The mental health gap in endometriosis opens years before the diagnosis does

That endometriosis is associated with depression and anxiety is established. What has been harder to characterise is the shape of that association over time — specifically whether it begins after diagnosis, when a woman learns she has a chronic condition, or before it, during the years of unexplained pain that typically precede the diagnosis.

A Danish national registry study published in Human Reproduction on June 15 has the data to look at both sides of the index date [s1].

The dataset

The study covered 136,842 Danish women aged 15 to 55 between January 1, 2000 and December 31, 2019 [s1]. Within that population, researchers identified 22,807 women with a first-time hospital-based diagnosis of endometriosis, using density sampling [s1]. Each was matched on age at the date of diagnosis to five women without a diagnosis, giving a comparison group of 114,035 [s1].

Every woman was followed for up to ten years before and ten years after the index date [s1] — a 20-year observation window centred on the diagnosis.

Outcomes came from national registries: redeemed prescriptions for antidepressants and anxiolytics, and psychiatric hospital contacts for depression or anxiety [s1]. Comparisons used negative binomial regression adjusted for age, region of residence, highest educational level, household type, labour market affiliation, origin and parity [s1].

Redeemed prescriptions rather than written prescriptions is a meaningful distinction. It records what was collected from a pharmacy, not what a clinician intended.

What the timeline shows

Women who would go on to receive an endometriosis diagnosis already had elevated rates before it.

For antidepressants, the adjusted incidence rate ratio was 1.29 (95% CI 1.23–1.36) before the index date, rising to 1.40 (95% CI 1.34–1.47) after [s1].

For anxiolytics: 1.16 (95% CI 1.05–1.28) before, 1.46 (95% CI 1.29–1.64) after [s1].

For psychiatric hospital contacts due to depression or anxiety: 1.28 (95% CI 1.09–1.49) before, 1.41 (95% CI 1.22–1.63) after [s1].

The trajectories differed. The antidepressant association was described as quite stable across the study period [s1]. The anxiolytic association rose significantly right before the index date, and psychiatric hospital contacts began increasing around five years before diagnosis [s1].

Reading the pre-diagnosis signal

Three explanations are compatible with this pattern, and the study cannot separate them.

Living with severe pelvic pain, heavy bleeding and repeated inconclusive medical encounters is a plausible cause of depression and anxiety in itself. On this reading, the pre-diagnosis elevation is the psychological cost of undiagnosed disease.

Alternatively, women presenting with pain who also carry a psychiatric diagnosis may be investigated differently — a well-documented pattern in chronic pain generally — which would make part of the association a consequence of how the health system responds rather than of the disease.

Third, endometriosis is a chronic inflammatory condition, and shared biological pathways between inflammation and mood have been proposed. The study does not test any mechanism.

The rise in the years immediately before diagnosis is consistent with all three, and the authors call for future work on causal pathways and mediating factors rather than asserting one [s1].

Limits the authors state

The cohort captures only hospital-based diagnoses. Women treated for suspected endometriosis in general practice, or diagnosed solely by private gynaecologists, are not included, so the findings apply to hospital-diagnosed disease [s1].

Depression and anxiety are captured through prescriptions and hospital contacts, which will miss women who receive neither. The authors expect that under-ascertainment to be similar in both groups and therefore not to bias the comparison [s1] — a reasonable assumption, though it is an assumption.

The study is Danish, and both the diagnostic pathway and the pharmaceutical prescribing environment differ across health systems.

What it adds

The strongest reason to report a registry study of this kind is that it measures something a clinical cohort cannot: what was happening to these women during the years nobody had named their condition. The finding that psychiatric contacts start climbing roughly five years before the endometriosis diagnosis is arrived at [s1] puts a number on a period usually described in testimony rather than data.

The funders are named in the paper: the European Union's Horizon 2020 programme, through a project on identifying endometriosis using machine learning, and Helsefonden [s1]. The authors declare no competing interests [s1].

This article is informational and is not medical advice.

Sources

• Endometriosis and the mental health burden: a registry-based study of redeemed prescriptions and psychiatric hospital contacts before and after diagnosis of endometriosis — Human Reproduction, 2026-06-15