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Sat 20 Sep 2008 04:00 AM

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Topical drug treatments for age spots

A bit of sun may give skin a youthful glow but, over time, too much can leave it looking old.

A bit of sun may give skin a youthful glow but, over time, too much can leave it looking old.

Photoaging (skin damage caused by the sun) not only contributes to fine lines, wrinkles and leathery-looking skin, but also can cause uneven skin darkening that gives rise to age spots, or solar lentigines (len-TIH-gen-eez) - also called liver spots because of their brownish colour.

These are areas where pigment (melanin) has clumped together, forming dark splotches.

Regular use of such broad-spectrum sunscreens will vastly increase the response to any prescription medication for photoaged skin.

They're most common on sun-exposed areas such as the backs of the hands and parts of the face. Solar lentigines occur occasionally in early adulthood, but mainly after age 40. More than 90% of white people over age 50 have at least one.

The upper layer of the skin (the epidermis) protects itself from the sun's ultraviolet rays by thickening and producing more melanin, the pigment responsible for tanning.

Age spots arise when melanin clumps together after years of sun damage, in much the same way that a callus develops in response to repeated contact and pressure.

Solar lentigines (a single one is called a lentigo) are most common on sun-exposed areas of the body, including the backs of the hands and parts of the face, back, arms, legs, feet and shoulders.

Even without years of sun exposure, some kinds of skin form the small brown spots that we call freckles.

Age spots differ in that they do not typically fade when protected from sunlight and they are often larger in size. Several can mass together and form more noticeable mottled patches.

Age spots are harmless, but they can be unattractive and give skin an older appearance. At one time, the only remedy was to cover them up with cosmetics.

Now, there are therapies that help reverse the signs of photoaging at the physiological level.

One approach is physical removal - by laser surgery, cryosurgery (freezing), microdermabrasion, or chemical peel.

Physical removal can be very effective, but it can be expensive and sometimes has harsh side effects, such as pain and reddening of the skin.

Many women prefer to start with something gentler - topical medications that help fade age spots over time.

Sunscreen first

The first line of defense against age spots is a sunscreen with a sun protection factor (SPF) rating of 30 or higher.

According to Dr. Mollie MacCormack, a dermatologist at Lahey Clinic in Burlington, Mass., the best sunscreens contain one of the following active ingredients: zinc oxide or titanium dioxide in a concentration of 9% or higher, ecamsule (Mexoryl), or helioplex (a proprietary formulation that includes both avobenzone and oxybenzone).

These kinds of sunscreens, she says, "will give you long-lasting protection against UVA and UVB light," the ranges of ultraviolet radiation wavelengths that damage skin. "Regular use of such broad-spectrum sunscreens will vastly increase the response to any prescription medication for photoaged skin."

Mostly by prescription

The topical drugs used in the treatment of age spots work mainly by interrupting melanin formation. Prescription topicals generally do the best job because they have active ingredients in higher concentrations than over-the-counter products.

One downside is that people with sensitive skin may not tolerate them as well.

The most commonly used agents include the following: Hydroquinone

Many dermatologists consider hydroquinone the best choice for treating age spots. As a prescription drug, it's available in a 4% cream, which is usually applied twice daily. (Over-the-counter preparations may contain up to 2% hydroquinone.)

You can expect to see results in four to six weeks, with the greatest improvement after four to six months. The most common side effect is irritation or reddening of the skin.

Hydroquinone may soon be harder to come by. In August 2006, the FDA proposed a ban on all over-the-counter sales of hydroquinone-based cosmetics because studies turned up evidence that the drug may cause cancer when it is fed to rats and mice.

This is very different from how it is used in humans, and so far, there are no studies showing any increased risk to humans when the drug is used topically. As we went to press, the FDA was still responding to challenges from critics who oppose the ban.

Age spots or something else?It's important to distinguish age spots from other discoloured, irregular lesions, such as actinic keratoses (dry, discoloured patches that can develop into squamous cell skin cancer) and melanoma, the deadliest form of skin cancer. Be sure to see a dermatologist about any persistent skin lesion that is dark with irregular borders or colours, has raised areas, is itchy or painful, or has recently grown or otherwise changed in appearance.


One of the vitamin A-related compounds known as retinoids, topical tretinoin first received FDA approval in 1971 for treating acne. Since then, it has also been approved (at a concentration of 0.05%) for the reduction of wrinkles, roughness, and age spots.

Randomized placebo-controlled trials have consistently demonstrated that tretinoin improves photoaged skin.

Tissue studies indicate beneficial changes in collagen production and melanin distribution. Applied once a day at bedtime, tretinoin works by accelerating the turnover of skin cells and suppressing melanin-producing cells (melanocytes).

Remember that after any treatment for age spots, you must unfailingly use sun block.

It can take several months to lighten age spots. Brand names include Retin-A, Retin-A Micro, Renova and Avita.

Possible side effects include irritation, redness, scaling, itchiness burning, and dryness, though these generally subside after a few weeks. The irritation may actually be beneficial, because it helps tretinoin to penetrate the dermis (the layer below the epidermis) and stimulate the production of new blood vessels, collagen, and elastic tissue.

A warning: tretinoin makes the skin more sun-sensitive, so if you use it, you must apply a high-SPF, broad-spectrum sunscreen before going outdoors.

Animal experiments have shown that oral tretinoin can harm a foetus. It's not known whether topical tretinoin has any effects on developing humans, but because of the potential risk, women should not use it during pregnancy or lactation, or if they are trying to conceive.

To help avoid side effects, be sure to tell your doctor if you're taking other skin medications, such as the oral psoriasis drug acitretin (also a retinoid) or oral tretinoin.

For overall improvement in photoaged skin, tretinoin and other retinoid drugs are a better choice than hydroquinone. But if you need to treat specific age spots, hydroquinone or the depigmenting agent mequinol (4-hydroxyanisole) are preferable.

In a pair of randomized trials involving 1,175 subjects, a combination of mequinol with tretinoin in a liquid preparation (brand-named Solagé) was found to be superior to either of the active ingredients alone, and to a placebo, for the treatment of age spots on the forearms and face.

Adapalene gel

This prescription drug is approved only for treating acne but sometimes is used off-label to improve photoaged skin. In one controlled trial involving 90 men and women, solar lentigines lightened more in patients using adapalene than in those using a placebo.

Other prescription topicals

Another topical agent, azelaic acid, inhibits tyrosinase, an enzyme involved in melanin production. Although more irritating to the skin than hydroquinone, it may be an alternative for people reluctant to use hydroquinone because of the possible cancer connection.

Both drugs are effective in treating a condition known as melasma that often develops during pregnancy - diffuse mottled pigmentation on the cheeks and forehead and around the eyes.

Because age spots are considered a cosmetic problem, health insurance may not cover the cost of topical prescription medications. A 45-gram tube of generic tretinoin sells for $50 to more than $80 and lasts up to three months; a one-month supply of generic hydroquinone (30 grams) costs about $50.

A 30-gram tube of Tri-Luma - a popular combination of hydroquinone and tretinoin, plus a steroid to reduce redness - costs more than $100. Although these prescription drugs seem expensive, they may actually cost less than some over-the-counter skin-improvement products.

With summer behind us, it may be a good time to start treating photoaged skin. But remember that after any treatment for age spots, you must unfailingly use sun block. If you don't, just 10 minutes of sun on a spring day can cause them to become dark again, reversing the months of effort it took to lighten them.

What about applying vitamins & antioxidants to the skin?• When vitamins and antioxidants are used in cosmetics, they are often called cosmeceuticals - a word that refers to topically applied ingredients with druglike effects that change the skin's appearance. The FDA does not recognise the term, but it regulates some of the substances involved and makes recommendations on others. The use of vitamins and antioxidants (such as vitamins A, C and E) in moisturisers and other cosmetics makes sense theoretically because antioxidants counter harmful molecules called free radicals, which cause oxidative deterioration. Several cosmeceuticals have shown promise in treating symptoms of photoaging, including age spots.

• Many anti-aging skin products contain retinol, a vitamin A derivative and part of the same retinoid family that includes tretinoin. Retinol has less biological activity than tretinoin but works the same way - by interrupting melanin production. It also helps reduce wrinkles. Though not as effective as tretinoin, retinol may be easier to take for women with sensitive skin.

• Of the antioxidant vitamins touted to reverse skin aging - vitamins A, C and E - vitamin A (as retinol) has proven most effective, says dermatologist Dr. Mollie MacCormack. Many skin care products contain vitamin E, but no clinical studies have shown that it prevents or reverses signs of photoaging. In a 12-week clinical trial, a 10% concentration of vitamin C reduced wrinkles and improved skin tone and hue. Other studies suggest it helps increase collagen.

• Many creams, lotions and oils contain ascorbyl palmitate, a derivative of vitamin C. Because it's not acidic, it's less irritating to the skin. But at the low concentrations typically found in skin care products, it's doubtful whether ascorbyl palmitate is effective. Another antioxidant, alpha-lipoic acid, has shown promise in decreasing age spots, wrinkles, and roughness, but research on this compound is still in the early stages.

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