Serum and Tissue Hormone Levels of Vaginally and Orally Administered Estradiol

Am J Obstet Gynecol. 1999 Jun;180(6 Pt 1):1480-3. doi: 10.1016/s0002-9378(99)70042-6.


Objective: Our purpose was to determine serum and endometrial estradiol levels when micronized estradiol is administered vaginally and orally.

Study design: Five subjects were given oral estradiol (2 mg twice daily), during an artificial luteal phase, and another group of 5 subjects were given the same dose of estradiol by the vaginal route. Endometrial biopsies and blood samples were obtained on day 21 of the cycle, 2 hours after the last dose was administered. Tissue and blood samples were assayed for estradiol.

Results: Serum estradiol levels were significantly higher with vaginally administered estradiol than with orally administered estradiol (2344 +/- 398 vs 279 +/- 76 pg/mL, P <.005). Endometrial estradiol concentrations were also significantly higher with vaginally administered estradiol than with the oral preparation (918 +/- 412 vs 13 +/- 2 pg/mg protein, P <.05).

Conclusions: Vaginal administration of estradiol is more effective in increasing serum and endometrial levels of estradiol than the oral route and may represent the optimal route of administration for recipients of egg donation. If the vaginal route of estradiol administration is considered for menopausal replacement therapy, much lower doses of the standard oral quantities should be used. Furthermore, if the uterus is present, a progestin must be used to compensate for the high tissue levels of estradiol.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravaginal
  • Administration, Oral
  • Adult
  • Embryo Transfer
  • Endometrium / metabolism*
  • Estradiol / administration & dosage*
  • Estradiol / blood
  • Estradiol / pharmacokinetics*
  • Female
  • Humans
  • Kinetics
  • Middle Aged
  • Progesterone / administration & dosage


  • Progesterone
  • Estradiol