Comparative estrogen exposure from compounded transdermal estradiol creams and Food and Drug Administration-approved transdermal estradiol gels and patches.

OBJECTIVE: The aim of this study was to evaluate the amount of estrogen exposure associated with the use of compounded transdermal estradiol (E2) creams and compare it with estrogen exposure associated with the use of Food and Drug Administration (FDA)-approved transdermal E2 patches and gels. METHODS: This was a retrospective cohort study that used clinical laboratory data collected from January 1, 2016, to December 31, 2019. Participants were first divided into three groups: postmenopausal women on no menopausal hormone therapy (n = 8,720); postmenopausal women using either a transdermal E2 patch, gel, or cream (n = 1,062); and premenopausal women on no hormonal therapy (n = 16,308). The postmenopausal menopausal hormone therapy group was further subdivided by formulation (patch [n = 777], gel [n = 132], or cream [n = 153]) and dose range (low, mid, or high). The Jonckheere-Terpstra trend test was used to determine if there was a dose-dependent trend in urinary E2 with increasing dose of compounded E2 cream (dose categories for E2 cream subanalysis, <0.5 mg [n = 49], ≥0.5-≤1.0 mg [n = 50], ≥1.0-≤1.5 mg [n = 58], and >1.5-≤3.0 mg [n = 46]). Urinary E2 and other characteristics were compared across formulations (within each dose range) using Kruskal-Wallis one-way analysis of variance. RESULTS: A dose-dependent, ordered trend existed for urinary E2 with increasing doses of compounded E2 cream (urinary E2 medians [ng/mg-Cr], 0.80 for <0.5 mg, 0.73 for ≥0.5-≤1.0 mg, 1.39 for ≥1.0-≤1.5 mg, and 1.74 for >1.5-≤3.0 mg; Jonckheere-Terpstra trend test, P < 0.001). Significant differences in urinary E2 concentrations were observed in all three dose ranges (Kruskal-Wallis one-way analysis of variance, P = 0.013 for low dose, P < 0.001 for mid dose, P = 0.009 for high dose). Comparison of E2 concentrations of compounded creams to E2 concentrations obtained with similar doses of FDA-approved patches and gels showed that the creams had significantly lower values than the patches and gels. CONCLUSIONS: Estrogen exposure from compounded transdermal E2 creams increases in a dose-dependent manner; however, the amount of estrogen exposure associated with compounded creams is significantly lower than estrogen exposure associated with FDA-approved transdermal E2 patches and gels. Clinicians should be aware of the direction and magnitude of these potential differences in estrogen exposure when encountering women who have either previously used or are currently using compounded E2 creams.

The Effects of Rhamnan Sulfate From Monostroma Nitidum: A Vascular-Focused Literature Review.

No Abstract Available.

Assessing estrogen exposure from transdermal estradiol patch therapy using a dried urine collection and a GC-MS/MS assay.

BACKGROUND: Transdermal estradiol patch therapy is often dosed based on patient reported symptoms. Although dosing based on serum estradiol concentrations has been considered, serum sampling is too invasive and inconvenient to use in real-world settings. The primary aim of this study was to determine if a dried urine assay could be used to assess estrogen exposure resulting from transdermal estradiol patch therapy at increasing doses. METHODS: This was a retrospective analysis of clinical laboratory data. Urinary estrogen profiles of postmenopausal women being treated with transdermal estradiol patches at differing doses (age = 56.8 ± 7.5) were selected from the database along with the profiles of women on no therapy for comparison (age = 55.1 ± 9.5). Metabolite concentrations were obtained using a multi-spot dried urine collection and a gas chromatography-tandem mass spectrometry assay. The Jonckheere-Terpstra test was used to assess for ordered differences across dose groups to determine if dose-dependent increases in urinary estrogens occurred with increasing doses. RESULTS: Median concentrations of estradiol and other estrogen metabolites increased with increasing doses of transdermal estradiol patch therapy (p < 0.001; Jonckheere-Terpstra test). For women who collected samples before and after initiating therapy, there were significant differences between before and after concentrations of estradiol and other estrogen metabolites. CONCLUSION: This large study conducted using real-world data demonstrated that a dried urine assay offers a viable method of assessing estrogen exposure differences that occur with the use of differing doses of transdermal estradiol patches. Further studies with prospective designs that include outcome measures are needed to confirm the findings of this study.

Assessment of estrogen exposure from transdermal estradiol gel therapy with a dried urine assay.

Transdermal estradiol gel is a commonly used menopausal hormone therapy. In research studies investigating the pharmacokinetics and clinical utility of transdermal estradiol gels, serum is often used to measure estradiol levels. Serum results only represent a moment in time during phlebotomy and thus provide little information and allow for limited inference unless serial measurements are performed. In contrast, dried urine may provide a representation of serum estradiol levels over a longer period of time, while also being non-invasive and easier to collect. The primary aim of this study was to evaluate a dried urine method to determine if it may be a viable option for evaluating estrogen exposure resulting from transdermal estradiol gel use. A secondary aim was to explore differences in the urinary estrogen profiles of premenopausal women on no therapy and postmenopausal women who were either on transdermal estradiol gel therapy or no therapy at all. The results of this study demonstrated that the expected dose-proportional changes in estrogen exposure can be observed in the urinary estrogen profile using a GC-MS/MS dried urine assay. The GC-MS/MS assay also showed the differences in the urinary estrogen profiles of premenopausal women, postmenopausal women on estrogen replacement therapy, and postmenopausal women on no therapy.