Neurol Sci (2004) 25:S229–S231
DOI 10.1007/s10072-004-0292-6
G. Allais • C. Benedetto
Update on menstrual migraine: from clinical aspects to therapeutical
strategies
Abstract Migraine occurrence is strongly influenced by the
hormonal fluctuations of the female reproductive cycle; at
least 60% of women affected by migraine relate the period-
icity of their attacks to the menstrual cycle. The so-called
menstrual migraine, which occurs immediately before, dur-
ing or at the end of the menstrual flow, has been a largely
undefined condition, including some clinical subtypes which
are not well defined. In the last edition of the International
Classification of Headache Disorders (ICHD-II), menstrual
migraine gained new attention in the Appendix, where three
clinical patterns were pointed out: pure menstrual migraine
without aura; menstrually related migraine without aura and
non-menstrual migraine without aura. Menstrual migraine
attacks show severe intensity, long duration (lasting even
more than 72 h), marked unresponsiveness to pharmacolog-
ical treatments, and present higher recurrence rate and work-
related disability than non-menstrual attacks. The pharma-
cological treatment of menstrual migraine can require spe-
cific cyclic prophylactic approaches (non-steroidal anti-
G. Allais () • C. Benedetto
Woman’s Headache Center
Department of Gynecology and Obstetrics
University of Turin
Via Ventimiglia 3, I-10126 Turin, Italy
e-mail: gb.allais@tiscali.it
inflammatory drugs, coxibs, magnesium, long half-life trip-
tans or oestrogen supplements in various formulations), but
usually the low frequency of attacks suggests a first
approach with specific symptomatic drugs. Preference
should be given to triptans, due to their specificity in con-
trolling migraine pain and its accompanying symptomatol-
ogy; among them, in particular for sumatriptan, many spe-
cific studies proved a real effectiveness in the management
of acute menstrual migraine attack.
Key words Headache classification • Menstrual cycle •
Migraine • Sumatriptan • Treatment
Migraine occurrence is strongly conditioned by the hor-
monal fluctuations of the female reproductive cycle, the
major determinant of head pain attacks probably being the
fall of oestrogen levels during the premenstrual phase of the
cycle [1, 2].
At least 60% of women affected by migraine relate the
periodicity of their attacks to the menstrual cycle: this is the
so-called menstrual migraine, which occurs immediately
before, during or at the end of the menstrual flow.
Introducing a criterion of simple temporal definition, in
the past some authors distinguished between premenstrual
migraine, related to the wider symptomatology of the pre-
menstrual syndrome, and the so-called menstrual migraine,
which is associated with the painful phase of menstrual
flow. To these two different entities we could probably add
a third one, the late menstrual migraine, in order to
embrace those attacks which occur at the end of the men-
strual flow [3].
To better define the widely undetermined “perimen-
strual period” in which attacks must develop to be proper-
ly called “menstrual”, in the last few years the concept of
a “menstrual window” was introduced. This period, fol-
lowing the most restrictive criteria in recent literature,
S230
spreads from days –2 and +2 in relation to the beginning
of the menstrual flow (which is day +1) or, according to
the less severe inclusion criteria, from –3 to +5 (some-
times even +7).
In the last edition [4] of the International Classification
of Headache Disorders (ICHD-II), published by the
International Headache Society (IHS), menstrual
migraine, not clearly defined in the former Classification
[5], finally gains new attention and appears in the
Appendix. Three clinical patterns are pointed out:
- pure menstrual migraine (PMM) without aura (code
A1.1.1) in which attacks, fulfilling criteria for
migraine without aura, exclusively occur in the men-
strual window, extended from days –2 to +3 of men-
struation in at least two out of three menstrual cycles;
- menstrually related migraine (MRM) without aura
(code A1.1.2), in which the attacks of migraine without
aura always occur on days –2 to +3, in at least two out
of three menstrual cycles and additionally at other
times of the cycle, due to different trigger factors or
also apparently without any specific reason;
- non-menstrual migraine (NMM) without aura (code
A1.1.3), in which the attacks, fulfilling criteria for
migraine without aura, have no menstrual relationship,
in a menstruating woman.
Menstrual attacks are mostly migraine without aura (an
aura could occur only in some exceptional cases).
Generally, every menstrual cycle is associated with an
attack of very severe intensity, of long duration (lasting
even more than 72 h according to the IHS Classification),
aggravated by very important vegetative phenomena, par-
ticularly unresponsive to pharmacological treatments and
with high probabilities of relapse.
In the past, some authors [2, 6], according to their clin-
ical experience, reported that menstrual migraine attacks
are longer, produce a greater disability and are less
responsive to pharmacological approaches than the non-
menstrual ones. Only recently, these assertions have been
confirmed by controlled trials.
An Italian multicentric study [3] carried out on women
affected by MRM, where migraine attack features,
migraine work-related disability and response to sympto-
matic drugs were considered comparing the perimenstrual
attacks to the non-menstrual attacks, demonstrated that the
former were significantly longer, associated to a greater
work disability and to a less pharmacological response
than the latter. Perimenstrual attacks were split into three
groups (premenstrual, occurring on days –2 and –1; men-
strual, on the first and second day of menstruation; and
late menstrual, on days +3 to +7 of the cycle). Many dif-
ferences were found between perimenstrual and non-men-
strual attacks: the former were significantly longer and
significantly less responsive to acute attack treatment;
from the point of view of disability, a significantly greater
number of work hours was lost due to premenstrual
G. Allais, C. Benedetto: Update on menstrual migraine
attacks and headache recurrence was significantly higher
in premenstrual and menstrual attacks.
From a therapeutical point of view, menstrual migraine
could require a specific prophylaxis [2, 6]. Depending on
each woman’s wishes, the regularity of menstrual cycle,
need for contraception, timing of attacks in relation to
bleeding, presence of dysmenorrhoea or menorrhagia, sev-
eral options can be tried, both non-hormonal and hormon-
al. At the present, non-steroidal anti-inflammatory drugs
(NSAIDs), coxibs, magnesium supplementation, long
half-life triptans and oestrogen supplements in various
formulations, administered perimenstrually, are frequently
used drug strategies. However, as menstrual migraine has
a relatively low frequency of attacks, it needs above all a
correct prescription of a specific treatment. The same
classes of drugs used to treat migraine tout-court are pre-
scribed, and so we can use triptans, ergot derivatives,
NSAIDs, various analgesics and antiemetic agents, alone
or in combination. The preference is always granted to
triptans, because of their ability to control head-pain and
accompanying symptomatology and also because for some
of them, in particular sumatriptan [7], many specific stud-
ies proved a real effectiveness in the acute attack treatment
of menstrual migraine. The administration of subcuta-
neous or oral sumatriptan in order to achieve pain relief
(defined as the reduction of headache severity from severe
to mild or from moderate to none) at two hours post-dos-
ing has proved to be significantly more effective than
placebo.
The result obtained by Nett et al. [8] is still more
encouraging, as it shows the possibility of oral sumatriptan
(100 mg and 50 mg) obtained a pain-free condition at two
hours in a high percentage of menstrual migraine sufferers
(51% and 47% respectively for the two dosages), provided
that the drug is taken in the first phases of pain, when allo-
dynia [9], which compromises a good therapeutic result of
triptans, is not yet started.
References
1. Somerville BW (1972) The role of estradiol withdrawal in
the etiology of menstrual migraine. Neurology 22:355–359
2. MacGregor A (ed) (1999) Migraine in women. Martin
Dunitz Ltd., London
3. Granella F, Sances G, Allais G, Nappi RE, Tirelli A, Ferraris
A, Benedetto C, Brundu B, Facchinetti F, Nappi G (2004)
Characteristics of menstrual and non-menstrual attacks in
women with menstrually related migraine referred to
headache centers. Cephalalgia (in press)
4. Headache Classification Committee of the International
Headache Society (2004) The international classification of
headache disorders, 2nd Edn. Cephalalgia 24[Suppl
1]:139–140
5. Headache Classification Committee of the International
G. Allais, C. Benedetto: Update on menstrual migraine
Headache Society (1988) Classification and diagnostic cri-
teria for headache disorders, cranial neuralgias and facial
pain. Cephalalgia 8[Suppl 7]:19–28
6. Allais G, De Lorenzo C, Zonca M, Benedetto C, Nattero G
(1993) The challenge of menstrual migraine therapy. In:
Genazzani AR, Volpe A, Facchinetti F (eds) Management
of menstrual migraine. The Parthenon Publishing Group,
Casterton Hall, Carnforth (UK), pp 27–38
7. Salonen R, Saiers J (1999) Sumatriptan is effective in the
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treatment of menstrual migraine: a review of prospective
studies and retrospective analyses. Cephalalgia 19:16–19
8. Nett R, Landy S, Shackelford S, Richardson MS, Ames M,
Lener M (2003) Pain-free efficacy after treatment with
sumatriptan in the mild pain phase of menstrually associat-
ed migraine. Obstet Gynecol 102:835–842
9. Landy S, Rice K, Lobo B (2004) Central sensitisation and
cutaneous allodynia in migraine: implications for treat-
ment. CNS Drugs 18:337–342