Androgenic Alopecia in Women

The intent of this paper is to help female patients obtain the correct diagnosis and treatment of their hair loss. Clinically significant hair loss occurs in 20% of adult women and it presents in many forms. The type we choose to discuss here is the most common form called androgenetic alopecia (AGA) and is responsible for two thirds of all the causes of hair loss in women.

To determine the proper treatment for hair loss in women it is very important to obtain a correct diagnosis. Because in one-third of female patients hair loss is due to other potentially serious medical conditions, extra attention must be given to the female patient to rule out these medical conditions before proceeding on to treat AGA.

As the name implies, androgenetic alopecia is a hormonal as well as a genetically based hair loss, resulting in a thinning that occurs to terminal hair in both women and men. Both male and female hair thinning can begin as early as the mid to late teens, but is frequently not fully expressed until the 40s. There can be significant differences between male and female hair thinning.

Cause

Androgenetic alopecia (AGA) is characterized by the gradual transformation of terminal (long, thick, pigmented) hair to atrophied (short, fine, non-pigmented) hair. Men and women with AGA both express an increased sensitivity to dihydrotestosterone (DHT). For reasons not yet totally understood, when DHT attaches to the androgen receptor protein on the hair follicle, there is the formation of an autoimmune complex, which ultimately attacks and destroys the hair papilla. It is the loss of the hair papilla, which results in the transformation of terminal hair to the cosmetically less acceptable vellus hair.

In both male and female hair thinning, there is an increase in the transformation of testosterone to DHT by both Type 1 and Type 2 5-alpha reductase enzymes. However, women have only half the amount of the 5-alpha reductase enzyme in the scalp, as do men. In addition, women have increased aromatase enzyme in the scalp follicles as compared to men. This enzyme changes testosterone to the estrogen precursors estradiol and estrone. This local formation of estrogen at the follicle, along with the lower levels of 5-alpha reductase and a lower level of androgen receptor protein, may contribute to the milder hair thinning generally experienced in women. Most women never become totally bald. Another notable difference between male and female hair thinning is that most woman exhibit a central diffuse thinning pattern whereas men generally lose hair in an M-shape at the frontal-parietal hair line and/or exhibit symmetrical thinning at the vertex.

The gene or genes for androgenetic alopecia are autosomal dominant. Autosomal dominant genes can be inherited from either side of the family or from both sides and have variable penetrance of gene expression. That is, one might inherit androgenetic alopecia from either mother or father. Hair loss can also suddenly find expression without any detectable family history. Affected members of the same family may have varying degrees of hair thinning, because other genetic factors may play a role in the expression of ones hair loss while not affecting his or her siblings.

Determination of Correct Diagnosis of AGA in Women

This list is not comprehensive but will cover most other causes of non AGA forms of hair hair loss.

To determine androgenetic alopecia in women, we first must rule out other causes of hair loss:

. medical problems

Inadequate dietary protein and iron. Iron deficiency anemia is one of the major causes of hair loss in women and is often unrecognized.

. thyroid disease

Both hypo and hyperthyroidism can cause hair loss

. medications such as

Anticancer drugs

Anticoagulant drugs

Anticonvulsant drugs

Antithyroid drugs

Beta-blockers

Birth control pills

Tricyclic antidepressants

The following information is helpful in determining if the hair loss is androgenetic alopecia.

. At what age did you first notice the thinning?

. How long have these symptoms been present?

Androgenetic alopecia usually begins in the teens, 20s, or 30s.

. Did you first notice a gradual thinning, or was massive shedding of hair the first observation? In typical androgenetic alopecia, there is usually no increase in the daily shedding of hair. However, in some women, hereditary thinning is first unmasked by an episode of markedly increased hair shedding following childbirth, a high fever, or other illness. Usually this type of shedding (telogen effluvium) runs its course over a period of months and is followed by hair regrowth and full recovery within a year. However, a woman with the genetic predisposition to hereditary hair thinning may not fully regrow her hair following the shedding episode.

. Do you have a family history of thinning hair?

It is easy to misunderstand this question. This history includes parents, brothers and sisters, grandparents, and aunts and uncles on both sides of the family.

. Have you been cutting your hair shorter and shorter?

Patients often cut hair shorter to compensate for the increased skimpiness of the distal ends (the end of the hair projecting away from the scalp). When you gather your hair into a ponytail, you have probably noticed that its diameter has become smaller over time.

. Do you have regular menses? How many days do they last? Are they heavy? Have you had pregnancies? When was the last one? Have you had a problem with infertility? Do you have galactorrhea (a white discharge from the nipple that is persistent and looks like milk) or a continued discharge of milk from the breasts between intervals of nursing or after the child has been weaned?

Women with androgenetic alopecia have normal menses, normal pregnancies, and no infertility or galactorrhea. However, hereditary thinning may be first unmasked by postpartum effluvium (shedding).

Heavy and/or prolonged menses may result in iron deficiency, usuallywithout anemia, which may cause increased hair shedding.

. Are you taking any medications that could be causing or contributing to the thinning?

A variety of drugs in the categories listed above may cause hair loss, but if you discontinue using them you usually have hair regrowth.

. What is your past health history?

A prior illness that caused rapid weight loss or high fever may have contributed to your hair thinning.

. What is your hair care routine?

Excessive or harsh brushing, improper or excessive use of perms, coloring, or bleaching may contribute to hair breakage. The end of a broken hair is blunt; the end of a hair that is not broken or cut has a tapered tip.

. Have you worn a hairstyle that resulted in prolonged traction of your hair?

Hairstyles such as braiding, cornrows, or ponytails may result in traction alopecia if the hair is pulled too tightly. Traction alopecia occurs along the temporal (near the temple or temples) and frontal hair margins.

. Is your diet adequate?

In particular, check your sources of protein and iron.

Examination

. Is there increased spacing between your hairs?

If you have androgenetic alopecia, you may have increased spacing between the hairs and a central parting of the hair appears widened.

. Is the diffuse hair thinning everywhere on the scalp, or is the thinning more evident in some areas, such as the frontoparietal (front, top and sides of the skull) and temporal scalp, and less in the occipital (back of the head) area?

If there is a distinct patchiness to the hair-loss pattern, it is not likely androgenetic alopecia. AGA tends to involve the frontal areas more than the back and spares the frontal hairline.

. Is the pull test normal?

A pull test is performed by squeezing a bunch of hair (usually 25-30 hairs) and giving them a quick tug. It would be abnormal to pull out more than three hairs in any one pull. Five or more hairs in a pull test may indicate telogen effluvium rather than androgenetic alopecia. The hairs that have been pulled out should have a small, whitish friable bulb at the 'root'. Before doing the pull test, it is important that you have washed you hair regularly (3 or 4 times a week). With infrequent washing, more hair than normal may pull out giving an erroneous interpretation

. Is there much variation in the diameter and length of the hair shafts? Are there many miniaturized hairs?

The presence of many miniaturized hairs of varying diameter and length is an essential sign of androgenetic alopecia. Note, that short hairs along the frontal hairline are normal whether you have androgenetic alopecia or not.

. Are your hair ends short, blunt or tapered?

If they are tapered, these hairs represent new growth. If they are blunt, the hair have been broken or cut.

. Is your hair all the same length?

In women with androgenetic alopecia, the hair is not all the same length. The distal ends are skimpier, with the mass of distal hair shafts much smaller than the mass of the proximal (hair at the scalp) hair shafts.

. Have you retained the normal straight or M-shaped frontal hairline?

If you have androgenetic alopecia, you retain a rim of hair along their frontal hairline.

. Are there normal follicular markings on the scalp? Is there inflammation on the scalp?

If you have diminished or absent follicular markings or if there is inflammation of the scalp, it is probably not androgenetic alopecia.

. Do you have severe, non-responsive acne or hirsutism (presence of excessive body and facial terminal hair in a male pattern)?

Increased facial and body hair may be present in normal adults as an expression of an ethnic characteristic or may develop in children or adults as the result of androgen excess due to drugs or tumors, especially those involving the adrenals and gonads. If you have severe acne, hirsutism, or virilization you would require a hormonal evaluation.

Women with androgenetic alopecia usually first notice a gradual thinning of their hair, mostly on the top of their heads, and their scalp becomes more visible. Over time, the hair on the sides may also become thinner. Women retain their frontal hairline, which may be straight or M-shaped, resembling the bitemporal recession (thinning at the temples), which men with AGA often exhibit.

The gradual hair thinning is not usually accompanied by increased numbers of hairs coming out during combing, brushing, or shampooing. Shedding 50-100 hairs/day is normal. However, as previously mentioned. in some instances an episode of telogen effluvium (extensive shedding), such as occurs following childbirth, major illnesses, or a prolonged high fever, may uncover a latent predisposition (present but invisible tendency) to hereditary hair thinning.

Without looking carefully, even the trained physician or office staff member may not realize the woman is truly losing her hair. Women develop time-consuming and often elaborate hairstyles as an adaptive behavior to mask their hair loss. Yet, even if the hair loss is not instantly obvious, it is important that a woman's concerns and fears be acknowledged and addressed.

Women who are experiencing hair loss consistently report feeling "devastated," and need to be treated with compassion and understanding. Understandably, treating patients with hair loss is psychologically challenging for the physician.

In the last few years, medical science has learned a good deal about the pathophysiology (reduction in function) of androgenetic alopecia. In simplest terms, androgenetic alopecia represents the gradual transformation of normal-sized terminal hair follicles to small, hypopigmented (decrease in pigmentation), miniaturized hair follicles. All hair follicles remain present in a patient with androgenetic alopecia. However, many of these hairs have become miniaturized. Patients with androgenetic alopecia as opposed to other forms of alopecia do experience a normal hair-growth cycle. As follicles become miniaturized, new hair growth becomes thinner and shorter. That is, normal sized terminal hair may grow to a length of 2 to 3 feet in a single two to three-year growth cycle. On the other hand, miniaturized hair may grow only a few inches during a much shorter growth cycle.

The fact that the follicles remain present even though they are miniaturized means that it is possible to recruit some of these follicles to generate normal terminal hairs again.

Treatment

To effectively treat your androgenetic alopecia, there are now two classes of drugs available:

1) A growth stimulant to extend the anagen phase of the growth cycle.

2) An anti-androgen to decrease or remove DHT from the androgen receptor sites of the susceptible scalp follicles. If your hair follicles are deprived of DHT, your hair follicles stop atrophying.

This combination is the only proven, safe and effective therapy to prevent or reverse androgenic alopecia.

Minoxidil is the only FDA proven and approved hair growth stimulant. The results are dose related. The higher the concentration the better the response is to treatment.

There are many drugs effective in reducing the levels of DHT and more drugs are currently being clinically tested. Our current recommendations include the following:

1.) Finasteride (Propecia/Proscar) is an oral medication manufactured by Merck Pharmaceuticals. It lowers the serum level of DHT 50 to 70% and inhibits one of the two enzymes that converts testosterone to DHT. This drug is not recommended for women of child bearing age, because there is a theoretical risk of birth defects to the male fetus.

2) Spironolactone can be used as a topical medication. It blocks the androgen receptor sites from DHT. Women can also take oral spironolactone; it helps about 50% of female patients. Men should not use oral spironolactone, because of its feminizing effects.

3) Azelaic acid is a topical medication. It removes greater than 98% of scalp DHT where it is applied. This drug is effective for both men and women.

You could use a combination of 5% minoxidil and spironolactone. Spironolactone should not be combined with minoxidil in solution, otherwise they would react and emit an offensive odor. However, the two solutions can be applied to the scalp in succession without compromising the pharmacologic action of either medication. Minoxidil should be applied morning and evening. Spironolactone should be applied once a day, preferably in the evening.

For most patients, the single best medication is Xandrox, which is a combination of 5% minoxidil and 5% azelaic acid. We are finding that the extra reduction of DHT in the scalp due to azelaic acid helps some patients to grow hair who would not otherwise regrow hair. This preparation is the most convenient to use, and it does not have an offensive odor. 1 mL of this alcohol-based topical solution should also be applied morning and evening.

Minoxidil is very insoluble in water. With alcohol-based solutions of minoxidil less than 2% absorbs into your scalp. Approximately 4% of the azelaic acid will absorb. This amount is sufficient to inhibit >98% of the DHT synthesis in the scalp. For nighttime application, we offer the addition of 0.025% retinoic acid (Retin-A), which is a skin peel, and improves the penetration of minoxidil up to 20%.

Our most usual recommendation for androgenetic alopecia is the use of Xandrox 5% day/night formulation. The night formula contains 0.025% retinoic acid. You should use retinoic acid no more frequently than once a day, applied at night. Use the white labeled Xandrox bottle in the morning and the black-labeled Xandrox bottle, which has the additional 0.025% retinoic acid in the evening. Any evening that you are not using the night formula, you should use the day formula.

Start your treatment with 5% Xandrox liquid twice daily. There is no need to soak your hair. As much as is practical, it is important to apply the topical directly on your scalp. Fill a medicine dropper with 1 ml of liquid. Part your hair in several places and apply a portion of the medicine dropper to these areas. Lightly spread the topical to cover the thinning areas of your scalp. In solution form, it is the alcohol that allows for penetration into the scalp; so heavy massaging contributes very little. Even if the minoxidil/Xandrox is not evenly distributed on the scalp, there is diffusion in the layers under the stratum corneum (outer layer of the skin).

So, in essence, the most effective use of topical minoxidil/Xandrox is a consistent twice/day application at least eight hours apart.

If you are going to use the Xandrox or plain minoxidil solutions containing retinoic acid, please be aware that the retinoic acid may cause mild scalp irritation, flaking and drying of the scalp where applied. This is because of retinoic acid's direct effects as a chemical peel. It may also cause the skin where it is applied to be more sensitive to being sunburned. If you use any of the products containing retinoic acid, take preventive measures such as using a sunscreen or wearing a hat if you are going to get direct sun exposure. Light complexioned patients may want to adjust to the retinoic acid by using the Xandrox, which contains retinoic acid or the Minoxidil 5%/retinoic acid solution only once during the first week, twice during the second week, etc., until they have accommodated the skin to the effects of the retinoic acid. Retinoic acid has the ability to increase the size of those hair follicles, which have become smaller and now only produce 'peach fuzz'. It can likewise significantly increase the effects of the anti-androgens. Recent studies have shown that "retinoic acid, if used for a long time, may reduce the number of androgen receptors by 30-40%".

A small percentage of patients, male and female, experience slightly increased shedding of hair when they start the using any topical minoxidil product. The shedding affects only telogen hairs, which are those that have finished the growth phase and usually represents about 10% of the hairs on the scalp. Although this is understandably frustrating and exasperating, actually, it's a good indication that the patients should have ultimately good results with the therapy. All of the hair that is shed will be replaced with hair that is thicker because the atrophic process is being reversed. However, the replacement usually requires that the follicle cycle complete its telogen (resting) phase, which lasts approximately 100 days.

Since the reversal of alopecia androgenetica requires replacement of atrophic hairs with more cosmetically acceptable ones, positive results are generally not appreciated until after 4 to 6 months of treatment. Most dermatologists don't recommend trying to assess therapeutic results until at least one year of treatment