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Problems in evaluating chronic toxicity of contraceptive steroids in dogs.

The long-term effects of oral contraceptive steroids including a combination of norethindrone and ethynylestradiol, a sequential regimen of dimethisterone and ethynylestradiol, and daily administration of megestrol acetate were studied in female beagle dogs at dose levels of 1, 10, or 25 times the projected human dose levels. The major findings included cystic endometrial hyperplasia and pyometra requiring hysterectomies and alopecia for the norethindrone-ethynylestradiol and dimethisterone-ethynylestradiol treated dogs. These groups did not have accentuated mammary development or treatment-related hyperplastic or neoplastic changes. For dogs given dimethisterone-ethynylestradiol, numerous acne-like lesions occurred in the skin of the mammary areas. Dogs given the higher dose levels of megestrol acetate had marked mammary stimulation, hyperplastic and neoplastic changes in the mammary glands, and clinical and pathologic changes typical of diabetes mellitus. Mammary changes of nodular hyperplasia, benign mixed tumor, and adenocarcinoma appeared as distinct entities although constant and intense mammary stimulation may be a common denominator. Such mammary changes have not been found in long-term studies in monkeys or rats with megestrol acetate, and the relevance of the canine mammary changes to projecting potential tumorigenesis in women is questioned.

Alopecia↗

Benign breast tumor and estrogenic hormones: a population-based retrospective study.

Histories of the usage of oral contraceptives and other estrogens were obtained from 320 women 20-49 years of age who had pathologically confirmed diagnoses of benign breast disease made at Washington County Hospital in Hagerstown, Maryland, during the period 1968 through 1972. Similar histories were obtained from 320 controls matched for race, sex, age, residence in county, and willingness to participate in a health survey. No association could be found between oral contraceptive usage and benign breast tumor. The use of other estrogens, notably diethylstilbestrol, was significantly related to the presence of benign breast disease.

Adenofibroma↗

Benign liver cell adenoma associated with use of oral contraceptive agents.

A benign hepatic adenoma in a young woman taking oral contraceptives for 7 years is reported. The diagnosis must be suspected in any young woman taking oral contraceptive agents who develop signs and symptoms of acute cholecystitis with hepatomegaly or mass, or when signs and symptoms of non-traumatic intraabdominal hemorrhage are present. Rupture of the tumor is a life-threatening complication. Treatment should be either hepatic lobectomy or wide local resection.

Adult↗

Effect of oral contraceptives on plasma androgenic steroids and their precursors.

Plasma dehydroepiandrosterone (DHEA), its sulfate ester (DHEAS), and androstenedione (A2), delta5-pregnenolone (delta5-P), and 17 alpha-hydroxypregnenolone were measured in women using estrogen-containing oral contraceptives and in female controls of similar age. All three androgenic steroids and their two C21 precursors were reduced in the oral contraceptive users compared with the controls. It is concluded that oral contraceptives cause a decrease in plasma DHEA, DHEAS, and A2, one possible mechanism for which is the inhibition of delta5-P synthesis from cholesterol.

17-alpha-Hydroxypregnenolone↗

Effect of progestins on glucose and lipid metabolism.

Gestamimetic amounts of progesterone enhance basal and glucose-stimulated insulin production. Contraceptive doses of synthetic progestins cause a moderate increase or no change in glucose-stimulated insulin production, depending on route of administration and species tested. Estrogens potentiate the insulinotropic effects of progesterone and the synthetic progestins. Basal serum triglyceride concentrations are generally unaffected by progesterone or 17 alpha-acetoxyprogesterone treatment but may decrease during 19-nortestosterone administration. Glucose tolerance does not change during treatment with gestamimetic doses of progesterone alone but may improve in rats and monkeys during concurrent estrogen administration. By contrast, deterioration of glucose tolerance is observed in women treated concurrently with synthetic estrogen plus 19-nortestosterone derivatives and, occasionally, with 19-nortestosterone derivatives alone. No consistent changes in glucose metabolism have been observed after treatment with 17 alpha-acetoxyprogesterone derivatives alone. The cause of the species-related differences in glucose metabolism during 19-nortestosterone treatment is obscure.

Animals↗

[Effects of estrogenic hormones on blood lipids].

The authors have followed the effects of application of the deposit estradiolbenzoat on the blood lipides level of women at the beginning of menopause and women with arteriosclerosis. They have registered a moderate drop of the concentration of cholesterol, beta-lipoproteins, and slight changes of the non-esterified fatty acids level. Women using contraceptive hormonal mixtures were found with higher level of cholesterol in the blood serum than those being watched. The application of a single dose of androgen did not have any substantial effects on the blood lipides level.

Adult↗

[Long-term effect of hormonal contraceptives on the behavior of serum lipids].

In order to check the long-term effects of oral contraceptives used in the GDR on certain serum-lipid-fractions, triglycerides, phospholipids, total and free cholesterol, and beta-lipoproteins were determined in four groups of 15 women each, taking the contraceptive preparations Ovosiston, Nonovlon, Gravistat, and Deposiston. Determinations were carried out before and following 3, 6, 12, and 18 month of drug administration. Statistically significant increases of triglycerides occurred under the combined preparations, of phospholipids under Ovosiston and Deposiston and of the beta-lipoproteins under Ovosiston and Gravistat. Total cholesterol showed a slight decrease under all preparations tested. At present the prognostic significance of these slight alterations of serum-lipid-concentrations cannot be estimated completely.

Adult↗

[Changes in heparinocytes during the administration of Depositon and Sequenz-Ovosiston].

During hormonal contraception with Deposiston (once a week pill) and with Sequenz-Ovosiston (14 days mestranol 0.1 mg, 7 days mestranol 0,08 mg and 2 mg chlormadinone acetate) doesn't take place a change of basophil granulocytes (heparinocytes) in blood. Under Deposiston the small elevation is somewhat lengthened, under Sequenz-Ovosiston the elevated phase is similar to those of the normal menstrual cycle. The smaller risk of thromboembolia under heparinocytopenia preventing contraceptives is discussed.

Agranulocytosis↗

[Modification of the thrombocyte function using hormonal contraception. 1. Thrombocyte count, thrombocyte propagation and platelet aggregation under hormonal contraception].

The number of platelets, spreading and aggregation of platelets in plasma of 102 women treated with Ovosiston, an anticonceptive agent, were investigated. A significant increase of the number of platelets, spreading and aggregation of platelets was observed. Conclusions from isolated observations are not possible.

Adolescent↗

Relations between fibrinogen degradation products and heparinocytes.

In the emergency reaction there is a short-time increase of the values of basophilic leukocytes in connection with normal values of fibrinogen degradation products (FDP). After diminuation of basophils FDP are to be detected. In the chronical ill and under different hormonal contraceptives these two processes are overlapped disturbing a unique negative or positive correlation of heparinocytes and FDP. Concerning the situation under standardized conditions or in single cases worthful conclusions are possible about compensation or decompensation of a latent disseminated intravascular coagulation.

Arterial Occlusive Diseases↗

[Liver function tests under the influence of sequential treatment using ethinyl estradiol-norethisterone acetate and ethinyl estradiol-chlormadinone acetate].

30 young healthy women were investigated during the first therapy cycle with ethinyl-estradiol-norethisterone acetate and ethinyl-estradiol-chlormadinone acetate as a sequential regime. The following laboratory data were achieved by each of the investigated group of young women: serum aminotransferase (GOT and GPT), serum alkaline phosphatase and alpha-amylase-activity in serum, serum proteins, serum cholesterol, serum bilirubin, serum ZST, serum TTT and the indocyaningreen-clearance of the liver. The serum protein pattern was determined by the paper electrophoretic method. A significant decrease of the aminotransferase GPT was viable during the sequential therapy with ethinyl-estradiol and norethisterone acetate. This viable decrease of the GPT was induced through the application of norethisterone acetate to estrogen. The alkaline phosphatase was significant lightly lower and the beta-globuline lightly elevated at the end of the therapy cycle. The sequential therapy with ethinyl-estradiol and chlormadinone acetate induced only a significant increase of the ZST in serum.

Adolescent↗

[A gradual method for a more physiological hormonal contraception].

The multiple physiologie stages of method by oral hormonal anticonception was reported, which have been in use in combination. Since 1969 about 362 women at the average age of 27,5 years received 10281 cycles, that means in an average cycles from 28,4 days, the stage method from 11/10 days or 7-7-7 days rhythmus.

Adult↗