Caution on the use of saliva measurements to monitor absorption of progesterone from transdermal creams in postmenopausal women.

Objectives: To determine the levels of progesterone in plasma, red cells and saliva as well as pregnanediol-3-glucuronide excretion in postmenopausal women using transdermal progesterone creams.

Methods: A double-blind placebo controlled study was carried out using 24 postmenopausal women. Creams (placebo, 20 or 40 mg progesterone/g) were applied twice daily for 3 weeks followed by 1 week without before a further 3-week treatment. Morning samples were collected at 0, 1, 3, 4, 7 and 8 weeks for analysis.

Results: There were small increases in plasma progesterone levels and pregnanediol-3-glucuronide excretion compared to the placebo group and red cell progesterone levels never exceeded plasma levels during progesterone cream use. Saliva progesterone levels were very high and variable in the progesterone cream groups compared to the placebo group and presented a paradox to the usual relationship observed between plasma and saliva progesterone in premenopausal women.

Conclusion: The absorption of progesterone from transdermal creams is low and we caution against the use of saliva measurements to monitor progesterone absorption. The low systemic absorption of progesterone may not be due to peripheral conversion by 5 alpha-reductase(s). We also conclude that the low level of progesterone associated with red cells suggests they are not important in the delivery of progesterone to target tissues.