#397 ‒ Endometriosis and adenomyosis: diagnosis, fertility, reproductive aging, and emerging treatments | Renato Tomioka, M.D., Ph.D.

Episode Summary

Executive Summary: Peter Attia and Dr. Hanato Tomiyoka unpack endometriosis, adenomyosis, and infertility, emphasizing that these are common, underdiagnosed, and often mismanaged conditions. The conversation covers pathology, symptom patterns, modern imaging-based diagnosis, medical vs surgical treatment, and how age and ovarian reserve drive fertility decisions. A central message: earlier recognition and tailored treatment can preserve fertility, reduce pain, and prevent years of suffering.

Main Topics: What endometriosis and adenomyosis are (Priority: 5/5): Endometriosis is endometrial-like tissue outside the uterus; adenomyosis is similar tissue within the myometrium. The discussion clarifies uterine anatomy, disease phenotypes, and why the two conditions are related but distinct. Why these diseases are missed and delayed (Priority: 5/5): Diagnosis is often delayed because menstrual pain is normalized, biomarkers are lacking, and reliance on surgical laparoscopy has historically slowed recognition. Modern MRI and expert ultrasound can now identify many cases noninvasively. Symptoms, pain mechanisms, and clinical presentation (Priority: 5/5): Endometriosis commonly causes dysmenorrhea, dyspareunia, dyschezia, dysuria, infertility, and chronic pelvic pain. Pain may arise from nociceptive, neuropathic/nociplastic, and centrally sensitized mechanisms, which explains why surgery alone may not solve symptoms. Treatment strategies: hormones, surgery, and multidisciplinary care (Priority: 5/5): Treatment is individualized based on pain, fertility goals, lesion type, and age. Hormonal suppression, IUDs, and surgery are used selectively; central sensitization requires pain-focused and pelvic floor therapy alongside gynecologic treatment. Infertility, IVF, and age-related fertility decline (Priority: 5/5): The episode details how endometriosis, adenomyosis, tubal damage, and age affect fertility. Egg quality declines sharply after 35 due to rising aneuploidy, making IVF timing and fertility preservation crucial. Fertility preservation and emerging technologies (Priority: 4/5): Egg freezing, ovarian tissue preservation, mitochondrial replacement therapy, and stem-cell-derived gametes are discussed as present and future options, though many remain limited, expensive, or experimental. Future directions in endometriosis care (Priority: 4/5): The conversation highlights promising developments such as updated ACOG guidance, improved imaging, and a potential first biologic therapy (HMI115) that may reduce pain and disease progression without hormones.

Key Arguments: Endometriosis is a chronic, systemic-like gynecologic disease that is often genetically influenced and likely promoted by repeated ovulation/menstruation, immune dysregulation, and modern reproductive patterns. Adenomyosis is not the same disease as endometriosis; it has distinct molecular pathways and is frequently underrecognized, especially in infertility. Normal ultrasound does not rule out endometriosis; diagnosis often requires expert transvaginal ultrasound protocols and/or MRI. Pain in endometriosis is not always purely lesion-driven; central sensitization can persist even after technically successful surgery. Surgery is not always first-line because disease can recur, and in some patients surgery harms fertility—especially when removing endometriomas or damaged tubes. Fertility planning depends heavily on age: aneuploidy rises nonlinearly after 35, so waiting can sharply reduce the probability of success with one’s own eggs. For adenomyosis, pre-transfer hormonal suppression can improve implantation and reduce miscarriage in IVF. Egg freezing offers optionality, but economics and low return rates mean it should be individualized rather than universally recommended. Emerging treatments may shift endometriosis care from symptom control toward disease modification, but earlier diagnosis is likely the biggest near-term win.

Data Points: Prevalence of endometriosis: ~10% of reproductive-aged women; ~200 million globally - Discussed as the baseline prevalence of endometriosis worldwide Infertility association with endometriosis: 30% to 50% - Share of infertile women who may have endometriosis Infertility risk in women with endometriosis: ~40% - Estimated chance of infertility among women with endometriosis Heritability of endometriosis: ~50% - Genetic contribution discussed with family-risk implications Family history risk: ~7x higher - First-degree relative with endometriosis increases risk Retrograde menstruation prevalence: ~90% of women - Retrograde flow is common but only some develop disease Historical ovulatory cycles: ~100 cycles in a woman’s lifetime 200 years ago - Used to explain why modern reproductive patterns may increase endometriosis risk Modern ovulatory cycles: ~400 cycles - Approximate lifetime cycles in contemporary women without interruption Diagnosis delay: 5 to 12 years - Average lag between symptom onset and diagnosis varies by country U.S. diagnosis delay: ~6 years - Estimated delay in the United States Brazil diagnosis delay: ~7 years - Estimated delay in Brazil Economic burden of endometriosis: $80 to $120 billion per year - Includes major productivity losses Productivity loss share: ~Two-thirds - Most economic burden comes from lost productivity rather than direct care Teenagers with pelvic pain who have endometriosis: 50% to 75% - Used to emphasize adolescent underdiagnosis Adenomyosis prevalence: 20% to 30% of women - Speaker suggested it may be more prevalent than endometriosis Endometriosis/adenomyosis overlap: Up to 70% - Estimate of adenomyosis among endometriosis patients Adenomyosis contribution to infertility: ~30% less IVF success - Discussed as reduced chances of successful conception/implantation Miscarriage risk with junctional-zone involvement in adenomyosis: ~3x higher - When the junctional zone is affected Aneuploidy at age 31: ~30% to 35% - Embryo chromosomal abnormality rate cited as surprisingly high even in early 30s Aneuploidy at age 35: ~40% - Inflection point where risk rises further Aneuploidy at age 38: ~60% - Illustrates steep decline in egg quality with age Aneuploidy at age 40: ~70% - High proportion of embryos expected to be chromosomally abnormal Aneuploidy at age 42: ~80% to 85% - Very steep late-30s/early-40s decline Egg freezing uptake return rate: ~10% return to use their oocytes - Only a small fraction of women who freeze eggs later use them Egg freezing cost in Brazil: ~$5,000 per cycle - Approximate cash price for one retrieval cycle Storage cost in Brazil: ~$500 per year - Ongoing storage fee mentioned Risk of egg-retrieval complications: ~1% - Risk of over-stimulation, bleeding, infection AMH around age 40: ~1 - Example value given for ovarian reserve Expected eggs from a 40-year-old cycle: ~8 eggs - Illustrative retrieval yield for a woman around age 40 Endometrioma surgery impact on AMH: ~40% to 50% reduction - Cystectomy can remove healthy ovarian tissue and reduce reserve Post-op recurrence without suppression: ~10% per year - Especially after endometrioma surgery Mirena after surgery effect: 88% lower recurrence vs placebo - Reported benefit of post-op intrauterine progestin device Hydrosalpinx effect on IVF: ~50% reduction in IVF chances - Damaged tubes can wash out or harm embryos Ovarian reserve at age 25: ~15 eggs and >80% chance of at least one baby with freezing strategy - Example of favorable fertility preservation timing

Pivotal Quotes: "The diagnosis delay period is five to 12 years, depending on the country." — Dr. Hanato Tomiyoka: Explaining why women often suffer for years before receiving a diagnosis "If you have just based on clinical symptoms, right? If you have a patient that has pelvic pain, dysmenorrhea, dyspareunia, and so on, you can give her a medication to avoid this disease burden." — Dr. Hanato Tomiyoka: Describing a shift toward earlier clinical diagnosis and treatment without waiting for surgery "When I tell them, you know, you are suffering, I know that's real. It has a name. We have a plan for that." — Dr. Hanato Tomiyoka: Closing reflection on the emotional relief patients feel when finally diagnosed

Implications: Earlier recognition, expert imaging, and individualized fertility planning could sharply reduce suffering and preserve reproductive options. For patients, the message is to seek evaluation early; for the field, better diagnostics and non-hormonal therapies may soon change care.