GAHT Plotter

Estimated serum hormones

Injectable estradiol cypionate

FAQ
Total E2Total E1Total TSHBG-adjusted androgenicity proxyInjectable EC
Estimated serum hormone levels over timeEstimated estradiol, total E1 context, and heuristic androgen overlays across one or more overlapping regimens.0501001502000100200300400500600W0W1W2W3W4W5Injectable EC ~95% accumulationWeeks on regimenEstradiol / E1 context (pg/mL)Total testosterone (ng/dL)

Build an estradiol regimen.

Estradiol forms

Injectable estradiol cypionate

Route: Depot injection (shared IM/subQ proxy). Formulation: Estradiol cypionate oil depot.

Dose
mg

Shared IM/subQ proxy anchored mainly to older IM oil-depot PK. Weekly use is a route-context default, and the subQ evidence is cohort-based rather than serial PK.

Total T suppressors

Estimated summary values

Late peak

178 pg/mLHighest estimated value in the final summary window.

Late trough

128 pg/mLLowest estimated value before the next late dose.

Late average

158 pg/mLMean estimated level across the last 14 days.

Late total T

164 ng/dLMean estimated total T across the final summary window.

Late SHBG-adjusted androgenicity proxy

142 ng/dLMean SHBG-adjusted androgenicity proxy across the same window.

95% T suppression

After W8.6Injectable EC reaches about 95% of its testosterone-suppression response after this 5-week view.

95% accumulation

W4.3Injectable estradiol cypionate reaches about 95% of its repeating-dose accumulation within this view.

Plot coverage

6 regimen events1 estrogen form and 0 T suppressors over 5 weeks.

Research basis for the current model

Show section

Every cited source currently used by the active MTF view is listed below. The estradiol PK curves, total E1 line, total-T estimate, SHBG-adjusted androgenicity proxy, and antiandrogen or suppressor models all draw from these active-view sources.

Active view evidence posture

Show details
Injectable estradiol cypionate

Moderate fit confidence. Multi-phase fit. Evidence population: Primary oil-depot EC PK plus mixed-ester IM/subQ cohort and timing context. Modeled androgen-response timescale: 14.00 days. Caution: Shared IM/subQ proxy anchored mainly to older IM oil-depot PK. Weekly use is a route-context default, and the subQ evidence is cohort-based rather than serial PK.

All works cited

Show details
Kariyawasam 2025Show details

Role in model: Qualitative guardrail

Kariyawasam NM, Ahmad T, Sarma S, Fung R. Comparison of Estrone/Estradiol Ratio and Levels in Transfeminine Individuals on Different Routes of Estradiol. Transgend Health. 2025;10(3):261-268.

Provides route-level estrone-to-estradiol ratio context in transfeminine patients: oral estradiol had the highest mean E1/E2 ratio (9.28), followed by sublingual (6.88), with lower ratios on transdermal (2.22) and injectable estradiol (0.84).

Open source
Tebbens 2022Show details

Role in model: Qualitative guardrail

Tebbens M, et al. The Role of Estrone in Feminizing Hormone Treatment. J Clin Endocrinol Metab. 2022;107(2):e458-e466.

Supports two key caveats at once: oral estradiol produces much higher estrone and SHBG than transdermal estradiol, but estrone itself was not associated with breast development or body-fat change.

Open source
Cortez 2024Show details

Role in model: Qualitative guardrail

Cortez S, et al. Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial. J Endocr Soc. 2024;8(8):bvae108.

Used to support route-weighting notes: transdermal 17-beta estradiol suppressed testosterone more rapidly than once- or twice-daily sublingual estradiol and produced lower estrone levels, with no meaningful advantage for twice-daily over once-daily sublingual dosing.

Open source
Liang 2018Show details

Role in model: Supporting cross-check

Liang JJ, et al. Testosterone Levels Achieved by Medically Treated Transgender Women in a United States Endocrinology Clinic Cohort. Endocr Pract. 2018;24(2):135-142.

Provides contextual evidence from a U.S. oral-estrogen-plus-spironolactone cohort: patients starting therapy required about 9 months on average to reach a steady-state testosterone level, highlighting that suppression in practice may take substantially longer than a few days.

Open source
Yaish 2023Show details

Role in model: Qualitative guardrail

Yaish I, et al. Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6):485-493.

Provides contextual evidence against overselling sublingual dosing frequency: in this small 6-month prospective study, 0.5 mg sublingual estradiol four times daily did not show a clear clinical or biochemical advantage over combined oral estradiol plus cyproterone acetate.

Open source
Slack 2025Show details

Role in model: Supporting cross-check

Slack DJ, et al. Examining the Influence of the Route of Administration and Dose of Estradiol on Serum Estradiol and Testosterone Levels in Feminizing Gender-Affirming Hormone Therapy. Endocr Pract. 2025;31(1):19-27.

Provides comparative route evidence from a large retrospective cohort: oral estradiol was the only route showing a clear linear dose-response, with testosterone falling about 19.03 ng/dL per 1 mg/day, while intramuscular estradiol was associated with lower testosterone and higher estradiol than oral or transdermal routes.

Open source
Collet 2023Show details

Role in model: Supporting cross-check

Collet S, et al. Changes in Serum Testosterone and Adrenal Androgen Levels in Transgender Women With and Without Gonadectomy. J Clin Endocrinol Metab. 2023;108(2):331-338.

Supports keeping a nonzero androgen floor in the model. Testosterone and adrenal androgen profiles remain low rather than disappearing entirely, even after gonadectomy.

Open source
Zhou 2024Show details

Role in model: Qualitative guardrail

Zhou C, Jones Q, Kokosa S, Kelley C. 7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients. J Endocr Soc. 2024;8(Suppl 1):bvae163.1680.

Conference abstract providing contextual evidence that estradiol monotherapy can suppress testosterone in some transfeminine patients: in this small retrospective cohort, testosterone suppression to under 50 ng/dL was achieved in 100% of the transfeminine subgroup when serum estradiol was above 100 pg/mL, most often with injectable estradiol valerate and less often with transdermal patches.

Open source
Misakian 2025 (Endocr Pract)Show details

Role in model: Supporting cross-check

Misakian AL, et al. Injectable Estradiol Monotherapy Effectively Suppresses Testosterone in Gender-Affirming Hormone Therapy. Endocr Pract. 2025;31(11):1462-1469.

Supports the higher-exposure end of the experimental testosterone overlay: in this multisite cross-sectional cohort on weekly injectable estradiol, median estradiol was 232 pg/mL and median total testosterone was 17 ng/dL overall, and estradiol monotherapy achieved testosterone suppression in 82.6% of patients without performing significantly worse than combination therapy.

Open source
Kanin 2025Show details

Role in model: Supporting cross-check

Kanin M, et al. Injectable Estradiol Dosing Regimens in Transgender and Nonbinary Adults Listed as Male at Birth. J Endocr Soc. 2025;9(5):bvaf004.

Provides contextual timing evidence from a treatment-naive weekly injectable estradiol cohort: the first on-treatment laboratory assessment was obtained an average of about 85 days after initiation, 90% were already below 50 ng/dL at that first follow-up, and all reached below 50 ng/dL during the study period.

Open source
Chadid 2019Show details

Role in model: Supporting cross-check

Chadid S, et al. Age-Specific Serum Total and Free Estradiol Concentrations in Healthy Men in US Nationally Representative Samples. J Endocr Soc. 2019;3(10):1825-1836.

Provides healthy male estradiol reference data. In nonsmoking, lean men without comorbidities from continuous NHANES 1999 to 2004, median total estradiol was 29.1 pg/mL at age 20 to 39 years, 22.7 pg/mL at 40 to 59 years, and 26.1 pg/mL at 60 years and older.

Open source
MacDonald 1979Show details

Role in model: Qualitative guardrail

MacDonald PC, et al. Origin of Estrogen in Normal Men and in Women with Testicular Feminization. J Clin Endocrinol Metab. 1979;49(6):905-916.

Classic production study showing that in normal young men, estrone production was accounted for by extraglandular formation and only a minority of estradiol production could not be explained by extraglandular conversion from plasma C19 precursors, supporting a mainly peripheral origin of male estrogen production.

Open source
Diver 2003Show details

Role in model: Primary anchor

Diver MJ, Imtiaz KE, Ahmad AM, Vora JP, Fraser WD. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol (Oxf). 2003;58(6):710-717.

Primary 24-hour diurnal testosterone study. Both young and middle-aged healthy men showed significant rhythms, with total testosterone falling at least 43% from peak to nadir and acrophase around 07:00 to 07:30, supporting a repeating morning-peaked baseline rather than a perfectly flat untreated line.

Open source
Ahokoski 1998Show details

Role in model: Supporting cross-check

Ahokoski O, Virtanen A, Huupponen R, Scheinin H, Salminen E, Kairisto V, Irjala K. Biological day-to-day variation and daytime changes of testosterone, follitropin, lutropin and oestradiol-17beta in healthy men. Clin Chem Lab Med. 1998;36(7):485-491.

Small healthy-male repeated-sampling study. Testosterone was higher at 08:00 and 12:00, while estradiol-17beta peaked at 12:00 with a decline toward evening, supporting a visible daily testosterone rhythm but a smoother and less aggressively modeled endogenous estradiol swing.

Open source
Oriowo 1980Show details

Role in model: Primary anchor

Oriowo MA, Landgren BM, Stenstrom B, Diczfalusy E. A comparison of the pharmacokinetic properties of three estradiol esters. Contraception. 1980;21(4):415-424.

Classic three-ester IM comparison after a single 5 mg dose in arachis oil. Estradiol valerate and benzoate peaked at about 2 days, while cypionate peaked at about 4 days with lower peak levels but longer persistence. Elevated estrogen levels lasted about 4 to 5 days for benzoate, 7 to 8 days for valerate, and about 11 days for cypionate; none of the esters remained elevated at 2 weeks in this older cohort.

Open source
Lichten 1996Show details

Role in model: Supporting cross-check

Lichten EM, Lichten JB, Whitty A, Pieper D. The confirmation of a biochemical marker for women's hormonal migraine: the depo-estradiol challenge test. Headache. 1996;36(6):367-371.

In 28 postmenopausal women already on continuous estrogen replacement therapy, a 5 mg intramuscular Depo-Estradiol cypionate challenge was followed with labs on days 4, 7, 14, 21, and 28. In the migraine subgroup, the worst migraine occurred on average at 18.5 +/- 2.8 days, when mean serum estradiol was 46.4 +/- 5.6 pg/mL. This is useful only as a rough late-tail cross-check for estradiol cypionate, not as a clean primary PK calibration study.

Open source
Herndon 2023Show details

Role in model: Supporting cross-check

Herndon JS, Maheshwari AK, Nippoldt TB, Carlson SJ, Davidge-Pitts CJ, Chang AY. Comparison of the Subcutaneous and Intramuscular Estradiol Regimens as Part of Gender-Affirming Hormone Therapy. Endocr Pract. 2023;29(5):356-361.

Retrospective GAHT route-comparison study found similar estradiol and testosterone levels on subcutaneous and intramuscular injectable estradiol despite slightly lower median weekly doses on the subcutaneous route (3.75 vs 4 mg). Multiple regression showed dose remained associated with estradiol after adjustment for route, BMI, antiandrogen use, and gonadectomy status. This supports a shared route-proxy approach when direct route-specific PK data are sparse, but it is not a dense serial PK equivalence study.

Open source
Poage 2026Show details

Role in model: Supporting cross-check

Poage AC, et al. Comparison of Subcutaneous Versus Intramuscular Estradiol Administration for Feminizing Gender-Affirming Hormone Therapy. Pharmacy (Basel). 2026;14(1):13.

Single health-system retrospective cohort of 70 adults on feminizing GAHT found no difference between subcutaneous and intramuscular estradiol in the proportion reaching therapeutic estradiol levels at 6 months. Secondary exploratory analyses of continuous estradiol values suggested somewhat higher measured estradiol concentrations with IM administration. This supports route-comparison context more than route-specific PK calibration.

Open source
Aaron 2025Show details

Role in model: Supporting cross-check

Aaron MS, Phulwani P. Single-Center Retrospective Analysis of Safety and Efficacy of Subcutaneous Estradiol Use in Transgender and Nonbinary Adolescents and Young Adults. Transgend Health. 2025;10(4):316-324.

Retrospective single-center TGNB adolescent and young adult cohort found therapeutic estradiol concentrations in 75% overall on subcutaneous estradiol cypionate, valerate, or both. Among those on subcutaneous estradiol cypionate, 52% reached 100 to 300 pg/mL at a median weekly dose of 2 mg, while 75% of those on subcutaneous estradiol valerate reached that range at a median weekly dose of 4 mg; many cypionate users could not titrate because of nationwide shortage, and most patients used concurrent antiandrogens.

Open source
Sierra-Ramirez 2011Show details

Role in model: Supporting cross-check

Sierra-Ramirez JA, et al. Pharmacokinetics and pharmacodynamics of a contraceptive formulation containing medroxyprogesterone acetate and estradiol cypionate after subcutaneous and intramuscular administration. Contraception. 2011;84(6):565-570.

Combined medroxyprogesterone acetate plus estradiol cypionate contraceptive study. After 5 mg estradiol cypionate given subcutaneously, serum estradiol Cmax was 1.31 nmol/L, Tmax was 2.32 days, and AUC was 14.57 day*nmol/L; the study also reported similar main PK parameters after intramuscular and subcutaneous dosing. The app uses this only as formulation and route-feasibility context, not as a primary calibration source for contemporary oil-depot GAHT EC.

Open source
Misakian 2025Show details

Role in model: Supporting cross-check

Misakian AL, et al. Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States. J Clin Endocrinol Metab. 2025;110(9):e2898-e2907.

Multicenter cross-sectional retrospective study of 562 TGD adults on injectable estradiol found that dose and timing in the injection cycle were major drivers of estradiol concentration, while route of administration and type of ester were not significant covariates. In the 7-day cohort, the median dose among patients within the 100 to 200 pg/mL guideline range was 4.0 mg, most patients overall were above 200 pg/mL, and estradiol fell by about 18.65 pg/mL per day since the last injection after adjustment.

Open source

Experimental estimates

Show details
Estimated endogenous estradiol background

The total E2 line includes a small endogenous background tied to the entered baseline morning testosterone. It starts near 25 25 pg/mL at the default 500 ng/dL baseline, scales with that input, flattens that daily rhythm in the longer views for readability, and then falls toward a small floor as testosterone and aromatization decline.

Total E1

The yellow line is estimated from the total E2 line using formulation-level or route-level estrone context, a short rolling-average component, and a small endogenous background. It is more than a fixed multiplier, but it is still not a separately validated estrone PK model.

Total testosterone

The light-blue line is an educational estimate. It starts from your entered morning baseline of 500 ng/dL, smooths estradiol exposure over 14 days, applies route-specific suppression weighting, layers in any active antiandrogens or total-T suppressors, and keeps a nonzero low-range floor, flattens that daily rhythm outside the 1-week view to keep longer windows readable, and moves toward that estimate gradually rather than instantly.

SHBG-adjusted androgenicity proxy

The darker blue androgen line starts from the estimated total-T line and applies a route-weighted SHBG multiplier so oral regimens can read as less androgenic than total testosterone alone would suggest. Direct antiandrogens such as spironolactone can also nudge it lower than serum testosterone alone would imply. It is a free-T-like educational proxy, not a laboratory free testosterone result.

Kariyawasam 2025Show details

Role in model: Qualitative guardrail

Kariyawasam NM, Ahmad T, Sarma S, Fung R. Comparison of Estrone/Estradiol Ratio and Levels in Transfeminine Individuals on Different Routes of Estradiol. Transgend Health. 2025;10(3):261-268.

Provides route-level estrone-to-estradiol ratio context in transfeminine patients: oral estradiol had the highest mean E1/E2 ratio (9.28), followed by sublingual (6.88), with lower ratios on transdermal (2.22) and injectable estradiol (0.84).

Open source
Tebbens 2022Show details

Role in model: Qualitative guardrail

Tebbens M, et al. The Role of Estrone in Feminizing Hormone Treatment. J Clin Endocrinol Metab. 2022;107(2):e458-e466.

Supports two key caveats at once: oral estradiol produces much higher estrone and SHBG than transdermal estradiol, but estrone itself was not associated with breast development or body-fat change.

Open source
Cortez 2024Show details

Role in model: Qualitative guardrail

Cortez S, et al. Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial. J Endocr Soc. 2024;8(8):bvae108.

Used to support route-weighting notes: transdermal 17-beta estradiol suppressed testosterone more rapidly than once- or twice-daily sublingual estradiol and produced lower estrone levels, with no meaningful advantage for twice-daily over once-daily sublingual dosing.

Open source
Liang 2018Show details

Role in model: Supporting cross-check

Liang JJ, et al. Testosterone Levels Achieved by Medically Treated Transgender Women in a United States Endocrinology Clinic Cohort. Endocr Pract. 2018;24(2):135-142.

Provides contextual evidence from a U.S. oral-estrogen-plus-spironolactone cohort: patients starting therapy required about 9 months on average to reach a steady-state testosterone level, highlighting that suppression in practice may take substantially longer than a few days.

Open source
Yaish 2023Show details

Role in model: Qualitative guardrail

Yaish I, et al. Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6):485-493.

Provides contextual evidence against overselling sublingual dosing frequency: in this small 6-month prospective study, 0.5 mg sublingual estradiol four times daily did not show a clear clinical or biochemical advantage over combined oral estradiol plus cyproterone acetate.

Open source
Slack 2025Show details

Role in model: Supporting cross-check

Slack DJ, et al. Examining the Influence of the Route of Administration and Dose of Estradiol on Serum Estradiol and Testosterone Levels in Feminizing Gender-Affirming Hormone Therapy. Endocr Pract. 2025;31(1):19-27.

Provides comparative route evidence from a large retrospective cohort: oral estradiol was the only route showing a clear linear dose-response, with testosterone falling about 19.03 ng/dL per 1 mg/day, while intramuscular estradiol was associated with lower testosterone and higher estradiol than oral or transdermal routes.

Open source
Collet 2023Show details

Role in model: Supporting cross-check

Collet S, et al. Changes in Serum Testosterone and Adrenal Androgen Levels in Transgender Women With and Without Gonadectomy. J Clin Endocrinol Metab. 2023;108(2):331-338.

Supports keeping a nonzero androgen floor in the model. Testosterone and adrenal androgen profiles remain low rather than disappearing entirely, even after gonadectomy.

Open source
Zhou 2024Show details

Role in model: Qualitative guardrail

Zhou C, Jones Q, Kokosa S, Kelley C. 7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients. J Endocr Soc. 2024;8(Suppl 1):bvae163.1680.

Conference abstract providing contextual evidence that estradiol monotherapy can suppress testosterone in some transfeminine patients: in this small retrospective cohort, testosterone suppression to under 50 ng/dL was achieved in 100% of the transfeminine subgroup when serum estradiol was above 100 pg/mL, most often with injectable estradiol valerate and less often with transdermal patches.

Open source
Misakian 2025 (Endocr Pract)Show details

Role in model: Supporting cross-check

Misakian AL, et al. Injectable Estradiol Monotherapy Effectively Suppresses Testosterone in Gender-Affirming Hormone Therapy. Endocr Pract. 2025;31(11):1462-1469.

Supports the higher-exposure end of the experimental testosterone overlay: in this multisite cross-sectional cohort on weekly injectable estradiol, median estradiol was 232 pg/mL and median total testosterone was 17 ng/dL overall, and estradiol monotherapy achieved testosterone suppression in 82.6% of patients without performing significantly worse than combination therapy.

Open source
Kanin 2025Show details

Role in model: Supporting cross-check

Kanin M, et al. Injectable Estradiol Dosing Regimens in Transgender and Nonbinary Adults Listed as Male at Birth. J Endocr Soc. 2025;9(5):bvaf004.

Provides contextual timing evidence from a treatment-naive weekly injectable estradiol cohort: the first on-treatment laboratory assessment was obtained an average of about 85 days after initiation, 90% were already below 50 ng/dL at that first follow-up, and all reached below 50 ng/dL during the study period.

Open source
Chadid 2019Show details

Role in model: Supporting cross-check

Chadid S, et al. Age-Specific Serum Total and Free Estradiol Concentrations in Healthy Men in US Nationally Representative Samples. J Endocr Soc. 2019;3(10):1825-1836.

Provides healthy male estradiol reference data. In nonsmoking, lean men without comorbidities from continuous NHANES 1999 to 2004, median total estradiol was 29.1 pg/mL at age 20 to 39 years, 22.7 pg/mL at 40 to 59 years, and 26.1 pg/mL at 60 years and older.

Open source
MacDonald 1979Show details

Role in model: Qualitative guardrail

MacDonald PC, et al. Origin of Estrogen in Normal Men and in Women with Testicular Feminization. J Clin Endocrinol Metab. 1979;49(6):905-916.

Classic production study showing that in normal young men, estrone production was accounted for by extraglandular formation and only a minority of estradiol production could not be explained by extraglandular conversion from plasma C19 precursors, supporting a mainly peripheral origin of male estrogen production.

Open source
Diver 2003Show details

Role in model: Primary anchor

Diver MJ, Imtiaz KE, Ahmad AM, Vora JP, Fraser WD. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol (Oxf). 2003;58(6):710-717.

Primary 24-hour diurnal testosterone study. Both young and middle-aged healthy men showed significant rhythms, with total testosterone falling at least 43% from peak to nadir and acrophase around 07:00 to 07:30, supporting a repeating morning-peaked baseline rather than a perfectly flat untreated line.

Open source
Ahokoski 1998Show details

Role in model: Supporting cross-check

Ahokoski O, Virtanen A, Huupponen R, Scheinin H, Salminen E, Kairisto V, Irjala K. Biological day-to-day variation and daytime changes of testosterone, follitropin, lutropin and oestradiol-17beta in healthy men. Clin Chem Lab Med. 1998;36(7):485-491.

Small healthy-male repeated-sampling study. Testosterone was higher at 08:00 and 12:00, while estradiol-17beta peaked at 12:00 with a decline toward evening, supporting a visible daily testosterone rhythm but a smoother and less aggressively modeled endogenous estradiol swing.

Open source

Important caveats

  • The E1 line is still experimental and should be read as context, not as a validated treatment target or a predictor of feminization outcomes.
  • The endogenous E2 background is a physiologic estimate rather than a measured lab value. It uses healthy male estradiol reference data, while the endogenous E1 background is only a heuristic ratio informed by classic production studies; both then follow a smaller smoothed daily rhythm and fall with testosterone suppression.
  • The testosterone overlay is not a validated clinical predictor and should be treated as a rough educational estimate only.
  • The SHBG-adjusted androgenicity proxy is even more inferential than the total-T line because it does not use measured baseline SHBG, albumin, free-testosterone chemistry, or a full receptor occupancy model.
  • It includes a low-range floor plus a route-informed response time to reflect persistent adrenal or peripheral androgen contribution and avoid implausibly fast hour-to-hour gonadal shutdown, while still allowing direct suppressors to accelerate the decline when evidence supports that behavior.
  • The route-specific suppression differences are inferences from comparative clinical route studies, not published exact potency conversions.
  • Injectable estradiol esters now use multi-phase depot fits when the literature clearly implies staggered release or a fast rise plus a slower tail, but the routes are not equally certain: valerate and cypionate are shared IM or subQ proxies rather than route-separated serial PK fits, enanthate relies partly on mixed EEn or DHPA monthly evidence, and benzoate and undecylate remain historical low-confidence illustrations. Gel and pellets also stay lower-confidence because gel is technique- and timing-sensitive and modern pellet PK tables remain sparse, especially above 25 mg or with short reinsertion intervals.
  • The antiandrogen and total-T suppressor curves model net suppressor activity, not measured serum concentrations of cyproterone, spironolactone, or GnRH agonists on the chart.
  • The GnRH agonist entries include a small first-dose flare proxy, but they do not model every real-world variation in flare size, repeat-dose flare, or missed-dose behavior.
  • Individual suppression depends on more than estradiol alone, including gonadal function, assay method, blood-draw timing, SHBG, smoking, BMI, adherence, and whether other agents are being used.

Injectable EC

Show details

Injectable EC

Injectable estradiol cypionate

Apparent elimination half-life
7.00 days
Weighted absorption half-life
34.0 hours
Modeled androgen-response timescale
14.00 days
Modeled peak time
95.0 hours
Calibration strategy
Multi-phase fit
Evidence fit
moderate fit confidence, primary oil-depot ec pk plus mixed-ester im/subq cohort and timing context

The literature suggests staggered release or a fast rise plus a slower tail, so the app uses a multi-phase fit scaled to the published or review-supported peak window.

Route: Depot injection (shared IM/subQ proxy). Formulation: Estradiol cypionate oil depot.

Route-specific caution

Shared IM/subQ proxy anchored mainly to older IM oil-depot PK. Weekly use is a route-context default, and the subQ evidence is cohort-based rather than serial PK.

Oriowo 1980Show details

Role in model: Primary anchor

Oriowo MA, Landgren BM, Stenstrom B, Diczfalusy E. A comparison of the pharmacokinetic properties of three estradiol esters. Contraception. 1980;21(4):415-424.

Classic three-ester IM comparison after a single 5 mg dose in arachis oil. Estradiol valerate and benzoate peaked at about 2 days, while cypionate peaked at about 4 days with lower peak levels but longer persistence. Elevated estrogen levels lasted about 4 to 5 days for benzoate, 7 to 8 days for valerate, and about 11 days for cypionate; none of the esters remained elevated at 2 weeks in this older cohort.

Open source
Lichten 1996Show details

Role in model: Supporting cross-check

Lichten EM, Lichten JB, Whitty A, Pieper D. The confirmation of a biochemical marker for women's hormonal migraine: the depo-estradiol challenge test. Headache. 1996;36(6):367-371.

In 28 postmenopausal women already on continuous estrogen replacement therapy, a 5 mg intramuscular Depo-Estradiol cypionate challenge was followed with labs on days 4, 7, 14, 21, and 28. In the migraine subgroup, the worst migraine occurred on average at 18.5 +/- 2.8 days, when mean serum estradiol was 46.4 +/- 5.6 pg/mL. This is useful only as a rough late-tail cross-check for estradiol cypionate, not as a clean primary PK calibration study.

Open source
Herndon 2023Show details

Role in model: Supporting cross-check

Herndon JS, Maheshwari AK, Nippoldt TB, Carlson SJ, Davidge-Pitts CJ, Chang AY. Comparison of the Subcutaneous and Intramuscular Estradiol Regimens as Part of Gender-Affirming Hormone Therapy. Endocr Pract. 2023;29(5):356-361.

Retrospective GAHT route-comparison study found similar estradiol and testosterone levels on subcutaneous and intramuscular injectable estradiol despite slightly lower median weekly doses on the subcutaneous route (3.75 vs 4 mg). Multiple regression showed dose remained associated with estradiol after adjustment for route, BMI, antiandrogen use, and gonadectomy status. This supports a shared route-proxy approach when direct route-specific PK data are sparse, but it is not a dense serial PK equivalence study.

Open source
Poage 2026Show details

Role in model: Supporting cross-check

Poage AC, et al. Comparison of Subcutaneous Versus Intramuscular Estradiol Administration for Feminizing Gender-Affirming Hormone Therapy. Pharmacy (Basel). 2026;14(1):13.

Single health-system retrospective cohort of 70 adults on feminizing GAHT found no difference between subcutaneous and intramuscular estradiol in the proportion reaching therapeutic estradiol levels at 6 months. Secondary exploratory analyses of continuous estradiol values suggested somewhat higher measured estradiol concentrations with IM administration. This supports route-comparison context more than route-specific PK calibration.

Open source
Aaron 2025Show details

Role in model: Supporting cross-check

Aaron MS, Phulwani P. Single-Center Retrospective Analysis of Safety and Efficacy of Subcutaneous Estradiol Use in Transgender and Nonbinary Adolescents and Young Adults. Transgend Health. 2025;10(4):316-324.

Retrospective single-center TGNB adolescent and young adult cohort found therapeutic estradiol concentrations in 75% overall on subcutaneous estradiol cypionate, valerate, or both. Among those on subcutaneous estradiol cypionate, 52% reached 100 to 300 pg/mL at a median weekly dose of 2 mg, while 75% of those on subcutaneous estradiol valerate reached that range at a median weekly dose of 4 mg; many cypionate users could not titrate because of nationwide shortage, and most patients used concurrent antiandrogens.

Open source
Sierra-Ramirez 2011Show details

Role in model: Supporting cross-check

Sierra-Ramirez JA, et al. Pharmacokinetics and pharmacodynamics of a contraceptive formulation containing medroxyprogesterone acetate and estradiol cypionate after subcutaneous and intramuscular administration. Contraception. 2011;84(6):565-570.

Combined medroxyprogesterone acetate plus estradiol cypionate contraceptive study. After 5 mg estradiol cypionate given subcutaneously, serum estradiol Cmax was 1.31 nmol/L, Tmax was 2.32 days, and AUC was 14.57 day*nmol/L; the study also reported similar main PK parameters after intramuscular and subcutaneous dosing. The app uses this only as formulation and route-feasibility context, not as a primary calibration source for contemporary oil-depot GAHT EC.

Open source
Misakian 2025Show details

Role in model: Supporting cross-check

Misakian AL, et al. Injectable Estradiol Use in Transgender and Gender-Diverse Individuals throughout the United States. J Clin Endocrinol Metab. 2025;110(9):e2898-e2907.

Multicenter cross-sectional retrospective study of 562 TGD adults on injectable estradiol found that dose and timing in the injection cycle were major drivers of estradiol concentration, while route of administration and type of ester were not significant covariates. In the 7-day cohort, the median dose among patients within the 100 to 200 pg/mL guideline range was 4.0 mg, most patients overall were above 200 pg/mL, and estradiol fell by about 18.65 pg/mL per day since the last injection after adjustment.

Open source

Model assumptions

  • The injectable estradiol cypionate curve is anchored mainly to the classic 5 mg oil-depot peak around day 4, while the later-day Depo-Estradiol migraine-challenge study is used only as a rough late-tail cross-check that helps keep the curve from running too high at 2 to 3 weeks.
  • The older contraceptive aqueous-suspension study remains in the source list only as a route-timescale and vehicle contrast, not as the main calibration for contemporary GAHT-style oil-depot estradiol cypionate.
  • Direct modern subQ-only serial PK tables remain sparse, so the app currently uses one shared IM/subQ injectable cypionate curve rather than separate route-specific fits.
  • That shared route treatment is backed by transfeminine cohort and clinic-timing studies, all of which support similar therapeutic attainment once dose and timing are considered rather than proving dense serial PK equivalence.
  • The 4 mg weekly default is a modern route-context example rather than the calibration dose itself; real-world weekly 5 mg schedules can still run high depending on cycle timing and assay method.
  • Contemporary transfeminine weekly injection data are used as a clinic-timing cross-check rather than a clean route-specific single-dose calibration source.
  • The experimental E1 layer uses a low parenteral estrone context rather than a separate estrone PK model.
  • The experimental testosterone overlay treats injectable estradiol cypionate as depot-injectable-strength suppression and oral estradiol as less suppressive per pg/mL, which is an inference from comparative route data rather than a validated equivalence formula.

Disclaimer

We aim to make this calculator as useful and transparent as possible using publicly available studies, prescribing information, and clinical guidance. It is still a simplified, population-average pharmacokinetic model with important assumptions, uncertainty, and confidence limits, and real lab results and clinical responses vary between people. Use it for educational and informational purposes only, not to diagnose, prescribe, or change treatment on your own. It is not medical advice and it is not a substitute for clinician judgment, individualized care, or real laboratory follow-up.

What this model does not capture

  • Uses one-compartment oral or transdermal fits and multi-phase depot fits for injectable esters, plus dose superposition for overlapping administrations.
  • Shows approximate estradiol in pg/mL and androgen estimates in ng/dL, not treatment advice or personalized forecasts.
  • The Total E1 line, Total T estimate, and SHBG-adjusted androgenicity proxy are all more heuristic than the estradiol PK line.
  • Very long-acting forms such as pellets, estradiol undecylate, and long-acting GnRH suppressors can outlast the current plot window.
  • The SHBG-aware androgenicity proxy does not model albumin, measured SHBG, BMI, smoking, assay method, individual free-T chemistry, or full receptor occupancy.
  • The current MTF catalog covers estradiol forms plus selected antiandrogens and total-T suppressors, but not progesterone or 5-alpha-reductase inhibitors.
  • Spironolactone can pull the androgenicity proxy below the serum total-T line, but that direct antiandrogen adjustment is still a simplified heuristic rather than a receptor-occupancy model.
  • 5-alpha-reductase inhibitors are intentionally excluded for now because their neurosteroid effects, including possible allopregnanolone reduction, remain controversial.

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What does the purple curve represent, and why is it a little lower than Total E2?Show answer

The purple curve is the estradiol coming directly from the regimen itself. The pink Total E2 line adds the app’s endogenous estradiol context on top of that. As testosterone suppression builds, there is less endogenous contribution, so the two lines move closer together.

What does the loading dose toggle do for EC, EEn, or EUn?Show answer

For eligible injectable estradiol forms, it makes only the first injection larger. Every later injection stays at the maintenance dose you entered, which lets you preview the common “get up to speed faster” use case without changing the rest of the schedule.

Does this recommend a dose for me?Show answer

No. The plot is an educational, population-average estimate of curve shape and timing, not personalized medical advice.

What happens if I add more than one estrogen form or suppressor?Show answer

The app layers the selected scenarios into one combined preview. That can be useful for overlap or transitions, but real hormone responses can still be messier than the simplified model.

Why does changing frequency matter so much?Show answer

Frequency changes how much doses overlap. Shorter intervals usually smooth peaks and troughs, while longer intervals usually create wider swings.

For questions, suggestions, requests, or corrections please email Maeve @maeve@gahtplotter.com