Bioidentical compounded hormones: A pharmacokinetic and pharmacogenomic evaluation in a randomized clinical trial

ABSTRACT 1: Bioidentical Hormone Pharmacokinetics: A Randomized Trial. The objective of this study was to compare the pharmacokinetics of different strengths of bioidentical compounded estrogen creams and conventional bioidentical estradiol patch. A secondary outcome was the comparison of compounded and conventional bioidentical progesterone preparations.;Results: Fifty four women were screened and forty were enrolled in the study. All participants completed the study; results were analyzable for 37 women. The average age of the participants was 54.8 years; their average BMI was 29 kg/m2. Side effects with study medications were rare, and included abdominal bloating and fluid retention. Pharmacokinetics of E1, E2 and E3 were compared across treatment groups, with E2 kinetics serving as the primary treatment outcome.;At baseline, all participants had postmenopausal levels of E2, thereby confirming the absence of endogenous hormone production. Although serum E2 levels increased incrementally as the dose of Bi-est cream increased, they remained consistently lower than the patch. The absorption patterns for the cream groups were variable and inconsistent, unlike those with the E2 patches. The area under the curve (AUC) for E2 at 24-hours and at steady-state was lower for all Bi-est groups compared to the patch. Serum E1 levels increased progressively with higher dose of Bi-est cream; but they remained lower with all cream groups compared to the patch. Serum E3 levels increased only marginally in all treatment groups, and the patch group had the highest levels. Serum progesterone levels after compounded and commercial preparations were comparable.;Conclusion: The study provides novel and clinically relevant information regarding pharmacokinetics of bioidentical compounded hormones. The study suggests that the current dosing regimens for the compounded creams in Vanicream provide much lower than expected levels of estrogen fractions. The absorption from the creams was significantly more unpredictable compared to the skin patches, despite optimal standardization of dosing and technique of administration. Further, E3 levels increased with E2 containing patch, likely secondary to endogenous conversion from E2, and E3 levels were actually higher in the patch group compared to the creams.;ABSTRACT 2: Pharmacogenomics Of Estrogen Sulfatase Enzymes: A Clinical Trial. Serum estrogen levels may be affected by the variations in the copy numbers and single nucleotide polymorphisms (SNPs) of genes coding for estrogen metabolizing enzymes, called sulfotransferases or SULT enzymes. We measured the genetic variations in SULT1A1 copy number and SNPs and assessed their effects on serum estrogen levels in 40 women who participated in the pharmacokinetic component of our study, as described above.;Results: Of the 40 women who enrolled in the pharmacokinetic study, genotyping data was analyzable for 33 women. We measured the effects of copy number variation (CNV), metabolism status and 3 polymorphisms (RS3760091, RS750115, RS9282861) on E2 levels at 24-hours and at steady-state. None of the genetic markers were found to have a statistically significant association with E2 at 24-hours, either in the Vivelle-Dot group or the Bi-est groups. With the exception of RS9282861, these genetic markers were also not found to be significantly associated with the steady state E2. For RS9282861, some evidence of an association at steady state E2 suggested that E2 may be lower in those with a higher number of T alleles (p=0.025). However, taking into account multiple testing (5 variants and 2 phenotypes), this p-value was not statistically significant (Bonferroni adjusted p-value = 0.025*10 = 0.25).;Conclusions: This study did not detect any statistically significant effects of copy number variations or polymorphisms of SULT1A1 on E2 kinetics, although there was a non-statistically significant association between RS9282861 and steady state E2. We were not adequately powered to detect smaller effects due to small sample size and highly variable E2 kinetics. (Abstract shortened by UMI.)...