Is early age at menarche a risk factor for endometriosis? A systematic review and meta-analysis of case-control studies

In this systematic review and meta-analysis of case-control studies, we found a small but statistically significant effect of early menarche on endometriosis risk when potential confounders are adequately controlled for.

Kelechi E. Nnoaham, M.D., Premila Webster, M.D., Jharna Kumbang, M.D., Stephen H. Kennedy, M.R.C.O.G., Krina T. Zondervan, D.Phil.

Volume 98, Issue 3, Pages 702-712.e6, September 2012


To review published studies to evaluating the association between early menarche risk of endometriosis.

Systematic review and meta-analysis of case-control studies


Eighteen case-control studies of age at menarche and risk of endometriosis including 3,805 women with endometriosis and 9,526 controls


Main Outcome Measures:
Medline and Embase databases were searched from 1980 to 2011 to locate relevant studies. Results of primary studies were expressed as effect sizes of the difference in mean age at menarche of women with and without endometriosis. Effect sizes were used in random effects meta-analysis.

Eighteen of 45 papers retrieved met the inclusion criteria. The pooled effect size in metaanalysis was 0.10 (95% CI -0.01-0.21), and not significantly different from zero (no effect). Results were influenced by substantial heterogeneity between studies (I2=72.5%), which was eliminated by restricting meta-analysis to studies with more rigorous control of confounders; this increased the pooled effect size to 0.15 (95% CI 0.08-0.22), which was significantly different from zero. This represents a probability of 55% that a woman with endometriosis had earlier menarche than one without endometriosis if both were randomly chosen from a population.

There is a small increased risk of endometriosis with early menarche. The potential for disease misclassification in primary studies suggests this risk could be higher.

  • kcnnoaham

    The method employed in this study perhaps helps to progress the debate about whether earlier age at menarche is associated with increased risk of endometriosis. It is however worth noting that the nature of the primary studies and the potential role of alternative explanations for the association we found mean that this conclusion needs to be made cautiously. More important is the question of how clinically useful a history of early menarcheal age is in diagnosing or raising the clinical possibility of endometriosis. Our study does not provide evidence to suggest that it is but does highlight the need for well-designed studies into the causes and risk factors for endometriosis.

  • Sérgio Soares

    Congratulations for the work done. A couple of questions about the study:
    a) Isn’t it an important methodological limitation the fact that endometriosis was ruled out in controls by surgery in only eight of the 18 studies included in the meta-analysis?
    b) Considering we are talking about case-control studies, can we refer to ‘greater risk of endometriosis’? Would not the real issue ascertained by the study be ‘the odds-ratio of early menarche in women with endometriosis’, instead of ‘age at menarche and the risk of endometriosis’?

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