Short answer: Lupron Depot 3.75 mg (leuprolide) is a monthly muscle injection approved for endometriosis and fibroid-related anemia. Zoladex 3.6 mg (goserelin) is an implant placed under the belly skin every 28 days, approved for endometriosis, thinning the uterine lining before ablation, and some prostate and breast cancers.12 Both lower estrogen and bone density. Neither label reports a trial against the other.
| Lupron Depot 3.75 mg (leuprolide) | Zoladex 3.6 mg (goserelin) | |
|---|---|---|
| Form | Injection into a muscle once a month, given by a healthcare provider1 | Implant injected under the belly skin every 28 days2 |
| Approved for | Endometriosis (alone or with norethindrone add-back); with iron, anemia from fibroids before surgery1 | Endometriosis; thinning the uterine lining before ablation; prostate cancer; advanced breast cancer before menopause2 |
| Endometriosis course | Up to 6 months; one retreatment course of up to 6 months with add-back only, 12 months total1 | 6 months; retreatment cannot be recommended because safety data are lacking2 |
| Late dose | No missed-dose rule1 | A delay of a few days is permissible2 |
| Spine bone density | −6.3% at 52 weeks without add-back; −1.0% with add-back1 | −4.3% after 6 months; still −2.4% 6 months after stopping2 |
| Hot flashes (endometriosis) | 84% vs 29% on placebo1 | 96% vs 67% on danazol2 |
| Storage | 20 to 25 C (68 to 77 F)1 | Room temperature, not above 25 C (77 F)2 |
| Boxed warning | None1 | None2 |
Lupron Depot 3.75 mg is one injection into a muscle a month, given by a healthcare provider and not more often than monthly.1 Zoladex 3.6 mg is a small implant injected under the skin of the front of the belly, below the navel, every 28 days; the label warns about injection site injury and blood vessel damage.2 In women, Zoladex lowers estradiol to postmenopausal levels within 3 weeks.2
Both lower estrogen, and bone loss limits how long they are used. In Lupron Depot's add-back trials, spine bone density fell 6.3% over 52 weeks on Lupron alone vs about 1% with daily norethindrone 5 mg, and was still down 2.2% a year after stopping in the Lupron-only group.1 With Zoladex, spine bone density fell 4.3% after 6 months and was still down 2.4% to 2.5% 6 to 12 months after stopping.2 These numbers come from separate trials with different people, lengths and methods, so they are not a head-to-head comparison. The Zoladex label notes that adding estrogen and/or progestin reduced bone loss and hot flushes in studies.2
Most side effects come from low estrogen. In Lupron Depot's endometriosis trials: hot flashes or sweats 84%, headache 32%, vaginitis 28% and mood changes 22%, vs 29%, 6%, 0% and 3% on a small placebo group.1 In Zoladex's endometriosis trial against danazol: hot flushes 96%, vaginitis 75%, headache 75% and decreased libido 61%.2 The comparison groups and counting methods differ, so the rates are not directly comparable.
Which one, and for how long, is a decision for you and your gynecologist. More detail: Lupron Depot side effects, Zoladex side effects, the Lupron Depot and Zoladex dosing schedules, and the Leuprolide and Goserelin guides.