Endometriosis: Mitigating Risk, Progression, and Severity

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

The underlying trigger of endometriosis so far remains unclear and thus eludes prevention. "We don't know the precise cause, so it's quite difficult to prevent it," said Linda C. Giudice, MD, PhD, of the University of California San Francisco. "About 50% of endometriosis cases are thought to be genetic, but there is no endometriosis gene to test for. Although about 50% are thought to be due to environmental factors, there are no studies on the impact of environmental factors on the type of endometriosis and the speed of progression."

That being said, while certain acknowledged risk factors for this chronic inflammatory disease are not modifiable – for example, heredity, height, race/ethnicity, early menarche, and late menopause – as with other chronic illnesses, some measures may mitigate the risk of developing it, slowing its progression, or at least staving off the more severe form of the condition.

If, for example, an adolescent girl or young woman has a family history of severe endometriosis or shows precursor symptoms such as pelvic pain, severe dysmenorrhea, or menstrual cycles of less than 27 days with longer bleeding times, what variables might be modified to lower her risk of developing widespread and entrenched disease?

Lowering Estrogen Levels with Contraceptives

Joseph Nassif, MD, MBA, of Baylor College of Medicine in Houston, said that if an at-risk individual has had early menarche, say at age 8 instead of 13, the most expeditious preventive step is to put her on combination contraceptives to lower her estrogen levels, reduce bleeding, and control the intervals of menstruation even if she is not sexually active or concerned about pregnancy.

"Birth control can regulate her short menstrual cycles and lengthen them from, say 22 days to 35 days, and shorten the time of bleeding from more than 7 days," Nassif explained.

Giudice noted that although continuous birth control medication to eliminate bleeding altogether and reduce the risk of extrauterine seeding is a possible option, not many patients would choose this route. "Teenage girls don't want to feel different from their peers, and many women find having a period reassuring since it tells them they're not pregnant," she said, adding that adolescent girls need estrogen to form strong bones.

But with early-onset menarche and premature exposure to ovarian estrogen such a strong risk factor, is it feasible to consider pharmaceutical intervention to postpone menarche altogether? "There are no studies on that, and we don't know how that would affect the development of an adolescent girl," Nassif said.

Joseph M. Gobern, MD, MBA, of Main Line Health in Wynnewood, Pennsylvania, added: "The hormonal cycle contributing to menarche may impact other developmental conditions and should be considered cautiously in consultation with the patient's physician."

Correcting Anatomical Abnormalities

If a young patient presents with pain and cramping in the mid-abdomen, she should be checked for uterine and vaginal abnormalities that may lead to hematocolpos, including various uterine anomalies and imperforate hymen, since these may block the normal exit of blood and foster retrograde menstruation, Nassif said. "An exceptionally tight cervix causing obstruction, or a uterine anomaly leading to hematocolpos can be modified surgically to normalize menstruation."

Weight Management

While many women are focused on having a low body mass index (BMI), a too-low BMI is another modifiable risk factor for endometriosis, he noted. "The very thin are more prone to endometriosis, so doctors should advise a person at risk or with early disease to keep her BMI in the normal range of 20 to 25."

Earlier Pregnancy

Obviously, many life factors enter into the decision about when to have a child, but if having a baby earlier rather than later is feasible, a patient should consider it. "Patients who never have children are at higher risk, and pregnancy generally eases endometriosis symptoms. So if a young woman is planning on having a family and is at high risk, it may be advisable to have a baby at 20 rather than 30," Nassif said.

In Utero and Neonatal Exposures

For a woman with a family history who is concerned about her daughters having endometriosis, it's especially important to avoid adverse pregnancy outcomes – to the extent that these can be prevented.

A 2020 meta-analysis found that the following risk factors slightly increased the chance of a female infant developing endometriosis in adult life:

• Premature birth (logRR 0.21)

• Low birthweight (0.35)

• Formula-feeding (0.65)

• Gestational exposure to the anti-miscarriage drug diethylstilbestrol (0.65); an earlier, 2004 analysis of Nurses' Health Study II data identified an even higher risk of 80% for laparoscopy-confirmed endometriosis in adult life in women exposed to diethylstilbestrol in utero

Diet and Supplements

Consuming a diet aimed at reducing inflammation as well as keeping estrogen levels in check and reducing its uptake from the blood may be of benefit and has the added effect of empowering patients. Diet can be a central part of a proactive self-management approach to chronic illness and has been associated with a decrease in depression and helplessness and an increase in quality of life.

And although the precise dietary connections are inconclusive and require further study, a 2020 review suggested that nutrients with anti-inflammatory properties such as omega-3 fatty acids might be of benefit in endometriosis. As for minerals, magnesium, may help to relax uterine and pelvic muscles and reduce pain.

In a 2021 endometriosis survey, respondents perceived benefits from dietary changes such as eliminating gluten and dairy and consuming more vegetables. No correlations with specific foods were found, however.

"Some research has supported a lower risk of endometriosis associated with a high intake of green vegetables and fresh fruit," said Gobern. The Nurses' Health Study II, for example, found a risk reduction in women who ate a lot of fruit, especially citrus.

As in other estrogen-sensitive diseases such as breast cancer, a diet that reduces circulating levels of estrogen may be of benefit in endometriosis. According to Nassif, a high-fiber regimen may slow the absorption of endometriosis-fueling estrogen, while anti-inflammatory and antioxidant foods rich in vitamins and minerals may have a further positive impact on inflammation. "A Mediterranean-type diet with legumes, whole grains, ground flaxseed, fatty fish, and foods with good fats like avocado and olive oil could help," he said.

Other experts recommend avoiding proinflammatory items such as hydrogenated fats and the omega-6 fats found in some vegetable oils. Sugar and artificially sweetened drinks and foods, additive-rich ultra-processed foods, and those high in saturated lipids such as full-fat dairy and fatty red meat should also be avoided.

Limiting intake of alcohol, which is known to raise estrogen levels, may also be wise for other health benefits, although there is no clear evidence. A 2019 analysis by Rachael Hemmert and colleagues found no association between endometriosis and alcohol (or smoking).

The jury is still out on dietary soy and other sources of phytoestrogens: some researchers believe the phytoestrogens in soy may block the impact of more potent endogenous estrogens, while other experts think that in some patients these isoflavone compounds may detrimentally boost estrogen levels. An empirical trial-and-error approach may be the way to go.

A 2021 meta-analysis found no conclusive evidence either way, but suggested that favorable isoflavone characteristics such as antiproliferative, anti-angiogenic, anti-inflammatory, pro-apoptotic, and anti-oxidant properties could make phytoestrogen compounds a viable alternative in the future for the control and prevention of endometriosis.

As for caffeine, a 2014 meta-analysis found no association between caffeine and endometriosis as did the study by Hemmert's group. In 2012, however, Karen Schliep and associates reported that moderate consumption of caffeine was tied to reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intake were associated with increased estradiol concentrations among women of all races.

Further research into the caffeine connection is warranted.

Supplements

Although, again, data are lacking, there may be a possible role in relieving the symptoms of endometriosis for anti-inflammatory supplements such as fish oil and other omega-3 fatty acids, tart cherries, and turmeric. Probiotic supplements to strengthen the gut microbiota, which is involved in regulation of the immune system, are also under consideration.

"In the case of probiotics, the best initial approach would be to manipulate the gut microbiome in animal models of endometriosis to see what happens to the lesions," Giudice said adding that in the meantime, there is not much downside to trying probiotic or anti-inflammatory supplements to see if they help.

Exercise and Management Techniques

Regular exercise has been demonstrated to lower the risk of endometriosis and be an effective way to help control chronic pelvic pain, Gobern noted. Moreover, physical activity is another empowering patient-managed measure that may lower estrogen levels by increasing lean muscle mass and reducing estrogen-producing fat cells.

Exercise may also favorably alter the way the body metabolizes this reproductive hormone. In 2013, the Women In Steady Exercise Research (WISER) study found that aerobic exercise led to an improved metabolite profile resulting in significant increases in 2-hydroxyestrone concentrations and decreases in 16-hydroxyestrone. Increases in the urinary 2/16 estrogen metabolite ratio have been associated with a possible reduction in the risk of breast cancer and other estrogen-sensitive diseases.

Hemmert's study, however, found no association with exercise but did note a modest trend toward increased risk of endometriosis related to total daily sitting time.

Regular physical activity can improve psychological health, Giudice said. "Not only is exercise good for the heart, but it also has positive effects on mood. Many endometriosis patients with chronic pain and infertility experience depression, and regular exercise may be beneficial for mood."

As with other painful chronic disorders such as irritable bowel syndrome, symptoms may be better tolerated with cognitive behavioral therapy, biofeedback, yoga, and meditation.

Overall, the combination of diet and exercise may offer a measure of protection via endogenous estrogen reduction and, equally important, impart a sense of empowerment and control to patients.

Reducing Exposure to Pollutants

According to Gobern, there is currently no solid evidence to support or dispute any impact of environmental contaminants on endometriosis. Still, the modern environment is rife with endocrine-disrupting chemicals such as phthalates, dioxins, PCBs, and parabens found in sources ranging from plastic containers, can linings, and pesticides to shower curtains, body washes, and face makeup. Some of these compounds are estrogen-mimicking and so could potentially impact circulating estrogen levels in an adverse way.

One simple measure that at-risk or affected women can take is to make sure they know what's in the personal-care products they use, advised Giudice. "They should also thoroughly wash all fresh fruits and vegetables before eating and wash their hands after handling and peeling them."

The Endocrine Society offers a list of common endocrine disruptors and how to avoid them.

Routine Early Screening

Experts agree on the need for more prospective research into prevention and mitigation strategies. In the meantime, physicians can outline some ways to lighten patients' burden. One approach would be routine screening of young girls and women for early diagnosis.

Endometriosis will strike approximately 11% of U.S. women over their lifetimes. In comparison, cervical cancer will affect just 0.7%, yet many young women undergo screening for its precursors with regular Pap smear tests. To that end, French endometriosis researchers led by Charles Chapron, MD, recently validated a patient questionnaire to identify women at high risk to allow timely referral to definitive diagnosis and medical care.

Read previous installments of this series:

Part 1: Endometriosis: Understanding the Pathogenesis and Pathophysiology

Part 2: Diagnosing Endometriosis

Part 3: Managing Endometriosis: Research and Recommendations

Part 4: Case Study: Endometriosis or Hernia?

Part 5: Endometriosis: Fertility and Pregnancy

Part 6: The Latest on What to Know About Managing Endometriomas

Part 7: Enhancing the Doctor-Patient Dialogue About Endometriosis

Part 8: Case Study Mystery: Swollen, Painful Belly Button During Menstruation

Part 9: Endometriosis: Why Is Research Funding So Low?

Part 10: Endometriosis's Links to Inflammatory Conditions and Other Diseases