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Approximate Comparable Dosages of Estradiol by Different Routes

By Aly W. | First published April 19, 2020 | Last modified February 28, 2021

Introduction

People often ask about comparable or equivalent dosages of estradiol by different routes of administration. I put this page together to help facilitate answering these questions.

Table of Comparable Estradiol Dosages

The following is a table of estimated equivalent dosages of estradiol by different routes:

RouteLow doseModerate doseHigh doseVery high dose
Orala2 mg/day4 mg/day8 mg/day12 mg/day
Sublingual/buccalb0.5–1 mg/day1–2 mg/day2–4 mg/day3–6 mg/day
Transdermal patchc,d50–100 μg/day100–200 μg/day200–400 μg/day300–600 μg/day
Transdermal gelc1.5 mg/day3 mg/day6 mg/day9 mg/day
IM or SC injectione1 mg/week2 mg/week4 mg/week6 mg/week
SC pellet implant25 mg/6 months50 mg/6 months100 mg/6 months150 mg/6 months
~Average estradiol level50 pg/mL
(184 pmol/L)
100 pg/mL
(367 pmol/L)
200 pg/mL
(734 pmol/L)
300 pg/mL
(1101 pmol/L)
Equivalent cycle phaseFollicularWhole cycleLutealOvulation

a For oral estradiol. Oral estradiol 1.5 mg is equivalent to about 2 mg oral estradiol valerate (Wiki). b Based on sublingual estradiol having ~2- to 5-fold greater bioavailability than oral estradiol per studies (Wiki). c Much lower transdermal doses can be used in the case of genital administration (Aly W., 2019; Aly W., 2019). d Different patch brands may result in differing estradiol levels (Langley et al., 2008; Langley et al., 2015). e For IM or SC injection, total dose per week of an estradiol ester like estradiol valerate, estradiol cypionate, estradiol enanthate, or estradiol benzoate. Differences in molecular weight between these esters are minor (Wiki-Table) and can be ignored for simplicity. Optimal injection intervals vary depending on the ester and doses should be scaled by injection interval to match the listed total dose per week.

Notes

  1. These doses are not absolute and should be considered a rough guideline. They represent a generalized model based on many different studies often with very different individual findings.
  2. These doses are approximate equivalent or comparable doses and don’t necessarily correspond to typical or recommended clinical doses. Injections are often used at higher doses for instance.
  3. The comparable doses are based on total estradiol exposure rather than therapeutic estrogenic potency. Time dynamics of exposure are known to modify potency (e.g., Parkes, 1937; Bradbury, Long, & Durham, 1953). However, this has not been factored in due to a lack of available data/analysis on the influence. In any case, it may be relevant to routes with large fluctuations in estradiol levels like sublingual administration and shorter-acting injections.
  4. A transdermal estradiol spray sold under the brand name Lenzetto is available. In a study in postmenopausal women, mean baseline-adjusted estradiol levels with Lenzetto over the course of a week following achievement of steady state were about 13 pg/mL with 1 spray/day (1.53 mg/day), 19 pg/mL with 2 sprays/day (3.06 mg/day), and 26 pg/mL with 3 sprays/day (4.59 mg/day) (Morton et al., 2009; Wiki-Graph). Hence, this form of estradiol appears to achieve relatively low estradiol levels that likely aren’t well-suited for transfeminine hormone therapy. No data are available on higher doses (i.e., more sprays per day) and so this formulation has not been included in the table.

Discussion

For reference, mean integrated levels of estradiol during the normal menstrual cycle in premenopausal women are about 100 pg/mL and during the luteal phase (the latter half of the menstrual cycle) are about 150–200 pg/mL (Wiki-Graphs). The total production of estradiol over a single menstrual cycle (i.e., one month) is about 6 mg on average (Rosenfield et al., 2008). Slightly higher doses are required for injectable estradiol esters since they contain less estradiol by weight.

Note that there is high interindividual variability (i.e., variability between individuals) in terms of estradiol levels achieved with different forms and routes of estradiol. As an example, some people may get relatively low estradiol levels with the oral route and others may get relatively low levels with the transdermal route. Conversely, some people may get relatively high levels with the transdermal route or with injections. For data showing the substantial variability even with injections, see e.g. Vermeulen (1975) (Wiki-Graph), Oriowo et al. (1980), Derra (1981) (Graph), and Schug, Donath, & Blume (2012) (Graph). Due to the variability in estradiol levels between individuals, the appropriate doses will often not be the same for different people. Doses should be adjusted as necessary based on blood work. It should also be noted that there are large time-dependent changes in estradiol levels with certain routes, namely sublingual/buccal administration and intramuscular/subcutaneous injection (Wiki-Graphs; Wiki-Graph; Wiki-Graphs). Due to these changes, estradiol levels will be vastly different when measured at different time points with these routes (e.g., around peak versus around trough).

For transfeminine people who have not yet undergone or do not plan to undergo gonadectomy, a high to very high dose of estradiol can be used to achieve strong suppression of testosterone levels. On average, the high dose will suppress testosterone levels by about 90%, to around 50 ng/dL (Wiki). Hence, the high to very high doses are indicated for estradiol monotherapy (i.e., estradiol alone without an antiandrogen). After gonadectomy, testosterone suppression is no longer needed and lower doses of estradiol, such as the moderate dose, can be used. High doses of estradiol are not necessarily required if estradiol is used in combination with an antiandrogen, for instance cyproterone acetate (Aly W., 2019), bicalutamide (Aly W., 2018), or a GnRH agonist/antagonist (e.g., buserelin) (Aly W., 2018).

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