THE ROLE OF MINOXIDIL IN THE HAIR TRANSPLANTS

The Role of Minoxidil in the Hair Transplantation Setting

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Marc R. Avram, MD, New York, NY
John P. Cole, MD, Atlanta, GA, Cyprus
Marcelo Gandelman, MD, Sao Paulo, Brazil
Robert Haber, MD, Mayfield Heights, OH
Russell Knudsen, MBBS, Sydney, Australia
Matt L. Leavitt, MD, Heathrow, FL
Robert T. Leonard, Jr., DO, Cranston, RI
Carlos J. Puig, DO, Houston, TX
Paul T. Rose, MD, New Port Richey, FL, New York, NY
James E. Vogel, MD, Baltimore, MD
Craig L. Ziering, DO, New York, NY

Minoxidil in Hair Transplant

Recently, a distinguished group of 11 international experts on hair loss and hair transplantation convened to review the physiology and effects of pharmacologic treatments of hair loss and to discuss the value of administering topical minoxidil therapy as an adjunct to hair transplantation. This article presents the key findings and consensus points among the participants.

Introduction

Hair growth is a dynamic processes characterized by repeated cycles of active growth (anagen, 2-–6 years), involution (catagen, 2-–3 weeks), and rest (telogen, 2-–3 months).1 At any one time, approximately 90% of all scalp follicles are undergoing active growth in the anagen phase.2,3 Temporary or permanent hair loss can be caused by a number of factors, including medication, hair styling, chemotherapy, exposure to chemicals, hormonal and nutritional factors, generalized or local skin disease, chronic disease and stress. However, by far, the most common type of hair loss, by far, is androgenetic alopecia (AGA; also known as male or female pattern hair loss), which is estimated to affect half of all men and women by the age of 50. Androgenetic alopecia is the hereditary thinning of the hair that is induced by androgens in genetically (polygenic autosomal trait) predisposed hair follicles. As a result of these hormones, particularly dihydrotestosterone (DHT), hair follicles shrink and the anagen phase of hair growth becomes progressively shorter, resulting in finer, shorter , finer hairs that provide less scalp coverage. Cycle after cycle, the follicle produces an increasingly finer, wispy hair with less pigment until, eventually, there is no visible or perceptible growth at all. Studies have demonstrated that AGA is a clearly a stressful condition with psychologically detrimental effects on both sexes, especially particularly on women patients and on individualsthose who seek professionaling treatment.4-6

Hair Transplantation

Surgical hair transplantation is an extremely popular treatment method for male and female pattern hair loss. The quality of hair transplantation procedures has improved dramatically over the past decade, and modern techniques and instrumentation have eliminated the cosmetically unnatural "corn-row" appearance of hair transplants performed during the 1960s into the 1990s. Hair transplantation involves surgical removal of a strip of hair-bearing scalp tissue (usually 8-–20 cm long by 0.6–- 1.0 cm wide ) from the "donor dominant" hair-bearing areas on the back and sides of the head in which the hair follicles are not susceptible to DHT and continue to normally cycle normally for decades . Traditionally the donor hair was divided into grafts containing 10-–25 hairs each. HIn nature, hair on the scalp grows naturally in follicular groupings of 1-–3 hairs. Thus, larger grafts of 10-–25 hairs appear "pluggy" and unnatural. Recent advances in dividing the donor hair strip into natural 1-–3 hair follicular units (micrografts) and strategically implanting them into hundreds or thousands of recipient sites in the balding area have created consistently natural appearing transplanted hair for men and women.

Fig 1b. Same 5 hair follicular group appears to consist of a two hair and three hair unit.

Follicular groups exist in symmetrical patterns, although there is a somewhat irregular arrangement of the follicular groups within the pattern. Jimenez and Ruifernandez first noted the formula L = k / sq rt of n, where L is the density of hairs in square millimeters, k is a constant depending on the geometric spacing of the follicular units, and n is the density of hair in square centimeters. I have evaluated their formula and found it to be accurate. The geometric arrangement of follicular units follows a triangular pattern (fig 2). k is 10.7 for a triangular pattern. In this case the density of follicular units must equal 114.5 per square centimeters for the distance between the follicular units to equal 1 mm. The distance between the follicular units should be measured from the center of the follicular unit..

Medical Therapy

A better understanding of the biochemistry and physiology of hair growth and hair loss has also resulted in advances in the medical non-surgical medical treatment of hair loss. Currently, there are two pharmacological treatments approved by the United States Food and Drug Administration (FDA) to treat pattern hair loss: topical minoxidil solution and oral finasteride tablets. Well-controlled clinical trials have demonstrated that these agents are safe and effective treatments capable of retarding progression of hair loss and inducing hair regrowth in many individuals with mild to moderate hair loss.3 Recently, a distinguished group of 11 international experts on hair loss and hair transplantation convened to review the physiology and effects of nonsurgical medical treatments of hair loss and to discuss the value of administering topical minoxidil therapy as an adjunct to hair transplantation. The roundtable consensus meeting was held during the 9th Annual Meeting of the International Society of Hair Restoration Surgeryeons in Puerto Vallarta, Mexico, October 2001. This article presents the key findings and consensus points among the participants.

Minoxidil

In 1979, oral minoxidil was approved for the treatment of patients with severe hypertension.8 3 Observations of increased body hair growth in the majority of patients using this antihypertensive preparation led to clinical development of a topical formulation of the drug. Minoxidil 2% topical solution via prescription was approved by the FDA for the treatment of androgenetic alopecia in men (1988) and women (1992). In 1996, the minoxidil 2% solution was approved for over-the-counter use for males and females with androgenetic alopecia. Subsequently, in 1997, minoxidil 5% topical solution was approved for nonprescription use in males with androgenetic alopecia.83 Off-label studies of minoxidil have shown that it stimulates hair regrowth in patients with patchy and extensive alopecia areata and reduces the duration of alopecia caused by chemotherapy. (Fiedler et al., Dermatol Clin. 1996; Duvic et al., JAAD. 1996) Minoxidil is considered a nonspecific biological response modifier. It is thought to act directly on viable, suboptimally functioning follicles via its function as a potassium channel agonist.8,9 (Buhl et al., 1992). Minoxidil topical solution acts directly to enlarge miniaturized follicles and the diameters of the hair shafts they produce. In addition, it converts telogen hair to anagen hairs and prolongs the anagen phase of hair growth, thus slowing the progression of hair loss.3 Although the growth phase maybe prolonged, the follicle will continue to cycle, thus several months use (up to 1 year) may be necessary before maximum optimum potential hair growth is achieved. An important factor that favors regrowth is the presence of a large number of partially miniaturized follicles that are still producing hair 3/8 of an inch or more in length. Studies of minoxidil topical solution in men and women have demonstrated significant increases in both hair count10 and hair weight11,12 compared with a vehicle placebo control, with the minoxidil 5% solution significantly more effective to the 2% solution in male subjects.10 Recently, Rundegren and Trancik9 Trancik12 evaluated the effects of minoxidil 5% and 2% topical solution the on stabilization of hair loss in men and women with androgenetic alopecia. This retrospective analysis was based on comparative data obtained from 4 randomized, double-blind, placebo-controlled trials (n=1,054) and from a major post marketing surveillance study.8 The stabilization response (ie, the percentage of patients showing either an increased or unchanged number of non-vellus, pigmented hairs) varied from 85% to 89% in female studies (n=438) and 75% to 96% in male studies (n=616) (Table 1). Both strengths concentrations of minoxidil topical solution were significantly superior to placebo. The response rates noted in placebo patients is likely due to the excipient propylene glycol. Data from the the postmarketing surveillance study found that of 80% (n=11,000) of patients being treated with minoxidil 2% topical solution reported slowing or stopping of hair loss.13 "Off-label" studies of minoxidil have shown that it stimulates hair regrowth in patients with patchy and extensive alopecia areata and reduces the duration of alopecia caused by chemotherapy.14,15 Three Several studies have examined the use of minoxidil as an adjunct to hair transplantation surgery in men with androgenetic alopecia.1016-12 18 Kassimir10 Kassimir16 conducted an uncontrolled study in 12 male patients with androgenetic alopecia. Minoxidil 3% topical solution was administered twice daily to the transplant area starting 48 to 72 hours after hair transplant surgery. Two patients demonstrated hair growth without the usual shedding 2–4 weeks post-surgery and two additional patients had regrowth within 4 weeks after postsurgical telogen effluvium. This is far sooner than the typical 3 to 5 months. Bouhanna11 Bouhanna17 conducted an uncontrolled study of minoxidil 2% in 16 male patients with androgenetic alopecia. In this study, mMinoxidil was given for 4 weeks prior to surgery, interrupted for 3 weeks, then restarted and continued for 3 months postsurgery. They The study found that in 71% of grafts, partial or total hair was still growing without usual shedding that occurs 2 to 4 weeks postsurgery. The effectiveness of administering minoxidil prior to hair transplant surgery ws also reported by Roenigk and Berman.12 18 In this double-blind trial, 12 males with androgenetic alopecia were randomized to have either minoxidil 2% topical solution or placebo applied to donor area for 6 weeks prior to transplantation and to recipient areas for 17 weeks after surgery. After 17 weeks, significantly less grafted hair was lost by minoxidil-treated patients (22%) compared with placebo-treated patients (22% vs 52%; P=0.001).

Finasteride

Finasteride was originally developed for the treatment of benign prostatic hypertrophy. It differs from minoxidil in that finasteride inhibits the intracellular enzyme 5 a alpha-reductase, which converts testosterone to dihydrotestosterone.3 It is thought that hHigh levels of dihydrotestosterone are thought to act directly on the hair follicle and are a contributing factor to androgenetic alopecia. Oral administration of finasteride produces a reduction in circulating and skin levels of dihydrotestosterone without reducing testosterone. Finasteride 1 mg/day significantly lowers levels of dihydrotestosterone in the scalp, retards progression of hair loss, and induces hair growth in men with androgenetic alopecia. Finasteride is not indicated for use in women. Because of 5a 5 alpha-reductase inhibitors may cause abnormalities of the external genitalia in the male fetus, women who are or may be become pregnant should not use finasteride nor should they handle crushed or broken tablets. Data from three randomized, double-blind, placebo-controlled trials demonstrated that finasteride significantly increased hair counts and improved scalp coverage of both the vertex and frontal regions compared with placebo.1319-15 21 The greatest benefit with regard to hair counts occurred within the first year of therapy with finasteride. Scalp coverage, however, may appear to progressively increase with increased duration of use. , with approximately 66% of men achieving improved scalp, 33% having the same amount of hair as they did on the onset, and 1% lose hair. There are no reports published studies of the use of finasteride as an adjunct to hair replacement surgery in men with androgenetic alopecia.

Other Therapies

There are a number of prescription products that are approved for use in other medical conditions that may have some theoretical effect on hair loss. These include spironolactone, aldactone, flutamide, progesterone, cyproterone acetate, and cimetidine. However, well-controlled trials in patients with androgenetic alopecia are lacking.16 22 In addition, there are countless unapproved treatments—many with an herbal or "natural product" basis— that are sold directly to patients., most with largely unprovenNeither the efficacy nor even the safety of the majority of these products for treatment pattern hair loss have been established. Several roundtable participants stated reported that patients’ negative experiences with some of the costly "snake oil" preparations advertised in magazines and over the internet Internet have resulted in a great amount of cynicism about treatment of hair loss in general.

Current Use of Non-Surgical Medical Treatments in the Hair Transplant

The roundtable participants noted that tThe majority of prospective hair transplant patients report previous use of non-surgical medical treatments prior to their seeking an initial consultation about hair transplant surgery. Approximately 40% of the panel members’ prospective hair transplant patients have used minoxidil (range: 15% to 90%), and about 15% have used finasteride (range: 10% to 50%). A smaller percentageFewer patients (~ 5% to 10%) have tried a combination of both agents. Additionally, more than half of their new patients have experimented with other, unapproved preparations. However, at the time of initial consultation, many of these patients are not using minoxidil and/or finasteride on a regular basis, which is essential to achieving optimal results. Moreover, a few roundtable participants noted d that some of their prospective patients are not evenuna aware of the available approved medical treatments for hair loss. Additional physician and patient education about medical treatments are is critical in managing patients’ expectations and improving patient compliance. Depending on their age, degree of hair loss, and their comfort level with their current appearance and the amount of hair they have currently, approximately 15%–20% of the surgeons’ prospective hair transplant patients are started on non-surgical medical treatments rather than proceeding with a hair transplant. All members of the consensus panel currently recommend minoxidil and/or or finasteride, when indicated, to a large percentage of their patients. More than half of the surgeons recommend minoxidil and finasteride equally, and greater than 70% will sometimes recommend a combination of both. Recommendations center primarily on efficacy, patient preference, and cost. Panel members noted that both agents are safe and well tolerated, although there is a general perception among their patients that minoxidil is a safer treatment. Because minoxidil and finasteride are routinely used as adjuncts to hair transplant surgery, it is important to obtain a detailed history of the patient’s past use of these agents. This may help in the selection of an agent that is both efficacious and addresses patient preferences. It may also provide a gauge as to the level of patient education and follow-up with regard to potential compliance issues that is needed.

Strategies for Optimal Results with Adjunctive MinoxidilMinoxidil Treatment

For patients with existing thinning hair undergoing hair transplantation with existing thinning hair, it is strongly advised to use a one or both of the FDA approved medications to limit further loss and optimize the density from a hair transplant. Recognizing that it usually takes about 2 to 4 months to achieve stabilization of hair loss with minoxidil treatment, the group generally recommends that their patients begin treatment as soon as possible prior to hair transplantationfollowing the initial transplant consult visit. The majority of participants panel members noted that the following advantages of regular minoxidil application prior to surgery: stabilization of progressive hair loss, increased number of number hairs in the anagen phase, increased hair weight and density, and decreased post-surgical telogen shedding. Overall, the groupy agreed that the primary benefit of minoxidil application was within and surrounding the area of hair loss, although a few panel members speculated that its use in the donor area may convert some telogen follicles into anagen follicles, making them more visible during the graft preparation process and possibly even increasing the number of units available for implantation. e potentially viable hair follicles more visible during harvest.

Reported pPotential benefits of regular minoxidil administration following hair transplant surgery included increase in the number of anagen hairs, promotion of hair growth in the transplanted grafts and surrounding area, and reduction of post-surgical shock and telogen effluvium.

Most of the surgeons advise their pPatients are told to stop using minoxidil at least 2 to 3 days prior to surgery (range: 1 to 14 days) to reduce a theoretical risk of increased intra-operative bleeding and minimize skin irritation. Similarly, the surgeons prefer to reinitiate minoxidil administration between 2 and 14 days postsurgery. This allows the epithelium time to heal and minimizes the potential for alcohol theoretical damage to the graft area. By contrast, fFinaesteride use is uninterrupted in the pre- and postsurgical period.

The majority of physicians reported greater efficacy in men and women with mindoxidil 5% compared to minoxidil 2%, including earlier recognition of results. While most noted no increase in adverse negative effects with the 5% solution, some suggested that its benefit should be weighed against a potential for increased scalp irritation, precipitation, and facial hypertrichosis in women.

In addition, most physicians panel members recognized the potential advantages of the combined use of minoxidil in combination with finasteride, based primarily on the different mechanisms of actions of these agents. However, clinical data demonstrating additive or synergistic efficacy in humans with this combination are lacking.

The importance of postsurgical follow-up visits and on-going patient counseling was acknowledged by all of the participants, especially for their patients who continue to use medical therapy to complement the results of their hair transplantation. To enhance surgical outcomes, slow progression of future hair loss, and to prevent the rapid shedding that may accompany discontinuation of pharmacological treatments, the panel members generally recommended their continued, indefinite use. While their scheduling of visits varied among the participants, most reported seeing their patients approximately1- 2 weeks after surgery, and every 3 months after that for the first year, followed by visits every 6 months thereafter.

Over a decade of successful use of topical minoxidil in the treatment of patients with pattern hair loss and in the nonsurgical setting, coupled with eEncouraging results from the three, small, preliminary studies^10-12 of minoxidil topical solution as an adjunct to hair transplant surgery, have facilitated its acceptance and successful use in this setting among the specialists. However, the group was unanimous in advocating for additional, larger clinical studies, which would serve to both strengthen their recommendations and to aid in patient education and compliance.

Conclusions

Minoxidil and finesteride finasteride are proven, safe and effective medications for androgenetic alopecia. The use of topical minoxidil and/or oral finaesteride in patients undergoing hair transplant patients with viable but suboptimally functioning follicles in the region to be transplanted ation with remaining thinning hair canwill add to the density and complement the surgical result from the surgery by slowing down or stopping further hair loss. Results from preliminary clinical trials suggest that minoxidil may speed regrowth in transplanted follicles, prolong the anagen phase, and slow progression of future hair loss. Controlled clinical trials are needed to substantiate these preliminary data and what impact other factors such as patient education and compliance may have in enhancing hair transplant outcomes.

REFERENCES

Paus R. Principles of hair cycle control. J Dermatol 1998;25:793-802.

Sperling LC, Mezebish DS. Hair diseases. Med Clin North Am 1998;82:1155-1169.

Price VH. Treatment of hair loss. N Engl J Med 1999;341:994-973.

Cash TF. The psychosocial consequences of androgenetic alopecia: a review of the research literature. Br J Dermatol 1999;141:398-405.

Cash TF, Price VH, Savin RC. Psychological effects of androgenetic alopecia on women: comparisons with balding men and with female control subjects. J Am Acad Dermatol 1993;29:568-575.

Cash TF. The psychological effects of androgenetic alopecia in men. J Am Acad Dermatol 1992;26:926-931.

Adler SC, Rousso D. Evaluation of past and present hair replacement techniques. Aesthetic improvement, effectiveness, postoperative pain, and complications. Arch Facial Plast Surg 1999;1:266-271.

Buhl AE. Minoxidil’s action in hair follicles. J Invest Dermatol. 1991:96(suppl):73S–74S.

Buhl AE, Waldon DJ, Conrad SJ, et al. Potassium channel conductance: a mechanism affecting hair growth in vitro and in vivo. J Invest Dermatol. 1992;98:315–319.

Olsen EA, Funicella T, Koperski JA, Tschen-Cabrera EH. J Am Acad Dermatol. 2001; in press.

Price VH, Menefee E. Quantitative estimation of hair growth. I. Androgenetic alopecia: effect of minoxidil. J Invest Dermatol. 1990;95:683–687.

Price VH, Menefee E, Strauss PC. Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5 percent and 2 percent topical solution, placebo, and no treatment. J Am Acad Dermatol. 1999;41(5, pt 1):717–721.

Rundegren T, Trancik RJ. Stabilization of hair loss with minoxidil topical solution. Presented at the 9^th annual Meeting of the International Society of Hair Restoration Surgery. Puerto Vallarta, Mexico. October 18-22, 2001.

Fiedler VC, Alaiti S. Treatment of alopecia areata. Dermatol Clin 1996;14:733-777.

Duvic M, Lemak NA, Valero V, et al. A randomized trial of minoxidil in chemotherapy-induced alopecia. J Am Acad Dermatol. 1996;35(1): 74–78.

Data on file. Pharmacia Consumer Healthcare.

Kassimir JJ. Use of topical minoxidil as a possible adjunct to hair transplant surgery. JAAD 1987;16:685-687.

Bouhanna P. Topical minoxidil used before and after hair transplantation. J Dermatol Surg Oncol 1989;15:50-53.

Roenigk HH, Berman MD. Topical 2% minoxidil with hair transplantation. Face 1993;4:213-216.

Kaufman KD, Olsen EA, Whiting D, et al. Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol 1998;39:578-589.

Leyden J, Dunlap F, Miller B, et al. Finasteride in the treatment of men with frontal male pattern hair loss. J Am Acad Dermatol 1999;40:930-937.

Physicians circular for Propecia. West Point, Pa.: Merck, December 2001.

Sawaya ME, Shapiro J. Androgenetic alopecia. New approved and unapproved treatments. Dermatol Clin 2000;18:47-61.

Table 1. Stabilization of Hair Loss With Minoxidil Topical Solution

			Patients With Stabilization of Hair Loss (%)
			Minoxidil Topical Solution
Study	Gender	Duration(wk)	5%	2%	Placebo
1	Male(n=295)	32	96	90	67
2	Male(n=321)	48	75	77	56
3	Female(n=193)	32	85	87	73
4	Female(n=245)	48	89	88	69

Stabilization of hair loss=either an increase or unchanged number of non-vellus (pigmented) hairs at the end of the study compared with baseline hair counts.

Adapted from Rundegren and Trancik.⁹ ¹³

Minoxidil as an Adjunct to Hair Transplantation:
Key Consensus Points

Educating patients about medical treatments is essential to managing expectations and improving compliance
Minoxidil treatment should be started as soon as possible prior to surgery to:
Stabilize hair loss
Increase the number of hairs in anagen phase
Increase hair weight and density by enlarging miniaturized, suboptimal follicles
Decrease postsurgical telogen shedding
Following surgery, minoxidil treatment can:
Prolong the anagen phase
Promote hair growth in transplanted grafts
Reduce postsurgical shock and telogen effluvium