Disappearance and unexpected reappearance of progesterone in the circulation of the monkey: novel hormone kinetics.

Abstract

1. Intravenous injection of [3H]progesterone in non-pregnant monkeys resulted in total disappearance of the labelled hormone from the circulation within 3 h. However, 0-5-1P75 h after disappearance the hormone reappeared, reaching 20% (median, 5%) of the initial maximal concentration. 2. Reappearance of labelled hormone was accompanied by similar fluctuations in the levels of labelled metabolites, [3H]20a-dihydroprogesterone and [3H]17a-hydroxyprogesterone, which reached 61 % (median, 14%) and 120% (median, 13%), respectively, of the initial maximal concentrations. 3. Chromatography was used to separate labelled progesterone and its metabolites. Efficiency of the procedure was determined separately in each sample and for each steroid. All data were corrected for percentage recovery. 4. Analytical equations were devised, based on the theory of compartmental systems with continuously distributed time lags, to describe the unexpected kinetics of progesterone levels. The coefficients of determination ranged from 86 to 99% (median, 96%) which indicates that the equations enabled reliable prediction of hormone levels in blood within the time range studied. 5. The unexpected reappearance of labelled progesterone cannot be explained by hormone secretion but only by a delayed release from tissue stores, since progesterone does not undergo enterohepatic recirculation. Thus, a previously undescribed mechanism affecting circulating progesterone levels, and perhaps those of other hormones, exists.

A double-blind placebo-controlled study to evaluate the effect of progestelle progesterone cream on postmenopausal women

“…22 Estrogen priming of the skin may help. 23 Once absorbed progesterone distributes to the fat compartment 24,25 and may accumulate in the uterus, lung, salivary gland, liver and kidney 26 and breast, 27 which suggests that serum levels might not accurately reflect tissue levels.…”

Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

“…The rate-limiting factor for skin absorption of ovarian corticosteroids may be related to the individual transport and metabolism differences in the skin and its appendages. 12,14 This study has demonstrated that progesterone is absorbed through the skin and that luteal levels of serum progesterone can be achieved. It appears that the progesterone cream used in this study may be a reasonable delivery system for elevating progesterone in postmenopausal women and thus for managing part or possibly all symptoms of ovarian corticosteroid deficiency.…”

“…Pharmacokinetics of progesterone are quite complex, and thus the serum levels are not obvious and may be counterintuitive. 14 No evidence exists as to whether percutaneous progesterone creams are protective against endometrial cancer. This study reports that percutaneous absorption of a progesterone cream occurred in 6 postmenopausal women treated with estrogen.…”

Cortisol response and ovarian hormones in juvenile and cycling female Cebus monkeys: effect of stress and dexamethasone

“…The question arises as to why the progesterone overshoot induced by glucocorticoids was not accompanied by a modification in estradiol. Reports revealing some kinetic particularities of progesterone and showing that the glucocorticoid excess directly increases the production and the metabolic clearance rate of this steroid might be of particular interest to answer this question [Kowalski et al, 1993[Kowalski et al, , 1996.…”