DOSING MASTER DOC

Estradiol-Only Monotherapy (Estrogen-Only HRT)

Estradiol-only monotherapy relies on estrogen’s ability to directly suppress testosterone production at high levels, eliminating the need for a separate T-blocker. In high doses, estradiol triggers negative feedback in the hypothalamic-pituitary-gonadal (HPG) axis, reducing gonadotropins and thereby lowering testicular testosterone output. The goal is to achieve blood estradiol concentrations high enough to shut down endogenous testosterone (often aiming for estradiol levels above 200 pg/mL at trough [1, 2], which typically keeps total testosterone <50 ng/dL).

However, estradiol monotherapy is generally effective only at the upper end of dosing ranges, so careful attention to dose and delivery method is critical. Below I talk about common delivery routes for estradiol in monotherapy, with typical dosing and considerations for each.

A SMALL NOTE:

This document originally covered pellets as well but since nobody really uses pellets it’s been removed.

ORAL/PATCH IS INCLUDED BUT INJECTIONS IS ALWAYS BEST FOR MONOTHERAPY

Injectable Estradiol (IM or Subcutaneous)

• Form and Dosing: Intramuscular or subcutaneous injections of estradiol esters are highly effective for monotherapy. Common esters used include estradiol valerate (EV) , estradiol cypionate (EC) , estradiol enanthate (EEn) , and estradiol undecylate (EUn) . These are typically compounded in oil for injection. Typical monotherapy injection doses are:

• Estradiol Valerate : 4–6 mg per week (for example, 4 mg every 5 days is a common schedule). Recent large-scale reviews have found median doses of ~4 mg/week often sufficient to reach suppression levels [2].
• Estradiol Cypionate or Enanthate : 5–7 mg per week (Standard starting dose is often 5 mg/week, but many individuals titrate up to 6–7 mg/week or 7–10 mg every 10–14 days for stable monotherapy suppression).
• Estradiol Undecylate : a very long-acting ester, dosed at ~20–40 mg every 3–4 weeks (e.g. 20 every 14 days, or up to 40 mg monthly).

• 
  
• 
  
• These doses are on the higher side of standard, intended to produce estradiol levels well above normal female range initially, ensuring that even at trough (right before the next shot) levels stay high enough to suppress testosterone. For instance, the Endocrine Society notes that 10 mg EV weekly IM can yield peak E ~1250 pg/mL and trough ~200 pg/mL at 7 days – sufficient to drive T down [5]. DIY guidelines similarly list injection regimens (e.g. 4 mg EV every 5 days, 5–6 mg EEn weekly, etc.) designed so that “the vast majority of people [on these doses] have high enough estradiol levels to suppress testosterone on its own.” . In practice, many individuals start around 4–5 mg per week and adjust if needed based on bloodwork, targeting trough estradiol typically >200 pg/mL for full T suppression [1, 2].

• Effectiveness : Injectable estradiol is widel y regarded as the most consistently effective monotherapy method for testosterone suppression [3]. Because injections can deliver very high levels and maintain relatively stable blood concentrations (especially with appropriate dosing intervals for each ester’s half-life), they reliably shut down gonadal testosterone production for the majority of people. Community experience and medical studies show for example, an endocrine clinic review found that all transfeminine patients who achieved T <50 ng/dL on monotherapy were on either injectable or high-dose patch; 5 of 7 were using injectable estradiol valerate 4–6 mg weekly [1]. The DIY HRT community often recommends estradiol injection monotherapy as an optimal regimen: it "ticks a lot of boxes" by providing stable levels, predictable results, infrequent dosing, and cost-effectiveness. In fact, a weekly subcutaneous injection of ~5–7 mg estradiol enanthate is said to bring “almost anyone” into a high estrogen range sufficient to turn off testosterone without any blocker. With proper technique and scheduling, injection monotherapy can maintain female-range or castrate-range T levels continuously.
• 
  

• Some considerations:

• Injection Technique : Monotherapy injections can be given subcutaneously (into fat) or intramuscularly; both routes achieve similar estradiol levels [2]. Subcutaneous injections with a small needle (e.g. insulin syringe read this!!! ) are generally well-tolerated; intramuscular injections might be chosen if larger volumes are used or if subcutaneously the solution causes irritation (some homebrew preparations use solvents like benzyl benzoate that can sting subq).
• Dosing Frequency : To maintain stable levels, one time the injections according to the ester’s half-life (see Table below). For example, valerate (half-life ~3–4 days) is dosed every 5–7 days; cypionate or enanthate (half-life ~5–7 days) every 7–10 days; undecylate (half-life ~20–30 days) every few weeks. Adjusting the schedule can fine-tune peak/trough – some monotherapy users prefer slightly more frequent, lower-dose shots (e.g. split weekly dose into twice weekly) to keep levels very steady.
• Monitoring: Because injection monotherapy often achieves higher estradiol levels, regular blood tests are advised to ensure estradiol isn’t excessively high and testosterone is indeed suppressed. Typically, trough estradiol >200–250 pg/mL is needed to fully suppress T, but extremely high peaks are not necessary and could increase side effects. The aim is the lowest dose that keeps T at goal (<50 ng/dL at trough).

In summary, injectable estradiol is the preferred method for DIY estrogen monotherapy and is increasingly recognized medically as a viable single-medication regimen for transfeminine therapy. It provides robust feminization and T suppression, often obviating the need for any anti-androgen.

Summary of Estradiol Monotherapy Dosing by Route

The following table summarizes typical estradiol dosing ranges for monotherapy, along with notes on effectiveness and considerations:

References & Citations

[1] Rothman MS, Ariel D, Kelley C, et al. The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels. Endocrine Practice. 2024;30(9):870-878.

[2] Misakian AL, Kelley CE, Sullivan EA, et al. Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States. The Journal of Clinical Endocrinology & Metabolism. 2025;110(9):e2898–e2907.

[3] Cortez S, Moog D, Lewis C, et al. Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial. Journal of the Endocrine Society. 2024;8(8):bvae108.

[4] Tebbens M, Heijboer AC, T’Sjoen G, et al. The Role of Estrone in Feminizing Hormone Treatment. The Journal of Clinical Endocrinology & Metabolism. 2022;107(2):e458–e466.

[5] Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2017;102(11):3869–3903.

Medical Disclaimer: This document contains medical information that should be reviewed by qualified healthcare professionals. Dosages and protocols may vary based on individual circumstances, medical history, and healthcare provider recommendations. This information is for educational purposes only and does not constitute medical advice.