CERSI Collaborators: Audra Stinchcomb, PhD, RPh (University of Maryland, Baltimore)

FDA Collaborators: Daiva Shetty, MD; Raquel Tapia, MD; Yanhui Lu, PhD; Marianne San Antonio, DO; Erin South, PharmD; Susan Bersoff-Matcha, MD

Project Start: April 5, 2022

Regulatory Science Challenge

Estradiol is a hormone that plays important roles in overall human health and reproductive function. Estradiol is secreted by the ovaries, and when levels decrease as women age, menopausal symptoms such as hot flashes, sweating, vaginal dryness, insomnia, and depression may occur. Many types of compounded1 topical estradiol products are available to the public to treat menopausal or postmenopausal symptoms. Current most popular compounded estradiol products use gel, cream, or ointment preparations to help the hormone absorb through the skin and into the blood circulation. Pharmacy compounded drug products are not regulated using the same process as FDA-approved drug products. This means that FDA does not review these compounded drug products to evaluate their safety, effectiveness, or quality before they reach patients.

Project Description and Goals

The overall goal of this study is to initiate the gathering of data that enables the FDA to assess the absorption of active ingredients from topically applied compounded estradiol products. This study design will include evaluating skin permeation of estradiol from EstroGel® 0.06%, an FDA-approved estradiol transdermal gel as a safe and effective product control, and a compounded estradiol product. The clinical study will evaluate estradiol concentrations in the blood from the compounded product as compared to the FDA-approved EstroGel® 0.06% product. Results from this study will be used to design future clinical studies to evaluate additional compounded hormone products.

Specific aims:

1. Develop a method to measure the level of estradiol and its metabolites (i.e., estrone and estriol) in blood samples collected from participants who will be treated with topical estradiol products.
2. Conduct a clinical study to determine the rate and extent of estradiol absorption through the skin from a single dose of EstroGel® 0.06% and the compounded estradiol product, and compare estradiol absorption after four days of putting each product on the skin.

Project scope expansion may also include additional formulation evaluation in the laboratory testing by a human skin permeation test as a potential surrogate for healthy human skin absorption studies. These tests are conducted in the laboratory using surgical waste skin from tummy tuck surgeries to evaluate formulations.