摘要:

Oral contraceptives have now been used clinically for over 15 yr. The present brief review discusses the discovery and development of the first oral contraceptive.

ISSN:0098-4108    

DOI:10.1080/15287397709529554

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

The metabolism of mestranol, ethynylestradiol, norethynodrel, norethindrone, ethynodiol diacetate, lynestrenol, and norgestrel is reviewed.

ISSN:0098-4108    

DOI:10.1080/15287397709529555

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

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.

ISSN:0098-4108    

DOI:10.1080/15287397709529556

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

In a study that has been in progress for 8 yr, ethynerone (MK 665) plus mestranol, chloroethynyi norgestrel (Wy‐4355) plus mestranol, anagestone acetate plus mestranol, ethynerone, and mestranol have been administered at levels up to 25 times the human use level to female beagle dogs and 50 times the human use level to female rhesus monkeys. Both species have shown a mild, nonprogressive, dose‐dependent decrease in hemoglobin and hematocrits when treated with the three progestogen‐mestranol combinations, mestranol, or ethynerone. Pyometra occurred in some dogs from progestogen‐treated groups. Dogs from the groups that received the three progestogen‐mestranol combinations and ethynerone alone developed more hyperplastic and neoplastic mammary nodules than control dogs. Dogs that received mestranol alone had no more mammary nodules than control dogs. None of the drugs has produced an increased incidence of mammary nodules in monkeys. Clinically malignant mammary tumors occurred in a small number of dogs that received each progestogen‐mestranol combination but did not occur in control dogs or dogs that received only mestranol or ethynerone. Ductal epithelial hyperplasia was seen in mammary gland biopsies from some monkeys receiving each drug but was not seen in biopsies from controls. Diabetes mellitus developed in ten dogs from chloroethynyi norgestrei‐mestranol and anagestone acetate‐mestranol groups and in three monkeys from ethynerone‐mestranol and anagestone acetate‐mestranol groups. Generalized cystic hyperplasia of the gallbladder mucosa occurred in a small number of dogs from the anagestone acetate‐mestranol groups.

ISSN:0098-4108    

DOI:10.1080/15287397709529557

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287397709529558

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

Concern has been expressed about the possible untoward effect of oral contraceptives on the liver. During the past 10 yr an increasing number of cases of hepatic adenomas and related lesions has been reported in women using oral contraceptives. Such lesions occur only rarely, but it is the rarity itself that makes it difficult to evaluate the role of the contraceptive steroids. The enormity of the denominator in contraceptive steroid usage is so unwieldy that mechanisms to measure accurately the difference in an extremely small numerator are still plaguing the epidemiologist, who at best can supply only estimates. The data to date support an exceedingly low incidence of disease. This is much below the greater risks faced in accepted activities of daily living, particularly as affected by pregnancy itself. A plea is made to develop programs for better prospective evaluations of newer medications along with better animal experimental models.

ISSN:0098-4108    

DOI:10.1080/15287397709529559

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

In the post 3 yr, over 140 cases of benign liver cell adenomas in young women who have used oral contraceptives have been reported in the world's medical literature. In the past, these tumors have been considered rare. Although hepatic cell tumors are benign, reports have indicated that the onset of the disease is of a critical nature‐victims are frequently subject to sudden pain, shock, and hemorrhage, and a fatality rate of 10% was recorded in the aforementioned reports. In light of these facts, an epidemiological study was initiated in Nebraska. As a result, 20 new cases hove been recorded of hepatic cell tumors in oral contraceptive users.

ISSN:0098-4108    

DOI:10.1080/15287397709529560

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

Two strains of mice, CF‐LP and Swiss‐Webster random‐bred, were evaluated for liver neoplasia after administration of oral contraceptive steroids. No increased incidence of hepatocellular tumors was found beyond the variation expected by chance. The overall tumor incidence in treated and untreated groups was identical. No significant increase in tumor size was observed in the treated animals. Liver weights progressively increased in several of the treated groups. In both treated and untreated animals hepatocellular neoplasia was usually accompanied by intracytoplasmic inclusions similar to those observed in human liver tumors. Vascular lesions were observed in some of the animals receiving large doses of contraceptive steroids. While these may be the result of local toxicity, their similarity to lesions observed in benign liver tumors warrants further investigation. No evidence was found to suggest that contraceptive steroids act as initiators of liver neoplasia.

ISSN:0098-4108    

DOI:10.1080/15287397709529561

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

The pharmacokinetics and metabolic conversion of the ethynylated estrogens are reviewed. Special emphasis is given to the comparative pharmacokinetics of ethynylestradiol in different populations of women. Similarly, the variability of ethynylestradiol and mestranol metabolism in humans resulting from presentation of radio‐labeled steroid and purification of the metabolic products is presented and discussed. The concepts of estrogen hepatotoxicity are reviewed with respect to the known phenomenon of estrogen oxidative metabolism and covalent binding. Recent evidence for the metabolic removal of the 17α‐ethynyl group is discussed, and its relationship to estrogen hepatoxicity is considered and related to the covalent binding phenomenon.

ISSN:0098-4108    

DOI:10.1080/15287397709529562

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor

摘要:

The effects of estrogen, progestogens, and combination steroids on the endometrium and cervix are reviewed. Prolonged administration of estrogen or sustained production of unopposed endogenous estrogenic substances may be associated with an increased risk of endometrial hyperpfasia and atypical adenomatous hyperplasia leading to well‐differentiated adenocarcinoma of the endometrium. The development of endometrial cancer does not seem to depend on the presence of the ovaries or the administration of estrogen, since the cancer is known to occur in women with dysgenetic ovaries and in surgical castrates who have never received exogenous estrogen. Endogenous estrone appears to play a role in the genesis of endometrial cancer and its precise function needs to be investigated.

ISSN:0098-4108    

DOI:10.1080/15287397709529563

出版商:Taylor & Francis Group    

年代:1977

数据来源: Taylor