Exogenous sex hormone therapy and long-term outcomes in spontaneous coronary artery dissection: insights from the Australian–New Zealand registry

Background Spontaneous coronary artery dissection (SCAD) predominantly affects women, and endogenous hormonal influences are well recognised. However, the impact of exogenous sex hormone therapy on long-term cardiovascular outcomes remains uncertain, and current guideline recommendations are based on limited observational data. Purpose To evaluate whether exogenous sex hormone therapy at the time of SCAD, or after the index event, is associated with major adverse cardiovascular events (MACE). Methods Female patients with core laboratory–adjudicated SCAD enrolled in the Australian–New Zealand SCAD registry1 (23 centres) were analysed. Exogenous hormone exposure included oral contraceptive pills (OCP), menopausal hormone therapy (MHT), and non-oral contraceptives (NOC). The primary endpoint was MACE (all-cause death, myocardial infarction, stroke/TIA, heart failure, unplanned revascularisation, or SCAD recurrence). Cox proportional hazards models assessed associations between baseline hormone use and MACE during follow-up. In prospectively recruited patients, post-SCAD hormone use was analysed as a time-varying covariate. Results Among 601 women (median age 53 years [IQR 45–60]), 10.8% were using exogenous hormones at the index SCAD event (MHT 40.0%, OCP 32.3%, NOC 23.1%, combined 4.6%). Baseline clinical and angiographic characteristics were similar between groups. Over a median follow-up of 13.7 months (IQR 2.5–35.6), MACE occurred in 54/601 patients (9.0%): 46/536 (8.6%) non-users and 8/65 (12%) hormone users in the unadjusted cohort. In the adjusted primary model (n=524), MACE occurred in 45 patients (8.6%): 37/470 (7.9%) non-users and 8/54 (15%) hormone users. After multivariable adjustment using LASSO variable selection (ACS type, revascularisation strategy, and coronary tortuosity), baseline hormone use was associated with an approximately twofold higher risk of MACE (adjusted HR 2.35, 95% CI 1.09–5.10; p=0.047). In a prospective subgroup (n=216), post-SCAD hormone therapy was not associated with recurrent MACE when modelled longitudinally (adjusted HR 1.27, 95% CI 0.37–4.38; p=0.712) [Figure1]. Hormone prescribing patterns shifted over time: by three years, 23.3% of women were using hormone therapy, predominantly lower-dose non-oral contraceptives (71.4%), mainly intrauterine devices [Figure 2]. Conclusion Exogenous sex hormone therapy at the time of SCAD was associated with an approximately twofold higher risk of MACE during follow-up. In contrast, initiation or continuation of predominantly lower-dose, non-oral hormone therapy after SCAD was not associated with recurrent events. These findings support a formulation-specific, individualised approach to hormonal management in SCAD survivors rather than universal avoidance.