Supplementary information files for "Association between endometriosis and type and age of menopause: a pooled analysis of 279 948 women from five cohort studies"

Supplementary files for article "Association between endometriosis and type and age of menopause: a pooled analysis of 279 948 women from five cohort studies"

STUDY QUESTION - What is the association between endometriosis and the type and age of menopause?

SUMMARY ANSWER - Women with endometriosis had a 7-fold increased risk of undergoing surgical menopause rather than natural menopause and were more likely to experience premature or early menopause, both surgically and naturally.

WHAT IS KNOWN ALREADY - Endometriosis is associated with reduced ovarian reserve, but evidence on its relationship with the type of menopause (surgical vs natural) and timing (especially premature and early menopause) is limited. Women with endometriosis are more likely to undergo hysterectomy and/or oophorectomy (either unilateral or bilateral), but the average age of these surgeries remains unclear.

STUDY DESIGN, SIZE, DURATION - The study analysed individual-level data from 279 948 women in five cohort studies conducted in the UK, Australia, Sweden, and Japan between 1996 and 2022.

PARTICIPANTS/MATERIALS, SETTING, METHODS - Women whose menopause type and age could not be determined due to premenopausal hysterectomy with ovarian preservation or use of menopausal hormone therapy were excluded. Endometriosis was identified through self-reports and administrative data. Surgical menopause was defined as premenopausal bilateral oophorectomy. Fine–Gray subdistribution hazard models estimated hazard ratios (HRs) for surgical and natural menopause. Age at menopause was determined by the ages at the final menstrual period or bilateral oophorectomy. Linear regression assessed mean differences in menopause age, while multinomial logistic regression estimated odds ratios (ORs) for categorical menopause age: <40 (premature), 40–44 (early), 45–49, 50–51 (reference), 52–54, and ≥55 years. Spontaneous premature ovarian insufficiency (POI) was defined as natural menopause before age 40 years.

MAIN RESULTS AND THE ROLE OF CHANCE - Endometriosis was identified in 3.7% of women. By the end of follow-up, 7.9% had surgical menopause and 58.2% experienced natural menopause. Using a competing risk model, women with endometriosis had a 7-fold increased risk of surgical menopause (HR: 7.54, 95% CI 6.84, 8.32) and were less likely to experience natural menopause (HR: 0.40, 95% CI 0.33, 0.49). On average, surgical menopause occurred 1.6 years (19 months) earlier (β: −1.59, 95% CI −1.77, −1.42) in women with endometriosis. Among women who experienced natural menopause, it was 0.4 years (5 months) earlier (β: −0.37, 95% CI −0.46, −0.28) for those with endometriosis. Women with endometriosis were twice as likely to experience premature surgical menopause (<40 years) (OR: 2.11, 95% CI 2.02, 2.20) or 1.4 times more likely to develop spontaneous POI (OR: 1.36, 95% CI 1.17, 1.59). They were also at increased odds of early surgical and natural menopause (40–44 years).

LIMITATIONS, REASONS FOR CAUTION - This study could not differentiate between subtypes and stages of endometriosis or assess treatments for ovarian endometrioma, which may impact ovarian reserve. Self-reported menopause type and age could introduce recall bias.

WIDER IMPLICATIONS OF THE FINDINGS - Given the consistent findings across individual studies, our results are likely to be generalizable to different populations, highlighting the need for tailored management of endometriosis to prevent medically induced or premature menopause. Long-term monitoring of women with endometriosis is recommended, given their elevated risk of surgical menopause and premature or early menopause, which are associated with adverse health outcomes in later life.

STUDY FUNDING/COMPETING INTEREST(S) - The InterLACE Consortium is funded by the Australian National Health and Medical Research Council project grant (APP1027196) and Centres of Research Excellence (APP1153420). G.D.M. is funded by the Australian National Health and Medical Research Council Leadership Fellowship (APP2009577). This research is funded in part by the Japan Society for the Promotion of Science (JSPS KAKENHI: 19KK0235, 23KK0167). The authors have no conflict of interest. Where authors are identified as personnel of the International Agency for Research on Cancer or WHO, the authors alone are responsible for the views expressed in this article, and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer or WHO.

TRIAL REGISTRATION NUMBER - N/A.


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