Nafarelin (Synarel)

Prescription

Nafarelin acetate (brand name Synarel) is a synthetic decapeptide GnRH agonist distinguished by how it is delivered: as a metered nasal spray rather than by injection or implant. A single position-6 substitution (3-(2-naphthyl)-D-alanine) makes it roughly 200 times more potent than native GnRH and gives it enough stability to be absorbed across the nasal mucosa, which is why a needle-free formulation is feasible. Mechanistically nafarelin behaves like every GnRH agonist. Delivered continuously (twice daily via the nose), it initially stimulates and then, through receptor downregulation and desensitization, suppresses pituitary release of LH and FSH — reducing ovarian estrogen production in women and halting premature sex-steroid production in children with central precocious puberty. The nasal route provides steady systemic exposure without the depot implants used for goserelin or leuprolide. Nafarelin is FDA-approved for two indications: endometriosis (where lowering estrogen shrinks and quiets ectopic endometrial tissue and relieves pain) and central precocious puberty (where suppressing the prematurely activated pituitary-gonadal axis pauses pubertal development, protecting final adult height and delaying secondary sexual characteristics until an appropriate age). For precocious puberty a higher daily dose is used than for endometriosis. Because it is a nasal spray, nafarelin carries some route-specific practicalities: nasal irritation is common, and a decongestant or rhinitis can reduce absorption, so timing around nasal sprays matters. As with all GnRH agonists in women, hypoestrogenic effects — hot flashes, vaginal dryness, and, with prolonged use, bone density loss — are expected; endometriosis courses are therefore usually limited to about six months. Treatment is directed by a gynecologist or pediatric endocrinologist.