Study 4

HEADLINE:
Androgenetic alopecia in men and women: an overview of cause and treatment; Continuing Education Series, with test

BYLINE:
Roberts, Janet L.

AUTHOR-ABSTRACT:
Hair loss is a cause of anxiety and distress in both men and women. New understanding of the causes of androgenetic alopecia is leading to potential new medical therapies. Pathophysiology, clinical presentations, diagnosis, current and future treatments are discussed.

BODY:
Objectives

This independent study offering is designed for nurses and other health care professionals who care for and educate patients regarding androgenetic alopecia. A multiple choice examination follows this article and is designed to test the reader’s achievement of the objectives listed below. After studying the information presented in this article, the reader will be able to:

1. Understand the causes of androgenetic alopecia.

2. Distinguish androgenic alopecia in men and women.

3. Describe the psychological effects of androgenetic alopecia.

4. Distinguish androgenetic alopecia from other causes of hair loss.

5. List current and potential treatments.

A brief review of the anatomy of hair follicles and the continuous cycles they undergo will provide the basis for describing the alterations that occur in androgenetic alopecia. The hair follicle comprises the dermal papilla which invaginates into the base of the follicle where rapidly dividing matrix cells are located (see Figure 1). Matrix cells differentiate into the hair shaft and several specialized layers. The rich environment of the dermal papilla provides nutrients and signals for differentiation and proliferation.

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Each hair follicle undergoes continuous cycles of growth, rest, and regrowth. The timing of these phases varies from site to site on the body. The growth cycle is called the anagen phase which lasts from 2 to 8 or more years on the scalp. This is followed by a brief transition phase called the catagen phase lasting no more than 2 to 3 weeks, progressing into the telogen (resting) phase lasting 2 to 3 months on the human scalp. The hair then immediately begins a new anagen growth phase (see Figure 2).

[Figure 2 ILLUSTRATION OMITTED]

Clinical Presentation of Androgenetic Alopecia

Alopecia is a general term for hair loss and requires further description. Androgenetic alopecia (AGA) is the most common cause of hair loss, presenting as loss of hair over the top (vertex) of the scalp in affected men and women. AGA is associated with normal levels of estrogens and androgens in both men and women. The term androgenetic alopecia denotes that both a genetic predisposition and the presence of androgens are necessary to cause expression. The specific mode of inheritance is not known.

Androgenetic Alopecia in Men

In men, androgenetic alopecia, also called male pattern hair loss, is characterized by hair loss in the frontal and vertex areas of the scalp. Several patterns are commonly recognized and classified according to the Hamilton (Hamilton, 1942) and Norwood classifications (Norwood, 1975). These classifications are based on the degree of hair thinning and the affected areas of the scalp (see Figure 3). AGA in men begins anytime after onset of puberty.

[Figure 3 ILLUSTRATION OMITTED]

Androgenetic Alopecia in Women

In women, androgenetic alopecia, also called female diffuse thinning, presents with more diffuse thinning in a mosaic pattern over the vertex of the scalp. The frontal hairline is usually retained. Occasionally there is a prominent triangle of thinning behind the retained frontal fringe (see Figure 4). Part width over the vertex is widened when compared to the back of the scalp (see Figures 5 and 6). Onset is generally in late 20s to 30s. The hair loss in women is usually less dramatic than that seen in men. Originally, the degrees of thinning were divided into three categories by Ludwig (1977) (see Figure 7). More recently, Savin (1994) devised a scale based on eight categories of density and part width over the vertex of the scalp. Affected women are not virilized. Onset and exacerbation of hair loss often occurs at times of hormonal upheavals such as puberty, postpartum, use of oral contraceptives, and the early post-menopausal period. See Figures 8 and 9 for comparisons of AGA in men and women.

[Figures 4-9 ILLUSTRATION OMITTED]

Prevalence

Approximately 20% of Caucasian men are affected by the age of 20 with incidence increasing 10% per decade. Fifty percent of Caucasian women are affected by age 50. Racial differences are noted with more Caucasians affected PAGE 3 Dermatology Nursing December, 1997

than Asian and Negroid races (Olsen, 1993).

Psychosocial Aspects

Recent studies on the quality of life in men and women with AGA show that loss of scalp hair can have major psychologic effects. Men with AGA may feel less attractive and older than their peers leading to diminished self-esteem, stress, anxiety, depression, and social inadequacy (Cash, 1992). Women with AGA have both social and emotional concerns. They may be frustrated at the time and trouble necessary to camouflage thinning hair and the inability to style their hair as they would like. They may feel self-conscious that others will notice hair loss, embarrassment, decreased self-esteem, and jealousy of other women who are blessed with bountiful scalp hair (Cash, Price, & Savin 1993; Girman, Hartmaier, Roberts, Bergfeld, & Waldstriecher, 1996).

Pathophysiology of Androgenetic Alopecia

Although the clinical presentation is different in men and women, the underlying cellular processes causing AGA are thought to be similar. AGA is caused by androgens in both men and women. Androgens are produced in men by the testes and adrenal glands. In women, androgens are produced by the ovaries and adrenal glands. Androgens produced peripherally by endocrine-sensitive hair follicles and sebaceous glands also contribute significantly to circulating androgens in both men and women. All men and women with AGA have normal levels of circulating androgens.

The androgen dihydrotestosterone (DHT), a potent metabolite of the androgen testosterone (T), causes a gradual, progressive shrinkage in the length and caliber of genetically programmed hair follicles. This process is called miniaturization. Miniaturization results from shortening of the anagen phase and a decrease in the sit of the dermal papilla and volume of matrix cells. Consequently, each succeeding hair cycle results in production of smaller, finer hairs which contribute less to the overall appearance and density of the hair (Messenger, 1993) (see Figure 10). Increased shedding of miniaturized hairs and minor inflammation, as manifested by seborrheic dermatitis, may occur.

[Figure 10 ILLUSTRATION OMITTED]

These biochemical events occur at the cellular level of the hair follicle. Because the dermal papilla is highly vascular, it is continuously bathed in circulating androgens. It has been demonstrated that the dermal papilla is rich in androgen receptors and is the primary target of androgen action (Choudhry et al., 1996; Randall, Thornton, Hamada, & Messenger, 1992). Cells in genetically programmed hair follicles contain the enzyme 5[Alpha]-reductase (5[Alpha]R). 5[Alpha]R converts T into the more potent DHT (Chen, Zouboulis, & Orfanos, 1996) (see Figure 11). 5[Alpha]R is found in higher quantities in the scalp follicles of affected men and women (Sawaya & Price 1997). Androgen receptors in the cells of the dermal papilla bind with circulating DHT, forming androgen-receptor complexes. These complexes are presented to binding sites on the DNA in the cell nuclei of the dermal papilla. Modified DNA sends messages via messenger RNA to the matrix cells, creating proteins to carry out the androgen effects of miniaturization on the hair follicle (Randall et al., 1992) (see Figure 12).

[Figures 11-12 ILLUSTRATION OMITTED] PAGE 4 Dermatology Nursing December, 1997

Aromatase, present in the outer root sheath of the hair follicle, is another enzyme that plays an important function in androgenetic alopecia. This enzyme converts testosterone and dihydrotestosterone back into estrogens. Aromatase is approximately six times more abundant on the female frontal scalp as compared to males, and may be responsible for the less severe expression of AGA in women (Sawaya & Price, 1997). It may also explain retention of the anterior hairline in women.

Differential Diagnosis of Androgenetic Alopecia

In general, the clinical appearance and history of AGA in men is straightforward and does not present a diagnostic challenge. Because the pattern is more ambiguous in women, several other types of hair loss may mimic AGA and should be kept in mind when evaluating patients.

Telogen effluvium. Women are especially prone to increased shedding of telogen hairs from various physical insults, a condition called telogen effluvium. Acute and chronic illnesses, abrupt hormonal changes, iron and dietary protein deficiency, and many medications can all cause an increased shift of hairs into the telogen phase with a resultant increase in shedding. This shedding is accentuated along the frontal hairline and vertex of the scalp and can easily mimic AGA. Sometimes an episode of telogen effluvium hastens expression of AGA in genetically prone individuals (see Figure 13).

[Figure 13 ILLUSTRATION OMITTED]

Alopecia areata. Alopecia areata is an autoimmune condition which usually presents as patchy hair loss, but occasionally presents initially as increased shedding and diffuse hair loss. The onset tends to be more dramatic and severe than AGA and alopecia areata is usually progressive to a patchy hair loss pattern (see Figure 14).

[Figure 14 ILLUSTRATION OMITTED]

Scarring or permanent alopecia. There are several types of hair loss which cause permanent destruction of the follicles. Hair loss is usually patchy with obvious signs of scalp inflammation. However, hair loss can be diffuse and the scalp may not appear clinically inflamed. Early recognition and treatment are important to prevent permanent hair loss (see Figure 15).

[Figure 15 ILLUSTRATION OMITTED]

Androgenic alopecia. Androgenic alopecia is caused by increased androgen production in women. It is usually accompanied by other signs of androgen excess such as irregular menstruation, infertility, hirsutism (increased secondary sexual hair in the male distribution), acne, and oily skin. Onset is generally earlier than AGA. Hair loss is more severe and may mimic the pattern of AGA in men (see Figure 16). Women with suspected androgenic alopecia should be evaluated by an endocrinologist or by a dermatologist with special expertise in androgen-related hair conditions.

[Figure 16 ILLUSTRATION OMITTED]

Clinical evaluation. Evaluation of women with hair loss should include documentation increased hair loss by actual hair counts. An average daily PAGE 5 Dermatology Nursing December, 1997

count of 50 to 100 hairs is normal. A careful medical history should be taken, including recent surgeries or illnesses, dietary habits, weight loss, medications, menstrual and pregnancy history. Clinical examination of the patient includes evaluating hair density, pattern, length, and evidence of regrowth. The scalp should be checked for signs of scarring alopecia including inflammation, obliteration of follicular orifices, and atrophy. At a minimum, laboratory examinations, including thyroid and iron evaluation, should be obtained. Serum ferritin levels are the most helpful; desired values are 40-300 ng/ml. Women with AGA having regular menses, normal fertility, and no stigmata of virilization do not require endocrinologic evaluation.

Treatments for Androgenetic Alopecia

Surgical treatments. Surgical treatments for AGA, including hair follicle transplantation, have been increasingly refined in the past several years and are beyond the scope of this article. Readers are referred to the September 1997 issue of Dermatologic Surgery for a complete review of this subject (Slough, 1997).

Medical treatments. Medical therapy for androgenetic alopecia can be divided into the following categories: (a) nonspecific promoters of hair growth, (b) topical and systemic anti-androgens, (c) 5-reductase inhibitors.

Nonspecific promoters of hair growth. Minoxidil is the best known drug in this category. Minoxidil is an oral medication used to treat refractory hypertension. It was noted to cause hypertrichosis (increased nonsexual hair growth). Mechanism by which it stimulates hair growth is unknown. Clinical trials have shown that a 2% solution applied topically to the scalp can stimulate hair growth in some men and women. Fewer than 5% of patients have dense regrowth while approximately 30% have moderate regrowth (Olsen, Weiner, DeLong, & Pinnell, 1985; Roberts, 1987). Continued use is required to maintain hair growth. Currently, it is the only drug FDA approved for treating AGA. Five-percent topical minoxidil solution has proven more effective than the 2% solution in men and has been approved by the FDA for sale over-the-counter in the United States. (It has been available in Canada).

Anti-androgens. This term describes topical or systemic drugs which reduce production of androgens, interfere with androgen metabolism, or prevent androgen activity at target sites such as endocrine-sensitive hair follicles. Because systemic anti-androgens reduce circulating testosterone, which is required for normal male sexual functioning, their use is limited to women (Straw, 1996). Numerous topical preparations, such as estrogen, progesterone, and cyoctol have not been thoroughly tested in clinical studies (Olsen, 1993).

Spironolactone is a potassium-sparing diuretic used for treating mild hypertension. Oral spironolactone is used fairly widely for treating women with AGA although literature documentation of efficacy is sparse. Spironolactone works by decreasing adrenal and ovarian androgen production. It also competes with T and DHT for androgen receptors in the hair follicle cells. Doses in the range of 100 to 200 mg are used. Side effects can include breast tenderness and menstrual irregularities. Women using spironolactone should be protected from pregnancy and have yearly Pap smears and mammograms (Straw, 1996).

Oral contraceptive pills (OCP) decrease production of ovarian androgens (Shaw, 1996). The progestin component also competes with T and DHT for PAGE 6 Dermatology Nursing December, 1997

androgen-receptor binding in the hair follicles. Oral contraceptive pills can be relatively estrogenic or androgenic. Estrogenic OCPs are suggested if used for women with AGA (see Table 1).

Table 1. Oral Contraceptive Pills

Progestins (Most to Least Estrogenic) Brand Names

Desogestrel Desogen, Ortho-Cept

Norgestimate Ortho-Cyclen,

Ortho-Tri-Cyclen

Norethindrone Micronor, Nor-QD,

Ovcon-35, Brevicon,

Modicon

Ortho-Novum 7/7/7,

Ortho-Novum 10-11.

Tri-Norinyl, Norinyl,

Ortho 1/35

Ethnodiol diacetate Demulen 1/35

Levonorgestrel Triphasal, Tri-Leviin,

Nordeue, Alesse-28

Norgestrel Lo/Ovral, Ovreue, Ovral

Norethindrone acetate Loestrin 1/20, Loestrin

1.5/30 PAGE 7 Dermatology Nursing December, 1997

5[Alpha]-reductase inhibitors. Drugs in this class work by inhibiting the enzyme 5[Alpha]R, which limits the conversion of T to DHT (Chen et al., 1996). Finasteride is the first drug in this class to undergo extensive clinical trials in men. Finasteride has selective activity against 5[Alpha]R. As a result, serum and follicular DHT levels are significantly reduced (Dallob et al., 1994). Finasteride has no androgenic or estrogenic hormonal activity. Because testosterone levels are not significantly affected, finasteride is not considered an anti-androgen and may be safely used in men.

Summary

Androgenetic alopecia occurs frequently in both men and women. It is caused by the action of dihydrotestosterone, a potent metabolite of testosterone, on endocrine-sensitive hair follicles. It can be the cause of significant social and emotional distress. Dermatology nurses can help educate their androgenetic alopecia patients by understanding the clinical presentation, differential diagnosis, pathophysiology, and current and future therapies related to this condition.

References

Cash, T.F., Price, V.H., & Savin, R.C. (1993). Psychological effects of androgenetic alopecia on women: Comparisons with balding men and with female control subjects. Journal of the American Academy of Dermatology, 29(4), 568-575, 926-931.

Cash, T.F. (1992). The psychological effects of androgenetic alopecia in men. Journal of the American Academy of Dermatology, (26), 926-931.

Chen, W., Zouboulis, Ch.C., & Orfanos, C.E. (1996). The 5-reductase system and its inhibitors. Dermatology, 193, 177-184.

Choudry, R., Hodgins, M.B., Van der Kwast, T.H., Brinkmann, A.O., & Boersma, W.J.A. (1992). Localization of androgen receptors in human skin by immunohistochemistry: Implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands. Journal of Endocrinology, 133 467-475.

Dallob, A.L., Sadick, N.S., Unger, W., Lipert, S., Geissler, L.A., Gregoire, S.L., Nguyen, H.H., Moore, E.C., & Tanaka, W.K. (1994). The effect of finasteride, a 5-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. Journal of Clinical Endocrinology and Metabolism, 79(3), 703-706.

Girman, C.J., Hartmaier, S., Roberts, J., Bergfeld, W., & Waldstreicher, J. (1996). Patient-perceived importance of negative effects of androgenetic alopecia in women. Unpublished manuscript.

Hamilton, J.B. (1942). Male hormone is a prerequisite and an incitant in common baldness. American Journal of Anatomy, 71, 451-480.

Ludwig, E. (1977). Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. British Journal of Dermatology, 97, 127-254. PAGE 8 Dermatology Nursing December, 1997

Messenger, A.G. (1993). The control of hair growth: An overview. Journal of Investigative Dermatology, 101, 4S-9S.

Norwood, O.T. (1975). Male pattern baldness: Classification and incidence. Southern Medical Journal, 68, 1359-1365.

Olsen, E.A., Weiner, M.S., Delong, E.R., & Pinnell, S. (1985). Topical minoxidil in early male pattern baldness. Journal of the American Academy of Dermatology, 13, 185-192.

Olsen, E.A. (1993). Androgenetic alopecia. In E.A. Olsen (Ed.), Disorders of hair growth: Diagnosis and treatment (pp. 257-283). New York: McGraw-Hill, Inc.

Randall, V.A., Thornton, M.J., Hamada, K., & Messenger, A.G. (1992). Mechanism of action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo. The Journal of Investigative Dermatology, 98(6), 86-91.

Roberts, J. (1987). Androgenetic alopecia: Treatment with topical minoxidil. Journal of the American Academy of Dermatology, 16(3), 705-710.

Savin, R.C. (1994). Upjohn Dermatology Division. Kalamazoo, MI: Upjohn Company.

Sawaya, M.E., & Price, V.H. (1997). Different levels of 5[Alpha]-reductase type I & II, aromatase, and androgen receptors in hair follicles of women and men with androgenetic alopecia. The Journal of Investigative Dermatology, 10(3), 296-300.

Shaw, J.C. (1996). Antiandrogen therapy in dermatology. International Journal of Dermatology, 35(11), 770-776.

Stough, D. (Ed.). (1997). Special issue: Hair. Dermatologic Surgery, 23(9).

Janet L. Roberts, MI), is Clinical Professor of Dermatology, Oregon Health Sciences University, Portland, OR; and is in Private Practice in Portland.

GRAPHIC: Photograph; Table; Chart; Diagram; Illustration

LANGUAGE: ENGLISH