Research Article: Risk of gestational hypertension-preeclampsia in women with preceding endometriosis: A nationwide population-based study

Date Published: July 17, 2017

Publisher: Public Library of Science

Author(s): Mei-Lien Pan, Li-Ru Chen, Hsiao-Mei Tsao, Kuo-Hu Chen, Andrew Wolfe.


To investigate the association between preceding endometriosis and gestational hypertension-preeclampsia (GH-PE).

In this nationwide population-based longitudinal study, data from 1998–2012 Taiwan National Health Insurance Research Database were used. We used ICD9-CM codes 617.X and 642.X respectively for the diagnoses of endometriosis and GH-PE, which were further confirmed by examining medical records of surgeries, blood pressure and urine protein to ensure the accuracy of the diagnoses. The study excluded women diagnosed with endometriosis at < 15 or > 45 years of age, chronic hypertension, and GH-PE prior to endometriosis. Each pregnant woman with a prior diagnosis of endometriosis was matched to 4 pregnant women without endometriosis by age. Logistic regression analysis was used to calculate odds ratios (ORs) for the risk of GH-PE with adjustment for age, occupation, urbanization, economic status and comorbidities.

Among 6,300 women with a prior endometriosis diagnosis who were retrieved from a population of 1,000,000 residents, 2,578 (40.92%) had subsequent pregnancies that were eligible for further analysis and were compared with 10,312 pregnant women without previous endometriosis. GH-PE occurred more in women with prior endometriosis as compared to those without endometriosis (3.88% vs. 1.63%, p<0.0001). Further analysis revealed prior endometriosis was associated with GH-PE (adjusted OR = 2.27; 95% CI:1.76–2.93). For danazol-treated and non-danazol-treated subgroups, the incidences of GH-PE were 3.13% (15/480) and 4.05% (85/2,098), respectively. Although the risk for subsequent GH-PE was lower (adjusted OR = 1.49; 95% CI:0.86–2.56) after receiving danazol treatment than average (adjusted OR = 2.27; 95% CI:1.76–2.93) for women with preceding endometriosis, the reduction of risk was not statistically remarkable for danazol-treated (adjusted OR = 1.49) vs. non-danazol-treated (adjusted OR = 2.48) subgroups (p heterogeneity = 0.12). Preceding endometriosis is an independent and significant risk factor for the occurrence of GH-PE.

Partial Text

Endometriosis, a common cause of pelvic pain and subfertility, is characterized by endometrial-like tissue outside the endometrium, primarily on the uterine myometrium, ovaries, rectovaginal septum and pelvic peritoneum [1]. The prevalence of endometriosis is estimated to be approximately 6%-10% of reproductive-aged women [1, 2] Although the etiology and pathogenesis of endometriosis remain uncertain, the ectopic endometrial cells and tissues, which are dependent on estrogen for growth, can implant on peritoneal surfaces and elicit a chronic inflammatory response and subsequent adhesions, fibrosis, scarring, neuronal infiltration, and anatomical distortion [1–3]. Invasion of the peritoneal epithelium is postulated to be mediated by an immune response, with subsequent activation of macrophages, increased production of cytokines, growth factors, and angiogenic factors [2]. In contrast, natural-killer-cell (NK cell) activity in peritoneal fluid in women with endometriosis is compromised, which can lead to decreased surveillance of ectopic tissue [2].

Among the population of 1,000,000 residents who were insured in 2010, there were 492,423 males and 507,577 females. The latter included 250,804 females of reproductive age (age 15–45) and 256,773 females of non-reproductive age. Based on the inclusion and exclusion criteria, 6,300 women of reproductive age diagnosed with endometriosis between 1998 and 2012 were identified (Fig 1). Among these women, 2,578 (40.92%) had subsequent pregnancies and were eligible for further analysis. They were compared with 10,312 pregnant women without previous endometriosis. For every female in the exposed and unexposed groups, the follow-up duration for the occurrence of GH-PE was 15 years since the index date. In the current study, the mean and median follow-up duration was 7.24–7.35 years and 7.06–7.18 years, respectively. The main reasons for censored data were deaths of nationals (55/2,578 in exposed group and 158/10,312 in unexposed group) and withdrawal of nationals from the National Health Insurance (38/2,578 in exposed group and 227/10,312 in unexposed group). Table 1 compares the characteristics between the exposed and unexposed groups. The age in Table 1 provides the age (three age groups: 15–25, 26–35, and 36–45 years) of the women when endometriosis was initially diagnosed. During pregnancy, every woman with previous endometriosis (exposed group) was matched with 4 other women of the same age (unexposed group). For the exposed group, the average age at the time of initial diagnosis of endometriosis was 31.8 ± 5.8 years. Nearly 60% of these women were initially diagnosed with endometriosis between 26 and 35 years of age, followed by age 26.4% at 36–45 years, and age 14.2% at 15–25 years. The parities of pregnancies complicated with GH-PE were analyzed. For the exposed and unexposed groups, there were no differences in the ratios of primi-parity and multi-parity (p > 0.05). Compared with the unexposed group, a higher percentage (21.30%) of women in the exposed group had a high insurable wage (≥ NTD 40,000); a lower proportion (20.05%) of women had a low insurable wage (< NTD 20,000), and spouse/dependents had the lowest percentage of women (13.85%). The average age (30.1 ± 5.1 years) at first pregnancy in the exposed group was older than that (29.3 ± 4.8 years) in the unexposed group (p < 0.0001). Compared with the unexposed group, women in the exposed group were more likely to be white-collar workers (p = 0.0006), to reside in urban areas (p = 0.0298), and to have a higher level of economic status (p = 0.0008). In addition, they were more likely to have dyslipidemia (p = 0.0155) and autoimmune disease (p = 0.0153) (Table 1). In the current study, women with prior endometriosis have a higher incidence of GH-PE in subsequent pregnancies compared to women without endometriosis (3.88% vs. 1.63%, p < 0.0001). Further analysis shows that preexisting endometriosis is an independent and significant risk factor (adjusted OR = 2.27; 95% CI: 1.76–2.93) for GH-PE. Women with preceding endometriosis are associated with a higher risk of developing GH-PE in subsequent pregnancies and require closer surveillance for maternal and fetal well-being. After confirmation of preexisting endometriosis, appropriate information and suggestions should be provided to pregnant women at-risk to facilitate earlier intervention or specialty referral. When affected women become pregnant, monitoring and preparation should be intensified before and during delivery to avoid obstetric complications due to the increased risk of GH-PE. In addition, the risk of subsequent GH-PE was not significantly reduced for women with endometriosis who received danazol treatment.   Source:


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