Migraine is an acute form of headache affecting more women than men. In some women suffering from migraine, the cyclic ovarian sex steroids may worsen the attacks during menses. Studies have also shown that these women improve with pregnancy when the menstrual cycle ceases.
Experimental studies have observed that estrogen withdrawal at the time of menses aggravates migraine and it can be reduced by supplementation of estrogen. Supplementation with progesterone does not show a similar effect. A study conducted by Lichen and colleagues also supports the role of estrogen withdrawal to be a trigger for worsening migraine in postmenopausal women. This is attributed to the down regulation of anti-inflammatory genes with decreasing estrogen concentration thereby increasing the neuronal excitability in women prone to migraine.
Loder et al in their review article have tried to focus on the various hormonal strategies that can be used for hormone induced migraines. Nonhormonal treatment methods used include nimesulide, triptans, naproxen, prostaglandin inhibitors, acupuncture, biofeedback etc. All the hormonal regimens target minimal fluctuation of the estrogen during the menstrual cycle. Some strategies used are as follows:
1) Estrogen supplements:
Estrogen has been used in different forms as gels, creams, subcutaneous or intradermal patches for supplementation. Different studies conducted to study the effects of estrogen supplementation did not prove to be conclusive due to methodological deficiencies. A double blind placebo controlled trial by Martin et al concluded that estrogen supplementation could even provoke a migraine attack in some women.
2) Modifying the contraceptive regimen:
Migraine attacks among users of oral contraceptives have often been linked to the 7-day pill free duration of the conventional 21-day regime. Addition of estrogen for supplementation and extending the duration of continuous oral contraceptive use not only improves headaches but also provides contraception. Long acting estrogens used as transdermal patches used have raised concerns in the FDA about their safety issues.
3) Other treatment methods:
Tamoxifen, an estrogen modulator is often used for the treatment of breast cancers may have some benefits on menstrual migraine. However, Tamoxifen is poorly tolerated by breast cancer affected women and hence its long-term use for migraine is unlikely to hold promise. Danazol, a synthetic steroid has also been tried for hormone induced migraine in women. Larger studies are required to establish its efficacy for menstrual migraines. Phytoestrogens like black cohosh, soy isoflavonones and dong quai have also being investigated for their potential to benefit women with hormone induced migraine.
Hormonal treatment of migraines induced in the menopausal period:
The decreasing concentration of estrogens during menopause is known to exacerbate migraine in the perimenopausal period in women. It is also seen in postmenopausal women who take hormone replacement therapy (HRT) to relieve symptoms of menopause. Evidence on HRT suggests that intermittent HRT often aggravates symptoms while continuous HRT tends to reduce migraine in women.
Clinical evidence indicates that hormonal treatments need further investigation before they can be used as first line therapy for hormone induced migraines. Appropriate screening for risk factors is very important before considering hormones to treat hormone induced migraines.
Elizabeth Loder, Paul Rizzoli, Joan Golub. Hormonal Management of Migraine associated with menses and the menopause: A clinical review. Headache Feb 2007; 329 – 340