ANDROGEN SUPPRESSIVE EFFECT OF GNRH AGONIST IN OVARIAN HYPERTHECOSIS AND VIRILIZING TUMORS

OBJECTIVE Recent studies have suggested that androgen secretion by ova rian virilizing tumours may be gonadotrophin dependent. The aim of thi s study was to investigate the suppressive effect of GnRH agonist admi nistration on androgen secretion in women with such tumours. DESIGN AN D PATIENTS A single i.m. injection of D-Trp-6-GnRH (GnRHa), 3-75 mg, w as given to five unrelated patients referred for clinical symptoms of virilization with plasma testosterone (T) levels greater than 7 nmol/l but with normal dehydroepiandrosterone sulphate (DHEAS) levels. Diagn oses of adrenal tumour or a nonclassical 21-hydroxylase deficiency wer e screened for by the dexamethasone suppression test, ACTH stimulation test and adrenal CT scanning, and were ruled out in all patients. The one premenopausal patient received cyproterone acetate in a dose of 5 0 mg twice daily for 3 weeks, starting 1 week before GnRHa administrat ion. MEASUREMENT Testosterone, androstenedione (A), DHEAS, 17-hydroxyp rogesterone (OHP), LH and FSH plasma concentrations were measured by r adioimmunoassay of blood samples taken before and 3 weeks after GnRHa. RESULTS In each patient, GnRHa suppressed gonadotrophin levels and re duced T and A to the range for normal control women. With these result s, and because accurate localization of an ovarian androgen secreting tumour could not be achieved by pelvic ultrasonography and CT scanning , exploratory laparotomy was undertaken. A Sertoli-Leydig cell tumour was found in the premenopausal patient, and granulosa cell tumour, hil us cell tumour and two hyperthecoses in the four post-menopausal patie nts. After bilateral ovariectomy and hysterectomy in the post-menopaus al woman and after unilateral ovariectomy in the premenopausal women, androgen levels were normalized. CONCLUSIONS In virilized women, the f indings of increased serum testosterone with normal gonadotrophin leve ls and GnRHa suppression of gonadotrophins leading to normalization of testosterone levels, suggest that various ovarian androgen-secreting tumours, as well as hyperthecosis, are not autonomous but apparently d epend upon continuous gonadotrophin stimulation.