㈼-2-15 AF

月経時片頭痛の診断と治療

OBJECTIVE: To define the term "menstrual" migraine and to determine the prevalence of "menstrual" migraine in women attending the City of London Migraine Clinic . DESIGN: Women attending the clinic were asked to keep a record of their migraine attacks and menstrual periods for at least 3 complete menstrual cycles. RESULTS: Fifty-five women completed the study. "Menstrual" migraine was defined as "migraine attacks which occur regularly on or between days -2 to +3 of the menstrual cycle and at no other time". Using this criterion, 4 (7.2%) of the women in our population had "menstrual" migraine. All 4 women had migraine without aura. A further 19 (34.5%) had an increased number of attacks at the time of menstruation in addition to attacks at other times of the cycle. Eighteen (32.7%) had attacks occurring throughout the cycle but with no increase in number at the time of menstruation. Fourteen (25.5%) had no attacks within the defined period during the 3 cycles studied. DISCUSSION: A small percentage of women have attacks only occurring at the time of menstruation, which can be defined as true "menstrual" migraine. This group is most likely to respond to hormonal treatment. The group of 34.5% who have an increased number of attacks at the time of menstruation in addition to attacks at other times of the month could be defined as having "menstrually related" migraine and might well respond to hormonal therapy. The 32.7% who have attacks throughout the menstrual cycle without an increase at menstruation are unlikely to respond to hormonal therapy. The 25.5% who do not have attacks related to menstruation almost certainly will not respond to hormonal therapy.

文献 PubMed−ID

エビデンスレベル

文献タイトル (日本語)

片頭痛と月経：パイロット試験

“月経”片頭痛を定義し， the City of London Migraine Clinicに通院中の女性患者における“月経”片頭痛の頻度を確認する．

研究デザイン

３回以上の月経周期に渡って，片頭痛発作と月経期間を記録する．

City of London Migraine Clinic.

17-50歳の女性片頭痛患者55例（前兆のある片頭痛11例，前兆のない片頭痛44例）

月経１４日前を排卵日とした．

片頭痛発作は月経１日目に明らかに増加したが，排卵日には増加しなかった．６例（ 10.9％）は月経時にのみ片頭痛発作が起こった．これらのうち４例（7.2％）は３回の月経周期で，月経２日前から月経３日目のみに発作があった．残りの２例は月経４日前，月経４日目にも発作がみられた．１例のみ月経２日前から月経３日目までと排卵日に発作があった．これらの７例は全例前兆のない片頭痛であった．多くの患者は月経以外のときにも片頭痛発作があった．37例（67.3％）は月経３周期を通してすべての時期に発作があった．そのうち19例（34.5％）は「月経片頭痛」と定義された期間（月経２日前から月経３日目）に発作が増加したが，18例（32.7％）はこの期間に増加せず．14例（25.5％）は３周期を通してこの期間に１回も発作がなかった．

1.「月経時」片頭痛は7.2％
2.「月経関連」片頭痛は34.5％
3.月経周期のいずれの時期にも片頭痛が起こるもの32.7％
4.月経時に片頭痛発作なし25.5％
「月経時片頭痛」と「月経関連片頭痛」の２つの用語の定義を提案した．

4) Loder E, Silberstein SD , Abu-Shakra S, Mueller L, Smith T. 　 Efficacy and tolerability of oral zolmitriptan in menstrually associated 　 migraine: a randomized, prospective, parallel-group, double-blind, 　 placebo-controlled study. Loder E, Silberstein SD , Abu-Shakra S, 　 Mueller L, Smith T.
論文抄録	BACKGROUND: Approximately 60% of female migraineurs report experiencing migraine in association with menstruation, while 7% to 25% experience attacks almost exclusively with menstruation. OBJECTIVE: To examine the efficacy and tolerability of oral zolmitriptan in the acute treatment of menstrually associated migraine. In this study, menstrually associated migraine was defined as migraine that consistently occurred from 72 hours before to 5 days after onset of menses. Methods.-Participants were women with regular menstrual cycles, aged 18 to 55 years, who had experienced migraine with at least two thirds of prior menstrual cycles. Subjects were randomized to treat one attack per menstrual cycle for 3 months with either zolmitriptan or placebo. Treatment was intensity based: mild migraines were treated with half of a 2.5-mg zolmitriptan tablet, moderate migraines were treated with zolmitriptan 2.5 mg, and severe migraines were treated with 5 mg (two 2.5-mg tablets) of zolmitriptan, or placebo. RESULTS: Of the 579 women enrolled in the study, 260 were treated with zolmitriptan and 251 were assigned placebo. Twelve hundred thirty-two attacks were treated, and a 2-hour headache response was achieved in 48% of zolmitriptan-treated attacks as compared with 27% of placebo-assigned attacks (P <.0001). Zolmitriptan was superior to placebo in achieving a headache response as early as 30 minutes (18% versus 14%, P=.03) and at 1 hour (33% versus 23%, P <.001). Drug-related adverse events were reported in 16% of subjects receiving zolmitriptan and 9% of subjects receiving placebo. CONCLUSION: Oral zolmitriptan exhibits efficacy and good tolerability in the treatment of menstrually associated migraine. Improvement over placebo was observed as early as 30 minutes following treatment.
文献 PubMed−ID	14756849
エビデンスレベル	㈵ b
文献タイトル (日本語)	月経関連片頭痛におけるゾルミトリプタンの効果と忍容性：無作為，前向き，平行，二重盲検，プラセボ対照試験
目的	月経関連片頭痛の急性期治療における経口ｿﾞﾙﾐﾄﾘﾌﾟﾀﾝの効果と忍容性
研究デザイン	無作為，前向き，平行，二重盲検，プラセボ対照試験
研究施設	米国とカナダの 18 施設
対象患者	規則正しい月経周期を持つ 18〜55歳までの女性片頭痛患者579例．
介入	月経開始 72時間前から開始後５日までの期間に起こった片頭痛を月経関連片頭痛とした．３ヶ月間で，１月経周期につき１回の発作を治療．軽度の発作には 2.5mgゾルミトリプタン1/2錠，中等度の発作には2.5mgゾルミトリプタン1錠，重度の発作に2.5mgゾルミトリプタン2錠またはプラセボを投与．
主要評価項目とそれに用いた統計学的手法	服用２時間後の頭痛改善度（中等度・重度→軽度・頭痛なし，軽度の痛み→痛みなし） 2-sided test with a significance level of .50
結果	２時間後の頭痛改善率はゾルミトリプタン群（ 48%）がプラセボ群（27%）に比し，有意に高かった（p<.0001）．ゾルミトリプタンは30分後，１時間後の頭痛改善度もプラセボに比し有意に高かった．有害事象の発現率はゾルミトリプタン16%，プラセボ9%であった．
結論	経口ゾルミトリプタンは月経関連片頭痛の治療に有効で忍容性が高く，服用後 30分後にプラセボを上回る効果が確認された．
作成者	五十嵐久佳
備考	Multicenter Study Randomized Controlled Trial

5) Silberstein SD, Massiou H, Le Jeunne C, Johnson-Pratt L, McCarroll 　 KA, Lines CR. Rizatriptan in the treatment of menstrual migraine. 　 Obstet Gynecol. 2000;96:237-42.
論文抄録	OBJECTIVE: To determine the efficacy of oral rizatriptan 10 mg and 5 mg for treating menstrually associated migraine attacks. METHODS: Data from two large clinical trials with identical designs were included in a retrospective analysis. The studies were randomized, double-masked, placebo-controlled, incomplete block, two-period, crossover designs. Women with migraines were randomly assigned to one of five treatment sequences for the treatment of two migraine attacks. Only data from the first attack in women with migraines who were treated with rizatriptan or placebo were included in the analysis. A menstrually associated attack was defined as one that occurred within 3 days before or after the onset of the last menstrual period. RESULTS: In the subgroup of 335 women with menstrually associated migraine, rizatriptan was effective compared with placebo. At 2 hours after dosing, 68% of 139 women taking rizatriptan 10 mg and 70% of 115 women taking rizatriptan 5 mg with a menstrually associated migraine had pain relief compared with 44% of 81 patients taking placebo (P <.05). In all women, rizatriptan was as effective in treating menstrual as well as nonmenstrual migraine: 68% of 139 patients taking rizatriptan 10 mg with a menstrually associated migraine had pain relief at 2 hours after dosing compared with 69% of 393 patients with nonmenstrually associated attacks (test of menstrual association = nonsignificant; the analysis had 80% power to detect a difference of six percentage points between groups). Similar results were found for rizatriptan 5 mg (menstrual = 70%, nonmenstrual = 66%; not statistically significant). CONCLUSION: Rizatriptan is effective in the treatment of menstrually associated migraine attacks.
文献 PubMed−ID	10908770
エビデンスレベル	㈵ b
文献タイトル (日本語)	月経片頭痛の治療におけるリザトリプタン
目的	月経関連片頭痛発作に対する経口リザトリプタン 10mgと5mgの効果を裁定する．
研究デザイン	無作為，二重盲検，プラセボ対照，不完全ブロック，２期間，交差試験
研究施設	Jefferson Headache Center , Thomas Jefferson University Hospital , Philadelphia , Pennsylvania , USA .
対象患者	2715例の男女の片頭痛患者なかから，最初の発作にリザトリプタン10mg，5mg，プラセボのいずれかを服用した患者1419例．このうち，月経関連片頭痛に服用したもの335例．
介入	最終月経開始前後３日間以内に起こった発作を月経関連片頭痛とした．
主要評価項目とそれに用いた統計学的手法	服用２時間後の頭痛改善率
結果	リザトリプタンはプラセボに比し，月経関連片頭痛に対して有意に効果が見られた．服用２時間後の改善率はリザトリプタン 10mg群68%，5mg群70%，プラセボ群44%．リザトリプタンは月経関連片頭痛と非片頭痛発作のいずれにも有効であった．
結論	リザトリプタンは月経関連片頭痛に有効な治療法である．
作成者	五十嵐久佳

6) Nett R, Landy S, Shackelford S, Richardson MS , Ames M, Lener M. 　 Pain-free efficacy after treatment with sumatriptan in the mild pain 　 phase of menstrually associated migraine. Obstet Gynecol. 　 2003;102:835-42.
論文抄録	OBJECTIVE: To estimate the efficacy of sumatriptan 50-mg and 100-mg tablets in menstrually associated migraine when treatment is administered during the mild pain phase. METHODS: A randomized, double-blind, placebo-controlled, single-attack study was conducted. Menstrually associated migraine was defined as any migraine beginning on or between day -2 and day 4, with day 1 = first day of flow. Patients had at least a 1-year history of migraine as defined by International Headache Society criteria and reported regularly occurring menstrually associated migraines typically having a mild pain phase. Patients treated attacks within 1 hour of the onset of pain but only if the pain was mild at onset and while the pain was still mild. RESULTS: In the 349 women with menstrually associated migraine, sumatriptan was significantly more effective than placebo: 61% and 51% of patients who used sumatriptan 100 mg and 50 mg, respectively, were pain-free 2 hours after treatment compared with 29% of patients who used placebo (P <.001 for both comparisons). At 2 hours, 51% and 45% of patients who used sumatriptan 100 mg and 50 mg were free of pain and associated symptoms (photophobia, phonophobia, nausea, vomiting) compared with 25% of placebo patients (P <.001 for both comparisons). Adverse events were low for sumatriptan 100 and 50 mg, and both doses were generally well tolerated. CONCLUSION: Sumatriptan 50-mg and 100-mg tablets are generally well tolerated and effective in providing pain-free relief and relief of the associated symptoms of menstrually associated migraine when administered in the mild pain phase.
文献 PubMed−ID	14551015
エビデンスレベル	㈵ b
文献タイトル (日本語)	月経関連片頭痛の軽度頭痛期におけるスマトリプタンによる治療後の痛み消失効果
目的	月経関連片頭痛で頭痛が軽度の時期に服用した場合のスマトリプタン 50mgと100mgの効果をみる．
研究デザイン	無作為，二重盲検，プラセボ対照試験
研究施設	Texas Headache Associates, San Antonio , Texas , USA .
対象患者	月経関連片頭痛を持つ 349例の女性患者
介入	月経関連片頭痛は月経開始２日前から月経４日目の間に起こった片頭痛とした．頭痛開始１時間以内で，頭痛開始時から痛みが軽度のもの
主要評価項目とそれに用いた統計学的手法	服用２時間後の頭痛改善率
結果	服用２時間後の頭痛改善率はスマトリプタン 100mg（61%），50mg（51%）がプラセボ（29%）に比し有意に高値であった．２時間後に頭痛，随伴症状とも消失は，スマトリプタン100mg（51%），50mg（45%）がプラセボ（25%）に比し有意に高値であった．有害事象は少なく，忍容性が高かった．
結論	月経関連片頭痛で頭痛が軽度の時期に服用した場合にスマトリプタン 50mg，100mgは忍容性が高く，痛みと随伴症状消失に有効である．
備考	Randomized Controlled Trial
作成者	五十嵐久佳

7) Newman L, Mannix LK, Landy S, Silberstein S, Lipton RB, Putnam 　 DG, Watson C, Jobsis M, Batenhorst A, O'Quinn S. Naratriptan as 　 short-term prophylaxis of menstrually associated migraine: a 　 randomized, double-blind, placebo-controlled study. Headache. 　 2001;41:248-56.
論文抄録	OBJECTIVE: To determine the efficacy of naratriptan 1-mg and 2.5-mg tablets twice daily compared with placebo as short-term prophylaxis of menstrually associated migraine. BACKGROUND: Approximately 60% of women with migraine report headaches associated with their menstrual cycles. Results from an open-label study suggest that short-term administration of sumatriptan is useful in the prophylaxis of menstrually associated migraine. METHODS: A randomized, double-blind, three-arm, parallel-group, placebo-controlled study was conducted in women aged 18 years or older with a history of migraine with or without aura, as defined by the International Headache Society, of at least 6 months. Two dose strengths of naratriptan (1 mg, 2.5 mg) or identical-appearing placebo tablets (1:1:1) were administered twice daily for 5 days starting 2 days prior to the expected onset of menses across four perimenstrual periods. End points included the number of menstrually associated migraines, total migraine days, peak headache severity, lost work/activity time, migraine-related quality of life, and incidence of adverse events. RESULTS: Overall, the intent-to-treat population comprised 206 women (naratriptan 1 mg, n = 70; naratriptan 2.5 mg, n = 70, and placebo, n = 66); 171 women treated four perimenstrual periods. Significantly more perimenstrual periods per subject treated with naratriptan, 1 mg, were headache-free compared with placebo (50% versus 25%, P =.003). Naratriptan, 1 mg, significantly reduced the number of menstrually associated migraines (2.0 versus 4.0, P <.05) and menstrually associated migraine days (4.2 versus 7.0, P <.01) compared with placebo. More patients treated with naratriptan, 1 mg, were headache-free across all treated perimenstrual periods compared with placebo (23% versus 8%). No difference in headache severity was observed in breakthrough headaches. The incidence and severity of adverse events was similar across treatment groups. Naratriptan, 2.5 mg, was not statistically superior to placebo for any measure. CONCLUSIONS: Naratriptan, 1 mg, with tolerability similar to placebo, is an effective, short-term, prophylactic treatment for menstrually associated migraine.
文献タイトル (日本語)	月経関連片頭痛の短期間予防薬としてのナラトリプタン：無作為，二重盲検，プラセボ対照試験
エビデンスレベル	㈵ b
目的	月経関連片頭痛の短期間予防療法としてのならトリプタン 1mgと2.5mg１日２回投与の効果をプラセボと比較する．
研究デザイン	無作為，二重盲検，プラセボ対照試験
研究施設	米国の 18 施設
対象患者	18歳以上の片頭痛患者206例
介入	月経開始予想日２日前から５日間投与．４周期
主要評価項目とそれに用いた統計学的手法	月経関連片頭痛の回数，全片頭痛の起こった日数，痛み極期の強さ，仕事や活動のできなかった日数，仕事のできなかった日数， QOL，副作用
結果	171例が４周期治療した．ナラトリプタン1mg群はプラセボに比し，月経周辺の頭痛がなかった（50%対25%, P=.003）．ナラトリプタン1mg群はプラセボに比し，月経関連片頭痛発作回数を減少させ（2.0対4.0, P<.05），月経関連片頭痛日数を減らした（4.2対7.0, P<.01）．痛みの強さには差はなかった．有害事象の頻度と強さは治療群間では同等であった．ナラトリプタン2.5mgはすべての項目でプラセボより統計学的に優れてはいなかった．
結論	ナラトリプタン 1mgは忍容性がプラセボと等しく，月経関連片頭痛の効果的な短期間予防療法である．
備考	Randomized Controlled Trial
作成者	五十嵐久佳

8) Sances G, Martignoni E, Fioroni L, Blandini F, Facchinetti F, Nappi 　 G. Naproxen sodium in menstrual migraine prophylaxis: a double- 　 blind placebo controlled study. Headache. 1990;30:705-9.
論文抄録	In this study, the efficacy of Naproxen sodium (Nxs) in the prophylaxis of Menstrual Migraine (MM) was tested, versus Placebo (PL). Forty women suffering from MM were admitted to a double-blind treatment protocol with Nxs 550 mg twice each day by mouth or Placebo (PL), for 3 months; in the next 3 months all the women were treated with the active drug in an open study. The headache intensity and duration, as well as the number of days of headache and the analgesic consumption, were significantly reduced with Nxs compared to PL. The efficacy of Nxs, shown also in improving premenstrual pain, and its good tolerability, support the use of this drug in the prophylactic therapy of MM.
文献 PubMed−ID	2074162
エビデンスレベル	㈵ b
文献タイトル (日本語)	月経片頭痛の予防におけるナプロキセンナトリウム：二重盲検プラセボ対照試験
目的	ナプロキセンの月経片頭痛予防効果をプラセボと比較する．
研究デザイン	プラセボ対照二重盲検試験
研究施設	University Centre for Headache and Adaptive Disorders: Unit of Pavia , Italy .
対象患者	19〜45歳の月経片頭痛患者40例
介入	片頭痛発作は月経の１週間前，月経中，ときに排卵期のおこり，他の時期は発作なし．３ヶ月間ナプロキセン 550mg，またはプラセボを１日２回経口投与し，次の３ヶ月間はすべての患者に試験薬を投与．
主要評価項目とそれに用いた統計学的手法	頭痛の強さ，持続時間，頭痛日数，鎮痛薬使用量
結果	ナプロキセン群では頭痛の強さ，持続時間，頭痛日数，鎮痛薬使用量がプラセボに比し有意に減少した．ナプロキセンは月経前の痛みも改善し，忍容性もよかった．
結論	月経片頭痛の予防にナプロキセンの使用を支持する．
コメント	Randomized Controlled Trial
作成者	五十嵐久佳

3) MacGregor EA, Chia H, Vohrah RC, Wilkinson M. Migraine and 　 menstruation: a pilot study.Cephalalgia. 1990;10:305-10.
論文抄録	OBJECTIVE: To define the term "menstrual" migraine and to determine the prevalence of "menstrual" migraine in women attending the City of London Migraine Clinic . DESIGN: Women attending the clinic were asked to keep a record of their migraine attacks and menstrual periods for at least 3 complete menstrual cycles. RESULTS: Fifty-five women completed the study. "Menstrual" migraine was defined as "migraine attacks which occur regularly on or between days -2 to +3 of the menstrual cycle and at no other time". Using this criterion, 4 (7.2%) of the women in our population had "menstrual" migraine. All 4 women had migraine without aura. A further 19 (34.5%) had an increased number of attacks at the time of menstruation in addition to attacks at other times of the cycle. Eighteen (32.7%) had attacks occurring throughout the cycle but with no increase in number at the time of menstruation. Fourteen (25.5%) had no attacks within the defined period during the 3 cycles studied. DISCUSSION: A small percentage of women have attacks only occurring at the time of menstruation, which can be defined as true "menstrual" migraine. This group is most likely to respond to hormonal treatment. The group of 34.5% who have an increased number of attacks at the time of menstruation in addition to attacks at other times of the month could be defined as having "menstrually related" migraine and might well respond to hormonal therapy. The 32.7% who have attacks throughout the menstrual cycle without an increase at menstruation are unlikely to respond to hormonal therapy. The 25.5% who do not have attacks related to menstruation almost certainly will not respond to hormonal therapy.
文献 PubMed−ID	2289231
エビデンスレベル	㈼ b
文献タイトル (日本語)	片頭痛と月経：パイロット試験
目的	“月経”片頭痛を定義し， the City of London Migraine Clinicに通院中の女性患者における“月経”片頭痛の頻度を確認する．
研究デザイン	３回以上の月経周期に渡って，片頭痛発作と月経期間を記録する．
研究施設	City of London Migraine Clinic.
対象患者	17-50歳の女性片頭痛患者55例（前兆のある片頭痛11例，前兆のない片頭痛44例）
介入	月経１４日前を排卵日とした．
結果	片頭痛発作は月経１日目に明らかに増加したが，排卵日には増加しなかった．６例（ 10.9％）は月経時にのみ片頭痛発作が起こった．これらのうち４例（7.2％）は３回の月経周期で，月経２日前から月経３日目のみに発作があった．残りの２例は月経４日前，月経４日目にも発作がみられた．１例のみ月経２日前から月経３日目までと排卵日に発作があった．これらの７例は全例前兆のない片頭痛であった．多くの患者は月経以外のときにも片頭痛発作があった．37例（67.3％）は月経３周期を通してすべての時期に発作があった．そのうち19例（34.5％）は「月経片頭痛」と定義された期間（月経２日前から月経３日目）に発作が増加したが，18例（32.7％）はこの期間に増加せず．14例（25.5％）は３周期を通してこの期間に１回も発作がなかった．
結論	1.「月経時」片頭痛は7.2％ 2.「月経関連」片頭痛は34.5％ 3.月経周期のいずれの時期にも片頭痛が起こるもの32.7％ 4.月経時に片頭痛発作なし25.5％「月経時片頭痛」と「月経関連片頭痛」の２つの用語の定義を提案した．
作成者	五十嵐久佳

9) Al-Waili NS . Treatment of menstrual migraine with prostaglandin 　 synthesis inhibitor mefenamic acid: double-blind study with placebo. 　 Eur J Med Res. 2000 19;5:176-82.
論文抄録	The therapeutic effect of mefenamic acid, prostaglandin synthesis inhibitor, on pain of acute menstrual migraine and at the following days during menstrual bleeding period was studied and compared with placebo. 24 patients, 18 to 35 years old, with menstrual migraine were entered for study. They had regular menstrual cycles and they had been diagnosed as experiencing menstrual migraine without aura for more than one year. The patients were treated for 2 consecutive menstrual cycles, one cycle with 500 mg mefenamic acid and one cycle with placebo. Each drug was given at beginning of complaint and similar dose was repeated 8 hourly at following days during the menstrual bleeding period (Total dosage used 1500 mg per day). The use of medication was double blind. Pain intensity was rated by means of a 4 points scale and functional disability was rated from 0 to 3. Results showed that 79.16% of the patients showed significant pain relief with mefenamic acid as compared to 16.6% with placebo. The mean pain score of the mefenamic acid treated attacks decreased significantly from 2.46 +/- 0.5 to 0.62 +/- 1.0 at 2hr postdose. 83.3% of patients treated with mefenamic acid was able to function with or without little effort whereas 12.4% restored their activities with placebo. All the patients (100%) who showed significant initial responses to placebo experienced headache recurrence as compared to 26.3% with mefenamic acid. When considering mean pain scores, percentage of patients with pain free at 2h postdose, percentage of patients required rescue treatment, percentage of patients with headache recurrence and percentages of patients restored full activities, mefenamic acid is significantly superior to placebo in treatment of acute menstrual migraine. It might be concluded that mefenamic acid is safe and effective for treatment of acute menstrual migraine.
文献 PubMed−ID	10799353
エビデンスレベル	㈵ b
文献タイトル (日本語)	プロスタグランディン合成阻害物質メフェナム酸による月経片頭痛の治療：プラセボとの二重盲検試験
目的	急性月経片頭痛の痛みに対するメフェナム酸の治療効果をプラセボと比較した．
研究デザイン	プラセボとの二重盲件試験
研究施設	Dubai Specialized Medical Center and Medical Research Laboratories, Dubai , United Arab Emirates.
対象患者	18~35歳の月経片頭痛患者24例
介入	規則正しい月経周期があり，１年以上前兆のない月経片頭痛を経験している患者で，月経２周期（連続）を１周期はメフェナム酸 500mg，１周期はプラセボを使用した．症状開始時から８時間毎に月経出血がある間投与．
主要評価項目とそれに用いた統計学的手法	痛みの強さを４ポイントで評価，機能支障度を０〜３で評価
結果	メフェナム酸群ではプラセボに比し有意な痛み改善がみられた（ 79.16%対16.6%）．メフェナム酸群では服用３時間後に痛みスコアが有意に低下した（ 2.46 +/- 0.5 から 0.62 +/- 1.0 ）．メフェナム酸群では 83.3% が機能支障度が改善した（プラセボは 12.4% ）．
結論	メフェナム酸は急性期月経片頭痛薬として安全で有効である．
備考	Clinical Trial Controlled Clinical Trial
作成者	五十嵐久佳

10) Martin V, Wernke S, Mandell K, Zoma W, Bean J, Pinney S, Liu J, 　 Ramadan N, Rebar R. Medical oophorectomy with and without 　 estrogen add-back therapy in the prevention of migraine headache. 　 Headache. 2003;43:309-21
論文抄録	OBJECTIVES: To determine the preventive benefit of "medical oophorectomy" and transdermal estradiol in women with migraine. BACKGROUND: Epidemiological studies have demonstrated that declines in serum estrogen levels occurring during normal menstrual cycles can trigger headache in women with migraine. Prior to this study, no randomized controlled trials have evaluated whether minimizing these hormonal changes pharmacologically can prevent headache. METHODS: Twenty-one women with regular menstrual cycles and a diagnosis of migraine headache were enrolled. After a 2.5-month placebo run-in phase, all patients received a subcutaneous goserelin implant (a gonadotropin-releasing hormone agonist) to induce a medical oophorectomy. One month later, while continuing goserelin, participants were randomized to receive a transdermal patch containing 100 microg of estradiol-17beta (gonadotropin-releasing hormone agonist/estradiol group, n = 9) or a placebo patch (gonadotropin-releasing hormone agonist/placebo group, n = 12) during a 2-month treatment phase. The primary outcome measure was the headache index, which was defined as the mean of pain severity ratings (0 to 10 scale) recorded three times per day by daily diary. Secondary outcome measures included headache disability, headache severity, headache frequency, and the percentage of headaches with a pain severity rating of 7 or greater. RESULTS: The headache index was significantly lower during the treatment period in the gonadotropin-releasing hormone agonist/estradiol group than in the gonadotropin-releasing hormone agonist/placebo group (P =.025). Similar improvements were observed in the gonadotropin-releasing hormone agonist/estradiol group for all secondary outcome measures with the exception of headache frequency, which was unchanged between the groups. Within the gonadotropin-releasing hormone agonist/estradiol group, there was a 33.7% reduction (95% confidence interval, -64.4 to -3.0) in the headache index during the treatment phase when compared with the placebo run-in phase; no difference was seen between those phases within the gonadotropin-releasing hormone agonist/placebo group. CONCLUSIONS: Minimization of hormonal fluctuations with gonadotropin-releasing hormone agonist therapy alone is inadequate to prevent headache in women who are premenopausal with migraine. The addition of transdermal estradiol to existing gonadotropin-releasing hormone agonist therapy provides a modest preventive benefit.
文献 PubMed−ID	12656701
エビデンスレベル	㈵ b
文献タイトル (日本語)	片頭痛予防におけるエストロゲンありとなしの内科的卵巣摘出術
目的	片頭痛を持つ女性にたいする内科的卵巣摘出と経皮エストロゲンの予防効果を決定する．
研究デザイン	無作為，ラセボ対照，パイロット試験
研究施設	Department of Internal Medicine, University of Cincinnati College of Medicine , USA .
対象患者	21例の規則的月経周期をもつ女性
介入	2.5ヶ月のプラセボ投与期間後に，内科的卵巣摘出を引き起こすために全例が経口ゴセレリンインプラント（ゴナドトロピン放出ホルモン作動薬）を受けた．１ヵ月後に，無作為に100μｇのエストラジオール-17β（ゴナドトロピン放出ホルモン作動薬/エストラジオール群）含有経皮パッチ，またはプラセボパッチ（ゴナドトロピン放出ホルモン作動薬/プラセボ群）を２ヶ月間受けた．
主要評価項目とそれに用いた統計学的手法	平均頭痛強度（０〜 10で評価），頭痛による支障度，重症度，頻度，強さ７以上の頭痛の割合
結果	頭痛強度はゴナドトロピン放出ホルモン作動薬 /エストラジオール群（試験薬群）で有意に低かった．頭痛頻度以外で同様の改善が試験薬群で認められた．試験薬群では，頭痛強度はプラセボ投与期間中に比し治療期間中に33.7％減少したが，ゴナドトロピン放出ホルモン作動薬/プラセボ群では，プラセボ投与期間中のと差がなかった．
結論	片頭痛を伴う閉経前の女性において，ゴナドトロピン放出ホルモン作動薬のみの治療によるホルモン変動の最小化は頭痛を予防するためには不適当である．ゴナドトロピン放出ホルモン作動薬に経皮エストラジオールを追加することにより適度な予防効果をもたらす．
備考	Randomized Controlled Trial
作成者	五十嵐久佳