What is add back therapy for Elagolix (Gonadotropin-releasing hormone receptor antagonist)?

Add-Back Therapy for Elagolix: Purpose and Implementation

Add-back therapy with low doses of estrogen and progestin is essential when using elagolix to mitigate hypoestrogenic side effects while maintaining therapeutic efficacy for conditions like endometriosis and uterine fibroids. 1, 2

What is Add-Back Therapy?

• Add-back therapy typically consists of 1 mg estradiol and 0.5 mg norethindrone acetate given once daily alongside elagolix treatment 2
• It is specifically designed to counteract the hypoestrogenic effects that occur with GnRH antagonists like elagolix 1
• The combination allows for suppression of endogenous ovarian sex-steroid production while minimizing side effects 1

Why Add-Back Therapy is Necessary

• Elagolix as monotherapy causes significant hypoestrogenic effects including 2, 3:

  • Hot flashes
  • Headaches
  • Bone mineral density loss (approximately 2.43% at lumbar spine after 6 months of monotherapy)
  • Vaginal dryness
  • Hypertension

• Without add-back therapy, approximately 1% of bone mass is lost per month after the onset of hypoestrogenism 1

Efficacy of Add-Back Therapy

• Clinical studies demonstrate that add-back therapy effectively mitigates bone mineral density loss, with changes of <1% at 12 months compared to >2% with elagolix monotherapy 2
• The addition of add-back therapy does not reduce the efficacy of elagolix for treating conditions like endometriosis-associated pain or heavy menstrual bleeding associated with uterine fibroids 2, 4
• In clinical trials, elagolix with add-back therapy maintained significant improvement in dysmenorrhea and non-menstrual pelvic pain compared to placebo 2

Implementation in Clinical Practice

• Add-back therapy should be initiated simultaneously with elagolix rather than added later, as studies show better bone mineral density preservation when started together 2
• For uterine fibroids, the recommended regimen is elagolix 300 mg twice daily with add-back therapy consisting of 1 mg estradiol/0.5 mg norethindrone acetate once daily 4
• For endometriosis, add-back therapy is particularly important when using the higher dose of elagolix (200 mg twice daily) 5

Clinical Considerations

• Add-back therapy is FDA-approved in combination with elagolix for fibroid-related heavy menstrual bleeding 1
• The American College of Obstetricians and Gynecologists (ACOG) recommends add-back therapy when using GnRH agonists for endometriosis pain management 1
• Add-back therapy allows for longer duration of treatment than would be possible with elagolix monotherapy due to bone density concerns 2, 5

Monitoring Recommendations

• Bone mineral density should be monitored in patients receiving long-term therapy, even with add-back therapy 2
• Estradiol levels should be monitored in premenopausal women treated with GnRH agonists and add-back therapy using high-sensitivity assays 1

Limitations and Considerations

• Despite add-back therapy, elagolix treatment remains expensive, with reported costs of approximately $845 per month in the United States 3
• Add-back regimens increase the overall cost of therapy but are essential for long-term management 1, 3
• The efficacy of add-back therapy has been primarily demonstrated in placebo-controlled trials rather than comparative effectiveness studies against standard treatments 3

Add-back therapy represents a critical component of elagolix treatment, allowing for effective management of conditions like endometriosis and uterine fibroids while minimizing the adverse effects associated with hypoestrogenism.