Classification of leuprolide:
Chemical class:
It is an oligopeptide chain that mainly contains pyroglutamic, histidyl, tryptophyl, seryl, tyrosyl, Dleucyl, leucyl, arginyl, and N-ethylprolinamide residues.
Chemical name: 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-Larginyl-N-ethyl-Lprolinamide.
Pharmacological class:
Antineoplastic, Gonadotropin-releasing hormone (GnRH) agonists (long-acting).
International trade names:
Lupron, Lupron Depot-ped, Eligard, Luprodex, Lupron Depot, Fensolvi
Mechanism of action and effects:
First, the gonadotropin-releasing hormone is produced by the hypothalamus in its neurons. This
hormone has a major role in the production of sex hormones from the gonads. Gonadotropinreleasing hormone bind to its receptors (GnRHRs) on the anterior pituitary gonadotropes. As a
result, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are released, which will
act on gonads to produce testosterone and dihydrotestosterone from testicles in men, while
estrogen and progesterone from women’s ovaries.
However, Leuprolide is a gonadotropin-releasing hormone analog (has the same mechanism and
effect). Therefore, it will stimulate the release of LH and FSH hormones, which increased
steroidogenesis in ovaries and testes. Finally, increased female estrogen and increased testosterone
and dihydrotestosterone in males.
In leuprolide continuous administration, the levels of gonadotropins and gonadal steroids
decreased. Therefore, the levels of testosterone in males and estrogen in females decreased as a
result of LH and FSH production inhibition (negative feedback).
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Doses, dosage forms, routes of administration:
Indication
Dose
Dosage form
Route of administration
For adults
7.5 mg/month
injection
Intramuscular
7.5 mg/month
injection
Subcutaneous
Endometriosis
3.75 mg/month, up
to 6 months
injection
Intramuscular
Uterine Leiomyoma
(Fibroids)
3.75 mg/month, up
to 3 months
injection
Intramuscular
Pre- and
premenopausal breast
cancer
3.75 mg/28 days
11.25 mg/3 months
(up to 24 months)
injection
Intramuscular
Advanced Prostate
Cancer
For children (>2 years old)
Central Precocious
Puberty
Lupron Depot-Ped:
11.25 mg or 30 mg
once every 3 months
Fensolvi: 45 mg
once every 6 months
injection
Intramuscular
injection
Subcutaneous
Clinical uses:
1. Advanced prostate cancer treatment (Palliative treatment only: just relieve pain without
treating the real cause). It decreases levels of testosterone with continuous use, so
minimizes the stimulatory effect on androgen-sensitive prostate cancer cells, making them
undergo apoptosis.
2. In combination with iron, use in anemic patients with uterine leiomyoma (a condition that
appears during childbearing years that is characterized by noncancerous growths of the
uterus) to improve hematological before a surgical operation.
3. In combination with norethisterone, used in the treatment of endometriosis (a condition of
pelvic pain that results from the endometrial tissue appearance outside the uterus). The aim
is to improve pelvic pain and reduce endometriotic lesions. (Note: after 6 months’
treatment, the treatment course should not repeat)
4. In children: for central precocious puberty treatment slows down the secondary sex
characteristics progression until the appropriate age of puberty.
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Off-label use:
Use in breast cancer management, paraphilia, and hypersexuality management. Also, hormone
therapy for transgender patients (male to female) and suppression of premenopausal ovarian.
Side Effects:
In children:
1. More common:
SC injection: injection site pain, nasopharyngitis (inflammation of the pharynx and nasal
cavities), pyrexia (increase in body temperature), headache, and cough
IM injection: injection site pain
2. Less common:
SC injection: abdominal pain, constipation, vomiting, upper respiratory tract infection,
irritability.
IM injection: increased weight, headache, altered mood, injection site swelling.
In adults:



More common with IM injection: hot flashes (due to vasodilation), general pain, testicular
atrophy (shrinking of testicles), gastrointestinal disorders, urinary disorders, injection site
reaction, joint disorders.
Less common with IM injection: neuromuscular disorders, skin reaction, insomnia,
asthenia, headache, vertigo, respiratory disorders.
Less common with SC injection: Sweating, insomnia, weakness, lethargy (sleepiness)
constipation, weight gain, etc.
Drug-drug or drug-food interactions:



Metformin + leuprolide:
pharmacodynamic antagonism interaction (metformin acts as an antagonist at the same
receptor of leuprolide). So, the effects of metformin will decrease.
Dichlorphenamide + leuprolide:
Both of them have the action to decrease the serum level of potassium since
dichlorphenamide is a carbonic anhydrase inhibitor that may cause electrolyte imbalances
(hypokalemia). As a result, the serum level of potassium will drop.
Digoxin + Leuprolide:
The excretion rate of digoxin decreases when taken with leuprolide. So, the serum level of
digoxin and its toxicity increased (we have to decrease the dose of digoxin).
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


Erythromycin + Leuprolide:
Because leuprolide is an androgen deprivation therapy that prolongs QT interval. Both
drugs have the action to prolong the QT interval (QT greater than 440 ms in men or greater
than 460 ms in women). So the risk of QT prolongation increased. We have to be careful
with hypertensive patients and other cardiovascular diseases.
Trimethoprim + Leuprolide:
increased risk of myopathy, rhabdomyolysis, and myoglobinuria.
No known drug-food interaction
Contraindications:
1. Hypersensitivity to leuprolide or other GnRH agonists.
2. Should not use in pregnant women or who plan to be pregnant, since studies show it may
harm the fetus and decreased its weight, and increased pregnancy complications risk.
Therefore, a pregnancy test is necessary to do before therapy starts. Also, the patient should
take non-hormonal contraceptives during therapy to avoid any unexpected pregnancy.
3. In addition, should not be used in breastfeeding and females with undiagnosed vaginal
bleeding.
Precautions:
Generally, use leuprolide with caution in patients with:




Diabetes; leuprolide has a role in increased blood glucose levels.
Family history of osteoporosis and other metabolic bone diseases, since leuprolide can
decrease and increase bone loss risk.
Cardiovascular diseases; leuprolide increased risk of heart attack, stroke, and sudden death.
Prostate cancer patients have a high risk of spinal cord compression and ureteric
obstruction.
In addition, use with caution in children and young adults, since it increases puberty signs and
vaginal bleeding during the beginning of therapy. Moreover, it increased the risk of depression and
other psychiatric illnesses. Convulsions risk may also be increased.
Studies show that using leuprolide in adults has a role in improving many complications, therefore,
use with caution in the following cases:


In patients with metastatic vertebral lesions; leuprolide increases the risk of spinal cord
compression.
In prostate cancer patients; leuprolide in the first weeks causes bone pain, hematuria,
bladder outlet obstruction, and neuropathy. Therefore, we have to closely monitor patients
for urinary tract obstruction and hematuria.
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References
Leuprolide. (2022). Retrieved 17 March 2022, from https://reference.medscape.com/drug/luproneligard-leuprolide-342221#0
Swayzer, D., & Gerriets, V. (2021). Leuprolide. Retrieved 17 March 2022, from
https://www.ncbi.nlm.nih.gov/books/NBK551662/
Leuprolide: Uses, Interactions, Mechanism of Action. (2022). Retrieved 17 March 2022, from
https://go.drugbank.com/drugs/DB00007
Leuprolide (Intradermal Route, Intramuscular Route, Subcutaneous Route). (2022). Retrieved 17
March 2022, from https://www.mayoclinic.org/drugs-supplements/leuprolide-intradermal-routeintramuscular-route-subcutaneous-route/description/drg-20067038
Drugs, H. (2022). Leuprolide Injection. Retrieved 17 March 2022, from
https://medlineplus.gov/druginfo/meds/a685040.html
Leuprorelin. (2022). Retrieved 17 March 2022, from
https://pubchem.ncbi.nlm.nih.gov/compound/Leuprorelin
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