Ethinylestradiol
Synthetic, orally potent estrogen that forms the estrogen backbone of most combined oral contraceptives. The 17-alpha-ethinyl group resists hepatic metabolism, making it highly bioavailable orally but disproportionately impactful on liver-derived clotting factors.
01 Overview
Ethinylestradiol is a semi-synthetic estrogen used for decades in combined oral contraceptives and, historically, in feminizing regimens. Its ethinyl group blocks first-pass inactivation, giving strong, predictable oral activity at microgram doses.
That same hepatic stability means it exerts an outsized effect on liver protein synthesis, including clotting factors, so it carries a higher thrombotic risk than transdermal or bioidentical estradiol. For this reason it has largely been abandoned in transfeminine care in favour of estradiol, though it remains a contraceptive mainstay.
02 Mechanism
A potent estrogen receptor agonist resistant to first-pass metabolism; in contraceptives it suppresses FSH/LH to inhibit ovulation and stabilise the endometrium.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Combined oral contraceptive | 20–35 mcg/day | Oral | Modern COCs use 20-35 mcg with a progestin. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Ovulation suppressionWith a progestin, reliably prevents ovulation and provides contraception. | Clinical | ||
| Cycle controlStabilises the endometrium, reducing irregular bleeding. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Venous thromboembolismHigher VTE risk than bioidentical estradiol due to strong hepatic first-pass effect on clotting factors. | Life-threatening | Uncommon but elevated vs estradiol | Clinical | |
| HypertensionCan raise blood pressure via hepatic angiotensinogen synthesis. | Moderate | Uncommon | Clinical | |
| Nausea and breast tendernessCommon in the first cycles, usually settling. | Mild | Common early | Clinical |