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Estrogen's role in endometrial cancer.

Data reported since 1975 indicate that the natural hormone estrogen may act as a carcinogen when unopposed by an adequate amount of progesterone. Carcinogenesis may proceed when it is present at a high level for a short time. It is generally accepted that 3 groups of women have been at risk of developing cancer from exogenous estrogen exposure: 1) women who took sequential oral contraceptives; 2) post-menopausal women who received estrogen replacement therapy; 3) girls with ovarian dysgenesis who received unopposed estrogen therapy at puberty. Similarly, 4 groups of women appear to be at risk of developing cancer form endogenous estrogen sources: 1) women with granulosa-cell or theca-cell ovarian tumors; 2) anovulatory women; 3) obese postmenopausal women; 4) women with liver disease. The falling incidence of endometrial cancer associated with diminished estrogen sales is the final proof of an association of estrogen exposure with development of disease.

Anovulation↗

Sequential therapy to achieve anovulatory cycles.

Sequential oral contraceptive therapy was devised to inhibit ovulation by a potent estrogen alone. A progestational agent was added at the end of the course of therapy to prepare the endometrium for adequate withdrawal bleeding. The program consisted of giving 80 mug. of metranol daily for 15 days and then a combination of 80 mug. of mestranol and 2 mg. of chlormadinone acetate for five additional days. Such a regimen proved to be effective in 6070 patients carefully observed for 82,085 cycles of therapy at 25 medical centres.INCREASED CYCLE REGULARITY WAS NOTED: 98.1% of the cycles were 25 to 31 days long. In 80.1% of cycles, the withdrawal interval was two to five days in length. Duration of flow was four to six days in 85.3% of the therapeutic cycles. The amount of flow decreased as compared with pretreatment values. The incidence and severity of dysmenorrhea during sequential therapy were significantly lower than before treatment. Side effects, usually infrequent, diminished as therapy was continued; the average incidence of breakthrough bleeding was 1.9% and nausea was 2.9%. Extensive laboratory studies showed no consistent abnormalities. For oral contraception, sequential therapy has proved to be virtually 100% effective when taken as directed.

Adult↗

Failure of a pure progestogen contraceptive to affect serum levels of iron, transferrin, protein-bound iodine, and transaminase.

Medroxyprogesterone acetate, a pure progestational agent which is not metabolized to oestrogen, was given to 30 women and shown to have no effect on the serum levels of iron, total iron-binding capacity, transferrin, and protein-bound iodine. Eighteen of these women had previously taken oral contraceptives of the combined oestrogen-progestogen "sequential" type, and during that time these serum levels were raised. Nevertheless, the levels all fell significantly after medroxyprogesterone acetate was given and the "sequential" oral contraceptive was stopped. In a further 12 postpartum women the serum levels did not change significantly after medroxyprogesterone acetate.These observations strongly suggest that raised plasma protein levels resulting from the administration of oral contraceptives are due to the oestrogen component.

Adolescent↗

Oral contraceptives and breast disease. An epidemiological study.

A case-control study of the relationship between use of oral contraceptives and cancer of the breast, cancer of the corpus uteri, cancer of the ovary, and benign breast diseases was undertaken among women in the age group 20--44 years who had been admitted to several large hospitals in Connecticut. No significant association was seen between use of oral contraceptives and breast cancer. It was found that the longer a woman had used sequential oral contraceptives, the lower her relative risk of benign breast disease. Use of combination oral contraceptives, however, did not appear to influence the risk of benign breast diseases. The numbers of cases with cancer of the ovary and of the corpus uteri in this age group were too small for any conclusions to be reached.

Adenofibroma↗

Role of estrogens and progesterone in the etiology and prevention of endometrial cancer: review.

Our present knowledge of the role of sex steroids in the development as well as the prevention of endometrial cancer is reviewed. Factors which increase the exposure of the uterus to unopposed estrogens, either exogenous or endogenous, are associated with increased risk of endometrial adenocarcinoma. However, there is increasing evidence that progestogens can reverse endometrial hyperplasia and protect against the development of endometrial cancer. The mechanisms to explain the antiestrogenic effects of progestogens include changes in enzyme activity and steroid receptors in endometrial tissue. Postmenopausal women treated with combined estrogen and progestogen have the lowest incidence of endometrial carcinoma. Oral contraceptives containing both estrogen and progestogen in each tablet are protective against adenocarcinoma of the endometrium, while the sequential oral contraceptive pills afforded less protection. The risks and benefits of these hormone therapies are discussed in relation to the etiology and prevention of endometrial cancer.

Animals↗

Thrombosis-perspective on a major side effect of oral contraceptives.

Evidence from retrospective studies suggests that the risk of thrombosis is related to the dose of oestrogen in oral contraceptives. Postoperative thrombosis is four times more likely to occur if oral contraceptives containing oestrogen are used before a major surgical procedure. Older women who smoke are at greater risk, especially when the surgery is performed during the winter months. It is recommended that barrier methods of contraception (condom or vaginal diaphragm) be employed during the six weeks before an elective major surgical procedure or that a progestogen-only pill be used in place of a combined or sequential oral contraceptive for this period of time.

Adult↗

[Use of oral contraceptives in East Germany by middle-aged females].

This study was based on the data from 1214 women included in the controlled group within a hospital-based case-control study on the association between breast cancer and the use of oral contraceptives. This is a sample of middle-aged women. Women with a reason for referral, presumably associated with infertility, were excluded. Oral contraceptives are (apart from coitus interruptus) in 76% of the cases the method of contraception most frequently used, followed by the rhythm method and condoms. The use depends strongly on the age. Only 40% of the women, now 55-60 years of age, ever used oral contraceptives, whereas 91% of those now under 40 have been using them. Other connections can be seen with level of education, marital status, and reproduction and sex life. With the use of special preparations, there are differences between women of younger and older generations, partially based on the different times these preparations were introduced to the market. The exclusive use of sequential oral contraceptives decreases in the older cases.

Breast Neoplasms↗

[Endometrial cancer in a young woman taking oral contraceptives for a long time].

The authors report a rare case of endometrial adenocarcinoma occurred in a 35-year old woman, who had taken oral contraceptives for 13 years. She came for consultation with irregular vaginal bleeding. Diagnostic curettage and histologic examination confirmed the diagnosis as endometrial adenocarcinoma. This case deserve special attention due to the rarity of the disease among young women. The authors emphasize the necessity of appropriate diagnostic work-up. In such cases histological examination is strongly recommended, since irregular vaginal bleeding might be caused by malignant disease even at young women using sequential oral contraceptives.

Adenocarcinoma↗

[Striking accumulation of vascular-induced homonymous defects of the visual field in young women].

An accumulation of vascular-induced, irreversible homonymous defects in the visual field of young women is reported. 9 of the 10 patients had taken oral contraceptives, sequential and combined preparations. Compared to a similar period before the introduction of the Pill, a threefold increase was observed. Factors disposing to vascular occlusion were found in only half of the patients.

Adult↗

[Current status of gestagen administration. 2. Gestagen therapy in the area of reproduction].

The spectrum of progestin therapy has changed and expanded during the last few years. 1. The drug-therapy of choice in endometriosis is the medication of progestins for at least six months, for instance ethinyl-testosterone. If a patient wants additional children the "more gentle" dydrogesterone should be considered. 2. In the treatment of dysmenorrhea combination pills should be given, sequentials should be avoided. In the case of incompatibility of estrogens or in danger of oversuppression syndrome dydrogesterone should be applicated. 3. Dysfunctional bleedings should lead to an intense search for their cause. The treatment consists in an estrogen-progestin combination for 9 days and in cyclic continuation of this therapy for at least a further three months. In the case of hemorrhagic diathesis progestin treatment should be continued. 4. Cyclic adequate progestins have proofed to be successful in handling of hirsutism. The choice of the preparation depends on the patient's wish for children. 5. The progestin test is still the first step in diagnosis of amenorrhea. 6. Progestin therapy is indicated in progressive endometrial carcinoma. Some medical centres treat carcinoma of the mamma successfully with progestins. 7. Nowadays fast and early hormonal pregnancy tests are available. The progestin-pregnancy-test is limited to cases of premenopause. 8. The so-called short luteum phase has received considerable attention as a possible cause of infertility. In these cases a substitutional therapy of progestins should follow. Clomiphene or HCG-therapy is advisable. In short luteum phase and premenstrual spottings potent progestins should be given. 9. High dosage of progestins are in common use in the treatment of abortus imminens. 10. Combination pills and sequentials are widely used, the possible methods of a pure progestin contraception are: minipills, three-month-injections, implanted silastic capsules with progestional compounds, progestin impregnated intrauterine devices, vaginal silastic rings impregnated with progestional compounds. 11. Carcinogenesis of progestins was not detectable. 12. Some progestins are teratogenic.

Abortion, Threatened↗