Medication Guide App

Gonadorelin (Systemic)



JAN:

Gonadorelin acetate—Gonadorelin diacetate

VA CLASSIFICATION
Primary: HS900
Secondary: DX900

Commonly used brand name(s): Factrel; Lutrepulse; Relisorm.

Other commonly used names are
luteinizing hormone–releasing hormone (LHRH), luteinizing hormone–releasing factor dihydrochloride (for gonadorelin hydrochloride), luteinizing hormone–releasing factor diacetate tetrahydrate (for gonadorelin acetate), and luteinizing hormone–/follicle-stimulating hormone–releasing hormone (LH/FSH–RH).
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Gonadotropin-releasing hormone—

diagnostic aid (hypothalamic-pituitary-gonadal axis function)—

infertility therapy agent—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Hypogonadism (diagnosis)—Gonadorelin as a single dose (gonadorelin test) is indicated for evaluation of the functional capacity and response of gonadotropes in the anterior pituitary in postpubertal patients who are suspected of having gonadotropin deficiency, whether due to hypothalamic function impairment alone or in combination with anterior pituitary function failure. The gonadorelin test can confirm, with other laboratory and clinical tests, the diagnosis of hypogonadotropic hypogonadism in adult males and females. The single-dose test is also indicated for evaluation of residual gonadotropic function of the pituitary in patients following removal of a pituitary tumor by surgery, irradiation, or their combination. {01} {08} In long-standing gonadotropin-releasing hormone (GnRH) deficiency, a single dose will not stimulate the pituitary. However, repetitive dosing can prime the pituitary and increase the gonadotropins luteinizing hormone and follicle-stimulating hormone {21}.
—A single-dose or series of gonadorelin tests will confirm the presence of functional pituitary gonadotropes, but it can not differentiate pituitary disorders from hypothalamic disorders or measure pituitary gonadotropic reserve. A single dose of gonadorelin will not stimulate a gonadal steroid response large enough or reproducible enough to test gonadal steroidogenic potential. Also, single-dose gonadorelin administration is not capable of stimulating prepubertal gonadotropes in children or adolescents when the hypothalamic-pituitary-gonadal axis is relatively inactive. {04} {08}

Amenorrhea, primary hypothalamic (treatment) or
Infertility, female, due to primary hypothalamic hypogonadism (treatment) or
[Infertility, male, due to primary hypothalamic hypogonadism (treatment)]1 or
[Puberty, delayed (treatment)]1—Gonadorelin acetate administered through an infusion pump set for pulsatile or intermittent dosing is indicated for induction of ovulation in females who experience hypogonadotropic amenorrhea or infertility due to hypogonadotropic hypogonadism {18} {19}. It may be used alone or in conjunction with other agents, such as chorionic gonadotropin, as a separate injection {18} {19}. Intermittent administration of gonadorelin, which is postulated to simulate normal release of gonadotropin-releasing hormone from the hypothalamus, may be useful in males experiencing infertility due to hypothalamic hypogonadism and in children experiencing delayed puberty resulting from hypothalamic impairment {07} {08} {09} {10} {11} {12} {13} {14} {15} {17}.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Gonadorelin is synthetic gonadotropin-releasing hormone (GnRH) {01}.
Molecular weight—
    Base: 1182.33 {01}

Mechanism of action/Effect:

Like naturally occurring gonadotropin-releasing hormone (GnRH), gonadorelin primarily stimulates the synthesis and release of luteinizing hormone (LH) from the anterior pituitary gland {05} {06} {17}. Follicle-stimulating hormone (FSH) production and release is also increased by gonadorelin, but to a lesser degree. In prepubertal females and some gonadal function disorders, the FSH response may be greater than the LH response {05}.



For the treatment of amenorrhea, delayed puberty, and infertility:

Administration of gonadorelin is used to simulate the physiologic release of GnRH from the hypothalamus in treatment of delayed puberty, treatment of infertility caused by hypogonadotropic hypogonadism, and induction of ovulation in those women with hypothalamic amenorrhea. This results in increased levels of pituitary gonadotropins LH and FSH, which subsequently stimulate the gonads to produce reproductive steroids. {08}



For diagnosis of hypogonadism:


After intravenous or subcutaneous administration of a single dose of gonadorelin, quantitation of the LH response to gonadorelin allows for detection of hypothalamic or pituitary dysfunction. It is recommended that a series of seven blood samples be drawn to evaluate the LH response to gonadorelin. A response is considered subnormal if three or more LH values fall below the 10th percentile curve established in the clinical studies for patients with normal LH responses using gonadorelin. {01} The incidence of patients with hypogonadism who showed subnormal responses in the clinical studies when they were tested with a single dose of gonadorelin included:    • Postpubertal panhypopituitarism—100% {01}.
   • Prader-Willi syndrome—100% {01}.
   • Prepubertal panhypopituitarism—95% {01}.
   • Sheehan's syndrome—84% {01}.
   • Kallmann's syndrome—77% {01}; response may increase with repetitive dosing {21}.



Biotransformation:

Rapid metabolism to various biologically inactive peptide fragments {18}.

Half-life:

Initial, 2 to 10 minutes; terminal, 10 to 40 minutes {18}.

Duration of action:

3 to 5 hours {18}.

Elimination:
    Renal excretion of inactive metabolites {18}.


Precautions to Consider

Pregnancy/Reproduction
Fertility—
High doses admininistered repeatedly in humans may lead to luteolysis and inhibition of spermatogenesis. {01}

Pregnancy—
Studies in pregnant humans show that gonadorelin did not cause adverse effects in the fetus {18} when it was used in the first trimester. Intermittent pulse dosing of gonadorelin used for 2 weeks after conception helps to establish the corpus luteum, and then it is discontinued {18}. Multiple follicle development, multiple gestations, and spontaneous termination of pregnancy have been reported. Multiple gestations occurred in 12% of 89 patients using intermittent pulse dosing (10 sets of twins, one set of triplets) {18}.

In animal studies, gonadorelin did not cause adverse effects in the fetuses of mice, rats, and rabbits {01} {18}.

FDA Pregnancy Category B {01}.

Breast-feeding

It is not known whether gonadorelin is distributed into breast milk {18}. Problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of gonadorelin as a diagnostic test have not been performed in children up to 12 years of age. Safety and efficacy have not been established {01} {18}. Children would not be sensitive to single doses of gonadorelin until after the onset of puberty.

Newborn infants are very sensitive to the effects of GnRH (peak responsiveness is at 1 to 3 months of age). Responsiveness declines dramatically until puberty (except for FSH in prepubertal females). However, there are no medically accepted indications for the use of gonadorelin in newborn infants.



Adolescents

Appropriate diagnostic studies performed to date using the single-dose gonadorelin test have not demonstrated specific problems in postpubertal adolescents that would limit the usefulness of gonadorelin in this age group {01}. Safety and efficacy for use of gonadorelin in an intermittent pulse dosing schedule have not been established for adolescents up to 18 years of age. {18} Use of gonadotropin-releasing hormone analogs in multiple doses or intermittent pulse dose schedules for the treatment of delayed puberty have been successful.


Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

See also Laboratory value alterations .
» Infertility therapy agents, other, including clomiphene    (gonadorelin should not be used for ovulation induction concurrently with other infertility therapy agents because of the rare risk of causing ovarian hyperstimulation {18})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With results of this test

Due to other medications
Androgens or{01}
Estrogens or{01}
Glucocorticoids or{01}
Progestins{01}    (may alter results of the gonadorelin test by affecting pituitary secretion of gonadotropins through feedback mechanism)


Contraceptives, estrogen and progestin oral or{01}
Digoxin{01}    (may suppress serum gonadotropin concentrations)


Dopaminergic blocking agents, including metoclopramide{01}
Phenothiazines{01}    (may blunt the response to gonadorelin by increasing serum prolactin concentrations)


Levodopa or{01}
Spironolactone{01}    (may elevate serum gonadotropin concentrations)

With physiology/laboratory test values
Estradiol in females{10}    (serum concentrations may initially decrease within the first 90 minutes after gonadorelin administration, then increase, reaching a peak at 6 hours and returning to normal by 18 hours)


Testosterone in males{07}{09}{11}    (serum concentrations may increase transiently)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Adenoma, gonadotropin-releasing hormone    (pituitary apoplexy and sudden blindness occurred in one patient receiving a single dose of a gonadotropin-releasing hormone analog; this may occur also with gonadorelin {01})


Allergy to gonadorelin
» Any condition that may be worsened by reproductive hormones, such as hormone-dependent tumor    (the increase of estrogen and progestins in women or androgens in men that results from multiple doses of gonadorelin may exacerbate any condition dependent on reproductive hormones {18})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Catheter site inspection and
Physical examination and
Progesterone concentration, serum, at mid-luteal phase and
Ultrasound examination of ovaries    (monitoring of patient for asepsis may be accomplished by regular inspection of the catheter site; monitoring of patient for ovulation by measuring ovarian follicle size and mid-luteal serum progesterone concentration, physical examination, especially of the pelvic area, and ultrasound examination of the ovaries for baseline measurements and on the seventh and fourteenth days of gonadorelin pulse therapy {18})


Luteinizing hormone (LH){01}{09}{10}{11}{16}    (measurement of serum concentrations recommended at timed intervals before and after gonadorelin administration for diagnostic procedures {01}. The LH peak occurs approximately 30 minutes after injection; however, the time to peak response and the peak LH concentrations vary significantly in the control population and measurements will depend on each laboratory's standards and the different assay methods used for the age-group tested. It is recommended that seven venous blood samples be taken—at baseline and at 15, 30, 45, 60, and 120 minutes after administration. Two samples should be averaged for the baseline value and should be taken at least 15 to 20 minutes apart. A response is considered subnormal if three or more blood LH concentrations fall below the 10th percentile curve established in the clinical studies for patients with normal LH responses using gonadorelin {01})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
    
Anaphylaxis, generalized (difficulty in breathing; hardening of skin at injection site; hives; persistent flushing; rapid heartbeat)—following multiple doses{01}{11}
    
infection
mild phlebitis
or hematoma, local (itching, pain, redness, or swelling at place of injection{01}{18})—following single or multiple doses
    
skin rash, generalized or local —following multiple doses{01}


Those indicating need for medical attention only if they continue or are bothersome
Incidence rare
For single dose injection only
    
Abdominal or stomach discomfort{01}
    
flushing, transient{01}
    
headaches{01}
    
lightheadedness{01}
    
nausea{01}






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Gonadorelin (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Allergy to gonadorelin

Pregnancy—Gonadorelin has not caused adverse effects in the fetus when used in the first trimester; multiple births occur
Other medications, especially infertility therapy agents, such as clomiphene
Other medical problems, especially gonadotropin-releasing hormone adenoma (for single or multiple doses of gonadorelin) or any condition that may be worsened by reproductive hormones, such as a hormone-dependent tumor (for multiple dose gonadorelin)

Proper use of this medication
Test procedure: Blood samples taken; injection given; several blood samples taken again; measurement of luteinizing hormone in blood

» Understanding the directions for use if using the pump for gonadorelin at home

» For brand name Lutrepulse: Proper care of catheter site and pump, including warning signals for pump malfunction and proper placement of tubing on body

» Proper dosing

Proper storage

Precautions while using this medication

For brand name Lutrepulse
» Importance of close and frequent monitoring by physician during use of the pump

» If desiring pregnancy, importance of following physician's instructions for timing of sexual intercourse to become pregnant and to reduce the chances of multiple gestations

» Telling physician immediately if pregnancy is suspected


Side/adverse effects
Signs of potential side effects, especially anaphylaxis (following multiple dosing); generalized or local skin rash (following multiple dosing); infection, mild phlebitis, or hematoma, local (following single or multiple dosing)


General Dosing Information

For single-dose use (diagnostic)
Results of the gonadorelin test should be interpreted by someone familiar with hypothalamic-pituitary-gonadal physiology and the clinical status of the patient. {01} For accurate interpretation of the test, the controls for the assay being used should be established and relayed to physician {01}. If the results are blunted or borderline, the gonadorelin test should be repeated {20}.

To determine the baseline luteinizing hormone (LH) concentration, the LH concentrations of two samples of venous blood drawn at least 15 to 20 minutes apart are averaged. {01}

Following gonadorelin administration, venous blood samples are drawn at regular intervals (for example, at 15, 30, 45, 60, and 120 minutes after administration) and analyzed for serum LH concentration. {01}

Depending on the laboratory and assay method used, normal baseline serum LH concentrations may vary. Even though the LH response is greatest in females when gonadorelin is given during the luteal phase, the gonadorelin test is given to females during the follicular phase, if that can be established, since females respond the same as males during this phase {01}.

In menopausal and postmenopausal females, baseline LH concentrations are elevated and the maximum LH increases are exaggerated compared to premenopausal concentrations {01}.

Basal LH and follicle-stimulating hormone (FSH) concentrations increase with age (over 50 years) in males; however, time to peak LH response after gonadorelin administration in older males is significantly delayed and may be diminished {01}.

For pulsatile dosing (brand name Lutrepulse only)
Physicians prescribing intermittent pulsatile dosing with gonadorelin should be familiar with its use and with the clinical response to ovulation induction. Ovarian hyperstimulation is rare when using pulsatile dosing because of the body's natural negative feedback mechanism, but the physician should be aware of its symptoms (ascites, pleural effusion, hemoconcentration, rupture of a cyst, fluid or electrolyte imbalance, or sepsis). Hyperstimulation is more likely to occur if the patient is taking an ovulation induction agent, such as clomiphene, or has spontaneous changes in the endogenous gonadotropin-releasing hormone. {18}

Pituitary hyperstimulation or multiple follicle development can be minimized by adhering to recommended dosing schedules. The possibility of a multiple pregnancy may be minimized by monitoring ovarian follicles by ultrasound examination at baseline and on the seventh and fourteenth days of therapy and by recommending proper timing of sexual intercourse to patient. {18}

If a malfunction of the device occurs and all contents of its reservoir are released at full dose, no harmful effects are expected, since doses as high as 3000 mcg of gonadorelin have not caused adverse effects. However, patients should be monitored for multiple follicles, and temporary pituitary desensitization would be expected. Also, continuous, nonpulsatile exposure to gonadorelin acetate would temporarily reduce pituitary responsiveness. {18}

Patients should be provided with oral and written instructions on proper use of the pump and proper care of the pump and catheter site to minimize the chance of pump malfunction and development of sepsis (inflammation, infection, mild phlebitis) or hematoma. The injection site should be monitored and the cannula and catheter site should be changed at 48-hour intervals. {18}

Response to intermittent dosing usually occurs within 2 to 3 weeks after treatment initiation {18}.

Eight milliliters of solution will supply 90-minute pulsatile doses for approximately 7 consecutive days. The pump can be set to deliver 25 or 50 microliters of solution, based on the dose selected, over a pulse period of 1 minute, and at a pulse frequency of 90 minutes. {18}

A reconstituted 0.8 mg vial of gonadorelin acetate yields:

• 2.5 mcg/25 microliters per 90-minute pulse {18}.


• 5 mcg/50 microliters per 90-minute pulse {18}.


A reconstituted 3.2 mg vial of gonadorelin acetate yields:

• 10 mcg/25 microliters per 90-minute pulse {18}.


• 20 mcg/50 microliters per 90-minute pulse {18}.



Parenteral Dosage Forms

Note: Dosage and strength of gonadorelin hydrochloride for injection is expressed in terms of gonadorelin base.


GONADORELIN ACETATE FOR INJECTION

Usual adult and adolescent dose
Hypogonadism (diagnosis)
Intravenous or subcutaneous, 100 mcg (0.1 mg) {01} {02}.

Note: In females, gonadorelin should be administered within the early follicular phase of the menstrual cycle, if the phase can be determined. {01}


Amenorrhea, primary hypothalamic or
Infertility, female, due to primary hypothalamic hypogonadism or
[Infertility, male, due to primary hypothalamic hypogonadism]1
Adults: Intravenous or subcutaneous, 5 mcg every 90 minutes delivered by intravenous or subcutaneous pump, usually for twenty-one days. Doses between 1 and 20 mcg have been used clinically. Check the manufacturer's labeling for the doses the pump is capable of delivering. The pump should be set to deliver 25 or 50 microliters of solution, based on the dose selected, over a pulse period of one minute and at a pulse frequency of ninety minutes. Dose may be changed in a stepwise fashion if no results are seen after three doses while monitoring patient for an inappropriate response. When ovulation occurs, treatment should continue for two more weeks to maintain the corpus luteum. {18}

Adolescents up to 18 years of age: Safety and efficacy have not been established {18}.


Usual pediatric dose
Hypogonadism (diagnosis)
Children 12 years of age and over: Intravenous or subcutaneous, 2 mcg per kilogram of body weight, not to exceed a single-dose of 100 mcg {02}.

Children up to 12 years of age: Safety and efficacy have not been established {01}.

[Puberty, delayed]1
Adolescents up to 18 years of age: Intravenous or subcutaneous, 5 mcg every 90 minutes delivered by intravenous or subcutaneous pump. Doses between 1 and 20 mcg have been used clinically. Check the manufacturer's labeling for the doses the pump is capable of delivering. The pump should be set to deliver 25 or 50 microliters of solution, based on the dose selected, over a pulse period of one minute and at a pulse frequency of ninety minutes. Dose may be changed in a stepwise fashion if appropriate. {18}


Size(s) usually available:
U.S.—
Not commercially available.

Canada—



For intermittent dosing


0.8 mcg (Rx) [Lutrepulse{19}]


3.2 mcg (Rx) [Lutrepulse{19}]



For single-dose


100 mcg (0.1 mg) (Rx) [Relisorm (mannitol 5 mg){20}]


500 mcg (0.5 mg) (Rx) [Relisorm (mannitol 500 mg){20}]

Packaging and storage:
Store unreconstituted gonadorelin for injection and diluent below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer {19} {20}.

Preparation of dosage form:
For brand name Lutrepulse—Using standard aseptic technique, add provided diluent (8 mL of Sodium Chloride Injection USP containing hydrochloric acid) to the 0.8-mg vial to make 5 mcg of gonadorelin in 50 microliters or to the 3.2-mg vial to make 20 mcg of gonadorelin in 50 microliters {18}.

For brand name Relisorm—Using standard aseptic technique, add provided diluent.

• 100-mcg vial: Add 1 mL of Sodium Chloride Injection USP {20}.


• 500-mcg vial: Add 5 mL of Bacteriostatic Sodium Chloride Injection USP {20}.


Stability:
Reconstituted solutions should be clear and colorless. Do not use if precipitate has formed or solution is discolored in appearance. {18} {20}

For brand name Lutrepulse—Reconstituted gonadorelin acetate for injection should be made immediately before use and placed within the pump's plastic reservoir {18}.

For brand name Relisorm—Reconstituted 100 mcg gonadorelin acetate for injection should be made immediately before use {20}. Unused reconstituted 500 mcg gonadorelin acetate for injection can be stored in the refrigerator for up to 14 days {20}.

Note: Lutrepulse for injection is intended for use in Lutrepulse pumps that are included in the kits. Injection may be intravenously or subcutaneously administered, depending on the kit used, Lutrepulse IV Kit or Lutrepulse SC Kit {19}. The injection volumes and concentrations are specific to the type of pump to achieve proper dosing. Eight milliliters of solution will supply 90-minute pulsatile doses for approximately 7 consecutive days. {18}



GONADORELIN HYDROCHLORIDE FOR INJECTION

Usual adult and adolescent dose
Hypogonadism (diagnosis)
Intravenous or subcutaneous, 100 mcg (0.1 mg) (base). {01} {02}

Note: In females, gonadorelin should be administered within the early follicular phase of the menstrual cycle, if that can be determined. {01}



Usual pediatric dose
Hypogonadism (diagnosis)
Children 12 years of age and over: Intravenous or subcutaneous, 2 mcg per kilogram of body weight, not to exceed a single dose of 100 mcg (base) {02}.

Children up to 12 years of age: Safety and efficacy have not been established {01}.


Size(s) usually available:
U.S.—



For single-dose


100 mcg (0.1 mg) (base) (Rx) [Factrel (diluent—benzyl alcohol 2%) (lactose 100 mg){01}]


500 mcg (0.5 mg) (base) (Rx) [Factrel (diluent—benzyl alcohol 2%) (lactose 100 mg){01}]

Canada—



For single-dose


100 mcg (0.1 mg) (base) (Rx) [Factrel (diluent—benzyl alcohol 2%) (lactose 100 mg){02}]


500 mcg (0.5 mg) (base) (Rx) [Factrel (diluent—benzyl alcohol 2%) (lactose 100 mg){02}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
Using standard aseptic technique, add 1 mL of diluent provided to the 100-mcg vial or 2 mL of diluent to the 500-mcg vial. The solution should be made immediately before use. Unused reconstituted solution and diluent should be discarded. {01}

Stability:
Reconstituted gonadorelin injection should be stored at room temperature and used within 24 hours {01}.



Revised: 06/29/1998



References
  1. Factrel package insert (Wyeth-Ayerst—US), Rev 7/25/97, Rec 1/26/98.
  1. Factrel product monograph (Wyeth-Ayerst Canada—Canada), Rev 2/16/95, Rec 2/12/98.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1997. p. 346.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopeia. 31st ed. London: The Pharmaceutical Press, 1996. p. 1281-3.
  1. Lambalk CB, van Rees GP, Schoemaker J, et al. Pulsatile GnRH treatment of the ovariectomized rat and release of LH and FSH. Acta Endocrinol (Copenh) 1988 Sep; 119(1): 27-32.
  1. Padmanabhan V, Kelch RP, Sonstein J, et al. Bioactive follicle-stimulating hormone responses to intravenous gonadotropin-releasing hormone in boys with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1988 Oct; 67(4): 793-800.
  1. Shargil AA. Treatment of idiopathic hypogonadotropic hypogonadism in men with luteinizing hormone-releasing hormone: a comparison of treatment with daily injections and with the pulsatile infusion pump. Fertil Steril 1987 Mar; 47(3): 492-501.
  1. Goodpasture JC, Rosenfield RL, Ehrman DA. In: Polan ML, Henzl MR. Infertility and reproductive medicine: Clinics of North America. The clinical use of GnRH superactive analogs. Philadelphia: W.B. Saunders; 1993. p. 129-45.
  1. Aulitzky W, Frick J, Galvan G. Pulsatile luteinizing hormone-releasing hormone treatment of male hypogonadotropic hypogonadism. Fertil Steril 1988 Sep; 50(3): 480-6.
  1. Lambalk CB, Schoemaker J, van Rees GP, et al. The frequency of pulsatile luteinizing hormone-releasing hormone treatment and luteinizing hormone and follicle-stimulating hormone secretion in women with amenorrhea of suprapituitary origin. Fertil Steril 1989 Mar; 51(3): 416-22.
  1. Hart LL, Lingle L. Gonadotropin-releasing hormone in infertility [letter]. DICP 1989 Mar; 23: 246-7.
  1. Homburg R, Armar NA, Eshel A, et al. Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome. BMJ 1988 Oct; 297: 1024-6.
  1. Burger CW, Hompes PG, Korsen TJ, et al. Ovulation induction with pulsatile luteinizing hormone-releasing hormone in women with clomiphene citrate-resistant polycystic ovary-like disease: endocrine results. Fertil Steril 1989 Jan; 51(1): 20-9.
  1. Reid RL, Fretts R, Van Vugt DA. The theory and practice of ovulation induction with gonadotropin-releasing hormone. Am J Obstet Gynecol 1988 Jan; 158(1): 176-85.
  1. Berezin M, Weissenberg R, Rabinovitch O, et al. Successful GnRH treatment in a patient with Kallmann's syndrome, who previously failed hMG/hCG treatment. Andrologia 1988 Jul-Aug; 20(4): 285-8.
  1. Bernasconi S, Orlandini G, Reali N, et al. Effect of GnRH administration on blood polymaines and LH levels in normal and obese children. Horm Metab Res 1988 Oct; 20(10): 648-51.
  1. Furr BJA, Woodburn JR. Luteinizing hormone-releasing hormone and its analogues: a review of biological properties and clinical uses. J Endocrinol Invest 1988; 11(7): 535-57.
  1. Lutrepulse package insert (Ferring—US), Rev 12/91, Rec 1/10/94.
  1. Factrel product monograph (Wyeth-Ayerst Canada—Canada), Rev 7/27/93, Rec 2/12/98.
  1. Relisorm (Serono). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 32nd ed. Ottawa: Canadian Pharmaceutical Association; 1998. p. 1350-1.
  1. Panel comment, 4/98.
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