Histrelin. A Review of Its Pharmacological Properties and Therapeutic Role in Central Precocious Puberty

Histrelin is a synthetic gonadotrophin-releasing hormone (GnRH) agonist which, when administered over a prolonged period, suppresses the release of gonadotrophins from the anterior pituitary. Data from clinical trials undertaken in small numbers of patients with idiopathic central precocious puberty have demonstrated that histrelin 8 to 10 micrograms/kg/day administered subcutaneously desensitises the anterior pituitary to gonadotrophin secretion within 3 months, ablating the pubertal gonadotrophin response to GnRH stimulation and reducing circulating gonadal sex steroid levels. When histrelin is administered to treat central precocious puberty, the rate of secondary sexual maturation is slowed and in some cases there is a reversal of maturation which occurs before initiation of treatment. Of equal importance, histrelin therapy appears to have decelerating effects on skeletal maturation, allowing more statural growth; an increase in final adult height is predicted from available data, but will need to be confirmed in long term follow-up studies currently being undertaken. The most common adverse event reported during histrelin therapy was a skin reaction at the site of subcutaneous injection. Few patients have discontinued therapy because of any adverse event. Although experience with histrelin is limited, the absence of effective clinically available alternatives and the demonstrated efficacy of histrelin justifies its place as a first-line therapy for patients with central precocious puberty.