Considerations for hormonal therapy in migraine patients: a critical review of current practice

Abstract

Introduction: Migraine, a neurovascular headache disorder, is a leading cause of disability worldwide. Within the multifaceted pathophysiology of migraine, hormonal fluctuations play an evident triggering and exacerbating role, pointing toward the need for identification and proper usage of both existing and new hormonal targets in migraine treatment.

Areas covered: With a threefold higher incidence of migraine in women than in men, the authors delve into sex hormone-related events in migraine patients. A comprehensive overview is given of existing hormonal therapies, including oral contraceptives, intrauterine devices, transdermal and subcutaneous estradiol patches, gnRH-agonists, oral testosterone, and 5α reductase inhibitors. The authors discuss their effectiveness and risks, noting their suitability for different patient profiles. Next, novel evolving hormonal treatments, such as oxytocin and prolactin, are explored. Lastly, the authors cover hormonal conditions associated with migraine, such as polycystic ovary syndrome, endometriosis, and transgender persons receiving gender affirming hormone therapy, aiming to provide more personalized and effective solutions for migraine management.

Expert opinion: Rigorous research into both existing and new hormonal targets, as well as the underlying pathophysiology, is needed to support a tailored approach in migraine treatment, in an ongoing effort to alleviate the impact of migraine on individuals and society.

Keywords: Females; males; menopause; menstruation; migraine; pharmacology; sex hormones; treatment.

Figure 1.

Menstrual cycle and migraine frequency. In this figure, serum levels of hormones and their effect on the endometrium over the course of the menstrual cycle are depicted, as well as the concurrence of fluctuations in the incidence of migraine attacks in women with menstrual migraine. Lasting around 28 days, the cycle starts with the release of FSH, stimulating the growth of ovarian follicles. The maturation of these follicles leads to an increasing production of estradiol, which triggers a surge in LH and causes ovulation. After ovulation, the ruptured follicle transforms into the corpus luteum which produces progesterone and prepares the endometrium for possible fertilization. If fertilization does not occur, the corpus luteum breaks down progesterone and estradiol levels drop, which triggers menstruation and the start of a new menstrual cycle [23]. The decline of estradiol, also referred to as estradiol-withdrawal, is also thought to precipitate a migraine attack without aura in women with menstrual migraine [24]. The figure is based on the data from Martin et al. [25] and MacGregor et al. [26] and was created using BioRender.

Figure 2.

Hormonal treatment of migraine, their advantages and disadvantages. this figure provides an overview of existing hormonal therapies, their benefits, risks and potential challenges. Figure was created using BioRender.