One of my new patients had recently been diagnosed with early menopause at the age of 43. She had been started on hormone therapy by her gynecologist, but she wanted to discuss the long-term health effects of her early menopause — defined as menopause before age 45 — and how best to minimize her risk. She was especially concerned about managing her risk for cardiovascular disease. Her father had had a heart attack in his late 50s. She wanted to do all she could to avoid that herself.
During our conversation, she shared that she was relieved to be in menopause because she had endometriosis her entire adult life. Her periods had been painful, and she had required surgeries to remove the endometriosis from one of her ovaries and around her intestines.
The same week, I was excited to come across an article in the latest issue of the Journal of Clinical Endocrinology & Metabolism that helped inform my thinking about this patient and the many women like her with endometriosis and early menopause.
What is endometriosis?
Endometriosis is a common condition in which cells from the uterine lining are carried out of the uterus through the fallopian tubes and are able to settle and grow throughout the pelvis, abdomen, and even the chest.
These nests of endometrial tissue are benign. But like the endometrial tissue that grows in the uterus, endometrial tissue outside the uterus grows in response to estrogen and breaks down when progesterone levels fall during each menstrual cycle. Depending on the location of this endometrial tissue, this cycle of growth and breakdown can cause pelvic and abdominal pain and infertility. Occasionally endometrial cells can be found as far afield as the lungs.
About 10% of women of reproductive age have endometriosis. Upward of 25% of women with endometriosis do not have symptoms. Women struggling with infertility are about eight times as likely to have endometriosis as women who are fertile, though exactly how endometriosis affects fertility is poorly understood and may differ from one woman to the next.
What is the connection between endometriosis and early menopause?
The authors of the recent article note that there is convincing evidence that women with endometriosis are about 30% more likely to experience primary ovarian insufficiency (POI) — menopause before age 40 — and early menopause.
One theory is that women with endometriosis have increased inflammation in their body and that this inflammation damages the ovaries and accelerates the depletion of eggs. However, there may be a more direct effect of endometriosis on the ovaries. The risk for POI and early menopause seems to be particularly pronounced in women who have endometrial tissue growing on one or both of the ovaries (the medical term for this is endometriomas). The growth and breakdown of this endometrial tissue directly damages the ovaries.
Additionally, in some cases endometriomas are surgically removed. One review looked at several studies that demonstrated that anti-Mullerian hormone levels — levels of a hormone used as an indicator of ovarian reserve — dropped by 39% and 57% after removing endometriomas from one versus both ovaries, respectively. This drop suggests that the reproductive lifespan is shortened, meaning that some treatment options for endometriosis also affect the timing of menopause.
How are endometriosis, early menopause, and cardiovascular disease linked?
The exact ways in which endometriosis, early menopause, and cardiovascular disease are linked is not well researched. There are two main theories. The first notes that estrogen protects the arteries and prevents the formation of plaques that can block blood flow.
Estrogen levels drop during perimenopause and remain low. As a result, women who have menopause earlier are at increased risk for cardiovascular disease and can experience cardiovascular disease earlier. If women with endometriosis experience menopause earlier, it then follows that they would also be at increased risk for cardiovascular disease.
The authors of the review linked above note a second possible mechanism to explain the increased risk of cardiovascular disease in women with endometriosis. Animal studies suggest that endometriosis may directly cause blockages in the arteries. And a human study found that women with an endometrioma on one side only had higher resistance in the artery to the uterus on that side. Increased resistance is indirect evidence that the artery contains blockages.
Scientists think that endometriosis causes local inflammation around the nest of endometrial cells. Inflammation in the arteries is known to trigger the formation of plaques in the arteries. But there is still work to do improve our understanding of the mechanisms linking endometriosis and cardiovascular disease.
What can women with endometriosis do to reduce their risk for cardiovascular disease?
Certainly, all the recommendations to the general population — following a healthy diet, getting regular exercise, and stopping smoking — apply to women with endometriosis as well. If high blood pressure or high cholesterol develop, treating those conditions aggressively has been shown not only to reduce the risk of cardiovascular disease but to cause existing plaques in the arteries to be reduced in size or resolve.
The data regarding estrogen and cardiovascular disease is mixed. While we know that POI increases the risk of cardiovascular disease, there is no definitive data that treating POI mitigates that risk. However, in studies of estrogen use among women who have menopause at a typical age, there is some evidence that estrogen may reduce the risk of cardiovascular disease. It would be reasonable to consider hormone therapy especially for women with endometriosis and POI or early menopause.
There is also value in just knowing you are at increased risk for cardiovascular disease. A patient who knows and understands their risks and what symptoms to look out for can better advocate for themselves with their doctors.
The bottom line
- Endometrial tissue, particularly when it grows on the ovaries, is associated with primary ovarian insufficiency and early menopause.
- Surgical removal of endometriomas from the ovaries has been shown to reduce ovarian reserve and increase the risk of primary ovarian insufficiency and early menopause.
- In women with endometriosis, increased risk for cardiovascular disease may be due to both the risk for primary ovarian insufficiency and early menopause, and the inflammation that endometriosis causes.
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The first paragraph about what endometriosis is contains just a single theory about endometriosis. It’s actually unknown how endometriosis lesions form, and the theory that endometriosis lesions are formed from actual endometrial tissue carried out of the uterus through the fallopian tubes is generally considered an outdated. Endometriosis lesions are *similar* to the tissue that lines the uterus but are often not *identical* to the tissue that lines the uterus. Endometriosis is so poorly understood, diagnosed, and treated that it’s really, really important to accurately identify the information we actually have, especially when discussing new studies about the disease.
Thank you so much for your research/info sharing on anything mentioning POI. There is so little info and as a 37y/o diagnosed with POI it’s scary not knowing much about it.