What is the efficacy of Ryeqo (relugolix, estradiol, and norethisterone acetate) in treating endometriosis cysts in ovaries?

Efficacy of Ryeqo (Relugolix Combination Therapy) in Treating Endometriosis Cysts in Ovaries

Ryeqo (relugolix, estradiol, and norethisterone acetate) demonstrates significant efficacy in treating endometriosis-associated pain but has not been specifically validated for the treatment of endometriosis cysts in ovaries.

Mechanism of Action and General Efficacy

Ryeqo combines three active ingredients that work synergistically:

• Relugolix (40mg): A GnRH receptor antagonist that reduces estradiol and progesterone levels
• Estradiol (1mg): Prevents hypoestrogenic side effects
• Norethisterone acetate (0.5mg): Provides progestogenic activity and prevents endometrial hyperplasia

This combination therapy has demonstrated effectiveness in:

• Significantly improving dysmenorrhea (painful periods) and non-menstrual pelvic pain in women with moderate to severe endometriosis 1
• Reducing overall pelvic pain and dyspareunia (painful intercourse) 2
• Decreasing analgesic and opioid use in patients with endometriosis 2
• Improving health-related quality of life 1

Efficacy for Endometriosis Cysts (Endometriomas)

While Ryeqo shows strong evidence for managing endometriosis-associated pain, the available clinical evidence does not specifically address its efficacy in treating endometriosis cysts in ovaries (endometriomas). The SPIRIT 1 and SPIRIT 2 trials, which were pivotal phase 3 studies for Ryeqo's approval, focused on pain outcomes rather than anatomical changes in endometriotic lesions 2.

Management Considerations for Endometriosis Cysts

For endometriosis cysts in ovaries, treatment approaches should follow these principles:

1. Surgical Management:

   • Surgical excision remains the treatment of choice for endometriomas causing discomfort, showing growth during follow-up, or with suspicious features 3
   • Laparoscopic surgery is recommended as first-line treatment for benign ovarian cysts 3

2. Medical Management:

   • According to ACOG recommendations, pain caused by endometriosis can be managed medically, but no medical therapy has been proven to eradicate endometriotic lesions 4
   • Progestins, oral contraceptives, NSAIDs, and GnRH agonists have been shown to reduce the size of endometriotic lesions, but not necessarily eliminate them 4

3. Monitoring:

   • For endometriomas with classic benign appearances, annual ultrasound surveillance is recommended 3
   • Transvaginal ultrasound combined with transabdominal ultrasound is the first-line imaging study for evaluating cystic lesions 3

Ryeqo Compared to Other Treatment Options

Ryeqo offers several advantages over other hormonal treatments for endometriosis:

• Unlike GnRH agonists, relugolix does not cause initial flare-up of endometriosis symptoms 5
• The addition of estradiol and norethisterone acetate minimizes bone mineral density loss and vasomotor symptoms 1, 5
• Once-daily oral dosing provides convenience compared to injectable therapies 1
• Efficacy is maintained over longer-term treatment (up to 2 years) 1

Limitations and Caveats

1. Lack of Specific Evidence: Current studies do not specifically evaluate Ryeqo's effect on endometriosis cysts
2. Bone Health Considerations: Even with add-back therapy, minimal bone mineral density changes were observed (−0.70% to −0.78% at lumbar spine) 2
3. Common Side Effects: Headache, nasopharyngitis, and hot flushes are the most commonly reported adverse events 2
4. Not a Curative Treatment: Like other medical therapies, Ryeqo manages symptoms but may not eliminate endometriotic lesions 4

Conclusion for Clinical Practice

While Ryeqo effectively manages endometriosis-associated pain, its specific efficacy for treating endometriosis cysts in ovaries remains unproven. For patients with symptomatic endometriomas, a combined approach may be necessary, potentially including surgical management for the cysts and Ryeqo for ongoing pain management and prevention of recurrence.

For definitive treatment of endometriosis cysts, surgical excision remains the gold standard, particularly for cysts causing symptoms or showing concerning features.