Some Off-Label Uses of Medications Promote Hair Growth

While Propecia (finasteride 1 mg) and Rogaine (minoxidil 2% and 5%) are the only available US Food and Drug Administration (FDA)-approved drugs for hair loss, some doctors are finding that other, non-approved medications can be useful options for treating hair loss.

"Dermatologists often write off-label prescriptions to help patients," said Ken Washenik, MD, PhD, medical director of BOSLEY, a hair restoration clinic in Beverly Hills, California. Off-label treatments for hair loss include Proscar (finasteride 5 mg) and Avodart (dutasteride 0.5 mg), approved to treat prostate enlargement (symptomatic benign prostatic hyperplasia); Aldactone (spironolactone), a weak diuretic ("water pill") approved for congestive heart failure; and Retin-A (tretinoin), a topical acne medication, prescribed in combination with Rogaine.

Proscar
Proscar, approved to treat prostate enlargement, and Propecia, which is FDA-approved to treat hair loss, are actually different strengths of the same drug: finasteride. Finasteride slows hair loss by blocking the conversion of testosterone to dihydrotestosterone (DHT), which has been definitively linked to baldness in genetically susceptible men.

Testosterone is normally converted into DHT by two types (type 1 and type 2) of the enzyme 5-alpha reductase. Finasteride works by inhibiting the type 2 form of the enzyme, the type that is concentrated in hair follicles.

Proscar is essentially a higher dose of Propecia. "It's like Tylenol versus Extra Strength Tylenol," Dr. Washenik explained. While Proscar is dispensed as a 5 mg tablet, Propecia is a 1 mg tablet.

Some doctors don't recommend that patients take a full Proscar tablet because they believe 5 mg of finasteride isn't any more effective for hair loss than 1 mg of the drug, according to Peter Proctor, PhD, MD, a pharmacologist and toxicologist who treats patients for various hair loss conditions in Houston, Texas.

The same can be said of Propecia dosing. "A little bit [of Propecia] does the same as a lot," according to Dr. Proctor.

Some doctors who prescribe Proscar for hair loss recommend that patients divide the tablet up into four or five sections simply in order to save money. Dr. Procter notes, however, that the tablets are difficult to break up because of their shape.

Although used in men, women who are or who may become pregnant should not take this medication and are told not to handle crushed finasteride tablets. If absorbed through the skin, the medication could, theoretically, cause birth defects in a male fetus.

While Propecia blocks approximately 55% of DHT activity, Proscar blocks 70%. In the experience of Dr. Michael Reed, a dermatologist and hair transplant surgeon in New York City, who has treated hundreds of men and women for hair loss with these medications, there are a number of individuals who respond better to Proscar than Propecia, especially post-menopausal women and older men.

"Doctors who say that these medications don't work or that there is no difference between them usually have not treated enough people long enough to make such statements, or have drawn over-conclusions from limited data," Dr. Reed said. "I have treated some patients for over 10 years with Proscar, and I know it works better for some patients than its 'weaker brother' Propecia."

Avodart
Avodart (dutasteride) is FDA-approved for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate. Like Proscar, this drug appears to have some impact on hair growth as well.

The excitement around Avodart stems from early clinical tests sponsored by the drug's manufacturer, GlaxoSmithKline. These trials indicated that dutasteride results in a greater and longer inhibition of DHT than finasteride. Researchers theorize that dutasteride may be more effective than finasteride because it blocks both type 1 and type 2, 5-alpha reductase, while finasteride blocks only type 2.

According to a GlaxoSmithKline spokesperson, Phase III trials comparing the effectiveness of both drugs were discontinued because the company wanted to reallocate resources toward more medically oriented research.

Based on the limited data available to researchers, dutasteride appears to lower DHT by 94% in patients, while finasteride appears to lower DHT by about 70%, Dr. Washenik said. He cautions that Avodart's longer half-life could result in lingering side effects.

Physicians can't be certain of Avodart's safety because Phase III trial data are not available and because the incidence of side effects is significantly higher than with Propecia. It is known, however, that women, especially those who are pregnant, should not use the drug because of an increased risk of birth defects.

Aldactone
Aldactone (spironolactone) is an oral FDA-approved diuretic used to treat congestive heart failure and high blood pressure. The drug also tends to block testosterone, helping to stop hair loss and promote some hair re-growth.

Off-label sprionolactone use is limited to women who may be experiencing hair loss due to the presence of excessive male hormones. It is not used in men because it can cause sexual side effects, Dr. Washenik said.

"This drug has been used for decades even though it is not approved for treating hair loss," Dr. Washenik said. "It's proven to be very safe in women of normal health."

Some women take spironolactone to counteract hair loss caused by oral contraceptives. Oral contraceptives either contain progestin, estrogen or a combination of the two hormones. While estrogens tend to be protective of hair, progestin, like testosterone, can cause hair loss. Women taking oral contraceptives who are experiencing hair loss may want to talk to their physicians, Dr. Proctor said. Such women can either switch to a pill with more estrogen and less progestin, or take spironolactone.

Dr Reed points out that women who are or may become pregnant should avoid this drug, just as they would avoid finasteride. "In my experience, Aldactone has more side effects than finasteride and does not work as well," Dr. Reed said.

Retin-A/Rogaine Compounding
Retin-A, a topical cream or gel that has been FDA-approved to treat acne, is used off-label, in combination with Rogaine, to treat hair loss. Although its exact mechanism of action is unknown, Rogaine increases the size of the follicle and promotes hair growth.

While Retin-A may have some hair growth properties, its real purpose is to increase the absorption of Rogaine. Some studies indicate that Retin-A seems to synergize with Rogaine, though Dr. Proctor said that this synergy is limited. Applying the two drugs at different times is important because in higher concentrations Rogaine actually inhibits Retin-A.

A number of patients may experience irritation of their scalp from the Retin-A. Applying the drugs separately—the Retin-A once a day and the Rogaine twice daily—may help patients avoid inflammation of their skin, Dr. Washenik noted. If the scalp becomes irritated, the Retin-A may be stopped and the Rogaine continued

Not all physicians recommend the combination, however. "There are conflicting reports about the Retin-A/minoxidil combination," Dr. Washenik said. "I haven't been impressed enough by it to routinely prescribe it."

Dr. Reed has used this combination to enhance penetration of minoxidil since the 1980s and has found that 20% to 30% of patients don't tolerate the 0.025% concentration of Retin-A needed to enhance penetration. In these patients, he skips the Retin-A. "The 5% minoxidil penetrates just fine without help from Retin-A," Dr. Reed said. "And patients don't get much help from topical medication that causes so much irritation that they can't use it regularly."

In general, the primary side effect from Retin-A other than local irritation is photosensitivity, which can lead to sunburn. Rogaine should not be used in people with heart disease because the drug can cause heart palpitations, Dr. Washenik added.

Whether people are interested in Retin-A/Rogaine or other off-label medications for hair loss, experts agree that patients' hair loss needs should be addressed individually. Treatment that works for one person may not work for another, whether it's an off-label drug or an FDA-approved medication.