Many women are prescribed oral estrogen without ever being told what happens after it enters the body. In this episode, Dr. Brendan McCarthy takes a deeper look at estrone, the estrogen metabolite created when estradiol is taken orally, and explains why the delivery method of hormone therapy matters. You'll learn: The difference between estradiol and estrone Why oral estrogen creates significantly higher estrone levels How estrone may contribute to inflammation and insulin resistance The connection between estrogen metabolism and weight gain during perimenopause and menopause Why monitoring labs is essential when using hormone therapy The importance of understanding risks, benefits, and treatment options before starting hormones Dr. McCarthy also discusses the role of inflammation, body fat, metabolic health, and hormone delivery systems in creating long-term outcomes for women navigating menopause. This episode is about education, informed consent, and helping women better understand the science behind their care. Citations: There is more than one estrogen; after menopause, estrone dominates Kuhl, Herbert. “Pharmacology of Estrogens and Progestogens: Influence of Different Routes of Administration.” Climacteric, vol. 8, no. S1, 2005, pp. 3–63. Body fat is an endocrine organ — aromatase converts androstenedione into estrone, and adipose becomes the dominant post-menopausal estrogen source Lee, Angel A., and Laura J. Den Hartigh. “Metabolic Impact of Endogenously Produced Estrogens by Adipose Tissue in Females and Males across the Lifespan.” Frontiers in Endocrinology, vol. 16, 2025, article 1682231. Inflamed fat raises IL-6; IL-6 tracks the insulin-resistant state Kern, Philip A., et al. “Adipose Tissue Tumor Necrosis Factor and Interleukin-6 Expression in Human Obesity and Insulin Resistance.” American Journal of Physiology-Endocrinology and Metabolism, vol. 280, no. 5, 2001, pp. E745–E751. IL-6 is part of the insulin-resistance machinery — it correlates with impaired insulin-stimulated glucose uptake Bastard, Jean-Philippe, et al. “Adipose Tissue IL-6 Content Correlates with Resistance to Insulin Activation of Glucose Uptake Both In Vivo and In Vitro.” The Journal of Clinical Endocrinology & Metabolism, vol. 87, no. 5, 2002, pp. 2084–2089. Inflammation amplifies aromatase — IL-6 raises aromatase via COX-2/PGE2 Bowers, Laura W., et al. “Obesity-Associated Systemic Interleukin-6 Promotes Pre-Adipocyte Aromatase Expression via Increased Breast Cancer Cell Prostaglandin E2 Production.” Breast Cancer Research and Treatment, vol. 149, no. 1, 2015, pp. 49–57. Human-tissue confirmation: HOMA-IR, IL-6, insulin, leptin, hsCRP track breast aromatase after menopause Brown, Kristy A., et al. “Menopause Is a Determinant of Breast Aromatase Expression and Its Associations with BMI, Inflammation, and Systemic Markers.” The Journal of Clinical Endocrinology & Metabolism, vol. 102, no. 5, 2017, pp. 1692–1701. Iyengar, Neil M., et al. “Effects of Obesity on Breast Aromatase Expression and Systemic Metabo-Inflammation in Women with BRCA1 or BRCA2 Mutations.” npj Breast Cancer, vol. 7, no. 1, 2021, article 18. The molecular crux: estrone drives ERα/NF-κB inflammatory signaling while estradiol opposes it Qureshi, Rehana, et al. “The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development.” Cell Metabolism, vol. 31, no. 6, 2020, pp. 1154–1172.e9. Estrone as a metabolic-risk signal — prospectively associated with diabetes (note: male cohort) Jasuja, Guneet Kaur, et al. “Circulating Estrone Levels Are Associated Prospectively with Diabetes Risk in Men of the Framingham Heart Study.” Diabetes Care, vol. 36, no. 9, 2013, pp. 2591–2596. Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he’s helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He’s also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more. If you’re ready to take your health seriously, this podcast is a great place to start. 👇 Tap Subscribe to learn more about what’s actually happening in your body, and what to do about it. 📘 Read Dr. McCarthy’s Book: Jump Off the Mood Swing – A Sane Woman’s Guide to Her Crazy Hormones https://www.amazon.com/Jump-Off-Mood-... 📲 Follow Dr. McCarthy: Instagram: @drbrendanmccarthy TikTok: @drbrendanmccarthy Website: www.protealife.com 💬 Got a question or topic for a future episode? Let us know in the comments!
