GAHT Plotter

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Zimmermann H, Koytchev R, Mayer O, Borner A, Mellinger U, Breitbarth H. Pharmacokinetics of orally administered estradiol valerate. Results of a single-dose cross-over bioequivalence study in postmenopausal women. Arzneimittelforschung. 1998;48(9):941-947.

Classic oral estradiol valerate tablet PK paper used as the oral EV anchor. In the test formulation arm, 4 mg oral estradiol valerate reached mean estradiol Cmax 39.8 pg/mL at 8.2 hours with terminal half-life 16.9 hours; the reference formulation was similar, and the app now uses those directly matched test-arm values.

Nolan BJ, et al. Relationships between body mass index with oral estradiol dose and serum estradiol concentration in transgender adults undergoing feminising hormone therapy. Ther Adv Endocrinol Metab. 2020;11:2042018820924543.

Direct transfeminine oral estradiol valerate concentration study. After at least 6 months of therapy, median estradiol was 328 pmol/L [89 pg/mL] on 6 mg/day, with dose-specific medians of 293 pmol/L at 4 mg/day, 362 pmol/L at 6 mg/day, and 319 pmol/L at 8 mg/day. The dose-concentration correlation was weak and timing of blood sampling was not standardized.

Jarvinen A, et al. Pharmacokinetics of estradiol valerate and medroxyprogesterone acetate in different age groups of postmenopausal women. Maturitas. 2004;47(3):209-217.

Repeated-dose oral estradiol valerate steady-state PK cross-check. Participants used daily oral estradiol valerate for 12 or 14 days, and serum estradiol was sampled at steady state with reported Cmax, Tmax, AUC, and elimination half-life across age groups, making it useful as a repeated-dose comparison source rather than a single-dose-only anchor.

Cattani VB, et al. Estradiol and Spironolactone Plasma Pharmacokinetics Among Brazilian Transgender Women Using HIV Pre-Exposure Prophylaxis: Analysis of Potential Interactions. Clin Pharmacokinet. 2023;62(7):1031-1041.

Direct transfeminine 24-hour oral estradiol valerate pharmacokinetic study. After 15 days of feminizing hormone therapy, plasma estradiol, estrone, and estrone sulfate were sampled from pre-dose through 24 hours after observed dosing, with the oral EV PK sample dominated by 2 mg users and smaller 4 mg representation, supporting the apps short-pulse oral profile and high first-pass estrone context.

Kim SM, et al. Serum estradiol level according to dose and formulation of oral estrogens in postmenopausal women. Sci Rep. 2021;11:3585.

Morning steady-state oral estrogen assay cross-check. In a cross-sectional postmenopausal cohort, women were advised to take oral therapy before sleep and have blood drawn the next morning after overnight fasting. Because estradiol hemihydrate and estradiol valerate were not significantly different at the same dose, they were combined for comparison: mean serum estradiol was 65.8 pg/mL for 1 mg and 107.6 pg/mL for 2 mg. This is useful only as a rough morning assay cross-check because the study used immunoassay, was not transfeminine, and had relatively small EV-only subgroups.

Doll E, Gunsolus I, Thorgerson A, Tangpricha V, Lamberton N, Sarvaideo JL. Pharmacokinetics of Sublingual Versus Oral Estradiol in Transgender Women. Endocr Pract. 2022;28(3):237-242.

Direct transfeminine single-dose PK study. After 1 mg dosing, oral estradiol reached about 35 pg/mL at 8 hours, while sublingual estradiol reached about 144 pg/mL at 1 hour. Sublingual AUC (0-8 hours) was 1.8-fold higher than oral, and the E2-to-estrone ratio was higher at all measured time points with sublingual dosing (1.1 +/- 1.0 vs 0.7 +/- 0.4).

Sipinen S, Lahteenmaki P, Luukkainen T. Pharmacokinetic studies on low dose estradiol 17 beta administered orally to postmenopausal women. Acta Obstet Gynecol Scand. 1980;59(2):149-153.

Foundational oral micronized estradiol pharmacokinetic paper. In small postmenopausal cohorts, 1 mg once daily and 0.2 mg three times daily were followed over 24 hours on day 1 and after 1 month, showing rapid gastrointestinal absorption, substantial conversion to estrone, and a more constant estrone profile with divided dosing. This supports the oral-tablet evidence base and estrone-context assumptions more than a precise numeric PK fit.

Wiegratz I, et al. Cross-over comparison of the pharmacokinetics of estradiol during hormone replacement therapy with estradiol valerate or micronized estradiol. Zentralbl Gynakol. 2001;123(9):505-512.

Repeated-dose oral cross-over study. With 2 mg micronized estradiol, serum estradiol rose from about 10 pg/mL pre-dose to about 80 pg/mL on day 21, compared with about 60 pg/mL on estradiol valerate, and by day 28 remained around 40 pg/mL versus about 10 pg/mL on estradiol valerate. That makes it a useful shape check for daily oral micronized estradiol accumulation and slower late-day carryover than oral EV.

Price TM, et al. Single-dose pharmacokinetics of sublingual versus oral administration of micronized 17 beta-estradiol. Obstet Gynecol. 1997;89(3):340-345.

Randomized cross-over study in postmenopausal women found that sublingual micronized estradiol produced rapid burst-like absorption with high estradiol levels that fell rapidly over the first 6 hours. Sublingual dosing also had a lower E1:E2 ratio over 24 hours than oral dosing.

Fiet J, et al. Post-menopausal concentrations of plasma oestradiol, oestrone, FSH and LH and of total urinary oestradiol and oestrone after a single sublingual dose of oestradiol-17 beta. Acta Endocrinol (Copenh). 1982;101(1):93-97.

After a single 0.5 mg sublingual estradiol dose in postmenopausal women, plasma estradiol concentrations ranged from 133.2 to 320 pmol/L, and the plasma estrone-to-estradiol ratio stayed close to that of premenopausal women.

Cirrincione LR, et al. Sublingual Estradiol Is Associated with Higher Estrone Concentrations than Transdermal or Injectable Preparations in Transgender Women and Gender Nonbinary Adults. LGBT Health. 2021;8(2):125-132.

LC-MS/MS cross-sectional transfeminine study found higher estrone concentrations with sublingual estradiol than with transdermal or injectable estradiol. Estradiol concentrations with sublingual tablets were similar to the other routes in this cohort, underscoring that sublingual monitoring depends strongly on lab timing.

Rohr UD, Nauert C, Stehle B. 17Beta-estradiol delivered by three different matrix patches 50 microg/day: a three way cross-over study in 21 postmenopausal women. Maturitas. 1999;33(1):45-58.

In the Estraderm MX 50 mcg/day arm, estradiol Cmax was 38.9 pg/mL, AUC0-96h was 3192.1 pg*h/mL, and Tmax was 32 hours. The app uses this paper as the main 50 mcg/day twice-weekly matrix-patch exposure anchor, especially for Cmax and AUC.

Setnikar I, Rovati LC, Vens-Cappell B, Hilgenstock C. Pharmacokinetics of estradiol and of estrone during application of a new 7-day estradiol transdermal patch with active matrix. Arzneimittelforschung. 1998;48(3):275-285.

In a randomized cross-over study of 18 postmenopausal women, the 7-day matrix patch reached estradiol Cmax about 45 pg/mL after 25 hours and maintained average week-3 estradiol around 31 pg/mL across the wear period. Because it studied a 7-day matrix system rather than a 96-hour twice-weekly patch, the app now keeps it as supportive sustained-exposure context rather than the main timing anchor.

Brennan JJ, Lu Z, Whitman M, Stafiniak P, van der Hoop RG. Serum concentrations of 17beta-estradiol and estrone after multiple-dose administration of percutaneous estradiol gel in symptomatic menopausal women. Ther Drug Monit. 2001;23(2):134-138.

In postmenopausal women at week 12, a 50 mcg/day patch produced median serum estradiol and estrone of about 38.5 and 40.0 pg/mL, while 2.5 g gel (1.5 mg estradiol) produced about 60.0 and 62.5 pg/mL. This is useful as an older gel-versus-patch concentration comparison, not as a transfeminine PK anchor.

Trovato A, Leinung MC, Joseph J, Nguyen S. Achieving Physiologic 17-beta-Estradiol Levels in Transgender Females on Estradiol Transdermal Patches and Optimal Dosing. J Endocr Soc. 2021;5(Suppl 1):A787-A788.

Transfeminine chart review of 41 patch users found that the highest 100 mcg/day patch was often needed to achieve the clinic target estradiol level above 100 pg/mL. Among the 18 patients on 100 mcg, 11 reached goal and 1 more was just under goal.

Scott RT Jr, Ross B, Anderson C, Archer DF. Pharmacokinetics of percutaneous estradiol: a crossover study using a gel and a transdermal system in comparison with oral micronized estradiol. Obstet Gynecol. 1991;77(5):758-764.

In a 14-day crossover study of 15 postmenopausal volunteers, Oestrogel 1.5 mg/day produced a mean steady-state serum estradiol level of 68.1 +/- 27.4 pg/mL and estrone of 90.6 +/- 45.7 pg/mL. The app uses this paper mainly as the gel mean-exposure anchor rather than a direct peak-timing source.

Jarvinen A, Nykanen S, Paasiniemi L. Absorption and bioavailability of oestradiol from a gel, a patch and a tablet. Maturitas. 1999;32(2):103-113.

In randomized cross-over postmenopausal studies, 1.5 mg estradiol gel produced a peak serum estradiol concentration about 4 to 5 hours after administration. In the gel-versus-patch comparison, gel peak-trough fluctuation was about 56% to 67%, while the 50 mcg/24 h patch changed every 72 hours fluctuated about 89%. The app uses this paper mainly for gel timing and fluctuation context rather than as a direct Cmax anchor.

Cravioto MC, Larrea F, Delgado NE, Escobar AR, Diaz-Sanchez V, Dominguez J, de Leon RP. Pharmacokinetics and pharmacodynamics of 25-mg estradiol implants in postmenopausal Mexican women. Menopause. 2001;8(5):353-360.

In 15 postmenopausal hysterectomized women, a 25 mg subcutaneous estradiol implant kept serum estradiol in the early follicular range throughout 24 weeks and achieved a physiologic premenopausal E2:E1 ratio with symptom relief. This supports the classic 25 mg implant plateau concept more than a precise first-week peak calibration.

Mesure J, Afrin S, Fitzgerald S, Luu J, Gibberd A, Leigh L, Wynne K. Oestradiol implants for gender-affirming hormone therapy: an observational study of serum oestradiol levels and consumer survey. Sex Health. 2023;20(6):550-557.

Direct transfeminine implant cohort of 38 clients receiving 88 implants found median serum estradiol stayed within the 250 to 600 pmol/L target range at 1, 3, 6, 9, and 12 months after insertion. For 100 mg implants, the predicted time to fall to 250 pmol/L was about 4 months after an initial insertion versus about 13 months after subsequent insertions, underscoring major durability variability and accumulation across repeated use.

Jacobsen L, Fernandes DM, Nagel ML, de Souza EL, Viana DPC. Subcutaneous Estradiol Pellets as Hormone Therapy in Menopause: Clinical Pharmacology, Patient Selection and Safety Considerations. J Clin Med. 2025;15(1):48.

Narrative review of estradiol pellet literature reported an initial first-week peak followed by relatively stable serum estradiol in the early-to-mid follicular range for about 4 to 6 months, with the 25 mg dose typically producing mean levels around 50 to 70 pg/mL and a near-physiologic E2:E1 ratio. This is useful as plateau-and-duration context for implants, not as a direct PK calibration source.

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.

Schug BS, et al. Bioavailability and pharmacodynamics of two 10-mg estradiol valerate depot formulations following IM single dose administration in healthy postmenopausal volunteers. Int J Clin Pharmacol Ther. 2012;50(2):100-117.

Randomized crossover single-dose IM estradiol valerate bioavailability study in 24 postmenopausal volunteers. The abstract reports geometric mean estradiol Cmax values of 543.5 pg/mL and 505.7 pg/mL with AUC0-t values of 84,734 and 82,660 pg*h/mL for the two 10 mg depot formulations over a 2-week assessment. This is a strong modern single-dose IM EV exposure anchor, but the accessible abstract does not expose every PK shape parameter used for solver tuning.

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.

Rothman MS, Ariel D, Kelley C, Hamnvik OP, Abramowitz J, Irwig MS, Soe K, Davidge-Pitts C, Misakian AL, Safer JD, Iwamoto SJ. The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels. Endocr Pract. 2024;30(9):870-878.

Scoping review of modern transfeminine injectable estradiol literature concluded that common guideline starting doses for estradiol valerate or cypionate are often too high, suggested starting at 5 mg weekly or less, and emphasized that route, ester, and lab timing need more precise study. This is useful as a dose-range and timing-interpretation review for modern EV/EC use, not as a primary PK calibration source.

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

Retrospective feminizing GAHT cohort comparing subcutaneous versus intramuscular estradiol found no difference in the proportion reaching therapeutic estradiol levels at 6 months, while exploratory continuous analyses suggested IM administration was associated with somewhat higher measured estradiol concentrations.

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.

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.

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 TGNB youth cohort on subcutaneous estradiol cypionate or valerate found therapeutic estradiol concentrations in 75% overall. Among those on subcutaneous estradiol cypionate, 52% reached 100 to 300 pg/mL and the median weekly dose was 2 mg, though many could not titrate because of nationwide shortage and many used concurrent antiandrogens.

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.

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.

Wiemeyer JC, Fernandez M, Moguilevsky JA, Sagasta CL. Pharmacokinetic studies of estradiol enantate in menopausic women. Arzneimittelforschung. 1986;36(11):1674-1677.

After 10 mg intramuscular estradiol enanthate, serum estradiol was sampled through day 31. The reported elimination rate constant was 0.12445 day^-1 with an apparent half-life of about 5.57 days, and the abstract also reported an absorption rate constant of 1.5050 day^-1. The app uses this paper mainly for the apparent half-life anchor rather than as a full-shape PK fit.

Schiavon R, et al. Serum estrogens and ovulation return in chronic users of a once-a-month injectable contraceptive. Contraception. 1988;37(6):591-598.

In chronic users of a monthly injectable containing 10 mg estradiol enanthate plus 150 mg dihydroxyprogesterone acetophenide, post-injection estradiol peaked at about 314 pg/mL in chronic users and 283 pg/mL in controls, with Tmax about 4.2 versus 6.3 days.

Ribeiro CT, et al. Assessment of parenteral estradiol and dihydroxyprogesterone use among other feminizing regimens for transgender women: insights on satisfaction with breast development from community-based healthcare services. Ann Med. 2024;56(1):2406458.

Retrospective trans women cohort found that estradiol enanthate plus dihydroxyprogesterone acetophenide administered every three weeks produced mean estradiol about 186 +/- 32 pg/mL, providing a contemporary transfeminine cross-check for longer-interval repeated dosing.

Leyendecker G, et al. Estradiol-17beta, estrone, LH and FSH in serum after administration of estradiol-17beta, estradiol benzoate, estradiol valerate and estradiol undecylate in the female. Arzneimittelforschung. 1975;25(4):684-688.

Compared equimolar injections corresponding to 20 mg free estradiol in postmenopausal women and female castrates. The accessible abstract reports the compounds were clearly different in depot effect, with estradiol benzoate shortest and estradiol undecylate longest.

Vizziello G, et al. [Estradiol benzoate test in the study of pituitary block induced by triptorelin]. Minerva Ginecol. 1993;45(4):185-189.

In adults receiving long-acting triptorelin, a single 2.5 mg intramuscular estradiol benzoate test produced estradiol concentrations above 400 pg/mL at 24 hours, giving a direct human cross-check for the very early benzoate spike.

Wied GL, et al. [Estradiol valerate and estradiol undecylate, two new estrogens with prolonged action; comparison with estradiol benzoate]. Arzneimittelforschung. 1954;4(1):45-52.

Early delayed-estrogen paper that introduced estradiol undecylate as a prolonged-action ester and directly contrasted it with estradiol valerate and estradiol benzoate.

Speck U, et al. Pharmacokinetics of cyproterone acetate following oral and intramuscular administration. Contraception. 1976;14(2):151-163.

After a 50 mg oral cyproterone acetate tablet, the maximum plasma concentration was reached after about 3.8 hours and the terminal half-life was about 1.6 days.

Appu S, et al. Effectiveness of cyproterone acetate in achieving castration and preventing luteinizing hormone releasing hormone analogue induced testosterone surge in patients with prostate cancer. J Urol. 2005;174(1):140-142.

In a prospective 28-day cyproterone acetate lead-in study, mean testosterone had already fallen to near-castrate levels by day 7, and 2 weeks did not improve suppression over 1 week.

Angus L, et al. Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy. Endocr Connect. 2019;8(7):935-940.

In transfeminine adults on estradiol for more than 6 months, the cyproterone group had a median testosterone of 0.8 nmol/L versus 2.0 nmol/L with spironolactone and 10.5 nmol/L with estradiol alone.

Kuijpers SME, et al. Toward a Lowest Effective Dose of Cyproterone Acetate in Trans Women: Results From the ENIGI Study. J Clin Endocrinol Metab. 2021;106(10):e3936-e3945.

In 882 trans women, estrogens alone yielded mean testosterone about 5.5 nmol/L, while daily cyproterone acetate at 10, 25, 50, or 100 mg all reduced testosterone below 2 nmol/L. The 10 mg arm averaged about 0.9 nmol/L.

Even Zohar N, et al. Low-Dose Cyproterone Acetate Treatment for Transgender Women. J Sex Med. 2021;18(7):1292-1298.

Low-dose cyproterone acetate 10 to 20 mg/day suppressed gonadotropins and testosterone similarly to 50 to 100 mg/day in trans women, supporting low-dose use as a high-effect total-T suppressor.

Gava G, et al. A comparison of 5-year administration of cyproterone acetate or leuprolide acetate in combination with estradiol in transwomen. Eur J Endocrinol. 2020;183(6):561-569.

In a 5-year transfeminine cohort, 50 mg/day cyproterone acetate plus estradiol and 3.75 mg monthly leuprolide plus estradiol both produced similarly suppressed gonadotropin and testosterone levels.

Maatman TJ, et al. Effectiveness of castration versus intravenous estrogen therapy in producing rapid endocrine control of metastatic cancer of the prostate. J Urol. 1985;133(4):620-621.

In men with metastatic prostate cancer, bilateral orchiectomy produced castrate testosterone levels within 2 to 6 hours, with a mean time of about 3 hours, supporting near-immediate onset for a one-time surgical suppressor model.

Borgmann V, et al. Treatment of prostatic cancer with LH-RH analogues. Prostate. 1983;4(6):553-568.

After an initial injection sequence, three daily intranasal doses of 400 mcg maintained serum testosterone within the castrate range during long-term treatment of locally advanced prostate cancer.

Soloway MS. Efficacy of buserelin in advanced prostate cancer and comparison with historical controls. Am J Clin Oncol. 1988;11 Suppl 1:S29-S32.

In 207 men, buserelin caused a week-1 testosterone flare but lowered testosterone below 100 ng/dL by week 4 in about 90% of patients; intranasal maintenance was typically 400 mcg every 8 hours after a short subcutaneous lead-in.

Spitz A, et al. Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Prostate Cancer Prostatic Dis. 2012;15(1):93-99.

Leuprolide acetate 45 mg depot suppressed mean testosterone to 15.9 ng/dL by week 4 and maintained suppression throughout each 24-week depot interval.

Paul D, et al. A phase 3 trial of once-monthly 7.5 mg leuprolide acetate for central precocious puberty. J Clin Endocrinol Metab. 2011;96(5):1352-1363.

In boys receiving monthly leuprolide depot, mean testosterone was suppressed to about 17.8 ng/dL by week 4, supporting a one-month onset anchor for modeled gonadal suppression.

Tanaka N, et al. Endocrine response to a single injection of goserelin 3.6 mg or leuprolide 3.75 mg in men with prostate cancer. Arch Androl. 2007;53(2):87-90.

After a first GnRH agonist dose, testosterone increased over the first week, with a larger day-3 surge after leuprolide than after goserelin. This informs the app's optional first-dose flare proxy for GnRH agonists.

Heidenreich A, et al. Efficacy of 3-month triptorelin and testosterone thresholds below 20 ng/dL in patients with advanced prostate cancer: results of a prospective, observational study. BMC Urol. 2015;15:12.

With triptorelin 11.25 mg every 3 months, 97.6% of patients were below 50 ng/dL and 79.5% were below 20 ng/dL at 1 month, rising to 92.2% below 20 ng/dL at 3 months.

Romero E, et al. Pharmacokinetic/pharmacodynamic model of the testosterone effects of triptorelin administered in sustained release formulations in patients with prostate cancer. J Pharmacol Exp Ther. 2012;342(3):788-798.

Semimechanistic PK/PD modeling of sustained-release triptorelin found that a maintained minimum triptorelin concentration was needed to keep testosterone at or below castrate levels, supporting a broad plateau-like depot effect rather than a short simple pulse.

Breul J, et al. Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer. Adv Ther. 2017;34(2):513-523.

Across pooled prospective sustained-release triptorelin studies, 79% of patients were below 20 ng/dL at 1 month and 92% by 3 months, supporting durable low-testosterone maintenance across 1-, 3-, and 6-month depot formulations.

Kuhn JM, et al. A randomized comparison of the clinical and hormonal effects of two GnRH agonists in patients with prostate cancer. Eur Urol. 1997;32(4):397-403.

In a randomized comparison of monthly triptorelin versus leuprolide, second and third injections were not followed by a significant testosterone rise, and 24- and 72-hour post-injection testosterone suppression was at least as strong with triptorelin as with leuprolide.

Schagen SEE, et al. Efficacy and Safety of Gonadotropin-Releasing Hormone Agonist Treatment to Suppress Puberty in Gender Dysphoric Adolescents. J Sex Med. 2016;13(7):1125-1132.

In 49 transfeminine adolescents treated with triptorelin, gonadotropins and sex steroids were suppressed within 3 months, supporting reliable strong suppression on standard depot triptorelin schedules.

Kotake T, et al. LH-RH agonist, Zoladex (Goserelin), depot formulation in the treatment of prostatic cancer. Randomized dose-finding trial in Japan. Am J Clin Oncol. 1988;11 Suppl 2:S108-S111.

With goserelin depot every 28 days, testosterone rose after the first injection and then fell markedly; castrate-range suppression was achieved in all but two patients in the underdosed 0.9 mg group, supporting standard 3.6 mg monthly dosing as a strong suppressor.

Debruyne FM, et al. A new long acting formulation of the luteinizing hormone-releasing hormone analogue goserelin: results of studies in prostate cancer. J Urol. 1996;155(4):1352-1354.

Across three prostate-cancer studies, the 10.8 mg 12-week depot and the 3.6 mg 4-week depot showed similar endocrine profiles, with castrate-range testosterone by about day 21 after depot administration.

Fernandez del Moral P, et al. Three-month depot of goserelin acetate: clinical efficacy and endocrine profile. Urology. 1996;48(6):894-900.

In randomized prostate-cancer studies comparing 10.8 mg every 12 weeks with 3.6 mg every 4 weeks, testosterone levels in both groups fell below castrate levels by day 21, giving a cleaner month-1 endocrine anchor for depot goserelin.

Mueller A, et al. Effects on the male endocrine system of long-term treatment with gonadotropin-releasing hormone agonists and estrogens in male-to-female transsexuals. Horm Metab Res. 2006;38(3):183-187.

In 40 transfeminine adults receiving 3.8 mg goserelin every 4 weeks plus oral estradiol valerate, mean testosterone fell by 97% to about 0.52 nmol/L at 12 months and remained about 0.59 nmol/L at 24 months.

Shim M, et al. Effectiveness of three different luteinizing hormone-releasing hormone agonists in the chemical castration of patients with prostate cancer: Goserelin versus triptorelin versus leuprolide. Investig Clin Urol. 2019;60(4):244-250.

At 3, 6, and 9 months, goserelin, triptorelin, and leuprolide all achieved comparable castration at thresholds of 50 or 20 ng/dL, though triptorelin achieved the lowest mean testosterone overall.

Chertin B, et al. An implant releasing the gonadotropin hormone-releasing hormone agonist histrelin maintains medical castration for up to 30 months in metastatic prostate cancer. J Urol. 2000;163(3):838-844.

In metastatic prostate cancer, histrelin implant placement after antiandrogen pretreatment produced complete LH and testosterone suppression by day 28; the early untreated flare was not directly quantified, which argues for a very conservative flare proxy rather than a larger numeric fit.

Schlegel PN, et al. Efficacy and safety of histrelin subdermal implant in patients with advanced prostate cancer. J Urol. 2006;175(4):1353-1358.

The once-yearly histrelin implant suppressed testosterone and LH to castrate levels at 4 weeks and maintained suppression during 52 weeks of therapy.

Lee JY, et al. Effectiveness of Puberty Suppression with Gonadotropin-Releasing Hormone Agonists in Transgender Youth. J Adolesc Health. 2021;68(5):891-897.

Transgender adolescents treated with histrelin or leuprolide showed gonadotropin suppression comparable to central precocious puberty cohorts; AMAB patients had testosterone around 17.0 +/- 20.6 ng/dL on therapy.

Olson-Kennedy J, et al. Histrelin Implants for Suppression of Puberty in Youth with Gender Dysphoria: A Comparison of 50 mcg/Day (Vantas) and 65 mcg/Day (SupprelinLA). Transgend Health. 2021;6(1):36-42.

Transgender-youth cohort with histrelin implants showed strong sex-steroid suppression on both common implant doses during the first 2 to 12 months after placement, supporting the long-maintenance portion of the implant model.