Estrogens

Estradiol (17β-estradiol, "E2") is the primary feminizing hormone — bio-identical to what cis ovaries produce, drives breast development, fat redistribution, skin softening, and at sufficient levels suppresses testosterone via negative feedback on the pituitary. Modern feminizing HRT uses bio-identical estradiol almost exclusively, in one of three delivery formats:

• Oral / sublingual estradiol — pills, swallowed or held under the tongue
• Transdermal estradiol — patches, gels, lotions, sprays
• Injectable estradiol esters — valerate (EV) or cypionate (EC), intramuscular

The historical alternatives (ethinyl estradiol, Premarin, esterified estrogens, estropipate, quinestrol) are largely abandoned for feminizing HRT — covered briefly at the bottom for reference.

Doses are reference, not prescription

Doses below come from the Endocrine Society 2017 guideline and hemingways.org provider regimens (2002-era). Real prescribing depends on your labs, target levels, route, and provider judgment. Don't titrate without monitoring.

At a glance

Drug	Brand(s)	Route	Typical M2F dose	Notes
Estradiol	Estrace, Climara, Vivelle, Estrogel	Oral / SL / patch / gel	2–6 mg/day oral · 0.025–0.2 mg/day patch	First-line; bio-identical
Estradiol acetate	Femtrace, Femring	Oral / vaginal ring	1–4 mg/day oral · 0.05–0.1 mg/day ring	Oral acetate ester; ring delivers systemic E2
Estradiol valerate	Delestrogen, Progynova	Oral / SL / IM	2–6 mg/day oral · 5–30 mg IM every 2 weeks	Most popular injectable
Estradiol cypionate	Depo-Estradiol	IM	2–10 mg IM every 1–2 weeks	Slower release than EV
Estradiol enanthate	Perlutal, Topasel (combo only)	IM	5–10 mg IM every 1–4 weeks	Latin America / DIY; standalone not officially sold
Estradiol undecylate	Progynon-Depot 100	IM	50–100 mg IM every 1–4 weeks (legacy)	Very long ester; discontinued
Polyestradiol phosphate	Estradurin	IM	80–320 mg IM every 4 weeks	Polymeric; lowest serum E2 per mg, longest interval
Estradiol benzoate	(compounded / veterinary)	IM	(rare in modern HRT)	Short-acting (1–3 days); largely historical
Ethinyl estradiol	Estinyl	Oral	(not recommended)	High thrombosis risk; modern guidelines exclude
Conjugated estrogens	Premarin, Cenestin	Oral	(legacy)	Premarin = mare urine; mostly abandoned
Esterified estrogens	Menest, Estratab	Oral	(legacy)	Similar limitations to Premarin
Estropipate	Ogen	Oral	(legacy)	Estrone-based, less effective
Quinestrol	Estrovis	Oral	(obscure)	Long-half-life ethinyl estradiol derivative

Choosing a route

Route	Absorption	Onset / steadiness	Effect on liver / SHBG / clotting	When it fits
Oral (swallowed)	~10%	Steady on twice-daily schedule	High first-pass; raises SHBG, clotting factors	Easy, cheap, simple
Sublingual	~70–90%	Peak ~2 h after dose, troughs between	Lower than oral but not zero	Cheap; good for getting higher serum E2 from same pills
Transdermal (patch / gel)	~90%	Very steady; weekly or twice-weekly	Bypasses liver — minimal SHBG/clotting impact	Older patients, cardiovascular risk, smokers
IM injection (EV / EC)	~100%	Sharp peak 24–48 h, slow trough over 1–2 weeks	Bypasses liver	Stable serum levels, less daily fuss; tolerates needles

The big practical divide is oral vs. transdermal-or-injection. Oral estrogen passes through the liver before entering the bloodstream, raising SHBG (binds free hormones) and several clotting factors — that's where most of estrogen's clot risk comes from. Transdermal and injected estradiol skip the first-pass liver metabolism and have a much lower thrombosis risk per equivalent serum E2. The Endocrine Society 2017 guideline recommends transdermal for patients over 40 or with any cardiovascular risk factor (smoking, family history, prior DVT/PE).

Estradiol (17β-estradiol)

The canonical bio-identical estrogen, available in just about every delivery format. This is what your body naturally produces; the molecule is identical regardless of brand. Choose the route based on the fit table above.

Common brands: Estrace (oral), Climara / Vivelle / Estraderm (patches), Oestrogel / Sandrena / Divigel (gels), Estrasorb (lotion).

Full detail (formulations, side effects, source notes)

Pharmacology: 17β-estradiol — molecularly identical to the principal estrogen produced by cis ovaries.

Delivery:

• Oral tablets: 0.5, 1, 2 mg (Estrace and generics)
• Transdermal patches (twice-weekly or weekly): 0.025, 0.0375, 0.05, 0.075, 0.1 mg/24h
• Topical gel: pump or sachet (Estrogel, Sandrena, Divigel)
• Vaginal cream / suppositories (typically for genital atrophy, not systemic feminization)

Source dose ranges: Oral 4–8 mg/day (pre-op), 1–4 mg/day (post-op). Transdermal: 2–4 patches at 0.1 mg, twice weekly (pre-op); single 0.05–0.1 mg patch (post-op).

Modern Endocrine Society 2017 dose: Oral 2–6 mg/day; transdermal 0.025–0.2 mg/day.

Comments from source: "The Climara and Vivelle films reportedly last longer, and probably deliver more, than the Estraderm brand."

Side effects: Nausea, bloating, breast tenderness (especially in early months); mood changes; rare contact-lens intolerance from corneal curvature shifts. Serious: blood clots (DVT/PE), gallbladder disease, elevated blood pressure, liver effects (oral form only).

Contraindications: Active or history of estrogen-associated blood clots, estrogen-dependent tumors, known/suspected breast cancer (in most cases).

Estradiol valerate

The most popular injectable ester. The "valerate" tail slows absorption from the injection site, giving steady serum E2 over ~1–2 weeks per shot. The same molecule (estradiol-valerate) is also sold as oral tablets (Progynova, Progynon) — once swallowed or dissolved sublingually, the body cleaves the ester off, leaving plain estradiol.

Full detail (pharmacokinetics, dosing, source notes)

Pharmacology: Ester of 17β-estradiol — the body cleaves the valerate group during absorption and first-liver passage, releasing free estradiol. Same physiologic effect as endogenous E2.

Delivery:

• Sustained-release IM injection (typical concentration 20 or 40 mg/mL)
• Oral tablets: 1, 2 mg (Progynova / Progynon-Depot, common outside the US)

Source dose ranges: IM 15–40 mg every 2 weeks or 7–20 mg every week (pre-op); 10–30 mg every 2–4 weeks (post-op). Oral: 6–12 mg/day pre-op, 2–6 mg/day post-op.

Modern Endocrine Society 2017 dose: IM 5–30 mg every 2 weeks.

Pharmacokinetics: "Rapidly and completely absorbs. The steroid ester cleaves into estradiol and valeric acid during absorption and first-liver passage. Maximum estradiol plasma concentrations generally reach between 4–6 hours after tablet intake. About 90% excretes via kidneys, 10% with bile."

Comments from source: "Progynon-Depot" by Schering Germany is distinct from "Progynon-Depot 100" (the latter is estradiol undecylate, longer chain, longer action — reportedly discontinued due to excessive feminization concerns in prostate cancer treatment). For nut-oil allergies: castor oil is the standard injection vehicle; some pharmacies use sesame oil for viscosity reasons.

Estradiol cypionate

A slower-release IM ester than valerate. The cypionate group's longer fatty-acid chain means a smaller, less-frequent dose — typically every 1–2 weeks — but with somewhat higher peak/trough variability. Sold in the US as Depo-Estradiol; common in informed-consent clinics.

Full detail (dosing, source notes)

Pharmacology: Ester of estradiol with longer cleavage time than valerate. Same physiologic effect as endogenous E2 once cleaved.

Delivery: Sustained-release IM injection, 5 mg/mL.

Source dose ranges: 1.5–4 mg every 2 weeks (pre-op); 1–3 mg every 2–4 weeks (post-op).

Modern dosing in IC clinics: typically 2–10 mg IM every 1–2 weeks.

Comments from source: "The 1997 PDR generics book shows a 1:10 ratio of cypionate:valerate ovarian failure replacement dosages" — i.e. 1 mg EC ≈ 10 mg EV by weight in the original PDR, though community/clinical practice generally treats them closer to 1:1 in feminizing HRT.

Other injectable esters

Beyond valerate and cypionate, several less-common estradiol esters exist. None of them are first-line for modern feminizing HRT, but they appear in DIY contexts, in non-US markets, in legacy regimens patients may still be on, and occasionally in specialty European clinic protocols.

Injectable ester comparison

Ester	Acid chain	Half-life (IM)	Typical dose interval	Status
Estradiol valerate (EV)	C5 valeric	~4 days	5–30 mg every 1–2 wk	Standard; widely available
Estradiol cypionate (EC)	C8 cypionic	~8 days	2–10 mg every 1–2 wk	Standard in US IC clinics
Estradiol enanthate (EEn)	C7 heptanoic	~5–7 days	5–10 mg every 1–4 wk	Latin America / DIY; not officially sold standalone
Estradiol undecylate (EU)	C11 undecanoic	~weeks	25–100 mg every 1–4 wk (legacy)	Discontinued
Polyestradiol phosphate (PEP)	polymeric	weeks–months	80–320 mg every 4 wk	Niche; high mg requirement, very long interval
Estradiol benzoate (EB)	C7 benzoic	~1–3 days	(rarely used)	Veterinary / historical

Pattern to keep in mind: longer ester chain → slower absorption → smaller dose, longer interval, flatter curve. PEP breaks the pattern entirely because it's a polymer, not a single-ester molecule, and releases very slowly via gradual hydrolysis.

Estradiol enanthate (EEn)

A C7 (heptanoic) ester, intermediate between valerate and cypionate in release profile. Pharmacokinetically similar to EV in half-life (~5–7 days) but with a flatter curve at comparable doses. Officially marketed only as part of monthly combined contraceptive injectables — Perlutal, Topasel, Yectames, others — paired with the progestin dihydroxyprogesterone acetophenide (DHPA), and only in Latin America and Hong Kong. Not sold as a standalone preparation anywhere. Despite that, EEn has grown noticeably in DIY transfeminine use since the early 2020s, with raw powder sourced from research-chemical suppliers and compounded in oil. Community dosing typically lands at 5–10 mg every 7–14 days, similar to EV.

The pharmacokinetic data is sparse — most of what's known comes from 1980s and 1990s studies of the contraceptive combination, not standalone feminizing-HRT use.

Estradiol undecylate (EU)

A C11 (undecanoic) ester, one of the longest single-ester estradiols ever produced. Sold by Schering Germany as Progynon-Depot 100 at 100 mg/mL, discontinued in the 2000s. Half-life is on the order of weeks; a single 100 mg dose holds serum E2 above 300 pg/mL for at least two weeks. Used historically for prostate-cancer palliative therapy at 100 mg monthly and in trans-feminine regimens at 100–800 mg monthly.

Mentioned only because (a) older patients may encounter the name in legacy prescription records, and (b) the existing valerate section already references this preparation in passing under its old "Progynon-Depot 100" name.

Polyestradiol phosphate (PEP / Estradurin)

Not a single-ester molecule but a polymer — on average 13 estradiol units linked by phosphate ester bonds. IM only. The polymer hydrolyzes very slowly after injection, releasing free estradiol over weeks to months. Originally developed for prostate-cancer therapy (Pfizer, Sweden, since the 1950s) and still produced as Estradurin.

The catch is dose-vs-AUC efficiency: PEP produces around 6–7× lower serum estradiol per mg than monomeric esters like EV. So a feminizing dose lands at 80–320 mg every 4 weeks, not the single-digit milligrams of EV. Some European clinics use it specifically when a patient wants once-monthly dosing without the EV peak/trough oscillation. Not common in the US or in informed-consent settings.

Estradiol benzoate (EB)

The original 1930s estradiol ester. Very short acting — half-life on the order of 1–3 days — which means daily or alternate-day injections to maintain steady levels. Largely displaced by valerate and cypionate by the 1960s. Still used in veterinary medicine and very occasionally compounded for human use; not a contemporary feminizing HRT option.

Estradiol acetate (Femtrace, Femring)

The acetate ester is unusual in that it's not used for injection — instead it's an oral tablet (Femtrace) and a vaginal ring (Femring). The acetate group improves oral bioavailability slightly over plain estradiol but the practical dosing is similar (1–4 mg/day oral). The vaginal ring delivers ~0.05–0.1 mg/day systemically over 90 days and is occasionally used in feminizing HRT for patients who want a hands-off long-term route without injections or patches. Niche.

Not recommended for modern feminizing HRT

The estrogens below were once used but have been largely or entirely displaced by bio-identical estradiol. Listed here for reference — if you're currently on one of these, talk to your provider about switching.

Ethinyl estradiol (Estinyl)

Synthetic estrogen designed to resist liver metabolism, which makes it long-acting and powerful — but also makes its first-pass liver effects (clotting factor synthesis, SHBG elevation) much higher than estradiol. Most thrombosis events in feminizing HRT historically traced to ethinyl estradiol. It's the estrogen used in combined oral contraceptives, where the dose is ~0.02–0.035 mg; M2F regimens once used 0.1–0.5 mg/day. The Endocrine Society 2017 guideline explicitly recommends against using ethinyl estradiol for feminizing HRT. The 0.5 mg pills are no longer manufactured.

Conjugated estrogens (Premarin, Cenestin)

Premarin is a mixture of ~10 estrogens extracted from pregnant mares' urine — including equilin and equilenin, which are horse-specific molecules humans lack the enzymes to fully metabolize. It dominated cis-female HRT for decades and was applied off-label to M2F patients, but bio-identical estradiol is more effective and lacks the unmetabolizable horse estrogens. There are also significant animal-welfare concerns with mare-PMU production.

Cenestin is a synthetic plant-derived alternative that mimics Premarin's mixture without the mare farm. Still mostly estrone-based, so less effective than 17β-estradiol per dose. Note: Cenestin uses a time-release coating, which makes it unsuitable for sublingual administration.

Esterified estrogens (Menest, Estratab)

Sodium salts of estrogen sulfates, principally estrone. Similar limitations to Premarin: estrone-dominant, oral-only, no advantage over bio-identical estradiol.

Estropipate (Ogen)

Estrone sulfate stabilized with piperazine. Same family as the above — estrone-based, oral, no advantage over estradiol.

Quinestrol (Estrovis)

Cyclopentyl ether of ethinyl estradiol with an extremely long half-life (oral once-weekly dosing). Inherits ethinyl estradiol's thrombosis profile. Obscure; not used in contemporary feminizing HRT.

Sources

• Hembree WC et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons. Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(11):3869–3903. doi:10.1210/jc.2017-01658
• Per-drug brands, formulations, side-effect lists, and historical doses adapted from the hemingways.org GIDinfo drug pages.
• Lawrence A. Suggested Hormone Regimens. (2002 reference handout, archived PDF) — for historical comparison.
• Estradiol enanthate — Wikipedia. Source for the EEn half-life (~5–7 days), C7 chain, Perlutal/Topasel combination formulations, and current Latin America / Hong Kong availability.
• Estradiol undecylate — Wikipedia. Source for the C11 chain, ~weeks half-life, 100 mg / month historical dosing, and Progynon-Depot 100 discontinuation.
• Polyestradiol phosphate — Wikipedia and Stege R et al. Plasma concentrations of estradiol and testosterone in single-drug polyestradiol phosphate therapy for prostatic cancer. 1987. PubMed. Source for the polymer structure (~13 estradiol units per PEP molecule), the 6–7× lower AUC vs monomeric esters, and the 40–320 mg/month dose range.
• An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations — Transfeminine Science. Article. Cross-ester pharmacokinetic comparison.
• The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels. Endocrine Practice 2024. PubMed. Source for current injectable dose recommendations.