As of 2021, more than 95% of prescriptions are for combined hormonal birth control forms containing the
synthetic estrogen
ethinylestradiol (EE).[7] Hence, estradiol-based birth control pills are still not widely used.[7]
Side effects
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).[8][9] 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.[10] The risk of VTE with
estradiol/nomegestrol acetate birth control pills is under study.[11]
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.[3]
^"WJPPS | ABSTRACT"(PDF). World Journal of Pharmacy and Pharmaceutical Sciences.
^
abMawet, M; Gaspard, Ulysse; Foidart, JM (2021).
"Estetrol as estrogen in a combined oral contraceptive, from the first in-human study to the contraceptive efficacy"(PDF). European Gynecology and Obstetrics. 3 (1): 13–21. On the other side, only three different estrogens have been used in COC since 1961: the first one was the pro-drug mestranol rapidly replaced by its potent active form, ethinylestradiol (EE). Ethinylestradiol has remained the only estrogen used in COC during more than four decades. After initial unsuccessful attempts, estradiol (E2) was finally introduced into two COCs in the early 2010': in the form of the pro-drug E2 valerate in combination with dienogest (E2V/DNG) and in the form of E2 in combination with nomegestrol acetate [4, 5]. However, these E2-containing COCs are less prescribed as over 95% of combined hormonal contraceptive users still utilize an EE-containing product.
^Douxfils J, Morimont L, Bouvy C (October 2020). "Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk". Semin Thromb Hemost. 46 (8): 872–886.
doi:
10.1055/s-0040-1714140.
PMID33080636.
S2CID224821517.
^Kuhnz W, Gansau C, Mahler M (September 1993). "Pharmacokinetics of estradiol, free and total estrone, in young women following single intravenous and oral administration of 17β-estradiol". Arzneimittelforschung. 43 (9): 966–73.
ISSN0004-4172.
PMID8240460.
^"A randomized, double-blind study of two combined oral contraceptives containing the same progestogen, but different estrogens. World Health Organization Task Force on Oral Contraception". Contraception. 21 (5): 445–59. May 1980.
doi:
10.1016/0010-7824(80)90010-4.
PMID7428356.
As of 2021, more than 95% of prescriptions are for combined hormonal birth control forms containing the
synthetic estrogen
ethinylestradiol (EE).[7] Hence, estradiol-based birth control pills are still not widely used.[7]
Side effects
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).[8][9] 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.[10] The risk of VTE with
estradiol/nomegestrol acetate birth control pills is under study.[11]
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.[3]
^"WJPPS | ABSTRACT"(PDF). World Journal of Pharmacy and Pharmaceutical Sciences.
^
abMawet, M; Gaspard, Ulysse; Foidart, JM (2021).
"Estetrol as estrogen in a combined oral contraceptive, from the first in-human study to the contraceptive efficacy"(PDF). European Gynecology and Obstetrics. 3 (1): 13–21. On the other side, only three different estrogens have been used in COC since 1961: the first one was the pro-drug mestranol rapidly replaced by its potent active form, ethinylestradiol (EE). Ethinylestradiol has remained the only estrogen used in COC during more than four decades. After initial unsuccessful attempts, estradiol (E2) was finally introduced into two COCs in the early 2010': in the form of the pro-drug E2 valerate in combination with dienogest (E2V/DNG) and in the form of E2 in combination with nomegestrol acetate [4, 5]. However, these E2-containing COCs are less prescribed as over 95% of combined hormonal contraceptive users still utilize an EE-containing product.
^Douxfils J, Morimont L, Bouvy C (October 2020). "Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk". Semin Thromb Hemost. 46 (8): 872–886.
doi:
10.1055/s-0040-1714140.
PMID33080636.
S2CID224821517.
^Kuhnz W, Gansau C, Mahler M (September 1993). "Pharmacokinetics of estradiol, free and total estrone, in young women following single intravenous and oral administration of 17β-estradiol". Arzneimittelforschung. 43 (9): 966–73.
ISSN0004-4172.
PMID8240460.
^"A randomized, double-blind study of two combined oral contraceptives containing the same progestogen, but different estrogens. World Health Organization Task Force on Oral Contraception". Contraception. 21 (5): 445–59. May 1980.
doi:
10.1016/0010-7824(80)90010-4.
PMID7428356.