New Study Questions Biomarker for Endometriosis

ANOGENITAL distance (AGD), a proposed biomarker for gynaecological conditions including endometriosis and polycystic ovary syndrome (PCOS), may have important limitations in clinical practice, according to new research involving 307 women.

Researchers found that AGD measurements were influenced by body mass index (BMI) and, for one measurement, parity, while substantial variation between observers raised concerns about reproducibility. The findings suggest that further standardisation is needed before AGD can be reliably used to assess gynaecological conditions.

Investigating a Potential Gynaecological Biomarker

AGD, the distance between the anus and external genital structures, has been proposed as an indicator of the prenatal hormonal environment.

Previous research has suggested that AGD may differ among women with endometriosis, PCOS, and impaired fertility, raising interest in its potential as a non-invasive biomarker.

However, before AGD can be incorporated into clinical assessment, researchers must establish typical measurement ranges, identify factors influencing measurements, and determine whether results can be reproduced consistently.

To investigate these questions, researchers conducted a cross-sectional study at the Royal Women’s Hospital in Melbourne, Australia.

The study included 307 women aged 18–50 years undergoing benign gynaecological surgery under general anaesthesia between March 2021 and September 2022.

Two AGD measurements were assessed: the distance from the anus to the clitoris (AGD-AC) and the distance from the anus to the posterior fourchette (AGD-AF).

Measurements were performed using disposable millimetre rulers while participants were under anaesthesia, with repeated assessments conducted by one or two clinicians.

Researchers also collected information on BMI, reproductive history, ethnicity, smoking status, and contraceptive use.

BMI and Parity Influence AGD Measurements

Both AGD measurements demonstrated approximately normal distributions across the study population.

The mean AGD-AF was 35.9 mm (standard deviation [SD]: 8.8; 95% CI: 34.9–36.9), while the mean AGD-AC was 121.0 mm (SD: 19.4; 95% CI: 118.9–123.2).

BMI was significantly associated with both measurements, and these relationships persisted after adjustment for other participant characteristics.

Parity was also independently associated with AGD-AC in multivariable analysis, suggesting that reproductive history may influence this measurement.

In contrast, neither AGD measurement differed significantly according to ethnicity, smoking status, or contraceptive use.

These findings highlight the importance of accounting for BMI and parity when investigating associations between AGD and gynaecological conditions.

Measurement Variability Raises Concerns

Researchers also evaluated how consistently AGD could be measured by the same clinician and between different clinicians.

For AGD-AC, the mean difference between repeated measurements by the same observer was 4.5 mm, equivalent to 3.7%. Between observers, the mean difference increased to 9.5 mm, or 8.0%.

Greater relative variability was observed for AGD-AF.

The mean intra-observer difference was 3.2 mm (9.1%), while the mean inter-observer difference reached 6.4 mm (17.9%).

Although AGD-AC demonstrated better reproducibility than AGD-AF, both measurements showed potentially important variation between clinicians.

Notably, the researchers reported that inter-observer measurement error exceeded half the differences in AGD previously described between women with and without endometriosis.

This raises concerns that differences attributed to underlying gynaecological conditions could be difficult to distinguish from ordinary measurement variability.

Implications for Endometriosis and Fertility Research

The findings suggest that AGD measurements may be influenced by factors unrelated to the gynaecological conditions they are intended to identify.

BMI and parity could affect comparisons between patient groups, while inconsistent measurements may reduce the reliability of AGD as a diagnostic marker.

The researchers emphasised that studies investigating AGD should adjust for BMI and parity and report measurement reproducibility to support accurate interpretation.

However, the study was conducted among women undergoing benign gynaecological surgery at a single tertiary centre, which may limit the generalisability of the reported measurements to the wider population.

Furthermore, the analysis focused on measurement characteristics rather than directly evaluating AGD’s diagnostic accuracy for endometriosis, PCOS, or infertility.

The researchers concluded that AGD-AC was the more reproducible measurement, but both approaches had limitations that constrain their potential clinical application.

Further research is needed to establish standardised measurement methods and determine whether AGD can provide sufficiently reliable information to support gynaecological diagnosis.

Reference

Kavanagh, T., McNamara, H.C., Harlow, K. et al. Anogenital distance in adult women: examining a new biomarker in gynaecology. BMC Women’s Health (2026). https://doi.org/10.1186/s12905-026-04992-0