Estradiol Cypionate
E2 Cyp Β· Depo-Estradiol
Injectable estradiol cypionate used in feminizing HRT.
Key takeaways
- Longest-acting common injectable estradiol ester; ~3.7-day half-life, peak ~17 hours.
- Approved (Depo-Estradiol) for menopausal symptoms; feminizing use is off-label community practice.
- Human PK data is real but old: 1980 ester comparison, monthly-injectable contraceptive trials.
- Titrate to serum estradiol at trough; excess levels raise thrombosis risk.
Reported dosing protocols
Protocols reported in research literature and clinic/community use β informational context, not a dosing recommendation.
| Use case | Dose | Route | Frequency | Duration |
|---|---|---|---|---|
| Menopausal symptoms (label) | 1β5 mg | IM | Every 3β4 weeks | Ongoing |
| Feminizing HRT (community/guideline) | 2β10 mg | IM or SubQ | Weekly, sometimes split every 5 days | Ongoing |
Pharmacokinetic summary
- Model tier
- Advanced (tΒ½ + Cmax + Tmax + F)
- Half-life
- 3.7 days
- Cmax
- 2.8 pg/mL
- Tmax
- 0.7 days
- Bioavailability
- 60%
- Typical dose
- 2β10 mg
Frequently asked questions
Cypionate vs valerate for injections?
Cypionate lasts longer and peaks lower. The 1980 head-to-head found cypionate produced significantly lower estradiol peaks than valerate with a longer tail, which is why cypionate stretches to weekly dosing comfortably while valerate users often notice a day-five dip.
Is there modern clinical evidence behind it?
For menopausal use, it's an approved drug with label dosing. For gender-affirming use, no randomized trials exist; practice rests on older PK studies, physiology, and community bloodwork. Guidelines support injectable estradiol generally without picking an ester.
What estradiol levels are too high?
There's no universal ceiling, but sustained levels far above the physiological follicular range raise thrombosis and breast-tenderness risk without added benefit. Community practice targets trough levels within the cisgender female range and adjusts from symptoms plus bloodwork.
References
- ScienceDirect (E2 Cyp PK)
- Oriowo et al., Contraception 1980: PK of three estradiol esters β Head-to-head IM PK; cypionate peaked lower and lasted longer than valerate and benzoate.
- Sierra-RamΓrez et al., Contraception 2011: MPA/estradiol cypionate SC vs IM β Comparative PK of the monthly combination injectable.
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