Padwick, M. L., Endacott, J., Matson, C., & Whitehead, M. I. (1986). Absorption and metabolism of oral progesterone when administered twice daily. Fertility and Sterility, 46(3), 402-407. https://doi.org/10.1016/s0015-0282(16)49576-2
Padwick ML, Endacott J, Matson C, Whitehead MI. Absorption and metabolism of oral progesterone when administered twice daily. Fertil Steril. 1986;46(3):402-407. doi:10.1016/s0015-0282(16)49576-2
Padwick, Malcolm L., et al. "Absorption and metabolism of oral progesterone when administered twice daily." Fertility and Sterility, vol. 46, no. 3, 1986, pp. 402-407.
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RRM Academy Synopsis
Oral progesterone taken twice daily raised blood levels within hours
In five postmenopausal women taking oral progesterone twice daily, average blood progesterone peaked 2 hours after each dose. A related hormone stayed raised for at least 12 hours. Blood progesterone then fell rapidly. Peak times varied widely among the five.
Study at a glance, pharmacokinetic study of five postmenopausal women: Blood progesterone peaked 2 hours after each oral dose in five women. Source: Padwick ML et al., 1986, PMID 12340955.
Key Findings
Five postmenopausal women took oral progesterone for 5 consecutive days, a smaller morning dose and a larger evening dose. Mean peak plasma progesterone came 2 hours after both doses.
Peak times ranged from 1 to 4 hours after the morning dose (mean 2.4 hours) and 2 to 8 hours after the evening dose (mean 3.6 hours).
Progesterone was significantly raised at its peak and for at least 12 hours after the last capsules (P < 0.01). Plasma progesterone fell rapidly after each dose.
20 alpha-dihydroprogesterone and pregnanediol-3 alpha-glucuronide stayed significantly raised for at least 84 hours after the last capsules (P < 0.05). 17-hydroxyprogesterone rose least.
Interpretation
This pharmacokinetic study followed five postmenopausal women through 5 days of twice-daily oral progesterone. Researchers drew blood at set times over 11 days. The active metabolite 20 alpha-dihydroprogesterone stayed raised long enough to act on tissue that responds to progesterone. The authors note the study measured blood levels. Tissue response was not measured directly. The findings support larger studies of oral progesterone dosing in other groups.
RRM Context
In restorative reproductive medicine, progesterone is the hormone the body raises after ovulation. It supports the uterine lining and early pregnancy. Data like this shows how oral progesterone moves through the body, so clinicians can give care that works with the body's own hormones.
Our editorial summary of this paper, not the article's abstract.
Abstract
The absorption, metabolism, and clearance of progesterone (P) from the peripheral circulation were investigated in five postmenopausal women after oral administration of 100 mg at 9:00 A.M. and 200 mg at 9:00 P.M. for 5 consecutive days. Mean peak plasma concentrations of P were observed 2 hours after ingestion of both the 100 and 200 mg doses and were 22.7 and 47.7 nmol/l, respectively. Of the three metabolites studied, the plasma concentrations of pregnanediol-3 alpha-glucuronide were most raised by treatment; those of 17-hydroxyprogesterone were least raised. Increases in the plasma levels of 20 alpha-dihydroprogesterone were more sustained than those of P, and the plasma concentrations remained elevated at approximately 20 nmol/l for at least 12 hours after P administration. We conclude that administration of oral P 100 mg in the morning and 200 mg at night increases the circulating concentrations of P and the biologically active metabolite 20 alpha-dihydroprogesterone, and that the duration of these increases is sufficient to evoke progestational responses in responsive end-organs.
