On Jan. 22, researchers from the University of Michigan announced results from a very small study about the curious side effect of a common acne medication.
From the resulting media hoopla and public fervor, one might have assumed this drug cured cancer. But, in fact, all the Vitamin A-based cream did was cure wrinkles.
Not even most wrinkles. Just the fine ones caused by overexposure to the sun. It also made the skin rosier and faded age spots, in some cases.
Dr. John Voorhees, the dermatologist who announced the finding at a packed New York news conference, appeared on network TV, on radio, in newspapers and magazines. He joked with reporters that it was difficult to keep the Retin-A cream around his Ann Arbor laboratory; people kept appropriating it.
“I use it myself,” the 49-year-old researcher confessed.
Mentioned in Comics
As far as the public was concerned, this was endorsement enough: time to slather on the Retin-A. Within weeks Retin-A had been mentioned in the popular comic strips “Doonesbury” and “Cathy.”
But a number of scientists and dermatologists are taking a second look at Retin-A. Some believe Retin-A might have beneficial effects beyond those already seen. But others remain concerned about the long-term effects of using the product and worry about all that is not known.
“Perspective,” said Dr. Arthur Balin, associate professor of investigative dermatology at Rockefeller University in New York. “It is important to keep perspective.”
“The Michigan study had only 30 subjects. The results were modest. There are some side effects. All this needs to be weighed.”
Although some dermatologists have been giving their patients Retin-A for a more than a year and were once themselves quite enthusiastic about the drug, there is now a sense of muted approval.
“For what it does, it’s fine,” said Dr. Elizabeth McBurney, an associate clinical professor at Tulane University in New Orleans.
“This not some new magical cream. It really has its limitations,” said Dr. Harold Brody, a dermatological surgeon from Emory University in Atlanta. “It is clearly not for everyone.”
The limitations of Retin-A are fairly well-defined by what it does: repair sun-damaged skin, skin that has become sallow, leathery and finely wrinkled.
That is wonderful, Brody said, “but the wrinkles most people worry about are not caused by the sun. They are caused by gravity and by age. Retin-A will do nothing for those.”
Consequently, Retin-A is most effective on people with fair skin that is easily sun-damaged. It will do very little for Latinos, blacks or olive-skinned whites.
“They’re protected from the sun’s rays because they have more melanin, which gives them their darker pigment,” Brody said. “If for some reason they did develop sun damage, Retin-A would help, but they usually don’t.”
The advantages of Retin-A need to be weighed against its disadvantages. The drug almost invariably produces a rash that is usually mild and goes away in a couple of months, but that can become quite severe--and in some people unbearable--if the ointment is misused.
“If you’ve got a lot of peeling and irritation, you’re putting too much on,” McBurney said. “Unfortunately, though, there are always going to be people who think if a little is good, then a lot is better.”
However, there is a far bigger disadvantage of Retin-A, one that directly affects those most likely to be drawn to it in the first place.
“If you use Retin-A, your days of a deep dark tan are over,” McBurney said.
Skin Sensitive to Sun
Because Retin-A essentially reverses the damage the sun has done to the skin, it makes the skin newly sensitive to the sun. Patients who put Retin-A on at night and do not judiciously apply a strong sunscreen during the day will “burn to a crisp,” McBurney said.
For all the caveats about Retin-A, it does have one major thing going for it.
“It only costs about $15 for a tube, which if you use it right, should last about four to six months,” Brody said.
A quick consumer warning: Retin-A is different from the Vitamin A derivatives cosmetic companies are claiming are in their products. The difference is rather basic: Retin-A gets into the skin cells themselves, and the cosmetics just sit there.
“It’s like trying to give yourself a blood transfusion by rubbing blood on your skin,” McBurney said.
Real Retin-A, manufactured by Ortho Pharmaceutical Corp. of Raritan, N.J., is available only by prescription. The company is involved in extensive clinical trials to prove the drug’s anti-wrinkle properties, but officials say they have not decided whether to seek over-the-counter approval for the drug.
“It’s quite an important drug--for acne,” Balin said. “We’ve been using it for 15 years for that purpose, and we have seen no real problems with long-term effects. But we do not know what effect this will have in the long haul on people using it for other purposes; that is true.”
“There are some very important questions we need to answer about Retin-A,” Brody added. “How it works, for example.”
Acts Directly on Cells
Retin-A is the trade name for an ointment containing tretinoin, a derivative of Vitamin A known as all-trans-retinoic acid. Tretinoin appears to act directly on skin cells, causing them to multiply and differentiate. This, in theory, is what replenishes the flesh and repairs sun-damaged dermis.
But it is only a theory.
“We do know that the skin cells do have receptor sites for the Vitamin A acid derivative,” McBurney said. “Apparently the medicine, when applied to the skin, does attach to the skin kind of like putting the key in the lock. It opens some sort of a door to development, though what that is is unclear.”
Skin biopsies on people using Retin-A show a thickening of the skin’s outer layer and the increased formation of collagen, the connective tissue underneath. But the biopsies do not answer some important questions.
“We do not know, for example, whether the effect is permanent, that it establishes a new set-point in the skin, or whether patients will deteriorate quickly should they stop using it,” Brody said. “It appears to be the former, but that remains to be proven.”
If Retin-A does indeed replace sun-damaged cells with new ones, it may also reverse or retard the development of skin cancers precipitated by the sun’s ultraviolet rays. Other forms of Vitamin A have been shown to do this, and there is some preliminary evidence that Retin-A may as well, at least hypothetically.
There is some evidence tretinoin is an effective treatment for actinic keratoses, rough red patches of skin believed to be precursors to skin cancer. Balin has recently completed a 15-month controlled study on this subject and says he may be ready to report results in a few months.
Other Treatments Available
One of the reasons dermatologists, and particularly dermatological surgeons, may seem less than deliriously happy about Retin-A is they believe there are already more effective treatments available.
“With a face lift, we can remove the deep wrinkles that Retin-A doesn’t affect, and for those sun lines and such, we’ve got dermabrasion and chemical peels,” Balin said.
Dermabrasion is a seemingly tortuous but actually relatively painless procedure in which the skin of the face is frozen and then literally sanded off, revealing fresh unwrinkled skin below. Chemical peels are less effective but work much the same way--trichloroacetic acid for light peels, phenol for deeper peels.
The effect can be quite dramatic.
“We can take a woman who’s 65 and who’s all wrinkly and stuff, and with a dermabrasion turn her skin into the skin of a 40-year-old in one day,” Balin said.
But even here, Retin-A may play some role.
“We have found the drug can aid the healing process of dermatologic surgical procedures such as dermabrasion and chemical peeling because it helps thicken the skin and improve resilence,” said Dr. James Stagnone, a clinical professor of dermatology at the University of New Mexico in Albuquerque.
Retin-A may also help clear up the pimples that often result as a side effect of the surgery, he said.
Despite the success of these procedures, they have failed to generate the excitement of Retin-A for a rather simple reason. Dermabrasions run about $2,500, and chemical peels several hundred dollars depending on the type and extent.
“I guess you get what you pay for,” Balin said. “Obviously, many people who cannot afford dermabrasions or peels will be able to afford Retin-A. Maybe millions of people.”