The majority of patients undergoing treatment with depot leuprorelin experience mild side effects. Fewer patients experience moderate adverse reactions, and severe toxicity is rarely reported. The most common side effects of leuprorelin are hot flashes, injection site reactions, fatigue, testicular atrophy, and gynecomastia.
After treatment with 45 mg 6-month depot leuprorelin, 82 (74%) of 111 participants reported 211 treatment-related side effects. One event was reported as severe, although the type of adverse reaction was not documented, and the other 210 events were mild to moderate.38
Depot leuprorelin 45 mg 6-month has a similar side effect profile to the other depot formulations. Fifty-seven percent of patients treated with 22.5 mg 3-month depot leuprorelin experienced mild side effects, 12% experienced moderate side effects, and no patients experienced severe side effects.49
Eighty-five percent of patients treated with 30 mg 4-month depot leuprorelin experienced treatment-related side effects, with 97% of these reactions being mild to moderate and 3% documented as severe hot flashes.50
Seventy-four percent of patients treated with monthly depot leuprorelin experienced side effects of treatment. Most events were graded as mild to moderate; however 4% were considered severe, including hot flashes in 1 case and injection site burning in 4 instances.48
Overall, with the exception of a notably higher rate of mild injection site reactions documented in patients receiving the 22.5 mg dosage, there were no substantial differences between the side effect profile of patients treated with the different depot formulations (Table ).
Table 2 Treatment-related adverse events of 6-month (45 mg), 4-month (30 mg), 3-month (22.5) mg, and 1-month (7.5 mg) depot leuprorelin38,48–50
No patients stopped treatment with the 45 mg, 22.5 mg, or 7.5 mg dosages due to treatment-related side effects. However, 3% of participants in the 4-month 30 mg depot leuprorelin clinical efficacy trial stopped because of side effects of treatment, although the specific reactions that caused patients to withdraw from the study were not documented.50
Treatment compliance of patients enrolled in the above clinical efficacy trials was good. Of the patients enrolled for treatment with 7.5 mg monthly, 22.5 mg 3-monthly, 30 mg 4-monthly, and 45 mg 6-monthly leuprorelin, 98%, 98%, 91%, and 93% completed the 1-year treatment course, respectively.
In the European randomized controlled trial evaluating the lower-dose formulations (11.25 mg 3-month depot and 30 mg 6-month depot leuprorelin), 4% of patients withdrew from the study because of treatment-related adverse events. The most common side effects were hot flashes and injection-site reactions. Hot flashes occurred in 43% versus 34% of patients treated with 3-monthly and 6-monthly injections, respectively, and injection site reactions occurred in 2% and 11% of patients, respectively. About two-thirds of the injection site reactions were considered severe.32
In summary, the available depot leuprorelin formulations are convenient and well tolerated with acceptable side effect profiles. Severe adverse events are rare, and patient compliance within published clinical studies is good. Few patients withdrew from the trials because of treatment-related side effects, and over 90% of patients completed the treatment course.