Version July 2025
Primary hypothalamic amenorrhea:
IV, SUBQ: Initial: 5 mcg every 90 minutes via suitable pulsatile pump for 21 days per treatment interval. Reduce dosage after 21 days if patient monitoring and laboratory testing indicate inappropriate ovarian response. If there is inadequate ovarian response after 3 treatment intervals, cautiously increase the dosage in a stepwise fashion. Dosage range: 1 to 20 mcg every 90 minutes via suitable pulsatile pump for 21 days per treatment interval. Continue treatment for 2 weeks after ovulation to maintain the corpus luteum. Follow current clinical practice to reduce the risk of ovarian hyperstimulation syndrome.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Superficial thrombophlebitis
Local: Injection site irritation
<1%, postmarketing, and/or case reports: Abdominal pain, anaphylactic shock, anaphylaxis, antibody development (with long-term therapy, resulting in therapy failure), erythema at injection site, fever, headache, hypermenorrhea, inflammation at injection site (mild and severe), nausea, ovarian hyperstimulation syndrome (moderate)
Hypersensitivity to gonadorelin or any component of the formulation; patients with any condition (eg, pituitary prolactinoma) that could be exacerbated by pregnancy; patients who have ovarian cysts; any condition (eg, hormone-dependent tumor) that may be worsened by reproductive hormones.
Concerns related to adverse effects:
• Hypersensitivity/anaphylactic reactions: Hypersensitivity and anaphylactic reactions have been reported rarely.
• Ovarian cancer: [Canadian Boxed Warning]: Ovarian cancer has been reported in a very small number of infertile women treated with fertility drugs. A causal relationship has not been established.
• Ovarian hyperstimulation syndrome: [Canadian Boxed Warning]: Ovarian hyperstimulation syndrome (OHSS) is a known risk with ovulation induction therapies but is rare with pulsatile gonadotropin releasing hormone (GnRH) therapy. While there have been few cases of hyperstimulation (<1%), this possibility must be considered. If hyperstimulation should occur, therapy should be discontinued and spontaneous resolution can be expected. OHSS is a rare, exaggerated response to ovulation induction therapy (Fiedler 2012; SOGC [Corbett 2014]). This syndrome may begin within 24 hours of human chorionic gonadotropin treatment but may become most severe 7 to 10 days after therapy (SOGC [Corbett 2014]). Mild/moderate OHSS signs/symptoms may include abdominal distention/discomfort, diarrhea, nausea, vomiting, and mild/moderate enlargement of ovaries/ovarian cysts. Severe OHSS signs/symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, hydrothorax, nausea/vomiting (intractable), pleural effusion, rapid weight gain, venous thrombosis, and large ovarian cysts. Decreased CrCl, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2024; Fiedler 2012; SOGC [Corbett 2014]). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (SOGC [Shmorgun 2017]).
Other warnings/precautions:
• Experienced physician: Therapy should only be conducted by clinicians familiar with infertility problems and their management.
• Multiple births: May result from the use of these medications; advise patients of the potential risk of multiple births before starting treatment.
Not available in the US
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Lutrepulse: 0.8 mg (1 ea)
IV, SUBQ: Lutrepulse vials for IV or SubQ use: Following reconstitution, administer IV or SubQ using a suitable pulsatile pump. Set the pump to deliver 25 or 50 mcL of solution, based upon the dose required and vial strength used. When using the 0.8 mg vial, the pump can be set to deliver a dose of 2.5 mcg (25 mcL) per pulse or 5 mcg (50 mcL) per pulse. Pump should deliver dose over a pulse period of 1 minute and a pulse frequency of 90 minutes.
Note: Not approved in the United States.
Induction of ovulation in patients with hypothalamic amenorrhea.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
ALERT: Canadian Boxed Warning: Health Canada-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Melperone: May decrease therapeutic effects of Gonadorelin. Specifically, melperone may diminish any prolactin-reducing effects. Risk C: Monitor
When needed for ovulation induction, should only be used by providers with expertise in managing infertility; exclude pregnancy prior to use. Multiple births may result from use of this medication; a low dose step-up protocol is recommended to increase the chance of monofollicular development. Gonadotropins are an alternative option for ovulation induction in patients with polycystic ovary syndrome with anovulatory infertility and no other infertility factors (Teede 2023).
The risk of fetal harm appears remote if gonadorelin is used during pregnancy. Clinical studies of pregnant patients have not demonstrated an increased risk of fetal abnormalities during the first trimester. Follow-up reports of infants born to exposed mothers revealed no adverse effects or complications attributed to gonadorelin therapy. Based on its indicated use, gonadorelin treatment is continued for 2 weeks following ovulation to maintain the corpus luteum; initiation of treatment is not appropriate if pregnancy has been established.
It is not known if gonadorelin is present in breast milk.
Not indicated for use in breastfeeding patients.
Ovarian ultrasound at baseline and at least weekly while on therapy or until ovulation is confirmed; LH, FSH, estradiol, progesterone (midluteal phase); basal body temperature; pelvic exam; injection site.
OHSS: Monitoring of hospitalized patients should include albumin, degree of ascites, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, hydration, serum creatinine, urine output, urine specific gravity, signs of thromboembolism, vital signs, weight (daily or as necessary), and liver enzymes (weekly) (SOGC [Shmorgun 2017]).
Stimulates the release of luteinizing hormone (LH) from the anterior pituitary gland
Onset of action: Response to therapy usually observed within 2-3 weeks
Distribution: Vd: ~10-15 L
Metabolism: Primarily renal
Half-life elimination: Terminal: ~10-40 minutes; increased in patients with renal impairment
Excretion: Urine (as inactive metabolites)
