Endometriosis After Menopause: Everything You Need To Know

If you’ve been told that endometriosis goes away after menopause, this may not be the case. So, this may not be a great strategy if you’re trying to “wait out” endo through perimenopause and into menopause. 

It is reasonable to think that chronic conditions of your female reproductive organs, like endo, might also go away when you stop having periods. Here’s a look at how endo may or may not change after menopause, based on what we know about molecular biology and hormonal changes as you get older.

Does Menopause Cure Endometriosis?

Natural menopause does not occur overnight and it might take years before estrogen levels from the ovaries become negligible.  Active growth of endo may decrease at this point but, given other estrogen sources discussed in this article and internal molecular factors, it may not stop. So, trying to wait out endometriosis until menopause is final may give it another 5 years or more to grow and cause problems.  An active treatment strategy to address endo that persists into peri-menopausal years might limit the damage and lead to better results.    

Endometriosis Management After Menopause

After menopause, the management of endometriosis may become more difficult because by this point in life endo may have been present for decades, even if previously removed partially once or twice by surgery.  At this point symptoms may be due to endo as well as scarring and fibrosis, which is part of the body’s normal healing process. The associated problem is that fibrosis and scar does not respond to any medical therapy.  This, in turn, means that surgery is the main, if not the only, option for treatment after menopause in many cases. Of course, everyone is different and pelvic floor therapy and supportive care are also in the mix.   

Endometriosis After Menopause: The Molecular Biology

Endometriosis cells and tissue look very similar to the normal uterine endometrial lining.  Both are stimulated to grow and both try to shed monthly under cycling hormonal influence.  During a menstrual period,  endometrial tissue has the ability to shed and exit via the cervix and vagina.  Unfortunately, the similar-looking endometriosis tissue has no way to exit the body and gets trapped, causing inflammation, scarring, and pain.

Uterine endometrial tissue needs the hormone estrogen to grow, and usually, but not always, so does endometriosis. When you go through menopause naturally, your ovaries produce less estrogen. This causes symptoms such as hot flashes and night sweats. But the commonly held belief is that endometriosis may improve, or even go away, with the reduction in estrogen production by ovaries. We now understand why this does not happen in all women through molecular biology research.   

Endometriosis at a Molecular Level

While many factors control endo growth, including immunologic ones, exploring the molecular biology of hormones in menopause suggests that hormones can undoubtedly be a big part of the picture. In addition to the usual conversation about external estrogen from ovaries, which decreases towards menopause, intra-cellular production of estrogens also plays a critical role in the pathogenesis of endometriosis. This increases in peri and postmenopausal women who have persistent active endometriosis lesions.  

Without getting lost in the details of hormone enzyme activation and deactivation, which results from genetic switches getting turned on and off, suffice to say that research supports the following. There is local estrogen production in endometriosis cells, which activates other feedback loops at the cellular level. This activation of loops causes even more estrogen production and resistance to progesterone (the balancing hormone). This affects macrophages and pro-inflammatory cytokines (e.g., TNF-α and IL-1β), which sets off another chain reaction. These also create molecular signals (e.g., VEGF) that stimulate microscopic blood vessel formation to feed the endo cells and activate anti-apoptotic genes (e.g., Bcl-2), creating more endo growth. This leads to local tissue trauma, nerve stimulation, fibrosis, and pain. 

Endometriosis Symptoms After Menopause

What happens to your symptoms could depend on the severity of your symptoms before menopause and hormonal and inflammatory balance. If your endometriosis is mild, it may get better with menopause. If your disease is severe, symptoms are more apt to persist. Why? Several reasons: scarring and fibrosis that only gets worse and a molecularly more active endo type that persists and keeps growing after menopause. It is currently impossible to predict what type you may have and what molecular signals are in play in any given individual.   

If your symptoms don’t improve even after you’ve stopped having menstrual cycles, surgery may be the best option for you. Surgery to remove all of your endometriosis and fibrosis will often be more effective than medication. Years of growth and fibrosis can lead to more local nerve noxious stimulation, and the first step is to remove this. Medications, including natural enzyme supplements, will not dissolve scars, and any persistent active endo is also more difficult to control after menopause. Many other molecular signaling paths are operational, making it harder to determine the best target to block abnormal effects. All the various inter and intracellular signaling forms are under intense research. 

Estrogen Replacement After Menopause with Endo: Is It Safe?

All of the above concerns how, when, and where estrogen is produced. But how this affects cells in your body, including endometriosis cells, depends on the presence or absence of estrogen receptors. You can think of the estrogen molecules as little keys which float through your bloodstream and tissues (or locally produced on or near the endo cells), and the estrogen receptors are like little locks present in and on the cells. The two have to connect, or the key has to fit the lock to produce a molecular signaling event at the cellular level. One of these signaling events is whether or not to stimulate growth. 

There are different estrogen receptors called estrogen receptor alpha (ERα) and beta (ERβ). In some estrogen-sensitive tissues, like the breast or uterus, these two types can be variably pro-growth, and in others, they can be inhibitory. In addition, there is a progesterone receptor (PR) that binds progesterone in the same fashion via a lock and key mechanism. Endometriosis cells have overexpression of mainly ERβ and underexpression of PR. This imbalanced expression of receptors leads to progesterone resistance and amplification of the growth signal provided by estrogen. This only scratches the surface of incredible complexity, but hopefully, you get the idea. 

In general, to alleviate postmenopausal hot flashes, depending on whether you have a uterus or not after menopause, estrogen alone is often prescribed (no uterus) or combined with progesterone (the uterus is in). This is because progesterone balances the effect of estrogen on the uterus and reduces the risk of endometrial cancer due to estrogen-induced overgrowth of the endometrium.   

The exact ratio of alpha (ERα) and beta (ERβ) and the amount of PR present can be variable in endometriosis. It can change over time into menopause or after surgically induced menopause due to early removal of the ovaries. So, theoretically, any hormonal replacement will affect endo cells to some degree and may amplify the degree to which local estrogen is produced, as discussed above. The degree to which this happens and evolves is not predictable from person to person. 

Where does that leave us? It comes down to risk vs. benefit discussion because a reasonable amount of estrogen replacement after menopause can help the quality of life and bone health. Studies have not proven whether or not this can activate or amplify endometriosis growth after menopause. 

How About Compounded Natural or Bioidentical Hormones?

The long answer to this is very complex and depends highly on the quality of these hormones and whether or not the dosages are correctly mixed and, if one were to use combinations that are applied to the skin, degree of absorption, and much more. The problem with synthetic vs. natural arguments notwithstanding, the effect on the very variable and unpredictable receptor signaling described above remains theoretically unchanged. There is also a higher risk of inadvertently taking a higher dose since many are locally prepared and thus subject to less regulation. Get a highly qualified opinion and possibly several opinions and do a lot of due diligence personal research before going this route.  

How About Plant-Based Phytoestrogens?

Plant estrogens, otherwise known as phytoestrogens, uniquely attach to estrogen receptors. They can bind to either type of estrogen receptor but preferentially bind to ERβ. In doing so, they take up space and block the ability of regular estrogen to bind to the receptor. In terms of helping menopausal symptoms, estrogen receptors also exist on blood vessels, and the binding of phytoestrogens helps stabilize the blood vessels, reducing hot flashes. The effect is less than that caused by regular estrogen but is helpful in many women. At the same time, there can be a relative blockade at the endometriosis cell level. Again, given the differences regarding receptors and signaling effects between individuals, this is not 100% predictable but can be a win-win nonetheless.  

Along the natural, integrative line of thought, a couple of corollary strategies is how the estrobolome and seaweed figure into this puzzle. First, the estrobolome is part of your gut microbiome that can metabolize the excess estrogen in your body and eliminate it. This includes the excess estrogen produced by ovaries, local estrogen created at the cell level, and the toxin type of estrogens called xenoestrogens. Keeping your microbiome healthy and happy with probiotic supplements or fermented foods is the action time. Second, we know that seaweed can predictably reduce circulating estrogen. This can retard any hormonal influence on the regrowth of endo, especially if the bulk of any disease is removed surgically. 

Read more: Postmenopausal Malignant Transformation of Endometriosis

When is Surgery an Option for Peri and Post-Menopause Endometriosis?

If symptomatic endo is suspected as one gets closer to menopause, it merits discussion about expert removal of as much as possible via excision surgery. Ideally, a surgeon should remove all visible lesions in this case. Even if undetectable microscopic implants are left behind, removal of pain-producing scars/fibrosis and the bulk of any active endo limits the number of cells that might grow back over time, whether or not hormonal replacement is taken. 

There is one more reason for considering surgical removal. If you have a family history of cancer or have active endo as you enter menopause, given the known molecular abnormality overlap between endo and cancer (e.g., ARID1A), the risk of malignant degeneration may be higher. This is a highly individualized situation, but some can be critical to balancing the surgical risks vs. potential benefits.    

Surgical Concerns

So, with all of the above in mind, is there a reason NOT to have surgery to remove endo, especially if you have symptoms as you get close to or enter menopause? Of course! Even minimally invasive surgery is not risk-free, and the risks can increase as you get older. Scarring and fibrosis from advanced endometriosis possibly increased from prior surgeries, leading to complications and damage to organs, including the bowel. For this reason, selecting an über expert surgeon at that point in life is crucial.   

An über expert surgeon can handle pretty much any possible finding in the pelvis and abdomen. Moreover, they can address oncology risk concerns if you are at higher risk with a family history. This means that the right surgery for cancer would be performed if cancer were suspected or found during surgery. But short of cancer, this surgeon needs to be able to handle small bowel, rectal, bladder, ureteral involvement, even disease in the upper abdomen and diaphragm. Deep infiltrating endometriosis implants are more common if they have been allowed to grow over the years. This full-spectrum surgeon might be a gynecologic oncologist who has experience in endo excision. But even they may need a cardiothoracic surgeon if endo involves the chest cavity. Cardiothoracic surgery is an entirely separate specialty of surgery. Alternatively, a minimally invasive surgery team including an endo excision trained GYN surgeon, a urologist, a general surgeon, and possibly more would need to be available. It can be a logistic challenge to gather such a team, but this is usually possible in centers that specialize in endometriosis surgery.

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More articles from Dr. Steve Vasilev:

Understanding the Connection between Endometriosis and Cancer

How to tell the difference between endometriosis and ovarian cancer

What would happen to the signs and symptoms of endometriosis after menopause?

The author of this article, Dr. Steven Vasilev MD is a fellowship-trained, triple board-certified integrative gynecologic oncologist specializing in complex pelvic robotic surgery. He focuses on advanced & reoparative endometriosis excision and molecular integrative healing, especially as it applies to women of older reproductive age and in menopause.

3 years ago Endometriosis , Endometriosis Education

Gut microbiota and endometriosis

There is a lot of interest in research about the effect of the gut microbiota on our health. The gut microbiota is the collection of microorganisms that live in the human gastrointestinal tract. The “intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens” and “altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections” (Thursby & Juge, 2017).

Xu et al. (2017) note that: 

“Gut microbiota can interact with the central nervous system through the gut–brain axis, thus affecting the host’s chronic stress level, such as anxiety and depression. Current researches show that patients with endometriosis often have a high level of chronic stress, which will in turn aggravate endometriosis by activating the β-adrenergic signaling pathway…. We found that in patients with endometriosis, the dysbiosis of gut microbiota was associated with their stress levels. Furthermore, the levels of Paraprevotella, Odoribacter, Veillonella, and Ruminococcus were significantly reduced in chronic stressed endometriosis patients, suggestive of a disease-specific change of gut microbiota at the genus level. Compared to the healthy women, the expression levels of inflammatory cytokines, nuclear factor-κB p65, and cyclooxygenase-2 increased in the chronic stressed endometriosis patients, indicating that the dysbiosis of gut microbiota may activate the inflammatory pathway of gut–brain axis.” 

Perrotta et al. (2020), while exploring the gut and vaginal microbiota of people with endometriosis, found that “vaginal microbiome may predict stage of disease when endometriosis is present”. That is pretty specific microbiota! It is not clear whether the inflammation from endometriosis causes changes to the gut microbiota and/or the gut microbiota increases inflammation associated with endometriosis (or both). However, Bolte et al. (2021) found that: 

“Higher intake of animal foods, processed foods, alcohol and sugar, corresponds to a microbial environment that is characteristic of inflammation, and is associated with higher levels of intestinal inflammatory markers…. Modulation of gut microbiota through diets enriched in vegetables, legumes, grains, nuts and fish and a higher intake of plant over animal foods, has a potential to prevent intestinal inflammatory processes at the core of many chronic diseases.”  

This suggests that a healthy diet may help improve the gut microbiota and potentially inflammation. It is not known whether this would have a significant impact on symptoms experienced.  

References 

Bolte, L. A., Vila, A. V., Imhann, F., Collij, V., Gacesa, R., Peters, V., … & Weersma, R. K. (2021). Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome. Gut, 70(7), 1287-1298. Retrieved from   https://gut.bmj.com/content/70/7/1287  

Perrotta, A. R., Borrelli, G. M., Martins, C. O., Kallas, E. G., Sanabani, S. S., Griffith, L. G., … & Abrao, M. S. (2020). The vaginal microbiome as a tool to predict rASRM stage of disease in endometriosis: a pilot study. Reproductive Sciences, 27(4), 1064-1073. Retrieved from https://link.springer.com/article/10.1007/s43032-019-00113-5 

Thursby, E., & Juge, N. (2017). Introduction fo the human gut flora. Biochem J, 474(11), 1823-1836. doi: 10.1042/BCJ20160510 

Xu, J., Li, K., Zhang, L., Liu, Q. Y., Huang, Y. K., Kang, Y., & Xu, C. J. (2017). Dysbiosis of gut microbiota contributes to chronic stress in endometriosis patients via activating inflammatory pathway. Reproductive and Developmental Medicine, 1(4), 221. Retrieved from https://www.repdevmed.org/article.asp?issn=2096-2924;year=2017;volume=1;issue=4;spage=221;epage=227;aulast=Xu