From the FDA Drug Label
8 Exacerbation of endometriosis Endometriosis may be exacerbated with administration of estrogens. A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen alone therapy. For patients known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered.
Endometriosis Exacerbation with HRT:
- The administration of estrogens, such as those used in hormone replacement therapy (HRT), may exacerbate endometriosis in post-menopausal women.
- This is a consideration for patients with a history of endometriosis who are being treated with estrogen-only HRT, especially those who have not had a hysterectomy.
- The addition of a progestin to the HRT regimen may be recommended for patients with known residual endometriosis post-hysterectomy to mitigate this risk 1.
From the Research
Hormone replacement therapy (HRT) can potentially exacerbate endometriosis symptoms in post-menopausal women who have a history of the condition, and thus, should be used with caution. Estrogen-containing HRT regimens are particularly concerning as they may reactivate endometriotic lesions that have become dormant after menopause. For post-menopausal women with a history of endometriosis who require HRT for severe menopausal symptoms, a tiered approach is recommended, as suggested by 2. First-line options include using the lowest effective dose of estrogen, preferably with continuous (not cyclic) progestin to counterbalance estrogen's stimulatory effects. Specific options might include transdermal estradiol (0.025-0.05 mg patches) with oral micronized progesterone (100-200 mg daily) or norethindrone acetate (0.5-1 mg daily). Alternatively, tibolone (2.5 mg daily), which has mixed hormonal effects, may be considered as it appears to have less risk of reactivating endometriosis, as noted in 2 and 3.
The biological mechanism involves estrogen's ability to stimulate endometriotic implants, causing them to grow and become symptomatic again, potentially leading to pelvic pain, bleeding, or even malignant transformation in rare cases. Regular monitoring for recurrent symptoms is essential, and if endometriosis symptoms return, the HRT regimen should be reevaluated or discontinued. It's also important to consider the decision-making algorithm proposed by 4 for endometriosis patients considering MHT, which suggests that those who have been treated with bilateral salpingo-oophorectomy and have no residual endometriotic disease can probably be treated using MHT without risk of endometriosis recurrence or fear of ovarian cancer.
Key considerations for managing post-menopausal women with a history of endometriosis include:
- Using the lowest effective dose of estrogen
- Combining estrogen with continuous progestin
- Considering alternative options like tibolone
- Regular monitoring for recurrent symptoms
- Reevaluating or discontinuing HRT if symptoms return, as supported by the findings in 5, 2, and 3.
Overall, while HRT can be beneficial for managing menopausal symptoms in post-menopausal women with a history of endometriosis, it's crucial to weigh the potential benefits against the risks and to closely monitor these patients for any signs of endometriosis recurrence.