Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study.

OBJECTIVE: To study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism. DESIGN: Nationwide cohort study. SETTING: Denmark through national registries. PARTICIPANTS: All 15-49 year old women living in Denmark between 1996 and 2017 with no medical history of any venous or arterial thrombotic event, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation, or infertility treatment (n=2 029 065). MAIN OUTCOME MEASURE: A first time discharge diagnosis of lower limb deep venous thrombosis or pulmonary embolism. RESULTS: Among 2.0 million women followed for 21.0 million person years, 8710 venous thromboembolic events occurred. Compared with non-use of NSAIDs, use of NSAIDs was associated with an adjusted incidence rate ratio of venous thromboembolism of 7.2 (95% confidence interval 6.0 to 8.5) in women not using hormonal contraception, 11.0 (9.6 to 12.6) in women using high risk hormonal contraception, 7.9 (5.9 to 10.6) in those using medium risk hormonal contraception, and 4.5 (2.6 to 8.1) in users of low/no risk hormonal contraception. The corresponding numbers of extra venous thromboembolic events per 100 000 women over the first week of NSAID treatment compared with non-use of NSAIDs were 4 (3 to 5) in women not using hormonal contraception, 23 (19 to 27) in women using high risk hormonal contraception, 11 (7 to 15) in those using medium risk hormonal contraception, and 3 (0 to 5) in users of low/no risk hormonal contraception. CONCLUSIONS: NSAID use was positively associated with the development of venous thromboembolism in women of reproductive age. The number of extra venous thromboembolic events with NSAID use compared with non-use was significantly larger with concomitant use of high/medium risk hormonal contraception compared with concomitant use of low/no risk hormonal contraception. Women needing both hormonal contraception and regular use of NSAIDs should be advised accordingly.

Long-term reproductive outcomes in women whose first pregnancy is ectopic: a national controlled follow-up study.

STUDY QUESTION: How does long-term reproductive prognosis among women whose first pregnancy is ectopic differ from prognosis in women with other initial pregnancy outcomes? SUMMARY ANSWER: Women with a first recorded ectopic pregnancy (EP) have a significantly lower long-term delivery rate and a manifold increased risk of further EPs. WHAT IS KNOWN ALREADY: Women with a first EP have an increased risk of further EPs. Few studies have assessed long-term reproductive outcomes after an EP, and none was controlled. STUDY DESIGN: The study was designed as a historical controlled cohort study. MATERIALS AND METHODS: Data were collected from four Danish registries covering the period 1977-2009. Women with an EP as their first recorded pregnancy during the period 1977-1982 were age matched with women whose first recorded pregnancy was a miscarriage, an induced abortion, a delivery, or women with no recorded pregnancies, respectively. The cohorts were followed until the end of 2009 or on average through 30 years. MAIN RESULTS: When compared with women with a first miscarriage, women with a first EP had a relative risk of deliveries of 0.55 [95% confidence interval (CI) 0.52-0.58], miscarriages of 0.46 (0.41-0.52) and induced abortions of 0.72 (0.65-0.80) and a 4.7 (3.8-5.8)-fold increased risk of further EPs. The relative delivery rate when compared with women with a first induced abortion was 0.89 (0.84-0.95) and with women with no pregnancy 0.69 (0.65-0.72). LIMITATIONS: We had no information about the attempts to become pregnant in the different cohorts. New fertility techniques may have improved the prognosis among women with a first EP. WIDER IMPLICATIONS OF THE FINDINGS: These results indicate that fertility is compromised in women whose first pregnancy is ectopic. It is possible that better assisted reproductive techniques that have been developed in recent years could improve the long-term delivery rates for women with EP. STUDY FUNDING: All the expenses were covered by Gynaecological Clinic, Rigshospitalet. Ø.L. has within the last 3 years received honoraria for speeches in pharmacoepidemiological issues. L.L.K., P.E. and C.W.S. had no conflict of interest to declare.