Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.