Understanding Progesterone Resistance in Endometriosis A Functional Medicine Perspective by Dr. Simone Sturm, Denver Holistic Medicine

Understanding Progesterone Resistance in Endometriosis

A Functional Medicine Perspective by Dr. Simone Sturm, Denver Holistic Medicine

Endometriosis is far more than a “bad period.” It’s a chronic, hormone-driven, inflammatory condition in which tissue similar to the uterine lining grows outside the uterus. It thrives on estrogen, scar tissue forms, pain develops, and fertility may be challenged. Many women with endometriosis also struggle with what’s called progesterone resistance— a silent but significant barrier to healing.

Let’s explore what progesterone resistance is, how we diagnose it, and how functional medicine supports reversing it.

What is Progesterone Resistance?

In a healthy cycle, progesterone helps to calm the uterine lining, support implantation, and regulate estrogen’s proliferative effects. But in endometriosis, the tissue becomes less responsive to progesterone’s signals—a condition known as progesterone resistance. Studies show that women with endometriosis often have reduced expression of the progesterone receptor (especially the PR-B form), altered gene signaling, and impaired decidualization of the endometrium. 

In essence: progesterone may be present, but the tissues aren’t “hearing” or responding to it well. That means the protective, calming effects of progesterone are diminished—allowing estrogen to dominate unchecked, inflammation to increase, and lesions to persist.

How We Diagnose Progesterone Resistance

While there is no single “progesterone resistance” blood test, functional medicine practitioners piece together a clinical & lab-based picture:

Clinical red flags:

  • Heavy or erratic menstrual flow

  • Endometriosis-associated pain despite typical hormone therapies

  • Difficulty conceiving or recurrent losses

  • Estrogen dominance symptoms (bloating, breast tenderness, mood swings) despite adequate progesterone levels

Lab & imaging clues:

  • Hormone panel: serum/free progesterone, estrogen (E2), and ratio analyses

  • Progesterone receptor (PGR) expression – more common in research than routine practice, but the science shows reduced PR-B in endometriosis lesions. 

  • Inflammatory markers (hs-CRP, cytokines) and oxidative stress markers

  • Evaluation of estrogen metabolism and detoxification (urine metabolites, liver enzymes)

  • Gut/liver imaging or functional testing if detox or elimination is compromised

In short: failure to respond to progesterone-based treatments is a strong clinical hint for resistance. A functional medicine workup dives deeper into the why behind the resistance.

How Functional Medicine Treats Progesterone Resistance

Because progesterone resistance is multi-factorial, our treatment strategy is layered and personalized. Here are key therapeutic domains:

1. Improve hormone receptor and cellular responsiveness

  • Support methylation & gene expression (B-complex vitamins, magnesium, zinc)

  • Reduce epigenetic and receptor dysfunction (via anti-inflammatory nutrients, antioxidant support)

  • Suggest botanical support: spearmint tea, NAC, DIM (when estrogen dominance co-exists)

2. Balance estrogen and reduce estrogenic load

  • Increase cruciferous vegetables (broccoli, kale) to support pathways that balance estrogen and improve receptor function

  • Enhance liver detox: crucifers, sulfur-rich foods, calcium-D-glucarate, adequate fiber

  • Limit xenoestrogen exposure (plastics, personal care products, pesticides)

3. Calm inflammation & improve immune response

  • Diet: anti-inflammatory (omega-3 rich, whole foods, minimal processed food)

  • Supplements: fish oil, curcumin, ginger, quercetin

  • Address gut integrity: daily fiber, probiotics, resolve dysbiosis, optimize bowel habits (important for hormone elimination) 

4. Support ovulation, fertility, and the nervous system

  • Balanced blood sugar: stabilize insulin to reduce androgen/estrogen excess

  • Stress & sleep optimization: adrenal support so draining the hormonal system lessens burden on progesterone signaling

  • Movement: gentle strength training + mobility work (not excessive cardio, which can worsen stress responses)

FINAL THOUGHTS

Progesterone resistance is like having the key (progesterone) but the lock (receptor/cell response) is sticky. The result? Lesions persist, inflammation circulates, fertility may be impaired, and standard hormone therapies may under-perform.

Through functional medicine, we aim to unstick the lock, rebuild receptor sensitivity and cellular communication, and create an environment where progesterone can truly do its job. When the internal environment is optimized—detox pathways, inflammation down, hormonal rhythms supported—it’s often at this stage that women start seeing real progress: less pain, improved fertility, and fewer recurrences.

If you’re struggling with endometriosis, heavy periods, infertility, or have been told “your hormones are fine” but you don’t feel fine—this deeper layer of treatment may make all the difference. At Denver Holistic Medicine, we’re committed to investigating the root causes and creating a truly personalized plan for your unique biology.

We work with all our patients on an individualized basis to develop the safest and most effective treatment plan for you. Schedule an appointment today to get started.

Simone Sturm