Widely used standards of care for administration of cross-sex hormones are published by the World Professional Association of Transgender Health (WPATH) and The Endocrine Society. Current guidelines also discuss the possible risks of estrogen therapy including breast cancer and venous thromboembolism (VTE). Estrogen tablets (17beta estradiol) are the most accessible form of cross sex hormone therapy for transgender females because of its wide availability and relative affordability. Literature show that oral estrogen converts into estradiol (E2), the main form of estrogen in women of childbearing age and has strong feminizing effects; and Estrone (E1), a less potent form of estrogen - which also has been linked to an increased risk for breast cancer, increased endothelial inflammation, and VTE in cisgender females. Oral forms of estrogen expose patients to overdose levels of estrone (E1) due to the first pass liver effect. Current recommended dosing goal for estrogen in cross sex hormone therapy is to match estrogen levels of a cisgender female.
Current guidelines discuss routine preventive measurements of lipids, hemoglobin A1c or glucose in addition to estradiol (E2) and testosterone levels to monitor therapy. Despite the mounting data associating estrone (E1) levels with breast cancer and venous thromboembolism, guidelines do not specify the measurement of this lab value to monitor the safety of estrogen for cross-sex hormone therapy.
The purpose of this pilot study is to assess the prevalence of increased estrone (E1) level as a result of cross-sex estrogen therapy for male to female transgender patients, and compare the levels of conversion of estrogen to estrone from oral, injectable, transdermal, and pellet therapy. Per standard reference ranges for females, estrone levels should be no more than 33% of total estrogen.
Methods:
A retrospective chart review from a primary care clinic that provides cross-sex hormone therapy. Sample comprised of 52 patients ages 15 to 66yrs. Median age is 24 and mean age is 26.1. Chart review includes dates of service between November 1, 2017 and October 31, 2018.
Ethnicities are as follows: White/Non-Hispanic (n=39), White/Hispanic (n=6), Black/Non-Hispanic (n=2), Other/Hispanic (n=2), and Other/Non-Hispanic (n=3). No ethnicities from the following were in the sample: American Indian, Alaska Native, Asian, Pacific Islander
Patients identify as either transgender male-to-female patients (n=48), or gender-non conforming, assigned male-at-birth patients (n=4). Payer sources are as follows: private insurance (n=43), government insurance (n=4), no insurance (n=5).
The initial form of estrogen therapy included oral synthetic estrogen (n=41), bioidentical transdermal estrogen (n=1), and implantable bioidentical estrogen pellets as first line therapy (n=10).
Fractionated estrogen, a measurement that quantifies the amount of total serum estrogen and compares the estradiol to estrone ratio, was measured between 6 weeks to 1 year after initiation of therapy. A secondary measurement was also performed after the estrogen therapy was changed (for example, from oral estrogen to injectable estrogen). Eleven of the samples did not have secondary measurements due to lost to follow up, or measurement fell outside of the review dates.
Results:
For purposes of this study, the conversion of estrogen into estradiol (E2) and estrone (E1) were measured using the fractionated estrogen lab value. The following values are of estrone (E1) as follows: Among oral users, 76.3%; oral estrogen dissolved sublingually, 69.7%; injectable estrogen, 32.1%; transdermal patch, 23.2%; and implantable pellets, 22.8%. The most desirable form of estradiol from “best to worst” are as follows: Implantable pellets, transdermal preparations/patches, and injectable estrogen.
Conclusion:
On this sample size, oral estrogen dissolved sublingually or swallowed were not desirable in terms of estradiol conversion.
No person chose to have injectable estrogen as first line therapy. This may infer that injections are the least favorite form of first line therapy.
There is a high percentage of private insurance patients which may infer that access to care may be more available for those with insurance coverage.
There is a disproportionate number of white non-Hispanic subjects in this population, which also supports that access to care may be limited in the racial minority populations.
Higher estrone (E1) levels correlate to a higher risk of breast cancer, venous thromboembolism, and endothelial inflammation in postmenopausal women. The ratio of estradiol (E2) to estrone (E1) may be used to monitor the risks of estrogen therapy for transgender females. This marker may be valuable in assessing and reducing the risk of this population as they will be exposed to estrogen earlier than postmenopausal age.