Polycystic ovary syndrome is associated with anogenital distance, a marker of prenatal androgen exposure

Abstract

Study question: Is the presence of polycystic ovary syndrome (PCOS) associated with anogenital distance (AGD), a biomarker for the prenatal hormonal environment?

Summary answer: The presence of PCOS is associated with longer AGD.

What is known already: Although the aetiology of PCOS is unclear, emerging data suggest that the natural history of PCOS may originate from intrauterine life. Prenatal exposure to androgen hormones is considered an important factor of PCOS. AGD is the distance measured from the anus to the genital tubercle and there is considerable evidence in humans and animals to support AGD as a sensitive biomarker of prenatal androgen activity.

Study design, size, duration: This case-control study of 156 PCOS patients and 180 reproductively healthy women (control subjects) was performed from October 2015 to July 2016.

Participants/materials, setting, methods: The patients and controls were recruited from the out-patient Department of Gynecology of Sun Yat-sen Memorial Hospital. Participants completed health questionnaires and provided a blood sample for evaluation of serum reproductive hormone profiles. Anthropometric indices of AGDAF (anus-fourchette) and AGDAC (anus-clitoris) were measured in all subjects. We used logistic regression to estimate the association between the presence of PCOS and AGD measurements while accounting for important confounders, including age and BMI. Multiple linear regression was used to analyse the relationships between PCOS characteristics (e.g. polycystic ovaries and total testosterone (T)) and two measurements of AGD in the PCOS group and controls.

Main results and the role of chance: Overall, logistic regression showed that women with AGDAF in the highest tertile were 18.8 times (95% CI 9.6-36.6; P < 0.001) more likely to have PCOS compared with those in the lowest tertile. Women with AGDAC in the highest tertile were 6.7 times (95% CI 3.7-12.1; P < 0.001) more likely to have PCOS than those in the lowest tertile. In the PCOS group, multiple linear regression analyses revealed that both AGD measurements were positively associated with T levels (β = 0.246 for AGDAC, β = 0.368 for AGDAF; P = 0.003 and P < 0.001, respectively), and AGDAF was positively associated with the presence of polycystic ovaries (β = 0.279; P < 0.001). In the controls, a positive association was found only between T levels with AGDAF (β = 0.177, P = 0.020), whereas no associations were found between the remaining covariates and AGD measurements.

Limitations, reasons for caution: As this was an observational study, causal inference cannot be obtained.

Wider implications of the findings: This study suggests that PCOS may originate in intrauterine life, and be affected by prenatal exposure to androgens.

Study funding/competing interest(s): This study was supported by funds obtained from the Science Technology Research Project of Guangdong Province (2010B031600058 and 2015A030310083) and the Major Science Technology Research Project of Guangdong Province (ZKM05602S). The authors have no competing interests to declare.

Trial registration number: Not applicable.

Keywords: androgens; anogenital distance; polycystic ovarian syndrome; polycystic ovaries; prenatal exposures.