Table 1.

Pharmacologic difference among progestogens

1. Progesterone	• A natural progestogen (21 carbons) • Undergoes extensive metabolism during hepatic first pass • Approximately 20% is bound to CBG • Has low bioavailability (<5%) • Half-life is 16–18 hours after oral dosing • Binds with relatively high affinity to the PRs and MR • Typical daily dose used for endometrial protection is 200 mg
2. Medroxyprogesterone acetate	• Structurally related to progesterone • Acetate group at the carbon 21 position limits metabolism (steric hinderance) • Does not bind to CBG or SHBG • Has high bioavailability (>90%) • Its half-life is ~22 hours • Binds with high affinity to the PRs • Has relatively high receptor/ligand binding affinity (RBA) for the AR but its androgenic activity is controversial • Has high RBA for the GR, displays higher binding affinity for the GR than cortisol • Common daily doses for endometrial protection are 2.5 and 5 mg
3. Norethindrone (Norethisterone)	• Structurally related to testosterone • Ethinyl group at carbon 17 limits metabolism; can be converted to ethinyl estradiol • Binds to SHBG • Its bioavailability is ~64% and half-life is ~8 hours • Binds with relatively high affinity to the PRs and has some androgenic activity
4. Levonorgestrel	• Structurally related to testosterone • Metabolism is very limited during hepatic first pass • Binds to SHBG • Its bioavailability is 89–99% and half-life 10–13 hours • It binds with high affinity to the PRs and AR, and has substantial androgenic activity
5. Desogestrel	• Structurally related to testosterone; it is prodrug that is rapidly converted to etonogestrel during hepatic first pass • Etonogestrel binds to SHBG, has a bioavailability of 62–76% and half-life of 12–24 hours, and has a high affinity for the PRs
6. Drospirenone	• Structurally related to spironolactone • Does not bind to SHBG or CBG • Has bioavailability of ~66% and half-life of ~32 hours • Has a relatively low RBA for the PRs but a very high RBA for the MR; exhibits both anti-androgenic and anti-mineralcorticoid properties

Adapted with permission from Stanczyk, F.Z., et al., Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr Rev, 2013. 34(2): p. 171–208.