Brand Names of Second-Line Agents for Endometriosis Treatment
The main brand names of second-line agents for endometriosis treatment include Zoladex (goserelin) as a GnRH agonist, and newer GnRH antagonists such as Orilissa (elagolix) and Myfembree (relugolix combination therapy). 1, 2
GnRH Agonists
- Zoladex (goserelin) - administered as a 3.6 mg subcutaneous implant every 28 days, FDA-approved for the management of endometriosis with a recommended treatment duration of 6 months 1
- Lupron Depot (leuprorelin acetate) - shown to be more effective than gestagens like lynestrenol in reducing endometriosis severity based on revised American Fertility Society (r-AFS) scores 3
- Synarel (nafarelin) - nasal spray formulation of GnRH agonist 4
GnRH Antagonists
- Orilissa (elagolix) - available in two dosing options:
- 150 mg once daily for less severe symptoms
- 200 mg twice daily for more severe symptoms 2
- Myfembree (relugolix 40 mg + estradiol 1 mg + norethindrone acetate 0.5 mg) - combination therapy that allows extended treatment up to 24 weeks with maintained efficacy and improved side effect profile 2
- Linzagolix (brand name varies by region):
- 75 mg/day can be used alone for endometriosis-associated pain
- 200 mg/day with hormonal add-back therapy for severe pelvic pain and dyspareunia 2
Add-Back Therapy Considerations
- Add-back therapy with low doses of estrogen and progestin is essential when using GnRH agonists to mitigate hypoestrogenic side effects while maintaining therapeutic efficacy 5
- Without add-back therapy, approximately 1% of bone mass is lost per month after the onset of hypoestrogenism 5
- The American College of Obstetricians and Gynecologists (ACOG) recommends add-back therapy when using GnRH agonists for endometriosis pain management 4, 5
Efficacy and Treatment Duration
- For pain relief, treatment with a GnRH agonist for at least three months or with danazol for at least six months appears to be equally effective in most women 4
- GnRH agonists with add-back therapy is currently considered the most effective long-term approach to the treatment of symptomatic endometriosis 6
- GnRH antagonists offer advantages over agonists including oral administration, dose-dependent reduction of estradiol levels, no initial flare-up of symptoms, and faster return of ovarian function after discontinuation 2
Important Clinical Considerations
- Therapy with a GnRH agonist is appropriate for managing chronic pelvic pain, even without surgical confirmation of endometriosis, provided other causes of pelvic pain have been ruled out 4
- For severe endometriosis, medical treatment alone may not be sufficient 4
- Common side effects of GnRH agonists include hot flashes, sexual dysfunction, and lower urinary tract symptoms in men; and hot flushes, headache, sweating, acne, emotional lability, depression, decreased libido, and peripheral edema in women 1