<p>The causal role of established risk factors for premenstrual disorders (PMDs) remains unclear. We used Mendelian randomization (MR) to assess causality for eight known-risk factors identified through a literature review. Summary statistics for these risk factors were from genome-wide association studies (GWAS) with sample size ranging from 129,017 to 1.2 million, and for PMDs from a GWAS of 72,297 participants. Findings were validated using one-sample MR in LifeGene cohort (<i>n</i> = 5674–5937). In two-sample MR, genetic liability to smoking initiation (OR = 1.25 (1.10–1.43)), earlier menarche (OR = 0.94 (0.89–0.98) per year), and higher BMI (OR = 1.19 (1.05–1.34) per kg/m²) were associated with PMD risk. No causal association was indicated for anemia, childhood abuse, childhood asthma, diabetes, and endometriosis. In one-sample MR, point estimates for BMI (OR = 1.10 (0.88–1.38) per kg/m²) and earlier menarche (OR = 0.98 (0.83–1.15) per year) were directionally consistent with the two-sample MR findings, but the confidence intervals included null effects. However, a null association was observed for smoking (OR = 0.94 (0.77–1.16)). The two-sample MR supports causal role of earlier menarche, higher BMI, and smoking in risk of PMDs. The lack of replication in one-sample MR highlights the need for triangulating evidence from future well-powered and methodologically comparable studies to strengthen these findings.</p>