Abstract
The absorption, metabolism, and clearance of progesterone from the peripheral circulation were investigated in five postmenopausal women after oral administration of 100 mg daily for five consecutive days. Maximal plasma concentrations of progesterone were observed within four hours after ingestion of the last dose, when the range (22.11-34.18 nmol/l; 696-1077 ng/100 ml) was comparable with that observed during the mid-luteal phase of the ovarian cycle. The surge in values lasted six hours, and progesterone concentrations remained raised for at least 96 hours. Of the three metabolites studied, the plasma concentrations of pregnanediol-3 alpha-glucuronide were most raised by treatment, the peak values ranging from 1097 nmol/l (54.9 microgram/100 ml) to over 2000 nmol/l (100 microgram/100 ml), which was the upper limit of the assay used. Concentrations of 17-hydroxyprogesterone were least raised, and the peak values ranged from 4.32 to 9.68 nmol/l (143-319 ng/100 ml). The plasma profile of 20 alpha-dihydroprogesterone most closely approximated that of progesterone, although the range of maximal values was lower (7.11-16.06 nmol/l; 228-514 ng/100 ml). Plasma concentrations of oestradiol were unchanged by giving progesterone. It is concluded that the increases in circulating concentrations of progesterone and the biologically active metabolite 20 alpha-dihydroprogesterone, and the duration of these increases, were sufficient to modulate the biochemistry of responsive tissues. Oral progesterone may thus have a therapeutic role, and this route of administration merits further investigation.
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Selected References
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