How Do You Advise the Balding Patient?

Sagar Mungekar

Faculty Peer Reviewed

The incidence of male pattern hair loss can reach almost 100% in some ethnic groups.1, 2 While treatment of the condition is usually deferred to dermatologists, it is often the primary care physician (PCP) who is first approached for advice. Several medical and surgical treatments exist for male pattern hair loss. Herbal supplements and products on infomercials make cursory non-FDA-approved claims of hair growth. Minoxidil, once developed for hypertension, is available over the counter as a scalp treatment. Finasteride and the newer dutasteride may curb hair loss but also cause sexual and developmental side effects that preclude use by couples who are pregnant or trying to conceive. Hair transplant surgery is a very expensive but effective and lasting procedure in persons with good occipital-parietal hair density. Given the myriad options, it is essential that the internist be able to offer advice and assist the balding patient in making an informed decision.

Male pattern hair loss is medically referred to as androgenetic alopecia (AGA). At initial presentation, it is important to differentiate between AGA and other causes of hair loss. As with any condition, the past medical history can yield clues. Febrile infections, major surgery requiring general anesthesia, cancer, hypothyroidism, and profound emotional stress can result in telogen effluvium: an acute, diffuse, reversible loss of terminal hair.3 Hair loss caused by malnutrition or protein deficiency may develop due to strict vegetarian or crash diets and sudden weight loss. Trichotillomania, the impulse control disorder of repeatedly pulling out hair, may result from a habit, an addiction, or an obsessive compulsive disorder.4, 5 Tight braids, hair extensions,6 orthodontic headgear,7 and turbans 8 can cause traction alopecia.

The gold standard for the diagnosis of AGA is scalp biopsy, though this invasive procedure is rarely required.3 In men, the diagnosis of AGA is often easy: the hair loss is characterized by an em-shaped balding pattern, variably thinning strands, and the presence of vellus-like hair in place of terminal strands. In women not suffering from androgen excess, AGA is diagnosed in those presenting with diffuse thinning over the frontal region; the stereotypical male frontotemporal balding pattern is often not present.1, 9

The cycle of hair growth mainly involves two phases: anagen, a long growing period, and telogen, a shorter resting period. In AGA, each successive anagen phase is reduced and delayed, leading to shorter strands, the appearance of thinning hair, and a decrease in the total number of terminal strands.10-12 This process is largely mediated by the potent androgen dihydrotestosterone (DHT), converted from testosterone by the enzyme 5-alpha-reductase, of which there are two isotypes.13-17

While more recent drug therapies have focused on DHT, the first FDA-approved drug for AGA, minoxidil, functions by an unknown mechanism, though vasodilatation is most frequently cited.18-26 Minoxidil, initially manufactured under the trade name Rogaine by Pfizer, is available without prescription as a 5% foam for men and a 2% solution for women for use twice daily. Due to its relatively long history on the market, there are several studies that show the efficacy of minoxidil compared to placebo; however, the results are not as promising as the lay public has been led to believe. A study in 1999 showed that while hair weight increased during treatment, the hair count did not change significantly.20 Two randomized trials reached different conclusions in their attempts to demonstrate a higher efficacy of the 5% over the 2% formulation.20, 27 Of particular note (and benefit to the pharmaceutical companies), virtually all studies show that a cessation of the therapy results in complete loss of newly acquired and thickened hair, making minoxidil application a lifelong commitment. Side-effects have been minor; the most common is hypertrichosis in unwanted areas, a special concern for women that usually precludes their acceptance of the 5% solution. Minoxidil remains the only FDA-approved drug for AGA in women, though it carries a category C status for pregnancy; a few case reports have suggested that birth defects are possible.28-30

Finasteride (Propecia, Proscar) is a pill approved by the FDA for men with AGA at a dosage of 1 mg per day. It exerts its action by inhibiting type II 5-alpha-reductase. As with minoxidil, finasteride is more potent at increasing hair weight and curbing hair loss than promoting new hair growth.31, 32 Even the chart on the package insert of finasteride indicates that the mean change of hair number over five years in those taking the drug is close to zero.33 There has been concern about finasteride’s effect on the reliability of the prostate-specific antigen (PSA) test, but recent studies suggest that finasteride enhances detection of prostate cancer by PSA and also improves the test’s ability to identify high-grade cancers.

Dutasteride (Avodart) is a potent inhibitor of both isotypes of 5-alpha-reductase, decreasing serum DHT levels more than finasteride.34, 35 It has been approved by the FDA for benign prostatic hypertrophy (BPH), but treatment of AGA has become an off-label use. Clinical trials were stopped prior to phase III, but a phase II study showed an increase in hair number over double that of finasteride.36 This study, though, used a maximum dosage of 2.5 g per day of dutasteride, which is 5 times the dosage approved for BPH.

Some have suggested that the trials for dutasteride were halted because of its long-lasting adverse effects. Both 5-alpha-reductase inhibitors have caused decreased libido, impotence, decreased sperm motility, and gynecomastia. These side effects reverse with discontinuation of the drug, but since the half-life of dutasteride is 5 weeks (versus 6-8 hours for finasteride), the adverse effects remain much longer.36, 37 Given the role of DHT in development, it’s not surprising that both finasteride and dutasteride are labeled as pregnancy category X by the FDA and not approved for use in women. The risk is so high that pregnant females are advised not to handle the tablets at all for fear of cutaneous absorption. This is a particular risk for finasteride, supplied in 5-mg dosages for BPH, which patients may crush and take as 1-mg aliquots, and in the process inadvertently spread the powder over the working surface. Similarly, dutasteride is supplied only as liquid-filled caplets, which must be taken whole; exposing the contents may result in oropharyngeal irritation38 and inadvertent cutaneous absorption. Taken together, the decrease in male fertility and libido and potential for feminization of male fetuses are crucial factors that must be considered in males planning families. Notably, studies showed no significant improvement in middle-age women with female-pattern alopecia and case reports have raised concern about promotion of breast cancer in women (and rarely in men).

Cost and efficacy are likely the patient’s more important considerations, since cosmetic treatments are not covered by insurance companies. One month’s supply of minoxidil, finasteride, and dutasteride costs approximately $10 (generic), $60, and $100, respectively.39 Since the treatment must be continued indefinitely, the total cost can easily approach that of hair transplant surgery (~$125 per square centimeter), which is permanent.40 However, these medications are invariably recommended after hair transplantation to preserve the remaining non-transplanted hairs. Women may not have adequate donor sites for hair transplantation. There are dozens of other OTC treatments and herbal supplements in the forms of pills, shampoos, cleansers, and other vehicles that claim to restore hair. In general, no clinical trials have been undertaken to substantiate the dubious claims41 and the costs of the “systems” may exceed that of the aforementioned drugs.

Patients should be informed that there isn’t a “magic bullet” for AGA, and that the few tested medical therapies may curb hair loss rather than promote hair growth. For couples with fertility issues, adverse sexual effects of the 5-alpha-reductase inhibitors must be considered. For pregnant couples, the act of crushing tablets to save on cost may result in significant birth defects. The balding patient should carefully consider the physiological and monetary costs associated with attenuating this common process.

Peer Reviewed by: Miguel Sanchez, MD Associate Professor, Department of Dermatology

Sagar Mungekar is a fourth year medical student at NYU School of Medicine

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