[10] Common side effects include hot flashes, unstable mood, trouble sleeping, headaches, and pain at the site of injection.

It may be used for precocious puberty in both males and females,[14] and to prevent premature ovulation in cycles of controlled ovarian stimulation for in vitro fertilization (IVF).

This use is controversial since the Lupron label advises against using the drug when one is considering pregnancy, due to a risk of birth defects.

[needs update][18] They are also sometimes used as alternatives to antiandrogens like spironolactone and cyproterone acetate for suppressing testosterone production in transgender women.

[24][25] Common side effects of leuprorelin injection include redness/burning/stinging/pain/bruising at the injection site, hot flashes (flushing), increased sweating, night sweats, tiredness, headache, upset stomach, nausea, diarrhea, impotence, testicular shrinkage,[8] constipation, stomach pain, breast swelling or tenderness, acne, joint/muscle aches or pain, trouble sleeping (insomnia), reduced sexual interest, vaginal discomfort/dryness/itching/discharge, vaginal bleeding, swelling of the ankles/feet, increased urination at night, dizziness, breakthrough bleeding in a female child during the first two months of leuprorelin treatment, weakness, chills, clammy skin, skin redness, itching, or scaling, testicle pain, impotence, depression, or memory problems.

[28] During the initial phase of luteinizing hormone-releasing hormone (LHRH) agonist therapy in individuals assigned male at birth, there is a notable phenomenon known as the "flare."

This increase is a response to the initial stimulation of luteinizing hormone (LH) by the LHRH agonist, leading to a rise in testosterone levels before they begin to decrease as intended.

For individuals receiving LHRH agonists as part of gender-affirming care, this temporary increase in testosterone can be particularly distressing, exacerbating gender dysphoria and discomfort.

To manage and mitigate these effects, healthcare providers often prescribe antiandrogens during this phase to help block the unwanted increase in testosterone and alleviate the associated distress.

Continuous exposure to an agonist such as leuprorelin for several weeks causes pituitary GnRH receptors to become desensitised and no longer responsive.

This desensitisation is the objective of leuprorelin therapy because it ultimately reduces LH and FSH secretion, leading to hypogonadism and a dramatic reduction in estradiol and testosterone levels regardless of sex.

Between 2010 and 2013, the FDA updated the Lupron drug label to include new safety information on the risk of thromboembolism, loss of bone density and convulsions.