|Year : 2005 | Volume
| Issue : 4 | Page : 179-190
|Androgenetic alopecia - Current status
Department of Dermatology, Apollo Hospitals, and KK Childs Trust Hospital,Chennai, India
2, West Mada Church Road,Royapuram, Chennai 600013
Source of Support: None, Conflict of Interest: None
Keywords: Alopecia, Androgenetic alopecia, Male pattern hair loss.
|How to cite this article:|
Thomas J. Androgenetic alopecia - Current status. Indian J Dermatol 2005;50:179-90
| Introduction|| |
Androgenetic alopecia is an extremely common disorder affecting both men and women. The incidence is generally considered to be greater in males than females, although some evidence suggests that the apparent differences in incidence may be a reflection of different expression in males and females.
| Epidemiology|| |
Universally this is an extremely common disorder that affects roughly 50% of men and perhaps as many women older than 40 years. As many as 13% of premenopausal women reportedly have some evidence of androgenetic alopecia. However, the incidence increases greatly in women following menopause, and, according to some authors, it may affect 75% of women older than 65 years. This is essentially a cosmetic disorder. Other than affecting the patient psychologically, the disorder is significant only in that it allows ultraviolet light to reach the scalp and, thus, increases the amount of actinic damage. Males with androgenetic alopecia may have an increased incidence of myocardial infarction. An increase in benign prostatic hypertrophy has also been associated. If these associations are proven conclusively, this disorder will be of greater clinical significance. The incidence and the severity of androgenetic alopecia tend to be highest in white men, second highest in Asians and African Americans, and lowest in Native Americans and Eskimos. Almost all patients have an onset prior to age 40 years, although many of the patients (both male and female) show evidence of the disorder by age 30 years.,
| Pathophysiology|| |
This genetically determined disorder is progressive through the gradual conversion of terminal hairs into indeterminate hairs and finally to vellus hairs. Patients have a reduction in the terminal-to-vellus hair ratio, normally at least 2: 1. Following miniaturization of the follicles, fibrous tracts remain. Patients with this disorder usually have a typical distribution of hair loss.
The scalp has a 3-phase cycle of hair with almost 90% of hair in the anagen or growth phase (which may last up to 2-6 years), 1 % in the catagen phase (which may last 3 weeks), and 10% in the telogen or resting phase (which may last 3 months). This ratio is usually uniformly distributed over the entire scalp. When the hair in the telogen phase is expelled, another follicle pile in the anagen VI phase emerges to replace it, though this does not always occur. In fact, some follicles may remain empty after the final moment of the telogen phase, and this new phase is known as the kenogen or lag phase. In androgenetic alopecia, the role of dihydrotestosterone (DHT) is universally accepted. However, the mechanism by which it acts is unclear. Three mechanisms have been proposed. A process known as miniaturization of scalp hair causes thinning and shortening of the hair shaft. Hair growth is cyclical and the phases include anagen, catagen and telogen phases. Miniaturization occurs during the anagen phase of hair growth when there is an increase in the mitotic rate of keratinocytes, a shortening of anagen VI, and the hair cannot differentiate. A second mechanism occurs as a result of the acceleration of the hair cycle: the number of shedding telogen hair increases. There is also a lag phase or delayed replacement of telogen hair, called kenogen. A third mechanism has been proposed in an increased number and duration of this phase, although it is not clear that this is related to DHT.
Normal hair cycle
A working knowledge of the anatomy of the normal hair cycle is useful in understanding the evolution of miniaturizing hairs. The average number of hairs in the adult scalp is 100,000, of which 90% are in anagen and 10% in telogen. The average duration of anagen is 1000 days, of telogen 100 days, and the average daily loss of telogen hairs is 100. Hair follicle cycling occurs in the impermanent lower follicle between the bulb and the bulge, which is situated in the area of insertion of the arrector pili muscle into the follicle. The bulb comprises the hair matrix cells that surround the dermal papilla. The vitreous layer around the outer root sheath is continuous with the basal lamina between matrix cells and demal papilla. The dermal papilla contains papillary mesenchymal cells, surrounded by extracellular matrix. It is continuous with the fibrous dermal sheath that surrounds the bulb and contains mesenchymal cells similar to those in the papilla.
The anagen bulb produces the hair shaft and the inner and outer root sheaths. The inner root sheath molds the hair shaft in the lower follicle and is shed in the isthmus region of the follicle. Several years of hair growth are followed by a resting phase: anagen is first succeeded by 2 weeks of catagen and ends in telogen, which lasts an average of 3 months. During this resting phase, the lower follicle retreats up to the level of the bulge during catagen, dragging the exposed miniaturizing dermal papilla behind it. The stella or fibrous tract marks the ascent of the follicle. The dermal papilla shrinks to its smallest size during telogen. With a new anagen cycle, the follicle follows the papilla down the fibrous tract, and the papilla generally enlarges once again.
Exact controls of hair follicle cycling are still unknown. Whether the cycle is initiated in hair follicle epithelium or in papillary mesenchyme is controversial. Some postulates hair cycling clocks. Others believe that repeated cycling may be an innate property of a follicle. Most will agree that follicular epithelium, dermal papillae, and dermal sheath cells all interact in follicular cycling. Cycling may initiate with either an anagen-to-catagen transition or a telogen-to-anagen transition. Cycling is probably driven by local signals changing the expression of cytokines, growth factors, hormones, neuropeptides, adhesion molecules and receptors. Various other factors, including telomerase activity, may be involved.
Regrowth of hair may well be initiated by stem cells in the bulge region. This is supported by the fact that the lower follicle retracts upward to the level of the bulge area in telogen. Slow-cycling cells have been demonstrated in the bulge region in murine follicles by autoradiography with thymidine labeling. The hypothesis is that entry into anagen occurs when stem cells in the bulge region are activated by signals from the dermal papilla. Daughter transient-amplifying cells form the hair bulb matrix and ultimately its differentiated cell products. It seems possible that cells in the hair bulb matrix have a finite proliferative potential that, once exhausted, would result in cessation of growth and entry into catagen. After transition from telogen to anagen I, and progression through subsequent stages into anagen VI, the complete hair follicle is regenerated. Hair shafts and root sheaths are generated throughout anagen. In catagen, the external root sheath shrinks by apoptosis during the ascent of the hair root to the bulge. ,,,,,,,,
Concepts of miniaturization
Traditional concepts state that in androgenetic alopecia, follicles undergo miniaturization, shrinking from terminal to vellus-like hairs perhaps 1 cm in length. The follicle then remodels as it does in follicular embryogenesis, but it forms a smaller hair. The process is traditionally thought to progress over a number of follicular cycles, implying the presence of a wide range of hairs of gradually diminishing length and diameter. As anagen duration decreases, more balding follicles are projected into telogen and hair shedding increases. In miniaturization, the duration of anagen may shrink from the normal of 2/ years to 1 month, but the duration of telogen (3 months) remains the same. As recently demonstrated in androgenetic alopecia, a latent lag period follows telogen after the hair is actually shed and before the new hair grows in, further reducing the proportion of hairs in anagen.
Some newer concepts
Why does follicular miniaturization occur in pattern hair loss? Apparently each hair has its own genetic makeup or altered gene expression and shows its own susceptibility to factors responsible for androgenetic alopecia such as androgens. This is shown by examination of hairs in follicular units in androgenetic alopecia. Follicular units are the hexagonal packets enclosed by collagen seen in the upper dermis at the level of entry of sebaceous ducts into follicles, each of which contains several terminal hairs and possibly a vellus hair plus sebaceous glands, sebaceous ducts, and arrector pili muscles. ln pattern hair loss, it can be seen that a variable number of hairs in anyone follicular unit can be affected by follicular miniaturization. Other influences besides genetic or hormonal, such as growth factors, cytokines, and neuropeptides, may well be important in miniaturization and are yet to be elucidated.
When does follicular miniaturization occur in androgenetic alopecia? Its initiation may occur at some stage in early catagen or early anagen, when the dermal papilla is moving up or down the temporary lower follicle and is vulnerable to external forces. It does not occur during established anagen, since anagen hairs maintain the same diameter during each hair cycle, nor in telogen where there is no metabolic activity.
Where does follicular miniaturization take place? It presumably occurs in the dermal papilla and dermal sheath, when initiated by stem cells in the follicular bulge. This terminal-to-vellus switch is influenced by androgen receptors, 5a-reductase, stem cell factors, drug factors, and cytokines.
How does miniaturization occur? It is unlikely that rapid hair loss in androgenetic alopecia can be explained simply by a series of progressively shorter anagen cycles. A simple calculation shows that this process would take too long for much miniaturization to occur, particularly if the recently described latent lag period between the loss of a telogen hair and the appearance of an anagen hair in androgenetic alopecia is factored in. This calculation of the expected hair cycle duration and therefore the expected length of the hair shaft are dictated by the relative percentages of hairs in anagen and telogen. It is based on the assumption that the length of telogen is 3 months. Thus, in normal subjects, there will be a 3-month period of no hair growth in each hair cycle. It is also assumed that in normal hair the average rate of hair growth is 1 cm per month. If 10% or 1/10 of scalp hairs are currently in telogen for 3 months, then the 90% or 9/1 0 of hairs currently in anagen will require an additional 27 months for all to cycle through anagen and telogen. Thus the normal steady 10% telogen count dictates a hair cycle of 30 months' duration. During that period each hair should reach a length of 27 cm. This means shoulder-length hair, which correlates well with a normal hair cycle of 2.5 years. By the same calculation, a constant 20% telogen count should result in a 12-cm hair, 40% telogen in a 4.5-cm hair, 60% telogen in a 2-cm hair, and 75% telogen in a 1-cm miniaturized hair.
The duration of hair growth is directly related to the proportion of telogen hairs, which averages 20% in male androgenetic alopecia patients, as shown by histologic follicular counts in horizontal sections of scalp biopsy specimens of males with androgenetic alopecia. Clearly there must be other explanations for miniaturization. Presumably not only the duration of anagen but also the rate of hair growth must change in pattern hair loss. In the above calculations, the duration of hair growth is directly related to the proportion of telogen hairs, which averages 20% in male androgenetic alopecia. With a hair growth rate of 1 cm/month and 80% of hairs in anagen, the hair would be expected to grow 24 cm long, which does not equate with reality. It is thus likely that the rate of hair growth in androgenetic alopecia is considerably reduced. An important factor here is the size of the dermal papilla, which determines the size of both hair bulb matrix and hair shaft. Human follicle dermal papilla miniaturization is the direct result of reduction in papillary cell numbers. Cell loss by apoptosis has not been reported in dermal papilla cells in normal cycling. However, displacement of less cohesive papillary cells may occur with upward or downward papillary shifts in catagen and early anagen. It is possible in androgenetic alopecia that balding starts with a loss of dermal sheath cells displaced in the upward movement of follicles in catagen. Since dermal papillae and dermal sheaths act as a functional unit, dermal papilla cells would be recruited and depleted to replace these lost sheath cells. Two-way traffic of cells between sheath and papilla may be important in the engineering of the varying size of the dermal papilla. It seems likely that follicular miniaturization is not a gradual process, but a series of comparatively large-step changes between growth phases. Large steps depend on marked reductions in papillary cell numbers. This change in papillary size results in a much smaller follicle with a reduced duration of anagen. It follows that when miniaturization is reversed, more papillary cells must be recruited, presumably from the dermal sheath, before a new cycle can begin. It seems likely that dermal papillary cell activity is dictated by outside influences.
| Clinical aspects|| |
Hstory reveals that the onset is gradual. Men present with gradual thinning in the temporal areas, producing a reshaping of the anterior part of the hairline. For the most part, the evolution of baldness progresses according to the Norwood/Hamilton classification of frontal and vertex thinning. Women usually present with diffuse thinning on the crown. The process in women is noted as widening of the central part. Bitemporal recession does occur in women but usually to a lesser degree than in men. In general, women maintain a frontal hairline. In both males and females with androgenetic alopecia, the transition from large, thick, pigmented terminal hairs to thinner, shorter, indeterminate hairs and finally to short, wispy, nonpigmented vellus hairs in the involved areas is gradual. As the disorder progresses, the anagen phase shortens with the telogen phase remaining constant. As a result, more hairs are in the telogen phase, and the patient may notice an increase in hair shedding. The end result can be an area of total denudation. This area varies from patient to patient and is usually most marked at the vertex. Women with androgenetic alopecia generally start as widening of the center part and then lose hair diffusely over the crown. This produces a gradual thinning of the hair rather than an area of marked baldness. The frontal hairline is often preserved in women with this disorder, whereas men note a gradual recession of the frontal hairline early in the process. This is specifically related to the presence of aromatase in females only.31
| Investigations|| |
The most important aspects are the history and the physical examination. In the case of a woman, if virilization is evident, laboratory analysis of dehydroepiandrosterone (DHEA) sulfate and testosterone may need to be obtained. Some authors have suggested that total testosterone level alone may be adequate to screen for a virilizing tumor. If a thyroid disorder is suspected, obtaining a thyroid-stimulating hormone (TSH) level is indicated. If telogen effluvium is present, laboratory analysis of serum iron levels or a biopsy to note an underlying papulosquamous disorder may be indicated. Telogen effluvium may accelerate the course of pattern alopecia. Iron deficiency is a common and reversible cause of telogen effluvium. A normal CBC result does not exclude iron deficiency as a cause of hair loss. While a low ferritin level is always a sign of iron deficiency, ferritin behaves as an acute phase reactant, and levels may be normal despite iron deficiency. Iron, total iron-binding capacity (TIBC), and transferrin saturation are inexpensive and sensitive tests for iron deficiency. Diffuse alopecia areata may mimic pattern alopecia. The presence of exclamation point hairs, pitted nails, or a history of periodic regrowth or tapered fractures noted on hair counts suggests the diagnosis of diffuse alopecia areata.
A biopsy is rarely necessary to make the diagnosis. ,, Some dermatopathologists recommend that if a biopsy is to be performed, a sample should be obtained from 2 sites: one for horizontal sectioning and one for vertical sectioning of the hair follicles. Other dermatopathologists point out that one may commonly obtain sufficient information from serial vertical sections to diagnose the condition. Histopathology offers another means of assessing hair density. Horizontal sections of scalp biopsies allow for identification and quantification of follicle stage (anagen, telogen, catagen), diameter of follicle (and hence, designation as vellus or terminal), and whether any other factors may be present that could potentially affect hair growth results (e.g., fibrosis, inflammation). Use of a digital microscope to capture images of biopsy sections taken at the same depth in both sequential intraindividual and interindividual subjects may then be subjected to sophisticated software manipulations to track changes in hair widths among categories of hair follicles designated by baseline diameter.
In pattern alopecia, an increase in vellus hairs is seen, and fibrous root sheath remnants (so-called streamers) can be found below miniaturized follicles. Although androgenetic alopecia is considered a noninflammatory form of hair loss, at times, a superficial, perifollicular, inflammatory infiltrate is noted. In long-standing disease, connective tissue may completely replace follicular structures. A mildly increased telogen-to-anagen ratio is often observed.
Trichograms offer additional information. The initial component of a phototrichogram is generally identical to performing a target area hair count, that is, identification and permanent marking (currently by a tattoo) of a given target area, clipping the hair to approximately 1 mm in length, and then photographing this area. Total hairs and/or designation by diameter into terminal, nonvellus, indeterminant, or visible hairs per unit area may then be determined from this photograph. As with all hair counts on the basis of macrophotography, the degree of magnification will affect the total and visible, but not terminal, hair count because only smaller diameter vellus or indererminate hairs become visible with increasing magnification. Phototrichograms then proceed to another step beyond the usual target area hair counts to include clipping the involved target area hairs to approximately 0.25 inch length (1 mm) and repeating the target area photograph 2 to 3 days later. The area is not shaved so as to not interfere with visibility of telogen hairs on the repeat photograph. At 2 to 3 days, the number of anagen hairs can be determined because only the anagen hairs will have gained in length. The percent anagen/telogen ratio and actual numbers of anagen and telogen hairs can then be derived from this anagen count and the total hair count performed 2 to 3 days previously. To facilitate the measurement of gray or white terminal or nonvellus hairs that are not well-captured photographically, applying a hair dye before photography is useful., However, it must be remembered that the very dyeing of these gray hairs may now also make visible all non-pigmented vellus hairs that previously were appropriately not captured by the photographic technique. Although the phototrichogram as described above should be able to give information on growth rate, the hairs are photographed from an aerial view that does not facilitate determination of hair length. An enhanced phototrichogram technique, which flattens the target area hair onto the scalp through direct contact with a digital microscope, enables reliable determination of hair length (and, thus, the extrapolation of hair-growth rate) as well. This technique uses digital luminescence microscopy at 20 to 50 times magnification, which can generally detect hairs ³5mm diameter and uses image-analysis software to measure hair numbers and hair length in a given target area. One such method has been tested in 150 men with androgenetic alopecia treated with 1 of 3 given hair growth promoters for 30 weeks : this demonstrated that small changes in hair width (2.6%) can be statistically significant with good interanalysis reproducibility (3%). Other parameters like global photography and hair weight are more useful to monitor the efficacy of hair growth promoters. ,,
The aforementioned enhanced phototrichogram technique may specifically address growth rate that is otherwise only indirectly captured with hair weight analysis. Another less technical and less expensive way of determining growth rate is to shave the hair in a given target area, allow a set period of time to elapse, and to then reshave and collect the hairs in the target area, determine the mean length of the collected hairs, and divide by the number of days. Both scalp biopsies and the noninvasive techniques of phototrichograms and enhanced phototrichograms can capture this information. Determining the change in percent anagen is useful in helping to sort out the etiology of any observed change in hair density, as also the outcome of hair transplantation if planned at a later date.
| Management|| |
The diagnosis should be confirmed and the patients approached with utmost care and sympathy. Counseling forms an essential part, as does the balance between realistic expectations and therapeutic limitations. Patients should be advised to avoid hair care products likely to damage scalp/hair. Patients should maintain an adequate diet, especially one with adequate protein. The recommended daily allowance for protein is about 1 gm/kg, which translates into 50 gm for a 50 kg. person. Topical medications work only where the medication is applied; therefore, the entire area at risk of hair loss (the top of the scalp) should be treated with a given topical agent. If possible, any drugs that could negatively affect hair growth should be stopped and alternative substitutes made. Although certain drugs are more commonly associated with hair loss than others, any drug can potentially cause a telogen effluvium. Medications for which hair loss is a common potential side effect include retinoids, cytotoxic agents, and anticoagulants. Treat any underlying scalp disorder such as seborrheic dermatitis or scalp psoriasis as these conditions can affect the ability to use topical treatments.
Medical treatment for men
Currently, only finasteride 1 mg and minoxidil topical solution (2% and 5%) are FDA approved for the treatment of male pattern hair loss (MPHL). Both drugs retard further thinning and increase scalp coverage. However, in many patients, the main perceived response might be maintenance of current hair density. Neither drug restores all the lost hair. Neither drug is able to reverse total baldness. Both drugs require chronic use to maintain effectiveness. If treatment is discontinued, the effects of the drug are lost over several months, and the hair density will evolve into what it would have been without treatment. Treatment should be used for 12 months before making a decision about efficacy although benefit may be seen sooner.
One mg orally is FDA-approved for men 18 years old. It is a competitive inhibitor of type II 5µR that decreases the conversion of testosterone (T) to DHT. DHT in serum and scalp is decreased to about two-thirds after treatment. Target area hair counts (T AHC) are generally used to assess efficacy in clinical trials of MPHL. TAHCs are circular target areas 1 cm to 1 inch in diameter typically at the anterior leading edge of the vertex balding area where the terminal, non-vellus, or visible hairs are counted pre and post-treatment. Target area hair counts increase over the first year and peak by 12 months. In men of age 18-41, hair counts increased 16. 9/cm for those on 1 mg finasteride as against 4.1cm2 for those on placebo. Hair growth continues to improve for at least the first 24 months of treatment as the hairs grow longer and thicker. In men aged 18-41, fifty percent show an increase in hair growth by 1 year, and 66% by 2 years on finasteride. A 5-year placebo-controlled trials using both hair counts and expert panel review of global photographs as endpoints confirm that continued use of finasteride helps to maintain this effect and to slow further hair loss. When treatment with finasteride is discontinued, any positive effect on hair growth will be lost in 12 months. The drug is quite safe with no known drug interactions and no effects on liver, kidney, bone marrow, or bone or serum lipids and no effect on spermatogenesis. Reversible sexually related side effects (decreased libido, erectile dysfunction, decreased ejaculate volume) are seen in about 2%. These side effects often resolve during continued treatment or within days to weeks after treatment with finasteride is discontinued. The level of finasteride in semen of men taking finasteride is very low and semen from a man taking finasteride poses no risk to a pregnant woman or to her fetus. ,,Reduction in prostate specific antigen (PSA) is physiologically based on the effect of decreased DHT on the prostate.
Recommendation is that any PSA test value should be doubled for any man taking finasteride to compensate for the effect of the drug. ,,, Recent data from a long-term (7 year) trial of 18,882 men greater than or equal to 55 years old with normal digital rectal examination and less than or equal to 3.0 ng/mL serum PSA who took 5 mg finasteride (5 the standard dose recommended for MPHL) as against placebo revealed a 25% decrease in prostate cancer for those on finasteride (803 on finasteride as against 1147 on placebo). However, 6.4% of men on finasteride developed histologically high-grade cancer (defined as Gleason score 7-10) as against 5.1% of those on placebo. This study only monitored changes in the number of prostate cancers and histologic subtype but did not address the biological aggressiveness of the tumors or outcome. Potential hypotheses for the findings include that: (a) finasteride may selectively inhibit low grade prostate tumors, (b) low DHT may induce histologic changes that mimic high-grade disease, or (c) low DHT may induce higher-grade prostate cancers. Further research and long-tenn observation of men taking finasteride 1 mg needs to be done on this issue.
Minoxidil topical solutions (2% and 5%)
It increases duration of anagen and enlarges miniaturized follicles. As a potassium channel opener and vasodilator the drug's precise mechanism of action is unknown but appears independent of vasodilation. The mode of application should be explained to the patient. One ml is applied twice daily to dry scalp, preferably using a dropper application. Topical minoxidil solution requires approximately 1 hour for absorption. If the patient shampoos or the scalp becomes wet, e.g., from excessive sweating or rain, the medication should be re-applied. If gel or hair spray is used, the medication should be applied first so that absorption is not affected. Target area hair counts and global photographs confirm a significant increase in hair density. The hair growth appears to peak at 16 weeks. Placebo-controlled trials of both target area hair counts and expert panel review of global photographs at 1 year and hair weight studies over 2 years confirm that continued use of topical minoxidil solution helps to maintain this effect and to slow further loss. Five percent topical minoxidil solution is superior to 2% topical minoxidil solution by target hair counts, expert panel review of global photographs, and hair weight studies in men with MPHL. If treatment is discontinued, any positive effect on hair growth will be lost in 4-6 months. Topical minoxidil solution may initially cause a telogen effluvium beginning 2-8 weeks after treatment initiation. This temporary shedding, resulting from the minoxidil initiated release of telogen hairs ("exogen") as anagen promotion begins, is self-limiting with continued treatment and should not be a cause for concern. Patients should be forewarned so that treatment is not interrupted. Adverse effects that are mainly dermatologic like scalp irritation, including dryness, scaling, itching, and/or redness, may occur; these are more common with the 5% topical minoxidil solution than the 2% topical minoxidil solution. Allergic contact dermatitis is uncommon. Patch tests may help to sort out whether a rash is an irritant or allergic contact dermatitis and whether it is related to minoxidil or propylene glycol.
Combination treatment of finasteride and topical minoxidil
There have been no well-controlled studies in humans. A study in the stumptailed macaque, an animal model for pattern hair loss in both sexes, showed an additive effect when both drugs were used concurrently. Men who wish to switch from treatment with one of these agents to the other should continue using the original medication in addition to the new agent for at least 3 months before discontinuing it. This cross over period is needed to provide time for the newer drug to reach a point of effectiveness to avoid excess shedding.
| Medical treatment for women|| |
Women with or without hyperandrogenism
If women are on hormone replacement therapy or an OCP, the dose and type should be stabilized. Over-the-counter DHEA or testosterone in hormone replacement therapies should be avoided. In this way, women with female pattern hair loss (FPHL) will minimize external additions to any potential underlying androgen sensitivity.
Currently, only 2% topical minoxidil solution is FDA approved for the treatment of "women with thinning hair." Five percent topical minoxidil solution, although not currently FDA approved for use in women, has been evaluated in women with FPHL and was found to be significantly more effective than placebo by both target area hair counts and subject assessment.There was a trend towards superior efficacy of 5% topical minoxidil solution over 2% topical minoxidil solution but this was not consistently statistically significant. The sensitivity of target area hair counts as a primary endpoint in FPHL has been questioned. Treatment should be used for 12 months before making a decision about efficacy although benefit may be seen sooner. Topical minoxidil solution works in those women with FPHL both with and without hyperandrogenism and in young and old, pre and postmenopausal women alike. Either 2% or 5% topical minoxidil solution appears safe to use in women with FHPL, with the only additional risk of the 5% topical minoxidil solution over the 2% topical minoxidil solution being a higher incidence of facial hypertrichosis. The hypertrichosis tends to occur over the cheeks and forehead as vellus, not terminal hair and disappears within 4 months of stopping the drug. Although this may be related to inadvertent spreading to the face after local application to the scalp, this may also be a result of hypersensitivity to low levels of systemic absorption of minoxidil. Other local side effects are the same as in men.
Women with hyperandogenism
Hyperandrogenism is synonymous with excessive secretion of androgens, the indirect evidence of which is the existence of hirsutism, severe or treatment refractory acne and/or irregular menses (the latter in a woman of childbearing potential off of OCPs), and/or the elevation of serum testosterone, free testosterone, or DHEAS. Less than 40% of women with FPHL have hyperandrogenism but this population, with clear-cut evidence of androgen hypersensitivity or overproduction, may respond differently to drugs that block the production or effect of androgens than those women with FPHL and no hyperandrogenism. There are few studies evaluating the effect of anti androgens or 5µR inhibitors in FPHL and only one that is large and placebo-controlled. Most studies showing efficacy of these agents have been done in women with hyperandrogenism, particularly those with hirsutism. Studies of these agents in women with FPHL who do not have overt hyperandrogenism have not specifically shown proven efficacy. All of these agents are used off-label for the treatment of hirsutism or female pattern hair loss. Since all antiandrogens or 5µR inhibitors may cause feminization of a male fetus, all women of childbearing potential should use effective means of contraception while taking any of these drugs. OCPs have the additional advantage of also lowering serum androgens. Women of childbearing potential who use an antiandrogen or 5µ-reductase inhibitor should be cautioned to stop the medication and call their doctor if their menses are late. If of childbearing potential and on an OCP for at least 1 month with a negative pregnancy test, or if of non-childbearing potential, one may try spironolactone, finasteride, or cyproterone acetate.
Spironolactone (100-200 mg per day)
Only small, uncontrolled studies with spironolactone in FPHL have been published but they support efficacy in the subset of FPHL with hyperandrogenism. For safety purposes, one should check serum potassium at baseline and 1 month after beginning treatment since hyperkalemia is a rare side effect. Patients should keep well hydrated.
Finasteride (1 mg per day)
In a well-controlled study, finasteride 1mg per day was not shown to be useful in postmenopausal women with FPHL. These subjects were not specifically stratified for hyperandrogenism. Some positive reports in women with hyperandrogenism treated with 1.25 mg per day have emerged. There are no anticipated side effects and no blood tests are necessary. 
One hundred miligram (100 mg) from days 5 to 15 combined with 50 mg ethinyl estradiol on days 5-25 of the menstrual cycle appears most useful. Only one well-controlled study has been done with FPHL and this proves the value of cyproterone acetate in women with hyperandrogenism only. Two mg cyproterene acetate days 5-15 and 50 mg ethinyl estradiol on days 5-25 of the menstrual cycle appears to be less effective in hair loss. No specific blood tests are necessary. 
Nonmedical approaches can provide cosmetic relief to men and women with thinning hair if medical treatments are not indicated, not effective, or not desired by the patient. They can also be used as adjuvant therapy if medical or surgical treatments are used. Tinted powders, lotions, and hair sprays can all provide a cosmetic covering of the scalp in areas of scalp hair thinning and can be useful in camouflaging it. Wigs, hair pieces, and hair extensions can be used to cover a thinning scalp. Advances in the technology of these prostheses have made their use much more acceptable.
Patients over the age of 25 years are preferable. The predictive value of future hair loss is much lower for individuals between the ages of 15 and 25 years of age and surgery in this young group of men may result in misplaced hairlines or an unnatural appearance 20 or 30 years later. Young men with early hair loss already have enough hair for facial framing and will receive limited aesthetic benefit from surgery. Vertex baldness is a progressive process and does not become "stable with time," and therefore, hair transplantation of the vertex should be approached with extreme caution, Ideal candidates are those with just frontal and mid-frontal hair loss. When frontal baldness is corrected, this creates the most dramatic positive change in appearance. Density of donor area should be adequate. Patients with <40 follicular units/cm2 in the donor area are considered poor candidates. Thicker hair shafts (>60-70 microns) demonstrate better coverage compared to finer hair. Lighter colored hair in caucasians gives a more natural look compared to dark colored hair since the contrast between hair and skin is not as apparent.
Women with mild female pattern alopecia (early Ludwig I) are not optimal surgical candidates since differences in pre-transplanted scalp as against post-transplanted scalp are difficult to appreciate. Those with diffuse unpatterned alopecia are poor surgical candidates for the obvious reason that the entire scalp is suffering hair loss, thus, the donor area is of limited value as it is also susceptible to loss. The ideal female patients for hair transplantation are those with high-density donor hair and extensive hair loss or thinning of the frontal scalp.
Experienced surgical teams can create significant coverage in one to two sessions with dense packing of higher number of grafts (1000-2000) being performed per'session. Final results are usually seen 5-6 months after the procedure, and thus, timing between sessions, if needed, is usually a minimum of 6 months. Complications include facial edema, scalp erythema, and recipient site crusts of the scalp are common but usually resolve within 3-7 days although crusting may persist a few additional days. Other possible complications of hair transplants include nausea and vomiting, post operative bleeding (less than 0.5%), infection (less than 0.5%), excessive swelling (5%), temporary headache, temporary numbness of the scalp, abnormal scarring around the grafts (less than 1 %), poor growth of grafts, fainting (less than 1%), folliculitis, keloid formation, neuroma, persistent scalp pain, telogen effluvium, and arterio-venous fistula formation.
This attempts at a procedure where hair-bearing skin is brought closer together by removing the center scalp affected by the alopecia. It is not commonly performed currently. There are many different designs employed in excising the balding area. Reductions may be performed in conjunction with hair transplantation to the remaining bald scalp for a more optimum result. One has to remember that the efficacy diminishes over time due to the unpredictable progression of hair loss in any given individual. Excision scars become noticeable over time. The scar may potentially widen secondary to stretching of adjacent scalp skin. Usually more than one scalp reduction is necessary to effectively address a person's baldness.
Adjunctive medical therapy with surgery
The use of finasteride and/or topical minoxidil may stabilize underlying hair loss therefore necessitating less donor harvesting and less scalp reductions. This will also allow the patient to maintain a more natural appearance over time.
| Conclusion|| |
Because hair loss is so distressing, patients are willing to try just about everything. There are countless products that claim to regrow hair, but there is not enough rigorous science behind most of them. Patients often ask questions about hair care and we tell them that in most cases frequency of shampoos, shampoos themselves, hair coloring and perms are irrelevant in the process of hair loss and that they can feel comfortable using any regular products. We do not suggest any specific shampoos unless there is seborrhoeic dermatitis or psoriasis present. There is so much quackery and we must discourage our patients from any 'miracle' treatments. Unfortunately, many patients have already spent great sums of money with no result. As our knowledge of androgenetic alopecia pathophysiology increases, novel targeted treatments will potentially be developed.
| References|| |
|1.||Norwood O. Male pattern baldness: classification and incidence. South Med J 1975;68: 1359-65. |
|2.||Lesko SM, Rosenberg L, Shapiro S. A case-control study of baldness in relation to myocardial infarction in men. JAMA 1993 ;269(8): 998-1003. |
|3.||Oh BR, Kim SJ, Moon JD, et al. Association of benign prostatic hyperplasia with male pattern baldness. Urology 1998;51(5): 744-8. |
|4.||Muller SA: Alopecia: Syndromes of genetic significance. J Invest Dermatol 1973;60(6): 475-92. |
|5.||Hamilton JB. Male hormone is pre-requisite and an incitant in common baldness. Am J Anat 1942;71 :451-80. |
|6.||Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE. Steroid 5a-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974;186:1213-5. [PUBMED] |
|7.||Kuster W, Happle R. The inheritance of common baldness: two B or not two B? J Am Acad Dermatol 1984; 11 :921-6. [PUBMED] |
|8.||Abell E. Embryology and anatomy of the hair follicle. In: Olsen EA, ed. Disorders of hair growth: diagnosis and treatment. New York: McGraw-Hill,1994;1-19. |
|9.||Whiting DA. Histology of normal hair. In: Hordinsky MK, Sawaya ME, Scher RK, eds. Atlas of hair and nails. Philadelphia: Churchill Livingstone, 2000;9-18. |
|10.||Stenn KS, Nixon AJ, Jahoda CAB, McKay lA, Paus R. Controversies in experimental dermatology: what controls hair cycling? Exp Dermatol 1999;8:229-36. |
|11.||Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev 2001 ;81 :449- 94. [PUBMED] [FULLTEXT]|
|12.||Paus R, Muller-Rover S, Botchkarev VA. Chronobiology of the hair follicle: hunting the hair cycle clock. J Investig Dermatol Symp Proc 1999;4:338-45. |
|13.||Koepp DM, Harper JW, Elledge SJ. How the cyclin becomes a cyclin: regulated proteolysis in the cell cycle. Cell 1999;97:341-4. |
|14.||Cotsarelis G, Sun T-T, Lavker RM. Label-retaining cells reside in the bulge area of pilosebaceous unit; implications for follicular stem cells, hair cycle and skin carcinogenesis. Cell 1990;61:1329-37. |
|15.||Courtois M, Loussouarn G, Hourseau C, Grollier JF. Hair cycle and alopecia. Skin Pharmacol 1994;7:84-9. [PUBMED] |
|16.||Courtois M, Loussouarn G, Hourseau C, Grollier JF. Aging and hair cycles. Br J Dermatol 1995; 132:86-93. [PUBMED] |
|17.||Guarrera M, Rebora A. Anagen hairs may fail to replace telogen hairs in early androgenetic female alopecia. Dermatology 1996; 192:28-31. [PUBMED] |
|18.||Jahoda CAB. Cellular and developmental aspects of androgenetic alopecia. Exp Dermatol 1998;7:235-48. |
|19.||Barraud-Klenovsek MM, Trueb RM. Congenital hypotrichosis due to short anagen. Br J Dermatol 2000;143:612-7. [PUBMED] [FULLTEXT]|
|20.||Hamilton JB. Male hormone stimulation is prerequisite and an incitant in common baldness. Am J Anat 1942;71 :451-80. |
|21.||Price VH. Testosterone metabolism in the skin. Arch Dermatol 1975; 111: 1496-502. [PUBMED] |
|22.||Russell DW, Wilson JD. Steroid 5a-reductase: two genes/two enzymes. Annu Rev Biochem 1994;63 :25-61. [PUBMED] [FULLTEXT]|
|23.||Harris G, Azzolina B, Baginsky W, Cimis G, Rasmusson GH, Tolman RL, et al. Identification and selective inhibition of an isozyme of steroid 5a-reductase in human scalp. Proc Natl Acad Sci USA 1992;89: 10787 -91. |
|24.||Thigpen AE, Silver RI, Guileyardo JM, Casey ML, McConnell JD, Russell DW. Tissue distribution and ontogeny of steroid 5a-reductase isoenzyme expression. J Clin Invest 1993 ;92:903-10. [PUBMED] [FULLTEXT]|
|25.||Bayne EK, Flanagan J, Azzolina B, Einstein R, Mumford J, Avala B, et al . Immunolocalization of type 2 5a-reductase in human hair follicles. J Invest Dermatol 1997; 108:651. |
|26.||Kaufman KD. Androgen metabolism as it affects hair growth in androgenetic alopecia. Dermatol Clin 1996; 14(4): 697-711. |
|27.||Hamilton JB. Patterned hair loss in man: types and incidence. Ann NY Acad Sci 1951 ;53 :708-28. [PUBMED] |
|28.||Ludwig E. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Br J Dermatol 1977;97:247-54. [PUBMED] |
|29.||Olsen EA. The midline part: an important physical clue to the clinical diagnosis of androgenetic alopecia in women. J Am Acad Dermatol 1999;40: 106-9. [PUBMED] [FULLTEXT]|
|30.||Hamilton JB. Patterned loss of hair in man: types and incidence. Ann N Y Acad Sci 1951;53:708-28. [PUBMED] |
|31.||Venning VA, Dawber RP. Patterned androgenic alopecia in women. JAm Acad Dermatol 1988;18:1073-7. [PUBMED] |
|32.||Derksen J, Nagesser SK, Meinders AE, et al. Identification of virilizing adrenal tumors in hirsute women. N Engl J Med 1994;331 :968-73. |
|33.||Whiting DA. Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia. J Am Acad Dermatol 1993;28:755-63. [PUBMED] |
|34.||Kaufman K, Binkowitz B, Savin R, Canfield D. Reproducibility of global photographic assessments of patients with male pattern baldness in a clinical trial with finasteride [abstract]. J Invest Dermatol 1995;104:659. |
|35.||Sperling LC, Lupton GP. Histopathology of non-scarring alopecia. J Cutan Pathol 1995; 22(2): 97-114. |
|36.||Braun-Falco O, Heilgemeir GP. The trichogram. Semin Dermatol 1985;4:4052. |
|37.||Pecoraro V, Astore IPL. Measurement of hair growth under physiological conditions. In: Orfanos CE, Happle R eds. Hair and hair diseases. Berlin: Springer-Verlag, 1990:237-54. |
|38.||Elliot K, Stephenson T, Messenger AG. Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: implications for the control of hair follicle size and androgen responses. J Invest Dermatol 1999;113:873-7. |
|39.||Birch MP, Messenger JF, Messenger AG. Hair density, hair diameter and the prevalence of female pattern hair loss. Br J Dermatol 2001;144:297-304. [PUBMED] [FULLTEXT]|
|40.||Canfield D. Photographic documentation of hair growth in androgenetic alopecia. Dermatol Clin 1996;14:713-21. [PUBMED] |
|41.||O'Brien PC. Procedures for comparing samples with multiple endpoints. Biometrics 1984;40: 1079-87. |
|42.||Sperling LC. Evaluation of hair loss. Curr Probl Dermatol 1996;8: 97-136. |
|43.||Whiting DA, Waldstreicher J, Sanchez M, Kaufman KD. Measuring reversal of hair miniaturization in androgenetic alopecia by follicular counts in horizontal sections of serial scalp biopsies: results of finasteride 1 mg treatment of men and post menopausal women. J Investig Dermatol Symp Proc 1999;4:282-4. |
|44.||Kaufman KD, Olsen EA, Whiting D, et al . Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol 1998;39:578-89. |
|45.||Olsen EA. Androgenetic alopecia. In: Olsen EA, editor. Disorders of hair growth: diagnosis and treatment. New York: McGraw-Hill,1994:257-83. |
|46.||Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, McConnell J, et al. The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med 1992;327: 1185-91. |
|47.||McConnell JD, Wilson JD, George FW, Geller J, Pappas F, Stoner E. Finasteride, an inhibitor of 5a-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab 1992;74:505-8. |
|48.||Dallob AL, Sadick NS, Unger W, Lipert S, Geissler LA, Gregoire SL, et al . The effect of finasteride, a 5a-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. J Clin Endocrinol Metab 1994;79:703-6. |
|49.||Waldstreicher J, Fiedler V, Hordinsky M, Swinehart JM, Thiboutot D, Unger W, et al . Effects of finasteride on dihydrotestosterone content of scalp skin in men with male pattern baldness [abstract]. J Invest Dermatol 1994; 102:615. |
|50.||Kaufman KD, Gormley GJ, Binkowitz B, Jacobsen CA, Bruno K, the Finasteride Male Pattern Baldness Study Group. The effects of oral finasteride on scalp hair growth in men with male pattern baldness. 77th Annual Meeting of the Endocrine Society, Program and Abstracts, Washington, DC, June 1417, 1995. Bethesda (MD): The Endocrine Society Press; 1995. p. 326. |
|51.||Kaufman KD. Clinical studies on the effects of oral finasteride, a type II 5a-reductase inhibitor, on scalp hair in men with male pattern baldness. In: Van Neste D, Randall V A, eds. Hair research for the next millennium. Proceedings of the First Tricontinental Meeting of Hair Research Societies; Brussels, Belgium, Oct 8-10,1995. Amsterdam (Netherlands): Elsevier Science BV; 1996. p. 363-5. |
|52.||Pocock SJ, Geller NL, Tsiatis AA. The analysis of multiple endpoints in clinical trials. Biometrics 1987;43:487-98. |
|53.||Moore E, Bracken B, Bremner W, Geller J, Imperato-McGinley J, McConnell J, et al. Proscar®: five-year experience. Eur Urol 1995;28:304-9. |
|54.||Guess HA, Gormley GJ, Stoner E, Oesterling JE. The effect of finasteride on prostate-specific antigen: review of the available data. J Urol 1992; 155 :3-9. |
|55.||Headington JT, Novak E: Clinical and histological studies of male pattern baldness treated with topical minoxidil. CUIT Ther Res Clin Exp 1984; 36: 1098-1106. |
|56.||Roberts J, Hordinsky M, Olsen E, Savin R, Bergfeld W, Price V, et al. The effects of finasteride on post-menopausal women with androgenetic alopecia. Hair Workshop, Brussels, Belgium, May 2-3, 1998. p. 16. |
|57.||Burke BM, Cunliffe WJ. Oral spironolactone therapy for female patients with acne, hirsutism or androgenic alopecia. [Letter]. Br J Dermatol 1985;112:124-25. |
|58.||Shum KW, Cullen DR, Messenger AG. Hair loss in women with hyperandrogenism: four cases responding to finasteride. J Am Acad Dermatol 2002;47:733-9 . |
|59.||Dawber RPR, Sonnex T, Ralfs I. Oral anti-androgen treatment of common baldness in women. Br J Dermatol 1982; 107:20. |
|60.||Stough D. Hair replacement. Surgical and medical. St. Louis: Mosby; 1996 . |
|61.||Bernstein RM, Rassman WR. Follicular transplantation: Patient evaluation and surgical planning. Dermatol Surg 1997;23:771-84. |
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