The risk of malignancy in women with endometriosis

The aim of this thesis was to investigate the association between endometriosis and malignancies also after controlling for parity, to investigate the impact of endometriosis on survival after a malignancy diagnosis and to investigate the association between treatment of endometriosis and ovarian cancer risk.

In a population based cohort study on the association between endometriosis and malignancy, 64 492 women with a first time discharge diagnosis of endometriosis between 1969 and 2000, were included and 3 349 incident cases of a malignancy recorded. The total Swedish female population was used as control group and SIRs were used as estimates of relative risk (paper I). There were statistically significant increased risks for ovarian cancer (SIR 1.43), endocrine tumors (SIR 1.36), non-Hodgkin s lymphoma (SIR 1.24) and brain tumors (SIR 1.22). Endometriosis in the ovaries, younger age at endometriosis diagnosis and long-standing endometriosis were all factors contributing to an even higher risk for ovarian cancer. Women with endometriosis developed ovarian cancer earlier in life than other women and hysterectomy seemed to have a protective effect against ovarian cancer.

The second population based cohort study included 63 630 women with a first time discharge diagnosis of endometriosis between 1969 and 2002 and who also had information on parity and age at first birth from the Multi Generation Register. The aim was to investigate the association between endometriosis and malignancy and control for parity. There were 3 822 incident cases of a malignancy recorded during follow up (paper II). The study showed a statistically significant increased risk of endocrine tumors (SIR1.38), ovarian cancer (SIR 1.37), kidney cancer (SIR 1.36), thyroid cancer (SIR 1.33), brain tumors (SIR 1.27), malignant melanoma (SIR 1.23) and breast cancer (SIR 1.08). There were no statistical difference in SIRs between nulliparous and parous women in any of the malignancies studied.

The third study was a cohort study on the impact of endometriosis on survival after a malignancy diagnosis. The study included 4 278 women with endometriosis and a malignancy diagnosis (exposed women) and 41 831 women with a malignancy diagnosis only (unexposed women). The results showed a statistically significant improved survival for women with endometriosis for all malignancies combined (HR 0.92), as well as for breast cancer (HR 0.86) and for women diagnosed with ovarian cancer after the age of 54 (HR 0.62). However, there was a worse prognosis after a diagnosis of malignant melanoma for women with endometriosis compared to other women (HR 1.52).

To study the impact of treatment of endometriosis and future ovarian cancer risk, medical records from 220 women with endometriosis and ovarian cancer (cases) and 416 controls were scrutinized (paper IV). The study showed strong reductions in risk for ovarian cancer after one-sided oophorectomy in both the univariate and multivariate analyses (OR 0.42 and OR 0.19, respectively) and when all visible endometriosis had been removed (OR 0.37 and OR 0.30, respectively). The only association between hormonal treatment and ovarian cancer was a borderline significance for months of danocrine use and ovarian cancer risk in the univariate analysis (OR 1.06).

This thesis shows that women with endometriosis have an increased risk of several types of malignancies, above all ovarian cancer. This increased risk is not related to parity. It is indicated that women with endometriosis have a better survival after a malignancy diagnosis than other women, especially for breast and ovarian cancer. However, the prognosis for malignant melanoma is worse for women with endometriosis. One-sided oophorectomy and removal of all visible endometriotic lesions strongly reduce the risk of ovarian cancer and the use of danocrine might be associated with an increased risk of ovarian cancer.

List of scientific papers

I. Melin A, Sparén P, Persson I, Bergqvist A (2006). "Endometriosis and the risk of cancer with special emphasis on ovarian cancer." Hum Reprod 21(5): 1237-42. Epub 2006 Jan 23
https://pubmed.ncbi.nlm.nih.gov/16431901

II. Melin A, Sparén P, Bergqvist A (2007). "The risk of cancer and the role of parity among women with endometriosis." Hum Reprod 22(11): 3021-6. Epub 2007 Sep 13
https://pubmed.ncbi.nlm.nih.gov/17855408

III. Melin A, Lundholm C, Malki N, Sparen P, Swahn M-L, Bergqvist A (2010). "Endometriosis as a prognostic factor for cancer survival." (Submitted)

IV. Melin A, Lundholm C, Malki N, Sparen P, Swahn M-L, Bergqvist A (2010). "Hormonal and surgical treatments for endometriosis and risk of ovarian cancer." (Manuscript)