postmenopausal women receiving
finasteride versus placebo (Price et al., 2000).
• Oral finasteride, 1.25 mg/d offer improvement in women with
hyperandrogenism (Shum et al., 2002).
• A small case series show improvement in alopecia in women without
hyperandrogenism treated with 2.5-5 mg/d of finasteride (Trueb,
2004).

• Unlike dutasteride, finasteride is also a potent inhibitor of type III 5a-reductase
(diffusely expressed in the dermis & epidermis) (Azzoni et al., 2012, Boyapati &
Sinclair, 2013).
• Concomitant use of both finasteride & dutasteride may also be warranted.
• Finasteride & dutasteride are considered equally effective and safe for the
treatment of AGA in men.

• As a potential future treatment option for male AGA, dutasteride 0.5 mg
exhibited long-term safety, tolerability and efficacy within this study.
 A 35 Korean men with AGA who had not shown significant clinical improvement when
treated with finasteride 1 mg/d for at least 6m received dutasteride 0.5 mg/d for 6m.
 Dutasteride is suggestive to be an alternative effective safe treatment option to patients
with AGA who do not clinically respond to finasteride in 6m.

C- Botanical 5AR inhibitors
• Owing to the systemic adverse effects associated
with FIN and dutasteride, extracts of herbs with 5AR
inhibitory effect have been explored as an alternative
• Saw Pametto & Berries extracts are the most popular

Herbal Extracts Used In Treatment Of AGA
(Hormonal Actions)
Cimicifuga racemosa:
Increase estrogen level
Millet seed (contains silicic acid, aminoacids,
vitamins and minerals )
Agents acting by inhibition of DHT:
(Botanical 5A Reductase inhibitors)
Saw palmetto, ß-sitosterol, green tea or polysorbate 60

Canadian Willow Herb
• Antiproliferative, anti-inflammatory and
antioxidant activities
• Inhibition of several key enzymes including
5α-reductase and aromatase, caspase 3,
metaloproteinases and PGD2 inhibiting
activities
No trials were found concerning the natural products gingko biloboa,
aloe vera, bergamot, hibiscus or sorphora

Therapeutic recommendation for 5
alpha reductase inhibitors
• Oral Finasteride 1 mg/day is recommended to improve AGA in males
above 18 years with mild to moderate AGA (Hamilton-Norwood IIv-V).
• The response to ttt assessed at 6 months, although in some men it may
occur after 12 months, if successful, treatment needs to be continued .
• Cannot make a recommendation for or against ttt with topical finasteride.
• For greater efficacy: oral finasteride 1 mg, 1/d + topical Minoxidil 2–5%
solution or 5% foam 2/d .

• Oral Dutasteride 0.5 mg/day can be considered in
case of ineffective previous ttt with 1 mg finasteride
over 12 months as a second line ttt to improve or to
prevent progression of AGA in male patients above
18 years with mild to moderate AGA (Hamilton-
Norwood IIIv-V).

• Oral finasteride 1 mg daily is not suggested in the treatment
of postmenopausal women with female pattern hair loss.
• We cannot make a recommendation for or against treatment
with oral finasteride 5 mg/day at the present time.

D- Oral Anti-Androgens And
Estrogens
Estrogen
Cyproterone
Acetate
Spironolactone Flutamide
Fluridil Alfatradiol

OCPs
• Progesterone-only OCPs are not effective in the management of
androgen-mediated skin conditions.
• Combination OCPs:
– Estrogen (ethinyl estradiol in various dosages).
– Progestational agent (varies from pill to pill).
• The progestins incorporated into OCPs vary in their androgenic
capabilities, some concern that they may worsen acne.
• When combined with ethinyl estradiol, however, the net effect of a
combination pill is antiandrogenic.

OCPs
• Combined OCP are available as 21-day & 28-day packs.
• Start on Day 5 for 21 days.

Cyproterone acetate
• Direct anti-antiandrogenic action.
• Progesterone like – inhibits LH causing antiandrogenic action.
• Competes with DHT for intracellular receptor.
Uses:
• Precocious puberty in Boys.
• Prostatic cancer
• Inappropriate sexual behaviour in men.
• Virilization in women.

Cyproterone acetate
• Dose: 20-200 mg daily.
• CPA 2 mg + ethinyl estradiol, 35 pg,
used as an OCP from day 5 of the
cycle for 21 days.
• CPA, 20-100 mg/day from day 5 of
the cycle to day 14.
• Side effects: Hepatotoxic, nausea
tiredness, depression, weight gain,
breast tenderness & loss of libido.

Spironolactone
• Anti-androgen most used for skin disease in the USA.
• Mechanism of action:
– K-sparing diuretic.
– Blocks the androgen receptor.
– Decreases testosterone production in the adrenal gland.
– Inhibits the 5a-reductase enzyme.
– Displaces estradiol from SHBG, increasing free estrogen levels.

Spironolactone
• Exposure of a male fetus may cause feminization.
• Coadministering with an OCP.
• Used effectively to treat AV, FPHL & hirsutism.
• It may take 6 or more months to see improvement.
• Guidelines for use as anti-androgen:
– Start with low dose (25-50 mg) reduces incidence of side effects.
– Effective maintenance doses range from 25-200 mg /day.

Why we can’t use systemic spironolactone as an
anti-androgen in males??
• Exceptional results for many men but at a high cost of side effects.
• Severe Gynecomastia is the most common side effect.

Flutamide
• Non-steroidal anti-androgen.
• Active metabolite “2-hydroxyflutamide” causes competitive
block Androgen action – Accessory sex organs & Pituitary.
• Increased LH secretion by blocking feedback inhibition.

Flutamide
• Uses:
– FDA approved for prostate cancer along with GnRH agonist.
– Female hirusitism.
– FPHL.
– Acne vulgaris.
• Side effects:
– Gynaecomastia and breast tenderness.
– Liver damage.
– There is a risk of feminization of the male fetus.

Flutamide
• In hirsutism: flutamide is more effective than spironolactone.
• High cost, hepatotoxic.
• Low starting dose (i.e., 125 mg 1-2/d) to minimize side effects.
• Depending on the clinical response, the dose can be increased to
125 mg t.i.d. or 250 mg b.i.d.

Flutamide
• As Flutamide is potent enough to have a feminizing effect in
men, its use is limited to females.
• Further studies are needed to evaluate the efficacy of
Flutamide as a topical agent in treating androgeneic alopecia.

• Novel topical non-steroidal antiandrogen that supress androgen receptor.
• Numerous studies ascertained the low systemic and topical toxicity.
• Authorized in Czech Republic.

hormonal treatment
• We do not recommend the use of oral oestrogens or
androgenreceptor-antagonists to improve or prevent
progression of AGA in males.
• We cannot make a recommendation for topical
alfatradiol in male patients at the present time.
• We suggest that topical fluridil should not be used in
male patients with AGA.

hormonal treatment
• We cannot make a recommendation for the use of oral anti-
androgens (CPA, spironolactone, flutamide) to improve or prevent
progression of AGA in normoandrogenic females at present time.
• Oral CPA can be considered to prevent progression of AGA in women
with clinical or biochemical evidence of hyperandrogenism.
• We cannot make a recommendation for the use of topical alfatradiol,
topical natural oestrogens or progesterones & topical fluridil to
improve or prevent progression of AGA in females at present time.

A- Topical valproic acid
• A widely used antiepileptic
• Now known to activate the Wnt/ β-catenin pathway, which is
associated with hair growth cycle and anagen induction

B- Methyl vanillate
• Applied topically
• Can increase hair count by inducing Wnt10B expression in the scalp

C- Hair Stimulating Complex
• Bioengineered human cell-derived formulation
containing:
• Derived from culture of newborn cells grown in
an oxygen-deficient embryonic environment
Wnt7a protein
Epidermal Growth
Factors
Follistatin

A- Ketoconazole
• Observed to impede synthesis of steroid at high
concentrations
• Inhibition of cytochrome P450 and lyase
• Inhibitory actions on inflammation and fungal
infections in the scalp

B- Prostaglandin-Based Therapies
Prostaglandin and prostamide analogues:
-Drugs that block PGD2 signaling or enhance PGE2
-The prostaglandin F2α analogue latanoprost
-Prostamide F2 α analogue bimatoprost

C- Melatonin
• Secreted from the pineal body
• Actions in humans
Interaction with
specific receptors
Inhibits both apoptosis
and expression of
estrogen receptor
Influence androgen
and estrogen receptor-
mediated downstream
processes
Free radical scavenging
and protective actions

D- Cetrizine
• H1 receptor blocker that reduce PGD2 release from mast cells
• Anti-inflammatory & anti-allergic activities of cetirizine can be
useful in AGA patients with scalp irritation and inflammation

Stem Cell-Based Therapies
• Possibility of creating a functional hair follicle from follicular
stem cells, i.e., bioengineering hair for transplant??
• Possibility of creating new hair follicles by injecting
autologous dermal and/or epidermal cells??

There is many publications
were published in recent
years & most of these
papers elicited the stem cell
in treatment of AGA

Role of Stem cell
1. Interplay
2. Competitive inhibtor of DHT
3. GF
ERK
Prolifration
”mitosis”
Akt
survival

Stimulation of ECM components
Tetrapeptides: AcSDKP,
Angiogenic factor
Diguanosine tetraphosphate
(GP4G):
liposomic solution of Artemia salina
extract
Stimulation of ECM protein synthesis-----Inhibition of 5 AR activity, and
reduction of follicular micro-inflammation

1- Hormone Antagonists, Hormone Receptor Modulators
3- Anti-infammatory, Antioxidant and Antimicrobial
Agents

Platelet Rich Plasma
Microneedling

DHT
Wnt
X
B-
Cat
TCF/L
EF
B-
Cat
X
Akt Erk
Proliferation
Survival

Therapeutic recommendation for PRP
• There is no standardized technique for performing
PRP to permit objective evaluation of its effects on
AGA.
• We cannot make a recommendation for or against
treatment of AGA with PRP at the present time

1- Hormone Antagonists, Hormone Receptor
Modulators
3- Ant-infammatory, Antioxidant and Antimicrobial
Agents

Oxidative Stress
• Apoptosis of HF cells followed by early onset of the catagen phase by lipid
peroxides that generate free radicals
• Balding areas of scalp show increased nuclear expression of markers of
oxidative stress and DNA damage including heat shock protein-27, super
oxide dismutase, catalase, and p16(INK4a)/pRB
Smoking and ultraviolet light induced
exacerbation of AGA

Non-Minoxidil Miscellaneous Treatment Options
Amino Acids (Cysteine)----
increased growth factors
Trace elements like copper
and zinc ------Improve hair
nutrition
Iron supplementation in
patients with low serum
Ferritin
Proanthocyanidines like
procyanidine B (flavonoid
working as an antioxidant)
Vitamins especially biotin and
niacin ----Improve hair
nutrition
Caffeine:
Prevent progression and
induce hair regrowth
Prostaglandine analogues like
viprostol or latanoprost
: Vasodilator effect
Aminexil is a vasodilatator
chemically similar to
minoxidil: Perifollicular
Vascularization

Main Active ingredients: (in highest concentration 40%)
• Grape seed oil (full of Proanthocyanidin)
• Omega 3
• Omega 6
• Omega 9
• Vitamin E
• Thio-lipisters ( Ecrinal Patency)
• 5ml ampoules x 8 = 745 LE
• Half amp day after day
Ecrinal Ampoules
Anti hair loss & hair stimulation
Intensive hair treatment
Suitable for fine hair (normal to dry
hair )

Indications : (in highest concentration 40%)
• FPHL hair loss, from the very first signs in women, thinning scalp, in
cases where hair growth is slowed down, or where it is necessary to
assist weakened hair by boosting regrowth.
• In certain cases of hair loss with dandruff.
• Anemic hair. in cases where the appearance of the scalp and hair
requires treatment in order to increase your hair’s vitality.
Ecrinal Ampoules
Intensive hair treatment

Main Active ingredients: (spray formula with high
compliance conc.20%)
• Grape seed oil ( full of Proanthocyanidin)
• Omega 3
• Omega 6
• Omega 9
• Vitamin E
• Thio-lipisters
• Suitable for fine hair (non-greasy & light weight)
• 200 ml 289 LE
• 6 puffs morning and evening
Ecrinal lotion
Daily treatment

Indications :
• In mild and moderate cases hair loss (TE)
• Maintenance after ampoules course
• Suitable for pregnant and lactating women
• In children starting from 2 years
Anti hair loss Lotion
Daily treatment 20%

ANP 2+ Complex (exclusive patent)
The Thiolipidic complex featuring Thiolipisters and 3 plant
origin oils that contributes to & play an important role in
boosting the keratin production ..
Provitamin B5 , vitamin B3 :
It improve your hair’s: Shine ,softness & strength
It can also help protect your hair from styling or
environmental damage by locking in moisture.
Helps to transport blood and oxygen to the scalp and hair
follicles.

•Inhibit DHT leading to:
• Stimulate hair production
• Slow down hair loss
Grape seed oil (Proanthocyanidin)
Enhance keratin synthesis
Thio-lipisters
Anti-hair loss
Stimulate healthy hair growth

Thio-lipesters of silk (Patency)
• THIO-LIPESTERS® C8SMET 8515 have a stimulating action that
boosts hair regrowth in particular thanks to the introduction
of L- Cysteine & L-Methionine sulfur amino acids which
contributes to the optimization of skin appendage growth and
the prevention of hair loss
• The very improved results explained by the fact that the
sulfur-containing amino acids are present in keratins,
particularly in the integuments in high proportion therefore
their presence are essential in the synthesis of keratins which
increases the growth of hair and improves the strength of
regrowth

Cysteineas a sulfurated amino acid does it
have a role in keratin synthesis and hair growth??

• Ensure healthy appearance of hair & scalp
• ↑ elasticity  ↓ brittle hair
• Sebum regulation  treat dry, dehydrated hair
• ↑ Moisture content
• Give shiny appearance
Great mix of EFA (Omega 3, 6 & 9)
Synergism between both potent antioxidants
Vitamin E & Proanthocyanidin
Stronger & Shiny hair
Anti-aging effect

Therapeutic recommendation for miscellaneous
molecules, substances and interventions
• Cannot make a recommendation for or against a
treatment with the mentioned molecules,
substances and interventions at the present time.

New And Emerging Treatment
Options

Nitric oxide (NO) gel:
Promote hair follicle formation through stem cell development, hair
regeneration, hair Shaft elongation and increased growth rate in rats
Vitamin D3:
-The Vitamin D receptor (VDR) is expressed in hair follicle keratinocytes
during late anagen and catagen
-Vitamin D3 has also been shown to modulate Wnt10b gene expression
-VD3 gene knock-out and VD3 supplementation in nude mice has revealed
encouraging hair growth

Topical roxithromycin:
-Inhibition of apoptosis of keratinocytes (via suppressing the production
of oxygen reactive species)
-Suppression of the AR in human dermal fibroblasts
Low-level laser/light therapy (LLLT) :
-
Modulation of reactive oxygen species (ROS),
-
Induction of transcription factors
Botulinum Toxin Scalp Injection:
-
A traction component by tension of the musculus occipitofrontalis is
discussed, but studies are missing
-
May act on the inflammatory component of androgenetic alopecia

Therapeutic recommendation for Low-level
Laser therapy (LLLT)
• Suggest using LLLT as ancillary therapy for AGA with
devices that use energy levels shown to be effective
in randomized controlled clinical trials.
• Cannot make a recommendation for or against
treatment for more than 6 months with LLLT for
AGA at the present time

Therapeutic recommendation for hair
transplantation
• Surgery, especially follicular unit transplantation
(FUT) can be considered in males and females with
sufficient donor hair.
• Suggest FUT to be combined with finasteride 1 mg
daily to achieve a better clinical outcome in males.

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Updates in management of aga.pptx

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