The Menopause Estrogen Face Cream Epidemic

When marketing outpaces science

Iryna Veklich/Getty Images

What if I told you there was a new topical product for women to reduce the physical signs of skin aging, but the pharmaceutical company that made it had not published any peer-reviewed studies to show it was safe, never mind effective? Oh, and the drug could cause endometrial cancer if used incorrectly? Also, what if the only available peer-reviewed literature was small, short-term, pilot studies? Oh…and the pharmaceutical company had managed to skirt FDA requirements, so you had no way of knowing if the jar contained the amount of drug that it claimed.

You’d probably be a little angry.

Wait, there’s more.

What if I then told you that sometime AFTER this topical product was already being sold to women and promoted heavily on social media by menopause influencers, one company that sells it FINALLY released a study to look at the safety and effectiveness of their specific product, but the study was not published in peer-reviewed literature.

I bet you by now would be incensed and think that Big Pharma was using the weight of the patriarchy to take advantage of women while leveraging the fact that menopause is finally getting some attention to make a buck (or hundreds of thousands or millions or more). And you might mutter about how women’s health is understudied, and here is just one more fucking example. And you might think, shouldn’t you do the study before you sell the drug?

All of that rage would be well placed, except it’s not a pharmaceutical company; it’s menopause telemedicine companies and many menopause influencers who are profiting from this new inadequately studied supposed anti-aging wonder drug–topical estrogen cream. And since most of the promoted products are compounded hormones, they are free of that pesky Food and Drug Administration (FDA) oversight.

Nice.

Look, I’m sure many of you have seen the videos of menopause influencers, including doctors, dabbing estrogen cream on their faces and making bold claims about the product. I know I have. However, they never seem to mention that it’s inadequately studied; in fact, it is woefully understudied. And yet, I have seen those same menopause influencers rail against the system that produces understudied, inadequate therapies for women. Hypocrisy much? It sure seems that for some influencers, the need for women to have quality science is flexible based on what is making money or getting a video to go viral. And right now the gold rush is fueled by estrogen face cream.

Estrogen and Skin

Menopause is associated with various skin changes, such as decreased sebum production, epidermal thinning, and reduced collagen and elastin. For some, this may result in an acceleration of skin aging, such as dryness, decreased elasticity, and an increase in fine wrinkles. This means evaluating estrogen for potential skin benefits is a valid hypothesis, not that we should sell estrogen face and body cream. Like science has a few steps between hypothesis and therapy.

An assortment of older observational and unblinded studies suggested estrogen in menopause hormone therapy (MHT) could reduce signs of aging on the face. However, this has not been born out in three randomized, placebo-controlled trials. The longest is KEEPs, which ran for four years and compared oral Premarin 0.45 mg/oral progesterone or 50 mcg transdermal patch/oral progesterone with placebo. There are shorter trials with either 5 or 10 mcg of ethinyl estradiol or 2 mg oral estradiol, showing no benefits (both with a progestogen).

Would higher doses or different regimens work? Maybe, but it’s equally plausible they won’t. Is it possible the progestogen is counteracting the estrogen somehow, and an estrogen-only regimen might be better? Maybe. But it's equally plausible there is simply no effect.

Researchers moved on to topical estrogen. This was a “thing” in the 1960s and 70s, so what’s old is new again; Avon even had an estrogen face cream! I have a jar I got on eBay for my little menopause museum. Various small animal and human studies suggested that topical estrogen could, among other things, increase skin thickness, prevent the loss of collagen, prevent wrinkles, and restore skin hydration. However, some studies showed no benefit. This initial work led to pilot studies, which is the appropriate next step.

Peer-reviewed Clinical Trials with Estrogen Face Cream or Gel

I found nine clinical trials, and they are all pilot/Phase 1 studies. While they are suitable for designing subsequent studies, they are grossly inappropriate for determining medical care. I know that the telemedicine company Alloy released some data, but I am not including it as it is not peer-reviewed. The podcast Ovary Active, hosted by two doctors I trust, did a good review of the study; you can find it here. It’s not very impressive (not the podcast, the study).

Here is a summary of the issues and findings with the peer-reviewed studies that I could find:

• Most are small and relatively short-term, ranging from 16 weeks to 6 months. This is fine for pilot studies but not for determining medical care.

• Only three of the nine studies are placebo-controlled. Drawing a conclusion from a pilot study without a placebo arm is absurd.

• A variety of products were studied: estradiol cream, estradiol gel, Premarin vaginal cream, estrone cream, and estriol cream. This makes it impossible to combine all the studies to look for a general estrogen effect.

• The participants vary a lot. Some could be on MHT, but it was a reason for exclusion in other studies. Some studies included both perimenopausal and menopausal women, and others were limited to those who were in menopause. This also makes it impossible to lump the studies together.

• Most of the products studied are compounded hormones. My best guess is seven of the nine papers used compounded hormones (three for sure, as this was stated explicitly, but the description for another four was so vague that I assume they are compounded, as typically a commercial product is expressly mentioned). The issue here is dosing can vary significantly with compounded products due to the inherent issues with compounding estrogens, so people could get more or less hormone than they think, which makes it harder to study appropriately and to advise about risks.

• Only six of the nine studies mention the dose of estrogen that was applied to the face. I mean, not describing the dose? Imagine if I submitted a study that said, “The patients each took an estradiol pill.”

• Some of the studies use estrogen doses that, if absorbed, could theoretically result in systemic levels. A single 2 g vaginal dose of estradiol cream results in significant estrogen levels, so the assumption should not be that 1 g daily to the face is safe. Estrogen levels weren’t adequately evaluated in most of the studies, so that’s problematic. In two studies several of the participants reported breast tenderness, which suggests absorption. As these products may be used for decades, it’s essential to understand the potential for absorption. We just can’t know much this from these studies.

• Only one of the nine studies evaluated the endometrium to see if any stimulation had occurred, which is important as if estrogen were absorbed it could lead to pre-cancer or cancer. Several studies used an older method of evaluating the vagina for signs of absorption, but this is not adequate to tell us the risk for the endometrium. Also, not all of the studies would have been long enough to make this kind of safety assessment regarding the endometrium.

• Melasma, brown to gray patches on the skin that can be caused by hormones, was noted by 11% of people who used a topical 0.01% estradiol. There is also a case report of melasma due to topical estrogen use. Spider angiomas (red or purple spider veins) can be hormonally related. While not described in these pilot studies, larger, more extended studies are needed to assess the risk of both melasma and spider angiomas.

You can see why I am not super impressed with making any kind of proclamation about estrogen face cream based on this hodgepodge of data.

Did these products work? Eight of the nine showed benefit, but the study with estrone (which was one of the higher quality studies and the largest study) showed no beneficial effect on wrinkles or collagen and significantly increased collagen-degrading enzyme, MMP-1 mRNA, which the authors concluded “could be deleterious to the UV-induced skin aging process.” Is this an estrone effect? Other investigators didn’t look for it? Who knows, but it means more work is needed!

Now, you might think, well, only one out of nine studies showed no benefit and potential harm, but eight were good, so maybe that one is a fluke. The one that showed no benefit was one of the better studies. If we only consider the placebo-controlled studies that also provided the dose of estrogen cream used, then one study showed benefits, and the other did not.

Here are some other thoughts:

• Estrogen face cream needs to be studied against modern evidence-based therapies, like retinoic acid. Only one study compared topical estrogen with another known active ingredient, 15% glycolic acid, and found no difference in effect.

• Estrogen face cream needs to be studied for women who are taking MHT and those who are not as responses could differ.

• The site of application of estrogen affects its absorption, so claiming that since vaginal estrogen is safe in the recommended doses when used in the vagina does not mean that these doses are safe for daily use on the face. Yes, I have seen the videos of influencers telling women to use their vaginal estrogen on their face. I’ve even seen an influencer who suggested you could just use your vaginal estrogen on your face and not even tell your doctor. Yikes. We know that in the right concentration and formulation estrogen can be absorbed across the skin, that’s why we have gels and sprays for MHT. There is a case report of a three year old child developing early puberty from exposure to a compounded estrogen hair lotion used by her mother. How did the exposure happen? According to the report, “the child was in the habit of playing with her mother's hair while falling asleep.” Yes, apparently she absorbed enough estrogen to trigger breast development and vaginal bleeding by repeatedly playing with her mother’s hair. When the product was stopped, the girls estrogen levels dropped back down. So, we shouldn’t be so cavalier about absorption until we have studies.

• We need endometrial safety data.

• While some telemedicine companies are promoting estriol, which was in a few pilot studies, others offer it with DHEA or with DHEA and vitamin C. Each formulation needs to be independently and appropriately studied as different formulations can result in different results and absorption, which can affect risks. However, this data does not exist.

• Claims that these products are safe for all women, even those who can’t take estrogen, should be met with skepticism since two of the pilot studies suggested some women were absorbing estrogen.

It’s impossible to conclude anything from these studies except that more studies are needed. Science-wise, that’s how it works. I am sure there are people who will reply with anecdotes, and to that I say, my mother had amazing skin (truly, she did) well into her 80s despite a lifetime of smoking like a chimney and never taking estrogen and going through menopause early. Whose anecdote do we use?

Personally, I would not use estrogen face cream because I want my medical care to be informed by good science, not pilot studies with no placebo arm. I want to know if something works and what the risks are before I use it, and so should you. Also, given the studies that we do have regarding compounded hormones, before I would use a compounded product, I’d want to see some independent quality testing.

Look, if a company believes in the product so much, do the studies. And preferably BEFORE selling it to women. To me, it is the definition of patriarchy to capitalize on how society treats women as they age by selling a grossly understudied estrogen face cream. But I get it, the road to quality science is expensive, and maybe some people think that women are just not worth that effort and expense.

References

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A.K. Rzepecki et al. / International Journal of Women's Dermatology 5 (2019) 85–90 87 (review)

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