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

Abstract

BACKGROUNDEndometriosis is typically regarded as a premenopausal disease, resolving after natural or iatrogenic menopause due to declining oestrogen levels. Nonetheless, case reports over the years have highlighted the incidence of recurrent postmenopausal endometriosis. It is now clear that both recurrence and malignant transformation of endometriotic foci can occur in the postmenopausal period. Postmenopausal women are commonly treated with hormone replacement therapy (HRT) to treat climacteric symptoms and prevent bone loss; however, HRT may reactivate endometriosis and stimulate malignant transformation in women with a history of endometriosis. Given the uncertain risks of initiating HRT, it is difficult to determine the best menopausal management for this group of women.OBJECTIVE AND RATIONALThe aim of this study was to systematically review the existing literature on management of menopausal symptoms in women with a history of endometriosis. We also aimed to evaluate the published literature on the risks associated with HRT in these women, and details regarding optimal formulations and timing (i.e. initiation and duration) of HRT.SEARCH METHODSFour electronic databases (MEDLINE via OVID, Embase via OVID, PsycINFO via OVID and CINAHL via EbscoHost) were searched from database inception until June 2016, using a combination of relevant controlled vocabulary terms and free-text terms related to ‘menopause’ and ‘endometriosis’. Inclusion criteria were: menopausal women with a history of endometriosis and menopausal treatment including HRT or other preparations. Case reports/series, observational studies and clinical trials were included. Narrative review articles, organizational guidelines and conference abstracts were excluded, as were studies that did not report on any form of menopausal management. Articles were assessed for risk of bias and quality using GRADE criteria.OUTCOMESWe present a synthesis of the existing case reports of endometriosis recurrence or malignant transformation in women undergoing treatment for menopausal symptoms. We highlight common presenting symptoms, potential risk factors and outcomes amongst the studies. Sparse high-quality evidence was identified, with few observational studies and only two randomized controlled trials. Given this paucity of data, no definitive conclusions can be drawn concerning risk.WIDER IMPLICATIONSDue to the lack of high-quality studies, it remains unclear how to advise women with a history of endometriosis regarding the management of menopausal symptoms. The absolute risk of disease recurrence and malignant transformation cannot be quantified, and the impact of HRT use on these outcomes is not known. Multicentre randomized trials or large observational studies are urgently needed to inform clinicians and patients alike.

Long‐term survival of a patient with malignant transformation of extragonadal endometriosis treated solely with chemotherapy: A case report

“…However, the patient had a recurrence 11 years later. Malignant transformation of extragonadal endometriosis has a favorable prognosis, and the standard therapy for endometriosis‐related malignancy remains surgery. Gemmell et al .…”

“…Malignant transformation of extragonadal endometriosis has a favorable prognosis, and the standard therapy for endometriosis‐related malignancy remains surgery. Gemmell et al . reported a systematic review of the management of menopause in women with a history of endometriosis including malignant transformation ( n = 25).…”

“…a,b). Sampson's and Scott's criteria include: the coexistence of carcinoma and endometriosis in the same tissue; the presence of tissue resembling endometrial stroma surrounding characteristic epithelial glands; no other primary tumor sites being found and the morphologic demonstration of benign endometriosis contiguous with malignant tissue is a prerequisite for malignancy originating in endometriosis . In this case, all criteria were met.…”

“…The major sites of extragonadal endometriosis are the rectovaginal septum, abdominal wall, pleura and vagina. It has been reported that malignant transformation of extragonadal endometriosis after hysterectomy is caused by unopposed estrogen therapy . In a systematic review of the management of menopause in women with a history of endometriosis including malignant transformation, the patients received unopposed estrogen replacement for a median duration of 6.7 years (range 3–20 years) .…”

“…It has been reported that malignant transformation of extragonadal endometriosis after hysterectomy is caused by unopposed estrogen therapy . In a systematic review of the management of menopause in women with a history of endometriosis including malignant transformation, the patients received unopposed estrogen replacement for a median duration of 6.7 years (range 3–20 years) . The most common cancerous histological types related to endometriosis are clear cell carcinoma, endometrioid adenocarcinoma and seromucinous borderline tumor .…”