Premarin Cream Content and Composition
Premarin vaginal cream contains conjugated equine estrogens derived from pregnant mare urine, with each gram containing 0.625 mg of conjugated estrogens in a cream base. 1
Active Ingredients
The cream contains a complex mixture of at least 10 biologically active estrogens, all present as sulfate esters 2:
Ring B saturated estrogens:
- Estrone sulfate
- 17β-estradiol sulfate
- 17α-estradiol sulfate 2
Ring B unsaturated estrogens:
- Equilin sulfate
- 17β-dihydroequilin sulfate
- 17α-dihydroequilin sulfate
- Equilenin sulfate
- 17β-dihydroequilenin sulfate
- 17α-dihydroequilenin sulfate
- Δ8-estrone sulfate 2
Typical Dosing
For moderate to severe dyspareunia due to vulvar and vaginal atrophy, the FDA-approved dosing is 0.5 to 2 grams intravaginally daily (delivering 0.3125 to 1.25 mg conjugated estrogens). 1 Historical studies used 1.25 mg conjugated estrogens daily (approximately 2 grams of cream). 3
Important Clinical Considerations
Systemic absorption is rapid, efficient, and sustained - vaginal application results in high systemic estrogen levels, not just local effects. 4 This means:
- Plasma estrone (E1) and estradiol (E2) levels rise significantly and progressively with daily use 3
- Sex hormone-binding globulin (SHBG) increases 3
- FSH and LH are suppressed 3
- Endometrial proliferation can occur, requiring progestin protection in women with intact uteri 3
Critical safety point: The vaginal route is contraindicated when systemic estrogen therapy is contraindicated, as absorption is substantial and sustained. 4
Pharmacological Activity
All 10 estrogen components demonstrate estrogenic activity through estrogen receptor binding, with individual components like equilin sulfate, Δ8-estrone sulfate, and 17β-dihydroequilin sulfate showing potent estrogenic effects. 2 The overall pharmacological effect represents the sum of these individual activities. 2