Miles, R. A., Paulson, R. J., Lobo, R. A., Press, M. F., Dahmoush, L., & Sauer, M. V. (1994). Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertility and Sterility, 62(3), 485-490. https://doi.org/10.1016/s0015-0282(16)56935-0
Miles RA, Paulson RJ, Lobo RA, Press MF, Dahmoush L, Sauer MV. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril. 1994;62(3):485-490. doi:10.1016/s0015-0282(16)56935-0
Miles, Rachel A., et al. "Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study." Fertility and Sterility, vol. 62, no. 3, 1994, pp. 485-490.
For EndNote, Zotero or Mendeley:
Open access
Free to read
No reuse license
Free to read at the publisher (reported by Unpaywall and OpenAlex, not verified by RRM Academy)
Vaginal progesterone gave higher uterine levels than shots in 20 women
In 20 women with ovarian failure, vaginal progesterone reached the lining more than shots did. The 1994 study enrolled candidates for oocyte donation. Four women who ovulate were controls. Blood levels were lower with the vaginal route at both time points checked.
Key Findings
Uterine lining progesterone was greatest after vaginal use, compared with injection and with 4 ovulating controls (P < 0.05).
Blood progesterone was lower with vaginal use than with injection, in the 6 hours after the first dose and again on cycle day 21 (P < 0.05).
On day-21 ultrasound, 10 of 15 women using vaginal progesterone and 3 of 5 using injections showed pattern II, an early secretory appearance. Lining thickness was similar on day 21.
Lining dating under the microscope was similar between groups. Glands ran slightly behind after injection, a difference that was not statistically significant. Receptor content was similar.
Neither group reported side effects such as drowsiness or stomach complaints. One woman using injections developed local cellulitis at the injection site.
Interpretation
This comparison study followed 20 women with ovarian failure. They were preparing for oocyte donation. Fifteen women used vaginal progesterone. Five used injections. Four ovulating women served as controls. The authors credit a local uterine effect for the higher lining progesterone levels seen with vaginal use. They suggest lining levels may be a better gauge of progesterone action than blood levels. The findings support larger studies of vaginal progesterone delivery in hormone replacement protocols.
RRM Context
Progesterone is the hormone an ovulation makes, a central point in restorative reproductive medicine. The women in this study had ovarian failure. They took replacement hormones to prepare for a donor-egg transfer, an IVF procedure that bypasses ovulation. It does not restore ovulation. Blood and lining levels differed in this study. The authors use that gap to argue blood tests alone can miss how much hormone reaches the uterus.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To determine pharmacokinetic and endometrial effects of vaginally delivered micronized P.
Design
Functionally agonadal estrogen-replacement recipients received either micronized P administered vaginally or bi-daily IM injections of P. Hourly blood samples were obtained, from baseline to 6 hours after the initial dose of P and again on simulated cycle day 21 when transvaginal ultrasound (US) measurements and tissue samples of the endometrium were performed. Blood and tissue samples were assayed for P. Endometrial histology, estrogen receptor (ER) and P receptor (PR) contents were evaluated.
Setting
University of Southern California School of Medicine, Los Angeles, California.
Participants
Twenty functionally agonadal and four normally ovulating women.
Main Outcome Measures
Delivery differences were assessed by [1] endometrial P concentrations; [2] USs; [3] histologic datings; [4] ER and PR contents, and [5] serum P levels.
Results
Endometrial P concentrations were higher with vaginally administered P than endometrial concentrations observed in normal ovulatory women or women who consistently had the highest serum P after IM administration (11.50 +/- 2.60 versus 1.40 +/- 0.40 versus 0.30 +/- 0.10 ng/mg protein [36.56 +/- 8.27 versus 4.45 +/- 1.27 versus 0.95 +/- 0.32 nmol/L], respectively). After 7 days of P, no differences between either treatment regimen and control groups were detected by histologic, ultrasonographic, or immunocytochemical receptor analyses.
Conclusion
Vaginal micronized P enhances P delivery to the uterus compared with a standard IM regimen and results in a synchronous secretory endometrial histology in agonadal women preparing for embryo donation.
