P-353 possible correlation between the second-to-four digit ratio (2d:4d) and endometriosis: a case-control study
Authors: Fornelli G , Buggio L , Dridi D , Viganò P , Reschini M , Galati G , Chinè A , Giola F , Somigliana E , Benaglia L 
Published: June 2023

Study question

This study investigates a possible association between the second-to-four digit ratio and endometriosis.

Summary answer

There is an association between a higher 2D:4D ratio and the presence of endometriosis.

What is known already

Endometriosis is characterised by the presence of endometrium epithelium and/or stroma outside the uterus. Recent findings suggest that endocrine disruptors during intrauterine life could determine the onset of the disease.The ratio between the length of the index finger (2D) and the ring finger (4D) is a sexually dimorphic feature. Moreover, it has been proposed as a marker of prenatal hormonal exposure since high level of androgens results in a lower 2D:4D ratio, whereas a prenatal oestrogenic environment results in a higher one. Therefore, a longer 2D:4D ratio could be considered as a silent sign of the disease.

Study design, size, duration

This study was conducted at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico. Participants were recruited from July 2021 to October 2022. Cases included women with a past surgical diagnosis of endometriosis or with a current nonsurgical diagnosis of the disease. Women attending the outpatient clinics for periodic visits, contraception, severe male infertility, and cervical cancer screening programme and without a previous clinical or surgical diagnosis of endometriosis were enrolled as the control group.

Participants/materials, setting, methods

Women with endometriosis were divided into two groups: deep infiltrating endometriosis (DIE) and ovarian endometrioma (OMA) depending on the lesion localization. Among controls, endometriosis was excluded based on gynaecological history, pelvic transvaginal ultrasound, gynaecological bimanual examination and vaginal inspection.The digit lengths were measured on the right hand's ventral surface because previous studies suggested that the right hand is more sensitive to androgens. In addition, other clinical details were collected on standardised forms.

Main results and the role of chance

A total of 424 participants (endometriosis n = 212; controls n = 212) were recruited for this study. The group of cases included 114 women with ovarian endometriomas and 98 patients with deep infiltrating endometriosis.Although the median age in the endometriosis group was 37 years, significantly higher than controls (p &lt; 0.01), other variables (such as BMI, ethnicity, smoking habit, age at menarche, parity, previous miscarriages and previous IVF) did not differ between the study groups.The right hand 2D:4D digit ratio resulted significantly higher in women with endometriosis compared to controls with 2D:4D ratio of 1.00 [0.97 - 1.03] and 0.99 [0.96 - 1.02] respectively (p = 0.002).The significant association remained when exclusively focussing on women with ovarian endometriomas (p = 0.002). In contrast, the association was no more significant when the analysis was restricted to women with deep infiltrating forms (p = 0.07).These findings support the potential role of intrauterine exposure of estrogen in the pathogenesis of the disease. A low ratio of testosterone-to-estradiol during fetal life may play a crucial role in endometriosis onset and progression.

Limitations, reasons for caution

The selection of controls may represent a source of bias since endometriosis was ruled out based on gynaecological and ultrasonography examination. Therefore, it could not be excluded having inadvertently included some cases among controls.

Wider implications of the findings

In conclusion, there is an association between a higher 2D:4D ratio and the presence of endometriosis. Our results support the hypothesis claiming potential influences of intrauterine hormonal and endocrine disruptors exposure during fetal life on the onset of the disease.

Trial registration number

not applicable