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Reduction of Prolactin Associated With Pain Relief, Headache Study Finds

Alison Rodriguez
Migraine was the most common type of headache in patients with hyperprolactinemia.
In the majority of hyperprolactinemic headache patients, reduction in prolactin (PRL) was followed by cessation or relief of pain, according to a recent study.

The research, published by Arquivos de Neuro-Psiquiatria, involved 69 hyperprolactinemic patients.

Characteristics and presence of headache were evaluated before and after hyperprolactinemia treatment. The patients completed a neurological examination and a questionnaire related to the headache and its clinical characteristics, including frequency and intensity, presence of associated symptoms, family history, and the use of medication to treat or prevent headache. The patients were separated into 2 groups based on whether they were experiencing headache. Six months following the original evaluation, the patients were assessed again in terms of maintenance and the pattern of headache, with the medication remaining the same.

According to the results, headache was reported by 65.2% of patients, independent of the etiology of hyperprolactinemia and the migraine phenotype was the most prevalent, at 66.6%. Additionally, the results suggested that the first line of treatment of hyperprolactinemia was dopaminergic agonists. Furthermore, in the last evaluation, PRL level under treatment was within the reference range in 54.7% of the cases and it was observed complete or partial resolution of headache in 75% of cases.

“Prolactin is associated to immune modulation, osmoregulation, personal behavior and metabolism, and has been implicated in the etiology of headache,” the authors explained. “The hypothalamus, vital to adjust PRL levels, could be involved in the onset of headache, as suggested by the occurrence of premonitory symptoms related to hypothalamic dysfunction in migraine (polyuria, polydipsia, food craving, mood disturbance), by the relation between menstrual cycle and migraine; and by the involvement of the trigeminovascular system and the presence of hypothalamic nociceptive peptides as neuropeptide Y, vasoactive intestinal polypeptide, among others.”

In cases with complete headache resolution, the researchers found that the median reduction of PRL levels was 89%;  in cases with partial headache resolution, PRL levels dropped 86%.

“We suggest that in hyperprolactinemic patients the reduction (not necessarily normalization) in the PRL level, regardless of the therapeutic modality, is closely related to the improvement or disappearance of headache,” the authors concluded. “To be confirmed, this fact should be taken into account in the individual therapeutic approach, since it suggests the necessity of a more rigorous control of the PRL levels also in those patients who did not have PRL secreting macroadenomas, in addition to reaching the required level to avoid clinical repercussion in the gonadal axis.”

The researchers concluded that these results support previous hypotheses from other studies, that the positive effect on headache is independent of PRL normalization but is related to PRL reduction.


Oliveira M, Barea L, et al. Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients [published online: January 13, 2020]. Arquivos de Neuro-Psiquiatria. doi: 10.1590/0004-282x20190143.

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