Hormone Replacement Therapy (HRT)/ Menopausal Hormonal Therapy (MHT) and Endometriosis – A Look at the Evidence

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Note on HRT/MHT

There’s a language shift in the menopause community from Hormone Replacement Therapy (HRT) to Menopausal Hormonal Therapy (MHT). I think this is a helpful shift, but I continue to use HRT throughout this website because I find more people are familiar with the term.

What research is there on endometriosis patients and HRT?

There isn’t much research on HRT in menopausal endometriosis patients, and the little research we have is on patients who have had hysterectomy with bilateral salpingo-oopherectomy. In the For More Info section below, you can read 2 studies that both did a review of the literature.

Highlights

• There were some case reports on malignancy for endometriosis patients taking HRT, mostly in patients taking estrogen only. “Although data are very scarce and regarded as low quality, it seems advisable to consider using continuous combined estrogen-progestogen or tibolone regimes in women requiring MHT over unopposed estrogen (Gemmell, et al., 2017).” [Source: ESHRE Guideline Endometriosis]
• For recurrence after surgical menopause “there appeared to be a small association between the treatment with MHT and recurrence of endometriosis, although none of the studies found a statistically significant difference between treatment and control groups.” However, they note that there’s a lack of information on surgery completeness, so it’s unclear if it’s recurrence or residual disease. [Source: ESHRE Guideline Endometriosis]
• “The impact of MHT on recurrence of endometriosis (2 small RCTs, 4 observational studies and 33 case reports) was recently summarised in a systematic review, showing a possibly increased risk. For malignancy, very few cases have been reported for combined MHT or tibolone. Considering the benefits and risks, combined MHT can be considered for the treatment of postmenopausal symptoms in women with a history of endometriosis (weak recommendation).” [Source: ESHRE Guideline Endometriosis]

The management of menopause in women with a history of endometriosis: a systematic review (1)

This 2017 review by Gemmell LC, Webster KE, Kirtley S, Vincent K, Zondervan KT, Becker CM, aimed to look at the medical literature available to investigate the following question and sub-questions:

• What is the current evidence on the management of menopausal symptoms in women with a history of endometriosis?
  • What are the various treatment options to manage menopausal symptoms in these women?
  • What are the risks associated with HRT in this cohort?
  • Should HRT be given immediately following surgically-induced menopause or be delayed?
  • What preparations are most appropriate, and for how long should treatment be given?

If you’re thinking about taking estrogen HRT, it’s an interesting review worth reading. It goes over the RCTs, observational studies, and case reports available on HRT in post-menopausal patients at the time of publishing.

Lesion recurrence: in the case reports, the time period of taking HRT between surgical menopause and endometriosis recurrence varied, from 4 months to 13 years.

Malignant transformation of endometriotic lesions: they found case reports on a total of 25 patients between 38 and 75 years old. 19 of them were taking unopposed oestrogens for a length of 3 to 20 years.

“Currently there are no data to indicate the absolute risk of malignant transformation in this group of women. It is likely that this is a rare outcome, but better data are urgently needed to enable women to make an informed decision about menopausal management. Fortunately, tumours arising from endometriosis are typically low grade and have a better prognosis (Heaps et al., 1990); only three deaths were reported in the literature identified by our search. Mortality was noted in the two case reports with patients who had histories of severe endometriosis and complicating factors, including increased age (Duun et al., 1993) or multiple malignancies (Reimnitz et al., 1988)” (1)

Endometriosis and menopause—management strategies based on clinical scenarios (3)

This article is worth the read and explores different aspects to consider HRT for patients in the following scenarios:

1. Prescribing HRT to an endometriosis patient who has had a hysterectomy
2. Prescribing HRT to an endometriosis patient who went into early menopause due to ovary removal
3. Prescribing MHT to a perimenopausal patient with endometriosis who is still menstruating
4. Managing suspected endometriosis recurrence in a postmenopausal patient with endometriosis
5. Managing suspected endometriosis symptoms in a postmenopausal patient currently using HRT

For scenario 3, we don’t currently have any studies done on perimenopausal people with endometriosis, as the studies for HRT and endometriosis have been done on patients with oopherectomies. In this article, the authors still feel that HRT should be offered to perimenopause patients undergoing natural menopause.

Recurrence of endometriosis in women with bilateral adnexectomy (with or without total hysterectomy) who received hormone replacement therapy (4)

This was a prospective randomized trial on patients with endometriosis and underwent bilateral salpingo-oophorectomy with 115 patients receiving HRT and 57 not receiving HRT. Recurrence was defined as histological confirmation (pathology report) or clinical findings and ultrasound findings suggestive of endometriosis.

The HRT was estradiol patches, with oral micronized prorgesterone cyclically for 2 weeks a month. The average follow up time was 45 months.

4 out of 115 on HRT had endometriosis recurrence (3.5%) and 0 who didn’t take HRT had recurrence.

Endometriosis recurrence is also possible in menopause in patients who haven’t taken HRT

“It is important to note that recurrence is possible even in the absence of HRT. There are reports of endometriosis recurrence in women not on any hormonal treatment (Fujiu et al., 2010; Bhat et al., 2014). In these women, other risk factors such as hyperestrogenemia and obesity may play larger roles in the pathogenesis (Punnonen et al., 1980). Incomplete definitive surgery and residual ovarian remnants are also considered risks factor for the development of postmenopausal endometriosis (Dmowski et al., 1988).” (1)