Understanding androgenetic alopecia

Abstract

Androgenetic alopecia is the most common type of alopecia in both women and men. Although there are clear clinical differences between its male and female patterns, there are physiopathogenic peculiarities in each gender. Changes in the hair cycle, with the shortening of the anagen phase, is responsible for the miniaturization process, transforming the terminal hair in a vellus hair. Treatment objectives are to increase the coverage of the scalp and to delay the progression of hair loss. In a didactic manner, this study goes over androgenetic alopecia’s physiopathogeny, clinical manifestations and therapeutic responses.

Keywords: ALOPECIA, ANDROGENS, FINASTERIDE, SPIRONOLACTONE, HAIR FOLLICLE

INTRODUCTION

According to the latest survey carried out by the Brazilian Society of Dermatology, complaints about alopecia are among the ten most frequent in dermatologic practices in patients aged 15-39. 1 Androgenetic alopecia (AGA) is the most common cause of alopecia in both genders. 2 It is characterized by chan- ges in the hair cycle that lead to progressive follicular miniatu- rization, with the conversion of terminal hair into vellus, which becomes thinner, shorter and less pigmented. 3, 4

AGA affects both genders; more than 50% of men over 50 years of age present some degree of baldness. 5 Estimates regar- ding women vary, with incidence peaking after the age of 50 and an incidence of approximately 30% around the age of 70. 6 Epidemiological data are diverse for different ethnic groups, with reports of a lower prevalence in individuals of Asian and African descent compared to Caucasians. 7

In men, the process is androgen dependent. In women, however, the hormone interference is uncertain, and the term female pattern alopecia (FPA) seems to better define the condi- tion. Despite the high frequency of FPA in medical practices, it still poses diagnostic and therapeutic challenges to dermatolo- gists.

This study reviews key aspects of understanding AGA, based on data compiled from articles retrieved from the Pubmed database.

CLINICAL FEATURES

Male AGA often begins after puberty with symmetrical bitemporal recession that progressively affects the vertex. Development is variable, and in general the earlier the process begins, the more exuberant it is. Early signs of baldness can be seen in up to 14% of boys between 15 and 17 years old. 8 In up to 5% of men, baldness assumes a more diffuse distribution, resembling the pattern occurring in women; this pattern is more common in Asians. 2

The female pattern usually occurs during the patients'''''''' 30s and 40s, with progressive worsening after menopause. The condi- tion is characterized by the diffuse thinning of hair, with the hair- line preserved. Figure 1 shows the widening of the central part. In the early stages, hair loss can be followed by a reduction in the central scalp''''''''s hair density. 6 Eighty-eight percent of women with FPA report negative effects on their lives due to hair loss; 75% have low self-esteem, and 50% report social problems. 9

The clinical changes that occur during the progression of male baldness were classified by Hamilton in 1951 and modified by Norwood in 1975 (Figure 2). In 1977, Ludwig proposed a diverse classification for the female pattern of baldness, and in 1996 the Savin scale was created, which also aimed to recogni- ze and classify the various degrees of female alopecia (Figure 3). More recently, the universal Basic and Specific Classification, which is applicable to both genders, was developed. The various classification scales are useful for patients'''''''' standardized follow- up documentation. 5,10-12

In women, in addition to evaluating the alopecia, it is important to check for possible signs of hyperandrogenism, such as acne, menstrual irregularity, infertility, hirsutism, seborrhoea, and acanthosis nigricans. 13,14

An association between AGA, metabolic syndrome and cardiovascular risk factors has been found in some groups asses- sed.15 Artery hypertension was observed more frequently in men with AGA that have increased concentrations of aldostero- ne, suggesting a possible correlation between these two condi- tions. 16 Additional research is necessary to confirm such fin- dings.

PHYSIOPATHOGENESIS

The hairs'''''''' cycle
Hair follicles evolve through three main developmental stages: proliferation (anagen phase), involution (catagen phase) and rest (telogen phase); regeneration takes place in successive cycles. In a normal scalp, the anagen phase lasts two to seven years, the catagen phase around two weeks, and the telogen phase roughly three months.

Serial assessments conducted using phototrichogram tests showed a delay between hair loss and the replacement of a new shaft. When the follicle is empty, this phase of real rest is called kenogen. Its identification was instrumental in understanding the follicular dynamics of AGA. 17, 18 Follicular growth occurs in a mosaic pattern on the scalp. Each follicle contains a single con- trol mechanism that is regulated by a number of substances, such as hormones, cytokines, and growth factors, and environmental influences including nutritional deficiencies and ultraviolet radiation. The mechanisms that control the hair cycle are loca- ted in the own follicle, and are a result of the interaction of regulatory molecules and their receptors. Evidence suggests that the dermal papilla and its fibroblasts influence follicular growth – especially in the proliferation of cells and in the differentiation of the hair follicle matrix. 19

With varying etiologies, hair loss is a hair follicle cycle disorder. In AGA, the anagen phase ends prematurely due to a reduction in the expression of stimulating factors and an increa- se in cytokines that promote apoptosis. 3 In addition, there is an increase in the number of follicles in the resting kenogen phase. 18 In AGA, in addition to alterations in the follicular cycle, the hair terminals are miniaturized into vellus. 20 These changes occur in both men and women.

THE ROLE OF ANDROGENS

In men
Male AGA was recognized as an androgen-dependent disorder in 1940, when it was noticed that eunuchs did not develop the condition, despite a decrease in the number of their body hairs. 21 This fact proved that androgens influence the growth of body hair in a reverse manner to hair growth on the scalp. 4,20

The primary target of the androgens'''''''' action in hair follicles is probably the dermal papilla, through a connection to specific receptors.22 The androgens present varying affinities to these receptors. Dihydroepiandrosterone (DHEA), in spite of its low affinity, can be transformed into strong androgens, such as tes- tosterone and dihydrotestosterone (DHT). 23

Testosterone is the most potent circulating androgen, with higher concentrations in men. Only a small fraction of testoste- rone circulates freely (70% is connected to sex hormone binding globulin (SHBG), the levels of which inversely correla- te with the severity of alopecia). 3, 24 Nonetheless, DHT – a tes- tosterone metabolite – causes the miniaturization of follicles and the development of AGA. DHT is also involved in the pathoge- nesis of benign prostatic hyperplasia, prostate cancer, hirsutism and acne vulgaris. 3,22,25 Its affinity for androgen receptors is five times greater than that of testosterone. The 5 -reductase is the enzyme responsible for converting testosterone into DHT. Patients who are homozygous for the 5 -reductase''''''''s gene muta- tion with inactive enzymes present incomplete male pseudoher- maphroditism with ambiguous genitalia and virilization only after puberty. Those individuals do not develop AGA, which proves that DHT is the main hormone in male AGA. 26

The skin and the pilosebaceous unit are enzymatically equipped to metabolize and convert sex steroids, converting weak androgens into stronger forms through the action of enzy- mes such as 5 -reductase (Types 1 and 2) and 3 -hydroxysteroid dehydrogenase (3 -HSD), among others. Strong androgens, such as testosterone and DHT, can be converted into weak androgens or estrogens by other enzymatic routes, including aromatase. Bald skin''''''''s sebaceous glands have presented higher 3 -HSD expression compared to non-bald areas, contributing to an increased formation of strong androgen in that region. 3, 25 The 5 -reductase enzyme, which is essential to the development of male AGA, is present in greater amounts and has increased acti- vity in the follicles of affected individuals. 26,27 In addition, there are greater amounts in frontal hair follicles compared to the occipital follicles of women and men with AGA. Higher levels of the aromatase enzyme in the occipital region (which is less affected in this type of alopecia) are associated with the persis- tence of the hair. Inherited or acquired aromatase deficiency (e.g., women using aromatase inhibitors to treat breast cancer) also results in an increase of circulating androgens and hair loss similar to that of AGA. 3

Although male AGA is a DHT-dependent process with the continuous miniaturization of androgen-sensitive hair follicles, most men with this condition have normal levels of circulating androgens. The overproduction of androgens in the piloseba- ceous unit, and the overexpression or hyper-responsiveness of androgen receptors can be responsible for this process. 28 Hamilton has demonstrated the castration before puberty, rather than the castration after puberty, as a protection against AGA. On the other hand, the administration of exogenous testostero- ne to patients who were castrated before puberty produced hair loss. The patients who did not develop baldness with this inter- vention had no family history of baldness, suggesting genetic influence. 20, 22 The absence of baldness in individuals with andro- gen insensitivity syndrome supports the role of the binding androgen/receptor in AGA. Nevertheless, FPA can occur in patients with that syndrome, suggesting that other mechanisms, in addition to hormonal action, contribute to this disorder. 29

IN WOMEN

Since the role of androgens in female AGA is unclear, some authors recommend avoiding the use of the term androgenetic for this type of alopecia. 19,22 FPA is associated with hyperandro- genemia in less than 40% of cases that do not have correlation to the distribution pattern (central or bitemporal).13 Currently, there are enough arguments for considering male and female AGA as different clinical entities. Finasteride, a selective inhibi- tor of 5 -reductase 2, is effective in men but has failed to pre- vent the progression of hair loss in normoandrogenic postme- nopausal women with FPA. 30 Likewise, the blocking of andro- gen receptors using Cyproterone acetate is not very effective in preventing the progression of hair loss in normoandrogenic pos- tmenopausal women. 31

In the majority of women with FPA, there is no increase in the levels of circulating androgens. Nevertheless, their recep- tors and their 5 -reductase levels are increased in the frontal region (less than in male AGA), and their enzyme levels of the cytochrome P450 (such as aromatase, which is responsible for converting testosterone into estrogen) are higher in the occipi- tal area and hairline of women (more than in male AGA). 14

Regardless of the etiology, follicular alterations seem to be similar among men and women, with a common route to folli- cular miniaturization. Although the histopathological alteration is indistinguishable between genders, and there is a difference in the areas that are more intensely affected, there are indications that more hairs are miniaturized in men than in women.32

INFLUENCE OF GENETICS

Hereditary factors that contribute to individual susceptibi- lity to AGA are still poorly understood, however there is suffi- cient evidence to confirm the involvement of genes. Family his- tory is usually a factor in cases of male AGA, but less frequently in women. 22 Evidence currently points towards a polygenic inheritance pattern. Genes such as the EDA2R, the ERb and that of the polycystic ovary syndrome have been associated with early AGA in men. 33 The most important evidence of gene influence was related to the genetic sequencing of the androgen receptor gene – known as the AR gene (androgen receptor) – in bald and non-bald men. Located in the X chromosome and belonging to the nuclear transcription factors family, the AR gene''''''''s amino-terminal domain contains the region encoded by the CAG repeats, which is involved in the activation of genetic transcription. 34 An inverse relationship between the length of the CAG repeats and AR activity was observed in the studied groups, meaning that a small number of repetitions are correla- ted to increased AR gene activity and a greater probability of baldness. Two other polymorphisms in that gene are associated with a predisposition to alopecia: the length of the GCC sequence and the presence of a STUL restriction fragment.

These findings about the AR gene do not explain the simi- larity between bald fathers and sons, given that sons inherit the X chromosome from their mothers, proving that the role of maternal inheritance in AGA is still unclear. 35

RESEARCH METHODS

There is no gold standard examination for the diagnosis of AGA. In addition to a physical exam that focuses on the pattern and degree of alopecia, it is critical to carry out a thorough the patient history. It is necessary to ask patients about possible fac- tors that might have triggered the process, such as variations in weight, steroid use, eating habits, use of chemical products, medications, family history and comorbidities. Additional met- hods include dermoscopy, trichogram and biopsy.

AGA''''''''s main differential diagnosis is telogen effluvium, par- ticularly its chronic form, which has long been considered a confounding factor. Initially, chronic telogen effluvium (CTE) was considered a possible prodrome of AGA. A 10-year follow- up in CTE patients demonstrated no signs of development of AGA. Based on a computerized analysis, the same study suggests a shortening of the anagen phase without miniaturization as the cause of CTE. 36 While the thinning of hair on the scalp is dif- fused with telogen effluvium, it occurs in a central pattern in AGA. Nonetheless, AGA patients can present typical acute telo- gen effluvium, making a clinical evaluation difficult. 23

LABORATORY

The serum dosage of thyroid-stimulating hormone, iron and ferritin are useful, since alterations may contribute to efflu- vium associated with AGA. The dosage of ferritin is the test that best reflects the bone marrow aspirate for the evaluation of iron reserves, and its value should exceed 60 ng/dl. 37 Tests such as iron''''''''s total capacity of binding and the saturation index seem to be less important. The evaluation of ferritin has always been controversial, for although reference values above 10 ng/dl are considered normal from a laboratory perspective, there no improvement was observed in cases of telogen effluvium treated with iron supplementation at levels of up to 20 ng/dl. 38 It is important to note that ferritin is an acute phase protein, which is subject to change in various ways due to inflammatory and infectious processes. In such cases, it is necessary to analyze the erythrocyte sedimentation rate. Ferritin levels below 40 ng/dl were observed in 72% of women with FPA. 39

In women with clinical manifestations of hyperandroge- nism, it is important to separately request the dosage of hormo- ne levels, which is part of the investigation. 22 Each androgen producer compartment can be evaluated by a specific serum marker. The dosage of total testosterone and dehydroepiandros- terone sulfate (DHEA-S) levels are sufficient in the early stage of investigation. Analysis of the total testosterone level is useful to exclude ovarian and adrenal neoplasms, for they may be noti- ceably elevated compared to the values presented by other cau- ses of hyperandrogenism. The DHEA-S dosage is used in the assessment of the adrenal gland; which is high in congenital adrenal hyperplasia, Cushing''''''''s syndrome, chronic hyperprolacti- nemia, and tumors. DHEA levels and androstenedione also play a role in the diagnostic algorithm of congenital adrenal hyper- plasia. The best marker for evaluating peripheral androgen pro- duction is the 3 -androstenediol glucuronide, which is high in hyperandrogenic women with alopecia. Nonetheless, its clinical evaluation poses technical difficulties and it is not available in the daily clinical routine. 14

GENETIC TEST

Genetic tests are carried out through the evaluation of a smear from the patient''''''''s oral mucosa, and can identify people at risk of developing AGA before the disease manifests clinically. Since there are differences in the condition''''''''s pathogenesis bet- ween genders, the test is different in men and women. In men, the test evaluates eight AR gene variants, focusing on the locus STUL (which is responsible for alterations in hair follicles influenced by DHT). An individual testing positive for this variant has a 70% chance of developing AGA, while a negative test means a 70% chance of not developing it. In women, the test assesses the length of CAG and GGC sequences in the AR gene. Sequences with 15 or fewer CAG repeats are correlated to a 97.3% chance of developing FPA. 34

HISTOPATHOLOGY

A scalp biopsy is recommended in cases of diagnostic uncertainty. It must be carried out in an area that is representa- tive of the hair loss, avoiding the bitemporal region, where there may be miniaturization independent of AGA. 22 The use of cross- sections allows the visualization of the hair follicles'''''''' density. The key alteration observed in histopathology is the miniaturization, with the transformation of terminal hair into vellus. A ratio ter- minal hair/vellus less than or equal to 3:1 indicates AGA (the normal ratio is 7:1). An increase in the number of telogen folli- cles, a decrease in the number of follicles in the subcutaneous fat, an increase in the volume of sebaceous glands, a variation in the diameter of the shaft, and an increase in the number of fibrous bands can also be observed in AGA cases. 40

The perifollicular inflammatory process can be observed, and miniaturization is often associated with a perifollicular lymphocytic infiltrate and possible fibrosis, which may suggest an inflammatory pathogenesis, which is still seldom considered in AGA. 3, 22 Microbial colonization of the follicular infundibu- lum, bacterial toxins or exposure of follicle antigens may explain the inflammation.

Biopsies in clinically evident FPA confirm 97% of diagno- ses, and seem to be unnecessary in such cases. In cases that are initially clinically uncertain, histopathologic criteria are able to confirm AGA in 60% of cases, suggesting the importance of the procedure in such cases. Taking more samples can assist in the diagnosis: when three biopsies are taken, the undetermined cases drop from 23% to 2%, without any drawback for the patient. 41

DERMOSCOPY

Dermoscopy is a quick and non-invasive examination that provides important data for diagnosis. The main alteration obser- ved is changes in hair diameter, which correspond to the minia- turization of the strands. Normal individuals, and those with CTE, usually have thicker strands in the scalp''''''''s frontal region and thinner strands in the occipital region. This pattern is reversed in AGA, with the advance of the miniaturization. Another impor- tant finding is a decrease in the number of strands per follicular unit. Healthy individuals usually have two or four hairs growing out of each follicular orifice – which is not seen in AGA, where pilosebaceous units contain one to two hairs. The peripilar sign (a brownish hyperpigmentation around the follicle) and yellow dots (empty follicular ostia filled with sebum) are also seen more frequently in AGA. Areas with exposure to the sun may have a pigmented network in a "honeycomb" pattern in addition to melanoses and other signs of photodamage. 42, 43

TREATMENT

AGA treatment objectives are to increase the scalp''''''''s cove- rage and slow the progression of hair loss. The standardized pho- tographic documentation from the beginning of treatment through the follow-up period allows more appropriate treat- ment decisions by both the physician and the patient.

General measures, such as the exclusion of medications that can cause ET, a balanced diet with an adequate intake of protein and iron, and the treatment of other scalp disorders such as seborrheic dermatitis, are important for successful therapy. Weight control in obese patients reduces the peripheral conver- sion of androgens, decreases their intolerance to glucose, increa- ses SHBG and reduces the free testosterone, improving their hormonal profile. 44

Pharmacological measures differ between men and women. Two drugs stood out for presenting more evidence of effectiveness: oral finasteride and topical minoxidil. Both requi- re chronic use for satisfactory results, and neither can restore hair loss completely. 3 22

MINOXIDIL

Minoxidil is a vasodilator that was first used to treat syste- mic arterial hypertension. Its action mechanism in AGA is unclear, however it increases the anagen phase''''''''s duration, con- tributing to an increase in hair density. The peak effect is noti- ced after around 16 weeks of use, and six months after discon- tinuing, any improvements are lost. 22 It is recommended in con- centrations of 5% for men and 2-5% for women. Notwithstanding the increased occurrence of pruritus, local irritation, and hypertrichosis that can be observed with 5% minoxidil, better results are obtained with this dose. 45 Topical minoxidil is the drug of choice in premenopausal and nor- moandrogenic women. 44

FINASTERIDE

Finasteride is the inhibitor of 5 -reductase type 2, reducing the conversion of testosterone into DHT by two thirds. It has been available in Brazil since 1990.27 Finasteride does not redu- ce the physiological effects of testosterone, but rather only decreases the DHT concentration. 25 Its efficacy in male AGA has been proven by extensive studies, including randomized and placebo-controlled studies, which have demonstrated improve- ment in the appearance of both the vertex and frontal regions with a 1 mg/day dose. 20,46 At the one-year evaluation of a group of men treated with 1 mg/day finasteride, an increase in the number of strands was observed in 80% of cases. 47 Initially there is an increase in the follicle count that peaks at 12 months, sub- sequently presenting an increase in the strands'''''''' thickness. The effects are lost 12 months after discontinuing use. 46 The prostate specific antigen must be adjusted when used to screen for pros- tate cancer in patients taking 5 mg/day finasteride for the treat- ment of benign prostatic hyperplasia, once the concentration of this parameter is reduced by the medication. It is recommended that the dose is doubled in such cases. Data on this adjustment need to be confirmed when using smaller doses. 48

Finasteride''''''''s sexual side effects (decreased libido, erectile dysfunction and decreased ejaculate volume) were observed in 4.3% of men aged 18-41 (versus 2.2% in the placebo group, p < 0.05). These effects often disappear during treatment or after discontinuation. 46 Alterations in spermatogenesis and fertility were not verified. 49

There is still no consensus on the use of finasteride in FPA. In 137 postmenopausal women there was no improvement with a 1 mg/day dose. 30 In restricted studies with no placebo, larger doses (2.5-5 mg/day), combined or not with oral contracepti- ves, showed varying results. 50 This medication may appeal to patients with postmenopausal FPA, since other types of anti- androgens can increase bone loss and the risk of cancer. The lack of other first-line treatment options justifies its occasional use.

DUTASTERIDE

Dutasteride is a non-selective inhibitor of 5 -reductase that is capable of inhibiting type 1 and 2 isoenzymes and provides greater reduction in DHT levels compared to finasteride. This option is rarely studied, and its practical clinical superiority has not yet been proven. In addition, side effects can be more inten- se due to its lower specifity. 20,51

FLUTAMIDE

Flutamide is a non-steroidal anti-androgen. It was initially used to treat prostate cancer, and had demonstrated effects on hair growth. Due to its severe hepatic side effects when admi- nistered systemically, its use was forbidden for alopecia by the Brazilian National Health Surveillance Agency in 2008. Other administration routes (topical or intradermal) present systemic effects in guinea pigs, with a decrease in the prostatic volume. 52

Bicalutamide and nilutamide acted as blockers of selective androgen receptors in a study on the treatment of prostate can- cer, and may be a future option in the topical treatment of AGA, with a lower risk of adverse reactions. 53

SPIRONOLACTONE

Spironolactone is an aldosterone inhibitor that works by blocking the androgen receptor and inhibiting androgen synt- hesis. Used to treat FPA in doses of 50-300 mg, 54 it slows the progression of hair loss and promotes the return of hair growth in women, and offers a good safety profile for long-term use. It can be used by itself or combined with minoxidil to enhance growth. This drug is not used in men due to the risk of femini- zation. Possible adverse effects are orthostatic hypotension, elec- trolyte imbalance (hyperkalemia), menstrual irregularities and fatigue.55 The adequate intake of fluids should be encouraged in order to mitigate side effects.

CYPROTERONE ACETATE

This is an anti-androgen, which by itself or combined with ethinyl estradiol can be useful in treating women with FPA and signs of hyperandrogenism, offering an efficacy similar to that of spironolactone. A daily dose of 50-100mg, for 10 days of the menstrual cycle, is recommended in premenopausal women. In postmenopausal women, the dose should be 50 mg/day, conti- nuously. Weight gain, fatigue, decreased libido, mastodynia, nau- sea, headache, depression, and hepatotoxicity can occur during use. Over 80% of women treated with oral anti-androgens (cyproterone and spironolactone) reported an improvement or stabilization of hair loss. 55

In patients in of childbearing age it is recommended that contraception is used due to the risk of menstrual irregularity and, in case of pregnancy, the feminization of male fetuses. Contraceptives promote the inhibition of gonadotropins and ovarian synthesis. The combination should be preferred, for estradiol increases SHBG (reducing the free testosterone) and the progestagens compete with androgen receptors. Some pro- gestagens, such as cyproterone acetate, drospirenone and chlor- madinone, have higher anti-androgenic action mechanisms (in descending order).

BOTANICAL DERIVATIVES AND -ESTRADIOL

Alpha-estradiol can reduce DHT formation and increase the conversion of testosterone into other, less active steroids. Compared to minoxidil during six months of use in women, alpha-estradiol led to the maintenance of the clinical pattern only, while with 2% minoxidil there was growth of new strands. 56

The botanical derivative inhibitor of 5 -reductase Serenoa repens was assessed in only one placebo-controlled study, wit- hout comparison to minoxidil. In this pilot study it showed benefits compared to the placebo. These options require further research to encourage their use. 57

VITAMIN SUPPLEMENTATION AND IRON REPLACEMENT

In general, vitamin replacement through supplements is not indicated in AGA. However, vitamin B12 and Biotin (B7) supplementation can be required in cases of chronic use of cyproterone acetate and ethinyl estradiol. A depletion of these vitamins without a known cause can occur with such treatments and cause apathy. ET can occur in patients with iron deficiency, and is generally reversible with supplementation. 44

OTHER ALTERNATIVES

Active principles delivered through shampoos have a low absorption in the scalp since they are quickly rinsed off, and generally do not present satisfactory results. However, ketocona- zole shampoo used in the treatment of AGA associated with seborrheic dermatitis seems to have an adjuvant effect when combined with options that have been proven effective. 58

Fluridil – a topical anti-androgen – looks promising for treating AGA. A double-blind placebo-controlled study in 43 men demonstrated an increase in the count of the anagen strands and a reduction in the number of telogen strands in the 23 individuals who applied the active principle for three months. No local or systemic side effects were observed in this sample. Further assessments are required – especially for use in FPA. 59

Metformin, isotretinoin, cimetidine and ketoconazole have anti-androgenic effects when used systemically, however no cli- nical results were demonstrated in AGA.

Regarding new pharmacological agents used in the mana- gement of hair loss, a study that was originally designed to test the power of topical thyroid mimetic agents in the treatment of obesity verified hair growth as a preliminary result. Those subs- tances have already been tested in vivo in mice and have a good safety profile. Nevertheless, no studies have been carried out in humans. 60

Finally, in addition to pharmacological measures, we can rely on the advent of hair transplants. Notwithstanding the disappointing aesthetic results from early versions of the techni- que, new methods have much better results and constitute an excellent tool when combined with clinical treatments.

CONCLUSION

AGA is a considerably common condition that affects both men and women. While the clinical picture is well established, its pathophysiology inspires investigations regarding genetic involve- ment, hormonal changes and, in particular, differences between male and female patterns. Explaining the condition''''''''s mechanisms and expectations regarding treatment to patients is key to obtai- ning adherence to the treatment regimen. While the first line of treatment in men is systemic finasteride and topical minoxidil, the therapeutic decision in women is variable: in premenopausal women the use of topical minoxidil, and possibly a hormone blocker, seems appropriate, since in post-menopausal women the treatment resembles that administered to men. Encouraging the study of these aspects and the pursuit of new knowledge is of fun- damental importance in the face of the high prevalence of this disorder and the psychosocial damage it causes.

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