Hypergonadotropic Hypogonadism in Female Patients with Galactosemia

We evaluated gonadal function in 18 female and eight male patients with galactosemia due to transferase deficiency; it was normal in the males, but 12 females had signs of hypergonadotropic hypogonadism. All female patients had a 46,XX karyotype, normal levels of thyroid hormone and prolactin, and no anti-ovarian antibodies. The biologic activity of urinary gonadotropins was normal. Ultrasonography of the pelvis revealed that ovarian tissue was diminished or absent. Total estrogens increased in one of two patients after administration of human menopausal gonadotropin. The frequency of hypergonadotropic hypogonadism was higher in females in whom dietary treatment for galactosemia was delayed. Clinical course and mean erythrocyte galactose-1-phosphate and urinary galactitol levels did not correlate with ovarian function. We conclude that female patients with galactosemia have a high incidence of ovarian failure due to acquired ovarian atrophy. Galactose or its metabolites may be toxic to the ovarian parenchyma, particularly during the immediate neonatal period. (N Engl J Med. 1981; 304:994–8.) GALACTOSEMIA, a disorder due to a deficiency of the enzyme galactose-1-phosphate (Gal1-P) uridyl transferase (transferase), represents an inborn error in the major pathway of galactose metabolism. As a consequence of the transferase defect, galactose and its metabolites accumulate in various tissues in untreated children with this condition and result in hepatic, renal, lenticular, and neurologic abnormalities. Early diagnosis and institution of dietary treatment permit survival and good health over the long term. 1 2 3 Many galactosemic women who have been treated since early childhood are now reaching childbearing age, and although their fertility rate is not known, several have borne healthy children. . . .