Systemic exogenous progestins with or without estrogens are associated with decreased rates of venous procedures for varicose veins

Objectives

Risk factors for varicose veins (VVs) such as female sex, pregnancy, and obesity are high estrogen states, yet the role of systemic progestins with or without estrogens (SPEs) in VV management is not well characterized. This study investigates how SPE use affects rates of venous procedures for patients with VV.

Methods

The TriNetX database was queried for subjects with International Classification of Diseases, 10th edition, diagnoses of asymptomatic VV, chronic venous insufficiency, and complicated VV (inflammation or ulceration). Patients were divided into a control cohort with no subsequent SPE use, a progestin-only cohort, and a combined estrogen-progestin (CEP) cohort. Further stratification by VV symptomology and premenopausal status (age <40 years) was also performed. Cohorts were one:one propensity matched on known and theorized risk factors for VV including age, race, prior pregnancy, and body mass index. The outcomes of interest were deep vein thrombosis, pregnancy, stab phlebectomy, endovenous ablation, and sclerotherapy.

Results

Database query yielded 674,838 controls, 7597 CEP patients, and 13,758 progestin-only patients before matching. After propensity matching, compared with controls, the CEP cohort received fewer stab phlebectomies (relative risk [RR], 0.52; 95% confidence interval [CI], 0.42-0.64; P < .001), endovenous ablations (RR, 0.50; 95% CI, 0.43-0.59; P < .001) or any venous interventions (RR, 0.68; 95% CI, 0.61-0.76; P < .001), with no difference in sclerotherapy (P = .12). Similarly, the progestin-only cohort was less likely to receive stab phlebectomy (RR, 0.37; 95% CI, 0.31-0.43; P < .001), endovenous ablation (RR, 0.35; 95% CI, 0.31-0.40; P < .001), sclerotherapy (RR, 0.65; 95% CI, 0.56-0.75; P < .001), and any venous procedure (RR, 0.57; 95% CI, 0.52-0.62; P < .001). Compared with the progestin-only cohort, the CEP cohort had higher rates of sclerotherapy (RR, 1.38; 95% CI, 1.12-1.72; P = .003) and overall venous procedures (RR, 1.16; 95% CI, 1.00-1.34; P = .048). When possible, analysis stratified by symptomatic status and menopausal status revealed similar findings for subcohorts. Finally, the CEP cohort had lower risk of pregnancy than controls during the first 1200 days of observation, but subsequently had greater risk of pregnancy (RR, 1.38; 95% CI, 1.21-1.57; P < .001). Kaplan-Meier analysis showed that the rates of venous intervention were lower throughout the observation period.

Conclusions

This large, population-based cohort study demonstrated that, despite variable risk of deep vein thrombosis and pregnancy for estrogen-progestin and progestin-only treatment cohorts, both SPE formulations were associated with significantly fewer venous procedures for VVs than controls, with progestin-only cohorts undergoing the fewest procedures. This warrants further investigation into the role of SPE in VV disease progression and the utility of systemic progestins as an adjunct therapy for VVs.