Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval.

BACKGROUND: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. METHODS: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 microg of ethinyl estradiol and 150 microg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. RESULTS: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P < 0.01) and a lack of cortisol response (F = 5.8; P < 0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P < 0.01) and cortisol responses (F = 18.9; P < 0.001) against placebo and positively affected the duration (P < 0.001), the number of hours in which pain intensity prohibits daily activity (P < 0.001), the episodes of vomiting (P < 0.001) and the consumption of analgesics (P < 0.001). CONCLUSIONS: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.

Role of testosterone in feminine sexuality.

Gonadal steroids play a crucial role in maintaining the anatomical and functional integrity of all the structures involved in feminine sexual response. While the role of estrogens on the activity of neuroendocrine circuitries and on the trophism of genital organs has been well established, the contribution of androgens to female physical and mental well-being is still a matter of debate. Recent studies reconsidered the sources, production rates, circulating concentrations and regulatory mechanism of the major androgen precursors and androgens in women throughout the reproductive life span, as well as the wide variety of actions at the target tissues. Collectively, these reports support the therapeutic use of androgens in women, mainly to cure sexual dysfunctions, one of the consequences of menopause.

GABAergic hippocampal neurons resistant to ischemia-induced neuronal death contain the Ca2(+)-binding protein parvalbumin.

Bilateral transient occlusion of carotid arteries in gerbils for 7 min results in delayed neuronal cell death in hippocampal field CA1. Local gamma-aminobutyric acid (GABA)ergic neurons survive the ischemic insult. Here we show that interneurons in gerbil hippocampus are parvalbumin-immunoreactive, that they contain the GABA-synthetizing enzyme glutamic acid decarboxylase (GAD), and that they are resistant to the effects of ischemia, being present up to 28 days after the insult. It might be concluded that the presence of the Ca2+-binding protein parvalbumin protects the GABAergic neurons from the deleterious consequences of ischemia-induced excitotoxin-mediated Ca2+-influx.