From the Guidelines
Ryeqo (relugolix, estradiol, and norethindrone acetate) is the preferred choice for long-term endometriosis treatment due to its less negative impact on bone mineral density compared to Lupron (leuprolide acetate). Ryeqo includes "add-back therapy" with its estradiol and norethindrone components, which helps protect bone density while managing endometriosis symptoms, as supported by the concept of add-back therapy minimizing side effects of medications that suppress estrogen 1. In contrast, Lupron, a GnRH agonist, creates a hypo-estrogenic state that can lead to significant bone density loss, highlighting the importance of add-back therapy in reducing or eliminating GnRH-induced bone mineral loss without reducing the efficacy of pain relief 1.
Key Considerations
- Ryeqo's all-in-one formulation provides effective endometriosis symptom relief while maintaining better bone health profiles during extended treatment.
- Lupron is typically limited to 6-12 months of use and often requires separate add-back therapy to mitigate bone loss.
- Regular bone density monitoring is still recommended for patients on either medication for extended periods.
- Individual factors like symptom severity, treatment response, and other health considerations should guide treatment selection, with Ryeqo being preferable for bone health in patients requiring long-term therapy.
Evidence-Based Decision
The recommendation to prefer Ryeqo over Lupron for long-term endometriosis treatment is based on the most recent and highest quality evidence available, considering the potential for significant bone density loss with Lupron use 1 and the protective effects of add-back therapy included in Ryeqo 1. This decision prioritizes the reduction of morbidity and improvement of quality of life for patients with endometriosis.
From the Research
Long-term Effects of Ryeqo (Add-back Therapy) on Bone Density
- The long-term effect of Ryeqo (add-back therapy) on bone density in patients with endometriosis compared to Lupron (leuprolide) has been studied in several research papers 2, 3, 4, 5, 6.
- Add-back therapy with norethindrone acetate alone or in combination with conjugated equine estrogens has been shown to eliminate bone mineral density loss during 12 months of GnRH-a therapy 2.
- A study using 25 micrograms oestradiol patches combined with continuous medroxyprogesterone acetate (5 mg) found that the loss of bone mineral density was significantly diminished 3.
- Another study found that mean bone mineral density values remained at or above baseline in all add-back groups, while the significant mean loss in bone density in the group without add-back therapy reversed slowly and had not returned to baseline at the final follow-up visit 4.
- However, a long-term follow-up study found that bone mineral density reduction occurs during long-term GnRH agonist use and is not fully recovered by up to 6 years after treatment, regardless of the use of hormone replacement therapy 5.
- A prospective, randomized, placebo-controlled, double-blind trial found that the effectiveness of GnRH agonist treatment for endometriosis was not decreased by the addition of add-back continuous combined hormone replacement therapy, and bone mineral density of the lumbar spine was maintained 6.
Comparison with Lupron (Leuprolide)
- The studies suggest that add-back therapy can help mitigate the negative effects of GnRH agonists like Lupron (leuprolide) on bone density 2, 3, 4, 6.
- However, the long-term effects of GnRH agonist use on bone density are still a concern, and add-back therapy may not fully prevent bone mineral density loss 5.
- The choice of add-back therapy regimen may affect the outcome, with some regimens being more effective than others in preserving bone mineral density 2, 3, 4.