Villanueva, B., Casper, R. F., & Yen, S. S. (1981). Intravaginal administration of progesterone: enhanced absorption after estrogen treatment. Fertility and Sterility, 35(4), 433-437. https://doi.org/10.1016/s0015-0282(16)45439-7
Villanueva B, Casper RF, Yen SS. Intravaginal administration of progesterone: enhanced absorption after estrogen treatment. Fertil Steril. 1981;35(4):433-437. doi:10.1016/s0015-0282(16)45439-7
Villanueva, Benito, et al. "Intravaginal administration of progesterone: enhanced absorption after estrogen treatment." Fertility and Sterility, vol. 35, no. 4, 1981, pp. 433-437.
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Vaginal progesterone raised blood levels fastest after estrogen
Women past menopause who took estrogen absorbed vaginal progesterone fastest and reached the highest early blood levels. In this 1981 study, small groups of women past menopause got the same progesterone liquid three ways. They used it vaginally, by injection, or under the tongue. Blood was tested for a day.
Key Findings
Four postmenopausal women taking estrogen reached 30 to 40 times their baseline progesterone level within 1 to 2 hours of vaginal use. Levels stayed high over the 7 hours of sampling.
Five women taking no hormone peaked at 20 times baseline after vaginal use. Their total absorbed over 24 hours was half that of the estrogen-treated vaginal group.
Eight women given an injection into the muscle rose gradually and reached 30 times baseline at 24 hours. Their total absorbed matched the estrogen-treated vaginal group.
Five women who took progesterone under the tongue reached about 10 times baseline within 2 hours and returned to baseline by 24 hours.
At 1 hour, the rise from baseline was 2 to 3 times larger after vaginal use than after injection or under-the-tongue use.
Interpretation
The study is a small 1981 absorption experiment in volunteers. Each route was tested in separate women. Researchers measured blood progesterone only. They reported no pregnancy, symptom, or uterine-lining outcomes. The women were postmenopausal, and no cycling women took part. The authors tested one liquid and suggested that the carrier liquid may change how fast the vagina absorbs progesterone. They also suggested that more blood flow in the vagina and more carrier proteins in estrogen-treated women might explain the higher levels. The paper presents both as possible explanations.
RRM Context
Restorative reproductive medicine favors the body's own hormones. The authors name one gain of the vaginal route: it makes natural progesterone possible. Synthetic progestins taken by mouth are a different substance. The paper covers no fertility, luteal support, or cycle-timed use.
Our editorial summary of this paper, not the article's abstract.
Abstract
A progesterone solution was administered by intravaginal instillation, intramuscular injection, and sublingually to estrogen-deficient women, with or without estradiol (E2) replacement, and serum progesterone (P) concentrations were measured by radioimmunoassay. Intravaginal application to postmenopausal subjects receiving E2 gave the highest values of serum P: 10 times baseline at 15 minutes and 30 to 40 times at 1 to 2 hours, with sustained levels, for 7 hours and decline to 10 times baseline at 24 hours. Intravaginal application to hypoestrogenic women gave similar results, but of much lower magnitude (highest value, 20 times baseline). Intramuscular injection, in contradistinction, showed gradually increasing levels over the study period, up to 30 times basal values at 24 hours. It contrast, sublingual application produced very modest serum increases, to approximately 10 times baseline within 2 hours and return to basal value at 24 hours. Since the most rapid and highest levels were observed by vaginal application to postmenopausal women receiving estrogen, and considering that the vagina has been similarly shown to be very effective for estrogen absorption, it is conceived that full hormone replacement could be accomplished in the deficient states by cyclic vaginal application of both steroids.
