Different effects of tibolone and low-dose EPT in the management of postmenopausal women with primary headaches.

OBJECTIVE: The present randomized prospective study aimed to compare the effect of tibolone (T) with conventional low-dose estrogen-progestogen therapy (EPT) administered in a combined continuous regimen on the course of primary headaches in postmenopausal women requesting hormone therapy (HT) for climacteric complaints. DESIGN: Forty women presenting for clinical evaluation of headache (migraine without aura and episodic tension-type headache) were enrolled. The observational period lasted 7 months during which women kept a diary of the clinical characteristics of headache attacks and analgesic use. Climacteric symptoms and both anxiety and depression were also measured. After a 1-month run-in period, women received two different HT regimens: 1 mg 17beta-estradiol + 0.5 mg norethisterone acetate (EPT) or 2.5 mg T. Follow-up evaluations were planned after 3 and 6 months of treatment. RESULTS: Although T did not affect the number of days with migraine without aura, it significantly reduced the number of hours during which pain intensity prohibited daily activities (P < 0.001) and the number of analgesics (P < 0.001) after 3 months. Conventional low-dose EPT administered in a combined continuous regimen was confirmed to have a mild, but negative, effect on the course of migraine without aura by increasing the number of days with head pain (P < 0.001) and the number of analgesics (P < 0.001). Interestingly, both treatments were effective in the management of episodic tension-type headache, significantly reducing the number of days with head pain, severity, and analgesic consumption. CONCLUSIONS: In postmenopausal headache sufferers, analgesics are more effective in alleviating severe head pain when women are treated with T in comparison with low-dose EPT for climacteric complaints.

Hormonal management of migraine at menopause.

In this review, we underline the importance of linking migraine to reproductive stages for optimal management of such a common disease across the lifespan of women. Menopause has a variable effect on migraine depending on individual vulnerability to neuroendocrine changes induced by estrogen fluctuations and on the length of menopausal transition. Indeed, an association between estrogen 'milieu' and attacks of migraine is strongly supported by several lines of evidence. During the perimenopause, it is likely to observe a worsening of migraine, and a tailored hormonal replacement therapy (HRT) to minimize estrogen/progesterone imbalance may be effective. In the natural menopause, women experience a more favourable course of migraine in comparison with those who have surgical menopause. When severe climacteric symptoms are present, postmenopausal women may be treated with continuous HRT. Even tibolone may be useful when analgesic overuse is documented. However, the transdermal route of oestradiol administration in the lowest effective dose should be preferred to avoid potential vascular risk.

Neuroendocrine response to the serotonin agonist M-chlorophenylpiperazine in women with menstrual status migrainosus.

To assess the neuroendocrine correlates of menstrual status migrainosus (MSM) and menstrual migraine (MM), we evaluated the prolactin (PRL) and cortisol responses to the direct central serotoninergic (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) administered orally (0.5 mg/kg) during the follicular (FP: +6, +8) and luteal phases (LP: -4, -6) of the same menstrual cycle. Ten women with MSM (migraine attacks occurring within 2 days of the onset of menstrual bleeding but lasting more than 72 h) and 9 women with MM (migraine occurring within 2 days of the onset of menstrual bleeding with a typical duration of attacks) were studied. Six healthy women served as controls. Blood samples were taken at times -30, 0 and every 30 min over 4 h. Statistical analysis was performed using MANOVA followed by Duncan's post hoc comparisons. We found that the PRL response to the m-CPP test was significantly blunted in MSM compared with MM and controls in both phases of the menstrual cycle (F = 4.6; p < 0.001). Indeed, the PRL area under the curve (AUC) after m-CPP was higher in both MM and controls compared with MSM (F = 12.7; p < 0.001). The m-CPP-induced cortisol response was absent in MSM compared with MM and controls in both FP and LP (F = 4.1; p < 0.001). On the other hand, the pattern of the plasma cortisol response to m-CPP was similar in MM and controls throughout the menstrual cycle. In addition, the basal plasma cortisol levels were significantly higher in MSM compared with controls (p < 0.001) and MM (p < 0.001) during FP, but not in LP, and progressively decreased over time. Thus, no significant effect of the menstrual cycle phase and diagnosis on the cortisol AUC was found, while a significant diagnosis effect (F = 25.6; p < 0.001) on %delta(max) plasma cortisol levels was evident and consistent with the lack of cortisol response to m-CPP in MSM during the FP and LP compared with MM and controls. A derangement in central 5-HT control of pituitary PRL, and even more so in cortisol release, is present in women with MSM, but not with MM, regardless of the phase of the menstrual cycle, suggesting the involvement of some 5-HT(1) and 5-HT(2) receptor subtypes in the occurrence of extremely severe migraine attacks triggered by menstruation.