Tretinoin Overview

Pregnant woman
Skin problems Image Gallery A developing fetus needs vitamin A, but tretinoin causes a vitamin A overload that can cause a miscarriage or birth defects. See more pictures of skin problems.

Acne is a problem that just about everyone experiences at some point. For some, it becomes a severe problem that can lead to permanent scarring, self-esteem issues and even serious skin infections. For the most persistent cases of acne, there's a drug called tretinoin (and its isomer, isotretinoin). Used either as a pill or a topical cream, it's sort of like an atom bomb in the war against acne. It's a weapon of last resort, one that might cause a lot of collateral damage in the quest for clear skin.

Tretinoin is a big deal for dermatologists for another reason: It can be used to reduce certain signs of aging. It's no fountain of youth, but it is a cornerstone of the multi-billion dollar per year anti-aging industry. This is despite the fact that in 2002 more than 50 scientists released a statement warning about the growing anti-aging industry and proclaiming that there really is no scientific way to "stop, slow or reverse human aging" [source: ScienceDaily].


Sadly, tretinoin use in the 1980s resulted in more birth defects than the use of thalidomide in the 1950s and '60s [sources: National Library of Medicine, Morbidity and Mortality Weekly Report]. Today, its use as an oral medication is strictly controlled and accompanied by an extensive program to prevent women who use the drug from becoming pregnant.

Tretinoin has also been studied extensively as a possible treatment for some forms of cancer and diabetes. Unfortunately, it's a powerful drug that has some significant side effects even when used correctly. There's concern that the drug can cause depression leading to suicide, and that it may cause chronic gastro-intestinal problems. In this article, we'll examine this potent drug and find out what it can and can't do, along with who should use it and who shouldn't.


Tretinoin as Acne Treatment

Accutane (marketed as Roaccutane outside the United States) must not be taken by pregnant women.
Michael Bradley/Getty Images

Tretinoin is derived from retinoic acid, which is the acid form of vitamin A. Vitamin A had traditionally been known as an acne reducer, but if it's taken in large-enough quantities, it's toxic. In the early 1980s, Swiss pharmaceutical company Hoffmann-La Roche developed synthetic tretinoin as an anti-acne medication [source: IBIS]. It's taken in pill form and is commonly known under the brand name Accutane (in a form called isotretinoin). It's effective as an anti-acne drug. Researchers are not really sure what makes tretinoin reduce acne -- they're pretty sure it slows the production of skin oils, but they're not sure how.

The most basic side effect is an increase in skin problems in the short term. Users may suffer worse acne, red skin with scaling or flaking, sensitive skin, dry skin or sensitivity to the sun. After a week or more, these symptoms fade and an overall improvement will be seen.


The most severe confirmed side effect occurs only when the drug is taken by pregnant women, or a woman becomes pregnant while taking it. Most of the time, this results in a miscarriage. If the baby is carried to term, it may be born with severe birth defects. As a result, in the United States, patients must go through a more rigorous process before being approved to take Accutane. Females who are old enough that they could potentially become pregnant must take part in the iPledge program, a system that ensures women exposed to teratogens (drugs or chemicals that cause birth defects) don't become pregnant. Two negative pregnancy tests are required prior to taking isotretinoin, along with monthly pregnancy tests throughout the course of treatment. It's also recommended that women use two concurrent forms of birth control to make sure they don't get pregnant while taking the drug [source: Medicinenet].

Oral tretinoin should be taken with the antibiotic tetracycline. It's OK to take tetracycline while using topical tretinoin (which we'll discuss in detail in the next section). In fact, this combination is often prescribed by dermatologists. There is one other interaction to watch out for, however. Because tretinoin is a form of vitamin A, it can lead to increased levels of vitamin A in the body. Other vitamin A supplements should not be taken while taking tretinoin, because this could lead to toxic levels of vitamin A in the patient's body.

Ironically, pregnant women often take Vitamin A supplements because developing fetuses need a certain level of retinoic acid to develop properly. The body converts the vitamin A partly into retinoic acid -- without it, the fetus could suffer from birth defects.

There are also reports that the use of Accutane leads to depression and suicide, and that it causes Crohn's disease and other inflammatory bowel disorders. However, research into these potential side effects has been inconclusive [source: Barnes]. Due to the potential severity of all these various side effects, tretinoin should only be used as a last resort for severe acne that doesn't respond to milder treatments.

Next, we'll look at the use of tretinoin in a cream or gel form.


Topical Tretinoin

Tretinoin can also be used topically, as a gel or a cream. In this form, it's been sold under the brand name Retin-A. In recent years, strides have been made in combining tretinoin with other drugs to both increase its effectiveness and reduce the unpleasant side effects [source: Melville]. Plus, using it topically (that is, just rubbing it directly onto the skin at the affected area) prevents the drug from having an overall systemic effect on your entire body. There are over-the-counter formulations containing tretinoin, although in lower concentrations than prescription strength versions.

Caution is still indicated for pregnant or breast-feeding women when taking tretinoin topically. Although it's estimated that a tiny amount of the drug enters the blood stream when applied in this way, there have been studies showing some birth defects coinciding with topical use [source: Shapiro et al.]. It's recommended that pregnant or breast-feeding women consult with a doctor before using any topical cream or gel containing tretinoin, even if it's an over-the-counter formulation. As a general rule, use should probably be delayed until after the breast-feeding period.


Since 1995, topical tretinoin has also been FDA approved for use in reducing signs of aging on the face caused by sun damage [source: Lutz]. In some animal tests, tretinoin stimulated the production of collagen, the connective tissue that supports our skin (it's the breakdown of collagen that's partially responsible for the visible signs of aging on our skin). Human trials showed some improvement in sun-damaged skin when combined with sun-avoidance [source: Triax Pharmaceutical]. It reduced colored spots, discolored skin and fine wrinkles. However, there are some caveats: Sun-avoidance measures must be followed after the round of tretinoin treatment is finished, or the results will fade quickly. Also, research showed similarly positive results from a sun-avoidance regimen combined with non-tretinoin creams.

Exposure to the sun does more to age our skin prematurely than just about anything else. Tretinoin may have some use in mitigating this damage, but many of the products containing it use misleading marketing to make it seem like a wonder drug that will "reverse the aging process" [source: FDA]. It won't. In particular, it can't do very much to slow or reverse genetic aging of your skin. In fact, the best way to slow aging is to use a good sunscreen whenever you're out in the sun. If you're looking for miracle youth cream, it's SPF-30.

There are other drugs that are chemically similar to tretinoin. In fact, anything derived from vitamin A is known as a retinoid. They may contain retinol or retinaldehyde (the name comes from the fact that they're needed for the proper development of human vision). Adapalene, Isoprex, and Differin are some examples of retinoids, too. They made not have the exact same effects or side effects as tretinoin, so consult your doctor before taking any of them.

For more information on taking care of your skin, see the links on the next page.


Lots More Information

Related HowStuffWorks Articles

  • Barnes, Connie L. "Isotretinoin Uses and Effects." U.S. Pharmacist. (Sept. 1, 2009)
  • International Birth Defects Information Systems. "Accutane - Isotretinoin." (Sept. 7, 2009)
  • Lutz, Brobson. "Wrinkle Creams and Potents that Work." New Orleans Magazine. May 2007.
  • "isotretinoin." (Sept. 1, 2009)
  • Melville, Nancy A. "Not Fading Away." Dermatology Times. July 2009.
  • Morbidity and Mortality Weekly Report. "Current Trends Birth Defects Caused by Isotretinoin." (Sept. 2, 2009)
  • National Library of Medicine. "Dr. Frances Kathleen Oldham Kelsey." (Sept. 2, 2009)
  • Roberts, Cheryl. "Re: NDA 19-963." FDA. Oct. 13, 2000. (Sept. 2, 2009)
  • ScienceDaily. "Scientists Warn Against Anti-Aging Hype." May 21, 2002. (Sept. 1, 2009)
  • Shapiro, Lori, Pastuszak, Ann, Curto, Giancarla and Koren, Gideon. " Safety of first-trimester exposure to topical tretinoin: prospective cohort study." Lancet. Oct. 18, 1997. Vol. 350, Issue. 9085. pp. 1143-1144.
  • Triax Pharmaceuticals. "Tretinoin." July 2009. (Sept. 2, 2009)