At a glance

What is leuprolide?

Leuprolide, known generically as leuprolide acetate (INN leuprorelin) and sold as Lupron, Lupron Depot, Eligard, Fensolvi, and Camcevi, is a synthetic nine-amino-acid analog of gonadotropin-releasing hormone. The natural hormone is released in pulses by the hypothalamus and tells the pituitary to make luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn drive the testes and ovaries to produce testosterone and estrogen. Leuprolide is a far more potent and longer-lasting version of that signal, first developed under the code TAP-144 and approved in the United States in 1985.

The history of leuprolide

Leuprolide grew directly out of the discovery of GnRH itself. Andrew Schally and Roger Guillemin shared the 1977 Nobel Prize in Physiology or Medicine for isolating and sequencing the hypothalamic releasing hormones, including GnRH. Once the ten-amino-acid structure was known, chemists built analogs that resisted breakdown and bound the receptor more tightly. Leuprolide, with a single amino-acid substitution and an ethylamide tail, was among the first of these "superagonists" to reach the clinic, and its approval in 1985 helped establish medical castration as an alternative to surgical removal of the testes for prostate cancer.

How does leuprolide work?

Leuprolide binds the GnRH receptor on the pituitary, and its effect depends on how it is delivered. A first dose actually stimulates the pituitary, producing a short-lived surge in LH, FSH, and testosterone known as the "flare." Because leuprolide then occupies the receptor continuously rather than in natural pulses, the pituitary gonadotrophs downregulate and desensitize. Within about two to four weeks LH and FSH fall, and testosterone in men, or estrogen in women, drops to castrate or postmenopausal levels.

That sustained suppression is the therapeutic goal, and the table below shows what it does in each condition.

The flare is why men with advanced prostate cancer are often given an anti-androgen in the first weeks, to blunt any transient worsening. Depot formulations release the drug slowly so a single injection maintains suppression for one, three, four, or six months. In the pediatric registration program, a three-month depot kept stimulated LH suppressed in 78 to 95%¹ of treated children.

Is it FDA-approved?

Yes. Leuprolide was first approved² by the FDA in 1985 as a daily subcutaneous injection, with the long-acting Lupron Depot following in 1989. Over the following decades the FDA cleared additional depot strengths, new indications, and several brands, including Eligard, the Fensolvi pediatric depot, and the ready-to-use Camcevi.

What is leuprolide prescribed for?

Leuprolide is prescribed for:

• Advanced or metastatic prostate cancer, as palliative hormone therapy
• Endometriosis
• Uterine fibroids with associated anemia, usually before surgery and combined with iron
• Central precocious puberty in children

Because it works by suppressing sex hormones, it is contraindicated in pregnancy; the gynecologic and pediatric uses are often time-limited in part to protect bone density.

What are the side effects?

According to the prescribing information², common side effects reflect low sex-hormone levels and the injection itself:

• Hot flashes and sweating
• Injection-site pain or reactions
• Decreased libido and erectile dysfunction
• Fatigue and mood changes
• Bone-density loss with long-term use

More serious considerations include:

• Transient tumor "flare" symptoms in 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 treated for precocious puberty, mood and behavior changes and raised pressure around the brain (pseudotumor cerebri), per the pediatric label³

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