Association between the use of hormonal contraceptives and risk of cholecystectomy in women of reproductive age.

PURPOSE: Previous studies have indicated an increased risk of gallbladder disease with hormonal contraceptives although with discordant results. The potential increased risk of gallbladder disease with hormonal contraceptives is concerning given that women are at increased risk of this disease. Thus, the aim of this study was to examine risk of surgery-confirmed gallbladder disease (cholecystectomy) with oral contraceptives, intrauterine devices, and injectable hormonal contraceptives. METHODS: We conducted a retrospective cohort study. Females aged 15-45 who initiated hormonal contraceptive use were identified in the United States IQVIA Ambulatory electronic medical record database between 2008 and 2018. Cox proportional hazards models were used to estimate adjusted hazards ratios and 95% confidence intervals for cholecystectomy with eight formulations of contraceptives compared with levonorgestrel and ethinyl estradiol combined oral contraceptive. Sensitivity analysis was conducted by lagging exposure by 90 days and by excluding patients with history of gallbladder disease. Secondary analyses were conducted by cumulative duration of use. RESULTS: We identified 1,425,821 females who initiated the use of hormonal contraceptives and generated 4417 cholecystectomy events. Overall, the use of medroxyprogesterone acetate (HR: 1.22, 95% CI: 1.07-1.40) and at least 1 year of levonorgestrel intrauterine device use (HR: 1.74: 95% CI: 1.19-2.54) were associated with increased risk of cholecystectomy when compared with levonorgestrel and ethinyl estradiol combined oral contraceptive. However, we did not observe an increased risk with other hormonal contraceptives. Consistent results were observed across sensitivity analyses. CONCLUSION: In this large population-based study, there was an increased risk of cholecystectomy with medroxyprogesterone acetate and intrauterine device but not other hormonal contraceptives. Additional large observational studies are required to corroborate these findings.

Oral fluoroquinolones and risk of fibromyalgia.

The Food and Drug Administration (FDA) has recently included a black box warning on fibromyalgia-like symptoms with fluoroquinolones (FQs) but no large epidemiologic study is to date available. We undertook a case-control study using a random sample of 9 053 240 subjects obtained from the PharMetrics Plus health claims database in the United States. Cases received at least two fibromyalgia diagnoses coded by a rheumatologist matched to ten randomly selected controls. After identifying 5148 cases of fibromyalgia and 51 480 controls, the adjusted rate ratio (RR) of fibromyalgia for use of any fluoroquinolones, amoxicillin and azithromycin were 1.63 (95% CI: 1.41-1.87), 1.64 (95% CI: 1.46-1.85) and 1.68 (95% CI, 1.49-1.89), respectively. The adjusted RR for any use of FQ compared to any use of amoxicillin or azithromycin was 0.99 (95% CI: 0.83-1.18) and azithromycin is 0.97 (95%CI: 0.82-1.16), respectively. The risk of fibromyalgia with FQs is similar to that with amoxicillin and azithromycin.