Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and virilizing turnours*

Abstract

OBJECTIVE Recent studies have suggested that androgen secretion by ovarian virllizing tumours may be gonadotrophin dependent. The aim of this study was to investigate the suppressive effect of GnRH agonist administration on androgen secretion. In women with such tumours. DESIGN AND PATIENTS A single 1.m. Injection Of D-Trp-6-GnRH (GnRHa), 3·75 mg, was given to five unrelated patients referred for clinical symptoms of virilization with plasma testosterone (T) levels greater than 7 nmol/l but with normal dehydroeplandrosterone sulphate (DHEAS) levels. Diagnoses of adrenal tumour or a non-classical 21-hydroxylase deficiency were 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 50 mg twice dally for 3 weeks, starting 1 week before GnRHa administration. MEASUREMENT Testosterone, androstenedione (A), DHEAS, 17-hydroxyprogesterone (OHP), LH and FSH plasma concentrations were measured by radioimmunoassay of blood samples taken before and 3 weeks after GnRHa. RESULTS In each patient, GnRHa suppressed gonadotrophin levels and reduced T and A to the range for normal control women. With these results, 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 Sertoll-Leydig cell tumour was found in the premenopausal patient, and granulosa cell tumour, hllus cell tumour and two hyperthecoses in the four post-menopausal patients. After bilateral ovarlectomy and hysterectomy in the post-menopausal woman and after unilateral ovarlectomy in the premenopausal women, androgen levels were normalized. CONCLUSIONS In virllized women, the findings of Increased serum testosterone with normal gonadotrophin levels and GnRHa suppression of gonadotrophins leading to normalization of testosterone levels, suggest that various ovarlan androgen-secreting tumours, as well as hyperthecosis, are not autonomous but apparently depend upon continuous gonadotrophin stimulation.