Hypergonadotropic Hypogonadism in Female Patients with Galactosemia

Abstract

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.

Gonadal function in patients with galactosaemia

“…Yearly erythrocyte Gal-I-P levels remained elevated in all patients despite dietary adherence with a mean value of 1.9+0.6mgd1-1 (SEM) and a range of 0.5-7.2mgdl-L DISCUSSION Despite the dietary restriction of galactose, previously felt to prevent tissue damage in galactosaemia, hypergonadotrophic hypogonadism occurs in female patients with this disorder. During the original study, ovarian damage appeared to occur in 66% of the female patients (Kaufman et al, 1981). This was manifested clinically by partial or complete failure of secondary sexual development and primary amenorrhoea or by the postpubertal occurrence of oligomenorrhoea or secondary amenorrhoea.…”

“…Structurally aberrant gonadotrophins could then be formed which may affect their ability to bind with receptors on the ovary. Since there is no abnormality in males and normal biologic function of gonadotrophins by the mouse-uterus-weight method has been demonstrated (Kaufman et al, 1981), this hypothesis seems unlikely.…”

“…The possibility that ovarian receptor activity is abnormal either as a result of interference with binding of gonadotrophins to the receptor by products of galactose metabolism or by chemical alteration in the receptor molecule is unlikely since one patient has had a child and another has responded to exogenous gonadotrophin (Kaufman et al, 1981). The near 100% incidence of ovarian failure in galactosaemia may be explained on the basis that in some as yet unrecognized way the enzymatic deficiency in galactosaemia affects ovarian function.…”

“…There appeared to be a significant difference between those with normal and abnormal gonadal function with regard to the age at which galactosaemia was diagnosed, suggesting that ovarian damage occurred within a short time after birth in untreated infants. Eight males were studied and all were found to have normal pubertal development and gonadotrophin and testosterone levels for age (Kaufman et al, 1981).…”

Primäre Ovarialinsuffizienz und Fertilität

“…Eine Einteilung in den afollikulären und follikulären POF-Typ erscheint sinnvoll, auch wenn einige Sonderformen des POF, z. B. infolge Galaktosämie oder bei Blepharophimose nicht eingeordnet werden kön-nen [15,20].…”