Key Moments
397 - Endometriosis and adenomyosis: diagnosis, fertility, reproductive aging, & emerging treatments
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Key Moments
Endometriosis lesions can grow like cancer and are progesterone-resistant, but don't metastasize, while adenomyosis is more prevalent and its early diagnosis is crucial to prevent long-term complications like infertility.
Key Insights
Endometriosis affects approximately 10% of reproductive-age women globally, rising to 30-50% among infertile women, with a 40% chance of infertility for those diagnosed with endometriosis.
The heritability of endometriosis is about 50%, with a seven-fold increased risk if a first-degree relative is affected.
Adenomyosis, which is the presence of endometrial-like tissue within the myometrium, is more prevalent than endometriosis, affecting up to 20-30% of women, and up to 70% of women with endometriosis may also have adenomyosis.
The diagnostic delay for endometriosis in the US averages around six years, leading to significant economic costs estimated at $80-$120 billion annually, primarily due to productivity loss.
Surgical removal of endometriotic lesions, particularly endometriomas larger than 5-6 cm, can significantly impair ovarian reserve, potentially reducing AMH by 40-50%.
For women with adenomyosis undergoing IVF, treatment with GnRH agonists for 2-4 months prior to embryo transfer can increase implantation rates and live birth rates while decreasing miscarriage rates.
Defining endometriosis and adenomyosis: distinct diseases with shared mechanisms
Endometriosis is a chronic condition where tissue similar to the endometrium, the inner lining of the uterus, grows outside the uterine cavity. This tissue can implant on organs like the fallopian tubes, ovaries, bowel, and bladder. Adenomyosis, on the other hand, involves endometrial-like tissue growing into the muscular wall of the uterus (myometrium). While often confused, they are distinct diseases with different molecular pathways, though they share some mechanisms like estrogen dominance, progesterone resistance, and the presence of somatic mutations in cancer-associated genes within the lesions. Adenomyosis is more prevalent, affecting up to 20-30% of women compared to endometriosis's 10%, and a significant overlap exists, with up to 70% of endometriosis patients potentially having some degree of adenomyosis. This overlap is critical for understanding infertility in affected couples.
The rising prevalence and genetic and environmental influences
The prevalence of endometriosis is estimated at 10% of reproductive-age women globally, translating to about 200 million women. This number escalates dramatically to 30-50% among women struggling with infertility. A striking 40% of women with endometriosis may experience infertility themselves. Research indicates a substantial genetic component, with a 50% heritability and a seven-fold increased risk for individuals with a first-degree relative affected by the condition. Environmental factors such as pollution are suspected triggers, but a significant contributing factor to the increased incidence is believed to be the modern reproductive pattern of women. Compared to women 200 years ago who had around 100 ovulatory cycles in their lifetime (later menarche, earlier pregnancies, longer breastfeeding periods), modern women experience about a four-fold increase in ovulatory cycles, leading to more frequent retrograde menstruation, a key factor in endometriosis development.
Complex pain pathways and the challenge of diagnosis
Endometriosis can manifest with a "six Ds" framework: dysmenorrhea (painful periods), deep dyspareunia (pain during intercourse), dyschezia (painful bowel movements), dysuria (painful urination), infertility, and chronic pelvic pain. Adenomyosis, while sometimes asymptomatic, often presents with significant uterine bleeding, leading to anemia, and can also cause painful and heavy periods. The pain associated with endometriosis is complex, involving nociceptive pain from lesions, neuropathic pain from nerve infiltration, and the most challenging, nociplastic pain stemming from central sensitization. This latter type, where the pain signaling pathways become hypersensitive, can persist even after lesions are removed, highlighting the importance of early diagnosis and treatment to prevent the rewiring of the nervous system. Unfortunately, diagnostic delays are common, averaging six years in the US and seven in Brazil, attributed to the cultural normalization of pain, lack of a simple biomarker, and reliance on invasive diagnostic laparoscopy.
Advanced imaging techniques for diagnosis
While diagnostic laparoscopy has been the gold standard, non-invasive imaging has advanced significantly. Specialized transvaginal ultrasounds, performed by experienced radiologists with detailed protocols including bowel preparation and the use of gel, can achieve 95-98% sensitivity and specificity for detecting endometriosis, including superficial lesions, deep infiltrative endometriosis, and endometriomas. MRI is also highly effective, particularly for extrapelvic lesions and lateral pelvic structures, offering complementary insights to ultrasound. However, a normal ultrasound report does not rule out endometriosis, emphasizing the need for clinical correlation and expert interpretation.
Treatment strategies: managing pain and preserving fertility
Treatment depends on the patient's goals, particularly fertility desires. For women not seeking immediate conception, hormonal therapies like low-dose combined oral contraceptives or progestin-only pills, or an IUD like Mirena, are first-line options to suppress ovulation and menstruation. Surgery, often laparoscopic excision, is considered when medical therapy fails, but recurrence is common, necessitating post-operative hormonal treatment to reduce the risk. For women of reproductive age, especially those over 30-35, fertility preservation is a priority. IVF is often recommended due to declining egg quality and aneuploidy rates, with egg or embryo freezing being crucial steps. Surgical intervention may be considered for large endometriomas or specific lesions, but care must be taken not to compromise ovarian reserve.
Addressing adenomyosis in fertility treatments
For women with adenomyosis and struggling with infertility, particularly those with frozen embryos, GnRH agonists or antagonists are used to chemically induce a temporary menopausal state. This treatment, lasting 2-4 months, suppresses estrogen and progesterone, reducing uterine contractions and improving implantation and pregnancy maintenance rates. While it doesn't significantly alter the uterine morphology, it creates a more receptive uterine environment. This approach can reduce the historical 30% decrease in success rates associated with adenomyosis in IVF, mitigating risks of miscarriage and improving live birth rates.
The impact of endometriosis classification and surgical pearls
The ASRM classification system for endometriosis (Stage I-IV) is based on surgical findings and does not always correlate with pain severity or fertility outcomes. The Endometriosis Fertility Index (EFI), a score based on factors like tube quality and fimbrial function post-surgery, can predict natural pregnancy rates. Surgery for endometriosis requires careful consideration: removing endometriomas can significantly reduce ovarian reserve (AMH can drop 40-50%), so egg preservation via IVF may be advised before excision. Furthermore, damaged fallopian tubes (hydrosalpinx) can halve IVF success rates by affecting embryo transport and potentially being embryotoxic, warranting removal (salpingectomy).
Future directions and the importance of early intervention
The field is moving towards more targeted treatments and earlier diagnosis. New guidelines from ACOG now permit clinical diagnosis and treatment of endometriosis, aiming to reduce diagnostic delays. Emerging treatments, like monoclonal antibodies targeting prolactin receptors (e.g., HMI115), show promise for non-hormonal pain and disease progression management. The long-term economic and personal burden of endometriosis underscores the need for increased research funding and public awareness. Early diagnosis and intervention are key to preventing disease progression, infertility, and the development of central sensitization, offering patients a better quality of life and improved reproductive outcomes.
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Aneuploidy Rates by Maternal Age (Approximate)
Data extracted from this episode
| Maternal Age | Aneuploidy Rate (%) |
|---|---|
| 20 | 20-25 |
| 25 | 20-25 |
| 31 | 30-35 |
| 35 | 40 |
| 38 | 60 |
| 40 | 70 |
| 40+ | 80-85 |
Endometriosis vs. Diabetes Economic Burden
Data extracted from this episode
| Condition | NIH Investment Ratio (vs. Endometriosis) | Annual Cost per Patient (USD) |
|---|---|---|
| Diabetes | 15x More | 12,000 |
| Endometriosis | 1x | 16,000 |
Common Questions
Endometriosis is a chronic disease where endometrial-like tissue grows outside the uterus, affecting about 10% of reproductive-aged women globally (around 200 million). It is strongly linked to infertility; 30-50% of infertile women have endometriosis, and roughly 40% of women with endometriosis experience infertility.
Topics
Mentioned in this video
A radiologist mentioned as one of the best in the world for endometriosis, who developed a detailed ultrasound protocol and used to correlate her findings directly in the operating room with surgeons.
A doctor at Mayo Clinic Arizona who is reportedly performing specialized ultrasound protocols for endometriosis.
A radiologist mentioned as highly experienced in diagnosing and following up with endometriosis patients in São Paulo.
A hospital system where a doctor, Scott Young, is performing specialized endometriosis ultrasound protocols, though it's not widely adopted there.
Published new guidance in March 2025/2026 allowing clinical diagnosis and empirical treatment of endometriosis without diagnostic laparoscopy.
A progestin-only pill mentioned for endometriosis treatment.
A medication available in the US for endometriosis, described as estrogen estradiol plus dionogest, but only the active dionogest part is used for treatment.
An oral GnRH antagonist available in the US for endometriosis, very expensive but with fewer side effects than agonists. It works by immediate hormonal suppression.
An oral GnRH antagonist available in the US for endometriosis, very expensive and offering immediate hormonal suppression without the flare-up effect of agonists.
A monoclonal antibody targeting the prolactin receptor, currently in phase three trials, which may lead to less pain and disease progression in endometriosis without using hormones.
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