Will estrogen hormone replacement therapy (HRT) cause endometriosis recurrence in a pre-menopausal patient with surgical menopause due to bilateral oophorectomy (removal of ovaries) for endometriosis?

From the Guidelines

Hormone replacement therapy (HRT) with estrogen is generally safe for patients in surgical menopause due to bilateral oophorectomy for endometriosis and is unlikely to cause endometriosis recurrence. Since the surgery removes the ovaries and typically the uterus, there is minimal or no endometrial tissue remaining that could respond to estrogen stimulation. According to the most recent guideline from 2016 1, combined estrogen/progestogen therapy can be effective for the treatment of vasomotor symptoms and may reduce the risk of disease reactivation in women with endometriosis who required oophorectomy.

Key Considerations

• Standard HRT regimens include estradiol 1-2 mg daily orally, estradiol patch 0.05 mg twice weekly, or estradiol gel 0.5-1.0 mg daily.
• If the uterus remains, progesterone must be added (such as micronized progesterone 100-200 mg daily or medroxyprogesterone acetate 2.5-5 mg daily) to prevent endometrial hyperplasia.
• HRT should be initiated soon after surgery to prevent menopausal symptoms and continued until the average age of natural menopause (around 51 years) to protect bone health and reduce cardiovascular risk.
• The risk of recurrence is low because surgical menopause removes the primary source of estrogen production and most endometriotic implants, while any microscopic residual tissue typically becomes inactive without ovarian hormones.
• The benefits of HRT in preventing bone loss, vasomotor symptoms, and other menopausal complications generally outweigh the small theoretical risk of endometriosis recurrence, as supported by the American College of Obstetricians and Gynecologists guidelines from 2000 1.

Important Points to Note

• The 2016 guideline from the European Society of Human Reproduction and Embryology (ESHRE) 1 provides the most recent and highest quality evidence on this topic.
• The decision to initiate HRT should be individualized, taking into account the patient's symptoms, medical history, and preferences.
• Regular follow-up and monitoring for signs of endometriosis recurrence are essential for patients undergoing HRT after surgical menopause for endometriosis.

From the Research

Estrogen Replacement Therapy and Endometriosis Recurrence

• The use of estrogen replacement therapy (ERT) in patients with a history of endometriosis has been studied to determine its safety and effectiveness in preventing recurrence of the disease 2, 3, 4, 5.
• A study published in 2003 found that HRT is safe for postmenopausal women with underlying endometriosis, and recurrence of endometriosis is rarely a problem with HRT, especially in those who received the combination of estrogen and progestin regimens 2.
• Another study published in 1998 found that the combination of bilateral oophorectomy plus postoperative low-dose estrogen treatment produces sustained improvement in pain symptoms and reduces the hypoestrogenic side effects associated with bilateral oophorectomy 3.
• A 2018 review of the literature found that hysterectomy with or without bilateral oophorectomy, associated with endometriotic lesions exeresis, could decrease the rate of recurrence and surgical reoperations compared to resection alone endometriosis lesions, and that the use of menopausal hormone therapy (THM) does not appear to increase the symptoms of endometriosis after surgical castration 4.
• A 1998 study found that the immediate initiation of estrogen replacement therapy in the postoperative period does not increase the incidence of symptom recurrence following total abdominal hysterectomy with bilateral salpingo-oophorectomy for the treatment of endometriosis 5.

Reoperation and Pain-Related Outcomes

• A 2023 study compared the rate and types of reoperations and use of other pain-related health services among patients who underwent a hysterectomy with conservation of both ovaries, those who underwent a hysterectomy with unilateral salpingo-oophorectomy, and those who underwent a hysterectomy with bilateral salpingo-oophorectomy 6.
• The study found that reoperation rates were low across all groups, and patients who underwent a hysterectomy with bilateral salpingo-oophorectomy had a lower reoperation rate than those who underwent a hysterectomy with conservation of one or both ovaries 6.
• However, there was little difference between the groups for secondary outcomes, including physician visits for endometriosis and pelvic pain, opioid use, and use of hormonal suppression medications, suggesting that persistent pelvic pain after hysterectomy for endometriosis may not differ substantively based on ovarian conservation status 6.