Morlirirus. I3 ( I99 I ) I I7- I22 Elsevier Scientilic Publishers Ireland
Ltd.
MAT 00617
Androgen production by epithelial ovarian tumours in post-menopausal women P. K. Heinonen Deparimenr of Obstetrics and G_vnaecology, Universiry Central Hospirul. Tampere (Finland) (Received
26 April
1990; revision
received
30 July
1990: accepted
I August
1990)
Peripheral serum concentrations of androstenedione (A) and testosterone (T) were measured in 31 post-menopausal women with epithelial ovarian tumours (I2 cancer, 5 borderline malignant and I4 benign tumours). and in 20 post-menopausal women who were free from ovarian neoplasms. The levels of these androgens were also measured in ovarian venous blood in I7 women with ovarian tumours. No significant differences were found between the mean serum androgen levels in patients with malignant, borderline malignant or benign ovarian tumours or the control group. The measured levels of A and T in peripheral and ovarian venous blood were highest in women with mutinous ovarian tumours. Histopathological examinations of the ovarian tumours showed hyperplasia or luteinization in ovarian tumour stroma in 5 out of I7 cases (3 mutinous turnours, I endometrioid adenocarcinoma and I serous adenocarcinema). The results indicate that of all epithelial tumottrs mutinous ovarian tumours most often demonstrate hormonal activity and that malignancy has no effect on hormonal activity.
(Key words:
Androstenedione,
Testosterone,
Ovarian
neoplasm)
Introduction
The highest incidence of ovarian cancer is found among post-menopausal women. Over 90% of all malignant ovarian tumours are of epithelial origin. Recent studies have demonstrated that epithelial ovarian tumours produce a small amount of steroid hormones, although such neoplasms are regarded as non-functional tumours [l-3]. Examples of epithelial tumours exerting virilizing effects have usually been reported in the form of case reports [4--6]. However, little attention has been paid to the study of androgens in benign and malignant ovarian tumours. The present study was accordingly carried out to investigate the levels of androstenedione and testosterone in both peripheral and ovarian venous blood in post-menopausal women with different types of common epithelial ovarian tumour.
Correspondence IO: Dr. P.K. Heinonen, Hospital, SF-33520 Tampere, Finland. 0378-5122/91/$03.50 0 1991 Elsevier Printed and Published in Ireland
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118
Subjects and methods Serum samples were obtained from 31 post-menopausal women with ovarian tumours and 20 control subjects who were free from ovarian neoplasms. Details of their age, post-menopausal age and weight are shown in Table I. All were nonsmokers and none had received oestrogen replacement therapy. The control subjects were post-menopausal women requiring surgery for uterine fibroids or genital prolapse. The study was approved by the Ethical Committee of Tampere University Central Hospital. Peripheral venous blood was collected pre-operatively from all patients at 0800 h-1000 h. To obtain the blood samples the ovarian vein was punctured during laparotomy on the side of the ovarian tumour. This procedure was successful in 17 cases. Tumour volume was measured immediately after removal. Serum was separated, frozen and stored at -20°C. Testosterone (T) was determined by direct radioimmunoassay using a commercial kit (Farmos Diagnostica, Turku, Finland). Androstenedione (A) determinations were performed at the Lauttasaari Research Centre (Helsinki, Finland) by a direct method after extraction with petroleum ether using anti-androstenedione-I lo-hemisuccinyl BSA from Steranti Research Ltd (St. Albans, U.K.). The intra-assay and interassay variation coefficients were 7 and 9% for T and 6 and 8% for A, respectively. In a few cases neither androgen could be determined owing to insufficient sample material. The types of ovarian tumour are listed in Table II. According to the FIG0 classification, 2 out of 12 patients with ovarian cancer had stage I tumours, 2 had stage II, 4 stage III and a further 4 stage IV. Ovarian sections were also examined by routine histological methods for evidence of hyperplasia and luteinization in ovarian tumour stroma. The r-test was used for comparison of the findings in the different groups. RCSU1t.S There were no significant differences in mean age or weight between the four groups studied (Table I). None of the patients had clinical signs of virilization or hirsutism. The mean peripheral serum levels of A and T were similar in the malignant, TABLE-i CHARACTERISTICS
OF OVARIAN
Group
Ovarian cancer Borderline malignant Benign ovarian tumour Control Values expressed
as mean f
S.D.
TUMOUR
PATIENTS
AND
CONTROL
SUBJECTS
No. of patients
Age (years)
Years since menopause
Weight
I2 5 14 20
62 ?? 9 65 f 8 66 ?? 9 66 f 9
14~ 16a 19* 15 f
66* 9 71* 5 72 f 18 69 zt 14
8 8 9 10
(kg)
119
TABLE
II
OVARIAN
TUMOUR
HISTOLOGY
IN THE POST-MENOPAUSAL
WOMEN
Ovaries
No. of Datients
Ovarian cancer Serous cystadenocarcinoma
I‘?
STUDIED
6
2 2
Mutinous cystadenocarcinoma Endometrioid adenocarcinoma Poorly differentiated adenocarcinoma Brenner tumour Borderline malignant turnour Serous cystadenoma Mutinous cystadenoma Benign iamour
5 3 2 14 4 5 5
Serous cystadenoma Mutinous cystadenoma Simple unclassified cyst
borderline malignant and benign ovarian tumour groups. These levels did not attain statistical significance in relation to the control group (Table III). Table IV shows the levels of A and T as measured in peripheral and ovarian venous blood in 17 cases. The women with mutinous ovarian tumours had the highest individual levels of both androgens in ovarian venous blood. The mean peripheral serum levels of A and T were significantly higher in women with mutinous ovarian tumours than in those with serous ovarian tumours (Table V). Histopathological examination of the tumours showed luteinized cells in the stroma in 5 out of 17 cases. Three of these had mutinous cystadenomas, 1 serous adenocarcinoma and 1 endometrioid adenocarcinoma. Discussion
Some previous studies have shown elevated plasma concentrations of A in postmenopausal women with benign or malignant ovarian tumours [7,8]. In the present TABLE
II1
PERIPHERAL MENOPAUSAL
SERUM LEVELS OF ANDROSTENEDIONE AND TESTOSTERONE WOMEN WITH OVARIAN TUMOURS AND CONTROL SUBJECTS
Group
Ovarian
cancer
Borderline malignant Benign ovarian tumour Control Values expressed
as mean
f
Androstenedione (nmol/l)
Testosterone (nmol/l)
5.3 1.6 4.6 3.3
I.1 2.2 1.8 1.3
f zt f f
5.7 (12) 5.2 (5) 3.2 (13) 1.2 (20)
S.D. (number
of samples)
f f f f
I.0 (12) 1.5 (5) 1.5 (14) 0.8 (IX)
IN POST-
120 TABLE IV ANDROSTENEDIONE AND TESTOSTERONE LEVELS MEASURED IN PERIPHERAL OVARIAN VENOUS BLOOD IN I7 PATIENTS WITH OVARIAN TUMOURS Histology of ovarian tumour
Patient no.
Mutinous tumours Malignant Borderline malignant Benign
Serous tumours Malignant
Borderline malignant Endometrioid adenocarinoma Brenner tumour Simple benign cyst
IO II I2 I3 I4 I5 I6 I7
AND
Androstenedione
(nmol/l)
Testosterone (nmolil)
Cubital vein
Ovarian vein
Cubital vein Ovarian vein
21.5 2.1 II.4 14.9 3.0 12.3 NO 4.0 5.2
84.0 5.0 15.4 85.0 12.8 62.0 82.0 18.9 28.0
3.6