Does hormone replacement therapy work?  Treating post-menopausal skin

Does hormone replacement therapy work? Treating post-menopausal skin

Posted by Team Maelove on

 

Today, we're going to discuss how the skin changes during menopause, how these changes are driven by estrogen, and how hormone estrogen therapy can affect your skin.

As you go through menopause, you might notice significant changes in your skin. This isn't just your imagination, and it's not merely a continuation of the typical aging process you've experienced up to this point. In fact, menopause brings about an accelerated type of skin aging due to shifts in hormonal levels.

But here's the good news: you can combat and treat these changes. Trustworthy anti-aging skincare ingredients, such as Vitamins A, B, and C, can help reverse post-menopausal skin changes and improve your skin's overall appearance. We'll explore retinoids (Vitamin A derivatives), niacinamide and panthenol (Vitamin B3 and provitamin B5), and Vitamin C for postmenopausal skin in a future article.

Furthermore, there are treatment options specifically designed to address hormonal changes during menopause, including estrogen replacement and topical estrogen-like compounds. Let's dive deeper into how these treatments work and how they can benefit your skin during this time of change.

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This content is provided as part of our commitment to bringing science-based information to the public, and it is intended to offer general scientific background on the topic. However, health is complex, and individual cases can vary significantly. We encourage you to consult with a healthcare provider who can diagnose and prescribe treatments specifically tailored to your needs.

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Changes in hormone levels during menopause

The key hormone here is estrogen.

At puberty, the ovarian follicles begin secreting estrogen.

And after menopause, the levels of these estrogens in your bloodstream drop to near zero as your ovaries shut down estrogen production.

However, there are other secondary sources of estrogen. The fat cells make some estrogen, as do the adrenal glands and the brain. And notably the skin is able to make estrogen on its own as well. But these minor sources also decline in estrogen production over time (Cui et al. 2013, Stevenson and Thornton 2007).

In the 1990s, it was discovered that skin cells have estrogen receptors. Discovery of estrogen receptors is significant because it explains how estrogen affects positive changes in the skin.

A quick note: Hormone receptors are like little docking stations found on or inside our cells. When hormones come by and attach to these stations, it sets off a chain reaction inside the cell, and that’s how hormones affect changes in our bodies. So the flip side is, even if there is hormone floating around, if there are no corresponding receptors, then the hormones do nothing.

These estrogen receptors are most dense on the genitalia, face, and lower limbs which are all skin regions that show significant aging post-menopause (Archer 2012).

So here is the thing. Not only do estrogen levels drop with menopause. The number of estrogen receptors in the skin also drop during perimenopause to menopause. So it’s a double whammy.

It’s kind of like getting your salary cut while also facing inflation. This compounds the bad times.

To recap, during menopause, your body and your skin undergo steep declines in estrogen and estrogen receptors. And these declines result in a number of bad things for your skin.

 

Here's How Menopause Affects Your Skin

Post-menopause, your skin becomes thinner and more frail and can become almost transparent. This is due in a big part to your skin collapsing from loss of collagen.

A study conducted by Brincat and colleagues found that as much as 30% of skin collagen content could be lost in the first 5 years after menopause (Brincat et al. 1985).

In the chart below (reproduced from Brincat et al. 1985) The line with white dots shows the progression of collagen post menopause. And as you can see the line declines dramatically once you hit menopause.

And the line with black dots is the progression of collagen post menopause but with estrogen supplementation. We’ll go into estrogen replacement therapy in a bit.

HRT vs no HRT treatment

(Image reproduced from Brincat et al. 1985)

 

And in a subsequent study, Brincat and colleagues estimated the average rate of collagen loss per post-menopausal year to be 2.1%. And that the thickness of the skin decreases at 1.1% each year following menopause (Brincat et al. 1987).To put that into perspective, on average, collagen loss per year is around 1% going into menopause (Schuster et al. 1975). So basically, your skin is aging at a much faster rate as you hit menopause.

Elastin and GAGs also decrease leading to loss of bounciness of the skin and decline of skin hydration (Brincat et al. 2005, Raine Fenning et al. 2003).

A quick note: In brief, GAGs or glycosoaminoglycans are polysaccharides like hyaluronic acid which can hold water many times its own weight. They keep skin hydrated and give the skin turgor, much like a filled water balloon is smooth but a deflated one is saggy.

Elastin is a stretchy material like lycra in your jeans that gives your skin its elasticity and bounciness.

Finally collagen is the main structural protein in your skin and it forms rigid fibers that hold up your skin like tent poles hold up a tent. The loss of collagen is the main driver of fine lines and wrinkles.

All these components are affected by the loss of estrogen and estrogen receptors, leading to post-menopausal skin.

Estrogen also affects blood vessels, and the loss of estrogen leads to lower blood flow to the skin which affects nutrient delivery and wound healing (Archer 2012).
These changes result in more wrinkled, saggy, sallow, and dry skin. All these things - all that accelerated aging - happen due to loss of estrogen and estrogen receptors in skin in menopause.

In rare instances, some women post-menopause get manifestations of hyperandrogenism such as postmenopausal acne, androgenic alopecia and hirsutism (Khunger and Mehrotra 2019, Hirschberg 2022), and we will have an upcoming article on sex hormones and skin that explain why this happens.

 

Treating post-menopausal skin: Addressing the hormone deficiency

HRT (Hormone Replacement Therapy): Works well but can have side effects

First off, hormone replacement therapy or HRT would never be prescribed just for cosmetic purposes. This is because it has worrisome side effects we will go into. However, one of the positive outcomes of HRT is that you reverse the skin changes that occur post-menopause, maintaining levels of collagen, hydration, elasticity, and levels of estrogen receptors (Archer 2012, Shu and Maibach 2011, Brincat et al. 1985).

In fact, it works so well that with HRT, Brincat and colleagues found that premenopausal levels of collagen could be maintained (Brincat et al. 1985). And subsequent studies have also shown a benefit in skin hydration, skin elasticity, wrinkling, and wound healing with HRT (Archer 2012, Dunn et al. 1997).

And these benefits occur whether the estrogen is delivered via oral, transdermal or topical means (Brincat et al. 2005, Rzepecki et al. 2019).

Interestingly, these benefits with HRT only occur in nonsmokers and not in smokers (Archer 2012). Smoking is also known to hasten the onset of menopause by about two years.

Why is that? This may be because nicotine affects estrogen metabolism. Smokers also experience more hot flashes during menopause, and generally, quitting smoking is recommended for postmenopausal women.

Now while HRT is good for skin, it can also come with profoundly worrisome side effects including increased risk for stroke, and increased risk of breast, ovarian and uterine cancer. Though the addition of progesterone can combat some of the risks associated with cancers of the uterus, they also increase the risk of blood clots and stroke. Hence, in many women, HRT is not recommended.

This risk is also present for topical supplementation as estrogen can be absorbed into the bloodstream. So HRT is not prescribed long term for use in treating skin disorders (Rzepecki et al. 2019, Stevenson and Thornton 2007).

Further, one other side effect of oral and topical estrogen is that it can result in hyperpigmentation as melanocytes (skin cells that produce melanin) are also stimulated by estrogen and can be driven to overproduce melanin (Stevenson and Thornton 2007).

 

Other estrogen-like compounds

To get around some of these negative side effects of estrogen replacement therapy, studies have been conducted to look at other estrogen-like compounds and some have been promising.

While these estrogen-like compounds avoid the complications of estrogen replacement, like increased breast cancer risk, overall they are generally either understudied or found to be much less effective than estrogen itself.

We go into more detail in Appendix A but in brief: Selective estrogen receptor modulators like tamoxifen and raloxifene and their effect on skin are still just in the research stage but can be useful in wound healing.

New compounds like MEP, which stands for Methyl Estradiolpropanoate has been shown to benefit dryness, laxity, atrophy, and dullness but the extent of benefits compared to other, known effective compounds is unclear (Cohen 2019, Draelos 2018).

Phytoestrogens from soy have been shown in clinical studies to have similar benefits as estrogen but to a much lesser extent. We will have a dedicated article in the future that goes deeper into soy and skin.

 

RECAP

Menopause brings a significant drop in estrogen levels, leading to various changes in the body and skin. Hormone replacement therapy (HRT) can help reverse these negative effects, but it comes with some serious potential risks, like a higher chance of breast cancer. Because of these risks, doctors usually prescribe HRT for a short time, often just 1 or 2 years.

Researchers are looking into alternatives to estrogen with the goal of keeping the benefits while reducing the side effects. Generally, these alternatives have fewer side effects but also less noticeable benefits.

 

Appendix A : Estrogen-like compounds

Selective Estrogen Receptor Modulators (SERMs): Tamoxifen and Raloxifene

While estradiol is always an agonist at both receptors, selective estrogen receptor modulators (SERMs) may have agonist or antagonist activity in that tissue depending on the receptor profile.

For example, Tamoxifen and raloxifene are both antagonists in breast tissue but agonists in bone tissue. Tamoxifen is better known as a hormone therapy used to treat hormone receptor-positive breast cancer, while raloxifene is better known as a drug used to prevent and treat osteoporosis in postmenopausal women although it too has been shown to prevent breast cancer.

Those of you on one of these drugs may be worried about the effects on your skin. Interestingly enough, they are under active research for positive effects on skin post-menopause (Stevenson et al. 2009, Lephart and Naftolin 2021).

Tamoxifen and raloxifene can improve wound healing in older adults. They can stimulate human dermal fibroblasts while avoiding stimulation of the breast tissue which is a big deal since one of the drawbacks of estrogen therapy is the increased chance of breast cancer.

Nonetheless, SERMs like Tamoxifen also carry risks as it can increase the risk of endometrial cancer by three-fold (Stevenson and Thornton 2007). So these are not exactly an ideal treatment for skin alone.

 

Phytoestrogens (Isoflavones) - estrogen like molecules from soy

Phytoestrogens are plant-based SERMs that have recently come to prominence.

Phytoestrogens in soy include equol and genistein. Soy isoflavonoid equol has in vitro and clinical study results that support their use in improving menopausal skin (Lephart and Naftolin, 2021).

Soy isoflavonoid genistein also has human studies that have shown skin benefits both in oral and topical forms. Clinical studies show genistein also has similar qualitative benefits to estrogen replacement although the benefits are significantly lower in magnitude.

Further, diets rich in soy such as the Asian diet, compared to the western diet, may provide estrogen-like benefits (Rzepecki et al. 2019, Thornton 2013, Accorsi-Neto et al. 2009, Irrera et al. 2017). We will go deeper into soy for skin in a separate article in the future.

Overall, studies show phytoestrogens have skin benefits although to a much lesser extent than estrogen itself. So while phytoestrogens do not carry the downsides of estrogen, they are also not as effective.

 

Methyl Estradiolpropanoate (MEP)

A more recent addition to post-menopausal skin treatment options is Methyl Estradiolpropanoate (MEP) found under the brand name Emepelle.

MEP is what’s known as a non-hormonal estrogen receptor activator. And as the name suggests, it works by activating the estrogen receptors in your skin cells. MEP is thought to metabolize within the skin to an inactive compound so that it does not enter the bloodstream as estrogen and avoids the side effects of estrogen such as increased breast cancer risk.

Both an open label and double-blind study of Emepelle found that MEP was highly tolerable and MEP-related benefits were found to dryness, laxity, atrophy, and dullness (Cohen 2019, Draelos 2018). However, no comparison was included to compare its effectiveness against potentially more effective tried and true ingredients.

 

REFERENCES

Accorsi-Neto A, Haidar M, Simoes R, Simoes M, Soares-Jr J, Baracat E (2009). “Effects of Isoflavones on the skin of Postmenopausal Women: A Pilot Study.” Clinics 64(5): 505-510.

Archer DF (2012). “Postmenopausal skin and estrogen.” Gynecological Endocrinology 28(S2): 2-6.

Brincat M, Moniz CJ, Studd JW, Darby A, Magos A, Emburey G, Versi E (1985). “Long-term effects of the menopause and sex hormones on skin thickness.” Br J Obstet Gynaecol 92:256–259.

Brincat M, Kabalan S, Studd JW, Moniz CF, de Trafford J, Montgomery J (1987). A study of the decrease of skin collagen content, skin thickness, and bone mass in the postmenopausal woman.” Obstet Gynecol 70: 840–845.

Brincat MP, Baron YM, Galea R (2005). “Estrogens and the skin.” Climacteric 8: 110-123.

Cohen JL (2019). Evaluation of Efficacy of a Skin Care Regimen Containing Methyl Estradiolpropanoate (MEP) for Treating Estrogen Deficient Skin.” 18(12): 1226-1230.

Cui J, Shen Y, Li R (2013). “Estrogen synthesis and signaling pathways during ageing: from periphery to brain.” Trends Mol Med 19(3): 197-209.

Draelos ZD (2018). “A Double-Blind Randomized Pilot Study Evaluating the Safety and Efficacy of Topical MEP in the Facial Appearance Improvement of Estrogen Deficient Females.” J Drugs Dermatol 17(11): 1186-1189.

Dunn LB, Damesyn M, Moore AA, Reuben DB, Greendale GA (1997). “Does Estrogen Prevent Skin Aging? Results From the First National Health and Nutrition Examination Survey (NHANES I).” Arch Dermatol 133(3): 339-342.

Hirschberg AL (2022). “Approach to Investigation of Hyperandrogenism in a Postmenopausal Woman.” J Clin Endocrinol Metab. Doi: 10.1210/clinem/dgac673.

Irrera N, Pizzino G, D’Anna R, Vaccaro M, Arcoraci V, Squadrito F, Altavilla D, Bitto A (2017). “Dietary Management of Skin Health: The Role of Genistein.” Nutrients 9, 622. Doi:10.3390/nu9060622.

Khunger N, Mehrotra K (2019). “Menopausal Acne - Challenges and Solutions.” Int J Womens Health 11: 555-567.

Lephart ED, Naftolin F (2021). “Menopause and the Skin: Old Favorites and New Innovations in Cosmeceuticals for Estrogen-Deficient Skin.” Dermatol Ther 11: 53-69.

Raine-Fenning NJ, Brincat MP, Muscat-Baron Y (2003). “Skin Aging and Menopause: Implications for Treatment.” Am J Clin Dermatol 4(6): 371-378.

Rzepecki AK, Murase JE, Juran R, Fabi SG, McLellan BN (2019). “Estrogen-deficient skin: The role of topical therapy.” Int J Women’s Dermatology 5(2): 85-90.

Schuster S, Black MM, McVitie E (1975). “The influence of age and sex on skin thickness, skin collagen and density.” Brit J Dermatol 93: 639-643.

Shu YY, Maibach HI (2011). “Estrogen and skin: therapeutic options.” Am J Clin Dermatol 12(5): 297-311.

Stevenson S, Sharpe DT, Thornton MJ (2009). “Effects of estrogen agonists on human dermal fibroblasts in an in vitro wounding assay.” Exp Dermatol 18: 988-990.

Stevenson S, Thornton J (2007). “Effect of estrogens on skin aging and the potential role of SERMs.” Clin Interv Aging 2(3): 283-297.

Thornton MJ (2013). “Estrogens and aging skin.” Dermato-Endocrinology 5(2): 264-270.

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