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Endometrial adenocarcinoma.

Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for some 36,000 cases of invasive cancer each year. Hyperplastic lesions of the endometrium follow a continuum, with the risk of progression to carcinoma being related to the severity of the disorder. Risk factors associated with the development of adenocarcinoma include hyperplasia, obesity, menstrual abnormalities, diabetes, hypertension, prior pelvic irradiation, sequential oral contraceptive use, diet, and exogenous estrogen use. There is also some evidence of genetic predisposition, and some data indicating the possibility of specific genetic abnormalities and activation of oncogenes as factors determining the etiology of the disease. At this time there is no accepted screening test for endometrial carcinoma, though the role of immunochemistry techniques for screening and follow-up has just begun to be realized. Dilatation and curettage along with hysteroscopy remain the major means of diagnosis. A variety of prognostic variables including tumor cell type, histologic grade, depth of myometrial invasion, status of peritoneal cytology, presence of disease in preformed vascular spaces, presence of adnexal metastases, and presence of cervical involvement have been defined. Although the treatment plan for each patient must be individualized, the mainstay of treatment remains total abdominal hysterectomy with bilateral salpingo-oophorectomy. Metastatic and recurrent disease is usually treated with hormonal therapy and systemic chemotherapy. Radiation therapy like surgery in recurrent disease is only applicable for the treatment of local recurrences.

Adenocarcinoma↗

Role of exogenous female hormones in altering the risk of benign and malignant neoplasms in humans.

The epidemiological and clinical evidence for various forms of exogenous estrogens altering the risk of neoplasms of the female genital system, breast, and liver are reviewed and evaluated. It is virtually certain that in utero exposure to diethylstilbestrol can cause clear cell adenocarcinomas of the vagina and cervix. There is strong evidence that various estrogens given for treatment of menopausal symptoms can cause endometrial carcinoma and that sequential oral contraceptives probably also do so. Oral contraceptives very probably reduce the risk of both cystic disease and fibroadenoma of the breast and increase the risk of liver cell adenomas. Studies to date do not provide consistent and convincing evidence that any form of exogenous estrogen alters the risk of cancers of the breast or ovary or that oral contraceptives alter the risk of cervical neoplasia or focal nodular hyperplasia of the liver, although recent reports suggest that continued vigilance is warranted. Specific topics requiring further epidemiological investigation are suggested.

Adenocarcinoma↗

Sex steroid hormones and antibodies to Candida albicans.

The effect of changes in progesterone (P) and estradiol (E2) on titres of antibodies to Candida albicans was studied by measurement of these three parameters in the following endocrinologically diverse human groups: normal females, gonadal dysgenetics, users of a sequential oral contraceptive (Oracon) and normal males. In females, C. albicans titres (mean +/- s.e.m.) were significantly higher (P less than 0.05) in the luteal (74 +/- 14) than in the follicular phase (34 +/- 19) of the cycle, and there were similar significant increases in P and E2. In the gonadal dysgenetic group (n = 29), with E2 levels comparable with males, the antibody titres were also equivalent to those in normal males (40 +/- 0.5), but were significantly lower than those of normal females in the follicular phase (P less than 0.05). In contrast, Oracon users, with high blood progestin levels, had C. albicans titres (118 +/- 15) significantly higher (P less than 0.001) than those of control subjects during the follicular phase. A significant correlation (P less than 0.05) was observed between P and C. albicans titres (mainly IgA) in randomly selected samples (n = 112) from normal females during the follicular and luteal phases, and in two subjects from whom blood samples were drawn daily for the entire cycle. In the latter, an increase in E2 but not P in the late follicular phase was accompanied by a marked decrease in C. albicans titres. No changes were observed in total immunoglobulin levels or antibodies to SRBC or Herpes virus in response to the marked changes in hormones. These results indicate that the production of antibodies to C. albicans may be specifically influenced by sex steroid hormones, being enhanced by P and E2 at low levels but depressed by E2 at high levels.

Antibodies, Fungal↗

The role of hormones in the etiology and prevention of endometrial cancer.

Unopposed estrogens, both exogenous and endogenous, increase the risk of endometrial cancer although the magnitude of the association between estrogen replacement therapy and adenocarcinoma has been exaggerated by the epidemiologic case-control studies. Not all postmenopausal women need estrogen replacement therapy since some produce sufficient endogenous estrogens to remain asymptomatic and prevent atrophic vaginitis, osteoporosis and atherosclerosis. However, within this group may be those at risk for endometrial cancer, so they need to be identified and treated with cyclic progestogens. Sequential oral contraceptives did not protect young women from adenocarcinoma of the endometrium because of too little progestogen for too short a duration in view of the relatively high dosage of estrogen. However, combination birth control pills significantly decrease the risk for endometrial carcinoma. Endometrial hyperplasia is a precancerous lesion in some women and can be effectively reversed with 10-13 days of progestogen monthly in at least 98% of patients. The progestogen challenge test has been devised to identify postmenopausal women at greatest risk for adenocarcinoma. It should be administered to all postmenopausal women with an intact uterus. This includes asymptomatic women, patients receiving estrogen replacement therapy and women being evaluated for hormone therapy. If there is a positive response to the progestogen challenge, as manifested by withdrawal bleeding, then the progestogen should be continued for 13 days each month for as long as withdrawal bleeding results. If there is no response then the progestogen challenge test should be repeated at each annual examination. Universal use of the progestogen challenge test should prevent nearly all endometrial cancers.

Combined Modality Therapy↗

[Influence of estrogens on pituitary responsiveness to LHRH and TRH in human (author's transl)].

Estrogens are supposed to be responsible for the increased sensitivity of the pituitary to LHRH and TRH observed in female in comparison to male adults. The influence of physiological and pharmacological variations of estrogens was studied throughout female life. Adolescents girls showed enhanced responses to both LHRH and TRH, as compared to cycling adult women. The adolescent pituitary seems to be particularly sensitive to the increasing estradiol secretion. Adult cycling women disclosed higher LH and FSH responses to LHRH during the periovulatory and luteal phases than during the follicular phase; prolactin response to TRH was enhanced only during the periovulatory phase while TSH response remained constant throughout the menstrual cycle. In adult women, sequential oral contraceptives increased LH, FSH and prolactin responses to LHRH and TRH while TSH response was unchanged. Combined contraceptives displayed an important inhibition of the LH, FSH and TSH responses but not of that of prolactin. The inhibitory effects on gonadotrophins and TSH may be due to the association of gestagens to estrogens. Postmenopausal women presented a TSH response to TRH similar to that found in male adults while prolactin response remained unchanged in spite of decreased basal values. The potentiatory effects of estrogens on the pituitary responsiveness to LHRH and TSH may be attributed either to an increased number or to an enhanced binding activity of the pituitary receptors to LHRH and TRH, as suggested by several experimental data.

Adolescent↗

[Investigation of the epidemilogy of fungal vaginitis in 1000 patients (author's transl)].

In the out-patient department and antenatal clinic 1000 patients were examined for yeast of the genital tract by the nickerson-medium. In 10.3% of the patients the cultures showed yeast. The wet-mount preparation examination under phase contrast microscopy was compared to the nickerson-medi-m culture. Patients with a past history of yeast infections or patients with an intrauterine device showed a statistically significant increase in the rate of yeast vaginitis compared to the control groups. Patients who had antibiotics or were treated with corticosteroids showed a higher incidence of yeast vaginitis than normal controls. Controls had a 9% incidence. The number of cases was too small for statistical analysis. The incidence of yeast vaginitis in patients on combined or sequential oral contraceptives was the same as in the control groups. The pregnant patients and obese patients did not show an increased incidence of yeast. High risk patients for yeast vaginitis are defined in which a culture for yeast is jusitfied. Especially antenatal patients in the last trimestre are a high risk group because of the possibility of neonatal thrush.

Adolescent↗

Solar urticaria: a case with increased skin mast cells and good therapeutic response to an antihistamine.

A 45-year-old woman with solar urticaria is described. She was found to have: (a) increase of skin mast cells; (b) a good therapeutic response to hydroxyzine hydrochloride; (c) frequent peptic ulcers of the stomach; (d) antinuclear IgM antibodies in a titre of 1 : 1 000; (e) cold urticaria and dermographism; (f) anamnestically, suppression of the solar urticaria by a sequential oral contraceptive.

Adult↗

Adenocarcinoma of the endometrium in women 40 years of age or younger.

Excluding cases associated with oral sequential contraceptives, adenocarcinoma of the endometrium in young women is rare, constituting about 3% of endometrial carcinomas. The present report, based on findings from one institution, notes that women 40 years of age or younger comprised 14.4% of the 111 patients with adenocarcinoma of the endometrium. Factors analyzed in patients 40 years of age or younger (group A) as compared with those 41 years of age or older (group B) include the following: obesity 43.8% (A) versus 17.9% (B), nulliparity 44% (A) versus 10.5% (B), hypertension 31.2% (A) versus 42.1% (B), and diabetes 6.2% (A) versus 21.1% (B). Patients in group A tended to have a well-differentiated tumor, and 31.2% had polycystic ovaries. Awareness of risk factors in young women who develop endometrial adenocarcinoma leads to earlier diagnosis and will preserve the historically excellent survival rate of young women.

Adenocarcinoma↗

[Histoautoradiographic examinations of benign and malignant cells and tissues during therapeutic interventions in gynecology].

The alteration of the proliferation activity of different tissues of the female genital tract was studied with the histo-autoradiographic method. Tissue samples from 1. the normal endometrium before and under treatment with the sequential oral contraceptive Ovanon, 2. carcinomas of the vulva before and under treatment with Bleomycin, 3. cervical carcinomas stage I-III before and under Co 60-radiation, and fluid material of cystic ovarian tumors and effusions before and under treatment with alkylating agents were incubated in 3H-thymidine. Morphologic and histo-autoradiographic alterations were observed during all investigations. It was demonstrated that the histo-autoradiographic method 1. gives informations about the proliferation activity of tissues of the female genital tract, 2. quantifies the success of treatment, 3. and allows prognosis about therapeutic results, as it was shown in the case of radiation sensitivity of cervix carcinomas.

Autoradiography↗

Endometrial carcinoma in women 40 years of age or younger.

Adenocarcinoma of the endometrium in patients 40 years of age or younger is rare and accounts for 2.9% of all endometrial cancers diagnosed in the study community. However, the diagnosis of malignancy was confirmed in only 32 of 54 patients (59.2%) with pathologic material available for review. None of the 32 patients had Stein-Leventhal syndrome or was receiving sequential oral contraceptives. Obesity was found in only 37.5%, nulligravidity in 37.5%, and hypertension in 25%. In 81%, the presenting symptom was abnormal vaginal bleeding, and 6 patients (19%) had coexisting ovarian neoplasms (4 endometrioid carcinomas, 1 mucinous cystadenocarcinoma, and 1 adenocarcinoma arising in a cystic teratoma). Atypical endometrial hyperplasia, previously interpreted as well-differentiated adenocarcinoma, was diagnosed in 11 of 22 patients. The pathologic criteria for establishing a diagnosis of atypical endometrial hyperplasia and distinguishing it from well differentiated adenocarcinoma of the endometrium are emphasized. Thirteen of 32 patients received no radiation therapy and none developed pelvic recurrence or metastatic tumor. The 2 deaths from tumor were in patients with stage 3 ovarian cancer, and no patients died of endometrial carcinoma. The current policy is to treat patients with atypical endometrial hyperplasia and well-differentiated adenocarcinoma (clinical stage I, pathology confirmed) by hysterectomy without irradiation treatment. Because of 6 of the 32 patients (19%) had coexisting ovarian neoplasms, careful examination of the adnexa at the time of clinical staging is emphasized.

Adenocarcinoma↗

[Study of the endometrium following voluntary interruption of pregnancy in relation to the contraceptive method used following abortion].

A study of endometrial biopsies that was carried out around the 21st day after abortions in 424 patients who had had therapeutic terminations showed the effects of giving a sequential type of oral contraceptive immediately after the abortion had been carried out. This did not increase the rate of regeneration nor the proliferation of the endometrium and did not alter the local inflammatory reactions. It did, however, make it more difficult to eliminate decidua that had been retained as well as trophoblastic and villous structures and made it more likely that the classical appearance of the endometrium following pregnancy would be maintained.

Abortion, Therapeutic↗

Studies on liver function under the influence of oral contraceptives.

The effects of two sequential therapies using mestranol as an estrogen and chlormadinone acetate and norethisterone acetate, respectively, as a gestagen on the aminotransferase (GOT and GPT), alkaline phosphatase and alpha-amylase activities, the cholesterol, total bilirubin and total protein contents and the indocyanine green (Ujoviridin, VEB Chemiekombinat Bitterfeld) half-life were studied in two groups, each comprising 12 women of fertile age. The serum protein was separated by paper electrophoresis and both the thymol turbidity and zinc sulphate tests were performed during the first treatment cycle. An estrogen-induced rise in alanine aminotransferase (GPT) activity from 6.31 U/liter to 12.14 U/liter was observed during application of the mestranol/chlormadinone acetate therapy. The value dropped to 5.34 U/liter when chlormadinone acetate was administered as a gestagen in addition to the estrogen. No significant changes were noted in the other biochemical parameters. Sequential therapy involving application of mestranol and norethisterone acetate produced only statistically secured rises in the alpha 1-globulin content and the GPT activity. All other changes in the different parameters remained within the normal range and were statistically insignificant.

Adolescent↗