By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Nov 25 2024

Endometriosis is linked to a 31% higher risk of early death, with increased mortality from gynecological cancers, nervous system diseases, and respiratory conditions.

Study: Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study. Image Credit: Shutterstock AI / Shutterstock.com

Endometriosis and uterine fibroids are gynecologic conditions affecting women of reproductive age. A recent study published in The BMJ examines the impact of these disorders on the risk of early death.

What causes premature death?

Premature mortality due to non-communicable diseases (NCDs) accounted for 15.6 million deaths in individuals between the ages of 30 and 69 years in 2019, thereby causing 76% of all premature deaths. Thus, it is crucial to identify risk factors for these deaths, especially those attributed to cancer, cardiovascular disease (CVD), and respiratory diseases.

Smoking, a poor diet, and excessive body weight contribute to the risk of premature mortality. However, recent research has also indicated the role of female-specific traits related to the menstrual cycle and pregnancy on premature death.

Endometriosis and uterine fibroids affect 10% and 15-30% of women in the reproductive age, respectively. These conditions have similar genetic characteristics and often involve shared immunologic, hormonal, and inflammatory pathways.

Women with these conditions are more likely to die prematurely, with a higher risk of CVD, hypertension, and cancer. Despite these observations, few studies have examined how these conditions and certain health factors like behaviors, hormone replacement therapy (HRT) or oral contraceptive use, hysterectomy or oophorectomy, infertility history, or the risk of both concurrent conditions may further contribute to the increased risk of premature mortality.

About the study

The current study analyzed the impact of endometriosis and uterine fibroids on premature mortality risk among women over a 30-year period. The aim of this study was to assess the risk of total and condition-specific premature mortality in women with either or both of these conditions confirmed by ultrasound, laparoscopy, or hysterectomy, as reported by questionnaires every two years from 1993 onwards.

The current prospective cohort study used data obtained from the Nurses Health Study II, which was conducted in the United States between 1989 and 2019. In 1989, 110,091 women between the ages of 25 and 42 were recruited.

None of these women had a history of hysterectomy, endometriosis, fibroids, CVD, or cancer at baseline. The mean participant age was 34.7 years in 1989 and 64.4 years in 2019, at which point most of the women had experienced menopause.

Endometriosis and uterine fibroids linked to higher infertility and increased surgical interventions

Women with endometriosis were more likely to be infertile at 52%, as compared to 16% of women without this condition. Furthermore, women with endometriosis were more likely to have undergone a hysterectomy and oophorectomy at 21% and 17%, respectively, as compared to 1%, and of women without endometriosis.

A diagnosis of endometriosis was accompanied by an increased likelihood of using non-steroidal anti-inflammatory drugs (NSAIDs) other than aspirin at 28% as compared to 19% of women not diagnosed with endometriosis. HRT was also prescribed in 32% of women with endometriosis as compared to 9% of non-endometriosis women.

Uterine fibroids were associated with an infertility prevalence of 27% as compared to 18% in those without fibroids. Women with uterine fibroids were also more likely to undergo a hysterectomy and oophorectomy at 20% and 10%, respectively, as compared to 1% of women without uterine fibroids.

Increased mortality risk

Women were followed up over a total of 2,994,354 person-years (PY) at an average of 27.2 years for each woman. Premature deaths were defined as those occurring in women younger than 70 years of age. A total of 1,459 premature deaths were due to cancer, followed by 304 from CVD and 90 from respiratory disease.

Premature mortality among those with endometriosis was two for every 1,000 PY as compared to 1.4 for those without endometriosis. The age-adjusted risk of early death was 19% higher in women with endometriosis and 31% higher after adjusting for other confounding factors.

Non-cancerous respiratory diseases increased the risk of premature mortality by two-fold, whereas disorders of the nervous system or sense organs increased the risk by 2.5-fold. Female reproductive tract cancers were 2.76-fold more likely to arise in women with endometriosis.

Endometriosis and uterine fibroids increased the risk of female reproductive tract cancers by 34% and 28%, respectively, with both conditions associated with an increased risk of 20%. In women with both disorders, CVD risk was 61% higher as compared to a 93% increased risk with isolated endometriosis and no increase for fibroids alone.

The presence of uterine fibroids did not increase the risk of premature death overall. However, fibroids were associated with a 2.32-fold increased risk of premature death from gynecologic cancers.

The risk of CVD and respiratory disease with premature mortality varied, both of which were higher if endometriosis and fibroids were present. Endometriosis was also associated with a 2.2-fold greater risk of premature death from respiratory causes.

Comparison with prior research

Previous studies have failed to consider confounding factors like hormone use, infertility, or health behaviors on the risk of premature death in women with endometriosis and/or uterine fibroids. Diagnostic biases, differences due to population characteristics, and access to treatment may also have contributed to differences between the current study findings and previous reports.  

Nevertheless, several studies have produced findings that agree with the current analysis. These studies have also identified associations between endometriosis and fibroids with a higher risk of gynecologic cancer.

Conclusions

Women with endometriosis and uterine fibroids might be at a higher risk of premature death, which remains increased after the end of their reproductive years. Women with both conditions were more likely to die from gynecological cancers, which was the most common cause of mortality in this subset of women.

Moreover, women with endometriosis were at increased risk of death from causes other than cancer. Endometriosis and fibroids interact to produce different mortality risks among women; therefore, additional mechanistic research is needed to support the development of preventive and therapeutic strategies. 

These findings highlight the importance for primary care providers to consider these gynecological disorders in their assessment of women's health.”

Journal reference:

Wang, Y., Farland, L. V., Gaskins, A. J., et al. (2024). Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study. The BMJ. doi:10.1136/bmj-2023-078797.