Endometriosis Therapy to be Added to the PBS

From 1 May 2025, Ryeqo® will be available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of endometriosis. Each Ryeqo® tablet contains relugolix (40mg), estradiol (1mg), and norethisterone acetate (0.5 mg).

Relugolix is a gonadotrophin-releasing hormone (GnRH) receptor antagonist. Inhibition of this receptor reduces the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. This, in turn, leads to a reduction in ovarian estrogen and progesterone production.

As endometriosis is an estrogen-dependent condition, relugolix can significantly improve symptoms. However, reduced estrogen is also associated with significant adverse effects such as hot flushes and reduced bone mineral density (BMD). Estradiol is included in the formulation in a low dose to minimise hypoestrogenic effects; norethisterone is added to protect the endometrium from the effects of unopposed estrogen.

The SPIRIT trials assessed the efficacy of Ryeqo® in premenopausal women with endometriosis-associated pain ranging from moderate to very severe. Ryeqo® was associated with a significant improvement compared to placebo, with benefits seen as early as eight weeks for dysmenorrhea and twelve weeks for non-menstrual pelvic pain. The SPIRIT open-label extension study demonstrated that these benefits are maintained with continued treatment of 104 weeks.

Relugolix may offer some advantages over GnRH agonists in the management of endometriosis: it is orally administered, does not trigger an initial disease flare-up, and can be used long-term. Assessment of BMD by dual-energy X-ray absorptiometry (DXA) is recommended at baseline and annually thereafter. The decision to continue treatment should be dependent upon stable DXA results.