L26/O-088 Risk of endometriosis, adenomyosis and related symptoms among women conceived by mothers on hormonal contraceptives

Abstract Study question Do women who were conceived by mothers on hormonal contraceptives have an increased risk of endometriosis, adenomyosis or related symptoms? Summary answer Women conceived by mothers on hormonal contraceptives have an increased risk of painful and heavy menstrual bleeding. What is known already Fetal exposure to exogenous hormones may conceivably influence the development of the female reproductive system. There is some evidence to support that endometriosis/adenomyosis might originate already from fetal life, although the retrograde menstruation theory is the most pervasive. It is possible that these conditions could have multiple potential etiological explanations. Study design, size, duration We conducted a nationwide registry-based cohort study of 142,230 women born in Norway between 2004 and 2009. Participants/materials, setting, methods The risk of diagnoses of endometriosis, adenomyosis and related symptoms (heavy menstrual bleedings, painful menstrual bleedings and pain during intercourse) among women according to whether they were conceived while the mother was using hormonal contraceptives was examined using Cox regression, adjusted for maternal age, parity, history of endometriosis/adenomyosis, immigrant status and use of ART. Women were followed from when they were 15 years of age for an average of 4 years. Main results and the role of chance A total of 12,230 (8.5%) of women studied were conceived while their mothers were on hormonal contraceptives, defined as having a filled prescription in the Norwegian Prescribed Drug registry within 90 days prior to the estimated date of conception. The risk of the outcomes per 10,000 follow-up days was 8 for endometriosis/adenomyosis, 355 for painful menstrual periods, 8 for pain during intercourse and 102 for heavy menstrual bleedings. Women conceived by mothers who were using hormonal contraceptives had a modest increased risk of heavy menstrual bleedings (adjusted hazard ratio [aHR] 1.15; 95% CI: 1.05, 1.27) and painful menstrual periods (aHR 1.12; 95% CI: 1.06, 1.18). There was no robust evidence of an increased risk of endometriosis/adenomyosis (aHR 1.06; 95% CI: 0.77, 1.57) or pain during intercourse (aHR 1.05; 95% CI: 0.74, 1.48). Secondary analyses evaluating the risk according to whether the mother had a dispensed prescription 60 days prior to the estimated date of conception yielded similar estimates. Sensitivity analyses will be conducted looking at subtypes of hormonal contraceptives. Limitations, reasons for caution We were only able to adjust for registered diagnoses of endometriosis/adenomyosis among mothers of the studied women. It is therefore possible that there is residual unmeasured confounding by underlying heredity of endometriosis/adenomyosis if these mothers were more likely to use hormonal contraceptives. We also had a modest follow-up period. Wider implications of the findings We observed an increased risk of menstrual symptoms that are often precursors to a diagnosis of endometriosis/adenomyosis associated with prenatal exposure to hormonal contraceptives, but additional studies with longer follow-up are necessary to confirm and further investigate these findings. Trial registration number No