Primary dysmenorrhoea in adolescents and young women: A twin family study of maternal transmission, genetic influence and associations

Abstract

The extent to which maternal transmission of primary dysmenorrhoea is genetically determined in adolescents and young women has yet to be determined. We aimed to assess heritability and associations relevant to primary pain syndromes using a twin family study. Methods:Participants were young menstruating female twins, and their oldest sisters and mothers, whose families were registered with Twins Research Australia and previously participated in a twin family study of primary paediatric pain disorders. Questionnaire packs were mailed, assessing current maximum and average menstrual pain intensity, current pain interference with activities and retrospective dysmenorrhea secondary symptoms. Results:The sample comprised 206 twin individuals (57 monozygous (MZ) and 46 dizygous (DZ) pairs) aged 10-22 years, eldest siblings (n = 38) aged 13-28 years and mothers (n = 101) aged 32-61 years. The estimated regression coefficient of the relationship between mother-daughter and twin-sibling dyads indicated significant associations for the measures of dysmenorrhea and supported heritability. Adjusted for age, the within twin-pair correlation for MZ twins was generally more than twice that of DZ twins. Heritability estimates were maximal pain intensity 0.67 (P = 3.8 × 10 −11 ), average pain intensity 0.63 (P = 3.7 × 10 −10 ), pain interference 0.57 (P = 1.8 × 10 −8 ) and retrospective symptoms 0.57 (P = 1.8 × 10 −8 ). Twin individuals with a lifetime (threemonth) history of iron deficiency and those with painless restless legs syndrome (RLS) were significantly more likely to have more intense pain associated with menstruation. Conclusion:Primary dysmenorrhea in adolescents and young women was shown to be relatively strongly genetically influenced and associated especially with a history of iron deficiency and painless RLS which have potential therapeutic implications.

Maternal transmission of dysmenorrhea includes substantial genetic influence

“…There is also the consideration that life prevalence (>3 months) of doctor-confirmed iron deficiency, notably including iron deficiency identified in the first year of life, be considered as an association, probably causal as suggested by application of the Bradford Hill criteria, with dysmenorrhea, and thus a biological influence. 1 There was an association between the history of iron deficiency and pain intensity of the current menstrual period after adjustment for age (OR 1.60, P < 0.01) 1 . The association between a history of doctor-confirmed iron deficiency and dysmenorrhea has been confirmed in adult women in a current twin family study.…”

“…Whether this is due to genetic or social learning factors is unknown.” I suggest that both are important. I was a co-author of a twin family study on dysmenorrhea in adolescents and young women, 1 published almost simultaneously with the review by Gagnon et al, and this publication would not have been apparent to the authors. After reviewing maternal transmission of dysmenorrhea, we presented evidence from a questionnaire survey of 103 twin pairs and their families for substantial genetic influence.…”

“…Adjusted for age, the within-pair correlation for monozygous twins (57 pairs) was generally more than twice that of dizygous twins (46 pairs) for maximal pain intensity, average pain intensity, pain interference with activities, and for retrospective dysmenorrhea-related symptoms, giving heritability estimates in the range 0.57 to 0.67.There is also the consideration that life prevalence (.3 months) of doctor-confirmed iron deficiency, notably including iron deficiency identified in the first year of life, be considered as an association, probably causal as suggested by application of the Bradford Hill criteria, with dysmenorrhea, and thus a biological influence. 1 There was an association between the history of iron deficiency and pain intensity of the current menstrual period after adjustment for age (OR 1.60, P , 0.01) 1 . The association between a history of doctor-confirmed iron deficiency and dysmenorrhea has been confirmed in adult women in a current twin family study.…”

Disease Burden of Dysmenorrhea: Impact on Life Course Potential

“…Aouad et al recently performed a twin study for primary dysmenorrhea, where monozygotic twins showed twice the correlation for different pain phenotypes compared to dizygotic twins, with heritability estimates between 57% and 67%. 21 A genome-wide association study https://doi.org/10.2147/IJWH.S380006…”

Reply to Champion

“…4,5 This would help explain the observed association between iron deficiency and period pain discussed in Dr. Champion's letter. Given the cross-sectional nature of the data, causality between dysmenorrhea and iron deficiency cannot be determined by the investigation of Aouad et al 1…”