Oral Contraceptives and Health Outcomes: an Umbrella Review of Systematic Reviews and Meta-analyses in Women and Offspring

Aim We herein provide an umbrella review of systematic reviews (SR) and meta-analyses (MAs) of studies of the association of oral contraceptives (OCs) with the risks of multiple health outcomes in women and their descendants. Methods Two investigators retrieved publications from four electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews up to March 15, 2021. For each association, random/fixed-effects summary effect size and 95％ CIs were estimated. Heterogeneity and publication bias were also assessed. The method quality and evidence level for each publication were respectively assessed utilizing the AMSTAR and GRADE checklists. Results A total of 68 articles with 82 unique outcomes were included based on the eligibility criteria. Numerous lines of evidence indicated that OCs had effects on nearly all cardiovascular disease-related outcomes, especially for cerebral venous sinus thrombosis (OR = 7.59, 95％ CI: 3.82-15.09). Harmful associations were also found for vulvar vestibulitis (OR = 2.31, 95％CI: 1.03-5.16), preterm birth (OR = 1.17, 95％ CI: 1.07-1.27), miscarriage (OR = 1.13, 95％ CI: 1.02-1.72), ulcerative colitis (OR = 1.22, 95％ CI: 1.06-1.41), Crohn's disease (OR = 1.24, 95％ CI: 1.09-1.40), alveolar osteitis (RR = 1.86, 95％ CI: 1.66-2.08), dry socket (RR = 1.8, 95％ CI: 1.33-2.43), and interstitial cystitis (OR = 2.1, 95％ CI: 1.26-3.49). However, oral contraceptives did not increase the risk of cancer except breast and cervical cancer. Maternal exposure to OCs was linked to an increased risk for the development of respiratory atopic disorders such as asthma (OR = 1.1, 95％ CI: 1.02-1.19) and rhinitis (OR = 1.34, 95％ CI: 1.07-1.68). Conclusion In summary, although their use obviously reduces the risk of pregnancy- and parturition-related morbidity and mortality for women, OCs were frequently related to more harm than benefit in terms of other health outcomes. This was true for both women and their descendants in this umbrella review. More large-scale prospective studies analysing different doses, structures, and durations of treatment with estrogen and progestin are needed to confirm these effects.