Production of Estrone and Fractional Conversion of Circulating Androstenedione to Estrone in Women with Endometrial Carcinoma

Abstract

Postmenopausal women convert circulatory C19 steroids to estrogen. In order to study the possible role of such estrogen in endometrial cancer, the determination of the fractional conversion of circulation delta-4-androstene-3,17-dione to estrone was attempted. However, in the course of this work it became apparent that the mathematical model upon which this determination is based does not adequately represent the true physiological conditions. The reasons for the inadequacy of the model are not apparent, although they seem to bear some relationship to obesity. The direction and magnitude of the deviation of the values; determined from the true values are unknown. The values for the apparent fractional conversion of androstenedione to estrone in 9 postmenopausal women with endometrial cancer are strongly correlated with values indices of obesity. These values also correlate well with values for the apparent rate of production of estrone in our 9 patients and also in 5 postomenopausal patients with uterine bleeding reported in the literature, but no such correlation is evident for postmenopausal women without endometrial abnormality reported in the literature. The range of values for both the apparent fractional conversion and the apparent rate of production of estrone are similar to those reported by other workers using the same model. However, the data suggest that women with endometrial cancer may produce estriol by a pathway not involving circulating estrone.

Oestrone sulphate, adipose tissue, and breast cancer

“…Adipose tissue has thus now been reported to contain three enzymes which may affect the oestrogenic environment: aromatases converting androgen to oestrogen (32)(33)(34), an oxido-reductase which interconverts oestrone and oestradiol (35), and sulphatase capable of releasing oestrone from its conjugate. The presence of these enzymes, and in particular aromatase, in adipose tissue is in accord with the finding that in obesity, the circulating levels of oestrogen are increased in proportion to excess body weight (29,36,37).…”

The relationship of body weight to response to endocrine therapy, steroid hormone receptors and survival of patients with advanced cancer of the breast

“…The strong correlation between the production of oestrone, the degree of this conversion and indices of obesity (e.g., weight, percentage of ideal weight and weight:height ratio) suggests that the excess production of steroid hormones within body fat which promotes the growth of mammary epithelial cells, may be the mechanism whereby there is an association between body weight and tumour incidence (Rizkallah et al, 1975;McDonald et al, 1978;Kirschner et al, 1982). This is supported by the report of lower levels of sex hormone binding globulin in the obese which may lead to higher levels of free oestrogens (Kirschner et al, 1982).…”

Hormonal Profile of Endometrial Cancer

“…After TAH and BSO were performed, Ei lev els dropped to normal values. It has been shown in the past that the womb and tumour tissues do not play any role in the conversion of A to E, [6]. Post-menopausal ovaries are able to produce androstenedione which, in turn, is converted to oestrone in the periph ery [3,16].…”

“…The oestrone hypothesis is based on the assumption that the effect of oestradiol on endometrial cells is self-limiting, and does not cause cancer. Several clinical facts support the hypoth esis: endometrial cancer appears frequently in obese women, in anovulatory states and in liver diseases in which the transfer of oes trone to oestriol in the liver is disturbed, other investigations showed that oestrone is produced in the fat tissue from androstenedione (A) [3][4][5][6], The high incidence of endometrial cancer in the polycystic ovary syndrome [5,7] and in feminizing ovarian tumours [8][9][10] also supports the assump tion that the influence of one of the oestrogens on the endometrium might cause neo plasia. The aim of this study was three-fold: (a) to check whether oestrone levels in endome trial cancer patients are higher than oestra diol levels, and whether these levels differ from those of healthy women; (b) to evalu ate the role of progesterone and testosterone in endometrial cancer, as it has been shown that these hormones inhibit growth in vitro, and (c) to assess the role of the ovaries in the production of oestrone, oestradiol, pro gesterone and testosterone in cancer pa tients.…”