Endometriosis recurrence from estrogen-only HRT


In a recent study, providers were more likely to recommend combined hormone replacement therapy (HRT) than estrogen-only HRT in patients with severe endometriosis because of recurrence risks from estrogen-only HRT.

Endometriosis recurrence from estrogen-only HRT | Image Credit: © Pixel-Shot - © Pixel-Shot - stock.adobe.com.

Endometriosis recurrence from estrogen-only HRT | Image Credit: © Pixel-Shot - © Pixel-Shot - stock.adobe.com.

According to a recent study published in the Journal of Clinical Medicine, there is a significant risk of recurrence of severe endometriosis when using estrogen-only hormone replacement therapy (HRT).

About 10% of women of reproductive age experience endometriosis, leading to severe and debilitating chronic pelvic pain (CPP). Endometriosis presents as endometrial-like tissue outside the uterine cavity which causes chronic inflammation and fibrosis.

Treatment methods focus on pain reduction and the removal of endometriotic lesions, and include pain control, suppressive hormonal therapy, and surgery. Conservative surgery has a recurrence rate of about 50%, leading many premenopausal women to undergo radical surgery. These women will need HRT until they reach menopause.

There is a prominent concern about recurrence with HRT, with multiple studies reporting high recurrence rates if the ovaries are preserved.Recurrence has been reported in a variety of sites and has presented with a multitude of symptoms. HRT, especially estrogen-only HRT (EO-HRT), has been associated with increased recurrence rates following hysterectomy.

To determine the risk of recurrence of severe endometriosis associated with EO-HRT, investigators conducted a cross-sectional survey of practitioners and clinicians managing surgical menopause in women following pelvic clearance for endometriosis. Pelvic clearance was defined as, “total hysterectomy and bilateral salpingo-oophorectomy with excision of endometriosis.”

A survey was developed by study authors and received peer-review from representatives of British Menopause Society and British Society of Gynecological Endoscopy. There were 21 questions included, focused on issues with HRT prescriptions following surgical menopause in women with endometriosis.

Initial survey questions were designed to determine if respondents had the relevant experience, with later questions discussing HRT characteristics. Investigators also presented a case report of severe endometriosis recurrence in a woman aged 45 years taking EO-HRT after subtotal hysterectomy and bilateral salpingo-oophorectomy.

In the case report, the woman aged 45 years presented with severe CPP while on a high dose of EO-HRT. This woman had received a subtotal hysterectomy rather than a total hysterectomy because of the extensive deep peri-cervical endometriosis.

The patient started on EO-HRT at 2 mg per day, which was increased to 3 mg per day. She remained pain free for about 3 years before a resurgence of pain, which gradually worsened over time until it was debilitating. Symptom management was accomplished through trachelectomy and endometriosis excision.

There were 216 responses to the survey, including 120 gynecology consultants, 85 primary care menopause practitioners, and 11 nurse practitioners. Over 10 years of experience was reported by 75% of participants, with over 55% having managed over 10 women after pelvic clearance for menopause per year.

An increasing percentage of providers not prescribing HRT as patients aged was observed, at 2.1% for women aged under 40 years and 23.9% in women aged over 50 years. Similar trends were observed for providers deciding to leave the choice of HRT to patients, from 7.6% in women aged under 40 years to 45.6% in women aged over 50 years.

Combined HRT was prescribed by 68.6% of providers, estrogen only by 13%, Tibolone by 11.1%, and varied HRT by 7.8%. Combined HRT or Tibolone was prescribed by 81.6% of endometriosis specialists, 70.8% of gynecology consultants, 45% of gynae consultants, and 81.4% of general practitioners.

EO-HRT was prescribed by 7.9% of endometriosis specialists, 12.5% of gynecology consultants, 25% of gynae consultants, and 4.7% of general practitioners. These rates are significantly lower than rates of combined HRT prescriptions, indicating providers recommend combined HRT over EO-HRT.

Overall, EO-HRT has been associated with increased risk of severe endometriosis recurrence, leading most providers to recommend combined HRT instead. Investigators recommended further studies to address the gap in knowledge on the optimal HRT regimen in women with endometriosis.


Amer S, Bazmi S. HRT in women undergoing pelvic clearance for endometriosis: A case report and a national survey. Journal of Clinical Medicine. 2023;12(336). doi:10.3390/jcm12010336

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