Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

Abstract

OBJECTIVE:The objective of this study was to evaluate the serum levels of progesterone resulting from the application of a progesterone cream to the skin. STUDY DESIGN: Six postmenopausal women were evaluated at a university clinic over a 4-week period. RESULTS: Transdermal estradiol 0.05 mg was applied 2 days before the first application of progesterone (30 mg/d) and was continued throughout the study. Patches were changed twice a week. Progesterone cream was applied once a day for 2 weeks. On day 15 and for the next 2 weeks, the progesterone cream was applied twice daily (60 mg/d). Serum 17β-estradiol and progesterone were measured at 9 different times over a 24-hour period on day 1 and at weekly intervals for the 4-week duration of the study. Serum 17β-estradiol concentrations varied among women, with mean concentrations of 40 to 64 pg/mL observed. Consistency in 17β-estradiol concentrations was found within individual persons throughout the study. Serum progesterone concentrations also varied among women, with mean concentrations ranging from 1.6 to 3.3 ng/mL. After 2 weeks of percutaneous dosing, progesterone concentrations were sustained for at least 8 hours and were consistent within a given person. An appropriate increase in progesterone concentration occurred after 4 weeks compared with 2 weeks of application. Individually, a 0.53 correlation, significant at P < .0001, was seen between the absorption of 17β-estradiol and progesterone. CONCLUSION: Significant increases in serum concentrations of progesterone were observed in all of the women studied. The percutaneous absorption of progesterone correlates strongly with the absorption of transdermal 17β-estradiol. There is variance in absorption of progesterone just as with 17β-estradiol, and the 2 measures are closely correlated. The percutaneous application of progesterone cream appears to be a safe and effective route of administration. (Am J Obstet Gynecol 1999;180:1504-11.)

A study to look at hormonal absorption of progesterone cream used in conjunction with transdermal estrogen

“…In our study, significant increases from baseline were seen in both estradiol and progesterone levels after 12 weeks of treatment. Burry and colleagues suggested that by use of 30-60 mg of progesterone cream, luteal levels could be achieved [17]. The maximum median plasma progesterone level in our study of 2.5 nmol/l is far lower than that typically seen in the luteal phase of a premenopausal woman, and lower than levels achieved with standard doses of oral or vaginal progesterone.…”

“…In a smaller study using 50 mg transdermal estrogen and 30-60 mg transdermal Progest 1 cream, a similar association between estradiol and progesterone levels was seen suggesting the possibility of similar mechanisms of absorption for both hormones [17].…”

Double-blind placebo-controlled study to evaluate the effect of pro-juven progesterone cream on atherosclerosis and bone density

“…This is consistent with reports from studies of other formulations of progesterone cream used for short durations, either with or without concomitant estrogen. [21][22][23][24][31][32][33] The effect of progesterone cream on progression of asymptomatic atherosclerosis was evaluated. Unadjusted results gave a mean (95% CI) increase in plaque thickness over the course of three years of 0.93 mm (0.3-1.6) in patients randomized to progesterone.…”

Novel actions of progesterone: what we know today and what will be the scenario in the future?

“…Natural progesterone is well absorbed transdermally, avoids first‐pass hepatic metabolism and is relatively free from adverse effects [95] . The percutaneous application of progesterone cream could be a safe and effective route of administration [96] …”