Hargrove, J. T., Maxson, W. S., & Wentz, A. C. (1989). Absorption of oral progesterone is influenced by vehicle and particle size. American Journal of Obstetrics and Gynecology, 161(4), 948-951. https://doi.org/10.1016/0002-9378(89)90759-x
Hargrove JT, Maxson WS, Wentz AC. Absorption of oral progesterone is influenced by vehicle and particle size. Am J Obstet Gynecol. 1989;161(4):948-951. doi:10.1016/0002-9378(89)90759-x
Hargrove, J. T., et al. "Absorption of oral progesterone is influenced by vehicle and particle size." American Journal of Obstetrics and Gynecology, vol. 161, no. 4, 1989, pp. 948-951.
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Oral micronized progesterone in oil gave the highest blood levels
A 1989 study gave five oral progesterone preparations to six postmenopausal women and one man, in separate test sessions. All five raised blood levels. In this small group, micronized progesterone in oil had a significantly higher average peak than the other four.
Key Findings
Seven volunteers, six postmenopausal women and one man, each took five preparations. Micronized progesterone was tested twice in each person: 14 tests, against 7 for the others.
Every preparation produced a significant rise in serum progesterone after oral dosing.
Micronized progesterone in oil had the highest average peak (p < 0.005). Its time to peak was the shortest: 2.0 ± 0.3 hours (mean ± SEM, p < 0.05).
The other four preparations did not differ significantly in peak, time to peak or area under the curve. Their times to peak ran from 3.2 to 4.1 hours.
Six hours after dosing, all preparations still sat above baseline and matched one another. The authors report no untoward effects in the 7 volunteers.
Interpretation
The study is a small single-dose comparison of blood levels. Six volunteers were postmenopausal women and one was a man, tested after an overnight fast. None was a woman of reproductive age. The authors measured only serum progesterone. A repeat run of micronized progesterone varied between sessions, though not significantly. The authors credit micronizing plus oil for the best absorption, since plain-milled progesterone in oil and enteric coating did not help. The results describe absorption after one dose.
RRM Context
The authors name luteal phase inadequacy as one use of progestins. They say synthetic progestins do not faithfully copy natural progesterone. NaProTechnology, developed by Dr. Thomas W. Hilgers, uses natural progesterone. How well it is absorbed by mouth depends on particle size and vehicle.
Our editorial summary of this paper, not the article's abstract.
Abstract
The oral route of progesterone administration has long been considered impractical because of poor absorption and short biologic half-life. Recent reports suggest that micronization of progesterone enhances absorption and increases serum and tissue levels of progesterone. This study checks serum progesterone levels before and 0.5, 1, 2, 3, 4, and 6 hours after oral administration of 200 mg of progesterone in seven subjects. Progesterone was plain milled, micronized, plain milled in oil, micronized in oil, or micronized in enteric-coated capsules. All patients exhibited a significant increase in serum progesterone levels after oral progesterone administration. Mean peak progesterone levels (30.3 +/- 7.0 ng/ml) (p less than 0.005) were achieved with micronized progesterone in oil at 2.0 +/- 0.3 (p less than 0.05) hours after administration. Four types of oral progesterone had equivalent mean peak elevations and mean times to peak: plain milled, 9.6 +/- 2.5 ng/ml at 4.0 +/- 0.5 hours; micronized 13.2 +/- 2.4 ng/ml at 3.2 +/- 0.4 hours; plain milled in oil, 11.3 +/- 3.0 ng/ml at 4.0 +/- 0.5 hours; and micronized in enteric-coated capsules, 11.2 +/- 3.0 ng/ml at 4.1 +/- 0.7 hours. Contrary to traditional teaching, these data show that significant serum progesterone levels can be achieved by oral administration. Absorption can be significantly improved by the physical characteristics of the progesterone and the vehicle used with oral administration.
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