Importance Hormonal contraceptives (HCs) support reproductive goals and alleviate symptoms of gynaecological conditions for millions of women. Despite widespread use, individual long-term HC use trends, medication switching, and impact of genetics on HC side effects remain uncharacterised.

Objective To study HC use trends among Estonian Biobank (EstBB) participants, compare with national statistics, and evaluate suitability of EstBB for studying genetic risk for HC side effects.

Design Longitudinal descriptive analysis of HC refill data collected from 2004–2022 and user profiles, integrating demographic, genetic, and electronic health records data.

Setting Volunteer-based longitudinal cohort representing 20% of Estonian adult population, where participants signed broad informed consent.

Participants Women aged 15–55 in 2004–2022 with complete health and medication history available through linked electronic health records.

Exposure HC use defined as prescription and purchase of drugs of the Anatomical Therapeutic Chemical (ATC) coding system level 3 G02B and G03A, and ATC level 5 G03HB01 during follow-up.

Main Outcomes and Measures Primary measures included age-stratified annual HC users prevalence rates, inferred HC usage period duration, switching frequencies, and user profiles. Secondary measures included HC use during COVID-19 period, and genetic and health-relatedthromboembolism risk factors.

Results Over 19-year study period, twenty HC formulations with five administration routes (intrauterine device, ring, pill, patch and implant) were used by 73,071 women (mean age at joining EstBB (sd) = 35.6 (10.6)). Comparable to the Estonian population, combined HCs dominated, while progestin-only HC use increased with age and time. Next, 64.3% of users switched formulations at least once, with 17.7% being rapid switchers. Rapid switchers showed side effect-related diagnoses before switching, indicating the dataset’s potential for studying genetic risk of side effects. Medical abortion overlapped with inferred usage periods in 3.2% of users, suggesting contraceptive failure. Finally, 5.3% of HC users carried at least one VTE-associated genetic variant, and 1.5% of carriers developed thromboembolism during inferred HC use.

Conclusions and Relevance These HC use trajectories, consistent with population statistics, provide insights into real-world use patterns, offering additional context and support for understanding prescription trends, women’s preferences, as well as HC effectiveness and safety. Moreover, EstBB dataset has potential for genetic analyses of HC use and associated side effects.

The authors have declared no competing interest.

This study was funded by Estonian Research Council grants TK (TK214), PSG776, PRG2625 and PRG1911. H.C. is funded by Wellcome Trust 318918/Z/24/Z.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The ethical approval 1.1-12/624 for the study was granted by the Estonian Committee on Bioethics and Human Research (Estonian Ministry of Social Affairs), using data according to release application number 6-7/GI/16011 from the Estonian Biobank. All participants have signed a broad consent form.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Pseudonymized data and/or biological samples can be accessed for research and development purposes in accordance with the Estonian Human Genome Research Act (https://www.riigiteataja.ee/en/eli/ee/531102013003/consolide/current). To access data, the research proposal must be approved by the Scientific Advisory Committee of the Estonian Biobank as well as by the Estonian Committee on Bioethics and Human Research. Access to samples requires the same approval process and an additional approval from the Senate of the University of Tartu. For more details on data access and relevant documents, please see https://genomics.ut.ee/en/content/estonian-biobank#dataaccess.