Progestins

Question 1

Which are the Progestins?

Answer 1

• Progesterone
• Micronized Progesterone (Promethium®)
• C-21 synthetic
• C-19
• 2nd Generation Progestins
• Drospirenone (Yasmin®)

Question 2

What are the characteristics of Progesterone?

Answer 2

● Competitive antagonist at aldosterone receptors
● Progesterone and synthetic analogs =”progestins”
● Significant 1st pass metabolism
● Metabolites: anxiolytic, sedative, hypnotic properties

Question 3

What are the characteristics of Micronized Progesterone (Promethium®)?

Answer 3

● Orally active – need to counteract large first-pass metabolism →get higher percentage absorbed which allows clinically-relevant serum concentrations to be attained (also true for micronized estrogen)

Question 4

What are the characteristics of C-21 synthetic?

Answer 4

● More like progesterone – retain all 21 carbons
● Produce more physiological endometrium than C19s
● 17 α- acetoxy derivatives: medroxyprogesterone
acetate (Provera®) , available in a depot formulation and megestrol acetate (Megase®) – stimulates appetite in HIV patients with wasting
● Promote secretory functions of endometrium
● Can maintain endometrium & placenta
● Compete with aldosterone (antagonists)
● No estrogenic or androgenic effects

Question 5

What are the characteristics of C-19?

Answer 5

● Remove 2 –carbon acetate group on D ring
● Decidual change in endometrium (glandular atrophy)
● Do not support pregnancy!
● Effective gonadotropin inhibitors (used in O.C’.s)
● Some androgenic and estrogenic effects
● Promote viscous secretion from endometrium to
cause hostile environment for sperm migration
● (important action in contraception)
● Examples of 1st generation progestins (referred to as
“no-“ or “nor-“ : norethindrone acetate, ethynodiol acetate, norgestrel, norethynodrel

Question 6

What are the characteristics of 2nd Generation Progestins?

Answer 6

● Examples: norgestimate, gestodene, desogestrel
● Have some inherent androgenic activity
● Decrease levels of free testosterone
● MOA = cause increase in sex-hormone binding
globulin synthesis which ties up testosterone
● Net effect = ↓ androgenic effects (less acne/oily skin

Question 7

What are the characteristics of Drospirenone (Yasmin®)?

Answer 7

● Considered a 3rd generation progestin, used in combo with ethinyl estradiol
● Structural analogue of spironolactone & blocks aldosterone receptors to prevent Na+ & water retention → can produce hyperkalemia
● Possess anti-androgenic activity to minimize acne, oily skin, hirsuitism, weight gain
● Adverse effects: Increased risk of hyperkalemia due to blockade of aldosterone receptor