Risks of Exogenous Sex Hormone Therapy Before and After Spontaneous Coronary Artery Dissection

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome in females. The impact of exogenous sex hormone therapy on major adverse cardiovascular events (MACE) remains uncertain. OBJECTIVES: This study estimated the effect of sex hormone therapy on MACE. METHODS: Females with SCAD and core laboratory-adjudicated coronary angiography were prospectively and retrospectively recruited from 23 sites in Australia and New Zealand. Cox proportional hazard modes estimated if sex hormone therapy at the index SCAD predicted long-term MACE. In the prospective cohort, post-SCAD sex hormone therapy was modeled as a time-varying covariate to assess for association with recurrent MACE. RESULTS: Among 601 females (median age: 53.0, IQR: 45.0 to 60.0), 10.8% (65/601) were using sex hormone therapy at the index SCAD, comprising menopausal hormone therapy (MHT) (40.0%, 26/65), oral contraceptive pill (32.3%, 21/65), nonoral contraceptives (NOCs) (23.1%, 15/65), and combined therapy (MHT+NOC; 4.6%, 3/65). There was no evidence of an association between sex hormone therapy at index SCAD and long-term MACE (adjusted HR: 1.88; 95% CI: 0.88-4.00; P = 0.130) nor between post-SCAD sex hormone use and recurrent MACE (adjusted HR: 1.21; CI: 0.35-4.16; P = 0.770), after median 13.7 (IQR: 2.5-35.6) months follow-up. At 3 years, 23.3% (7/30) reported sex hormone therapy, mainly NOC (71.4%, 5/7) and MHT combined with NOC (28.6%, 2/7). CONCLUSIONS: Exogenous sex hormone therapy was not associated with an increase in MACE in females with SCAD, including when initiated after SCAD, where lower-dose intrauterine devices predominated. These findings support an individualized approach to sex hormone therapy after SCAD, although wide CIs highlight the need for further study.