Endometriosis

 

Rethinking Endometriosis: What If We’ve Been Treating It All Wrong?

By James Nagel, MD

If you had asked me early in my career what to do for a patient with endometriosis, I probably would’ve given you the standard response: suppress the hormones. Shut down estrogen. Keep progesterone high. Repeat. It’s what we were taught. After all, estrogen fuels endometrial growth… right?

But years of working with patients, listening to their stories, and looking at their labs, their symptoms, and their progress has led me to a startling and—I’ll admit—initially uncomfortable conclusion: we’ve been thinking about this backwards.

What if endometriosis is not a condition of estrogen dominance, but of estrogen deficiency?

That’s what I believe now. And it’s what I’ve seen play out again and again in clinical practice.

Endometriosis and the Inflammation Trap

Let’s start with what we know. Endometriosis is a chronic inflammatory condition. It’s not just about hormones—there’s an immune system dysfunction at play. Gut dysbiosis, translocation of inflammatory molecules like lipopolysaccharides (LPS), and overexpression of certain gut microbiota all contribute to a cascade of systemic inflammation.

And what does that inflammation do? Among other things, it suppresses the hypothalamic-pituitary-ovarian axis, blunts ovulation, and reduces estrogen production. In other words: inflammation leads to estrogen deficiency.

Yet we continue to treat this condition by further lowering estrogen levels.

Here’s where I started to see the disconnect.

Estrogen: More Than a Growth Hormone

When we look deeper at how estradiol actually behaves in the body, we find that high levels of estradiol are anti-inflammatory. They reduce TNF-alpha, oxidative stress, and improve mitochondrial function. Estrogen also plays a key role in apoptosis—programmed cell death—which helps keep abnormal or ectopic endometrial tissue in check.

So yes, estrogen at low levels may stimulate growth, but it’s only at optimal, physiologic levels that estrogen can actually suppress proliferation and induce apoptosis. This is the key insight that changed how I approach endometriosis.

Case in Point: Joanna’s Story

Let me tell you about one of my patients, Joanna.

She’s 45, and she came to me desperate. Despite having had a hysterectomy, she was still dealing with relentless endometriosis symptoms. She had tried birth control, chemical castration—you name it. Nothing worked. She was losing hope.

When we started her on Physiologic Hormone Restoration Therapy (PHRT®)—not just estrogen replacement, but rhythmic, physiologic levels that mimic a healthy menstrual cycle—everything changed.

Her pain disappeared. Her mood, energy, mental clarity, and libido returned. At a follow-up appointment, even her endometriosis specialist was stunned by her progress. He asked her what her secret was.

“Estrogen,” she told him.

This wasn’t a fluke. I’ve seen this happen time and time again. When we replace hormones the way the body recognizes, at the levels needed to induce normal tissue turnover and immune modulation, patients thrive.

The Role of Gut Health and the Immune System

Of course, estrogen alone isn’t the whole story.

A big part of my work involves helping patients repair their gut, reduce their systemic inflammation, and support the immune system with dietary changes, lifestyle interventions, and targeted supplementation.

Think of PHRT as one powerful piece of a larger strategy. We also look at:

  • Omega-3s, NAC, curcumin, and other antioxidants

  • Gut healing protocols and microbiome support

  • Immune-balancing agents like low-dose naltrexone

  • Reducing xenoestrogen exposure from plastics, cosmetics, and food

  • Personalized lab work to assess vitamin D, zinc, methylation status, and more

Facing the Fear of Estrogen

Now, I know some practitioners worry about giving estrogen to patients with a history of endometriosis—especially if they’ve had severe cases or a hysterectomy. The fear of “feeding the fire” is real. I had it too.

But what I’ve seen is that under-dosing estrogen is more dangerous than giving too much. You have to reach a threshold where estradiol levels are high enough to properly stimulate progesterone receptors and facilitate the critical apoptotic process.

That’s when the magic happens.

A New Paradigm

Endometriosis can no longer be seen simply as a hormone problem. It’s a whole-body condition—immune, inflammatory, metabolic. And treating it requires a comprehensive, integrative strategy.

But one thing is clear to me now: restoring physiologic hormone rhythm is not just safe—it’s essential for healing.

If you’re a provider treating patients with endometriosis, I encourage you to reconsider what you’ve been told. And if you’re a patient struggling with pain, fatigue, or loss of quality of life, know that there is hope.

PHRT® isn’t experimental. It’s evidence-based, physiology-based, and life-changing.

Let’s give women their lives back.