[Diagnostic image (320). A new mother with opisthotonus and extensor spasms]. / Diagnose in beeld (320). Een kraamvrouw met opisthotonus en strekkrampe.

A 21-year-old woman was admitted to a rural hospital in Tanzania after a home delivery one week before. She had signs of general body rigidity due to maternal tetanus.

Aromatase in the context of breast and endometrial cancer. A review.

Generally, estrogens are considered to be involved in the neoplastic transformation of endometrium. After the menopause these estrogens mainly originate from conversion of adrenal androgens by aromatization in body fat. However, in case of stromal hyperplasia of the ovaries, it cannot be excluded that production of aromatizable androgens by postmenopausal ovaries leads to increased availability of androgen precursors for intratumoral estrogen synthesis in the endometrial tissue as well. The local presence of androgens and the local expression and activity of aromatase is considered important for this steroidogenesis. In this review, we will discuss the available evidence that androgens, produced in hyperplastic ovarian stroma or body fat tissues, play a role in the development of endometrial cancer through conversion into estrogens, a reaction catalyzed in the endometrium by the enzyme aromatase cytochrome P450. As the presence of aromatase appeared to be a pathophysiological factor in the formation of breast cancer, the latter will be evaluated in relation to the development of endometrioid endometrial cancer as well, since both disorders appear partly estrogen dependent. As treatment with aromatase inhibitors appeared feasible in breast cancer, current knowledge of comparable treatment modalities in hormone dependent endometrial cancer will be reviewed.

Is aromatase cytochrome P450 involved in the pathogenesis of endometrioid endometrial cancer?

Prospectively, the relationship between androgen levels in the utero-ovarian circulation, aromatase activity in endometrial and body fat tissue, and the presence or absence of endometrioid endometrial cancer was studied in postmenopausal women. In 43 women with endometrioid endometrial cancer and 8 women with a benign gynecological condition, a hysterectomy with bilateral salpingo-oophorectomy was performed. Using tritium water-release assays, aromatase activities in endometrial and body fat tissue were determined and related to the steroid levels from the peripheral and the utero-ovarian venous circulation (estradiol, androstenedione, testosterone) and to the presence or absence of endometrial cancer. Significant aromatase activity was found in both benign and malignant endometrial tissue samples. Aromatase activity in samples of endometrial tissue and in samples of body fat did not correlate with steroid levels in peripheral or utero-ovarian venous blood. Aromatase activity in samples of benign or malignant endometrium did not differ. Remarkably, in four women with mainly poorly differentiated endometrial cancer, very high aromatase activity was found in endometrial tissue. It is likely that multiple pathogenetic pathways exist that eventually lead to the formation of endometrioid endometrial cancer. The local availability of androgens and the finding that aromatase activity is present in both endometrial cancer and benign endometrial tissue support the hypothesis that aromatase activity in the endometrium may play a role in malignant transformation by converting androgens into mitogenic estrogens in the endometrial tissue.

Ovarian stromal hyperplasia and ovarian vein steroid levels in relation to endometrioid endometrial cancer.

OBJECTIVE: To study the relationship between the presence of endometrioid endometrial cancer, the degree of ovarian stromal hyperplasia and ovarian steroid production in postmenopausal women. DESIGN: Retrospective and prospective study, respectively. SETTING: Medical Centre Leeuwarden and the University Hospital Groningen, The Netherlands. Postmenopausal women with or without endometrial cancer, undergoing a hysterectomy with bilateral salpingo-oophorectomy. METHODS: In 112 women with endometrioid endometrial cancer, 47 women with a benign gynaecological condition and 10 women with non-endometrioid endometrial cancer, the degree of ovarian stromal hyperplasia was scored retrospectively on a semi-quantitative scale (atrophy, slight, marked). All women were postmenopausal and had undergone a hysterectomy with bilateral salpingo-oophorectomy. Prospectively, blood sampling from the ovarian veins was performed in a further 60 women. Steroid levels (oestrone, oestradiol, androstenedione, testosterone) were determined and related to the degree of ovarian stromal hyperplasia and the presence (n = 52) or absence (n = 8) of endometrioid endometrial cancer. MAIN OUTCOME MEASURES: Degree of ovarian stromal hyperplasia and steroid levels in the utero-ovarian circulation. RESULTS: In the retrospective study, the degree of ovarian stromal hyperplasia was higher in the presence of endometrioid endometrial cancer (P = 0.0001). The prospective study showed that an increasing degree of ovarian stromal hyperplasia was related to higher ovarian levels of both testosterone and androstenedione (P < 0.05 and P < 0.005, respectively), but not to oestrone or oestradiol. A non-significant increase in mean ovarian vein levels of both testosterone and androstenedione was seen in patients with endometrial cancer as compared with patients with benign conditions. CONCLUSION: In endometrioid endometrial cancer, higher degrees of ovarian stromal hyperplasia were found and with increasing degrees of ovarian stromal hyperplasia, levels of ovarian vein androgens were higher. A causal relationship in the origin of hormone-dependent endometrial pathology may exist between ovarian stromal hyperplasia, ovarian vein androgen levels and endometrioid endometrial carcinoma.

The postmenopausal ovary as an androgen-producing gland; hypothesis on the etiology of endometrial cancer.

Postmenopausal estrogens originate from the peripheral conversion of androgens, which are produced by the adrenal glands and the ovaries. Estrogens are considered to contribute to the neoplastic development of endometrium. Hyperplasia of ovarian stroma is associated with an increased androgen production by the ovaries and with the development of endometrial pathology. We hypothesize that, in cases of endometrial pathology, an increased production of aromatizable androgens by postmenopausal ovaries will lead to elevated prehormone availability for estrogen formation in utero. Following the conversion of ovarian androgens, a reaction catalyzed by the cytochrome p450 aromatase, estrogens may function as a local mitogenic factor eventually leading to the development of endometrial cancer. We consider the local availability of androgens and the local activity of aromatase relevant for this process. If this hypothesis proves to be right it may give rise to the introduction of aromatase inhibitors in treatment strategies of hormone dependent endometrial malignancies.