The second to fourth digit ratio (2D:4D): a risk factor of migraine and tension-type headache

Migraine and Tension-type headache (TTH) are common and disabling primary headache disorders. They are more prevalent in females. The second to fourth digit ratio (2D:4D) is sexually dimorphic in humans and is considered to be a marker for the balance of prenatal testosterone and estrogen exposure. Therefore, we investigated the hypothesis that prenatal sex steroids constitute an independent risk factor for adult headaches later in life.

A total of 891 individuals (303 males, 588 females) of 18-68 years in age (a mean of 37.0 ± 10.1 years), including 279 migraine, 300 TTH, and 312 healthy subjects were enrolled. The 2D:4D ratio was measured by a single investigator using a digital Vernier caliper.

The females in the migraine group had lower 2D:4D ratios than those in the control group (left hand: 0.947 ± 0.034 vs. 0.955 ± 0.038, p = 0.048; right hand: 0.952 ± 0.035 vs. 0.965 ± 0.037, p = 0.001). There was a similar relationship between the TTH group and the control group (left hand: 0.946 ± 0.034 vs. 0.955 ± 0.038, p = 0.034; right hand: 0.954 ± 0.035 vs. 0.965 ± 0.037, p = 0.005), although this was not observed in males. Males showed lower 2D:4D ratios than females for the right hand in the control group (0.954 ± 0.039 vs. 0.965 ± 0.037, p = 0.015). No significant difference was found in the left hand.

These results suggested that the 2D:4D ratio is a risk factor of migraine and TTH and that the balance of prenatal estrogen and testosterone in utero may impact adult primary headache disorders.