Hormone exposure and venous thromboembolism in commercially insured women aged 50 to 64 years

Weller, Susan C.; Davis, John W.; Porterfield, Laura; Chen, Lu; Wilkinson, Gregg S.

doi:10.1016/j.rpth.2023.100135

Cited by 5 publications

(46 citation statements)

References 31 publications

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“…15 A notable difference between this sample and the UK samples 17,27 was the number of women in the US sample on higherrisk combined hormone contraceptives. 15 Women older than 50 years exposed to combined hormonal contraceptives had 5 to 9 times higher risk of VTE compared with those with no hormone exposure. 15 The overall reduction in VTE risk with statin therapy observed in this study (12%) was smaller than estimated in previous observational studies but similar to the reduction found in randomized clinical trials (RCTs).…”

Section: Jama Network Open | Cardiologymentioning

confidence: 83%

“…The age range was selected because of the average age at menopause, higher rates of menopausal HT use in this age range, and the tendency to transition from commercial insurance to Medicare at age 65 years. The study focused on statin therapy and HT as part of a larger project on VTE; design details, including International Classification of Diseases, Ninth Revision [ICD-9] , International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) , and Current Procedural Terminology codes were reported previously …”

Section: Methodsmentioning

confidence: 99%

“…Exposure was evaluated regardless of route (oral or nonoral) or indication (eg, menopausal HT or contraception). Timing of HT exposure was defined as recent (≤60 days before index) vs past and none, because previous research indicated VTE risk diminishes after 60 days . National drug codes for hormones were identified using Red Book and/or from a list supplied by the US Food and Drug Administration (list published previously).…”

Section: Methodsmentioning

confidence: 99%

“…15 Women older than 50 years exposed to combined hormonal contraceptives had 5 to 9 times higher risk of VTE compared with those with no hormone exposure. 15 The overall reduction in VTE risk with statin therapy observed in this study (12%) was smaller than estimated in previous observational studies but similar to the reduction found in randomized clinical trials (RCTs). Cohort studies 25 suggest statin exposure may reduce VTE risk by 25%, whereas…”

Section: Jama Network Open | Cardiologymentioning

confidence: 99%

“…4,5 However, concerns regarding increased risk of venous thromboembolism (VTE), stroke, or myocardial infarction can prevent many symptomatic women from receiving HT. [6][7][8] HT may double the risk of VTE, [9][10][11] although the clinical trials were conducted with oral, conjugated equine estrogen (CEE), 9,12 and newer studies suggest risk may be lower with other types of estrogen, [13][14][15][16][17] routes of administration, 15,[17][18][19] and earlier initiation of therapy. [20][21][22] In the decades since initial HT trials were conducted, statin therapy has been associated with reduced risk for major cardiovascular events 23,24 and VTE, 25,26 but few studies have estimated statin's ability to mediate HT-associated VTE risk.…”

Section: Introductionmentioning

confidence: 99%

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Statin Use and the Risk of Venous Thromboembolism in Women Taking Hormone Therapy

Davis,

Weller,

Porterfield

et al. 2023

JAMA Netw Open

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ImportanceAlthough hormone therapy (HT) in perimenopausal women is associated with increased risk for venous thromboembolism (VTE), it is unclear to what extent statins may mitigate this HT-associated risk.ObjectiveTo estimate VTE risk in women aged 50 to 64 years taking HT with or without statins.Design, Setting, and ParticipantsThis nested case-control study analyzed data from a commercially insured claims database in the US. Eligible participants included women aged 50 to 64 years with at least 1 year of continuous enrollment between 2008 and 2019. Data analysis occurred from January 2022 to August 2023.ExposureFilled prescriptions for estrogens, progestogens, and statins were recorded in the 12 months prior to index. Recent HT was defined as any estrogen or progestogen exposure within 60 days before the index date. Current statin exposure was defined as 90 or more days of continuous exposure prior to and including the index date. Statin intensity was defined by the statin exposure 30 days prior to index.Main Outcomes and MeasuresCases were identified with VTE diagnoses (diagnostic codes) preceded by at least 12 months without VTE and followed within 30 days by anticoagulation, an inferior vena cava filter placement, or death. Controls were matched to cases (10:1) on date and age. Conditional logistic regression models estimated risk for HT and statin exposures with odds ratios (OR), adjusted for comorbidities. Conditional logistic regression models were used to estimate VTE risk for HT and statin exposures with odds ratios (ORs), adjusted for comorbidities. Intensity of statin therapy was measured as a subgroup analysis.ResultsThe total sample of 223 949 individuals (mean [SD] age, 57.5 [4.4] years) included 20 359 cases and 203 590 matched controls. Of the entire sample, 19 558 individuals (8.73%) had recent HT exposure and 36 238 individuals (16.18%) had current statin exposure. In adjusted models, individuals with any recent HT exposure had greater odds of VTE compared with those with no recent HT exposure (OR, 1.51; 95% CI, 1.43-1.60). Individuals receiving current statin therapy had lower odds of VTE compared with those with no current statin exposure (OR, 0.88; 95% CI, 0.84-0.93). When compared with those not recently taking HT or statins, the odds of VTE were greater for those taking HT without statins (OR, 1.53; 95% CI, 1.44-1.63) and for those taking HT with statins (OR, 1.25; 95% CI, 1.10-1.43), but were lower for those taking statins without HT (OR, 0.89; 95% CI, 0.85-0.94). Individuals taking HT with statin therapy had 18% lower odds of VTE than those taking HT without statins (OR, 0.82; 95% CI, 0.71-0.94) and there was greater risk reduction with higher intensity statins.Conclusions and RelevanceIn this case-control study, statin therapy was associated with reduced risk of VTE in women taking HT, with greater risk reduction with high-intensity statins. These findings suggest that statins may reduce risk of VTE in women exposed to HT and that HT may not be contraindicated in women taking statins.

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