Table 3.

Summary of Included Studies Assessing the Role of Sex Hormones in Postmenopausal Women with Migraine

Study	Publication Year	Design	Setting	N with Migraine	Age, Mean±SD	Time from Last Menstruation (Months)	Intervention	Outcome	Follow-Up (Months)	Main Results
Nappi et al16	2006	Randomized trial	Headache clinic	40	52.4±1.3 (treated with tibolone) 52.8±1.4 (treated with estrogen-progestogen)	≥12	Tibolone vs estrogen-progestogen	1) Change in number of headache days compared with baseline 2) Change in number of hours of severe headache (during which pain intensity prohibited daily activities) compared with baseline 3) Change in number of analgesics compared with baseline	6	1) Tibolone did not increase while estrogen-progestogen increased headache days 2) Tibolone decreased headache intensity, while estrogen-progestogen did not 3) Tibolone decreased while estrogen-progestogen increased analgesic consumption
Misakian et al15	2003	Cross-sectional (baseline data of a randomized controlled trial)	General population (healthcare professionals)	1909	55.2±6.2	NR	Any hormonal treatment	Association (OR) between hormonal treatments and migraine	NA	- Current hormonal treatments were associated with an OR for migraine headache of 1.42 (95% CI 1.24–1.62) after multiple adjustments - Any dose and type of treatment was associated with migraine
Aegidius et al17	2007	Population-based study	General population	801	NR	≥12	Any (subgroup analyses for local and systemic use)	Migraine prevalence	NA	- Previous use: OR 1.2, 95% CI 0.9–1.6 - Current local use: OR 1.3, 95% CI 0.9–1.7 - Current systemic use: OR 1.6, 95% Ci 1.4–1.9
Facchinetti et al14	2002	Observational prospective study	Gynecology clinic	38	51.1±1.9	10.4±4.4	3 regimens of treatment: A) estradiol hemihydrate 1 mg/day plus norethisterone 0.5 mg/day for 28 days in a continuous combined scheme; B) oral conjugated estrogens 0.625 mg/day for 28days plus medroxyprogesterone acetate 10 mg/day in the last 14 days in a sequential continuous scheme; C) estradiol valerate 2 mg/day for 21 days plus cyproterone acetate 1 mg/day from day 12 to 21 in a sequential cyclical scheme	1) Frequency (number of attacks per month) 2) Days with headache (number of days with headache per month) 3) Severity (score of 0 to 3, ranging from absent to severe headache) 4) Duration of attacks 5) Analgesic use (number of analgesics per month) 6) Greene scale for climacteric symptoms 7) Zung scale for anxiety and depression	3; 6	1) Increased for every treatment 2) Increased for every treatment (with smaller increase in group A compared with groups B and C) 3) Increased only in groups B and C and stable in group A 4) Decreased in groups A and B but remained stable in group C 5) Increased for every treatment (with smaller increase in group A compared with groups B and C) 6) Decreased for every treatment 7) Decreased for every treatment
Glaser et al19	2012	Prospective pilot study	Oncology clinic	11	55.5±8.7	NR	Testosterone pellet subcutaneous implants	Headache severity on a 5-point rating scale	3	Mean headache severity decreased from 3.5±0.59 to 0
Rustichelli et al23	2020	Cross-sectional	Gynecology clinic	30 (menstrual migraine) 30 (postmenopausal migraine)	33.5±7.1 (menstrual migraine) 56.6±4.5 (postmenopausal migraine)	≥12	Measurement of serum allopregnanolone, progesterone, and testosterone	Hormone levels in menopausal migraineurs compared with postmenopausal controls and with menstrual migraineurs	NA	- Allopregnanolone levels significantly lower in postmenopausal migraineurs compared with postmenopausal controls (25±13 pg/mL vs 80±17 pg/mL; P<0.001); progesterone, testosterone, and allopregnanolone levels similar between postmenopausal migraineurs and postmenopausal controls - All hormones had lower levels in postmenopausal migraineurs compared with menstrual migraineurs

Abbreviations: NA, not applicable; NR, not reported.