Menopause, Hormone Therapy, & Aging Skin – Is there a Connection?

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Women's Health Activist Newsletter
July/August 2011

By Cindy Pearson and Jonathan Raymond

Menopause hormone therapy (HT) offers probably the biggest example in modern medicine where enthusiasm for a drug’s reputed benefit trumped existing supporting science. As we’ve said before, menopause hormone “replacement” therapy was a triumph of marketing over science.  By 2002, some 38% of menopausal and older women in the U.S. were taking — or had taken — some form of HT.1 While evidence of HT’s effectiveness for menopausal symptom relief was well-supported, its supposed long-term health “benefits” (preventing everything from heart disease, osteoporotic fractures, dementia, and even colon cancer) actually had very little solid science behind them. We now have solid data from numerous clinical trials that HT poses multiple risks and provides few benefits to aging women’s health, and many women have stopped taking HT. But, one belief that continues to this day is that taking HT after menopause benefits a woman’s skin and can combat the natural signs of aging. Is there any proof that HT helps aging skin?

Estrogen’s effects on skin are largely believed to result from the hormone’s ability to increase collagen production and water content, two factors that seem to influence skin’s elasticity and moisture.2 The standard view is that, as women age, decreasing estrogen levels are responsible for skin’s wrinkling, sagging, and dryness. (Even though, as we all know, men’s natural aging process also leads to wrinkles, sagging, and dryness!) Menopausal women, who naturally have less estrogen, might be expected to have drier or more wrinkled skin than younger women. However, men also have estrogen receptors in their skin, and this basic cellular biology does not consistently translate into a simple relationship of: “more estrogen = better skin” and “less estrogen = wrinkles + dry skin” because studies trying to confirm that menopause makes women’s skin worse and hormone therapy makes it better have yielded mixed results.

There is little evidence for the theory that menopause and declining hormone levels, rather than age alone, are the cause of women’s wrinkles. For example, an on-going clinical trial called the Kronos Early Estrogen Prevention Study (KEEPS), which is studying HT’s effects in 720 recently menopausal women, found that causes other than estrrogen are responsible for aging skin's appearance. In these women, the amount of time passed since they entered the menopausal transition (when their natural estrogen levels started to decline) didn’t seem to make a difference to their skin. Of all the facial areas examined for signs of aging, only the “frown-lines” (lines on the corners of the mouth) seemed to be related to the amount of time that’s passed since a woman entered menopause. Other, more severe signs of aging — such as skin rigidity, deep lines between the bottom corners of the nose and the chin (nasolabial folds), and neck creases — were found to be related to increasing age and cigarette smoking, not to amount of time since menopause.3

But, even if menopause-related declines in estrogen aren’t the cause of skin problems, women might still want to use the hormone to prevent and minimize wrinkles, dryness, or sagging. If it works, that is. Here again, the evidence isn’t strong. Two small trials looked at both oral HT and topical HT to determine estrogen therapy’s effectiveness, with mixed results. The oral HT trial, conducted by Boston University in 2008, studied the results in 485 women of taking two doses of ethinyl estradiol and norethindrone acetate (a synthetic progesterone) compared to taking a placebo. The results showed no improvement in participants’ self-assessment of coarse and fine facial lines and wrinkles; the investigators’ assessment also found no positive effect on wrinkles, dryness, or sagging.4 The authors noted a possible benefit could not be excluded because only two doses were given and the study participants were, on average, five years post-menopausal.

The other trial, conducted by the University of Michigan in 2008, did suggest a benefit from topical estradiol cream. This study examined the effect on both men and women of applying topical estradiol over a two-week period. The cream stimulated collagen production, but measurable changes were only observed when it was applied to skin that hadn’t been greatly exposed to the sun (namely the inner thigh / hip). The effect was not observed in facial and forearm skin.5 This suggests that topical estrogen is likely to have very limited use, as most people have had more than brief sun exposure to their face and arms (presumably the areas where damaged skin is most bothersome). The results indicate, however, that both men and women have estrogen receptors in their skin and confirm that sun exposure — which has long been implicated in premature aging of the skin — indeed has a negative impact.

Another potential (though less well-studied) measure is the use of low-dose, topical progesterone cream. A small clinical trial of 40 peri- and post-menopausal women conducted at the University of Vienna in 2005 examined the effect of applying one gram of two percent topical progesterone cream on the face daily. This was found to significantly improve wrinkles and firm the skin, but not to have any positive effects against dryness. The treatment was well-tolerated, had a minimal effect on blood levels of progesterone, and had no measurable effect on other hormone levels.6 It is too soon to recommend this therapy, however, because such over-the-counter (OTC) progesterone creams do not require the same testing for purity and potency as branded hormone products approved by the Food and Drug Administration (FDA), and the solution that was studied here was not named — so the effects (such as potency and absorption) should not be assumed to be the same as the OTC formulary brands. Additionally, progesterone cream’s long-term effects have not been determined through high-quality clinical trials. All we can say now is that preliminary evidence seems to show that topical low-dose progesterone cream has a favorable impact on some signs of skin aging.

So, HT doesn’t improve skin, and there has yet to be enough research on progesterone cream to definitively say that it combats the signs of aging. Is there anything that does work? Well, prevention is a start! While no one can expect to look 20 years old for life and, unfortunately, you can’t change your genetic makeup, some common-sense health measures can help. Excessive sun exposure and cigarette smoking alone are probably the biggest factors in premature aging of the skin for both men and women. Not smoking, or quitting smoking (preferably when you’re young), and using sunscreen consistently all help keep skin healthy. For women who want to improve aged skin, the best bet is a topical medicine called Retin-A (retinoic acid/tretinoin), which can help erase wrinkles over time. Retin-A is used as an acne and blemish fighter for teens; its major side effect is burning and peeling.7

Although women hear about the estrogen’s supposed benefits for skin, they rarely, if ever, hear about HT’s possible negative side effects on the skin. An important side effect is melasma, a spotty darkening of the skin, which is often referred to as “the mask of pregnancy” due to its prevalence in pregnant women. Melasma is well-documented as a possible, long-lasting side effect of both HT and birth control pills.

In conclusion, it appears that the major determinants of poor skin quality in older people are cigarette smoking, sun exposure, and increasing age. Although estrogen clearly has activity in the skin, taking HT does not translate into an overall net benefit for skin. Other interventions may be beneficial, but lack either sufficient long-term safety data or have possible negative side effects. Despite HT being touted as a panacea for every ill women face as they age, research does not generally support its use to improve skin. HT’s lack of effect on skin is yet another reason why older women are better off avoiding HT except when they experience severe menopausal symptoms that do not respond to other treatments. And again, women should use the lowest dose for the shortest time possible and not rely on these drugs to preserve their health or restore/maintain youthful-looking skin.

References:

1. Fletcher SW, Colditz GA, “Failure of Estrogen Plus Progestin Therapy for Prevention”, JAMA 2002; 288(3):366-368. Available online at: http://jama.ama-assn.org/content/288/3/366.

2. Raine-Fenning NJ, Brincat MP, Muscat-Baron Y, “Skin Aging and Menopause: Implications for Treatment”, Am J Clin Dermatol. 2003; 4(6):371-8. Available online at: http://www.ncbi.nlm.nih.gov/pubmed/12762829.

3. Wolff EF, “Skin Wrinkles and Rigidity in Early Postmenopausal Women Vary by Race/Ethnicity: Baseline Characteristics of Participants Enrolled in the Skin Ancillary Study of the KEEPS Trial”, American Society for Reproductive Medicine, 64th Annual Meeting, 2008. Available online at: http://www.kronosinstitute.org/research/current/skin_wrinkles_and_rigidity.pdf.

4. Phillips TJ, Symons J, Menon S, “Does hormone therapy improve age-related skin changes in postmenopausal women? A randomized, double-blind, double-dummy, placebo-controlled multicenter study assessing the effects of norethindrone acetate and ethinyl estradiol in the improvement of mild to moderate age-related skin changes in postmenopausal women.” J Am Acad Dermatol. 2008; 59(3):397-404.e3. Epub 2008 Jul 14.

5.   Rittié L, Kang S, Voorhees JJ, et al., “Induction of Collagen by Estradiol: Difference Between Sun-Protected and Photodamaged Human Skin In Vivo”, Arch Dermatol. 2008; 144(9):1129-1140. Available online at: http://archderm.ama assn.org/cgi/content/short/144/9/11296. 

6. Holzer G, Riegler E, Hönigsmann H, et al., “Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study”,  British Journal of Dermatology 2005; 153(3):626–634.

7. Weiss JS, Ellis CN, Headington JT et al., “Topical Tretinoin Improves Photoaged Skin - A Double-blind Vehicle-Controlled Study”, JAMA 1988; 259:527-532. Available online at: http://jama.ama-assn.org/content/259/4/527.short

Cindy Pearson is the NWHN Executive Director; Jonathan Raymond is a long-term Network supporter and has written/co-written 2 previous articles for the Women’s Health Activist on HT and women’s health.