Prenatal oestrogen-testosterone balance as a risk factor of migraine in adults

J Headache Pain. 2021 Oct 7;22(1):119. doi: 10.1186/s10194-021-01326-3.

Abstract

Background: Migraine is a common neurological disease with extremely debilitating, but fully reversible symptoms. Women suffer from migraine more often than men. It was assumed that fluctuation of oestrogen level during menstrual cycle is one of many factors responsible for more frequent migraine attacks. The second-to-fourth digit ratio (2D:4D) is considered as an indicator of prenatal sex steroids. Balance of prenatal androgens (testosterone) and oestrogen has been studied in numerous diseases that are affected by hormones. However, the relationship between migraine and the sex steroids balance in prenatal development is still unexplained. The aim of this paper is to provide an evidence of relationship between prenatal oestrogen and testosterone exposure following 2D:4D digit ratio, and migraine prevalence in adults.

Methods: We examined a group of 151 adults (33 males, 118 females) with migraine and a control group of 111 adults (45 males, 66 females). 2D:4D digit ratio of both hands was measured using sliding Vernier calliper.

Results: Significant differences were found in the right hand. Female migraineurs had lower value of 2D:4D ratio than the control group and the right 2D:4D was lower than left 2D:4D (Δ2D:4D), suggesting prenatal testosterone dominance. The opposite relationship was observed in males. Male migraineurs had higher value of 2D:4D ratio and Δ2D:4D was greater than the control group, suggesting prenatal oestrogen dominance.

Conclusions: Our results suggest that depending on sex, different proportion of prenatal sex steroids might be a risk factor of migraine in adults. Women with migraine were presumably exposed in prenatal life to higher testosterone levels relative to oestrogen, while men with migraine were probably exposed in prenatal life to higher levels of oestrogen relative to testosterone.

Keywords: 2D:4D; Digit ratio; Intrauterine development; Migraine; Oestrogen; Prenatal; Sex hormones; Sex steroids; Testosterone.

MeSH terms

  • Adult
  • Estrogens
  • Female
  • Gonadal Steroid Hormones
  • Humans
  • Male
  • Migraine Disorders* / epidemiology
  • Risk Factors
  • Testosterone*

Substances

  • Estrogens
  • Gonadal Steroid Hormones
  • Testosterone