Leuprolide

In the normal cycle the hypothalamus sends out GnRH in bursts, and each burst prompts the pituitary to put out LH and FSH, the hormones that run the testes and ovaries. Leuprolide is a modified GnRH that binds the same pituitary receptor but lasts far longer. At first it over-stimulates the pituitary, so LH, FSH and sex hormones briefly rise; in men, testosterone can climb about 50% above baseline in the first weeks, the 'flare' the label warns about¹. With continued exposure the pituitary stops responding, gonadotropins fall, and testosterone or estrogen output drops sharply. Tissues that depend on these hormones, such as hormone-sensitive prostate cancer, endometriosis lesions and fibroids, become quiet. The suppression reverses after the drug is stopped, and leuprolide is not active when swallowed, so it is always given by injection^1,2.

Leuprolide rests on decades of human trials. In a 1984 randomized trial of 199 men with metastatic prostate cancer, it suppressed testosterone as effectively as the estrogen drug diethylstilbestrol (DES), with similar overall response rates counting stable disease (86% vs 85%). DES caused more painful breast enlargement, nausea and swelling, with a trend toward more blood clots, while hot flashes were more frequent on leuprolide³.

In a Phase 3 study of 84 children with central precocious puberty, two strengths of a longer-acting depot kept stimulated LH suppressed from months 2 through 6 in 78% and 95% of children, with similar growth and side-effect profiles⁴.

In endometriosis, label trials support pain relief and smaller lesions, and adding norethindrone 'add-back' therapy reduced the bone loss that estrogen suppression causes².

The FDA first approved leuprolide in 1985⁵. Current US products are approved for advanced prostate cancer (Lupron Depot, Eligard, Camcevi and generics), for endometriosis and preoperative treatment of fibroid-related anemia (Lupron Depot), and for central precocious puberty in children (Lupron Depot-PED, Fensolvi)^1,2,5,6.

Per FDA labels, hot flashes and sweating are hallmark effects, along with headache, mood changes or depression, lower libido, weight change, nausea and injection-site reactions. Warnings include an early symptom flare (in prostate cancer, bone pain or spinal cord compression), bone-density loss that limits treatment length in women, high blood sugar and other metabolic changes, cardiovascular events and QT prolongation in men, convulsions, severe skin reactions and fetal harm. In children, emotional lability and pseudotumor cerebri (raised pressure inside the skull) have been reported^1,2,5.

1. FDA label: Lupron Depot (prostate cancer)FDA label (DailyMed)
2. FDA label: Lupron Depot (endometriosis, fibroids)FDA label (DailyMed)
3. Leuprolide Study Group, N Engl J Med 1984PubMed
4. Lee et al., J Clin Endocrinol Metab 2012PubMed
5. FDA label: FensolviFDA label (DailyMed)
6. FDA label: EligardFDA label (DailyMed)