In utero exposures and endometriosis the Endometriosis Natural History Disease Outcome ENDO Study

In utero exposures were not associated with a visualized endometriosis diagnosis in either an operative or population cohort of women in contrast to earlier evidence.

Erin Foran Wolff, M.D., Liping Sun, M.S., M.D., Mary L. Hediger, Ph.D., Rajeshwari Sundaram, Ph.D., C. Matthew Peterson, M.D., Zhen Chen, Ph.D., Germaine M. Buck Louis, Ph.D.

Volume 99, Issue 3, Pages 790-795, 1 March 2013


To assess in utero exposures and the odds of an endometriosis diagnosis.

Matched cohort design.

Fourteen participating clinical centers in geographically defined areas in Utah and California.

Study cohorts:
The operative cohort comprised 473 women undergoing laparoscopy/ laparotomy, and was matched on age and residence to a population cohort comprising 127 women undergoing pelvic magnetic resonance imaging (MRI), 2007-2009.


Main outcome measures:
Women completed standardized interviews prior to surgery or MRI regarding in utero exposures: mothers’ lifestyle during the index pregnancy, and the index woman’s gestation and birth size. Endometriosis was defined as visually confirmed disease in the operative cohort, and MRI visualized disease in the population cohort. The odds of an endometriosis diagnosis and corresponding 95% confidence intervals (AOR; 95% CI) were estimated for each exposure by cohort using logistic regression and adjusting for current smoking, age at menarche, body mass index, and study site.

Endometriosis was diagnosed in 41% and 11% of women in the operative and population cohorts, respectively. In the primary analysis, AORs were elevated for maternal vitamin usage (1.27; 95% CI =0.85-1.91), maternal cigarette smoking (1.16; 95% CI=0.61-2.24), and low birth weight (1.1; 95% CI=0.92-1.32). Reduced odds were observed for maternal usage of caffeine (0.99; 95% CI=0.64- 1.54), alcohol (0.82; 95% CI=0.35-1.94), paternal cigarette smoking (0.72; 95% CI=0.43-1.19) and preterm delivery (0.98; 95% CI=0.47-2.03). Sensitivity analyses mostly upheld the primary results except for a decreased AOR for preterm birth (0.41; 95% CI=0.18-0.94) when restricting to visualized and histologically-confirmed endometriosis in the operative cohort.

In utero exposures were not significantly associated with the odds of an endometriosis diagnosis in either cohort.

  • Ivo Brosens

    The question may not be whether low birth weight is a risk factor of endometriosis, but both may be related to the fetal response to maternal pregnancy hormones in late pregnancy. The work by Ober and Bernstein (1955) from Harvard Medical School on newborn autopsies has nicely demonstrated that 68% of the newborns show proliferative endometrium, 27% secretory endometrium and 5% decidual or menstrual endometrium. German studies from the 1970s have shown that overt uterine bleeding occurs in 5% of the neonates and occult in some 25-50%. Clearly, neonatal uterine bleeding is a potential cause of early-onset endometriosis.
    It is interesting to note that in Ober’s study the bleeders had a low birth weight. Unfortunately we do not know the birthweight of the other newborns in the study. Clearly,the question may not be whether low birthweight is a risk factor for endometriosis, but rather whether the risk of both low birth weight and endometriosis are determined by the rise of progesterone response in the neonate in late pregnancy? It is indeed unfortunate that Ober’s study cannot be checked for birth weight of all the 169 newborns involved in thier study.

    For further correspondence or if anyone knows how to have access to the autopsies files of the Laboratory of Pathology, Boston Lying-in Hospital please contact me by e-mail:

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