Can women develop endometriosis after age 35 or post‑menopause, especially when on estrogen‑containing hormone therapy?

Can Women Develop Endometriosis Later in Life?

Yes, women can develop endometriosis after age 35 and even after menopause, though it occurs in only 2–4% of postmenopausal women and is most commonly associated with estrogen-containing hormone replacement therapy. 1

Epidemiology and Age Distribution

• Endometriosis affects 8–10% of women of reproductive age, but the traditional view that it exclusively impacts premenopausal women has shifted—the condition can present in both premenarchal girls and postmenopausal women. 2

• In women over 40 years undergoing surgery for adnexal masses, 27.2% were found to have endometriomas, with 20% of these patients being postmenopausal. 3

• The disease can persist or reactivate after menopause when iatrogenic (hormone replacement therapy) or endogenous hormones are present. 2

Pathophysiology of Late-Onset Endometriosis

• Postmenopausal endometriosis occurs primarily through extra-ovarian estrogen production by endometriosis lesions themselves and by adipose tissue, which becomes the major estrogen-producing tissue after menopause. 4

• Aromatase activity within endometriosis lesions creates a feed-forward stimulation loop between inflammation and local estrogen production, allowing lesions to persist even without ovarian function. 4

• Three documented cases of postmenopausal endometriosis in women aged 54,62, and 78 years—none of whom had prior hormone therapy or known endometriosis—support the celomic metaplasia theory, suggesting de novo development is possible. 5

Hormone Replacement Therapy as a Risk Factor

• Women with a history of endometriosis who are prescribed HRT after bilateral salpingo-oophorectomy (performed at age 40 for Lynch syndrome carriers or age 50 for PMS2 mutation carriers) face potential reactivation of dormant lesions. 6

• HRT is recommended up to age 51 years in women who undergo surgical menopause for risk-reducing surgery, provided there is no contraindication such as personal history of breast cancer or venous thromboembolism. 6

• Tamoxifen therapy increases the risk of late-onset endometriosis with a relative risk of 4.0, in addition to raising endometrial cancer risk (2.20 per 1,000 woman-years versus 0.71 for placebo). 7, 8

• The optimal formulation of HRT for women with endometriosis remains uncertain; current evidence is insufficient to determine whether estrogen-only, combined estrogen-progestin, or progestin-only therapy is safest. 4

Clinical Presentation in Older Women

• Postmenopausal endometriosis typically presents with chronic pelvic pain, painful abdominal wall masses (especially at prior surgical sites), or rectovaginal nodules discovered on examination. 5

• Pain in postmenopausal women with endometriosis is likely secondary to scarring or reactivation due to postmenopausal hormonal therapy rather than active disease progression. 7

• Women over 40 with endometriomas are younger and more frequently nulliparous compared to those with other benign ovarian masses. 3

Diagnostic Approach

• Transvaginal ultrasound with expanded protocol is the first-line imaging modality, though MRI pelvis provides superior detection of deep infiltrating disease and should be considered for comprehensive evaluation. 7

• Saline-infusion sonohysterography offers 96–100% sensitivity for detecting endometrial pathology when focal lesions are suspected. 8

• Hysteroscopy with directed biopsy is the definitive diagnostic step when initial imaging is inadequate or symptoms persist. 8

Management Considerations

• Postmenopausal women with symptomatic endometriosis should be managed surgically because of the risk of malignancy; medical treatments can be reserved for pain recurrence after surgery. 4

• Endometrioma-associated ovarian tumors develop in approximately 11% of women with endometriomas, particularly endometrioid and clear cell carcinomas. 3, 2

• Aromatase inhibitors are the preferred medical therapy for recurrent pain after surgery, as they decrease extra-ovarian estrogen production and block the feed-forward stimulation loop within endometriosis lesions. 4

• The only procedures that appear to cure endometriosis definitively are hysterectomy and bilateral salpingo-oophorectomy. 2

Special Populations Requiring Surveillance

• Women with Lynch syndrome who undergo risk-reducing hysterectomy and bilateral salpingo-oophorectomy at age 40 (MLH1 carriers) or age 50 (PMS2 carriers) should be counseled about the potential for endometriosis reactivation if HRT is initiated. 6, 8

• Women with a history of endometriosis who elect HRT after surgical menopause require long-term follow-up to evaluate the risk of malignant transformation, though current evidence is insufficient to quantify this risk. 4

Common Pitfalls to Avoid

• Do not assume that menopause eliminates the risk of endometriosis—adipose tissue and lesion-derived aromatase can sustain disease activity. 4

• Do not dismiss pelvic pain in postmenopausal women on HRT as benign without imaging and, if indicated, surgical evaluation to exclude malignancy. 4, 3

• Do not accept a normal endometrial thickness on ultrasound as reassurance in symptomatic patients—endometriosis lesions may be present outside the endometrium. 8