Female pattern hair loss (androgenetic alopecia in females): Pathogenesis, clinical features, and diagnosis

INTRODUCTION — Female pattern hair loss (FPHL) is a common form of nonscarring hair loss that primarily occurs in adult females. The condition is characterized by the progressive loss of terminal hairs over the frontal and vertex regions of the scalp, resulting in a visible reduction in hair density (picture 1A-C). Unlike many cases of androgenetic alopecia in males (male pattern hair loss), the loss of terminal hairs in affected areas is usually incomplete, and the frontal hairline is often spared.

The pathogenesis, clinical manifestations, and diagnosis of FPHL will be reviewed here. Other forms of nonscarring hair loss and the treatment of FPHL are discussed separately. (See "Evaluation and diagnosis of hair loss" and "Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis" and "Alopecia areata: Clinical manifestations and diagnosis" and "Alopecia related to systemic cancer therapy" and "Telogen effluvium" and "Traction alopecia" and "Female pattern hair loss (androgenetic alopecia in females): Management".)

TERMINOLOGY — In the past, the term "androgenetic alopecia" was the primary term used to refer to the appearance of the common, progressive loss of terminal hair on the frontal scalp and/or vertex of the scalp regardless of the patient's sex. The term "andro" signified a hormonal etiology and "genetic" signified a contribution of heredity to the clinical phenotype.

Over the years, as more work on hair loss was published, "female pattern hair loss" became the preferred term for this form of hair loss in females. This newer terminology helps to distinguish the different clinical features of this process in females versus males and reflects the lack of evidence to support a hormonal contribution in all cases of the condition.

Further, some authors use the terms "androgen-dependent FPHL" and "androgen-independent FPHL" to separate patients with FPHL due to androgen excess from patients with FPHL and normal androgen levels [1]. The term "female pattern alopecia" has also been used in place of FPHL.

EPIDEMIOLOGY — FPHL is a common condition, although the prevalence may vary in different populations. Studies from the United States, England, and Australia have reported prevalences higher than studies from South Africa, China, South Korea, and Taiwan; however, limitations of the available data preclude definitive conclusions on the relative prevalence of FPHL in different populations [2-4]. Examples of studies reporting prevalence include:

●A community-based study in China that assessed 8446 women found FPHL in 6 percent [5].

●A South African study that assessed 597 Black women identified FPHL in 4 percent [3].

●A United States study that assessed 1006 White women found FPHL in 19 percent [6].

Although FPHL can occur at any time in life beginning in childhood, the condition most commonly occurs following menopause [7-9]. The age-related rise in FPHL was clearly demonstrated in the American series mentioned above; FPHL was detected in only 4 of 121 women between the ages of 20 and 29 (3 percent), but in 41 of 140 women between ages 70 and 89 (29 percent) [6]. In a British study of 377 women who presented to a general dermatology clinic with concerns unrelated to hair loss, 38 percent of women over the age of 70 years had FPHL [10].

ETIOLOGY AND PATHOGENESIS — The visible thinning of hair over the frontal scalp and vertex of the scalp in FPHL results from a progressive decrease in the ratio of terminal hairs to shorter, thinner vellus hairs in the affected areas, a process known as follicular miniaturization [11]. As part of this process, the duration of the anagen (growth) phase of hair follicles shortens from a normal duration of a few years to only weeks to months [12].

The mechanism through which follicular transformation occurs in FPHL is not completely understood. Although the crucial roles of androgens and genetic susceptibility in male androgenetic alopecia are well accepted, the degree to which these factors contribute to FPHL in most patients is less clear. (See "Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis", section on 'Pathogenesis'.)

Androgens — Male androgenetic alopecia occurs as a consequence of the effects of dihydrotestosterone (a potent metabolite of testosterone) on susceptible hair follicles. Dihydrotestosterone binds to androgen receptors in hair follicles, resulting in the upregulation of genes responsible for the gradual transformation of terminal hair follicles to miniaturized hair follicles. The pattern of the hair loss, which typically spares the occipital scalp, reflects regional differences in the sensitivity of scalp follicles to androgens (picture 2) [12]. (See "Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis", section on 'Androgens'.)

Some authors have theorized that a similar process contributes to the development of FPHL [13]. This concept is supported by the observation that female patients with disorders of hyperandrogenism (eg, polycystic ovarian syndrome, ovarian hyperthecosis, or adrenal or ovarian androgen-secreting tumors) may develop early-onset FPHL as a feature of these diseases [14]. However, androgen levels are normal in most patients with FPHL, indicating that our understanding of the pathogenesis of this disorder remains incomplete [14,15]. In a series of 109 women with moderate to severe FPHL, laboratory evidence for hyperandrogenism was present in only 39 percent [14].

Proposed theories on the mechanisms through which female patients with normal androgen levels could develop FPHL include increased sensitivity of hair follicles to androgens and an influence of estrogens on the development of this condition [12,16]. The age-related increase in FPHL, with the highest rates in postmenopausal females, suggests the possibility of a role for estrogen. However, studies have demonstrated conflicting evidence on whether estrogens stimulate or inhibit hair growth [12].

Genetics — While it is known that genetic susceptibility influences the development of male androgenetic alopecia, relatively little is known regarding the genetic basis and inheritance pattern of female pattern hair loss [12]. An Australian gene-wide association study of White women suggested that the aromatase gene (CYP19A1) may contribute to FPHL [17]. However, no definitive familial inheritance has been identified. Multiple genes may contribute to susceptibility to FPHL. (See "Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis", section on 'Genetics'.)

CLINICAL MANIFESTATIONS — FPHL is a nonscarring form of hair loss that presents as a progressive reduction in the density of terminal scalp hairs in a characteristic distribution (picture 1A-C). The frontal scalp and vertex of the scalp are the primary sites of involvement. Although diffuse involvement occasionally occurs, the occipital scalp is usually relatively spared.

The exact pattern of hair loss varies among patients with FPHL. In some patients, the frontal scalp thinning is most prominent, resulting in the visualization of a "Christmas tree-like" pattern when the hair is parted at the midline [18,19], whereas in others, diffuse central thinning is the most pronounced feature [20]. The frontal hairline is usually relatively spared, though patients frequently exhibit mild bitemporal thinning [13,21,22]. A combined pattern that resembles male androgenetic alopecia (frontotemporal recession and vertex loss) is infrequently seen [21].

Scarring, inflammation, and scale are not clinical features of FPHL. If these features are seen in a patient with hair loss, another scalp disorder may be present in conjunction with FPHL or may be solely responsible for the clinical findings. (See "Evaluation and diagnosis of hair loss".)

A variety of methods have been used to classify the clinical features of FPHL. The Ludwig scale is one of the most commonly used grading scales (figure 1) [20]. Other scales that have been used to describe the severity of FPHL include the Sinclair (picture 3) [11] and Savin [18] scales.

The FPHL Severity Index, a three-component severity scale, has been proposed as a method to facilitate earlier recognition of FPHL and to assess disease severity over time [23]. The FPHL Severity Index involves assessment of hair shedding, midline hair density, and trichoscopic findings. This scale has not been validated.

ASSOCIATED DISORDERS

Psychosocial dysfunction — Many patients with FPHL experience negative psychosocial effects related to the condition [24-26]. As an example, in a questionnaire-based study that included 96 women with FPHL and 56 female control subjects, 70 percent of the affected women reported that they were very upset to extremely upset about their hair loss [26]. Women with hair loss experienced more feelings of negative body image, poorer self-esteem, less of a sense of control over their lives, and had a less satisfying quality of life than the control group. A separate study in which 58 women were interviewed about the effects of FPHL on their quality of life also found that hair loss frequently was accompanied by negative psychosocial effects. In this study, 88 percent of women felt that the hair loss negatively influenced daily life [25].

Adolescent girls with FPHL may also experience psychosocial dysfunction. Girls with FPHL may suffer from poor self-esteem and impaired functioning at home, school, or work and in interpersonal relationships [27].

When managing patients with FPHL, clinicians should remain cognizant that the clinical assessment of the severity of FPHL may not be consistent with the patient's perception of the severity of hair loss and the psychosocial impact of the condition. In a questionnaire-based study of 104 women with FPHL, telogen effluvium, or alopecia areata, the patient perception of the severity of hair loss tended to be greater than the perception of the examining dermatologist [28]. In addition, the patients' severity ratings correlated more closely with the effects of hair loss on patient quality of life than the severity ratings given by the dermatologist.

Associated medical conditions — Certain medical disorders may be associated with FPHL. In addition to causes of hyperandrogenism (eg, ovarian or adrenal tumors, polycystic ovarian syndrome, adrenal hyperplasia), links between FPHL and insulin resistance, hypertension, and increased risk for death from diabetes or heart disease have been reported [29-31]. Further study is necessary to clarify whether the associations between FPHL and these conditions are valid. Of note, cardiovascular risk factors have been associated with androgenetic alopecia in men. (See "Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis", section on 'Cardiovascular disease and metabolic syndrome'.)

DIAGNOSIS — The diagnosis of female pattern hair loss is usually made clinically. Scalp biopsies are helpful aids for diagnosis when concomitant disorders of the scalp confound the clinical findings or the diagnosis is unclear. Laboratory tests to assess for hyperandrogenism are performed when clinical findings suggestive of hyperandrogenism are present.

Patient history — The patient history can provide clues to support or negate a diagnosis of FPHL and to identify an underlying hyperandrogenic state. We typically inquire about the following:

●Age of onset, duration, and rate of progression of hair loss

●Presence of signs of virilization (hirsutism, deepening of voice, clitoral enlargement)

●Gynecologic and obstetrical history (menstrual irregularities, difficulty conceiving)

●Presence of other medical disorders, significant changes in health status, medication list

●Use of hormonal or nutritional supplements that may contain androgens

●Family history of male and female hair loss

A rapid onset of diffuse hair loss may suggest acute telogen effluvium, particularly when the history suggests a change in health status (eg, serious illness, pregnancy, significant weight loss) or medication changes within the preceding several months. Of note, telogen effluvium may coexist with FPHL, and an episode of telogen effluvium may unmask underlying FPHL. The gynecologic history and assessment for signs of virilization help to identify patients for whom an evaluation for hyperandrogenism is indicated. (See 'Differential diagnosis' below.)

Patients with FPHL may first notice their hair loss as the progressive thinning of a ponytail or as increasing visibility of the scalp through the hair in the frontal and vertex areas of the scalp. These features are typically noted over the course of months to years. Although the onset and progression of FPHL is often insidious, occasional patients describe noticing specific episodes of increased hair loss prior to a noticeable change in terminal hair density. Patients may also complain of an increased propensity for sunburns on the scalp as hair coverage diminishes.

Physical examination — A full skin examination that includes evaluation of the scalp, face, body, and nails is advised in patients who present with a new complaint of hair loss. (See "Evaluation and diagnosis of hair loss", section on 'Physical examination'.)

The examination of the scalp and scalp hair should focus on identifying the distribution of hair loss and the caliber of hairs within the involved areas. Findings consistent with FPHL include the detection of terminal hair loss that is primarily localized to the frontal scalp and/or vertex of the scalp and miniaturized hairs (shorter and thinner hairs or vellus hairs). The use of a sheet of paper as a contrasting background can facilitate visualization of individual hairs.

Comparing the part width in the frontal or vertex scalp with the occipital scalp, which is usually relatively spared, provides a visual aid for the assessment of the reduction in hair density. Even in patients who develop diffuse hair loss from FPHL, hair thinning usually remains most prominent in the frontal and vertex areas [13,32].

The examination of the scalp should also focus on the detection of clinical features such as inflammation, scarring, or scale. The presence of these features strongly suggests that the hair loss is caused by a different disease or that FPHL coexists with another scalp disorder. (See "Evaluation and diagnosis of hair loss".)

The examination of other body sites may result in the identification of features useful for diagnosis and patient management. For example, patients with diffuse alopecia areata may have nail abnormalities and patchy hair loss on other body sites, findings that are not associated with FPHL. In addition, the presence of hirsutism, acne, and obesity suggest the possibility of a hyperandrogenic state related to polycystic ovarian syndrome or another hormonal abnormality. (See "Alopecia areata: Clinical manifestations and diagnosis", section on 'Clinical features' and "Clinical manifestations of polycystic ovary syndrome in adults".)

Hair pull tests, which can identify increased shedding of telogen hairs, may be positive in early hair loss on the central scalp, but are typically negative in patients with long-standing FPHL [21]. A positive hair pull test suggests the possibility of active telogen effluvium or alopecia areata. (See "Evaluation and diagnosis of hair loss", section on 'Hair pull test'.)

Dermoscopy — Dermoscopy of the scalp (also known as trichoscopy) may be useful for diagnosis [33,34]. Dermoscopic features of FPHL and male androgenetic alopecia include hair diameter diversity, perifollicular pigmentation/peripilar signs, and yellow dots [34]. Focal atrichia may also be present. (See "Overview of dermoscopy".)

Scalp biopsy — Although scalp biopsies usually are not needed to diagnose FPHL, biopsies can be helpful in cases in which the clinical evaluation does not provide a definitive diagnosis. Examples of scenarios in which a biopsy may be particularly useful include:

●Distinguishing FPHL from telogen effluvium or diffuse alopecia areata

●Distinguishing FPHL from scarring alopecia when the clinical differentiation between scarring and nonscarring alopecia is difficult

●Identifying coexisting scalp disorders

Scalp biopsies should be performed within an affected area and should extend into the subcutaneous fat. It is best to avoid the bitemporal area, since follicular miniaturization in this area is common in individuals without hair loss [7].

A 4 mm punch biopsy usually provides sufficient tissue for histologic examination. We typically perform two 4 mm punch biopsies so that one specimen can be processed with vertical sectioning and the other with horizontal sectioning [35-37]. Doing so allows the pathologist to examine the hair follicles in both longitudinal and cross-sections. Many dermatopathologists prefer to receive two specimens. (See "Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis", section on 'Histopathology'.)

The typical histopathologic features of FPHL are identical to those of male androgenetic alopecia. They include [7,38] (see "Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis", section on 'Histopathology'):

●Increased number of miniaturized hair follicles and reduced size of sebaceous glands

●Decreased anagen to telogen ratio

●Increased number of follicular stelae

●Perifollicular inflammation around the upper portion of the hair follicle with or without perifollicular fibrosis

Laboratory tests — Although no serologic tests provide a definitive diagnosis of FPHL, such tests are helpful for identifying an underlying hyperandrogenic state. Testing for hyperandrogenism is performed in female patients with FPHL when the clinical features suggestive of hyperandrogenism are present (eg, hirsutism, irregular menses, moderate to severe acne, treatment-refractory adult acne, acanthosis nigricans, or galactorrhea). We typically obtain a free and/or total testosterone level and dehydroepiandrosterone sulfate (DHEAS) level as initial screening tests [21]. Hormonal contraceptives should be discontinued for at least two months prior to androgen testing [39]. Additional tests for specific disorders of hyperandrogenism are added as indicated. (See "Evaluation of premenopausal women with hirsutism", section on 'Biochemical testing'.)

Adjunctive tests — Additional procedures that may be utilized for the evaluation and follow-up of FPHL include trichograms and phototrichograms. A trichogram is a technique in which 25 to 50 hairs are grasped with a needle holder and plucked from the scalp followed by an examination of the proximal ends of the hair to assess for the proportion of hairs in telogen. Trichograms are now seldom used in the diagnosis of FPHL. The results of one retrospective study suggest that dermoscopy (trichoscopy) is more useful for the diagnosis of FPHL than trichograms [40]. (See 'Dermoscopy' above.)

Phototrichograms are imaging techniques used to closely examine the features of hair loss for diagnosis and follow-up. A small area of hair is trimmed and followed with imaging for the proportion of regrowing (anagen) hairs, resting (telogen) hairs, and shed hairs, as well as the rate of growth, and hair density [41]. Computerized techniques for performing phototrichograms have been developed (TrichoScan and Folliscope) [42-46]. Phototrichograms are primarily utilized in clinical studies and specialized hair clinics. (See "Evaluation and diagnosis of hair loss", section on 'Trichograms and phototrichograms'.)

DIFFERENTIAL DIAGNOSIS — Multiple hair and scalp disorders may present with clinical features that resemble FPHL [47]. Careful review of the patient history, physical examination findings, and biopsy (when necessary) is of value for differentiating these disorders from FPHL. Of note, since FPHL is a common condition, the coexistence of FPHL with other disorders must also be considered when patients present with features that are not entirely consistent with FPHL:

●Telogen effluvium – Telogen effluvium is the disorder that may be most difficult to distinguish from FPHL. Patients present with acute or chronic noninflammatory, diffuse hair loss [48]. The clinical history is often of value for identifying this diagnosis. For example, a major illness, severe psychologic trauma, significant weight loss, childbirth, and certain medications may precipitate an episode of acute telogen effluvium that begins a few months after the insult. In telogen effluvium, hair loss occurs in all areas of the scalp, although the hair loss may be most evident in the temporal area (picture 4). A hair pull test often demonstrates increased shedding of telogen hairs in patients with active telogen effluvium.

●Diffuse alopecia areata – The rare diffuse form of alopecia areata is characterized by diffuse reduction in hair density (picture 5) [47]. Due to the preferential loss of pigmented hairs, adult patients may complain of rapid graying of the hair. Though not always present, a personal or family history of alopecia areata, the detection of circumscribed areas of complete hair loss, and nail abnormalities offer support to this diagnosis. A biopsy is useful for confirming the diagnosis. (See "Alopecia areata: Clinical manifestations and diagnosis", section on 'Clinical features'.)

●Central centrifugal cicatricial alopecia – Central centrifugal cicatricial alopecia is a scarring alopecia that most commonly occurs in adult females of African descent [49]. The classic location on the vertex of the scalp contributes to the potential for confusion of this diagnosis with FPHL (picture 6). The detection of loss of follicular ostia indicates the presence of scarring. Pustules or inflammation may be detected in early disease. Biopsies are used to confirm the diagnosis. (See "Central centrifugal cicatricial alopecia".)

●Frontal fibrosing alopecia – Frontal fibrosing alopecia is an uncommon scarring alopecia that is usually characterized by frontotemporal recession, perifollicular erythema and follicular hyperkeratosis [50]. Eyebrow loss may also occur. The detection of clinical and histologic signs consistent with a lymphocytic scarring alopecia aid in diagnosis. (See "Lichen planopilaris", section on 'Frontal fibrosing alopecia'.)

●Traction alopecia – Traction alopecia is a form of hair loss that occurs as a result of chronic tension on the hair shaft and follicle (picture 7). Tight braiding of the hair is a common cause of this condition. Hair loss due to traction alopecia is often located at the hairline. Although the hair loss is reversible initially, hair loss may become permanent if tension on the hair follicles continues. The patient history is useful for diagnosis.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Alopecia".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Female pattern hair loss (FPHL) is a common, nonscarring form of hair loss that most commonly occurs in adult females. The highest prevalence of FPHL is found in postmenopausal females. (See 'Epidemiology' above.)

●Pathogenesis – Although hormonal factors and genetic predisposition are believed to contribute to FPHL, the mechanism through which these factors lead to FPHL is not entirely clear. The majority of female patients with FPHL do not have abnormal levels of serum androgens. (See 'Etiology and pathogenesis' above.)

●Clinical manifestations – Classically, FPHL presents with a slow, progressive transition of terminal hairs on the frontal scalp and/or vertex of the scalp to shorter, thinner hairs and vellus hairs. The process results in a visible reduction in hair coverage on the scalp (picture 1A-C). The occipital scalp and frontal hairline are often relatively spared. (See 'Clinical manifestations' above.)

●Psychosocial impact – Although FPHL does not cause physical discomfort or physical disability, the hair loss can contribute to significant psychologic distress. (See 'Psychosocial dysfunction' above.)

●Diagnosis – The diagnosis of FPHL is usually made clinically, based upon the patient history and physical examination. The diagnosis is suggested by the detection of a reduction in hair density in the characteristic distribution and an increased prevalence of miniaturized hairs. Skin biopsies are not usually performed but can be helpful when the diagnosis is uncertain or when a concomitant scalp disorder is suspected. (See 'Diagnosis' above.)

●Differential diagnosis – The differential diagnosis of FPHL includes several types of nonscarring and scarring hair loss. Telogen effluvium, central centrifugal cicatricial alopecia, and traction alopecia are examples of relatively common disorders that share features with FPHL. (See 'Differential diagnosis' above.)