“You know Ariana, I don’t want to scare you, but your estrogen levels are cancer-level. These are the highest levels I have ever seen in a patient,” Doctor Stephanie told me as she looked over my test results.

My heart sank in my chest. I was utterly terrified. So far nothing we had tried had worked, and I was prepared for some bad news. But the last thing I expected was to find out my melasma might be the least of my problems. I want you to have hope. If I could bring my estrogen back into balance, I think anyone can.

Estrogens are a group of hormones important for female sexual and reproductive development. Estrogen also prevents aging by boosting collagen synthesis, maintaining skin thickness, and improving elasticity. This is why after menopause the elasticity fades, the skin thins, and collagen production goes down, allowing gravity to take hold.

Estrogen plays a particular role in the formation of melasma. Some women get melasma from hormone replacement therapy when they're nearing or in menopause, many get melasma from birth control and others get melasma during pregnancy. During the menstrual cycle estrogen rises and falls, and for some women the intensity of their hyperpigmentation rises and falls as well. I once met a woman who had a form of catamenial hyperpigmentation, a condition similar to melasma (in fact most cases of catamenial hyperpigmentation are melasma) that caused her melasma spots to darken during certain parts of her menstrual cycle.

Regardless of how you got melasma, estrogen most likely plays a role. Let’s get into it!

Estrogen-Gut Connection.

Estrogen also has an important relationship with the gut microbiome. The gut has unique microbes called estrobolome that make a key enzyme called beta-glucuronidase that helps metabolize things like estrogen, medications, environmental toxins, and neurotransmitters. This process, called glucuronidation, prepares toxins for elimination through your stool. Too much β-glucuronidase can become carcinogenic, so a healthy balance is essential. When this process is impaired through gut microbiome dysbiosis, the results are a reduction of circulating estrogens and toxins.

High levels of circulating estrogen can be toxic to the body and create a condition called estrogen dominance, leaving one vulnerable to estrogen-related problems like PCOS, endometriosis, ovarian cysts, fibroids, and even estrogen-related cancers. Repairing your gut will boost your estrogen metabolism pathways and feed your estrobolome, which is essential for estrogen health.

Too much circulating estrogen causes estrogen dominance which can increase pigmentation and lead to vascular changes in the skin. Heightened levels of beta-glucuronidase have also been found in several different types of cancers like GI, lung, colon, breast, and pancreatic. B-glucuronidase causes high levels of carcinogens and promotes cancer cell growth.

Estrogen Dominance.

Estrogen dominance is caused by an accumulation of circulating estrogen in the body, and also refers to the estrogen-progesterone ratio. Estrogen and progesterone need to be in balance for optimized health. You can read about the ratios here from ZRT Labs.

Estrogen dominance can also be caused by gut problems and liver stagnation, which both play a major role in estrogen metabolism. B vitamin deficiency can also affect estrogen metabolism.

How you metabolize estrogen is also important. When estrogen is ready for elimination it is processed in the liver during Phase I detoxification. The liver breaks down estrogen into three metabolites, 2OH, 4OH and 16OH. The 20H pathway is least carcinogenic, while the other two are more carcinogenic and associated with breast and uterine tissue growth, including cancer.

Many women have estrogen dominance from the long-term use of supplemental estrogen after coming off birth control. This is why women get melasma from birth control and HRT. It is said that a woman will produce more estrogen during pregnancy than throughout the rest of her lifespan combined. This estrogen dominance combined with gut and liver stagnation can result in melasma.

Some symptoms of estrogen dominance include:

Painful, heavy or irregular periods
PMS
Weight gain
Mood swings & irritability
Hair loss
Breast swelling and pain
Fibrocystic breast changes

Estrogen dominance contributes to many different diseases like PCOS, endometriosis, fibroids, and cysts and if left untreated can cause cancer.

Estrogen regulates the PDZK1 gene which is found in epithelial cells. An increased level of PDZK1 gene expression is also correlated with melasma. Overexpression of the PDZK1 gene increases tyrosinase expression of pigmentation transfer in skin cells.

Here is the scary part, PDZK1 is a novel factor in breast cancer. There is not any correlation between melasma and breast cancer but estrogen dominance is clearly dangerous and needs to be taken very seriously.

Estrogen >---->PDZK1>---->Tyrosinase>---->Melasma

Xenoestrogens & Metalloestrogen.

Xenoestrogens are chemicals that come from our environment that mimic estrogen in the body by binding to estrogen receptors. Also known as endocrine-disrupting chemicals, they disrupt the normal function of hormones. These chemicals can be found in common household products, plastics, health and beauty products, offices, and in foods. They’re really all around us. See the list of chemicals here.

Metalloestrogen act like xenoestrogens but are in essential mineral form. Toxic minerals can bind to estrogen receptors by acting as xenoestrogens. Lead, copper, mercury, cadmium and other metalloestrogens wreak havoc in your body. This is why Heavy Metal Detox & Your Skin is vital.

Pigmentation.

While complicated, it seems estrogen plays both a direct and indirect role in the darkening of skin pigmentation. Progesterone has been shown to have the opposite effect which begs the question, why do some women get melasma from progesterone-based birth control. My guess is that synthetic progesterone has similar effects to xenoestrogens rather than acting as pure progesterone in the body:

“Since many progestins bind not only to the progesterone receptor, but also to the glucocorticoid, androgen, mineralocorticoid, and possibly the estrogen receptors, it is plausible that synthetic progestins exert therapeutic actions as well as side-effects via some of these receptors.”

Estrogen increases tyrosinase activity by binding the melanocortin1 receptor, which regulates pigmentation and regulates UV response. Since estrogen induces melanogenesis (a process that stimulates pigmentation) it can seem strange that menopausal women can get melasma, considering their lower estrogen levels. The reason is that most women in menopause take HRT, which usually consists of carcinogenic synthetic estrogen similar to birth control.

Conclusion.

It's amazing to see how a woman’s reproductive health is deeply connected to skin health through her hormones. Her body is an interdependent ecosystem, and balance is vital for reversing melasma.

Resources:

https://pubmed.ncbi.nlm.nih.gov/11705091/#:~:text=Estrogen%20appears%20to%20aid%20in,and%20therefore%20maintain%20skin%20thickness.

https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13915

https://pubmed.ncbi.nlm.nih.gov/21414337/

https://www.frontiersin.org/articles/10.3389/fgene.2016.00095/full

https://pubmed.ncbi.nlm.nih.gov/19179815/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276867/

https://pubmed.ncbi.nlm.nih.gov/12197785/

https://www.mskcc.org/cancer-care/integrative-medicine/herbs/calcium-glucarate#references-3

https://gremjournal.com/journal/03-2021/cutaneous-manifestations-of-estrogen-excess-and-deficiency/#:~:text=Variations%20in%20estrogen%20levels%20throughout,palmar%20erythema%2C%20and%20breast%20development.

https://elifesciences.org/articles/15104

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863824/