FSRH response to new study using a mathematical model to inform dose and regimen of exogenous hormones

A new mathematical model suggests that effective suppression of ovulation for contraception could be achieved using lower doses of progestogen and estrogen than those currently used in hormonal contraceptives. A paper published today in PLOS Computational Biology describes the model and its findings. The authors highlight that lower exposure to exogenous hormones could reduce associated health risks and side effects. The model could be used to inform dose and regimen of exogenous hormones to be investigated by future clinical trials seeking to find new options for safe, effective and acceptable contraception. Clinical trials would be required to investigate what outcomes, with such regimens, were found in practice.

It is important to note that health risks with currently available effective hormonal contraceptives are small, and many users have few or no side effects. But of course, if even safer options with fewer side effects were developed that still offered effective, acceptable contraception, these would be welcomed.

Crucially, preventing ovulation is far from the only consideration when thinking about hormonal contraceptive. Effective contraception can already be achieved without relying on stopping ovulation, for example, by intrauterine delivery of progestogen, which offers very low systemic exposure to the exogenous progestogen. Contraceptive effectiveness depends also on reliable use and continuation. That means that a regimen of hormone use must be convenient, and that the bleeding patterns and side effects experienced must be acceptable to users. During development of hormonal contraceptives, clinical trials seek to identify not only suppression of ovulation, but also the associated bleeding patterns, side effects, adverse health events, acceptability, adherence to correct use and incidence of contraceptive failure. During development of existing hormonal contraceptive products, a range of doses and regimens has been investigated to identify the most appropriate and acceptable preparation.

Currently available effective hormonal contraception already has low associated health risks and is well tolerated and effectively used by many, many people. There is a choice of methods, and there are additional non-contraceptive benefits. Health risks associated with use of combined hormonal contraception have reduced significantly over the decades since its introduction because it was demonstrated that the higher doses of ethinylestradiol initially used were not required to achieve effective, acceptable contraception. Doses are now very much lower. Progestogens are used alone to avoid the health risks associated with estrogen, and delivery by subdermal implant or intrauterine device enables systemic progestogen exposure to be reduced. New progestogens have been developed that offer benefits for suppression of ovulation, bleed control and tolerability.

Conclusion: FSRH CEU welcomes this mathematical model that could help to guide clinical studies in the development of new hormonal contraceptive regimens and broaden contraceptive choice. Lower doses of exogenous hormones could potentially offer fewer side effects and have lesser associated health risks. Clinical studies would be required to investigate how regimens suggested by a model like this performed in practice and whether there were significant benefits over existing contraceptive methods while maintaining contraceptive effectiveness.

References
Gavina BLA, de los Reyes V AA, Olufsen MS, Lenhart S, Ottesen JT (2023) Toward an optimal contraception dosing strategy. PLoS Comput Biol 19(4): e1010073. https://doi.org/10.1371/journal.pcbi.1010073 (accessed 13/04/2022)

Download the statement here.

ENDS

For further information, please contact: Lorna Kelly, External Affairs Manager via lkelly@fsrh.org

The Clinical Effectiveness Unit (CEU) was formed to support the Clinical Effectiveness Committee of the Faculty of Sexual & Reproductive Healthcare (FSRH), the largest UK professional membership organisation working at the heart of sexual and reproductive healthcare. The FSRH CEU promotes evidence based clinical practice and it is fully funded by the FSRH through membership fees. It is based in Edinburgh and it provides a members’ enquiry service, evidence-based guidance, new SRH product reviews and clinical audit/research. Find out more here.