Combined birth control pills that contain natural estradiol or an estradiol ester (e.g., estradiol valerate) include:
Estradiol, mainly as esters including estradiol valerate, estradiol cypionate, and estradiol enanthate, is also the exclusive estrogen used in combined injectable contraceptives.
As of 2021, more than 95% of prescriptions are for combined hormonal birth control forms containing the synthetic estrogen ethinylestradiol (EE). Hence, estradiol-based birth control pills are still not widely used.
Birth control pills containing estradiol have less impact on liver protein synthesis than ethinylestradiol-containing birth control pills, and it is thought that for this reason, they may pose less of a risk of venous thromboembolism (VTE). In accordance, although birth control pills containing estradiol valerate/dienogest are associated with a significantly increased risk of VTE, they are associated with a significantly lower risk of venous thromboembolism than birth control pills containing ethinylestradiol and a progestin. The risk of VTE with estradiol/nomegestrol acetate birth control pills is under study.
Incidence of irregular vaginal bleeding may be higher with estradiol-containing birth control pills in relation to the fact that estradiol is a weaker estrogen than ethinylestradiol in the endometrium.
The pharmacodynamics and pharmacokinetics of estradiol in the context of use in birth control pills have been studied and reviewed.
Experimental estradiol-containing birth control pills that were studied but never marketed include:
A large randomized controlled trial of a birth control pill containing ethinylestradiol/norethisterone acetate versus a birth control pill containing estradiol/estriol/norethisterone acetate has been conducted.