Summary of the studies in patients with MM
| Number | Study and year | Participants | Intervention | Route of administration | Duration | Key findings |
|---|---|---|---|---|---|---|
| 1. | Nappi et al., 2013 [19] | 32 women | Contraceptive pill containing E2V/DNG | Oral | 12–24 weeks | Migraine attacks, head pain duration, and severity significantly decreased in the third and sixth cycles of E2V/DNG use compared to baseline (p < 0.001 for all). Analgesic use also decreased significantly in the third cycle (p < 0.001) and further declined in the sixth cycle (p < 0.001). Among women with persistent dysmenorrhea, head pain duration and severity were significantly correlated with the number of dysmenorrhea days in both the third (r = 0.89, p = 0.000; r = 0.67, p = 0.02) and sixth (r = 0.76, p = 0.000; r = 0.62, p = 0.04) cycles. |
| 2. | Calhoun 2004 [20] | 11 women | Ethinyl estradiol (1–21 days) and conjugated equine estrogens supplementation (22–28 days) | Oral | 4 weeks | All patients saw at least a 50% reduction in headache days per cycle, averaging a 77.9% decrease. Among the 11 women, 10 experienced at least a 50% reduction in weighted headache score, with an average decrease of 76.3%. |
| 3. | LaGuardia et al., 2005 [21] | 239 women | Norelgestromin/ethinyl estradiol transdermal system | Transdermal | 4–12 weeks | Most women in the study experienced delayed menses and fewer mean headache days during the hormone-free interval with extended use of transdermal norelgestromin/ethinyl estradiol than with cyclic use. |
| 4. | Calhoun et al., 2012 [22] | 28 women | Etonogestrel/ethinyl estradiol | Transvaginal ring | 4–70 weeks | The use of extended vaginal ring contraceptives significantly reduced the median frequency of MwA from 3.23 to 0.23 per month (p < 0.0005) over an average of 7.8 months, with no participants reporting increased aura frequency and 91.3% of evaluable subjects experiencing complete cessation of MwA. |
| 5. | Coffee et al., 2014 [8] | 32 women | Levonorgestrel and ethinyl estradiol | Oral | 21/7 regimen and 168-day extended regimen | Daily headache scores significantly decreased (p = 0.034) from an average of 1.29 ± 0.10 in pre-study cycles, then further reduced to 1.10 to 0.14 with extended COCs. Frovatriptan prevented the increase in the headache score observed in the placebo group during hormone-free interval. However, after stopping frovatriptan, the headache scores increased (p > 0.01) despite resuming COCs. |
| 6. | de Lignières et al., 2002 [25] | 20 women | Estradiol gel | Transdermal | 12 weeks | Transdermal estradiol gel significantly reduced the frequency and severity of MM. |
| 7. | De Leo et al., 2011 [9] | 60 women | COCs | Oral | 12 weeks | COCs led to a reduction in the frequency, severity, and duration of MM. |
| 8. | Almén-Christensson et al., 2011 [29] | 38 women | Transdermal 17-β-estradiol vs. placebo | Transdermal | 12 weeks | Perimenstrual transdermal 17-β-estradiol significantly reduced MM incidence compared to placebo. |
E2V/DNG: estradiol valerate and dienogest; MwA: migraine with aura; COCs: combined oral contraceptives; MM: menstrual migraine
