Female patients with Ehlers–Danlos syndromes appear to face substantially higher risks of gynecologic and obstetric disorders than female patients without the condition, with some urogynecologic conditions up to 10 times more likely, according to a large retrospective database study.

“A considerable subset of literature exists on the gynecologic and obstetric manifestations of Ehlers–Danlos syndromes (EDS),” lead study author, Marisa R. Imbroane, BSc, of Case Western Reserve University, and colleagues explained. However, given the rarity of the condition—estimated at 1 in 5,000 births for hypermobile EDS—previous studies have been limited by sample size. The researchers sought to use a large database to validate prior observations and expand on the conditions patients with EDS may encounter.

Study Details

Using the TriNetX research network, the researchers identified female patients aged 18 to 44 years and divided them into two cohorts: one with EDS (54,558 patients) and one without (over 19 million patients). Following matching for age, each cohort comprised 50,809 patients with a mean age of 30 years. The study assessed the risk of 18 gynecologic and 6 obstetric diagnoses between the cohorts using ICD-10 codes.

Key Findings

Patients with EDS showed the greatest increase in risk for urogynecologic conditions. Compared with the non-EDS cohort, patients with EDS had 10 times the odds of fecal incontinence (1.7% vs 0.2%), 9 times the odds of female genital prolapse (3.2% vs 0.4%), and nearly 6 times the odds of urinary incontinence (4.8% vs 0.8%). They were also 8.5 times more likely to undergo surgical correction of prolapse.

The EDS cohort also demonstrated statistically significant differences in gynecologic diagnoses. Patients with EDS had 7 times the odds of endometriosis (6.3% vs 0.9%), nearly 4 times the odds of dyspareunia, and nearly 3 times the odds of pelvic and perineal pain (18.3% vs 6.2%) compared with the non-EDS cohort. They also had higher rates of abnormal menstruation, dysmenorrhea, and iron deficiency anemia secondary to chronic blood loss.

Among pregnant patients (6,343 per cohort following matching), those with EDS faced higher risks of adverse obstetric outcomes. They had 83% higher odds of postpartum hemorrhage (8.5% vs 4.7%), 68% higher odds of gestational hypertension, 46% higher odds of preeclampsia, 40% higher odds of spontaneous abortion, and 38% higher odds of preterm prelabor rupture of membranes. Patients with EDS were also 14% more likely to undergo cesarean delivery.

The researchers found that patients with EDS received more fertility care than the non-EDS cohort. They were more likely to have encounters for fertility testing, undergo anti-Müllerian hormone testing, and have assisted reproductive technology procedure cycles. The researchers noted that the mechanism behind infertility in patients with EDS is not well documented, though hormonal imbalances, abnormal menstruation, and elevated rates of spontaneous abortion may contribute.

Within the EDS cohort, the researchers identified racial disparities. Black patients with EDS had nearly 4 times the odds of leiomyoma compared with White patients with EDS (5.3% vs 1.4%), as well as higher rates of abnormal uterine bleeding and iron deficiency anemia. Hispanic patients with EDS had higher rates of excessive, frequent, and irregular menstruation compared with non-Hispanic patients with EDS.

The researchers acknowledged several limitations, including reliance on ICD-10 coding without confirmation of diagnostic accuracy, inability to determine whether patients with EDS receive more routine health care than the general population, and limited sample sizes for certain EDS subtypes (classical and vascular EDS) that prevented subtype-specific analyses for some outcomes.

“Through this large retrospective database study including over 50,000 [patients with EDS], we show that female patients with EDS have an increased risk for gynecologic and obstetric disorders compared with a non-EDS cohort,” the researchers wrote. “This innovative work validates prior observations and expands on what is known of EDS in the context of obstetrics and gynecology.”

The researchers concluded, “This risk should be considered when counseling patients on what they may experience with EDS and should prompt general practice clinicians to refer [patients with EDS] to specialists in obstetrics and gynecology. For diagnoses where connective tissue dysfunction is not readily apparent as a causal mechanism, more basic and translational studies are needed to better characterize why patients with EDS are facing this increased risk.”

The researchers reported no conflicts of interest. No funding was received for the study.

Source: Journal of Women’s Health