Background & Aims

Migraine is a highly prevalent and disabling disorder, affecting ?15% of the global population [1]. Migraine prevalence varies based on sex and age and is higher in females, often manifesting during adolescence thus, migraine onset may be related to changes in sex hormone levels during adolescence/puberty. Testosterone was found to have an antinociceptive effect in animals and humans in both males and females [2-5]. Consistent with this antinociceptive effect, adult patients with migraine, have overall lower testosterone levels than healthy controls [7]. Furthermore, testosterone treatment reduces clinical pain and experimental pain responses [6]. The aim of this study is to examine differences in sex hormone levels between adolescents with vs. without migraine and the relationships between sex hormone levels and migraine severity.

Methods

Adolescent girls with (n=13, mean age=12.7?1.0) and without migraine (n=13, mean age=13.5?1.3) partied in this study. Participants completed surveys about their health, puberty, and migraine, and a blood draw for the analysis of testosterone, estradiol, dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), dihydrotestosterone (DHT), androstenedione, and prolactin (PRL) levels using mass spectrometry. Participants were matched according to pubertal stage. T-tests were run between the groups for the various sex hormones levels. In addition, regression models were conducted to assess the role of group on sex hormones levels, controlling for time of blood draw, menstruation phase, and age. To note if any relationship existed between sex hormones and migraine frequency and disability, univariate correlations were run. This was repeated using regression models and controlling for time of blood draw, age, and menstrual phase.

Results

For all sex hormones, no significant differences were seen between the groups. Controlling for the time of blood draw, menstruation, and age did not change the results. Assessing the relationships between sex hormone levels and migraine severity, higher PRL was found to be correlated with higher headache frequency (last 90 days, r=0.736, p=0.004) and disability (PedMIDAS, r=0.572, P=0.041). After controlling for time of blood draw, menstrual phase, and age, only the relationship between PRL with headache frequency remained significant (F (1, 1) = 11.931, p=0.011).

Conclusions

These preliminary data show no differences in sex hormone levels between healthy adolescents and those with migraine, which may contradict some of the results from studies in adult participants. Thus, it is possible that migraine may not impact the normative hormonal changes during puberty. In addition, higher prolactin levels were related to higher headache frequency and disability in adolescents with migraine which could suggest that prolactin may have a pronociceptive effect which is in line with animal studies [8].

References

[1] Abu-Arefeh I, Russell G. Prevalence of headache and migraine in schoolchildren. BMJ (Clinical research ed) 1994;309(6957):765-769.

[2] Aloisi AM, Ceccarelli I, Fiorenzani P. Gonadectomy affects hormonal and behavioral responses to repetitive nociceptive stimulation in male rats. Ann N Y Acad Sci 2003;1007:232-237.

[3] Aloisi AM, Ceccarelli I, Fiorenzani P, De Padova AM, Massafra C. Testosterone affects formalin-induced responses differently in male and female rats. Neurosci Lett 2004;361(1-3):262-264.

[4] Fischer L, Clemente JT, Tambeli CH. The protective role of testosterone in the development of temporomandibular joint pain. J Pain 2007;8(5):437-442.

[5] Gaumond I, Arsenault P, Marchand S. Specificity of female and male sex hormones on excitatory and inhibitory phases of formalin-induced nociceptive responses. Brain Res 2005;1052(1):105-111.

[6] Nahman-Averbuch H, Shefi T, Schneider VJ, 2nd, Li D, Ding L, King CD, Coghill RC. Quantitative sensory testing in patients with migraine: a systematic review and meta-analysis. Pain 2018;159(7):1202-1223.

[7] Patacchioli FR, Monnazzi P, Simeoni S, De Filippis S, Salvatori E, Coloprisco G, Martelletti P. Salivary cortisol, dehydroepiandrosterone-sulphate (DHEA-S) and testosterone in women with chronic migraine. J Headache Pain 2006;7(2):90-94.

[8] Mecklenburg J, Wangzhou A, Hovhannisyan AH, Barba-Escobedo P, Shein SA, Zou Y, Weldon K, Lai Z, Goffin V, Dussor G, Tumanov AV, Price TJ, Akopian AN. Sex-dependent pain trajectories induced by prolactin require an inflammatory response for pain resolution. Brain Behav Immun. 2022 Mar.

Presenting Author

Joel Brown

Poster Authors

Joel Brown

RN

Washington University in St. Louis

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Migraine