Idealized curves of estradiol levels over a period of 30 days after injection of different estradiol esters in women. CICs contain an estrogen and a progestin. The estrogen is generally a short-acting estradiol ester, which acts as a prodrug of estradiol. Esters of estradiol are natural and bioidentical estrogens, and are believed to have more favorable effects on lipid metabolism, cardiovascular health, and hemostasis than synthetic estrogens such as ethinylestradiol. The progestin is a long-acting progestogen ester, which may or may not act as a prodrug. Progesterone derivatives including medroxyprogesterone acetate, algestone acetophenide (dihydroxyprogesterone acetophenide), hydroxyprogesterone caproate, and megestrol acetate are active themselves and are not prodrugs, whereas the testosterone derivative norethisterone enantate is a prodrug of norethisterone. Regardless of whether they are prodrugs or not, steroid esters form a depot and have an extended duration of action due to a depot effect when administered by intramuscular or subcutaneous injection. Because CICs are administered parenterally, they bypass the first-pass effect in the liver and intestines that occurs with oral administration of estrogens. However, is estimated that about 20% of an administered dose does still eventually pass through the liver. Hence, these preparations are not completely liver-neutral. Nonetheless, they have dramatically reduced hepatic effects relative to oral ethinylestradiol. In addition, parenteral estradiol in general has about 4- or 5-fold reduced potency in the liver than oral estradiol. + Estradiol levels with combined<unk>  contraceptives Preparation Form Dose Estradiol Cmax Estradiol Tmax EV/NETE Oil solution 5 mg/50 mg 232–428 pg/mL 2 days EC/MPA Aqueous suspension 5 mg/25 mg 184–736 pg/mL 2–4 days EEn/DHPA Oil solution 10 mg/150 mg 314–317 pg/mL 4.2–8.1 days 5 mg/75 mg 148 pg/mL 6.5 days
Combined injectable birth control
Injectable birth control
Long-acting reversible contraception
Heat-based contraception
Male contraceptive
Combined hormonal contraception
Extended cycle combined hormonal contraceptive
Intrauterine device