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Introduction

Endometriosis is a chronic oestrogen-dependent condition (1) where tissue similar to the endometrium grows outside the uterus. It can lead to severe symptoms that impact a woman’s quality of life, such as pelvic pain, dyspareunia, dysmenorrhea and infertility. It is estimated that 1 in 7 women are diagnosed with endometriosis by age 44-49 (2), with many more going undiagnosed.

The condition often evolves with age (3). Ovulatory cycles stimulate its growth, frequently leading to lesions accumulating and development of central pain sensitisation. Whilst symptoms can stabilise in the later reproductive years, the dramatic hormonal shifts of perimenopause may make symptoms worse (3). Endometriosis is also associated with earlier onset of both natural and iatrogenic menopause (4).

Following menopause, endometriosis typically becomes quiescent due to oestrogen deficiency. However, women with residual lesions may become symptomatic with administration of exogenous oestrogen as part of menopausal hormone therapy (MHT) (5). Therefore, managing the symptoms of menopause in women with known endometriosis can pose a particular challenge.

Premenopausal management of endometriosis

Endometriosis requires a stepwise, symptom-driven therapeutic approach which includes lifestyle measures, analgesia and allied health involvement (6,7). However, the core of premenopausal management of the condition is ovulation suppression. This approach reduces the oestrogenic stimulation of the ectopic endometrium and can induce decidualisation of the tissue.

This can be achieved with:

• The combined oral contraceptive pill, generally with higher doses of ethinyl oestradiol.
• Progestogen-only contraceptive pill, such as drosperinone 4mg or ‘mini-pill’.
• GNRH analogues and antagonists, typically considered second-line and in conjunction with add-back hormones.

Continuous progestogen administration has also been demonstrated as effective treatment, either orally or as the levonorgestrel IUD.

Endometriosis is also often managed surgically through laparoscopic excision or ablation. Definitive surgery which usually includes hysterectomy and bilateral oophorectomy can then be reserved for after completion of family (8,9). It is recommended that women undergoing this surgery are offered ongoing hormonal suppression to prevent recurrence and improve quality of life if they are still ovulating.

Postmenopausal patients with a history of endometriosis

As endometriosis is stimulated by oestrogen exposure, the loss of ovarian activity in menopause (either natural or iatrogenic) usually relieves symptoms directly related to the condition (10). Whilst it is often thought that it is the reduction in circulating oestrogen that leads to these changes, it may also be due to the cessation of direct exposure to the highly-concentrated oestrogen of pelvic follicular fluid during ovulation (11).

However, it is now known that endometriosis can continue to cause symptoms in the absence of active disease (12). Maladaptive pain responses, pelvic floor spasm, bowel symptoms and sexual dysfunction are multifactorial, and may persist independent of ovulation and past the menopause transition (3). Therefore, some postmenopausal women may still require treatment for their ongoing sequelae.

Risk of recurrence of endometriosis with menopausal hormone therapy

There is sparse evidence for the safety of MHT in menopausal women with a history of endometriosis (13). One key concern is the risk of reactivation or recurrence, which can manifest as non-specific symptoms like abdominal pain, vaginal bleeding, and haematuria (14). Recurrence has mainly been reported in users of unopposed estrogen and less so with women taking combined MHT.

Gemmell et al reviewed the evidence for menopausal management in the setting of a history of endometriosis (14). They found only 32 case reports/series including 42 patients. Recurrence of endometriosis was reported in 17 case reports. Of these, 12 patients with prior hysterectomy were taking oestrogen alone (some in high doses). Four patients were taking cyclical oestrogen plus progestogen therapy, and in one case the combined oestrogen-progestogen regimen is not specified. Most patients had extensive endometriotic disease before MHT administration.

Reassuringly, in these cases the symptoms of recurrence are resolved with addition of a progestogen or cessation of the MHT. It is therefore recommended to commence women on combined MHT if they have a history of endometriosis (15).

There is more discretion in women with a history of endometriosis who have had a hysterectomy with or without oophorectomy. Whilst such women are typically suitable for oestrogen-only MHT, there may be residual endometriosis susceptible to reactivation and thus a progestogen may be included after a discussion of the risks and benefits with the woman. A recent retrospective study however, did not identify an association between oestrogen-only MHT and recurrence of endometriosis after hysterectomy (16). Still, it is generally recommended that women are offered combined MHT if they’ve had a hysterectomy and have a history of endometriosis.

Malignant transformation of endometriotic deposits

Much like recurrence, there are theoretical concerns that use of postmenopausal MHT may lead to malignant transformation of residual endometriosis. A 2021 meta-analysis identified a total of 90 cases of postmenopausal malignant transformation, described across 75 studies (10). The findings were inconsistent and inconclusive. Less than two thirds of women had a known history of endometriosis, one in three women had not used MHT, and a group of women had developed extragonadal endometriosis (17).

Although the evidence remains sparse and case reports of recurrence or malignant transformation are few, current recommendations favour continuous combined oestrogen-progestogen preparations instead of unopposed oestrogens for women with a history of substantial endometriosis even after hysterectomy, especially if there has been extensive disease.

Implications for post-menopausal bone, cardiovascular health, and cancer

Menopause represents an opportunistic moment to screen and counsel women regarding long-term preventative health considerations. It is therefore important to acknowledge that women with a history of endometriosis may be at a higher risk of certain conditions.

Studies have demonstrated an association between surgically confirmed endometriosis and subsequent atherosclerotic cardiovascular disease. This association was more pronounced in younger women and those who had undergone hysterectomy and/or oophorectomy (18). It is thought that this occurs through both the hormone suppression of endometriosis treatment and the inflammatory nature of the condition (19).

Equally, endometriosis also appears associated with low bone density (18). This too is likely related to long-term hypo-oestrogenism stemming from hormonal treatment, surgery or iatrogenic menopause.

Women with endometriosis are also at higher risk of both gynaecological and non-gynaecological malignancy. A 2021 systematic review and meta-analysis found that endometriosis was associated with a higher risk of ovarian cancer, a slightly increased risk of breast cancer, and a lower risk of cervical cancer20. The same review found a robust association between endometriosis and thyroid cancer.

Knowledge of these associations are key to guiding proactive health strategies in postmenopausal women with a history of endometriosis.

Summary and recommendations

Menopausal women with a history of endometriosis may remain symptomatic with sequelae of the disease, even after ovarian function has ended.

The menopausal woman with a history of endometriosis presents a particular challenge in managing menopausal symptoms, bone health and prevention of cardiovascular risk. They are eligible for MHT but are recommended for combined oestrogen and progestogen to mitigate the very small chance of recurrence.

Further reading

- Erel CT, Nigdelis MP, Ozcivit Erkan IB, Goulis DG, Chedraui P, Giannini A, et al. Endometriosis and menopausal health: An EMAS clinical guide. Maturitas. 2025;202:108715.
 

References

1. As-Sanie S, Mackenzie SC, Morrison L, Schrepf A, Zondervan KT, Horne AW, et al. Endometriosis: A Review. JAMA. 2025;334(1):64-78.
2. Wang MH, Chen JH, Qi XY, Li ZX, Huang Y. Global prevalence of adenomyosis and endometriosis: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2025;23(1):148.
3. Raheem M, Condous G, Espada Vaquero M. Endometriosis During Peri-Menopause and Post-Menopause: A Review of the Literature. J Clin Med. 2025;14(22).
4. Chung H-F, Hayashi K, Dobson AJ, Sandin S, Ideno Y, Hardy R, et al. Association between endometriosis and type and age of menopause: a pooled analysis of 279 948 women from five cohort studies. Human Reproduction. 2025;40(6):1210-9.
5. Mantilidewi KI, Ridwan S, Kurniadi A, Harsono AB. Postmenopausal endometriosis. BMJ Case Rep. 2025;18(3).
6. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Human reproduction open. 2022;2022(2):hoac009.
7. RANZCOG. Australian Living Evidence Guideline: Endometriosis. 2025.
8. Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010;116(1):223-36.
9. Falcone T, Flyckt R. Clinical Management of Endometriosis. Obstet Gynecol. 2018;131(3):557-71.
10. Giannella L, Marconi C, Di Giuseppe J, Delli Carpini G, Fichera M, Grelloni C, et al. Malignant transformation of postmenopausal endometriosis: a systematic review of The literature. Cancers. 2021;13(16):4026.
11. Du YB, Gao MZ, Shi Y, Sun ZG, Wang J. Endocrine and inflammatory factors and endometriosis-associated infertility in assisted reproduction techniques. Arch Gynecol Obstet. 2013;287(1):123-30.
12. Vallée A, Carbonnel M, Ceccaldi PF, Feki A, Ayoubi JM. Postmenopausal endometriosis: a challenging condition beyond menopause. Menopause. 2024;31(5):447-56.
13. Alio L, Angioni S, Arena S, Bartiromo L, Bergamini V, Berlanda N, et al. Endometriosis: seeking optimal management in women approaching menopause. Climacteric. 2019;22(4):329-38.
14. Gemmell L, Webster KE, Kirtley S, Vincent K, Zondervan K, Becker C. The management of menopause in women with a history of endometriosis: a systematic review. Human reproduction update. 2017;23(4):481-500.
15. Erel CT, Nigdelis MP, Ozcivit Erkan IB, Goulis DG, Chedraui P, Giannini A, et al. Endometriosis and menopausal health: An EMAS clinical guide. Maturitas. 2025;202:108715.
16. Tanmahasamut P, Rattanachaiyanont M, Techatraisak K, Indhavivadhana S, Wongwananuruk T, Chantrapanichkul P. Menopausal hormonal therapy in surgically menopausal women with underlying endometriosis. Climacteric. 2022;25(4):388-94.
17. Leiserowitz GS, Gumbs JL, Oi R, Dalrymple JL, Smith LH, Ryu J, et al. Endometriosis-related malignancies. Int J Gynecol Cancer. 2003;13(4):466-71.
18. Mu F, Rich-Edwards J, Rimm EB, Spiegelman D, Missmer SA. Endometriosis and risk of coronary heart disease. Circulation: Cardiovascular Quality and Outcomes. 2016;9(3):257-64.
19. Taskin O, Rikhraj K, Tan J, Sedlak T, Rowe TC, Bedaiwy MA. Link between Endometriosis, Atherosclerotic Cardiovascular Disease, and the Health of Women Midlife. J Minim Invasive Gynecol. 2019;26(5):781-4.
20. Kvaskoff M, Mahamat-Saleh Y, Farland LV, Shigesi N, Terry KL, Harris HR, et al. Endometriosis and cancer: a systematic review and meta-analysis. Human reproduction update. 2021;27(2):393-420.

Author:

Dr James Brown BA MBBS MPH FRANZCOG

Clinical Co-Lead, Specialist Menopause Service, South-Western Sydney LHD
Gynaecologist, Women’s Health and Research Institute of Australia, Sydney NSW
Senior Lecturer, Western Sydney University, NSW

January 2026