MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Leuprolide Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Leuprolide (leuprolide acetate, brand names Lupron and Eligard) is a synthetic nonapeptide GnRH agonist that, with continuous dosing, paradoxically shuts down LH, FSH, testosterone, and estradiol by down-regulating the pituitary GnRH receptor. It is FDA-approved for advanced prostate cancer, endometriosis, uterine fibroids, and central precocious puberty, and is used off-label in IVF/ART. The classic daily dose is 1 mg (1000 mcg) subcutaneously once daily; long-acting depots run from 7.5 mg monthly up to 45 mg every 6 months and are clinician-administered with a supplied diluent. After an initial 1-2 week hormonal 'flare,' the drug drives testosterone to castrate levels (about 99% of men reach 50 ng/dL or below within a month). This page models the daily subcutaneous protocol for educational measurement; depot products are not bacteriostatic-water reconstitutions and must be given by a healthcare professional (PMID 6436700, PMID 17970643).
Reconstitute: Add 3 mL bacteriostatic water → 5 mg/mL concentration.
Typical dose: 1 mg (1000 mcg)/day SC; depot 7.5 mg monthly to 45 mg every 6 months
Easy measuring: At 5 mg/mL, 1 unit = 0.01 mL = 0.0500 mg (50 mcg) on a U-100 insulin syringe.
Storage: Daily leuprolide injection solution is stored at controlled room temperature, about 25 °C, with excursions permitted between 15-30 °C; protect from light and do not freeze. Commercial depot kits are stored at room temperature and reconstituted with their supplied diluent immediately before use. A modeled reconstituted research vial would be kept refrigerated at 2-8 °C and used within its dating period.
Half-life: ~3 hours for the non-depot form (≈2.9 h IV, 3.6 h SC); depots release continuously over 1-6 months.
Route: Subcutaneous once daily (1 mg) for the immediate-release form; depots given SC (Eligard) or IM (Lupron Depot).
Status: FDA-approved, prescription-only GnRH agonist; administer under medical supervision.
About Leuprolide
Leuprolide (leuprolide acetate) is a synthetic nonapeptide GnRH agonist used to shut down sex-hormone production by desensitizing the pituitary GnRH receptor [2][3]. Unlike most peptides on this site, its best-studied daily form is genuinely subcutaneous: the original Lupron daily injection is a 5 mg/mL solution dosed 1 mg once daily, the exact regimen used in the landmark 1984 metastatic prostate cancer trial [1]. The subcutaneous reconstitution figures below therefore mirror a real route rather than an educational approximation.\n\nThe head-keyword Leuprolide dosage most people search for is the 1 mg (1000 mcg) daily subcutaneous dose. Beyond the daily form, leuprolide is far more commonly given as long-acting depots (7.5 mg monthly up to 45 mg every six months, plus 3.75 mg/11.25 mg gynecologic depots); those depot suspensions are reconstituted with a manufacturer-supplied diluent and injected by a clinician, so they are not modeled as a bacteriostatic-water protocol here.\n\nThis guide models a 15 mg vial reconstituted with 3 mL of bacteriostatic water (5 mg/mL, matching the real daily-injection concentration) so doses land cleanly on a U-100 insulin syringe: 0.25 mg = 5 units, 0.5 mg = 10 units, and the standard 1 mg = 20 units. Lower 0.25-0.5 mg daily doses reflect the pituitary down-regulation step used in IVF/ART protocols.\n\nFrequency: Once daily, subcutaneously, at roughly the same time each day. Leuprolide is FDA-approved and prescription-only; this page is educational and is not medical advice.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 3 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner glass wall of the 15 mg leuprolide vial; do not aim the stream directly at the powder and avoid vigorous shaking, which can shear the peptide.
Gently swirl or roll the vial until the solution is completely clear; the result is a 5 mg/mL concentration (50 mcg per insulin-syringe unit), the same strength as the commercial daily injection.
Store refrigerated at 2-8 °C and draw the prescribed number of units per dose: 0.25 mg = 5 units, 0.5 mg = 10 units, 1 mg (standard) = 20 units on a U-100 syringe.
Rotate subcutaneous sites (abdomen, thigh), pinch the skin, inject slowly without aspirating, and wait a few seconds before withdrawing; note that long-acting leuprolide depots are NOT prepared this way and must be reconstituted with their supplied diluent and given by a clinician.
Interactive Leuprolide Syringe Calculator
Currently visualizing the 15 mg vial reconstituted with 3 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 15mg dry powder in 3mL water yields 5.00 mg/mL. To evaluate a 250mcg dose, pull to 5.0 units (5 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| IVF/ART luteal-phase or reduced down-regulation dose (0.25 mg) | 250 mcg | 5 units (0.05 mL) |
| IVF/ART pituitary down-regulation start (0.5 mg) | 500 mcg | 10 units (0.10 mL) |
| Advanced prostate cancer daily standard (1 mg) | 1000 mcg (1 mg) | 20 units (0.20 mL) |
Administration guidelines: Refer to guidelines | 3 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 15 mg vial.
Peptide Vials (Leuprolide, 15 mg each):
- check8-week daily course at 1 mg/day (~56 mg total): about 4 vials
- check12-week daily course (~84 mg total): about 6 vials
- check16-week daily course (~112 mg total): about 8 vials
- checkEach 15 mg vial reconstituted to 5 mg/mL provides roughly fifteen 1 mg daily doses
Insulin Syringes (U-100):
- checkOne syringe per daily injection: about 56 for an 8-week course
- checkAbout 84 for a 12-week course
- checkAbout 112 for a 16-week course
- checkKeep ~10% spares for dropped or mis-drawn syringes
Bacteriostatic Water (30 mL bottles): Use 3 mL per vial for reconstitution.
- check8-week course (~4 vials): ~12 mL, one 30 mL bottle is sufficient
- check12-week course (~6 vials): ~18 mL, one 30 mL bottle
- check16-week course (~8 vials): ~24 mL, one 30 mL bottle
- checkReconstitute each vial only when ready to begin using it
Alcohol Swabs: Clean the vial stopper and each injection site before use.
- checkAbout 120 swabs for an 8-week daily course (two per injection)
- checkAbout 180 swabs for a 12-week course
- checkAbout 240 swabs for a 16-week course
- checkUse a fresh swab for the vial top and a separate one for the skin
Mechanism of Action (MOA)
Leuprolide (leuprolide acetate) is a synthetic nonapeptide analog of gonadotropin-releasing hormone (GnRH/LH-RH) with the sequence 5-oxo-Pro-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-N-ethylamide. Substituting D-leucine at position 6 and an ethylamide at the C-terminus resists enzymatic degradation and increases receptor affinity, making leuprolide roughly 80-100 times more potent than native GnRH at the pituitary GnRH receptor [2][3].\n\nParadoxically for a receptor agonist, its therapeutic effect is suppression. Endogenous GnRH is secreted in pulses, and pituitary gonadotrophs require that pulsatility to keep releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Continuous, non-pulsatile occupancy of the GnRH receptor by leuprolide first triggers a surge ('flare') of LH and FSH, and therefore a transient rise in testosterone (men) or estradiol (women) during the first 1-2 weeks, then drives receptor down-regulation and desensitization. Within 2-4 weeks, LH, FSH, and gonadal sex steroids fall to castrate or menopausal levels, an effect that is reversible after the drug is stopped [1][3][7].\n\nIn men with prostate cancer, daily 1 mg subcutaneous leuprolide and the depot formulations lower serum testosterone to medical-castration thresholds: roughly 99% of patients reach 50 ng/dL or below within about a month, with mean nadir values near 12 ng/dL on the 45 mg six-month depot [4]. In women, suppression of ovarian estradiol underlies the use of leuprolide in endometriosis and uterine fibroids; in children, halting premature gonadotropin drive is the basis for treating central precocious puberty [2][5][8].\n\nPharmacokinetics: immediate-release (non-depot) leuprolide given subcutaneously has an elimination half-life of about 3 hours (approximately 2.9 hours intravenously and 3.6 hours subcutaneously) and is largely cleared within a day, which is why the daily formulation must be injected every 24 hours [3]. To avoid daily injections, leuprolide is formulated as polymer microsphere or in-situ gel depots that release drug continuously over 1, 3, 4, or 6 months, maintaining steady plasma concentrations and sustained castrate-level suppression between clinic visits [4][6]. The peptide is metabolized to smaller inactive fragments, and the labeling does not specify dose adjustment for renal or hepatic impairment.\n\nRoute note: the daily 1 mg protocol modeled on this page is genuinely subcutaneous, matching the original Lupron 5 mg/mL daily injection used in the pivotal 1984 trial [1]. The long-acting depots, by contrast, are supplied as suspensions that must be reconstituted with their own manufacturer-provided diluent (not bacteriostatic water) and administered by a healthcare professional; they cannot be drawn into an insulin syringe from a simple reconstitution.
Clinical Trial Efficacy Highlights
- starIn the pivotal Leuprolide Study Group trial (N Engl J Med, 1984), 1 mg/day subcutaneous leuprolide was compared with diethylstilbestrol (DES) 3 mg/day orally in 199 men with newly diagnosed stage D2 metastatic prostate cancer; testosterone and dihydrotestosterone suppression and acid-phosphatase decline were equivalent (objective response ~86% vs 85%), but leuprolide caused far less gynecomastia, nausea, edema, and thromboembolism, establishing GnRH agonists as a safer alternative to estrogen for androgen deprivation [1].
- starPooled analyses of long-acting leuprolide depots show rapid, durable medical castration: roughly 99% (108/109) of prostate cancer patients reached serum testosterone of 50 ng/dL or below within one month of the 45 mg six-month depot, with maintenance at 12 months and a mean nadir near 12 ng/dL, supporting interval dosing as long as every 6 months [4].
- starThe Eligard subcutaneous depot prescribing data report that the 1-, 3-, 4-, and 6-month formulations suppress testosterone to 20 ng/dL or below in up to ~98% of patients, with very low breakthrough (>50 ng/dL) rates during the dosing interval, demonstrating deep and reliable androgen suppression [6].
- starIn a phase 3 trial of leuprolide acetate 3-month depot for central precocious puberty (Lee, Klein, Mauras et al., J Clin Endocrinol Metab, 2012), peak-stimulated LH was suppressed to prepubertal levels in 78.4% of children on the 11.25 mg dose and 95.2% on the 30 mg dose from months 2 through 6, with the higher dose yielding fewer treatment failures [5].
- starA phase 3 study of a 6-month leuprolide depot for central precocious puberty confirmed sustained suppression, with peak-stimulated LH prepubertal in roughly 93-100% of children across weeks 72-144 and basal sex hormones suppressed in all participants, while pubertal progression halted or regressed [8].
- starReviews of leuprolide's diverse clinical applications (Wilson, Vadakkadath Meethal, Bowen, Atwood; Expert Opin Investig Drugs, 2007) document established efficacy across prostate cancer, endometriosis, uterine fibroids, central precocious puberty, and assisted reproduction, reflecting a single mechanism (gonadal steroid suppression) applied to multiple hormone-driven conditions [2].
- starAcross indications, hypothalamic-pituitary-gonadal suppression is reversible: after depot discontinuation, gonadotropins and sex steroids recover, and in pediatric precocious puberty studies a pubertal hormonal response and (in girls) menses returned within about one year, supporting its use as a temporizing, non-ablative therapy [5][8].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningVasomotor hot flashes are the most common adverse effect across all indications, reflecting the intended drop in sex steroids; sweating and flushing are frequently reported [1][7].
- warningA testosterone 'flare' occurs in the first 1-2 weeks as LH/FSH transiently surge; in advanced prostate cancer this can briefly worsen bone pain, urinary obstruction, or spinal-cord-compression risk, and is commonly pre-empted with an antiandrogen during initiation [1][6].
- warningHypogonadal effects predominate with continued use: in men, decreased libido, erectile dysfunction, and testicular atrophy; in women, hypoestrogenic symptoms such as vaginal dryness, irregular bleeding, and mood changes [2][7].
- warningProlonged therapy reduces bone mineral density and raises fracture risk; gynecologic courses are generally limited (e.g., ~6 months, or up to 12 months with add-back therapy), and bone monitoring or calcium/vitamin D and add-back hormones may be advised [2].
- warningMetabolic and cardiovascular warnings on GnRH agonist labeling include hyperglycemia and new or worsening diabetes, plus an increased risk of myocardial infarction, stroke, and sudden cardiac death; QT/QTc prolongation is also possible, so cardiometabolic risk should be monitored [6].
- warningConvulsions have been reported (including in patients with and without predisposing factors), and pediatric use has rarely been linked to pseudotumor cerebri (idiopathic intracranial hypertension); injection-site reactions, fatigue, headache, and mood disturbance also occur [6][8].
- warningLeuprolide is contraindicated in pregnancy and in women who may become pregnant (expected fetal harm/spontaneous abortion), and in patients with hypersensitivity to GnRH agonists; effective non-hormonal contraception is advised during daily-dosing windows.
- warningRegulatory status: leuprolide is FDA-approved and prescription-only for defined oncologic, gynecologic, and pediatric indications; it should be administered under medical supervision, and the reconstitution figures here are an educational reference, not a prescription or medical advice.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Leuprolide dosage?expand_more
The classic daily Leuprolide dosage is 1 mg (1000 mcg) injected subcutaneously once daily, the regimen used in the original prostate cancer trial. Most patients today receive long-acting depots instead: 7.5 mg every month, 22.5 mg every 3 months, 30 mg every 4 months, or 45 mg every 6 months for prostate cancer; 3.75 mg monthly (or 11.25 mg every 3 months) for endometriosis and fibroids; and weight-based depots for pediatric central precocious puberty. In IVF/ART down-regulation, lower daily subcutaneous doses of about 0.25-0.5 mg are used. Exact dosing is set by a clinician for the specific indication.
Is Leuprolide FDA approved?expand_more
Yes. Leuprolide acetate is FDA-approved and prescription-only. Approved indications include the palliative treatment of advanced prostate cancer, management of endometriosis, preoperative treatment of uterine fibroids (with iron for anemia), and treatment of central precocious puberty in children. Brand names include Lupron, Lupron Depot, and Eligard. It is also used off-label in assisted reproduction. It is a regulated drug that should be administered under medical supervision, not a research-only compound.
How is Leuprolide reconstituted and administered for the daily protocol?expand_more
Leuprolide reconstitution in this educational model uses a 15 mg vial plus 3 mL of bacteriostatic water, giving 5 mg/mL (the same strength as the commercial daily injection). Add the water slowly down the vial wall, swirl gently until clear, refrigerate, and draw the dose on a U-100 insulin syringe: 0.25 mg = 5 units, 0.5 mg = 10 units, 1 mg = 20 units, injected subcutaneously once daily into rotating sites. Important: the long-acting depots are different products that are reconstituted with their own supplied diluent and injected by a clinician, not prepared with bacteriostatic water.
What is Leuprolide's half life?expand_more
The immediate-release (non-depot) form has a short elimination half-life of roughly 3 hours, about 2.9 hours after intravenous and 3.6 hours after subcutaneous administration, which is why the daily formulation must be injected every 24 hours. The depot formulations are engineered to release leuprolide continuously over 1, 3, 4, or 6 months, so the practical duration of effect is governed by the polymer delivery system rather than the molecule's intrinsic half-life.
What are the most common Leuprolide side effects, and what is the testosterone flare?expand_more
The most common Leuprolide side effects are hot flashes, reduced libido, fatigue, injection-site reactions, and (with prolonged use) bone mineral density loss; women may have hypoestrogenic symptoms and men may have erectile dysfunction or testicular atrophy. The 'flare' is a transient surge in LH/FSH and testosterone or estradiol during the first 1-2 weeks of therapy before suppression sets in; in advanced prostate cancer this brief flare can temporarily worsen symptoms, which is why an antiandrogen is often started alongside leuprolide. Labeling also warns about hyperglycemia/diabetes, cardiovascular events, and QT prolongation.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Leuprolide, plus the universal dosing calculator.
Academic References & Study Citations
Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. N Engl J Med. 1984;311(20):1281-1286. View Scientific Paper →
Wilson AC, Vadakkadath Meethal S, Bowen RL, Atwood CS. Leuprolide acetate: a drug of diverse clinical applications. Expert Opin Investig Drugs. 2007;16(11):1851-1863. View Scientific Paper →
Leuprolide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; updated 2023. View Scientific Paper →
Crawford ED, Phillips JM. Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort. Cancer Manag Res. 2011;3:201-209. View Scientific Paper →
Lee PA, Klein K, Mauras N, et al. Efficacy and safety of leuprolide acetate 3-month depot 11.25 milligrams or 30 milligrams for the treatment of central precocious puberty. J Clin Endocrinol Metab. 2012;97(5):1572-1580. View Scientific Paper →
ELIGARD (leuprolide acetate) for injectable suspension. Prescribing information / drug label, DailyMed, U.S. National Library of Medicine. View Scientific Paper →
Leuprolide. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2019. View Scientific Paper →
Efficacy and safety of leuprolide acetate 6-month depot for the treatment of central precocious puberty: a phase 3 study. J Endocr Soc. 2023;7(7):bvad071. View Scientific Paper →