Ethynyl Estradiol/[email protected]

Ethinyl estradiol (EE2) also sometimes written as 17α-ethinyl estradiol, ethinylestradiol, ethynyl estradiol, or ethinyl œstradiol, is a derivative of 17β-estradiol (E2), the major endogenous estrogen in humans. EE2 is an orally bioactive estrogen used in many formulations of combined oral contraceptive pills. It is one of the most commonly used medications for this purpose.

Transdermal ethinyl estradiol carries a greater risk of clot formation and venous thromboembolism than naturally occurring 17β-estradiol, which some have theorized to be related to different amounts of hepatic metabolism after absorption. The same contraindications and precautions apply for EE2 as with other estrogen medications.

Estinyl was a preparation of EE2 alone that was used for the management of menopausal symptoms and female hypogonadism.

EE2 is released into the environment as a xenoestrogen from the urine and feces of people who take it as a medication.

The major concern with unopposed estrogen (without progestogen) is of endometrial cancer. As such, the medication is generally prescribed with progesterone in the setting of birth control.

While E2 is readily absorbed when taken orally, it is also quickly inactivated by the liver. Substitution at C17 of the estrane steroid with an ethinyl group served to provide an estrogen that is much more resistant to degradation and paved the way for the development of oral contraceptives.

EE2 is absorbed in the small intestine and reaches a serum peak about 2 hours later. It undergoes extensive metabolism in the liver involving the cytochrome P450 3A4 isoenzyme. EE2 and its metabolites are excreted with the bile. Due to the effect of enterohepatic circulation a second peak is seen several hours later. Individually, wide variations exist in the overall absorption process, and can be further modified by drugs (i.e. antibiotics) that affect the enterohepatic circulation or liver enzymes. In circulation EE2 is almost fully bound to plasma albumin. It is metabolized by hydroxylation of the aromatic ring and excreted in both feces and urine, in part as glucuronide and sulfate conjugate.