Rio de Janeiro Brazil Clomiphene treatment may be effective in refractory episodic and chronic cluster headache Disclosures I do not have any relevant financial relationships with a commercial interest ID: 1043955
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2. Maria Eduarda Nobre, MD, PhDRio de Janeiro, BrazilClomiphene treatment may be effective in refractory episodic and chronic cluster headache
3. Disclosures:I do not have any relevant financial relationships with a commercial interestNobre ME et al. Arq Neuropsiquiatr 2017;75(9):620-624Nobre ME et al. Arq Neuropsiquiatr 2017;75(9):620-624
4. Learner Outcomes:Describe strategies to treat refractory cluster headache patientsDefine patients who may benefit from clomiphene treatmentConduct hormonal treatment safely and tolerably minimizing possible side effectsNobre ME et al. Arq Neuropsiquiatr 2017;75(9):620-624
5. Introduction:Cluster headache is certainly the most painful and incapacitating of primary headaches, particularly for patients who suffer from long bouts or chronic form.Nobre ME et al. Arq Neuropsiquiatr 2017;75(9):620-624
6. Chronic cluster headaches affect nearly 10% of patients.These patients usually need one or two preventive drugs such as corticosteroids, verapamil, and lithium carbonate, among others. The need for high doses is common, often with many side effects.In addition, about 1% of patients become refractory to treatment. Nobre ME et al. Arq Neuropsiquiatr 2017;75(9):620-624
7. Objective: To describe the clinical response of 15 refractory episodic and chronic cluster headache patients with clomiphene. Nobre ME et al. Arq Neuropsiquiatr 2017;75(9):620-624Nobre ME et al. Arq Neuropsiquiatr 2017;75(9):620-624
8. The significant drop in plasmatic testosterone levels during bouts in cluster headache patients was the first evidence of hypothalamic involvement.May A, Leone M. Update on cluster headache. Curr Opin Neurol 2003;16: 333–340.Romiti A, Martelleti P, Gallo MF, et al. Low plasma testosterone levels in cluster headache. Cephalalgia 1983; 3:41-44.
9. Hypothalamic Dysfunction
10. These findings in relation to cluster headaches drive forward new surgical treatment with stereotactic stimulation of the posterior inferior hypothalamus, particularly for refractory chronic cluster headaches patients Leone M, Franzini A, Broggi G, Bussone G. Hypothalamic deep brain stimulation for intractable chronic cluster headache: a 3-year follow-up. Neurol Sci. 2003;24:143-5.
11. The Hypothalamic-Pituitary Axis
12. The Hypothalamic-Pituitary Axis The hypothalamus can be considered the coordinating center of the endocrine system. The connection with the pituitary gland lead a hormones releases that influence most endocrine systems in the body. There are two parts: Neurohypophysis Adenohypophysis
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14. Clomiphene is a non-steroid agent with estrogenic and anti-estrogenic properties. It competes with endogenous estrogen at hypothalamic estrogen receptors preventing the hypothalamus from recognizing sufficient levels and decreasing the secretion of GnRH (Gonadotropin-releasing hormone), therefore, without negative feedback. Without interruption, the hypothalamus continues stimulating the pituitary gland by means of the increase in GnRH secretion. The pituitary increases the levels of FSH and LH and these acts on the gonads stimulating the ovaries and testicles to produce estrogens and androgens.
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16. We report the clinical response of 8 ECH and 7 CCH to clomiphene treatment. These cases were refractory to current prophylactic medication. Clomiphene was prescribed in morning doses of 300 mg for 2 days, 100 mg for 9 days, followed by 50 mg. The research project was approved by the Ethics in Research Committee (nº 2.149.356). All individuals were informed about the purpose of the research and signed the informed consent document.
17. Main analysis:pain-free : time until pain-free after starting clomiphene treatment, still in the cluster periodcomplete remission: time until complete remission after starting clomiphene treatment, characterizing the end of the cluster periodtime between total absence of pain and complete remissionIncidence rates were calculated and the distribution of time elapsed until up until each successful event was described by means of respective quartiles. The accumulated probabilities up until each successful event were estimated based on the Kaplan-Meier method.
18. Results: Ten men and 5 women were studied. 7 were chronic and 8 episodic. Average age was 40.4 years old. The average time of pain before clomiphene was 41.7 months. Total testosterone was below in 3 patients and on the lower limit in all others. After the use of clomiphene there was an increase in testosterone for normal limits. Clomiphene was used for a minimum of 45 days and a maximum of 180 days. Average treatment time was 104 days. There were no significant side effects.
19. Results:pain-free : The average time to being pain-free was 15 days
20. Results:complete remission: The average time from the start of the treatment with clomiphene up until cluster remission was 60 days.
21. Results:3) time between total absence of pain and complete remission: After the disappearance of pain, the average time until cluster remission was 26 days.
22. ConclusionsOur study suggests clomiphene could be used for chronic and episodic cluster headache, considerably improving their quality of lifeIt was effective and well toleratedIt broke the headache cycle and turned chronic pattern into episodic in all patientsIf no contraindications (prostatic disease, polycystic ovarian, cancer, etc), clomiphene could be indicated for episodic and chronic casesClomiphene should be tried before surgeryPatients should only be considered refractory after clomiphene treatment
23. Thank you!!