Progress in the Pharmacotherapy of Menstrual Migraine

2011 ◽  
Vol 3 ◽  
pp. CMT.S6170 ◽  
Author(s):  
E. Anne MacGregor
Keyword(s):  
Clinical Trials ◽  
Menstrual Cycle ◽  
Prophylactic Treatment ◽  
Symptomatic Treatment ◽  
Menstrual Migraine ◽  
Therapeutic Options ◽  
Short Term ◽  
Neurological Condition ◽  
Prophylactic Drugs

Menstrual migraine is a common neurological condition reported to affect up to 60% of women with migraine. Most women manage migraine adequately with symptomatic treatment alone. However, in women with menstrual migraine, menstrual attacks are recognised to be more severe, last longer, and are less responsive to treatment compared with attacks at other times of the menstrual cycle. In these situations, prophylactic treatment may be necessary. Short-term perimenstrual and continuous prophylactic treatments have shown efficacy in clinical trials but none are licensed for menstrual migraine. This article reviews the evidence for acute and prophylactic drugs in the management of this condition and considers future therapeutic options.

Hypothalamus pituitary-ovarian axis in menstrual migraine: effect of dihydroergotamine retard prophylactic treatment

Cephalalgia ◽  
1983 ◽  
Vol 3 (1_suppl) ◽  
pp. 159-162 ◽  
Author(s):  
F. Facchinetti ◽  
G. Sances ◽  
A. Volpe ◽  
D. Sola ◽  
G. D'ambrogio ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Plasma Levels ◽  
Luteal Phase ◽  
Prophylactic Treatment ◽  
Menstrual Migraine ◽  
Ovarian Steroids ◽  
Control Subjects ◽  
Sono Stati ◽  
Before And After

LH, FSH, Prolactin (PRL), Estradiol (E) and Progesterone (P) plasma levels were measured in different periods of the menstrual cycle in 15 control subjects and in 9 women suffering from perimenstrual migraine before and after prophylactic treatment with 10 mg/day dihydroergotamine (DHE) retard. LH, FSH and PRL plasma levels were similar between patients and controls and were unaffected by DHE therapy. Migraineurs showed markedly reduced P levels in the entire luteal phase, concomitantly with higher E levels, leading to a P/E ratio significantly interfering with ovarian steroids secretion. These data indicate the presence of ovarian impairment in women suffering from perimenstrual migraine, whose symptoms could be successfully treated with DHE retard without interfering with the endocrine state. Les variations cicliques de LH, FSH, Prolactine (PRL) de la Estradiol (E) et de la Progesterone (P) ont ete evaluèes chez 15 subjets temoins et chez 9 femmes souffrant de la maladie migraineuse, en conditions de base et au cours d'un traitment prophilactique avec 10 mg par jour de Dihydroergotamine (DHE) rètard. LH, FSH et PRL etaient au meme niveau chez les temoins et les patients et n'ont pas ètè modifiès par le traitment avec DHE rètard; tandis que les taux plasmatiques de la P etaient rèduites et, au contraire, ceux de la E eatient elevèes pendant toute la phase luteale des migraineuses. Par consequence le rapport P/E les patientes etait significativement inferieur que chez les temoins. Le traitment avec la DHE rètard a presque totalement prevenue les accès migraineux, sans modifier le status normonal. Les femmes souffrant de maladie migraineuse au cours du cicle menstruel, notament dans la periode premenstruelle, montrent des affections de la secretion ovarienne qui doivent etre ancore expliquées. En tous cas las symptomatologie peut etre convenablement rèlevèe par le traitment prophilactique avec DHE rètard qui d'ailleur n'a aucune influence sur les secretions hypophisaires et ovariennes. I tassi plasmatici di LH, FSH, Prolattina (PRL), Estradiolo (E) e Progesterone (P) sono stati studiati nel corso del ciclo mestruale in 15 soggetti di controllo e in 9 pazienti affette da emicrania premestruale prima e dopo un trattamento profilattico con Diidroergotamina (DHE) ritardo (10 mg/die). LH, FSH e PRL sono risultati simili nei due gruppi e non ha mostrato variazioni in seguito al trattamento. Durante l'intera fase luteale, i tassi di P delle pazienti sono risultati significativamente ridotti, mentre quelli di E al contrario, erano più elevati, rispetto a quelli dei soggetti di controllo. La terapia con DHE ha pressoché abolito l'insorgenza degli attacchi emicranici, senza interferire con le concentrazioni di E e P. In conclusione, questi dati indicano che le pazienti affette da emicrania perimestruale presentano un'alterazione della funzione ovarica che resta da definire. Il trattamento profilattico conDHE ritardo però, è risultato efficacie nella abolizione delle crisi, senza interferire con le secrezioni ormonali.

Treatment of menstrual migraine

Cephalalgia ◽  
1997 ◽  
Vol 17 (20_suppl) ◽  
pp. 35-38 ◽  
Author(s):  
F Granella ◽  
G Sances ◽  
G Messa ◽  
M De Marinis ◽  
Gc Manzoni
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Menstrual Cycle ◽  
Ad Hoc ◽  
Acute Attack ◽  
Menstrual Migraine ◽  
Controlled Clinical Trials ◽  
Ergot Derivatives ◽  
Definition Of ◽  
Oestrogen Supplementation

Because of its pathophysiological and clinical peculiarities, true menstrual migraine (MM) (i.e. migraine starting exclusively between the days immediately before and immediately after the first day of the menstrual cycle) requires an ad hoc management different from that of other migraines. The paucity of well-conducted, controlled clinical trials and the lack of a universally accepted definition of MM have meant that the treatment of MM is still largely empirical. In our clinical practice, we adopt a sequential therapeutic approach, including the following steps: (i) acute attack drugs (sumatriptan, ergot derivatives, NSAIDs); (ii) intermittent prophylaxis with ergot derivatives or NSAIDs; (iii) oestrogen supplementation with percutaneous or transdermal oestradiol (100 Lig patches); (iv) antioestrogen agents (danazol, tamoxifen).

scholarly journals Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 14 (3) ◽  
pp. 280
Author(s):  
Rita Rebelo ◽  
Bárbara Polónia ◽  
Lúcio Lara Santos ◽  
M. Helena Vasconcelos ◽  
Cristina P. R. Xavier
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Pancreatic Ductal Adenocarcinoma ◽  
De Novo ◽  
Drug Repurposing ◽  
Metastatic Tumor ◽  
Therapeutic Options ◽  
Ductal Adenocarcinoma ◽  
Clinical Indication ◽  
Novel Treatments

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgently needed. Drug repurposing is a strategy for the development of novel treatments using approved or investigational drugs outside the scope of the original clinical indication. Since repurposed drugs have already completed several stages of the drug development process, a broad range of data is already available. Thus, when compared with de novo drug development, drug repurposing is time-efficient, inexpensive and has less risk of failure in future clinical trials. Several repurposing candidates have been investigated in the past years for the treatment of PDAC, as single agents or in combination with conventional chemotherapy. This review gives an overview of the main drugs that have been investigated as repurposing candidates, for the potential treatment of PDAC, in preclinical studies and clinical trials.

scholarly journals Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Peter Witters ◽  
Andrew C. Edmondson ◽  
Christina Lam ◽  
Christin Johnsen ◽  
Marc C. Patterson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Randomized Study ◽  
Short Term ◽  
Double Blind ◽  
Natural History Study ◽  
Natural History Studies ◽  
Carbohydrate Deficient Transferrin ◽  
Spontaneous Improvement

AbstractA recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study’s conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients’ lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.

Physiology of the Menstrual Cycle

Cephalalgia ◽  
2000 ◽  
Vol 20 (3) ◽  
pp. 148-154 ◽  
Author(s):  
S D Silberstein ◽  
G R Merriam
Keyword(s):  
Life Cycle ◽  
Menstrual Cycle ◽  
Sex Hormones ◽  
Neuronal Activity ◽  
Premenstrual Syndrome ◽  
Contraceptive Use ◽  
Menstrual Migraine ◽  
Normal Female ◽  
Receptor Density ◽  
Cns Neurons

The normal female life cycle is associated with a number of hormonal milestones: menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex hormones. All these events and interventions alter the levels and cycling of sex hormones and may cause a change in the prevalence or intensity of headache. The menstrual cycle is the result of a carefully orchestrated sequence of interactions among the hypothalamus, pituitary, ovary, and endometrium, with the sex hormones acting as modulators and effectors at each level. Oestrogen and progestins have potent effects on central serotonergic and opioid neurons, modulating both neuronal activity and receptor density. The primary trigger of menstrual migraine appears to be the withdrawal of oestrogen rather than the maintenance of sustained high or low oestrogen levels. However, changes in the sustained oestrogen levels with pregnancy (increased) and menopause (decreased) appear to affect headaches. Headaches that occur with premenstrual syndrome appear to be centrally generated, involving the inherent rhythm of CNS neurons, including perhaps the serotonergic pain-modulating systems.

Altered Serotonergic Activity in Women with Dysphoric Premenstrual Syndromes

1993 ◽  
Vol 23 (1) ◽  
pp. 1-27 ◽  
Author(s):  
Uriel Halbreich ◽  
Henry Tworek
Keyword(s):  
Treatment Outcome ◽  
Menstrual Cycle ◽  
Luteal Phase ◽  
Symptomatic Treatment ◽  
Gonadal Hormones ◽  
Interactive System ◽  
Library Search ◽  
Serotonergic Activity ◽  
Late Luteal Phase

Objective: Dysphoric Premenstrual Syndromes (PMS) are quite prevalent and in some women they are severe enough to warrant treatment. Their pathophysiology is still unknown, despite increased interest and research. Here we review the possible role of serotonin in the multidimensional interactive pathophysiology of PMS. Method: Over 170 articles are reviewed. An extensive library search has been conducted and articles are included because of their relevance to: 1) the phenomenology of PMS; 2) the putative association of serotonergic (5-HT) activity with syndromes that occur premenstrually; 3) changes in 5-HT activity along the menstrual cycle, especially the late luteal phase; 4) influence of gonadal hormones on serotonergic functions; 5) endocrine strategies for assessment of 5-HT abnormalities; and 6) treatment studies of PMS with serotonergic agonists. Results and Conclusions: The data presented here suggest that post-synaptic serotonergic responsivity might be altered during the late-luteal-premenstrual phase of the menstrual cycle. Some serotonergic functions of women with PMS might be altered during the entire cycle and be associated with a vulnerability trait. It is hypothesized that gonadal hormones might cause changes in levels of activity of 5-HT systems as part of a multidimensional interactive system. Strategies to evaluate 5-HT activities in the context of the menstrual cycle are discussed—leading to the conclusion that the most promising approach is active stimulation with specific post-synaptic serotonin agonists. Treatment outcome studies of some imperfect compounds that are currently applied as a symptomatic treatment of PMS support the notion that 5-HT is involved in the pathophysiology of these syndromes.

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