There are more than 80 recognized autoimmune diseases, and according to current estimates, up to 20 percent of Americans may be affected.
And here’s the most striking statistic:
80% of those affected are women
(Desai & Brinton, 2019)
That’s not a coincidence. It’s a hormonal phenomenon—and if you’re a provider prescribing hormone replacement therapy (HRT), you need to understand this.
The Three Major Hormonal Shifts in Women
Women undergo three distinct phases of massive hormonal change throughout life:
- Puberty
- Pregnancy and Postpartum
- Menopause
Each of these transitions creates dramatic fluctuations in estrogen and progesterone, which are directly tied to immune regulation.
At HRT University, we dedicate an entire section in the Master Course to Hashimoto’s thyroiditis and other autoimmune conditions, breaking down how these shifts correlate with increased risk.
How Estrogen and Progesterone Affect the Immune System
To understand why women develop autoimmunity more than men, you need to understand Th1 vs. Th2 immune balance.
- Th1: Intracellular defense—targets viruses and bacteria
- Th2: Extracellular defense—targets parasites, allergens, and promotes antibody production
In ideal physiology, the two systems balance one another. But guess what?
Estrogen and progesterone tip the scale.
High estrogen levels may shift the immune system toward Th2 dominance, while fluctuations can destabilize the system entirely. Progesterone, on the other hand, tends to have a calming, immunosuppressive effect, protecting against overactive responses.
These tipping points, especially during postpartum and perimenopause, can trigger or exacerbate autoimmune conditions.
What About Hormone Replacement Therapy and Autoimmunity?
Now here’s where it gets messy.
Most large-scale studies analyzing hormone use and autoimmunity have used oral contraceptives or synthetic HRT as their standard—this leads to confusion.
For example:
- Non-bioidentical birth control has been associated with increased risk of autoimmune disease
- But bioidentical hormones tell a different story
Recent literature suggests:
“Estradiol downregulates the AIRE gene, a key regulator of immune tolerance.”
(Constantin & Baicus, 2023)
The AIRE gene is crucial for central immune tolerance—without it, the immune system becomes more prone to attacking self-tissues.
Even more interesting? AIRE is also regulated by progesterone and dihydrotestosterone (DHT).
Which means the entire hormone ecosystem matters—not just estrogen alone.
So What Should Providers Do?
If you’re a nurse practitioner or medical provider considering adding HRT to your practice, here’s the takeaway:
âś… Autoimmunity is deeply influenced by hormone balance
âś… Properly prescribed HRT may reduce immune overactivation
âś… Women need early, safe, and intelligent hormone optimization
The truth is, you don’t need to fear prescribing HRT.
You just need to learn it correctly—so that your clinical judgment aligns with physiology, not pharmaceutical marketing or outdated dogma.
Join the HRTU Master Course
At HRT University, we teach providers the clinical foundations of hormone therapy—from sex hormones to thyroid, to adrenal and immune cross-talk.
We are not just building courses. We’re building a movement of confident, knowledgeable, and empowered providers who are ready to restore their patients’ lives.
If you’re ready to become the kind of provider your patients need, it’s time to learn this skill set.
👉 Enroll in the HRTU Master Course
We’re here to help you grow. And your patients are waiting.
