Treatment of Precocious Puberty in the McCune–Albright Syndrome with the Aromatase Inhibitor Testolactone

The McCune–Albright syndrome is characterized by café au lait spots, fibrous dysplasia of bones, and sexual precocity. Girls with precocious puberty due to this syndrome have episodic increases in serum estrogen levels together with the formation of large ovarian cysts. The serum gonadotropin levels are typically suppressed, and the precocious puberty has not responded to treatment with long-acting analogues of luteinizing hormone–releasing hormone (LHRH). Encouraged by our initial success in a pilot study of one patient, we have now treated five girls with the McCune-Albright syndrome with the aromatase inhibitor testolactone, which blocks the synthesis of estrogens. Testolactone decreased the levels of circulating estradiol (P<0.05) and the ovarian volume (P<0.05), and there was a return to pretreatment levels after testolactone was stopped. During treatment, the peak responses of luteinizing hormone and follicle-stimulating hormone to stimulation by LHRH rose above suppressed pretreatment levels — significantly above pretreatment levels for follicle-stimulating hormone (P<0.02) — and then returned to pretreatment levels after testolactone was discontinued. Growth rates fell in three patients during treatment but could not be assessed in the other two because of bone deformities. The mean rate of bone maturation decreased and menses stopped in three of the four girls who were menstruating regularly. We conclude that testolactone is an effective treatment of precocious puberty in the McCune–Albright syndrome. (N Engl J Med 1986; 315:1115–9.), The McCune–Albright syndrome was first recognized 50 years ago as the association of fibrous dysplasia of bone, café au lait pigmentation, and precocious puberty.¹ Although the underlying defect in this disorder remains obscure, recent studies have contributed to our understanding of the mechanism of sexual precocity in girls with the McCune–Albright syndrome. These studies have shown that plasma estrogen levels may fluctuate dramatically at intervals of four to six weeks. The peak estradiol levels during these cycles can approach 1000 pg per milliliter.² Sequential pelvic ultrasonography has demonstrated the growth and disappearance of large ovarian cysts that parallel the rise.