Summary
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.

Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and virilizing tumours.

Review of the granulosa-theca cell tumors from the emil Novak ovarian tumor registry.

Ovarian virilizing tumors are rare and can lead to assessment difficulties because of their small size. A 41-yr-old female was referred for evaluation of hirsutism that had increased within the previous 3 yr. Menstrual cycle length was normal. Plasma testosterone was 3.9 ng/ml (normal range, 0.2-0.8 ng/ml), was not suppressible by 2 mg dexamethasone (4.3 ng/ml), and was increased (6.3 ng/ml) after three daily injections of hCG (5000 IU). Abdominal computed tomography scan showed an adrenal nodule (13 x 6 mm) that remained unchanged after 3 months. Ultrasound examination of the pelvis was normal. Ovarian and adrenal venous catheterization did not yield additional information. Topographic assessment was made by intraoperative measurement of testosterone in the samples taken from each ovarian vein (competitive chemiluminescent immunoassay ADVIA Centaur; right ovarian vein, 105 ng/ml; left ovarian vein, 5 ng/ml; peripheral blood, 7 ng/ml). Right annexectomy resulted in normalization of testosterone levels (0.22 ng/ml). Histopathological examination found a Leydig cell tumor of hilar type (1.5 cm). This observation illustrates the usefulness of intraoperative measurement of testosterone by a rapid automated technique for topographic assessment of ovarian virilizing tumor in premenopausal women.

Intraoperative testosterone assay for virilizing ovarian tumor topographic assessment: report of a Leydig cell tumor of the ovary in a premenopausal woman with an adrenal incidentaloma.

Clinical signs of hyperandrogenism include hirsutism, acne and/or seborrhea, androgenic alopecia, menstrual disorders and at maximum virilization. Hirsutism is defined by the presence of a coarse and pigmented hair in male territory. In the Caucasian populations, a Ferriman Gallwey score ≥ 6 means hirsutism. Polycystic ovary syndrome is the most common cause of hyerandrogenism in women (70 % of cases) but must remain a diagnosis of exclusion. A neoplasm origin is suspected in case of recent onset of hyperandrogenism, which is rapidly progressive and with signs of virilization. The serum level of total testosterone and 17-hydroxyprogesterone and pelvic ultrasonography are the first line tests in case of clinical hyperandrogenism. Combined oral contraceptive pill can be the first line treatment in case of moderate hyperandrogenia, associated, if needed, with a specific acne treatment. Cyproterone acetate is the best-known and most effective antiandrogenic treatment. It decreases the hair density, speed of regrowth and pigmentation. It is indicated in severe hirsutism and must be combined with cosmetic cares.

Hyperandrogenism in women

Summary:We report the clinicopathologic findings of an unusual case of adult granulosa cell tumor with androgenic manifestations in a 13-year-old prepubertal girl. The patient had never had a menstrual period and presented with a 1 year history of hirsutism. Physical examination was only remarkable

Androgenic adult granulosa cell tumor in a 13-year-old prepubertal patient: a case report and review of the literature.

Androgenic granulosa cell tumors of the ovary are rare and have not been well studied hormonally. A 20-year-old woman complaining of secondary amenorrhea with high plasma testosterone (295 ng/dl) and a right ovarian tumor was studied. Plasma testosterone levels decreased after two days of dexamethasone (36 ng/dl), increased after hCG administration (538 ng/dl) and a unilateral right ovarian gradient of testosterone was noted at the selective catheterization of ovarian veins. After removal of the granulosa cell tumor, testosterone concentration returned to normal (68 ng/dl) and the patient had resumption of normal menses.

Androgenic granulosa cell tumor of the ovary: in vivo hormonal studies

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Androgenic granulosa cell tumor of the ovary: in vivo hormonal studies