A gonadotropin and alpha-subunit suppression test for the assessment of the ectopic production of human chorionic gonadotropin and its subunits after the menopause.

Abstract

One contraceptive tablet [(CP) containing 0.05 mg ethinyl estradiol and 0.5 mg norgestrel] was administered daily for 7 days to 38 hypergonadotropic postmenopausal women who had benign illness and to 34 similar women with cancer, in order to suppress the gonadotropins (LH and FSH) and their alpha-subunit secreted by the pituitary. LH, FSH, alpha-subunit, and hCG were measured using RIA in serum and urine extracts obtained before and on the seventh day of treatment. In the control group serum alpha-subunit fell to 53%, serum LH to 51%, serum FSH to 36%, urine alpha to 42%, urine hCG to 54%, urine LH to 53%, and urine FSH to 44% of their mean pretreatment values. Serum hCG was undetectable after treatment in all except 11 women in whom serum LH was not adequately suppressed. This fact and the significant positive linear correlation found between basal serum hCG and LH imply that serum hCG measured in postmenopausal women, with a RIA using the SB6 antiserum, is mainly cross-reacting LH. The suppression proved to be useful in the assessment of ectopic production of hCG and its alpha-subunit in the cancer group. Before treatment, 3 patients (8.8%) had elevated serum alpha-subunit levels, whereas after treatment 9 patients (26.5%) had elevated levels. For urine alpha-subunit 3 patients (8.8%) had elevated levels before and 13 (38.2%) after treatment. Six patients (17.7%) had elevated serum hCG levels before and 7 (20.6%) after treatment; however, for urine hCG, 3 patients (9%) had elevated levels before and 8 (24.2%) after treatment. Sephadex G-100 chromatography of urine extracts from two control women showed that the predominant form of free alpha-subunit secreted by the pituitary and excreted in the urine had lower apparent molecular weight after treatment with the CP. Chromatography of urine extracts from two cancer patients demonstrated that a small amount of beta-subunit of hCG produced ectopically by the tumor and excreted into the urine along with a core-type fragment of the hCG-beta was masked in the basal urine by cross-reacting LH; these ectopic peptides were not suppressible and could be specifically measured only after elimination of the urine LH by treatment with the CP. We conclude that administration of contraceptive steroid to post-menopausal women with cancer, by suppressing pituitary gonadotropin secretion and thus minimizing their interference in the hCG RIAs, can be useful in the detection of ectopic production of the hCG and its subunits.