The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels

Feminizing gender-affirming hormone therapy (GAHT) is the mainstay of treatment for many transgender and gender diverse (TGD) people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route. We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in TGD adults on feminizing GAHT. We also report on testosterone suppression, route (i.e., subcutaneous vs. intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available. The data we reviewed suggests that the current guidelines, which recommend starting doses 2–10 mg weekly or 5–30 mg every two weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle. The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol valerate via subcutaneous or intramuscular injections at a dose ≤ 5 mg weekly and then titrate accordingly to keep levels within guideline recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters.

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