Pubertal Hormones: Influence on Migraine in Girls

Mechanisms involved in balancing reproductive hormones in girls may influence the patterns of migraine headache onset.

Mechanisms involved in balancing reproductive hormones in girls may influence the patterns of migraine headache onset, according to a study recently published in Cephalgia.1 Headache patterns observed directly before and after puberty indicated correlations with greater variations in the urine levels of specific ovarian hormones.

For this pilot study, the investigators recruited 34 girls from the Cincinnati Children’s Headache Center from October 2011 to November 2012. The girls all met International Classification of Headache Disorder-II (ICHD-II) criteria for migraine with or without aura, or chronic migraine. The participants were stratified into 3 age groups: pre-pubescent (8 to 11 years; n = 12), pubescent (12 to 15 years; n = 11), and post-pubescent (16 to 17 years; n = 11). They all completed daily headache diaries and provided daily urine samples to track hormonal fluctuations.

A total of 1183 headaches were experienced on 3485 diary days, for a rate of 33.9%. The greatest headache frequency was in post-pubescent girls (40.6%), followed by pubescent girls (34.7), and pre-pubescent girls (24.8%). This significant difference in headache frequency (P <.001) was partially explained by the greater degree of hormonal fluctuations recorded in the older participants compared with the younger participants.

Urinary levels of pregnandiol glucuronide (PdG) corresponded with the number of headache onset days in all participants — although stage of puberty seemed to be a strong factor — after controlling for age and/or pubertal development scores (PDS). The probability of headache onset days in response to elevated progesterone increased in pre-pubescent girls and decreased in post-pubescent girls, with little effect in pubescent girls. The authors suggested that higher PdG levels at a younger age pointed to an increased risk for new onset headache before menarche. “There seems to be a graded effect to progesterone that is dependent on age,” they wrote.

The study found that increases in urine progesterone levels were more predictive of headache onset days than measures of estrogen, contrary to evidence pointing to declining estrogen during menstruation as the potential trigger for menstrual migraine attacks in adult women.2 This signified 2 main possibilities: 1) that the degree of estrogen decline in adolescence is not substantial enough to trigger a migraine attack, or 2) that the effect is cumulative over many years of repeated exposure to sudden declines of estrogen. It was also conceivable, the researchers acknowledged, that the sample size of the study was not large enough to detect a significant effect of estrogen in girls with migraine.

A univariate association between PdG and headache severity was detected, although the effect size was small, and was achieved on only 1 day in the entire cohort. The authors therefore concluded it was unlikely that ovarian hormones exert any significant effects on headache severity.

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  1. Martin VT, Allen JR, Houle TT, et al. Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: an observational cohort study. Cephalgia 2017; Jan 1:333102417706980. doi: 10.1177/0333102417706980. [Epub ahead of print]
  2. Somerville BW. The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 1972;22:355–365.
  3. Lipton RB, Stewart WF, Cady R, et al. 2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: Results of the Spectrum Study. Headache 2000;40:783–791.