The effects of two galenic processes (micronisation and addition of oil) on the bioavailability of progesterone administrated orally were studied. After ingestion of progesterone (200 mg), mean plasma progesterone rapidly rises up to the 2nd hour and reaches levels of the normal luteal phase (12.6 +/- 2.6 ng/mg). It then decreases progressively up to the 8th hour. Daily administration of progesterone (300 mg) for 8 days significantly increases the endometrial concentration of the steroid (18.3 +/- 2.9 ng/ml) and efficiently corrects the tissular hormone deficiency. The breast tissue uptakes and concentrates equally progesterone. After oral administration of the natural hormone, progesterone concentrations are considerably increased in the three tissue compartments studied (normal glands: 25.0 +/- 9.7 ng/g; benign tumor: 38.0 +/- 9.1 ng/g; adipose tissue: 160.2 +/- 65.4 ng/g). These pharmaco-kinetic results correspond to the requirements of general substitutive hormone therapy. They justify the use of natural oral progesterone therapy, providing the amount given is modified according to immediate clinical tolerance.
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