Leuprolide: effects, uses and side effects

What is leuprolide?

Leuprolide, also called leuprorelin, is usually administered as leuprolide acetate. Brand names include Lupron, Lupron Depot, Eligard, Fensolvi and Camcevi. It is a synthetic nine-amino-acid analogue of gonadotropin-releasing hormone. The natural hormone is released in pulses by the hypothalamus. It stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These in turn stimulate testosterone or estrogen production in the testes and ovaries. Leuprolide strengthens this signal and prolongs its effect. It was investigated under the development code TAP-144 and approved in the United States in 1985. Source

How was leuprolide developed?

Development followed directly from the discovery of GnRH. Andrew Schally and Roger Guillemin shared the 1977 Nobel Prize in Physiology or Medicine for work isolating and determining the structures of hypothalamic releasing hormones, including GnRH. Once its ten-amino-acid structure was known, analogues could be designed that broke down more slowly and bound more strongly to the receptor. Leuprolide differs through a substituted amino acid and a terminal ethylamide group. It was among the first such “superagonists” used clinically. Its 1985 approval helped establish medical suppression of testicular function as an alternative to surgical removal of the testes in prostate cancer.

How does leuprolide work?

Leuprolide binds to the GnRH receptor in the pituitary gland. Its effect depends on how long the receptor is stimulated. The first dose initially stimulates the pituitary: LH, FSH and testosterone temporarily increase, an effect called a “flare.” The medicine then occupies the receptor continuously rather than in natural pulses. Hormone-producing pituitary cells respond by reducing their receptors and becoming less sensitive. Within roughly two to four weeks, LH and FSH fall. In men, testosterone drops to the level reached when testicular function is suppressed; in women, estrogen falls to a postmenopausal level.

This sustained hormone suppression is the treatment goal. The table shows its effects in different conditions.

Because of the initial flare, men with advanced prostate cancer often also receive an antiandrogen during the first few weeks to lessen temporary worsening. Depot preparations release the medicine slowly. Depending on the product, one injection can maintain hormone suppression for one, three, four or six months. In the pediatric approval program, a three-month depot maintained suppression of stimulated LH in 78–95% of treated children 1.

Is leuprolide FDA-approved?

Yes. The first FDA approval came in 1985 for a daily subcutaneous injection 2. Long-acting Lupron Depot followed in 1989. Over subsequent decades, additional depot strengths, indications and brands were approved, including Eligard, the pediatric depot Fensolvi and ready-to-use Camcevi.

Which conditions is leuprolide prescribed for?

Uses include:

• Advanced or metastatic prostate cancer, as palliative hormone therapy.

• Endometriosis.

• Uterine fibroids with associated anemia, usually before surgery and together with iron.

• Central precocious puberty in children.

Because leuprolide suppresses sex hormone production, it is contraindicated during pregnancy. Gynecological and pediatric treatments are often limited in duration; the source article cites protection of bone density among the considerations.

What side effects have been described?

According to the prescribing information 2, common side effects are related to low sex hormone levels or the injection itself:

• Hot flashes and sweating.

• Pain or other injection-site reactions.

• Reduced libido and erectile dysfunction.

• Fatigue and mood changes.

• Loss of bone density with long-term use.

More serious risks and warnings include:

• Temporary worsening of tumor-related symptoms due to the flare during the first weeks of prostate cancer treatment.

• Increased risk of hyperglycemia, diabetes and cardiovascular events with long-term androgen deprivation.

• Rare seizures.

• Severe skin reactions.

• In children with precocious puberty: mood and behavioral changes and increased pressure inside the skull, also called pseudotumor cerebri; these risks appear in the pediatric prescribing information 3.

Studies at a glance

Condition	Effect of hormone suppression
Prostate cancer	Testosterone deprivation removes a growth stimulus from hormone-sensitive tumor cells.
Endometriosis and fibroids	Lower estrogen levels cause hormone-dependent tissue to shrink.
Central precocious puberty	Suppression of the premature hormonal signal slows early sexual development and helps preserve adult height.

References provided in the source article

Sources: FDA prescribing information for Lupron Depot, Eligard, and Fensolvi; a trial of the three-month pediatric depot (Lee et al., Journal of Clinical Endocrinology and Metabolism, 2012, DOI: 10.1210/jc.2011-2704 1 ), indexed on PubMed; and background on the Nobel-recognized discovery of GnRH.

Provenance and editorial review status

Adapted for Nutrient Desk from the source article. The claims and source attributions in the original text still require clinical review. This draft has not been cleared for indexing.