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Hair: W hat i s N ew in D iagn o s is

and M anagement ?
Female Pattern Hair Loss Update: Diagnosis
and Treatment
Natasha Atanaskova Mesinkovska, MD, PhD,
Wilma F. Bergfeld, MD*

KEYWORDS
 Alopecia  Pattern hair loss  New  Update  Treatment  Androgenetic

KEY POINTS
 Female pattern hair loss (FPHL) is the most common cause of alopecia in women, and it is charac-
terized by follicular miniaturization.
 Androgens and estrogens are the main hormonal regulators implicated in FPHL.
 Realistic expectations need to be set when treating patients with FPHL.
 All treatments seem to work best when initiated early and when used in combinations.

DEFINITION A 4-mm cylindrical punch from the central area of
hair loss is preferred. It is recommended to avoid
Female pattern hair loss (FPHL) is the most biopsies from the temporal area, because minia-
common cause of alopecia in women. It affects turized hair follicles can be found there even in
6% to 12% of women between the ages of 20 and the absence of FPHL.3 Preferably vertical and hori-
30 years, and more than 55% of women older zontal tissue sections should be processed, and
than 70 years.1 FPHL clinically presents with diffuse reviewed by a dermatopathologist experienced in
nonscarring loss of hair, with prominent thinning interpreting alopecia biopsies.
over the frontal, central, and parietal scalp. The FPHL is characterized histologically with increased
frontal hairline is characteristically retained. A numbers of miniaturized, velluslike hair follicles. In
similar pattern of hair loss with follicular miniaturiza- FPHL, the ratio of terminal to velluslike hairs is usually
tion is seen in male androgenetic alopecia (AGA). less than 3:1.4 There is a reduction in follicle size,
Because the role of androgens on alopecia in depth, and hair shaft diameter, with an increased tel-
women remains uncertain, FPHL has emerged as ogen/anagen ratio.5 Low levels of inflammation can
the preferred term rather than AGA in women.2 be found as lymphocytic microfolliculitis targeting
the hair bulge, with IgM and complement deposits
DIAGNOSIS on the basement membrane.6
Although most patients with FPHL have normal
The diagnosis of FPHL is made clinically based on levels of testosterone, this type of alopecia can
the appearance of the scalp. Biopsies are reserved be a marker of hyperandrogenism in women.7
only for situations when the diagnosis is uncertain. Evaluation of patients with FPHL should include
derm.theclinics.com

Department of Dermatology, Dermatology and Plastic Surgery Institute, Cleveland Clinic, A61, 9500 Euclid
Avenue, Cleveland, OH 44195, USA
* Corresponding author.
E-mail address: bergfew@ccf.org

Dermatol Clin 31 (2013) 119–127
http://dx.doi.org/10.1016/j.det.2012.08.005
0733-8635/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.

which In contrast. Hormonal studies should sudden loss of estrogen postpartum is believed include serum levels of androgens. Combina- affect hair loss through inhibition of 5a reduc.15 FPHL has been correlated with low nologist may be helpful in complicated cases.16 PATHOGENESIS Outside the sex hormonal milieu. systemic estrogen levels when aromatase inhibi- Additional useful laboratory tests include thyroid.11 Although it has cant risk of developing FPHL. are implicated in the prolongation of anagen. The normalities. hirsutism.9 The 5a reductase inhibitors. 1). or congen. tions of treatments tend to be more efficacious tase. known as telogen gravida- for presence of polycystic ovary syndrome rum. of CAG and GGC repeats within the AR gene. the circulating testosterone levels do not for FPHL and AGA. the role of androgens in FPHL has not affects its transcriptional activity. Estrogens may positively seem to work best when initiated early. In- regulators implicated in FPHL. androgen-producing tumors. The amino-terminal domain of the response to 5a reductase inhibitors. lower systemic estrogen levels (PCOS).12 The goal of treatment of FPHL is to arrest hair loss The observed differences between androgen progression and stimulate hair regrowth.19 Based on the experi- nasteride and dutasteride. prolactin. fibrinogen.20 The AR gene tional polymorphisms of AR can be a marker for is a nuclear transcription factor located on the premature AGA in men and can predict treatment X-chromosome. and zinc levels. accomplish complete regrowth. Estrogen signaling can to treat FPHL have mixed success and do not modify androgen metabolism at the hair follicle. Realistic regulation in FPHL and male AGA may lie in the expectations need to be set. menstrual ab. the Hair Genetic Test measures the length of circulating sex hormone binding globulin (SHBG). menopause. testos- terone is converted to DHT by the enzyme 5-a Genetic Studies reductase type II. to evaluate to lead to shedding.3% eral sensitivity to androgens in FPHL.8 Most of the prevalence of carotid atheromatosis. which differs for men and women.com). Also. FPHL may be influenced by insulin resistance.11 Although with PCOS. In scalp hair follicles. Shorter which may increase the available free testosterone CAG and GGC repeats are associated with a signifi- at the level of the hair follicle. in male patients. Topical estrogen iron studies with ferritin.120 Atanaskova Mesinkovska & Bergfeld clinical assessment for hirsutism. AR polymorphisms have not been TREATMENT uniformly confirmed and cannot completely explain the mechanism of FPHL. but their efficacy is questionable. All treatments by unclear mechanisms.21 These FPHL can be associated with hyperandrogenic findings led to the development of a screening test states. with higher evidence about the role of androgens comes from levels of inflammatory markers. have been implicated in the increase of FPHL after ital adrenal hyperplasia. The hair follicle is sulin resistance has been associated with low sensitive to alterations in circulating estrogen and circulating levels of SHBG and early onset of AGA androgen levels. Func- may lie in variations of the AR gene. preparations are used to treat FPHL in some coun- tries.17 Patients with FPHL show higher thesized and metabolized locally. and D-dimer. Androgens have a clearly protein. and acne. these hormones are also syn. the speculated FPHL genetic link DHT synthesis and arrest hair loss in men. tors are used in cancer therapy. A referral to an endocri. because the efforts presence of estrogens.7 Many women with FPHL have low levels women. In controls.14 Conversely.22 to treatment with 5a reductase inhibitors is unpre- dictable. Pattern hair loss has been function. male pattern hair loss. such as C-reactive studies of male AGA.10 AR gene contains a region of CAG repeats. and acne in women. microvascular in- Androgens and estrogens are the main hormonal sufficiency. Particular CAG variants in the AR gene are described in cases with complete androgen insen- implicated with a risk of developing AGA in men. DHT has a 5-fold higher affinity Studies on the genetic base of FPHL show increased for the AR and is believed to be the more important frequency of alopecia in both male (54%) and female player in AGA. can be used to block ence from AGA.20 The number of been clearly established and it does not seem to be CAG repeats inversely correlates with androgen as essential as in AGA. the response of patients. The treatments for . Short repeat lengths been postulated that there is an increased periph- (15 or less) correlate with types of FPHL in 97. suggesting that mechanisms Variations in the CAG length have been associated other than androgens may be involved. fi- (21%) first-degree relatives.10 sitivity syndromes. the Hair Genetic Test (http:// differ between patients with FPHL and normal hairdx. and inflammatory abnormalities.13 High systemic estrogen levels in pregnancy than single products (Fig.18 Increased sy- established role via binding of dihydrotestosterone stolic blood pressures are found in patients with (DHT) to hair follicle androgen receptors (AR) in FPHL in comparison to control individuals.

62. twice daily to scalp vasodilatory. light therapy.25–0. and daily in divided doses competitive AR blocker Cyproterone acetate Antiandrogen. Spironolactone and cyproterone acetate are the vided into 2 classes: the classic androgen receptor most commonly used oral antiandrogens in the Table 1 Treatments for FPHL Pregnancy Product Mechanism of Action Treatment Recommendations Category Spironolactone Antiandrogen. and the peripheral important adjuvant role for nutritional supple. and biotin/zinc supplement after 14 months. hair follicle. possible 2%–5% topical application once or C antiandrogenic. by mouth daily generally prescribed decreases testosterone together with an oral contraceptive. levels by suppressing or cyproterone acetate 25–50 mg/d luteinizing hormone on days 1–10 of menstrual cycle and follicle-stimulating hormone Flutamide Antiandrogen. spironolactone. (A) A 41-year-old patient with FPHL at initial visit. FPHL can be divided into androgen-dependent antagonists. There is an from binding to their receptors. Androgen receptor antagonists Antiandrogen Therapies Spironolactone The antiandrogenic agents used in FPHL can be di. 2 mg cyproterone acetate X competitive AR blocker. 1. which alter androgen levels at the ments. and hair transplants.2–5 mg by mouth once daily X Dutasteride 5-a reductase inhibitors 0. (B) Improvement with a combination therapy for minox- idil. antiandrogens. ketoconazole shampoo. Leave on for 5 min and then rinse . and antiinflammatory effects Ketoconazole Decreases DHT levels at Shampoo scalp every other day as C the hair follicle tolerated.5 mg–250 mg by mouth once daily D competitive AR blocker Finasteride 5-a reductase inhibitor 0. reduces 100–200 mg by mouth D testosterone levels.5 mg by mouth daily X Minoxidil Unknown. which prevent testosterone and DHT and androgen-independent (Table 1). Female Pattern Hair Loss Update 121 Fig.

finaster- warrants monitoring of potassium levels. with high local effi.5 mg/d) are low and well FPHL in postmenopausal women. women is limited because they are contraindicated which tend to improve after 3 months of therapy. in women of childbearing age. nausea. women. It can androgen to its receptor. It is absolutely contraindi. which over placebo.24 Spirono.122 Atanaskova Mesinkovska & Bergfeld treatment of FPHL. ideally for at terone to DHT. acne. AGA. whereas the efficacy in patients with with FPHL. by the advent of the 5-a reductase inhibitors. alone or in combination with ethinyl FPHL cannot be predicted with certainty. it seems to be efficacious when used in higher doses (5 mg) or in combination with drospir- Cyproterone acetate enone and ethinyl estradiol OCP. Dutasteride is a 5-a reductase inhibitor with supe- drogen that competitively blocks the binding of rior antiandrogenic effects to finasteride. This compound is highly hydrophobic. The effects of these agents are hair loss and increased hair diameter in an open clin- comparable.28 Its use is limited because of teride is not currently approved by the FDA for the risk of severe liver toxicity. Liver function needs to be moni- Fluridil tored in all patients.37 Finasteride is metabolized in the liver. a structural antagonist of and Drug Administration (FDA) in the United States. rope.23 Spironolactone is a potas. It acts as an antiandrogenic by 5-a reductase inhibitors reducing the levels of total testosterone and com- petitively blocking the androgen receptor in target The treatment of male AGA has been revolutionized tissues.25 This medica. These ciated with PCOS.39 This medica- tolerated. It is commonly used to treat hirsutism asso.25 Treatment with teride is correlated with shorter CAG repeats of the cyproterone can improve hair growth in patients AR gene. Fluridil is a novel topical antiandrogen. with 44% of patients with FPHL expe. fluridil 2% solution prevented progression of have shown that fulvestrant can increase hair . of a male fetus. dutasteride can stop women.5 mg/d) has led to resolution of efficacious in FPHL (62.33 In normoandrogenic success. In postmenopausal women.32 In premenopausal women. a 1-year course of finasteride 1 mg daily failed to improve hair loss lactone can be associated with hyperkalemia. aldosterone. Finasteride has not Low-dose oral contraceptive pills (OCP) can be shown the same efficacy in FPHL as seen in male added to help reduce the menorrhagia. Dutas- stability in FPHL. enzyme.36 estradiol or spironolactone. decrease serum DHT levels by more than 90%. In men with AGA. Fulvestrant cacy and tolerance.780).31 Fluridil is being used throughout Eu- riencing regrowth. and should not handle tion is not available in the United States.05% have shown efficacy in treating patients with FPHL with a potential role in the treatment of male AGA and both increased and normal androgen levels. approved for use in Europe and Canada to treat and it should be used with caution in patients hirsutism. application of fluridil for 3 months (ICI 182. greater efficacy of finas- stimulating hormone release.28 It is an effective treat. Spironolactone is pregnancy category D.29 Flutamide can improve hair growth after the progression of hair loss and increase scalp only 6 months of treatment. crushed or broken pills. It can cause with liver abnormalities. The doses that have been shown tasteride (0. The off.25 Commonly described transient and halt progression of hair loss. The pure estrogen receptor antagonist.34.24 It has been used to treat FPHL agents work by inhibiting the conversion of testos- off-label in doses of 50 to 200 mg daily. Flutamide Dutasteride Flutamide is a potent orally administered antian. and it is best used in gory X medication. and offers long-term hair growth in a dose-dependent fashion. and female alopecia. fulvestrant In men with AGA.30 In estrogen-sensitive breast cancer. ical study.25–0.38 ment of hirsutism and FPHL in hyperandrogenic In male patients with AGA.29 tion should not be administered to women of reproductive age. and menorrhagia.label use of du- dose-dependent.27 It is FPHL. use strict birth control. but is still awaiting approval from the Food sium-sparing diuretic.32 It is a pregnancy cate- feminization of the male fetus.35 The specific Cyproterone acetate is an oral antiandrogen that can subset of women who respond well to finasteride directly block AR and decrease testosterone levels may have excessive activity of the 5-a reductase by suppressing luteinizing hormone and follicle. Women of childbearing age should cated in patients with liver disease. and result in increased hair growth least 6 months. Their use in side effects are lethargy. associated with feminization combination with an OCP. was developed as a treatment of resulted in increased anagen to telogen rates. but systemically nonresorbable. In vitro studies FPHL. which seems to be the treatment of hair loss.26 Cyproterone has Topical preparations of finasteride 0. Topical spironolactone 2% solution exists and has been ide has shown benefit in treating FPHL associated used in combination with minoxidil with variable with hyperandrogenism.

which proposed enhanced vasodilatory. powders. In this scenario. including The efficacy of minoxidil in pattern hair loss has thinning of the occipital area. scale. with varied can benefit from the antiandrogenic mechanism success. and antiinflammatory effects. The medical side effects of hair- Ketoconazole pieces are limited to irritant dermatitis and traction Ketoconazole is an antifungal used in the treat. This trend has alle- associated side effects are facial hypertrychosis. Special attention should be used when ment of seborrheic dermatitis. Ketoconazole also affects steroido. with higher concentrations (5%) In recent years.51 Par- Adjunctive Therapies adoxic increase in hair growth has been observed Hair transplantation with the use of 810-nm pulsed laser and intense Hair transplant surgery is emerging as an important pulsed light intended for hair removal. or hair growth. hair extensions and wigs have potentially more effective. pins) to nazole shampoo.26 is more diffuse thinning of the scalp. When used in It was originally produced as an oral hypertensive hair transplant procedures. The most frequently for improving hair appearance. The hair transplant not yet known. CA). into individual hair follicles. hair growth is unclear.42. there antiandrogenic. where shown to be superior over control vehicle in the hair grows over the next 3 to 6 months. the hair grafts may agent. become widely accepted among women as tools established safety profile. use in FPHL. by stimulating telogen hair follicles procedure is an outpatient procedure performed to re-enter anagen.46 It should be part of the treatment sufficient density. choosing attachment methods (eg.50 solution or foam. addition.45 The mechanism by which it can improve traction damage. which limits the been proved in double-blind. results in increased hair growth in attached hair needs to be minimized to prevent FPHL. and vitronectin current standard of treatment of hair loss in women. regimen in women with FPHL who have accompa- Light therapy nying inflammatory seborrheic dermatitis or se- A variety of laser and light sources have been bopsoriasis. especially in combination with minimize damage to the scalp. In FPHL. Hyperandrogenic women with FPHL tried for treatment of hair loss. The use of ketoco. It has antiinflammatory Camouflage of frontal hair loss in FPHL with hair- properties.49 The growth factors and plasma compo- Minoxidil is a hair growth stimulator that is the nents such as fibrin. under local anesthesia.48 treatment of FPHL. may help increase the usefulness of ability to maintain and thicken preexisting hair. is typically found in men with AGA.48 The newer techniques of har- trials.40 Topical formulation of fulves. viated some of the stigma associated with their contact dermatitis. Minoxidil has a significant Jose. glue. Its mecha- Hair transplantation requires preservation of nisms of action remain unknown. placebo-controlled usefulness of hair. especially the prolongs the anagen stage of the hair cycle and robotic-assisted ones (Restoration Robotics. it is hypothesized that the light .44 Minoxidil has a well. and it reduces colonization of the skin pieces may create a challenge. San increases hair follicle size. In human studies. or genesis locally and it decreases DHT levels at the keratin fibers may be a better alternative to achieve hair follicle. can increase hair follicle growth.43 There is also evidence that minoxidil vesting follicular extraction units. In hair transplants in women. The transplanted hair topical fulvestrant preparations have not been follicles are then placed in recipient sites. fibronectin. use of camouflaging topical sprays. Female Pattern Hair Loss Update 123 growth in mice. in 2% or 5% strength. now available as placement of grafts. proliferative. The weight of the finasteride. This serendipitous discovery led to the PRP can be injected directly into the scalp before production of topical formulations. with a peculiar side effect of increased scalp be stored in PRP until placed on the scalp. The efficacy Androgen-Independent of adjuvant plasma and platelet growth factors has been well described in wound healing pro- Minoxidil cesses.52 The option for patients with FPHL who do not have mechanism of low-level lasers on hair growth is success with medical therapies. and include hair growth over the occipital donor area. pruritus. The idea to use laser light therapy stems of ketoconazole. patients with FPHL treated with minoxidil 2% have 10% to 16% more regrowth compared Camouflage with controls. and dryness.47 from experimental observations that low-powered ruby laser can increase hair growth in mice. the by Malassezia. in which classically har- trant was subsequently developed to be used as vested strips from the occipital area are divided a potential treatment of AGA. alopecia.41 A new trend in hair transplants is the adjuvant use of platelet-rich plasma (PRP).

deficiency nutritional or Supplement 8–15 mg by mouth daily iatrogenic causes alopecia66 (>18 years old) Zinc pyrithium shampoo Zinc ions have antiinflammatory and 1% pyrithione zinc shampoo daily antioxidant effects. 300 g by mouth 5 times per day blocks binding of DHT to AR61 (1500 mg/d) Not FDA approved for hair loss Ferritin Unclear.54 It is designed to be Innovative treatments for FPHL are in high used 3 times per week for 15-minute sessions.55 of different prostaglandin analogues and higher In addition to low-level lasers. ineffective in a patient with FPHL.53 potential use of lasers for the treatment of alopecia. LLC. patients with alopecia. no evidence that oral supplementation helps65 Zinc Unclear. stimulates cyclic adenosine potential increase in hair tensile monophosphate. men treated with the laser comb had may present a new option.69 The botulinum injections effects were immediate postprocedural erythema reduced hair loss significantly.68 The efficacy ance for use in women with FPHL in 2011. the current evidence supports the production of adenosine triphosphate.63 >40 ng/mL. blind study. Table 2 Adjuvant treatments of FPHL Product Mechanism of Action Treatment Recommendations Biotin Regulates mitochondrial No clinical trials showing efficacy carboxylase enzymes in hair treating hair loss58 roots57 Caffeine Inhibits phosphodiasterase. FL) is a handheld. a peripheral antiandrogen. Boca Raton. demand. topical applica- compared with the control group at 26 weeks. The Botulinum toxins have been introduced for fractional erbium-glass 1550-nm laser was used treatment of hair loss with some success. Botulinum toxin may stop anism of laser treatment in improving hair growth hair loss by improving blood flow to the hair follicle. male patients with AGA received with this laser. Supplement women with anemia and vegetarians Melatonin Antiandrogenic effects at the hair 1 mg topical compounded in alcohol follicle64 and glycerin.56 After 10 treatments open-label study. and in some men. high-energy lasers concentrations need to be studied in FPHL. In a double. Several products using low-energy laser light beams are available without a prescription for the Adjuvant therapies treatment of alopecia. A trial of injected bimatoprost solution was events. are being explored for treatment of hair loss. the scalp.54 The HairMax LaserComb received clear. Associated side surrounding the scalp. successfully used to treat eyelash hypotrichosis.124 Atanaskova Mesinkovska & Bergfeld enhances mitochondrial respiratory activity and is not clear.001). They are designed as a hair. The HairMax LaserComb (Lexington International. Although the mech. In an successfully to treat FPHL. Caffeine lotion and shampoo.15 and inhibit use results in significant (P<. FUTURE DIRECTIONS noninvasive device that was approved by the FDA for treatment of male AGA. which are with noted results in 8 to 16 weeks. There are high expec- a significantly greater increase in hair density and tations for the use of topical prostaglandin in better subjective assessments of hair growth. lack of ferritin causes hair Maintain serum ferritin level follicles to enter telogen62. However. and pruritus in some patients. Common topical and nutritional supplements are brush or comb. hair density and fiber thickness 150 units of botulinum toxin into the muscles markedly increased (P<.05) 5-a reductase in vitro67 net increase in total visible hair counts67 . which shines red light directly on listed in Table 2. tions of prostaglandins have not proved effica- No individual experienced any serious adverse cious. increased hair growth. counteracts strength and numbers60 testosterone effects on hair follicles59 Cimetidine H2 blocker. The prostaglandin analogues.

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