Topical estrogens hold promise for improving skin appearance

National report - Decreasing levels of estrogen in menopause are linked to effects on the skin, such as increased skin laxity, wrinkling and poor wound healing, prompting research targeted at topical administration of estrogens.

"In the literature, there are anecdotal reports that estrogens may improve the appearance of the skin, particularly the skin of women who are postmenopausal," says Tania Phillips, M.D., a dermatologist at SkinCare Physicians, Chestnut Hill, Mass., and professor of dermatology, Boston University, Boston.

 Dr. Phillips acted as an investigator for a study of 485 women that looked at the impact of low-dose hormone replacement therapy on the skin, and found no overall difference between those women who received low-dose hormone replacement therapy (HRT) versus those who received placebo over a 48-week period. Dr. Phillips and co-investigators did observe a trend, although not statistically significant, of improvement in the skin in women who were less than 24 months postmenopausal.

"The numbers in the subgroup were small," Dr. Phillips says.

Study results
The skin is an appropriate target for estrogen therapy, because both alpha and beta estrogen receptors are found in the skin, according to Dr. Phillips. One randomized study of 54 women found the application of Premarin cream (conjugated estrogens 0.625 mg/g, Pfizer) was more effective than a placebo in improving fine wrinkles at weeks 12 and 24. Two other studies concluded that the use of topical estrogens, such as Premarin cream or topical estradiol gel, could decrease fine wrinkling, improve roughness of the skin and stimulate collagen synthesis.

Still another investigation found local oestriol therapy, when applied to abdominal skin for three weeks, thickened fibers in the papillary dermis of patients.

Currently, the only topically-applied estrogen products that are available and approved by the Food and Drug Administration (FDA) are those that are indicated to alleviate symptoms of menopause, such as vaginal dryness. There is more caution around using estrogens, on the whole, given data that surfaced from the Women's Health Initiative, which concluded that long-term use of estrogen and progestin markedly increased the risk of breast cancer, heart disease, stroke, blood clots and urinary incontinence, Dr. Phillips says.

"There is more caution about prescribing estrogens given the whole 'estrogen scare' several years ago," she says.

"There has been interest in looking at (prescription) topical estrogens," Dr. Phillips says. "There is nothing in the marketplace now, but there are products in development. Ideally, the topical estrogens should be metabolized before they enter the body's circulation to avoid possible systemic effects."

Product development
One of those products in development is HYG-102, a topical estrogen made by Hygeia Therapeutics. The product is designed to biodegrade rapidly into an inactive metabolite, and has a short half-life.

Until 1994, estrogens were found in many over-the-counter (OTC) cosmetic products. In 1994, safety concerns about the side effects of the estrogens in OTC products prompted the FDA to remove all OTC products containing estrogens from the marketplace in the United States.

Currently, some OTC products purport to have an estrogen component in the form of phytoestrogens or isoflavonoids, with claims of relieving the effects of menopause such as hot flashes.

But according to Diane Thiboutot, M.D., professor and vice chairwoman of dermatology research, Penn State Hershey College of Medicine, Hershey, Pa., the amounts of phytoestrogens or isoflavonoids would not be sufficiently plentiful to have a beneficial effect on the skin or to have an impact on treating a condition like acne.

"The concentrations would not be enough to have a pharmacological effect," says Dr. Thiboutot, who specializes in hormonal therapy to treat acne. "Doses of estrogen needed to decrease sebum production would need to be very high. If there were high doses of topical estrogens, they might be able to reduce sebum production and offset the effects of androgen and the development of acne, but there would be concerns about systemic side effects."

Dr. Phillips agrees that any OTC topical skin products that allege to have estrogen-like effects are marketing claims that are not supported by scientific studies.

Another possible target for estrogen is in woundcare or in assisting in healing during elective surgery, particularly in older patients, according to Dr. Phillips.

One study published in 1999 found the use of a topical estradiol patch led to more rapid wound healing and increased collagen levels.

Disclosures: Dr. Phillips sits on the scientific advisory board for Hygeia Therapeutics. Dr. Thiboutot reports no relevant financial interests.