Endometriosis After Menopause: Insights & Management

Everything You Need To Know

If you’ve been told that endometriosis goes away after menopause, this may not be the case, so “waiting out” endo through perimenopause and into menopause may not be a great strategy. It is understandable to assume that chronic conditions involving the female reproductive organs might resolve once periods stop, but what we know about molecular biology and age-related hormonal changes shows that endo may or may not change after menopause (https://pubmed.ncbi.nlm.nih.gov/32121424/).

Does Menopause Cure Endometriosis?

Natural menopause unfolds over years before ovarian estrogen levels become negligible. While active growth of endo can decrease at that point, it may not stop because of other estrogen sources described below and internal molecular drivers. Waiting until menopause is complete can effectively give endo another five years or more to grow and cause problems. An active treatment strategy for endo that persists into the peri-menopausal years may limit damage and improve outcomes.

Endometriosis Management After Menopause

By postmenopause, endo may have been present for decades, even if partially removed once or twice by surgery, and symptoms may reflect both active endo and scarring or fibrosis, which is a normal part of healing. Fibrosis and scar do not respond to medical therapy, making surgery the main, and in many cases the only, effective treatment after menopause. Everyone is different, and pelvic floor therapy and supportive care also have roles.

Endometriosis After Menopause: The Molecular Biology

Endometriosis cells and tissue resemble the normal uterine endometrial lining, both are hormonally stimulated to grow, and both attempt monthly shedding. During menstruation, endometrial tissue sheds and leaves through the cervix and vagina, whereas endometriosis tissue is trapped, provoking inflammation, scarring, and pain.

Uterine endometrium needs estrogen to grow, and usually—though not always—endometriosis does too. Natural menopause reduces ovarian estrogen, causing symptoms like hot flashes and night sweats, and it has been commonly believed that endometriosis improves or disappears with this drop. Molecular biology research now clarifies why that does not happen for all women.

Endometriosis at a Molecular Level

Although multiple factors, including immunologic influences, control endo growth, the molecular biology of hormones in menopause (https://pubmed.ncbi.nlm.nih.gov/31717614/) shows that hormones are often a major driver. Beyond the decreasing external estrogen from ovaries near menopause, intracellular estrogen production plays a critical role in the pathogenesis of endometriosis, and this local production increases in peri- and postmenopausal women who have persistent active lesions.

Research shows local estrogen production within endometriosis cells triggers feedback loops at the cellular level. These loops increase estrogen production and create resistance to progesterone, the balancing hormone. This cascade affects macrophages and pro-inflammatory cytokines such as TNF-α and IL-1β, which in turn generates molecular signals like VEGF that drive formation of microscopic blood vessels to feed endo cells and activate anti-apoptotic genes such as Bcl-2, resulting in further growth. The downstream consequences include local tissue trauma, nerve stimulation, fibrosis, and pain.

Endometriosis Symptoms After Menopause

Symptom changes may depend on premenopausal severity and the balance of hormonal and inflammatory signals. Mild endometriosis may improve with menopause, while severe disease is more likely to persist because of worsening scarring and fibrosis and a more molecularly active endo type that continues to grow postmenopause. It is currently impossible to predict the specific type or molecular signaling present in any individual.

If symptoms do not improve after menstrual cycles cease, surgery may be the best option. Removing all endometriosis and fibrosis is often more effective than medication because years of growth and fibrosis can intensify local nerve noxious stimulation, and removing this is the first step. Medications, including natural enzyme supplements, do not dissolve scars, and persistent active endo is harder to control after menopause due to many simultaneously active molecular signaling pathways. Intense research is ongoing into inter- and intracellular signaling targets.

Estrogen Replacement After Menopause with Endo: Is It Safe?

The effects of any estrogen—whether produced by ovaries, locally within tissues, or taken as therapy—depend on estrogen receptors in or on cells. Estrogen molecules act like keys that must fit locks (receptors) to trigger cellular signaling, including growth signals. There are two main estrogen receptors, estrogen receptor alpha (ERα) and beta (ERβ), which can be pro-growth in some tissues such as breast or uterus and inhibitory in others, and there is a progesterone receptor (PR) that binds progesterone via the same lock-and-key mechanism (https://pubmed.ncbi.nlm.nih.gov/32316608/). Endometriosis cells typically overexpress ERβ and underexpress PR, leading to progesterone resistance and amplification of estrogen-driven growth. This only introduces the complexity; there is far more to it.

To alleviate postmenopausal hot flashes, estrogen alone is often prescribed when the uterus has been removed, or estrogen is combined with progesterone when the uterus is present because progesterone balances estrogen’s effects on the uterus and lowers the risk of estrogen-induced overgrowth and endometrial cancer. In endometriosis, the ratio of ERα to ERβ and the amount of PR can vary and can change over time into menopause or after surgically induced menopause due to early oophorectomy. As a result, any hormonal replacement may affect endo cells and could amplify local estrogen production. The extent and evolution of these effects are not predictable from person to person.

The practical takeaway is that decisions come down to a risk–benefit discussion. A reasonable amount of estrogen replacement after menopause can improve quality of life and support bone health, and studies have not proven whether this activates or amplifies endometriosis growth after menopause.

How About Compounded Natural or Bioidentical Hormones?

The longer answer depends heavily on the quality of these hormones, whether dosages are correctly mixed, and, for transdermal combinations, how well they are absorbed, among other variables (https://pubmed.ncbi.nlm.nih.gov/33403887/). Regardless of arguments about synthetic versus natural, the unpredictable receptor signaling described above remains a theoretical concern, and locally prepared products can carry a higher risk of inadvertent overdosing due to less regulation. Seek a highly qualified opinion—possibly several—and do extensive due diligence before choosing this route.

How About Plant-Based Phytoestrogens?

Plant estrogens, or phytoestrogens, can bind estrogen receptors, with a preference for ERβ (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535874/). By occupying these receptors, they can reduce binding of regular estrogen. Estrogen receptors on blood vessels mediate hot flashes, and phytoestrogen binding can stabilize vessels and reduce these symptoms, with less potency than regular estrogen but helpful for many women. At the same time, there may be partial receptor blockade at the endometriosis cell level. Given interindividual differences in receptors and signaling, responses are not fully predictable, but this can still be a win–win.

Two related, integrative strategies involve the estrobolome and seaweed. The estrobolome is the portion of the gut microbiome that metabolizes and helps eliminate excess estrogen, including ovarian estrogen, locally produced cellular estrogen, and xenoestrogens (https://pubmed.ncbi.nlm.nih.gov/28778332/). Supporting a healthy microbiome with probiotic supplements or fermented foods can help. Additionally, seaweed has been shown to predictably reduce circulating estrogen (https://academic.oup.com/jn/article/139/5/939/4670381), which can lessen hormonal influence on endo regrowth, especially if most disease has been surgically removed.

When Is Surgery an Option for Peri- and Postmenopause Endometriosis?

If symptomatic endo is suspected approaching menopause, discuss expert excision surgery to remove as much disease as possible. Ideally, all visible lesions should be excised. Even if microscopic implants remain, removing pain-generating scars and fibrosis and debulking active endo reduces the number of cells that could regrow over time, whether or not hormonal replacement is used.

Another reason to consider surgical removal is cancer risk. With a family history of cancer or active endo entering menopause, the known molecular abnormality overlap between endo and cancer, such as ARID1A, may increase the risk of malignant degeneration (https://pubmed.ncbi.nlm.nih.gov/30657901/). This is highly individualized, but it can be pivotal when weighing surgical risks against potential benefits.

Surgical Concerns

Surgery is not without risk, even when minimally invasive, and risks can rise with age. Advanced endometriosis often involves scarring and fibrosis, potentially worsened by prior surgeries, and can increase the chance of complications or injury to organs such as the bowel (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286861/). Selecting an über expert surgeon is therefore crucial.

An über expert surgeon can manage virtually any pelvic or abdominal finding and can address oncologic risk if family history raises concern, ensuring the appropriate cancer surgery would be performed if cancer is suspected or discovered intraoperatively. Outside of cancer, the surgeon must be able to handle involvement of the small bowel, rectum, bladder, and ureters, and even disease in the upper abdomen and diaphragm. Deep infiltrating endometriosis is more common after years of unchecked growth. A gynecologic oncologist with endo excision experience may fit this full-spectrum profile, though thoracic involvement might necessitate a cardiothoracic surgeon, a separate specialty. Alternatively, a minimally invasive team—such as an endo excision-trained gynecologic surgeon, a urologist, a general surgeon, and others—should be available. Assembling such a team can be logistically challenging but is usually feasible at centers specializing in endometriosis surgery.