VA Class: AN500
Chemical Name: 5-Oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt)
Molecular Formula: C59H84N16O12•C2H4O2
CAS Number: 74381-53-6
Brands: Eligard, Lupron, Lupron Depot
Medically reviewed on October 16, 2017
Antineoplastic agent and gonadotropin releasing hormone (GnRH) agonist; a synthetic nonapeptide analog of naturally occurring GnRH (luteinizing hormone releasing hormone [LHRH], gonadorelin).1 2 3 80 81 99 100 116 155 156 180 187 190 191 192
Uses for Leuprolide Acetate
Palliative treatment of endometriosis (e.g., pain relief, reduction in endometriotic lesions [dysmenorrhea and pelvic pain, tenderness, and induration]).5 55 71 96 105 106 107 108 116 126 131 191 Experience with leuprolide has been limited to women ≥18 years of age.105 116 126 191
Used in conjunction with norethindrone acetate (5 mg daily) if symptoms recur after the initial course of therapy (retreatment).116 191 Retreatment with leuprolide alone is not recommended.116 191 (See Endometriosis under Dosage and Administration and see Musculoskeletal Effects under Cautions.)
Correction of anemia associated with uterine leiomyomata (uterine fibroids) prior to surgery;116 181 191 used in conjunction with iron therapy.116 181 191 Experience with leuprolide has been limited to women ≥18 years of age.116 181 191
Treatment of central (via activation of the hypothalamic-pituitary-gonadal axis) precocious puberty (true precocious puberty, GnRH-dependent sexual precocity, complete isosexual precocity) in children155 156 157 158 159 160 161 162 163 164 165 166 177 (designated an orphan drug by FDA for this use).179
Treatment with a GnRH analog is indicated for children (girls <8 or boys <9 years of age) who have a clinical diagnosis (confirmed by pubertal response to a GnRH stimulation test) of central idiopathic or neurogenic precocious puberty with onset of secondary sexual characteristics155 156 157 159 160 177 and subsequent rapid advancement of height, height velocity, and/or bone age (e.g., ≥1 year more advanced than their chronologic age).155 156 157 159 160 161 162 163 164 165 177
Some clinicians also state that GnRH analog therapy is indicated in boys <8 years of age with a serum testosterone concentration >100 ng/dL157 177 and in girls with onset of menarche and recurrent menses at <9 years of age.177 178
GnRH analogs are ineffective as primary therapy in the treatment of GnRH-independent† (peripheral; gonadal steroid secretion is independent of gonadotropin secretion) precocious puberty, including familial male precocious puberty (testotoxicosis), congenital virilizing adrenal hyperplasia (e.g., secondary to steroid 21-hydroxylase, 11β-hydroxylase, or 3β-hydroxysteroid dehydrogenase deficiency), and McCune-Albright syndrome.157 158 169 170 171 172 173 174 177 178
Leuprolide Acetate Dosage and Administration
In patients with stage B2 or C prostate cancer, initiate leuprolide and antiandrogen 8 weeks prior to and continue during radiation therapy.200
In patients with stage D2 metastatic prostate cancer, initiate leuprolide and antiandrogen therapy concomitantly and continue until disease progression.200
Lupron Depot: Release characteristics of a fractional dose of the 11.25-mg (3-month) injectable suspension formulation are not equivalent to the same dose of the 3.75-mg (once-monthly) formulation and should not be used for monthly doses.116 191
Use of the 3-month formulation of leuprolide acetate injectable suspension (Lupron Depot-3 month 11.25 mg) recommended only when 3 months of hormonal suppression is necessary.191
Precocious Puberty: Baseline Evaluation Prior to Initiating Therapy
Leuprolide acetate injection and suspension (Lupron Depot) have comparable efficacy and safety in the treatment of advanced prostate cancer.100 101 In most patients, use of the suspension may be preferred to use of the injection because of greater convenience of administration and patient compliance with therapy.101 121
Administer leuprolide acetate suspension (Lupron Depot) by IM injection once monthly as the 3.75- or 7.5-mg depot 1-month formulation;100 101 116 155 180 187 once every 3 months as the 11.25- or 22.5-mg long-acting 3-month formulation;100 101 116 155 180 187 190 191 once every 4 months as the 30-mg long-acting 4-month formulation,100 101 116 155 180 187 190 or once every 24 weeks as the 45-mg long-acting 6-month formulation.190
Release characteristics of a fractional dose of the 22.5-mg (3-month), 30-mg (4-month), or 45-mg (6-month) suspension formulation (Lupron Depot) are not equivalent to the same dose of the 7.5-mg (once-monthly) formulation and should not be used for monthly doses for treatment of prostate cancer.180 187 190
Release characteristics of a fractional dose of the 11.25-mg (3-month) suspension formulation (Lupron Depot) are not equivalent to the same dose of the 3.75-mg (once-monthly) formulation and should not be used for monthly doses for treatment of endometriosis or uterine leiomyomata.116 191
Administer leuprolide acetate suspension (Lupron Depot-Ped) by IM injection once every 4 weeks as a 3.75-, 7.5-, or 15-mg depot 1-month formulation.155
Leuprolide acetate powder for injectable suspension (Lupron Depot) is available in a dual-chamber, disposable, single-use syringe;100 116 155 190 191 chamber 1 of the system contains leuprolide acetate lyophilized powder, and chamber 2 contains the sterile diluent supplied by the manufacturer.100 116 155 190 191
Reconstitute dual-chamber, disposable, single-use syringes containing 3.75, 7.5, 11.25, 15, 22.5, 30, or 45 mg of leuprolide acetate extended-release for injectable suspension with the accompanying diluent in accordance with the instructions provided by the manufacturer.100 116 155 190 191
Following reconstitution, immediately inject entire contents of the syringe to provide a 3.75-, 7.5-, 11.25-, 15-, 22.5-, 30-mg, or 45-mg dose, depending on the labeled concentration of the syringe used.100 116 155 190 191
Administer leuprolide acetate suspension (Eligard) by sub-Q injection once monthly as a 7.5-mg formulation, once every 3 months as a 22.5-mg formulation, once every 4 months as a 30-mg formulation, or once every 6 months as a 45-mg formulation.192
Administer leuprolide acetate suspension (Eligard) in an area with sufficient soft or loose sub-Q tissue (e.g., upper- or mid-abdominal area, upper buttocks).192 Avoid areas with excessive pigment, hair, or brawny or fibrous sub-Q tissue (nodules, lesions) or locations that could be rubbed or compressed (e.g., with a belt or clothing waistband).192
When substitution of another syringe for the one provided by the manufacturer for use with leuprolide acetate injection is required, a disposable, low-dose, U-100 insulin syringe is the only syringe that should be used.98 104 193
Leuprolide acetate powder for injectable suspension (Eligard) is available in a single-use kit, containing 2 separate disposable syringes;192 syringe 1 of the system contains leuprolide acetate powder, and syringe 2 contains the polymeric (non-gelatin-containing) delivery system (Atrigel).192
Allow the kit to reach room temperature before reconstituting.192
Reconstitute single-use syringes containing 7.5, 22.5, 30, or 45 mg of leuprolide acetate powder for injectable suspension with the accompanying polymeric delivery system in accordance with the instructions provided by the manufacturer.192
Central Precocious Puberty
Individualize dosage according to actual body weight;155 156 161 younger children (i.e., children weighing <25 kg) generally appear to require higher dosages on a mg/kg basis than older children (i.e., children weighing ≥25 kg).155 156
Confirm inhibition of gonadotropin secretion and suppression of ovarian or testicular steroidogenesis after 1–2 months of initial therapy or when changing dosage by evaluation of GnRH stimulation test, Tanner staging, and sex steroid concentrations.155 156 159
Data currently are insufficient for specific dosage recommendations in children in whom therapy was initiated at a low dosage and at a very young age and whose weight has changed such that the patient would be in a different weight range/dose category.155 156 The manufacturer recommends that inhibition of gonadotropin secretion and suppression of ovarian or testicular steroidogenesis be monitored closely in children whose weight has increased considerably while receiving therapy.155 156
Dosage of leuprolide acetate suspension (Lupron Depot-Ped)
7.5 mg every 4 weeks
11.25 mg every 4 weeks
15 mg every 4 weeks
Titrate dose upward in increments of 3.75 mg every 4 weeks until clinical or laboratory tests indicate no disease progression.155
Therapy usually is continued until fusion of the epiphyses157 or attainment of appropriate chronologic pubertal age (e.g., consideration made at 11 and 12 years of age in girls and boys, respectively).155 156 157
Leuprolide acetate injection (Lupron for Pediatric Use): Initially 50 mcg/kg once daily for girls <8 years of age or boys <9 years of age.156 158 If total suppression of ovarian or testicular steroidogenesis is not achieved, titrate dosage upward by 10 mcg/kg daily to establish maintenance dosage.156
Advanced Prostate Cancer
Daily Therapy with Leuprolide Acetate InjectionSub-Q
For patients at risk of serious adverse affects, consider initiating therapy with daily administration of leuprolide acetate injection for 2 weeks prior to IM administration of leuprolide acetate suspension (Lupron Depot) to permit discontinuance of therapy if warranted.101 180 187 (See Endocrine Effects under Cautions.)
Therapy with Extended-release SuspensionIM
7.5 mg once monthly as the monthly formulation (Lupron Depot),100 101 or 22.5 mg every 12 weeks as the 3-month formulation (Lupron Depot 22.5 mg for 3-month administration),180 190 or 30 mg once every 16 weeks as the 4-month formulation (Lupron Depot 30 mg for 4-month administration),187 190 or 45 mg once every 24 weeks as the 6-month formulation (Lupron Depot 45 mg for 6-month administration).190
If a monthly dose is missed, a delay of ≤12 days may or may not compromise the patient’s treatment; however, if a monthly dose is missed by ≥2 weeks, serum testosterone concentrations will increase substantially.101Sub-Q
Eligard: 7.5 mg once monthly as the monthly formulation, or 22.5 mg once every 3 months as the 3-month formulation, or 30 mg once every 4 months as the 4-month formulation, or 45 mg once every 6 months as the 6-month formulation.192
3.75 mg once monthly as the monthly formulation (Lupron Depot) for 6 consecutive months116 or 11.25 mg every 3 months as the 3-month formulation (Lupron Depot-3 month 11.25 mg) for a total of 6 months.191 Administer with or without norethindrone acetate (5 mg daily).116 191
Retreatment If Symptoms Recur after Initial Treatment
Retreatment with additional courses of leuprolide alone is not recommended; if retreatment is considered, administer a single 6-month course of leuprolide acetate suspension in conjunction with norethindrone acetate (and elemental calcium 1 g daily).116 191
3.75 mg once monthly as the monthly formulation (Lupron Depot) for a total of 6 months or 11.25 mg every 3 months as the 3-month formulation (Lupron Depot-3 month 11.25 mg) for a total of 6 months.116 191 Administer in conjunction with oral norethindrone acetate (5 mg daily).116 191
3.75 mg once monthly as the monthly formulation (Lupron Depot) for up to 3 consecutive months in conjunction with iron therapy.116
11.25 mg of the 3-month formulation (Lupron Depot-3 month 11.25 mg) as a single injection in conjunction with iron therapy.191 Use of the 3-month formulation recommended only when 3 months of hormonal suppression is necessary.191
Retreatment If Symptoms Recur after Initial TreatmentIM
Lupron Depot 3.75 mg monthly formulation: Maximum 3 consecutive months of therapy recommended.116
Lupron Depot 11.25 mg (3-month formulation): A single injection of 11.25 mg recommended.191
Safety and efficacy of >6 months of therapy not evaluated.191
Cautions for Leuprolide Acetate
Fetal/Neonatal Morbidity and Mortality
Expected hormonal changes increase the risk for pregnancy loss and fetal harm when administered to a pregnant woman; teratogenicity, fetotoxicity, and fetolethality demonstrated in animals.1 100 155 156 180 187 190 191 192 193 194
Women of childbearing potential should avoid pregnancy and use an effective nonhormonal method of contraception during therapy.116 191 If used during pregnancy or patient becomes pregnant, discontinue and apprise of potential fetal hazard.1 100 116 156 180 187 190 191 192 193 194
Initial Worsening of Hormone-dependent Disease
Transient increases in serum testosterone (in men) or estrogen (in women) concentrations1 10 32 33 35 99 100 108 115 116 145 146 155 156 180 187 190 191 192 may result in worsening (flare) of signs and/or symptoms (e.g., increased bone pain) of hormone-dependent disease (e.g., endometriosis, prostatic carcinoma, central precocious puberty) during the initial 1–2 weeks of therapy; generally subsides during continued therapy.1 10 32 33 35 99 100 108 115 116 145 146 155 156 180 187 190 191 192 Concomitant antiandrogen therapy (e.g., flutamide, nilutamide) has been used to decrease disease flare severity and improve overall response rates in patients with advanced prostate cancer.3 49 50 102 111 130
Risk of spinal cord compression which may contribute to paralysis with or without fatal complications and/or ureteral obstruction (dysuria, hematuria) in men with prostate cancer.1 82 100 145 187 190 192 Monitor patients with metastatic vertebral lesions and/or urinary tract obstruction closely during initial therapy for temporary weakness or paresthesia of the lower limbs and/or worsening of urinary signs and symptoms.99 100 180 190 192 If spinal cord compression or urinary obstruction develops, institute standard treatment.100 192
Use with extreme caution in patients with life-threatening disease in whom rapid symptomatic relief is necessary;1 2 4 exacerbation of signs and/or symptoms of the disease potentially may result in a rapid fatal outcome.1 75 99 100
Possible hyperglycemia and increased risk of diabetes in patients receiving GnRH agonists for treatment of prostate cancer.100 189 190 Studies evaluating risk of diabetes in women and children receiving GnRH agonists not performed to date.188
Periodically monitor blood glucose and/or HbA1c in patients receiving GnRH agonists for treatment of prostate cancer.189 190 Manage hyperglycemia or diabetes according to current standards of care.100 189 190
Combination Therapy with Norethindrone Acetate
If leuprolide acetate suspension (Lupron Depot) is used in conjunction with norethindrone acetate for management of endometriosis, consider the precautions, cautions, and contraindications associated with the concomitant agent.116 191
Noncompliance or Inadequate Dosage in Central Precocious Puberty.
Noncompliance with dosage regimen or use of inadequate dosage may result in inadequate control of the pubertal process including return of pubertal signs (e.g., menses, breast development, testicular growth).155 156 Long-term effects of inadequate control of gonadal (sex) steroid secretion are not known; further compromise of adult stature may occur.155 156
Serious and occasionally fatal hypersensitivity reactions, including anaphylactoid or asthmatic process reported rarely.99 100 116 155 156 187 190 191 192 194 Rash, urticaria, and photosensitivity reactions also reported.99 100 116 155 156 187 190 194
Leuprolide acetate injection contains benzyl alcohol as a preservative.1 99 156 193 194 Risk of local hypersensitivity reactions (e.g., erythema, induration at the injection site); use with caution in patients with known hypersensitivity to benzyl alcohol.1 156 193 194 99
Pituitary apoplexy, a clinical syndrome resulting from infarction of the pituitary gland, reported rarely.100 116 155 190 Most cases occur within 2 weeks of the first dose, sometimes within the first hour.100 116 155 190 If manifestations (e.g., sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, sometimes cardiovascular collapse) occur, immediate medical attention required.100 116 155 190 In most cases, pituitary adenoma diagnosed.100 116 155 190
Decreases in bone mineral density (BMD) have been reported in men100 190 192 193 187 and women.105 106 108 110 116 126 127 128 129 131 133 134 135 191 For management of endometriosis in women, concurrent use of norethindrone acetate (5 mg daily) and calcium supplementation (1 g elemental calcium daily) reduces the drug-induced loss of BMD without compromising the efficacy of the drug.116 191
Use in women for management of endometriosis for periods exceeding 6 months, for uterine leiomyomata for periods exceeding 3 months, or in patients with other risk factors for decreased BMD (e.g., chronic alcohol and/or tobacco use, strong family history of osteoporosis, chronic use of drugs that can reduce bone mass [e.g., corticosteroids, phenytoin]) may result in additional bone loss.116 191 Carefully weigh risks and benefits of therapy.116 191 In women with risk factors for decreased BMD, consider concomitant treatment with norethindrone acetate 5 mg daily.116 191
Adverse cardiovascular effects (e.g., hypotension,100 116 190 MI,100 116 190 DVT,116 PE,100 116 190 stroke,116 and TIA116 ) reported. Possible increased risk of certain cardiovascular diseases (e.g., MI, sudden cardiac death, stroke) in patients receiving GnRH agonists for treatment of prostate cancer.100 189 190 192 Studies evaluating risk of heart disease in women and children receiving GnRH agonists not performed to date.188
Periodically monitor patients receiving GnRH agonists for treatment of prostate cancer for manifestations of cardiovascular disease; manage cardiovascular disease according to current standards of care.100 189 190 192
Risk of prolonged QT interval associated with long-term androgen deprivation therapy.190 Carefully weigh benefits and risks of androgen deprivation therapy in patients with congenital long QT syndrome, electrolyte abnormalities, or CHF and in patients taking class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.190
Patient Monitoring in Prostate Cancer
Periodically determine serum testosterone1 64 100 190 192 193 and PSA1 64 100 192 193 concentrations to monitor therapeutic response. Precision of testosterone assays varies; consider specific type used.180 187 190 192
Patient Monitoring in Central Precocious Puberty
Determine serum sex steroid concentrations and perform GnRH stimulation test 1–2 months after initiation of therapy155 156 159 and periodically (e.g., every 6 months thereafter)159 to monitor therapeutic response.155 156 159
Inadequate dosage may lead to increased sex steroid concentrations;155 156 once a therapeutic dosage has been achieved, gonadotropin and sex steroid concentrations will decline to prepubertal concentrations.155 156
Risk of increased LDL-cholesterol/HDL-cholesterol ratio, increased total and LDL cholesterol and triglycerides, and decreased HDL-cholesterol in women receiving leuprolide acetate alone and in conjunction with norethindrone acetate for endometriosis.116 191
Assess and manage cardiovascular risk factors, including cigarette smoking, before initiating combined therapy with leuprolide acetate in conjunction with norethindrone acetate for endometriosis.116 191
Safety and efficacy of leuprolide acetate injection and leuprolide acetate injectable suspension (7.5-, 11.25-, or 15-mg pediatric formulations of Lupron Depot-Ped) for uses other than treatment of central precocious puberty not established.116 155
Safety and efficacy of the 3.75 mg (monthly), 11.25 mg (3-month), 22.5-mg (3-month), 30-mg (4-month), or 45-mg (6-month) formulations of leuprolide acetate injectable suspension (Lupron Depot) not established.116 190 191
Safety and efficacy of the 7.5-, 22.5-, 30-, 45-mg formulations of leuprolide acetate injectable suspension (Eligard) not established.192
Evaluate patients prior to initiating therapy and periodically during therapy to evaluate response to the drug.155 156 159 (See Baseline Evaluation prior to Initiating Therapy under Dosage and Administration and also see Patient Monitoring in Central Precocious Puberty under Cautions.)
Leuprolide acetate injection or leuprolide acetate injectable suspension (7.5-, 22.5-, 30-, 45-mg formulations of Eligard or Lupron Depot): Clinical studies for use in prostate cancer have been conducted principally in patients ≥65 years of age.100 190 192 193
Leuprolide acetate injectable suspension (11.25- or 15-mg pediatric formulations of Lupron Depot-Ped): Safety and efficacy not established in those ≥65 years of age.155
Common Adverse Effects
Men with metastatic prostate cancer (leuprolide acetate injection): Hot flushes (flashes),1 2 3 4 10 32 33 34 35 36 100 101 193 impotence,1 2 33 34 36 193 decreased libido,2 10 32 33 testicular atrophy,1 193 general pain,1 ECG changes/ischemia,1 193 peripheral edema,1 193 asthenia.1 193
Men with metastatic prostate cancer (leuprolide acetate suspension [Lupron Depot]): Hot flushes,100 121 180 187 190 impotence,100 180 190 decreased libido,100 180 testicular atrophy,100 180 190 general pain,100 180 187 190 GI disorders,100 187 190 edema,100 187 190 injection site reaction,180 187 190 urinary disorder,100 180 187 190 respiratory disorder,100 190 infection,100 joint disorder,180 187 190 peripheral edema,99 100 116 190 asthenia,100 190 fatigue/lethargy.190
Men with metastatic prostate cancer (leuprolide acetate injectable suspension [Eligard]): Injection site reactions (transient burning/stinging),192 hot flushes,192 malaise and fatigue,192 testicular atrophy.192
Women with endometriosis: Hot flushes, 105 106 108 116 121 126 amenorrhea,105 106 116 hypercholesterolemia,116 depression/emotional lability,116 dizziness,116 insomnia/sleep disorder,105 libido changes (e.g., decreased libido),116 asthenia,116 general pain,116 headache,116 nausea/vomiting,116 altered bowel function, weight gain/loss,116 acne,116 skin reactions,116 joint disorder,116 vaginitis.116
Children with precocious puberty: Injection site reaction (e.g., abscess),155 156 emotional lability,155 general pain,155 156 acne/seborrhea,155 156 headache,155 rash (e.g., erythema multiforme),155 156 vaginitis/bleeding/discharge,155 156 vasodilation.155
Interactions for Leuprolide Acetate
Specific Drugs and Laboratory Tests
Drug or Test
Antiandrogen (e.g., flutamide, bicalutamide, nilutamide)
Tests, diagnostic tests of pituitary gonadotropic and gonadal function
Leuprolide Acetate Pharmacokinetics
Peak plasma concentrations usually attained 3.3–5 hours following sub-Q administration of long-acting injectable suspension (Eligard) in prostate cancer patients.192
Following IM administration of the long-acting injectable suspension (Lupron Depot) or sub-Q administration of the long-acting injectable suspension (Eligard), the drug is released slowly and gradually from its biodegradable copolymer-containing vehicle.100 101 116 155 117 118 180 187 190 192
Onset of estradiol suppression occurs 4–28 days following IM administration of a single 11.25-mg dose of the long-acting injectable suspension in healthy women;191 mean estradiol concentration is in the menopausal range 21 days following administration.191
Peak plasma concentrations remain stable for approximately 2.5 weeks following IM administration of Lupron Depot 7.5-mg in prostate cancer patients, and then decline over the next several weeks.101
Plasma concentrations decrease to trough levels 4 weeks following IM administration of Lupron Depot 7.5-, 11.25-, or 15-mg in children with central precocious puberty.155
Steady plasma concentrations persist through the 1-, 3-, 4-, or 6-month dosing interval following IM administration of the 7.5-, 22.5-, 30-, or 45-mg long-acting injectable suspension (Eligard), respectively, in prostate cancer patients.192 No drug accumulation observed after repeated dosing.192
Similar changes from baseline in estradiol serum concentration observed in women with endometriosis receiving 11.25- or 3.75-mg IM doses of the long-acting suspension (Lupron Depot) every 12 weeks or every 4 weeks, respectively, for 24 weeks.191
Mean serum estradiol concentrations ranged from the menopausal to the early follicular range for 12 weeks following IM administration of a single 11.25-mg dose of the long-acting injectable suspension (Lupron Depot) in healthy women.191
Plasma Protein Binding
Injectable Suspension (Eligard)
Injectable Suspension (Lupron Depot or Lupron Depot-Ped)
A synthetic nonapeptide analog of GnRH; 1 2 3 80 81 99 100 116 155 156 structural modifications result in increased potency (in terms of luteinizing hormone release) compared with GnRH.1 3 4 8 155 156
A potent inhibitor of gonadotropin secretion and suppresser of ovarian and testicular steroidogenesis when given continuously;1 2 5 7 8 9 10 11 12 13 15 69 83 87 105 105 106 109 110 116 131 155 156 157 158 159 177 decreases release through down-regulation of GnRH receptors.1 2 6 7 10 11 12 13 15 16 11 12 13 14 13 19 24 105 106 110 116 157 109 158 159 177
Initially, circulating levels of LH, FSH, testosterone, dihydrotestosterone (DHT) estrone and estradiol surge transiently.1 10 12 15 24 Following long-term administration (generally, 2–4 weeks after initiation of therapy), produces a sustained decrease in LH and FSH secretion and a marked reduction of testicular and ovarian steroidogenesis.1 2 3 4 5 7 10 11 12 13 15 22 23 69 89 100 105 106 109 110 116 155 156 157
Reductions in serum testosterone concentrations in males during therapy are comparable to those achieved after surgical castration (i.e., <50 ng/dL).1 3 12 47 100 101 Testicular and prostatic atrophy may occur.2 12 13 24
Induces reductions in myometrial and leiomyomal volumes; possibly from decreased secretion of somatotropin (growth hormone) and estrogen-dependent growth factors (e.g., insulin-like growth factor I, IGF-I).137 138
Reduces gonadotropins in children with central precocious puberty and resultant depression of ovarian and testicular steroidogenesis may allow for normal physical and psychological growth and development.155 156 157 158 159 164 167 168 177 Effects appear to be reversible; pubertal development resumes following discontinuance of the drug.155 156 157 158 159 177
Advice to Patients
Importance of providing patients or caregivers administering leuprolide acetate injection adequate oral and written instructions regarding proper administration methods (including aseptic technique), use of appropriate syringe (as supplied or low-dose insulin type), drug storage, and proper disposal of used needles and syringes.1 156
Risk of worsening manifestations of disease, such as symptoms (e.g., bone pain, spinal cord injury, hematuria, urethral or bladder outlet obstruction) of prostate cancer, during initial weeks of therapy.1 100
Importance of informing clinicians of persistent skin reactions (burning, itching, or swelling) at injection site.1
Risk of anaphylactoid or other hypersensitivity reactions.1
Risk of new or worsening symptoms of depression while receiving leuprolide therapy.190
Importance of women informing their clinician if regular menstruation persists.116 166 191 Women also should be advised that breakthrough bleeding or ovulation (with potential for conception) may occur if one or more successive doses of the drug are missed.116 166 191
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and use nonhormonal contraceptive measures. Advise pregnant women of risk to the fetus.100 116 166 191
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
For injectable suspension, extended-release, for IM use
Lupron Depot (available as prefilled dual-chambered syringes)
Lupron Depot (available as prefilled dual-chambered syringes)
Lupron Depot-Ped (available as prefilled dual-chambered syringes)
Lupron Depot-Ped (available as prefilled dual-chambered syringes)
Lupron Depot (available as prefilled dual-chambered syringes)
Lupron Depot-Ped (available as prefilled dual-chambered syringes)
Lupron Depot (available as prefilled dual-chambered syringes)
Lupron Depot (available as prefilled dual-chambered syringes)
Lupron Depot (available as prefilled dual-chambered syringes)
For injectable suspension, extended-release, for subcutaneous use
Eligard (available in a 2-syringe Atrigel Delivery System)
Eligard (available in a 2-syringe Atrigel Delivery System)
Eligard (available in a 2-syringe Atrigel Delivery System)
Eligard (available in a 2-syringe Atrigel Delivery System)
Injection, for subcutaneous use
Leuprolide Acetate Injection
AHFS DI Essentials. © Copyright 2018, Selected Revisions October 16, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
1. TAP Pharmaceuticals. Lupron (leuprolide acetate) prescribing information. Chicago, IL; 1998 Jul.
2. Smith JA Jr. Androgen suppression by a gonadotropin releasing hormone analogue in patients with metastatic carcinoma of the prostate. J Urol. 1984; 131:1110-2. http://www.ncbi.nlm.nih.gov/pubmed/6427478?dopt=AbstractPlus
3. The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. N Engl J Med. 1984; 311:1281-6. http://www.ncbi.nlm.nih.gov/pubmed/6436700?dopt=AbstractPlus
4. Soloway MS. Newer methods of hormonal therapy for prostate cancer. Urology. 1984; 24(Suppl):30-40. http://www.ncbi.nlm.nih.gov/pubmed/6437034?dopt=AbstractPlus
5. Cutler GB, Hoffman AR, Swerdloff RS et al. Therapeutic applications of luteinizing-hormone-releasing hormone and its analogs. Ann Intern Med. 1985; 102:643-57. http://www.ncbi.nlm.nih.gov/pubmed/3920942?dopt=AbstractPlus
6. Heber D, Dodson R, Peterson M et al. Counteractive effects of agonistic and antagonistic gonadotropin-releasing hormone analogs on spermatogenesis: sites of action. Fertil Steril. 1984; 41:309-13. http://www.ncbi.nlm.nih.gov/pubmed/6421624?dopt=AbstractPlus
7. Rajfer J, Swerdloff RS, Heber DM. Testicular histology following chronic gonadotropin-releasing hormone agonist treatment. Fertil Steril. 1984; 42:765-71. http://www.ncbi.nlm.nih.gov/pubmed/6436070?dopt=AbstractPlus
8. Vilchez-Martinez JA, Pedroza E, Coy DH et al. Prolonged release of LH and FSH and depletion of pituitary gonadotropin content after administration of [d-leu6, desgly-NH210]-LH-RH ethylamide1 (39686). Proc Soc Exp Biol Med. 1977; 154:427-30. http://www.ncbi.nlm.nih.gov/pubmed/322156?dopt=AbstractPlus
9. Vilchez-Martinez JA, Coy DH, Arimura A et al. Synthesis and biological properties of [Leu-6]-LH-RH and [d-leu-6,desgly-NH210]-LH-RH ethylamide. Biochem Biophys Res Commun. 1974; 59:1226-32. http://www.ncbi.nlm.nih.gov/pubmed/4607145?dopt=AbstractPlus
10. Vance MA, Smith JA Jr. Endocrine and clinical effects of leuprolide in prostatic cancer. Clin Pharmacol Ther. 1984; 36:350-4. http://www.ncbi.nlm.nih.gov/pubmed/6432399?dopt=AbstractPlus
11. Bambino TH, Schreiber JR, Hsueh AJW. Gonadotropin-releasing hormone and its agonist inhibit testicular luteinizing hormone receptor and steroidogenesis in immature and adult hypophysectomized rats. Endocrinology. 1980; 107:908-17. http://www.ncbi.nlm.nih.gov/pubmed/6250797?dopt=AbstractPlus
12. Smith JA Jr, Urry RL. Testicular histology after prolonged treatment with a gonadotropin-releasing hormone analogue. J Urol. 1985; 133:612-4. http://www.ncbi.nlm.nih.gov/pubmed/3920405?dopt=AbstractPlus
13. Labrie F, Cusan L, Seguin C et al. Antifertility effects of LHRH agonists in the male rat and inhibition of testicular steroidogenesis in man. Int J Fertil. 1980; 25:157-70. http://www.ncbi.nlm.nih.gov/pubmed/6108924?dopt=AbstractPlus
14. Clayton RN. Gonadotropin-releasing hormone modulation of its own pituitary receptors: evidence for biphasic regulation. Endocrinology. 1982; 111:152-60. http://www.ncbi.nlm.nih.gov/pubmed/6282566?dopt=AbstractPlus
15. Warner B, Santen R, Demers L. Effects of [d/leu6,des-gly-NH2, pro-ethylamide9]-GnRH (leuprolide) on steroidogenesis when used to treat prostatic carcinoma. J Androl. 1982; 3:14.
16. Tcholakian RK, De la Cruz A, Chowdhury M et al. Unusual anti-reproductive properties of the analog [d-leu6,des-gly-NH210]-luteinizing hormone-releasing hormone ethylamide in male rats. Fertil Steril. 1978; 30:600-3. http://www.ncbi.nlm.nih.gov/pubmed/363462?dopt=AbstractPlus
17. Belanger A, Auclair C, Ferland L et al. Time-course of the effect of treatment with a potent LHRH agonist on testicular steroidogenesis and gonadotropin receptor levels in the adult rat. J Steroid Biochem. 1980; 13:191-6. http://www.ncbi.nlm.nih.gov/pubmed/6247573?dopt=AbstractPlus
18. Evans RM, Doelle GC, Lindner J et al. A luteinizing-hormone-releasing hormone agonist decreases biological activity and modifies chromatographic behavior of luteinizing hormone in man. J Clin Invest. 1984; 73:262-6. http://www.ncbi.nlm.nih.gov/pubmed/6228566?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=425009&blobtype=pdf
19. Auclair C, Kelly PA, Coy DH et al. Potent inhibitory activity of [d-leu6,des-gly-NH210] LHRH ethylamide on LH/hCG and PRL testicular receptor levels in the rat. Endocrinology. 1977; 101:1890-3. http://www.ncbi.nlm.nih.gov/pubmed/201452?dopt=AbstractPlus
20. Rajfer J, Swerdloff RS, Heber D. The pituitary gland is the primary site of action of GnRH agonist (d-leu6,des-gly10-GnRH ethylamide) in the male. Fertil Steril. 1982; 38:277-8.
21. Sharpe RM, Fraser HM. Inhibition of maturational changes in Leydig cell function by treatment of rats with an agonist of LH-RH. J Reprod Fertil. 1980; 60:359-68. http://www.ncbi.nlm.nih.gov/pubmed/6776279?dopt=AbstractPlus
22. Santen RJ, Demers LM, Max DT et al. Long term effects of administration of a gonadotropin-releasing hormone superagonist analog in men with prostatic carcinoma. J Clin Endocrinol Metab. 1984; 58:397-400. http://www.ncbi.nlm.nih.gov/pubmed/6420439?dopt=AbstractPlus
23. Santen RJ, Warner B. Evaluation of synthetic agonist analogue of gonadotropin-releasing hormone (leuprolide) on testicular androgen production in patients with carcinoma of prostate. Urology. 1985; 25(Suppl):53-7. http://www.ncbi.nlm.nih.gov/pubmed/3918377?dopt=AbstractPlus
24. Warner B, Worgul TJ, Drago J et al. Effect of very high dose d-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary-testicular axis in patients with prostatic cancer. J Clin Invest. 1983; 71:1842-53. http://www.ncbi.nlm.nih.gov/pubmed/6408125?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=370390&blobtype=pdf
25. Pollack A, Block NL, Stover BJ et al. Effects of the gonadotropin-releasing hormone agonist [d-leu6,desgly-NH210, proethylamide9]-GnRH (leuprolide) on R3327-G rat prostatic tumor growth. J Urol. 1984; 131:399-403. http://www.ncbi.nlm.nih.gov/pubmed/6422059?dopt=AbstractPlus
26. Okada H, Sakura Y, Kawaji H et al. Regression of rat mammary tumors by a potent luteinizing hormone-releasing hormone analogue (leuprolide) administered vaginally. Cancer Res. 1983; 43:1869-74. http://www.ncbi.nlm.nih.gov/pubmed/6403230?dopt=AbstractPlus
27. Schally AV, Redding TW, Comaru-Schally AM. Potential use of analogs of luteinizing hormone-releasing hormones in the treatment of hormone-sensitive neoplasms. Cancer Treat Rep. 1984; 68:281-9. http://www.ncbi.nlm.nih.gov/pubmed/6362868?dopt=AbstractPlus
28. Okada H, Yamazaki I, Ogawa Y et al. Vaginal absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide) in rats I: absorption by various routes and absorption enhancement. J Pharm Sci. 1982; 71:1367-71. http://www.ncbi.nlm.nih.gov/pubmed/6818337?dopt=AbstractPlus
29. Yamazaki I. Serum concentration patterns of an LHRH agonist, gonadotrophins and sex steroids after subcutaneous, vaginal, rectal and nasal administration of the agonist to pregnant rats. J Reprod Fertil. 1984; 72:129-36. http://www.ncbi.nlm.nih.gov/pubmed/6433008?dopt=AbstractPlus
30. Tharandt L, Schulte H, Benker G et al. Binding of luteinizing hormone releasing hormone to human serum proteins—influence of a chronic treatment with a more potent analogue of LH-RH. Horm Metab Res. 1979; 11:391-4. http://www.ncbi.nlm.nih.gov/pubmed/381140?dopt=AbstractPlus
31. Koch Y, Baram T, Hazum E et al. Resistance to enzymic degradation of LH-RH analogues possessing increased biological activity. Biochem Biophys Res Commun. 1977; 74:488-91. http://www.ncbi.nlm.nih.gov/pubmed/319798?dopt=AbstractPlus
32. The Takeda-Abbott Prostatic Cancer Study Group. leuprolide (d-leu-Des Gly10-Pro9-NH Et-LHRH) in the therapy of advanced prostatic carcinoma. In: Spitzy KH, Karrer K, eds. Proceedings of the 13th International Congress of Chemotherapy. 1983; 242:49-53.
33. Smith JA Jr, Glode LM, Max DT et al. Clinical effects of gonadotropin-releasing hormone analogue in metastatic carcinoma of prostate. Urology. 1985; 25:106-14. http://www.ncbi.nlm.nih.gov/pubmed/3918369?dopt=AbstractPlus
34. Winfield H, Trachtenberg J. A comparison of a powerful luteinizing hormone releasing hormone analogue agonist and estrogen in the treatment of advanced prostatic cancer. J Urol. 1984; 131:1107-9. http://www.ncbi.nlm.nih.gov/pubmed/6427477?dopt=AbstractPlus
35. Lee M, Stobnicki M, Ray P et al. Preliminary evaluation of the safety and efficacy of leuprolide versus diethylstilbestrol in the treatment of stage D2 prostatic adenocarcinoma. In: Spitzy KH, Karrer K, eds. Proceedings of the 13th International Congress of Chemotherapy. 1983; 242:54-8.
36. Trachtenberg J. The treatment of metastatic prostatic cancer with a potent luteinizing hormone releasing hormone analogue. J Urol. 1983; 129:1149-52. http://www.ncbi.nlm.nih.gov/pubmed/6406688?dopt=AbstractPlus
37. Torti FM. Hormonal therapy for prostate cancer. N Engl J Med. 1984; 311:1313-4. http://www.ncbi.nlm.nih.gov/pubmed/6436701?dopt=AbstractPlus
38. Henahan J. New prostate cancer drugs: few CV effects? JAMA. 1983; 250:2097-9. Editorial.
39. Stein BS, Smith JA Jr. DES lead-in to use of luteinizing hormone releasing hormone analogs in treatment of metastatic carcinoma of prostate. Urology. 1985; 25:350-3. http://www.ncbi.nlm.nih.gov/pubmed/3920802?dopt=AbstractPlus
40. Yamanaka H, Makino T, Yajima H et al. Efficacy of (d-LEU6)-DES GLY-NH210-LHRH ethylamide against prostatic cancer. Prostate. 1985; 6:27-34. http://www.ncbi.nlm.nih.gov/pubmed/3918298?dopt=AbstractPlus
41. Klein LA. Prostatic carcinoma. N Engl J Med. 1979; 300:824-33. http://www.ncbi.nlm.nih.gov/pubmed/106277?dopt=AbstractPlus
42. Schmidt JD, Scott WW, Gibbons R et al. Chemotherapy programs of the National Prostatic Cancer Project (NPCP). Cancer. 1980; 45:1937-46. http://www.ncbi.nlm.nih.gov/pubmed/6445225?dopt=AbstractPlus
43. Garnick MB, Glode LM, Smith JA et al. Leuprolide: a review of its effects in comparison with diethylstilboestrol in the treatment of advanced cancer of the prostate. Br J Clin Pract. 1985; 39:73-6. http://www.ncbi.nlm.nih.gov/pubmed/3921047?dopt=AbstractPlus
44. Paulson DF. Management of metastatic prostatic cancer. Urology. 1985; 25(Suppl):49-52. http://www.ncbi.nlm.nih.gov/pubmed/3918376?dopt=AbstractPlus
45. Tolis G, Ackman D, Stellos A et al. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists. Med Sci. 1982; 79:1658-62.
46. Elder JS, Catalona WJ. Management of newly diagnosed metastatic carcinoma of the prostate. Urol Clin North Am. 1984; 11:283-95. http://www.ncbi.nlm.nih.gov/pubmed/6428022?dopt=AbstractPlus
47. Drago JR, Rohner T, Santen R et al. Leuprolide: a review of its effects in animals and man. Br J Clin Pract. 1985; 39:77-9. http://www.ncbi.nlm.nih.gov/pubmed/3921048?dopt=AbstractPlus
48. Kirk D. Prostatic carcinoma. BMJ. 1985; 290:875-6. http://www.ncbi.nlm.nih.gov/pubmed/3919825?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1417682&blobtype=pdf
49. Labrie F, Dupont A, Belanger A et al. New approach in the treatment of prostate cancer: complete instead of partial withdrawal of androgens. Prostate. 1983; 4:579-94. http://www.ncbi.nlm.nih.gov/pubmed/6415630?dopt=AbstractPlus
50. Faure N, Lemay A, Laroche B et al. Preliminary results on the clinical efficacy and safety of androgen inhibition by an LHRH agonist alone or combined with an antiandrogen in the treatment of prostatic carcinoma. Prostate. 1983; 4:601-24. http://www.ncbi.nlm.nih.gov/pubmed/6415632?dopt=AbstractPlus
51. Brendler CB. Hormonal therapy of prostatic cancer. J Urol. 1985; 133:650. http://www.ncbi.nlm.nih.gov/pubmed/3920407?dopt=AbstractPlus
52. Harvey HA, Lipton A, Santen RJ et al. Phase II study of a gonadotropin-releasing hormone analog (leuprolide) in postmenopausal advanced breast cancer patients. Proc Am Soc Clin Oncol. 1981; 22:444.
53. Comite F, Cutler GB, Rivier J et al. Short-term treatment of idiopathic precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. N Engl J Med. 1981; 305:1546-50. http://www.ncbi.nlm.nih.gov/pubmed/6458765?dopt=AbstractPlus
54. Chang RJ, Laufer LR, Meldrum DR et al. Steroid secretion in polycystic ovarian disease after ovarian suppression by a long-acting gonadotropin-releasing hormone agonist. J Clin Endocrinol Metab. 1983; 56:897-903. http://www.ncbi.nlm.nih.gov/pubmed/6403570?dopt=AbstractPlus
55. Corbin A. From contraception to cancer: a review of the therapeutic applications of LHRH analogues as antitumor agents. Yale J Biol Med. 1982; 55:27-47. http://www.ncbi.nlm.nih.gov/pubmed/6810559?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2595998&blobtype=pdf
56. Schwarzstein L, Aparicio NJ, Turner D et al. d-Leucine-6-luteinizing hormone-releasing hormone ethylamide in the treatment of normogonadotropic oligoasthenospermia. Fertil Steril1978; 29:332-5.
57. Jacobi GH, Wenderoth UK. Gonadotropin-releasing hormone analogues for prostate cancer: untoward side effects of high-dose regimens acquire a therapeutical dimension. Eur Urol. 1982; 8:129-34. http://www.ncbi.nlm.nih.gov/pubmed/6281023?dopt=AbstractPlus
58. Grayhack JT, Kozlowski JM. Endocrine therapy in the management of advanced prostatic cancer: a case for early introduction of treatment. Urol Clin North Am. 1980; 7:639-43. http://www.ncbi.nlm.nih.gov/pubmed/7456176?dopt=AbstractPlus
59. Glode LM, Robinson J, Gould SF. Protection from cyclophosphamide-induced testicular damage with an analogue of gonadotropin-releasing hormone. Lancet. 1981; 1:1132-4. http://www.ncbi.nlm.nih.gov/pubmed/6112490?dopt=AbstractPlus
60. Tarnavsky GK, Reeves JJ. Pituitary binding of LNRH [sic: LHRH] analogs. J Anim Sci. 1976; 43:307.
61. Linde R, Doelle GC, Alexander N et al. Reversible inhibition of testicular steroidogenesis and spermatogenesis by a potent gonadotropin-releasing hormone agonist in normal men: an approach toward the development of a male contraceptive. N Engl J Med. 1981; 305:663-7. http://www.ncbi.nlm.nih.gov/pubmed/6267464?dopt=AbstractPlus
62. Heber D, Swerdloff RS. Male contraception: synergism of gonadotropin-releasing hormone analog and testosterone in suppressing gonadotropin. Science. 1980; 209:936-8. http://www.ncbi.nlm.nih.gov/pubmed/6773142?dopt=AbstractPlus
63. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther. 1993; 35:43-50. http://www.ncbi.nlm.nih.gov/pubmed/8487743?dopt=AbstractPlus
64. Gittes RF. Serum acid phosphatase and screening for carcinoma of the prostate. N Engl J Med. 1983; 309:852-3. http://www.ncbi.nlm.nih.gov/pubmed/6888470?dopt=AbstractPlus
65. TAP Pharmaceuticals. Lupron information for patients. Chicago, IL; 1985 Apr.
66. Anon. Leuprolide for prostatic cancer. Med Lett Drugs Ther. 1985; 27:71-2. http://www.ncbi.nlm.nih.gov/pubmed/2410765?dopt=AbstractPlus
67. Heber D, Swerdloff RS. Gonadotropin-releasing hormone analog and testosterone synergistically inhibit spermatogenesis. Endocrinology. 1981; 108:2019-21. http://www.ncbi.nlm.nih.gov/pubmed/6783399?dopt=AbstractPlus
68. Corbin A, Beattie CW, Rees R. Postcoital contraceptive effects of agonist analogs of luteinizing hormone-releasing hormone. Fertil Steril. 1977; 28:471-5. http://www.ncbi.nlm.nih.gov/pubmed/321265?dopt=AbstractPlus
69. Harvey HA, Lipton A, Max DT et al. Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. J Clin Oncol. 1985; 3:1068-72. http://www.ncbi.nlm.nih.gov/pubmed/3926958?dopt=AbstractPlus
70. DeSombre ER, Johnson ES, White WF. Regression of rat mammary tumors effected by a gonadoliberin analog. Cancer Res. 1976; 36:3830-3. http://www.ncbi.nlm.nih.gov/pubmed/782692?dopt=AbstractPlus
71. Meldrum DR, Chang RJ, Lu J et al. “Medical oophorectomy” using a long-acting GnRH agonist—a possible new approach to the treatment of endometriosis. J Clin Endocrinol Metab. 1982; 54:1081-3. http://www.ncbi.nlm.nih.gov/pubmed/6801075?dopt=AbstractPlus
72. Guitelman A, Mancini AM, Aparicio NJ et al. Effect of d-leucine-6-luteinizing hormone-releasing hormone ethylamide in patients with hypogonadotropic hypogonadism with anosmia. Fertil Steril. 1979; 32:308-11. http://www.ncbi.nlm.nih.gov/pubmed/385362?dopt=AbstractPlus
73. Tharandt L, Schulte H, Benker G et al. Treatment of isolated gonadotropin deficiency in men with synthetic LH-RH and a more potent analogue of LH-RH. Neuroendocrinology. 1977; 24:195-207. http://www.ncbi.nlm.nih.gov/pubmed/345145?dopt=AbstractPlus
74. Frick J, Danner C, Kunit G et al. The effect of chronic administration of a synthetic LH-RH analogue intranasally in cryptorchid boys. Int J Androl. 1980; 3:469-78. http://www.ncbi.nlm.nih.gov/pubmed/6108293?dopt=AbstractPlus
75. Kahan A, Delrieu F, Amor B et al. Disease flare induced by d-Trp6-LHRH analog in patients with metastatic prostatic cancer. Lancet. 1984; 1:971-2. http://www.ncbi.nlm.nih.gov/pubmed/6143912?dopt=AbstractPlus
76. Glode LM, Robinson J, Gould SF et al. Protection of spermatogenesis during chemotherapy. Drugs Exp Clin Res. 1982; 8:367-78.
77. Happ J, Weber T, Krause U et al. Gonadotropin secretion after subcutaneous and intravenous stimulation with d-Leu6-des-Gly10-GnRH-ethylamide in healthy human males. Infertility. 1978; 1:87-99.
78. Bhasin S, Heber D, Steiner BS et al. Hormonal effects of gonadotropin-releasing hormone (GnRH) agonist in the human male. III. Effects of long term combined treatment with GnRH agonist and androgen. J Clin Endocrinol Metab. 1985; 60:998-1003. http://www.ncbi.nlm.nih.gov/pubmed/3920237?dopt=AbstractPlus
79. Bartfai G, Sas M, Morvay J et al. Effects of LHRH and long-acting LHRH on serum LH and FSH levels of healthy women. J Endrocrinol Invest. 1981; 4:359-62.
80. Matsuo H, Baba Y, Nair RMG et al. Structure of the porcine LH- and FSH-releasing hormone. I: the proposed amino acid sequence. Biochem Biophys Res Commun. 1971; 43:1334-9. http://www.ncbi.nlm.nih.gov/pubmed/4936338?dopt=AbstractPlus
81. Burgus R, Butcher M, Amoss M et al. Primary structure of the ovine hypothalamic luteinizing hormone-releasing factor (LRF). Proc Nat Acad Sci USA. 1972; 69:278-82. http://www.ncbi.nlm.nih.gov/pubmed/4550508?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=427591&blobtype=pdf
82. Page JG (TAP Pharmaceuticals, North Chicago, IL): personal communication; 1985 Sep.
83. Fujino M, Fukuda T, Shinagawa S et al. Synthetic analogs of luteinizing hormone releasing hormone (LH-RH) substituted in position 6 and 10. Biochem Biophys Res Commun. 1974; 60:406-13. http://www.ncbi.nlm.nih.gov/pubmed/4608231?dopt=AbstractPlus
84. Eidne KA, Flanagan CA, Millar RP. Gonadotropin-releasing hormone binding sites in human breast carcinoma. Science. 1985; 229:989-91. http://www.ncbi.nlm.nih.gov/pubmed/2992093?dopt=AbstractPlus
85. Miller WR, Scott WN, Morris R et al. Growth of human breast cancer cells inhibited by a luteinizing hormone-releasing hormone agonist. Nature. 1985; 313:231-33. http://www.ncbi.nlm.nih.gov/pubmed/2982100?dopt=AbstractPlus
86. Reviewers’ comments (personal observations); 1985 Sep.
87. Manni A, Santen R, Harvey H et al. Treatment of breast cancer with GnRH. Endocr Rev. (in press).
88. Nillius SJ, Bergquist C. LHRH agonists for female contraception. In: Vickery BH, Nestor JJ Jr, Hafez ESE, eds. LHRH and its analogs: contraceptive and therapeutic applications. Boston, MA: MTP Press Ltd; 1984:207-17.
89. Harvey HA, Lipton A, Max DT. LHRH analogs for human mammary carcinoma. In: Vickery BH, Nestor JJ Jr, Hafez ESE, eds. LHRH and its analogs: contraceptive and therapeutic applications. Boston, MA: MTP Press Ltd; 1984:329-35.
90. Flouret G, Stetler-Stevenson MA, Carone FA et al. Enzymatic degradation of LHRH and analogs. In: Vickery BH, Nestor JJ Jr, Hafez ESE, eds. LHRH and its analogs: contraceptive and therapeutic applications. Boston, MA: MTP Prss Ltd; 1984:397-410.
91. Barron J, Griffiths E, Tsalacopoulos G et al. Metabolism of [d-Trp6] LHRH. In: Vickery BH, Nestor JJ Jr, Hafez ESE, eds. LHRH and its analogs: contraceptive and therapeutic applications. Boston, MA: MTP Press Ltd; 1984:411-9.
92. Byar DP. The Veterans Administration Cooperative Urological Research Group’s studies of cancer of the prostate. Cancer. 1973; 32:1126-30. http://www.ncbi.nlm.nih.gov/pubmed/4585929?dopt=AbstractPlus
93. Veterans Administration Co-operative Urological Research Group. Treatment and survival of patients with cancer of the prostate. Surg Gynecol Obstet. 1967; 124:1011-7. http://www.ncbi.nlm.nih.gov/pubmed/6022476?dopt=AbstractPlus
94. Waxman J. Cancer, chemotherapy, and fertility. BMJ. 1985; 290:1096-7. http://www.ncbi.nlm.nih.gov/pubmed/3921121?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1418723&blobtype=pdf
95. Johnson DH, Linde R, Hainsworth JD et al. Effect of a luteinizing hormone releasing hormone agonist given during combination chemotherapy on posttherapy fertility in male patients with lymphoma: preliminary observations. Blood. 1985; 65:832-6. http://www.ncbi.nlm.nih.gov/pubmed/3884062?dopt=AbstractPlus
96. Hammond CB, Ory SJ. Diagnostic and therapeutic uses of gonadotropin-releasing hormone. Arch Intern Med. 1985; 145:1690-7. http://www.ncbi.nlm.nih.gov/pubmed/2862854?dopt=AbstractPlus
97. Laue L, Comite F, Hench K et al. Precocious puberty associated with neurofibromatosis and optic gliomas: treatment with luteinizing hormone releasing hormone analogue. Am J Dis Child. 1985; 139:1097-1100. http://www.ncbi.nlm.nih.gov/pubmed/3933329?dopt=AbstractPlus
98. TAP Pharmaceuticals. Lupron information for pharmacists. Chicago, IL; 1985 Nov.
99. TAP Pharmaceuticals. Lupron (leuprolide acetate injection) prescribing information. Deerfield, IL; 1993 Aug.
100. Abbott Laboratories. Lupron Depot 7.5 mg (leuprolide acetate for depot suspension) prescribing information. North Chicago, IL; 2010 Dec. Available from website. Accessed 2011 Jul 18. http://www.rxabbvie.com
101. TAP Pharmaceuticals. Lupron Depot (leuprolide acetate for depot suspension) monograph: the next generation of GnRH agonist analogs. Chicago, IL; 1989. Publication No. 97-9625.
102. Crawford ED, Eisenberger MA, McLeod DG et al. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989; 321:419-24. http://www.ncbi.nlm.nih.gov/pubmed/2503724?dopt=AbstractPlus
103. MacLeod TL, Eisen A, Sussmar GL. Anaphylactic reaction to synthetic luteinizing hormone-releasing hormone. Fertil Steril. 1987; 48:500-2. http://www.ncbi.nlm.nih.gov/pubmed/3305090?dopt=AbstractPlus
104. Clarke CB (TAP Pharmaceuticals, North Chicago, IL): personal communication; 1989 Aug and 1990 Jan.
105. Dlugi AM, Miller JD, Knittle J et al. Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group. Fertil Steril. 1990; 54:419-27. http://www.ncbi.nlm.nih.gov/pubmed/2118858?dopt=AbstractPlus
106. Tummon IS, Pepping ME, Binor Z et al. A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis. Fertil Steril. 1989; 51:390-4. http://www.ncbi.nlm.nih.gov/pubmed/2522062?dopt=AbstractPlus
107. Seltzer VL, Benjamin F. Treatment of pulmonary endometriosis with a long-acting GnRH agonist. Obstet Gynecol. 1990; 76(5 Part 2):929-31. http://www.ncbi.nlm.nih.gov/pubmed/2120647?dopt=AbstractPlus
108. Rivlin ME, Miller JD, Kreuger RP et al. Leuprolide acetate in the management of ureteral obstruction caused by endometriosis. Obstet Gynecol. 1990; 75(3 Part 2):532-6. http://www.ncbi.nlm.nih.gov/pubmed/2106110?dopt=AbstractPlus
109. Dowsett M, Mehta A, Mansi J et al. A dose-comparative endocrine-clinical study of leuprorelin in premenopausal breast cancer patients. Br J Cancer. 1990; 62:834-7. http://www.ncbi.nlm.nih.gov/pubmed/2123115?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1971512&blobtype=pdf
110. Friedman AJ, Lobel SM, Rein MS et al. Efficacy and safety considerations in women with uterine leiomyomas treated with gonadotropin-releasing hormone agonists: the estrogen threshold hypothesis. Am J Obstet Gynecol. 1990; 163(4 Part 1):1114-9. http://www.ncbi.nlm.nih.gov/pubmed/2145765?dopt=AbstractPlus
111. Crawford ED, Blumenstein BA, Goodman PJ et al. Leuprolide with and without flutamide in advanced prostate cancer. Cancer. 1990; 66(Suppl):1039-44. http://www.ncbi.nlm.nih.gov/pubmed/2118417?dopt=AbstractPlus
112. Giraud B. Interim report of a large French multicentre study of efficacy and safety of 3.75 mg leuprorelin depot in metastatic prostatic cancer. J Int Med Res. 1990; 18(Suppl 1):84-9. http://www.ncbi.nlm.nih.gov/pubmed/1691113?dopt=AbstractPlus
113. O’Brien A, Hibberd M. Clinical efficacy and safety of a new leuprorelin acetate depot formulation in patients with advanced prostatic cancer. J Int Med Res. 1990; 18(Suppl 1):57-68. http://www.ncbi.nlm.nih.gov/pubmed/2108886?dopt=AbstractPlus
114. Rizzo M, Mazzei T, Mini E et al. Leuprorelin acetate depot in advanced prostatic cancer: a phase II multicenter trial. J Int Med Res. 1990; 18(Suppl 1):114-25. http://www.ncbi.nlm.nih.gov/pubmed/2108883?dopt=AbstractPlus
115. Thompson IM, Zeidman EJ, Rodriguez FR. Sudden death due to disease flare with luteinizing hormone-releasing hormone agonist therapy for carcinoma of the prostate. J Urol. 1990; 144:1479-80. http://www.ncbi.nlm.nih.gov/pubmed/2122011?dopt=AbstractPlus
116. Abbott Laboratories. Leupron Depot 3.75 mg (leuprolide acetate for depot suspension) prescribing information. North Chicago, IL; 2011 Jun. Available from website. Accessed 2011 Jul 18. http://www.rxabbott.com/pdf/lupron3_75mg.pdf
117. Mazzei T, Mini E, Rizzo M et al. Human pharmacokinetic and pharmacodynamic profiles of leuprorelin acetate depot in prostatic cancer patients. J Int Med Res. 1990; 18(Suppl 1):42-56. http://www.ncbi.nlm.nih.gov/pubmed/2108885?dopt=AbstractPlus
118. Toguchi H. Pharmaceutical manipulation of leuprorelin acetate to improve clinical performance. J Int Med Res. 1990; 18(Suppl 1):35-41. http://www.ncbi.nlm.nih.gov/pubmed/2138986?dopt=AbstractPlus
119. Meyer BR, Kreis W, Eschbach J et al. Transdermal versus subcutaneous leuprolide: a comparison of acute pharmacodynamic effect. Clin Pharmacol Ther. 1990; 48:340-5. http://www.ncbi.nlm.nih.gov/pubmed/2121407?dopt=AbstractPlus
120. Lemay A. Clinical appreciation of LHRH analogue formulations. Horm Res. 1989; 32(Suppl 1):93-102. http://www.ncbi.nlm.nih.gov/pubmed/2533161?dopt=AbstractPlus
121. Sharifi R, Soloway M, The Leuprolide Study Group. Clinical study of leuprolide depot formulation in the treatment of advanced prostate cancer. J Urol. 1990; 143:68-71. http://www.ncbi.nlm.nih.gov/pubmed/2104638?dopt=AbstractPlus
122. Matsubara M. [Effects of intranasal administration of LHRH superanalogue on endogenous LHRH and gonadotropins in humans.] (Japanese; with English abstract.). Nippon Naibunpi Gakkai Zasshi. 1986; 62:837-42. http://www.ncbi.nlm.nih.gov/pubmed/3096798?dopt=AbstractPlus
123. Yamazaki I. Serum concentration patterns of an LHRH agonist, gonadotrophins and sex steroids after subcutaneous, vaginal, rectal and nasal administration of the agonist to pregnant rats. J Reprod Fertil. 1984; 72:129-36. http://www.ncbi.nlm.nih.gov/pubmed/6433008?dopt=AbstractPlus
124. Meyer BR, Kreis W, Eschbach J et al. Successful transdermal administration of therapeutic doses of a polypeptide to normal human volunteers. Clin Pharmacol Ther. 1988; 44:607-12. http://www.ncbi.nlm.nih.gov/pubmed/3143511?dopt=AbstractPlus
125. Schering. Eulexin (flutamide) capsules prescribing information. Kenilworth, NJ; 1990 Jul.
126. Miller JD. Leuprolide acetate for the treatment of endometriosis. Prog Clin Biol Res. 1990; 323:337-41. http://www.ncbi.nlm.nih.gov/pubmed/2106145?dopt=AbstractPlus
127. Barbieri RL. New therapy for endometriosis. N Engl J Med. 1988; 318:512-4. http://www.ncbi.nlm.nih.gov/pubmed/2963214?dopt=AbstractPlus
128. Henzl MR, Corson SL, Moghissi K et al. Administration of nasal nafarelin as compared with oral danazol for endometriosis: a multicenter double-blind comparative clinical trial. N Engl J Med. 1988; 318:485-9. http://www.ncbi.nlm.nih.gov/pubmed/2963213?dopt=AbstractPlus
129. Anon. Nafarelin for endometriosis. Med Lett Drugs Ther. 1990; 32:81-2. http://www.ncbi.nlm.nih.gov/pubmed/2143265?dopt=AbstractPlus
130. Kuhn JM, Billebaud T, Navratil H et al. Prevention of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide). N Engl J Med. 1989; 321:413-8. http://www.ncbi.nlm.nih.gov/pubmed/2503723?dopt=AbstractPlus
131. Tummon IS, Ali A, Pepping ME et al. Bone mineral density in women with endometriosis before and during ovarian suppression with gonadotropin-releasing hormone agonists or danazol. Fertil Steril. 1988; 49:792-6. http://www.ncbi.nlm.nih.gov/pubmed/3129312?dopt=AbstractPlus
132. Lindsay R. Estrogen therapy in the prevention and management of osteoporosis. Am J Obstet Gynecol. 1987; 156:1347-51. http://www.ncbi.nlm.nih.gov/pubmed/3578455?dopt=AbstractPlus
133. Dawood MY, Lewis V, Ramos J. Cortical and trabecular bone mineral content in women with endometriosis: effect of gonadotropin-releasing hormone agonist and danazol. Fertil Steril. 1989; 52:21-6. http://www.ncbi.nlm.nih.gov/pubmed/2501109?dopt=AbstractPlus
134. Johansen JS, Riis BJ, Hassager C et al. The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism. J Clin Endocrinol Metab. 1988; 67:701-6. http://www.ncbi.nlm.nih.gov/pubmed/2971080?dopt=AbstractPlus
135. Gudmundsson JA, Ljunghall S, Bergquist C et al. Increased bone turnover during gonadotropin-releasing hormone superagonist-induced ovulation inhibition. J Clin Endocrinol Metab. 1987; 65:159-63. http://www.ncbi.nlm.nih.gov/pubmed/2953749?dopt=AbstractPlus
136. Friedman AJ. Vaginal hemorrhage associated with degenerating submucous leiomyomata during leuprolide acetate. Fertil Steril. 1989; 52:152-4. http://www.ncbi.nlm.nih.gov/pubmed/2501108?dopt=AbstractPlus
137. Friedman AJ, Rein MS, Pandian MR et al. Fasting serum growth hormone and insulin-like growth factor-I and -II concentrations in women with leiomyomata uteri treated with leuprolide acetate or placebo. Fertil Steril. 1990; 53:250-3. http://www.ncbi.nlm.nih.gov/pubmed/2105242?dopt=AbstractPlus
138. Rein MS, Friedman AJ, Pandian MR et al. The secretion of insulin-like growth factors I and II by explant cultures of fibroids and myometrium from women treated with a gonadotropin-releasing hormone agonist. Obstet Gynecol. 1990; 76:388-94. http://www.ncbi.nlm.nih.gov/pubmed/2116610?dopt=AbstractPlus
139. Surrey ES, Gambone JC, Lu JK et al. The effects of combining norethindrone with a gonadotropin-releasing hormone agonist in the treatment of symptomatic endometriosis. Fertil Steril. 1990; 53:620-6. http://www.ncbi.nlm.nih.gov/pubmed/2108056?dopt=AbstractPlus
140. Crawford ED. Hormonal therapy of prostatic carcinoma: defining the challenge. Cancer. 1990; 66:1035-8. http://www.ncbi.nlm.nih.gov/pubmed/2203516?dopt=AbstractPlus
141. Dupont A, Labrie F, Giguere M et al. Combination therapy with flutamide and [D-Trp6]LHRH ethylamide for stage C prostatic carcinoma. Eur J Cancer Clin Oncol. 1988; 24:659-66. http://www.ncbi.nlm.nih.gov/pubmed/3289945?dopt=AbstractPlus
142. Labrie F, Dupont A, Giguere M et al. Benefits of combination therapy with flutamide in patients relapsing after castration. Br J Urol. 1988; 61:341-6. http://www.ncbi.nlm.nih.gov/pubmed/3289676?dopt=AbstractPlus
143. Labrie F, Dupont A, Belanger A. Complete androgen blockade for the treatment of prostate cancer. In: DeVita VT Jr, Hellman S, Rosenberg A, eds. Important advances in oncology 1985. Philadelphia: JB Lippincott; 1985:193-217.
144. Crawford ED, Davis MA. Luteinizing hormone-releasing hormone analogues in the treatment of prostate cancer. Cancer Treat Res. 1988; 39:25-38. http://www.ncbi.nlm.nih.gov/pubmed/2908606?dopt=AbstractPlus
145. Wojciechowski NJ, Carter CA, Skoutakis VA et al. Leuprolide: a gonadotropin-releasing hormone analog for the palliative treatment of prostatic cancer. Drug Intell Clin Pharm. 1986; 20:746-51. http://www.ncbi.nlm.nih.gov/pubmed/2429815?dopt=AbstractPlus
146. Sharifi R, Lee M, Ojeda L et al. Comparison of leuprolide and diethylstilbestrol for stage D2 adenocarcinoma of prostate. Urology. 1985; 26:117-24. http://www.ncbi.nlm.nih.gov/pubmed/3927551?dopt=AbstractPlus
147. Friedman AJ, Harrison-Atlas D, Barbieri RL et al. A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata. Fertil Steril. 1989; 51:251-6. http://www.ncbi.nlm.nih.gov/pubmed/2492232?dopt=AbstractPlus
148. Waibel-Treber S, Minne HW, Scharla SH et al. Reversible bone loss in women treated with GnRH-agonists for endometriosis and uterine leiomyoma. Hum Reprod. 1989; 4:384-8. http://www.ncbi.nlm.nih.gov/pubmed/2526152?dopt=AbstractPlus
149. Matta WH, Shaw RW, Hesp R et al. Reversible trabecular bone density loss following induced hypo-estrogenism with the GnRH analogue buserelin in premenopausal women. Clin Endocrinol. (Oxford) 1988; 29:45-51.
150. Scharla SH, Minne HW, Schaible A et al. Decreases of plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and loss of spinal bone mass in women during treatment with GnRH agonists. Proc Workshop Vitam D; Volume 7 (Vitam D): Mol Cell Clin Endocrinol. 1988:840-1.
151. Dodson WC, Hughes CL, Whitesides DB et al. The effect of leuprolide acetate on ovulation induction with human menopausal gonadotropins in polycystic ovary syndrome. J Clin Endocrinol Metab. 1987; 65:95-100. http://www.ncbi.nlm.nih.gov/pubmed/2953752?dopt=AbstractPlus
152. Lewinthal D, Taylor PJ, Pattinson HA et al. Induction of ovulation with leuprolide acetate and human menopausal gonadotropin. Fertil Steril. 1988; 49:585-8. http://www.ncbi.nlm.nih.gov/pubmed/3127242?dopt=AbstractPlus
153. Kelly AC, Jewelewicz R. Alternate regimens for ovulation induction in polycystic ovarian disease. Fertil Steril. 1990; 54:195-202. http://www.ncbi.nlm.nih.gov/pubmed/2116328?dopt=AbstractPlus
154. Radwanska E, Rawlins RG, Tummon I et al. Successful use of gonadotropin-releasing hormone agonist leuprolide for in vitro fertilization in a patient with polycystic ovarian disease and infertility unresponsive to standard treatment. Fertil Steril. 1988; 49:356-9. http://www.ncbi.nlm.nih.gov/pubmed/3123281?dopt=AbstractPlus
155. Abbott Laboratories. Lupron Depot-Ped (leuprolide acetate for depot suspension) 7.5 mg, 11.25 mg and 15 mg prescribing information. North Chicago, IL; 2010 Sep. Available from website. Accessed 2011 Jul 18. http://www.rxabbott.com/pdf/lupronpediatric.pdf
156. TAP Pharmaceuticals. Lupron (leuprolide acetate) injection for pediatric use prescribing information. Deerfield, IL; 1993 Aug.
157. Kaplan SL, Grumbach MM. Pathophysiology and treatment of sexual precocity. J Clin Endocrinol Metab. 1990; 71:785-9. http://www.ncbi.nlm.nih.gov/pubmed/2205623?dopt=AbstractPlus
158. Stein DT. Southwestern Internal Medicine Conference: new developments in the diagnosis and treatment of sexual precocity. Am J Med Sci. 1992; 303:53-71. http://www.ncbi.nlm.nih.gov/pubmed/1728875?dopt=AbstractPlus
159. Clemons RD, Kappy MS, Stuart TE et al. Long-term effectiveness of depot gonadotropin-releasing hormone analogue in the treatment of children with central precocious puberty. Am J Dis Child. 1993; 147:653-7. http://www.ncbi.nlm.nih.gov/pubmed/8506834?dopt=AbstractPlus
160. Neely EK, Hintz RL, Parker B et al. Two-year results of treatment with depot leuprolide acetate for central precocious puberty. J Pediatr. 1992; 121:634-40. http://www.ncbi.nlm.nih.gov/pubmed/1403402?dopt=AbstractPlus
161. Cook JS, Doty KL, Conn PM et al. Assessment of depot leuprolide acetate dose-adequacy for central precocious puberty. J Clin Endocrinol Metab. 1992; 74:1206-9. http://www.ncbi.nlm.nih.gov/pubmed/1569169?dopt=AbstractPlus
162. Parker KL, Baens-Bailon RG, Lee PA. Depot leuprolide acetate dosage for sexual precocity. J Clin Endocrinol Metab. 1991; 73:50-2. http://www.ncbi.nlm.nih.gov/pubmed/1904452?dopt=AbstractPlus
163. Sklar CA, Rothenberg S, Blumberg D et al. Suppression of the pituitary-gonadal axis in children with central precocious puberty: effects on growth, growth hormone, insulin-like growth factor-I, and prolactin secretion. J Clin Endocrinol Metab. 1973; 73:734-8.
164. Lee PA, Page JG, the Leuprolide Study Group. Effects of leuprolide in the treatment of central precocious puberty. J Pediatr. 1989; 114:321-4. http://www.ncbi.nlm.nih.gov/pubmed/2492599?dopt=AbstractPlus
165. Kappy MS, Stuart T, Perelman A. Efficacy of leuprolide therapy in children with central precocious puberty. Am J Dis Child. 1988; 142:1061-4. http://www.ncbi.nlm.nih.gov/pubmed/3140654?dopt=AbstractPlus
166. Kappy M, Stuart T, Perelman A et al. Suppression of gonadotropin secretion by a long-acting gonadotropin-releasing hormone analog (leuprolide acetate, Lupron Depot) in children with precocious puberty. J Clin Endocrinol Metab. 1989; 69:1087-9. http://www.ncbi.nlm.nih.gov/pubmed/2507570?dopt=AbstractPlus
167. Oerter KE, Manasco P, Barnes KM et al. Adult height in precocious puberty after long-term treatment with deslorelin. J Clin Endocrinol Metab. 1991; 73:1235-40. http://www.ncbi.nlm.nih.gov/pubmed/1955504?dopt=AbstractPlus
168. Kauli R, Kornreich L, Laron Z. Pubertal development, growth and final height in girls with sexual precocity after therapy with the GnRH analogue D-TRP-6-LHRH: a report on 15 girls, followed after cessation of gonadotrophin suppressive therapy. Hormone Res. 1990; 33:11-7. http://www.ncbi.nlm.nih.gov/pubmed/2142928?dopt=AbstractPlus
169. Feuillan PP, Jones J, Cutler GB Jr. Long term testolactone therapy for precocious puberty in girls with the McCune-Albright syndrome. J Clin Endocrinol Metab. 1993; 77:647-51. http://www.ncbi.nlm.nih.gov/pubmed/8370686?dopt=AbstractPlus
170. Foster CM, Comite F, Pescovitz OH et al. Variable response to a long-acting agonist of luteinizing hormone-releasing hormone in girls with McCune-Albright syndrome. J Clin Endocrinol Metab. 1984; 59:801-5. http://www.ncbi.nlm.nih.gov/pubmed/6434582?dopt=AbstractPlus
171. Rosenthal SM, Grumbach MM, Kaplan SL. Gonadotropin-independent familial sexual precocity with premature Leydig and germinal cell maturation (familial testotoxicosis): effects of a potent luteinizing hormone-releasing factor against and medroxyprogesterone acetate in four cases. J Clin Endocrinol Metab. 1983; 57:571-9. http://www.ncbi.nlm.nih.gov/pubmed/6223935?dopt=AbstractPlus
172. Wierman ME, Beardsworth DE, Mansfield MJ et al. Puberty without gonadotropins: a unique mechanism of sexual development. N Engl J Med. 1985; 312:65-72. http://www.ncbi.nlm.nih.gov/pubmed/3917301?dopt=AbstractPlus
173. Holland FJ, Fishman L, Bailey JD et al. Ketoconazole in the management of precocious puberty not responsive to LHRH-analogue therapy. N Engl J Med. 1985; 312:1023-8. http://www.ncbi.nlm.nih.gov/pubmed/2984563?dopt=AbstractPlus
174. Laue L, Jones J, Barnes KM et al. Treatment of familial male precocious puberty with spironolactone, testolactone, and desorelin. J Clin Endocrinol Metab. 1993; 76:151-5. http://www.ncbi.nlm.nih.gov/pubmed/8421081?dopt=AbstractPlus
175. Holland FJ, Kirsch SE, Selby R. Gonadotropin-independent precocious puberty (“testotoxicosis”): influence of maturational status on response to ketoconazole. J Clin Endocrinol Metab. 1987; 64:328-33. http://www.ncbi.nlm.nih.gov/pubmed/3539979?dopt=AbstractPlus
176. Kaufman FR, Costin G, Reid BS. Autonomous ovarian hyperfunction followed by gonadotrophin-dependent puberty in McCune-Albright syndrome. Clin Endocrinol (Oxford). 1986; 24:239-42.
177. Grumbach MM, Styne DM. Sexual precocity. In: Wilson JD, Foster DW, eds. Williams textbook of endocrinology. 8th ed. Philadelphia: WB Saunders; 1992:1186-1221.
178. Reviewers’ comments (personal observations).
179. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 28, 1996. Rockville, MD; 1996 Jul.
180. TAP Pharmaceuticals. Lupron Depot-3 Month 22.5 mg (leuprolide acetate for depot suspension) prescribing information. Deerfield, IL; 1995 Dec.
181. Stovall TG, Muneyyirci-Delale O, Summitt RL et al. GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas: a randomized controlled trial. Obstet Gynecol. 1995; 86(1):65-71. http://www.ncbi.nlm.nih.gov/pubmed/7784025?dopt=AbstractPlus
182. Vogelzang NJ. One hundred thirteen men with hormone-refractory prostate cancer died today. J Clin Oncol. 1996; 14:1753-5. http://www.ncbi.nlm.nih.gov/pubmed/8656242?dopt=AbstractPlus
183. Prostate Cancer Trialists’ Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of 22 randomized trials with 3283 deaths in 5710 patients. Lancet. 1995; 346:265-9. http://www.ncbi.nlm.nih.gov/pubmed/7630245?dopt=AbstractPlus
184. Prostate cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1996 Dec 20.
185. Schellhammer P, Sharifi R, Block N et al. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995; 45:745-52. http://www.ncbi.nlm.nih.gov/pubmed/7538237?dopt=AbstractPlus
186. Friedman AJ, Harrison-Atlas D, Barbieri RL et al. A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata. Fertil Steril. 1989; 51:251-6. http://www.ncbi.nlm.nih.gov/pubmed/2492232?dopt=AbstractPlus
187. TAP Pharmaceuticals. Lupron Depot-4 Month 30 mg (leuprolide acetate) for depot suspension prescribing information. Deerfield, IL; 1998 Aug.
188. Food and Drug Administration. GnRH agonists: Safety review of drug class used to treat prostate cancer (sold under the brand names Lupron, Zoladex, Trelstar, Viadur, Vantas, Eligard, Synarel, and generics). Rockville, MD; 2010 May 3. From FDA web site. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm210576.htm
189. Food and Drug Administration. GnRH agonists: label change--increased risk of diabetes and cardiovascular disease (update). Rockville, MD; 2010 Oct 20. From FDA web site. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm230359.htm
190. Abbott Laboratories. Lupron Depot 22.5 mg for 3-month administration, 30 mg for 4-month administration, and 45 mg for 6-month administration prescribing information. North Chicago, IL; 2011 Jun. Available from website. Accessed 2011 Jul 30. http://www.rxabbvie.com
191. Abbott Laboratories. Lupron Depot-3 Month 11.25 mg (leuprolide acetate for depot suspension) prescribing information. North Chicago, IL; 2011 Jun. Available from website. Accessed 2011 Jul 18. http://www.rxabbott.com/pdf/lupron3month11_25mg.pdf
192. Sanofi-Aventis U.S. LLC. Eligard (leuprolide acetate) suspension for subcutaneous injection. Bridgewater, NJ; 2011 Mar. Available from website. Accessed 2011 Jul 20. http://products.sanofi-aventis.us/eligard/eligard.pdf
193. Teva Parenteral Medicines, Inc. Leuprolide acetate injection. Irvine, CA; 2010 Nov. Available from website. Accessed 2011 Jul 19. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=41015
194. Caraco Pharmaceutical Laboratories, Ltd. Leuprolide acetate injection for pediatric use. Detroit, MI; 2011 Apr. Available from website. Accessed 2011 Jul 19. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=43012#s14
195. Anon. Drugs of choice for cancer. Treat Guide Med Lett. 2003; 1:41-52.
196. Breast cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2011 Jul 14. Available from website. Accessed 2011 Jul 30. http://www.cancer.gov/cancertopics/pdq/treatment/breast/healthprofessional
197. Sharma R, Beith J, Hamilton A. Systematic review of LHRH agonists for the adjuvant treatment of early breast cancer. Breast. 2005;14:181-91.
198. Prowell TM, Davidson NE. What is the role of ovarian ablation in the management of primary and metastatic breast cancer today? Oncologist. 2004;9:507-17.
199. Tanaka T, Niimi H, Matsuo N et al. Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate: evaluation of effectiveness of treatment and recovery of gonadal function. J Clin Endocrinol Metab. 2005;90:1371-6.
200. Genpharm ULC. Flutamide capsules prescribing information. Toronto, ON; 2008 May. Available from website. Accessed 2011 Jul 19. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=7694
201. Prostate cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2010 Dec 9. Available from website. Accessed 2011 Jul 30. http://www.cancer.gov/cancertopics/pdq/treatment/prostate/HealthProfessional
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