Assessment of Bioavailability of Oral Micronized Progesterone Using a Salivary Progesterone Enzymeimmunoassay

Abstract

Salivary progesterone was measured sequentially by enzymeimmunoassay following 1 month and 6 months of oral therapy with 100 mg of micronized progesterone (MOP) in 40 healthy estrogenized postmenopausal women (aged 40-68 years). MOP was administered for 23 days every month.

There were striking differences in the absorption of MOP between various subjects. Significant increases occurred in salivary progesterone concentrations over baseline and pretreatment levels and persisted for at least 10 h. Levels of salivary progesterone remained higher than pretreatment levels for at least 24 h after administration of MOP. Maximum mean concentrations of salivary progesterone of 827.2 and 888pmol/l in the 1st and 6th months of therapy, respectively, were achieved within 2 h of administration and were above the 95th percentile of a control corridor which corresponds to the range found in the luteal phase. The areas under the salivary progesterone curve (AUC_o-24h, pmol/l) were 7177.75 and 7388.20 respectively, in the 1st and 6th months of therapy but the difference was not statistically significant. Serum and salivary progesterone peaked simultaneously and there was a significant correlation between the concentrations measured concurrently (y = 233.08 + 35.575yi; r=0.89, p < 0.001) thus supporting the current concept of a relatively rapid diffusion of steroids from plasma to saliva.

Results of this study confirm those of previous investigations which monitored the bioavailability of MOP with the use of serum progesterone measurements and showed that luteal phase progesterone concentrations can be attained easily. The use of non-invasive salivary sampling and a cost-effective, direct enzymeimmunoassay showed a considerable advantage in the present study, compared with previous ones. We conclude that 100 mg MOP should be given at least twice-daily to maintain a stable physiological luteal phase level of progesterone during clinical hormone replacement therapy.

Key Words:

• Micronized Progesterone
• Bioavailability
• Salivary Steroids
• Enzymeimmunoassay
• Postmenopause