(DHEA) and testosterone, free testosterone, the ratio of DHT : testosterone, and IGF-1 have all been measured in bald men.
two major features of male pattem hair loss are recession of the frontal hair line and balding of the scalp vertex. Eventually, hair loss may coalesce leaving a rim of normal hair growth at the sides and back of the scalp
Its primary use is as a diuretic and antihypertensive, and many of its side effects and numerous drug interactions relate to this.
(PDGFaa, PDGFbb, and PDGFab), transforming growth factor beta (TGFβ1 and β2), EGF, and VEGF.
Dr. U.S. Agarwal
• Androgenetic alopecia is an extremely common disorder
affecting both men and women.
• Incidence is generally considered to be greater in males than
females, although some evidence suggests that apparent
differences in incidence may be a reflection of different
expression in males and females.
• Male pattern hair loss (also known as male androgenetic
alopecia, male balding) is an androgen-dependent, genetically
• Female pattern hair loss has also been termed androgenetc
alopecia, in the belief that it is the same entity as in men, but
the requirement for androgens is less clearcut than in men
and the distribution of hair loss is generally different.
• however, in both men and women, pattern hair loss is
characterized by a progressive decline in the duration of
anagen, an increase in the duration of telogen, and
miniaturization of scalp hair follicles, indicating a final
common pathway of follicular regression.
• Pattern hair loss is a biologically normal trait.
• Nevertheless, the high value our societies place on
maintaining a full head of hair means that loss of hair can
have a significant adverse effect on quality of life.
• Both sexes are affected though, in general, the impairment of
psychosocial well-being is more frequent and more severe in
• Universally this is an extremely common disorder that affects
roughly 50% of men and perhaps as many women older than
• As many as 13% of premenopausal women reportedly have
some evidence of androgenetic alopecia.
• Incidence increases greatly in women following menopause,
and, according to some authors, it may affect 75% of women
older than 65 years.
• Other than affecting patient psychologically, disorder is
significant only in that it allows ultraviolet light to reach scalp
and, thus, increases the amount of actinic damage.
• Incidence and severity of androgenetic alopecia tend to be
highest in white men, second highest in Asians and African
Americans, and lowest in Native Americans and Eskimos.
• Almost all patients have an onset prior to age 40 years,
although many of patients (both male and female) show
evidence of the disorder by age 30 years.
• This genetically determined disorder is progressive through
the gradual conversion of terminal hairs into indeterminate
hairs and finally to vellus hairs.
• Patients have a reduction in the terminal-to-vellus hair ratio
• Following miniaturization of the follicles, fibrous tracts
• Patients with this disorder usually have a typical distribution
of hair loss.
Normal hair cycle
• A working knowledge of the anatomy of normal hair cycle is
useful in understanding the evolution of miniaturizing hairs.
• Average number of hairs in adult scalp is 100,000, of which
90% are in anagen and 10% in telogen.
• Average duration of anagen is 1000 days, of telogen 100 days,
and the average daily loss of telogen hairs is 100.
• Hair follicle cycling occurs in the impermanent lower follicle
between the bulb and the bulge, which is situated in the area
of insertion of the arrector pili muscle into the follicle.
• Bulb comprises the hair matrix cells that surround the dermal
• Dermal papilla contains papillary mesenchymal cells,
surrounded by extracellular matrix.
• It is continuous with the fibrous dermal sheath that surrounds
bulb & contains mesenchymal cells similar to those in papilla.
• Anagen bulb produces the hair shaft and the inner and outer
• Inner root sheath molds the hair shaft in the lower follicle and
is shed in isthmus region of the follicle.
• Several years of hair growth are followed by a resting phase:
anagen is first succeeded by 3 weeks of catagen and ends in
telogen, which lasts an average of 3 months.
• During this resting phase, the lower follicle retreats up to the
level of bulge during catagen, dragging the exposed
miniaturizing dermal papilla behind it.
• Stella or fibrous tract marks the ascent of the follicle.
• dermal papilla shrinks to its smallest size during telogen.
• With a new anagen cycle, the follicle follows the papilla down
the fibrous tract, and papilla generally enlarges once again.
• Exact controls of hair follicle cycling are still unknown.
• Whether the cycle is initiated in hair follicle epithelium or in
papillary mesenchyme is controversial.
• Some postulates hair cycling clocks.
• Others believe that repeated cycling may be an innate
property of a follicle.
• Most will agree that follicular epithelium, dermal papillae, and
dermal sheath cells all interact in follicular cycling.
• Cycling is probably driven by local signals changing the
expression of cytokines, growth factors, hormones,
neuropeptides, adhesion molecules and receptors.
• Regrowth of hair may well be initiated by stem cells in the
• This is supported by the fact that the lower follicle retracts
upward to the level of bulge area in telogen.
• Slow-cycling cells have been demonstrated in bulge region in
murine follicles by autoradiography with thymidine labeling.
• The hypothesis is that entry into anagen occurs when stem
cells in the bulge region are activated by signals from the
• Daughter transient-amplifying cells form the hair bulb matrix
and ultimately its differentiated cell products.
• It seems possible that cells in the hair bulb matrix have a finite
proliferative potential that, once exhausted, would result in
cessation of growth and entry into catagen.
• After transition from telogen to anagen I, and progression
through subsequent stages into anagen VI, the complete hair
follicle is regenerated.
Systemic hormonal effects
• Key role of androgens in the pathogenesis of male AGA was
revealed by the observations of the American anatomist
• He noted that men castrated before puberty did not develop
balding unless treated with testosterone.
• A number of studies have tried to determine whether balding
males have increased circulating androgens, but no
differences between patients and controls have been
• All these studies suffer from a lack of reproducibility, and
although differences in mean levels have been variously
detected, the substantial overlap in the absolute levels of all
androgens between cases and controls demonstrates that
normal male levels of androgen are sufficient to make
manifest the degree of baldness determined genetically for
• for women, androgens in the normal female range are
sufficient to induce early baldness in women with a strong
• In women without a strong predisposition, balding will not
occur until later in life unless endogenous androgen
production is increased or drugs with androgen-like activity
• Some women with even grossly abnormal levels of androgen
do not develop clinically significant baldness, although such
patients are generally hirsute.
Local hormonal effects
• Androgens do not affect all hairs equally.
• Body hair grows, scalp hair is lost whereas the eyebrows
remain essentially unchanged at puberty.
• On the scalp there is a hierarchy of sensitivity, with the most
anterior of the hairs at the temples being lost first, and
subsequent hairs miniaturizing in a highly ordered fashion to
produce patterned baldness.
• Similarly on the male beard, hairs first appear on the upper lip
at the lateral corners and then over the rest of the face in a
highly ordered fashion.
• In men, where circulating androgens are surplus to the
requirements of hair follicles for maximal stimulation, local
factors determine individual susceptibility and severity of
• This intrinsic regulation is best demonstrated in hair
• occipital hairs maintain their resistance to AGA when
transplanted to vertex, and scalp hairs from the vertex
transplanted to forearm miniaturize at same pace as hairs
neighbouring the donor site.
• In females, where circulating androgens are not sufficient to
maximally stimulate hair follicles, local factors still determine
susceptibility, but severity is influenced by both local factors
and levels of systemic hormone.
Hair cycle dynamics
• In AGA, the duration of anagen decreases with each
successive cycle, whereas the length of telogen remains
constant or is prolonged.
• Prolongation of telogen occurs particularly in latent phase of
telogen (also known as kenogen) that follows release of club
• This leads to a reduction of the anagen : telogen ratio and
corresponds to periods of excessive hair shedding, most
noticeable while combing or washing.
• Prolongation of latent phase increases the proportion of
empty hair follicles on scalp, further contributing to balding
• As the hair growth rate remains relatively constant, the
duration of anagen growth determines hair length.
• Thus, with each successively foreshortened hair cycle, the
length of each hair shaft is reduced.
• Ultimately, anagen duration becomes so short that the
growing hair fails to achieve sufficient length to reach the
surface of skin, leaving an empty follicular pore.
Hair follicle miniaturization
• Population density of hair follicles per unit area of scalp does
not change with balding.
• Rather there is a gradual diminution in size of follicles that
results from the transformation of terminal follicles into
• Hair follicle miniaturization leads to finer hair that is often
lighter in colour.
• On the balding scalp, transitional indeterminate hairs
represent the bridge between full-sized and miniaturized
• Although smaller follicles tend to cycle more quickly there is
no absolute correlation between hair follicle size and anagen
• Eyebrow, eyelash and nasal follicles are large but the hair is
• It is likely that separate factors control the miniaturization and
hair cycle changes.
• Dermal papilla is central to the maintenance and control of
hair growth and is likely to be the target of androgenmediated events leading to follicle miniaturization and hair
• Constant geometric relationship between the dermal papilla
size and the size of the hair matrix suggests that the size of
dermal papilla determines the size of hair bulb and ultimately
the hair shaft produced.
• cross-sectional area of individual hair shafts remains constant
throughout fully developed anagen, indicating that the hair
follicle, and its dermal papilla, remain the same size through
each individual anagen stage of the cycle.
• Thus, miniaturization occurs between rather than within
• Follicular miniaturization has been traditionally thought to
occur in a stepwise fashion although there have been
suggestions that it occurs rapidly, possibly in the space of a
single hair cycle.
• Follicular miniaturization leaves behind stellae as dermal
remnants of the full-sized follicle.
• These stellae, also known as fibrous tracts or streamers,
extend from the subcutaneous tissue up the old follicular tract
to the miniaturized hair and mark the formal position of the
original terminal follicle.
• History reveals that the onset is gradual.
• In both males and females there is transition from large, thick,
pigmented terminal hairs to thinner, shorter, indeterminate
hairs and finally to short, wispy, nonpigmented vellus hairs.
• As the disorder progresses, the anagen phase shortens with
the telogen phase remaining constant.
• As a result, more hairs are in the telogen phase, and patient
may notice an increase in hair shedding.
• End result can be an area of total denudation.
• This area varies from patient to patient and is usually most
marked at vertex.
• Men present with gradual thinning in the temporal areas,
producing a reshaping of the anterior part of the hairline.
• For the most part, evolution of baldness progresses according
to the Norwood/Hamilton classification of frontal and vertex
• Posterior and lateral scalp margins are relatively spared, and
only affected in most advanced cases and with old age.
• Female pattern hair loss is usually a more diffuse process than
• Typically, there is a reduction in hair density involving the
crown and frontal scalp with maintenance of frontal hair line.
• There may be miniaturized hairs in the frontotemporal region
but deep recession of a well-demarcated hair line is
• Unlike men, the parietal regions may also be involved.
• Female pattern hair loss may present with excessive hair
shedding and loss of hair volume, before there is an obvious
reduction in hair density.
• Differentiation from chronic telogen effluvium can be difficult.
• In such cases, diagnosis may be established by the presence
of a high propoftion of miniaturized follicles on biopsy.
Ludwig scale for grading female pattern hair loss
• Grade I rarefaction of the hair on the crown.
This produces an oval area of alopecia encircled by a band of variable breadth with
normal hair density.
Frontally the fringe is narrow (1–3 cm) and at the sides the margin is 4–5 cm wide.
• Grade II results in further rarefaction of the crown, with preservation of the fringe.
• Grade III is near-complete baldness of the crown.
Key elements of the histology of AGA are :
• a reduction in terminal hairs,
• an increase in secondary vellus hair with associated
• a variable increase in telogen and catagen hairs,
• a mild or moderate perifollicular lymphohistiocytic infiltrate,
with or without concentric layers of perifollicular collagen
• Many of these changes are best seen on horizontally
sectioned scalp biopsies.
• Horizontal sections reveal numerous pseudovellus hair
follicles in the papillary dermis, reflecting a miniaturization
• In the vast majority of cases there is no genuine reduction in
the number of follicles, and follicular fibrosis is seen in less
than 10% of cases.
• presence of arrector pili muscles and angiofibrotic streamers
distinguishes them from true vellus hairs.
• There is a change in the ratio of terminal : vellus hairs from
greater than 8 : 1 to less than 4 : 1.
• The diagnosis should be confirmed and the patients
approached with utmost care and sympathy.
• Counseling forms an essential part, as does the balance
between realistic expectations and therapeutic limitations.
• Patients should be advised to avoid hair care products likely to
• Patients should maintain an adequate diet, especially one
with adequate protein.
• recommended daily allowance for protein is about 1 gm/kg.
• Topical medications work only where the medication is
applied; therefore, the entire area at risk of hair loss (the top
of the scalp) should be treated with a given topical agent.
• Treat any underlying scalp disorder such as seborrheic
dermatitis or scalp psoriasis as these conditions can affect the
ability to use topical treatments.
Medical treatment for men
• Currently, only finasteride 1 mg and minoxidil topical solution
(2% and 5%) are FDA- approved for the treatment of MPHL.
• Both drugs retard further thinning and increase scalp
• Neither drug restores all the lost hair.
• Neither drug is able to reverse total baldness.
• Both drugs require chronic use to maintain effectiveness.
• Treatment should be used for 12 months before making a
decision about efficacy although benefit may be seen sooner.
Minoxidil topical solutions
• It increases duration of anagen and enlarges miniaturized
• As a potassium channel opener and vasodilator the drug's
precise mechanism of action is unknown but appears
independent of vasodilation.
• Mode of application should be explained to the patient.
• One ml is applied twice daily to dry scalp, preferably using a
• Topical minoxidil solution requires approximately 1 hour for
• If the patient shampoos or the scalp becomes wet, e.g., from
excessive sweating or rain, the medication should be reapplied.
• If gel or hair spray is used, the medication should be applied
first so that absorption is not affected.
• Minoxidil increases terminal hair density in up to 30% of
• Terminal hair appeared to regrow at the margins, but
complete covering of the bald areas was seen in less than 10%
• There is a slight increase in benefit if the concentration is
increased to 5%.
• Benefit is most pronounced in the first 6 months of therapy
and thereafter is marginal.
• If treatment is stopped, clinical regression occurs within 6
months, to the state of baldness that would have existed if
treatment had not been applied.
• Patients should be warned that in order to maintain any
beneficial effect, applications must continue twice daily for
the rest of their lives.
• Topical minoxidil solution may initially cause a telogen
effluvium beginning 2-8 weeks after treatment initiation.
• This temporary shedding, resulting from the minoxidil
initiated release of telogen hairs ("exogen") as anagen
promotion begins, is self-limiting with continued treatment
and should not be a cause for concern.
• Patients should be forewarned so that treatment is not
• Adverse effects that are mainly dermatologic like scalp
irritation, including dryness, scaling, itching, and/or redness,
may occur; these are more common with the 5% topical
minoxidil solution than the 2% topical minoxidil solution.
• Allergic contact dermatitis is uncommon.
• Patch tests may help to sort out whether it is related to
minoxidil or propylene glycol.
• Finasteride is a synthetic aza-steroid that is a potent and
highly selective antagonist of 5α-reductase type 2.
• It inhibits the conversion of testosterone to DHT.
• A scalp biopsy study of patients with AGA found that after 12
months of finasteride treatment, terminal hair counts
increase and vellus hair counts decrease, demonstrating the
ability of finasteride to reverse the miniaturization process
and to encourage the growth of terminal hairs.
• An oral dosage of 1 mg/day reduces scalp DHT by 64% and
serum DHT by 68%
• Target area hair counts (TAHC) are generally used to assess
efficacy in clinical trials of MPHL.
• TAHCs are circular target areas 1 cm to 1 inch in diameter
typically at the anterior leading edge of the vertex balding
area where the terminal, non-vellus, or visible hairs are
counted pre and post--treatment.
• Target area hair counts increase over the first year and peak
by 12 months.
• In men of age 18-41, hair counts increased 16. 9/cm2 for
those on 1 mg finasteride as against 4.1/cm2 for those on
• Hair growth continues to improve for at least the first 24
months of treatment as the hairs grow longer and thicker.
• When treatment with finasteride is discontinued, any positive
effect on hair growth will be lost in 12 months.
• Drug is quite safe with no known drug interactions and no
effects on liver, kidney, bone marrow, or bone and no effect
• Reversible sexually related side effects (decreased libido,
erectile dysfunction, decreased ejaculate volume) are seen in
• These side effect often resolve during continued treatment or
within days to weeks after treatment is discontinued.
• Level of finasteride in semen of men taking finasteride is very
low and semen from a man taking finasteride poses no risk to
a pregnant woman or to her fetus.
• Reduction in prostate specific antigen (PSA) is physiologically
based on the effect of decreased DHT on prostate.
• Dutasteride is a combined type 1 and 2 5α-reductase inhibitor.
• It produces a dose-dependent reduction in serum and scalp
DHT levels to a greater degree than that seen with finasteride,
and is more effective in stimulating hair regrowth in MPB.
• Dutasteride is currently marketed at a 0.5 mg dosage for BHP
and it is not licensed for treatment of MPB.
• Sexual side effects are more common with dutasteride, and
are also dose related, but appear to be reversible on
Medical treatment for FPHL
• Topical minoxidil has been shown to arrest hair loss or to
induce mild to moderate hair regrowth in approximately 60%
of women with FPHL.
• A clinical trial comparing 5% and 2% formulations of minoxidil
found a mean increase in non-vellus hair counts after 48
weeks of 18% and 14%, respectively.
• Currently, only 2% topical minoxidil solution is FDA approved
for the treatment of "women with thinning hair.“
• Five percent topical minoxidil solution has been evaluated in
women with FPHL and was found to be significantly more
effective than placebo by both target area hair counts and
• There was a trend towards superior efficacy of 5% topical
minoxidil solution over 2% topical minoxidil solution but this
was not consistently statistically significant.
• Topical minoxidil solution works in those women with FPHL
both with and without hyperandrogenism and in young and
old, pre- and postmenopausal women alike.
• Either 2% or 5% topical minoxidil solution appears safe to use
in women with FHPL, with the only additional risk of the 5%
topical minoxidil solution over the 2% topical minoxidil
solution being a higher incidence of facial hypertrichosis.
• Hypertrichosis tends to occur over the cheeks and forehead as
vellus, not terminal hair and disappears within 4 months of
stopping the drug.
• Although this may be related to inadvertent spreading to the
face after local application to the scalp, this may also be a
result of hypersensitivity to low levels of systemic absorption
• Oral antiandrogen therapy with cyproterone acetate,
spironolactone or flutamide is widely used in the treatment of
FPHL although there is a dearth of clinical trial data.
• Spironolactone is a synthetic steroid, structurally related to
aldosterone, which acts by competitively blocking androgen
• It also weakly inhibits androgen biosynthesis.
• Several studies have demonstrated the efficacy of
spironolactone in the treatment of hirsutism.
• There are no controlled trials in FPHL.
• Dosage ranges from 100 to 300 mg/day.
• Side effects are dose related and include menstrual
irregularities, postmenopausal bleeding, breast tenderness or
enlargement, and fatigue.
• Spironolactone has the potential to feminize a male fetus and
women should not become pregnant while taking
• Cyproterone acetate is an androgen receptor blocker and
• subset analysis showed some increase in hair density in
women with clinical evidence of androgen excess, suggesting
that antiandrogens may be more effective in women with
• There are no dose-ranging studies, but most practitioners use
cyproterone acetate 50–100 mg/day for the first 10 days of
each menstrual cycle.
• For postmenopausal women, cyproterone acetate may be
used continuously, with or without oestrogens.
• Flutamide is a non-steroidal antiandrogen that acts by
inhibiting androgen uptake and by inhibiting nuclear binding
of androgen within the target tissue.
• One study suggested that flutamide is superior to cyproterone
acetate and finasteride in the treatment of androgenetic
• In a double-blind, placebo-controlled study involving almost
100 postmenopausal women with FPHL, 1 mg finasteride was
found to be no better than placebo.
• Subsequent case reports and a case series have reported
benefits in both pre- and postmenopausal women, but
teratogenicity remains a relative contraindication to use in
• Nonmedical approaches can provide cosmetic relief to men
and women with thinning hair if medical treatments are not
indicated, not effective, or not desired by the patient.
• They can also be used as adjuvant therapy.
• Tinted powders, lotions, and hair sprays can all provide a
cosmetic covering of the scalp in areas of scalp hair thinning
and can be useful in camouflaging it.
• Wigs, hair pieces, and hair extensions can be used to cover a
• Advances in the technology of these prostheses have made
their use much more acceptable.
• A variety of surgical techniques have been developed for
treating pattern hair loss, of which hair transplantation is the
most widely used.
• All involve redistributing terminal hair to the balding areas so
the number of terminal hairs remains the same.
• In skilled hands, and with careful patient selection, good
cosmetic results can be obtained.
• Surgery is the only treatment that can improve hair coverage
on totally bald scalp, and quickly restore hair.
• Patients over the age of 25 years are preferable.
• Predictive value of future hair loss is much lower for
individuals between the ages of 15 and 25 years of age and
surgery in this young group of men may result in misplaced
hairlines or an unnatural appearance 20 or 30 years later.
• Young men with early hair loss already have enough hair for
facial framing and will receive limited aesthetic benefit from
• Vertex baldness is a progressive process and does not become
"stable with time," and therefore, hair transplantation of
vertex should be approached with extreme caution, Ideal
candidates are those with just frontal & mid-frontal hair loss.
• When frontal baldness is corrected, this creates the most
dramatic positive change in appearance.
• Density of donor area should be adequate.
• Patients with <40 follicular units/cm2 in the donor area are
considered poor candidates.
• Thicker hair shafts (>60-70 microns) demonstrate better
coverage compared to finer hair.
• Women with mild female pattern alopecia are not optimal
surgical candidates since differences in pre-transplanted scalp
as against post-transplanted scalp are difficult to appreciate.
• Those with diffuse unpatterned alopecia are poor surgical
candidates for the obvious reason that the entire scalp is
suffering hair loss, thus, the donor area is of limited value as it
is also susceptible to loss.
• Ideal female patients for hair transplantation are those with
high-density donor hair and extensive hair loss or thinning of
the frontal scalp.
• Experienced surgical teams can create significant coverage in
one to two sessions with dense packing of higher number of
grafts (1000-2000) being performed per session.
• Final results are usually seen 5-6 months after the procedure,
and thus, timing between sessions, if needed, is usually a
minimum of 6 months.
• Complications include facial edema, scalp erythema, and
recipient site crusts of the scalp are common but usually
resolve within 3-7 days although crusting may persist a few
• This attempts at a procedure where hair-bearing skin is
brought closer together by removing the center scalp affected
by the alopecia.
• It is not commonly performed currently.
• There are many different designs employed in excising the
• Reductions may be performed in conjunction with hair
transplantation to the remaining bald scalp for a more
• One has to remember that the efficacy diminishes over time
due to the unpredictable progression of hair loss in any given
• Excision scars become noticeable over time.
• The scar may potentially widen secondary to stretching of
adjacent scalp skin.
• Usually more than one scalp reduction is necessary to
effectively address a person's baldness.
Role of Platelet-rich Plasma in the Management
of Androgenetic Alopecia
Int J Trichology. 2012 Oct-Dec; 4(4): 291–292
• PRP has been used in the past to prevent infection and speed
up the wound healing process by reducing bleeding/swelling
after surgery by the plastic-, general-, and orthopedic
• PRP, an autologous concentration of human platelets in a
small volume of plasma has a higher platelet concentration (47 times) above the baseline.
• It is obtained from the patient's own blood after processing in
an automated centrifuge and it is injected subcutaneously
into the area of alopecia
• Ubel in 2005 studied 23 patients of hair transplant after enriching
the hair root grafts with PRP and without PRP.
• Two areas (2.5 cm2) each were marked on the scalp and planted
with 20 grafts/cm2.
• After 1 year, the area implanted with the PRP-enriched grafts
demonstrated a yield of 18.7 FU/cm2 versus 16.4 FU/cm2 of that
without PRP, an increase in follicular density of 15.7%.
• Li et al. performed an in vivo study, where mice received s.c.
injections of PRP, and their results were compared with control
• Activated PRP increased the proliferation of dermal papilla cells
• injection of mice with PRP induced faster telogen-to-anagen
transition than that was seen in control mice.
• The beneficial effects of PRP in AGA can be attributed to
various platelet-derived growth factors causing improvement
in the function of hair follicle and promotion of hair growth.
• It is safe, cheap, and non-allergic and it appears to be a useful
adjuvant in the management of AGA.
• Because hair loss is so distressing, patients are willing to try
just about everything.
• There are countless products that claim to regrow hair, but
there is not enough rigorous science behind most of them.
• Patients often ask questions about hair care and we tell them
that in most cases frequency of shampoos, shampoos
themselves, hair coloring are irrelevant in the process of hair
loss and that they can feel comfortable using any regular
• We do not suggest any specific shampoos unless there is
seborrhoeic dermatitis or psoriasis present.
• There is so much quackery and we must discourage our
patients from any 'miracle' treatments.
• Unfortunately, many patients have already spent great sums
of money with no result.
• As our knowledge of androgenetic alopecia pathophysiology
increases, novel targeted treatments will potentially be