Endometriosis and Insulin Resistance: The Overlooked Connection

Endometriosis is a painful, often debilitating condition affecting millions of women worldwide. It occurs when tissue similar to the lining of the uterus (the endometrium) grows outside the uterus, leading to inflammation, scarring, and severe pain. Despite how common it is, the exact cause of endometriosis remains unclear, and many women go years without answers.

One potential piece of the puzzle that is rarely discussed but cannot be ignored is insulin resistance. While endometriosis is often labeled as a strictly hormonal or immune-related condition, emerging research suggests insulin may play a significant role in its development and progression.

If your doctor is only looking at estrogen and progesterone levels without considering insulin, they may be missing a key driver of your symptoms.

1. Insulin Fuels Inflammation, Worsening Endometriosis Pain

Endometriosis is considered a chronic inflammatory condition, and insulin resistance is a major driver of inflammation in the body.

• High insulin triggers the release of pro-inflammatory cytokines, which can increase pain, swelling, and tissue damage.
• Inflammation makes endometrial lesions more aggressive, leading to faster growth and worsening symptoms.
• Women with insulin resistance tend to have higher levels of C-reactive protein (CRP), a marker of inflammation that has been linked to more severe endometriosis.

This means that even if your blood sugar looks “normal,” high insulin could be fueling inflammation, pain, and disease progression.

2. Insulin Increases Estrogen, Which Feeds Endometriosis Growth

Endometriosis is estrogen-dependent, meaning excess estrogen encourages lesions to grow and spread. High insulin increases estrogen levels in multiple ways:

• Insulin lowers SHBG (sex hormone-binding globulin), allowing more free estrogen to circulate in the body.
• Excess fat tissue (often seen in insulin resistance) produces even more estrogen, further fueling endometriosis growth.
• Insulin stimulates aromatase, an enzyme that converts androgens into estrogen, increasing overall estrogen levels.

This creates a vicious cycle: more insulin → more estrogen → more endometriosis growth → more inflammation.

3. Insulin Resistance Disrupts Progesterone, Making Symptoms Worse

Progesterone plays an important role in balancing estrogen levels and protecting against excessive endometrial growth. However, women with insulin resistance often experience progesterone resistance, meaning their bodies don’t respond to progesterone as effectively.

• Progesterone resistance makes it harder to keep estrogen in check, allowing endometrial lesions to grow unchecked.
• This imbalance can lead to irregular cycles, heavier bleeding, and worsening pain.
• Many women with endometriosis struggle with infertility, and progesterone resistance may play a role.

This is why simply taking progesterone or birth control isn’t always enough—if insulin resistance is present, the underlying hormone imbalance may continue.

4. Insulin Can Increase the Spread of Endometrial Cells

One of the mysteries of endometriosis is how endometrial-like tissue ends up outside the uterus and spreads to other organs.

• High insulin levels increase the activity of IGF-1 (insulin-like growth factor-1), which encourages cell proliferation and migration.
• Endometrial cells exposed to high insulin become more aggressive, making them more likely to implant and spread.
• This could explain why some women develop endometriosis after experiencing metabolic issues like PCOS or weight gain.

Essentially, elevated insulin may make endometriosis lesions more invasive, contributing to more widespread disease.

The Link Between Endometriosis and PCOS: A Shared Insulin Problem?

PCOS and endometriosis are often thought of as completely separate conditions, but there may be more overlap than previously recognized.

• Both conditions are associated with hormone imbalances, including excess estrogen.
• Both are linked to chronic inflammation.
• Many women with endometriosis also have insulin resistance, even if they don’t have PCOS.

If you have been diagnosed with endometriosis and haven’t had your insulin levels tested, it may be worth investigating. High insulin could be worsening your symptoms, even if you don’t have PCOS.

References

• Cao Y, et al. Relationship between triglyceride-glucose index and endometriosis: a cross-sectional analysis. BMC Womens Health. 2024. Read more
• Xin Q, et al. Causal effects of glycemic traits and endometriosis: a bidirectional and multivariate mendelian randomization study. Diabetol Metab Syndr. 2024. Read more