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Estrogen replacement in menopause should be used for specific symptoms such as ovarian failure, hot flushes, vaginal atrophy, atrophy of the vulva, and atrophic urethritis. The dose should be as low as possible to be effective and perscribed for as short as time as possible, since there are possible risks of uterine cancer, breast cancer, increased blood pressure, gallstones, deep vein thrombosis, and thromboembolism. Estrogens should be administered to provide the maximum benefit with the minimum risk involved. Estrogens should not be given to patients with known contraindications such as: suspected breast or uterine cancer; undiagnosed genital bleeding; Dubin-Johnson syndrome; acute hepatic disease; previous or present thromboembolism; or severe thrombophlebitis. Careful evaluation should be made before administering estrogen to women with uterine myomata, hyperlipidemia, hypercholesterolemia, sevare varicose veins, chronic hepatic dysfunction, diabetes mellitus, porphyria, or severe hypertension.
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PMID:Estrogen replacement in the menopause. 39 Apr 56

One of the major problems being researched and studied by the World Health Organization is the incidence of harmful side effects in users of steroid contraceptives. A literature search indicates that Anglo-Saxon countries report alarming hyperplastic changes, particularly in the liver, blood clots, hyperlipidemia leading to high blood pressure, porphyria, atypical leiomyomas and cervical hyperplasia. Currently attention is being focused on the relationship between steroid contraceptives and breast cancer. Fazala and Paffenbarger in their study of 1770 women found such benign changes as fibroadenoma, mastopathia fibrosa cystica and papilloma intraductale. In women who had used oral contraceptives for 2-4 yrs, malignancies were 1.9% to 2.5% more frequent than in non-users; in 6 yrs of use, 11 times greater than in non-users. Estrogens, particularly mestranol has been recognized as being harmful to the liver. Length of usage is a definite factor. Beginning with 1960, relatively frequent occurrences of hepotoma in young women on the pill were noted. Caught at an early stage, peliosis hepatis can be reversed if the patient discontinues the use of contraceptives. In some cases, even after a long interval of 6 months to 10 yrs, the disease continued to develop. Liver cell adenoma in the U. S. occurs 1/500,00 to 1/1,000,000. After 5 to 7 yrs of using oral contraceptives, the chance of developing liver cell adenoma is 5 times greater; after 10 yrs of use, 35 times greater. Hepatomas rupture in 43.4% of cases when the patient had been on a contraceptive, while in only 22.2% in cases of non-users. The literature which the author investigated did not establish a clear proof that the hyperplastic changes discussed were due exclusively to usage of oral contraceptives.
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PMID:[Hyperplastic changes and oral contraceptives in Anglo-Saxon countries]. 69 6

Certain physiological and pathological conditions in women require choice of a contraceptive method that will not aggravate the condition or exacerbate known side effects. IUDs and oral contraceptives (OCs) are not appropriate for the immediate postpartum. Low dose progestins appear best suited and can be started on the 5th day after delivery. IUDs and high dose discontinuous progestins are the best choices for the menopausal period, but contraindications to them must be respected. Contraception with a dominant progestational climate is required in case of benign breast disease. Low dose progestins may cause luteal insufficiency and low dose combined OCs may allow endogenous estradiol secretion poorly balanced by the progestin. All progestin-dominant formulations and discontinuous 19-norsteroids may be used. 19-norsteroids appear suitable for women with breast cancer because of their antiestrogenic activity. High dose progestins are advisable for women with precancerous or cancerous endometrial pathology. Estrogens should be avoided in such cases. Cervical cancer has never been proven to be hormonodependent, and at present the use of hormonal contraception in cervical dysplasia is not contraindicated except after pelvic radiation for invasive cancer. Use of the IUD has the same indications as for the general population after lesions have been treated. In cases of hyperlipidemia, low doses of continuously administered 19-norsteroids cause a decline of high density lipoprotein (HDL) cholesterol but are considered to be without longterm metabolic effects. The new progestin desogestrel does not diminish HDL cholesterol. Many cases of hyperlipidemia and hypercholesterolemia contraindicate OCs at the usual dose and require mechanical contraception, although low dose progestins may be considered. Derivatives of 17-hydroxyprogesterone are without effects on lipid metabolism but are less reliable. No contraceptive method is fully satisfactory for diabetics. Hormonal contraception is risky because of possible metabolic and vascular effects. Low dose progestins have the fewest side effects but are often poorly tolerated. IUDs are often used for diabetics despite possible increased risks of infection and failure. Hypertensive women should not use combined OCs or high-dose 19-norsteroids, but low dose progestins carry no risk of hypertension. Women at vascular risk are advised to use IUDs if no specific contraindications are found. Otherwise low-dose progestins are an acceptable choice. Low dose progestins are often the only possibility for cardiac patients. Nonhypertensive women with renal insufficiency can use OCs under careful supervision if there are no contraindications. Combined OCs are contraindicated when there is any disturbance of hepatic function, but low dose progestins or mechanical means are acceptable. Chronic use of certain drugs which act as enzymatic inductors is incompatible with hormonal contraception.
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PMID:[Contraception at risk]. 365 96

Endogenous sex hormone activity results in higher levels of VLDL, LDL, and apo B in males than in females, while HDL and particularly HDL2, and apo A1 levels are lower, apo A2 being reduced to a lesser degree. This sex-related difference appears progressively during puberty. There is increasing elevation of LDL cholesterol, apo B, and VLDL TG in women at the menopause, HDL cholesterol levels either diminishing or remaining constant. These differences in lipoprotein and apoprotein concentrations probably play a major role in protecting women against atherosclerosis development during the period of gonadal activity. Similar differences are provoked by exogenous hormone activity: the androgens increase LDL cholesterol and reduce HDL cholesterol, and total cholesterol is therefore only slightly altered. Estrogens provoke elevation of VLDL TG only at supraphysiological doses of the order of 30-50 mcg ethinyl estradiol. In contrast, reductions in LDL cholesterol and increases in HDL cholesterol occur even after low physiological doses of estrogens. This latter increase is dose-related and can be as high as 20%. The action of progestogens is less clearly defined and depends on the molecule administered, the dosage, and its possible androgenic action. When the latter activity is marked, lipoprotein and apoprotein variations are similar to those resulting from testosterone effects. The influence of sex hormones on the course of idiopathic hyperlipidemias varies. They may have a beneficial effect, but this is a fairly rare event and occurs only in very precise situations: improvement of type 3 hyperlipidemia by low dose estrogen therapy; improvement of moderate isolated hypercholesterolemia in menopausal women with low doses of estrogens, and improvement of type 5 mixed hypertriglyceridemia by certain progestogens such as oxandrolone. They usually produce the opposite effect, however, with marked increases of type 1, 4, and 5 hyperlipidemia under estrogens, sometimes leading to attacks of pancreatitis and elevation of preexisting hypercholesterolemias or mixed hyperlipidemias resulting in vascular accidents due to thrombosis. (author's modified)
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PMID:[Sex hormones and metabolism of lipoproteins]. 634 27

A case of acute intestinal vascular necrosis in a 19-year-old user of oral contraceptives (OCs) is described, and hypotheses explaining the digestive complications of synthetic estrogens are reviewed. The patient had originally presented with a violent gastric pain that subsequently spread to the entire abdomen. An abrupt worsening of her condition involved cardiovascular collapse associated with a peritoneal syndrome, vomiting and dehydration, and hyperleukocytosis. Emergency opening of the peritoneum was followed by evacuation of a large quantity of fetid gas and alimentary debris, and observation of a completely necrosed stomach. A careful lavage of the entire intestinal cavity led to temporary improvement, but it became clear during an attempt at gastrectomy that further treatment would be unavailing and the patient died shortly thereafter. Estrogens were believed to be responsible for the digestive necrosis because it occurred in a young woman who had used an estrogen-rich OC for 3 years and who smoked; a hapatic biopsy confirmed the diagnosis. No traces of other risk factors such as hypertension, hyperlipidemia, diabetes, neoplasia, or obesity were observed. Recent publications indicate that OCs are responsible for a certain number of digestive problems, which may include acceleration of intestinal transit, severe diarrhea, rectorrhagia, ischemic or ulcerative colitis, intestinal infarct which is usually localized, and hepatocellular problems ranging from moderate hepatic insufficiency to malignant tumor and Budd-Chiari syndrome. OCs do not modify hemodynamic regimes, but they may cause elevation of fibrinogen and thrombin, diminution of antithrombin III acitivty, increased platelet adhesivity, and decreased fibrinolysis leading to hypercoagulability. These modifications in hemostasis occur in all OC users and are not statistically correlated with occurence of thrombotic accidents. OCs are probably responsible for parietal vascular lesions; experimental injection of synthetic estrogens is associated with both arterial and venous lesions. The most characteristic anomaly is at the level of the intima, with proliferation of smooth muscle cells and increased conjunctive tissue fibers associated with proliferation of the media or the endothelium. The absence of lipid deposits, the simultaneous appearance of arterial and venous lesions, and other evidence argues against and atheromatous origin of parietal lesions. A significant correlation has been found between high levels of anti-synthetic ethinyl estradiol antibodies and the presence of vascular lesions. It is hypothesized that these circulating immune complexes penetrate the vascular walls of OC users and produce lesions, which may depend on factors such as smoking.
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PMID:[Digestive complications of oral contraceptives: a case of extensive digestive necrosis in a young woman]. 647 54

The incidence of thromboses among young women has increased with widespread use of oral contraceptives (OCs) due to the significant thromboembolic risk of estrogen. Estrogens intervene at the vascular, platelet, and plasma levels as a function of hormonal variations in the menstrual cycle, increasing the aggregability of the platelets and thrombocytes, accelerating the formation of clots, and decreasing the amount of antithrombin III. Estrogens are used in medicine to treat breast and prostate cancers and in gynecology to treat dysmenorrhea, during the menopause, and in contraception. Smoking, cardiovascular disease and hypertension, hypercholesterolemia, and diabetes are contraindicators to estrogen use. Thrombosis refers to blockage of a blood vessel by a clot or thrombus. Before estrogens are prescribed, a history of phlebitis, obesity, hyperlipidemia, or significant varicosities should be ruled out. A history of venous thrombosis, hyperlipoproteinemia, breast nodules, serious liver condition, allergies to progesterone, and some ocular diseases of vascular origin definitively rule out treatment with estrogens. A family history of infarct, embolism, diabetes, cancer, or vascular accidents at a young age signals a need for greater patient surveillance. All patients receiving estrogens should be carefully observed for signs of hypertension, hypercholesterolemia, hypercoagulability, or diabetes. Nurses have a role to play in carefully eliciting the patient's history of smoking, personal and family medical problems, and previous and current laboratory results, as well as in informing the patients of the risks and possible side effects of OCs, especially for those who smoke. Nurses should educate patients receiving estrogens, especially those with histories of circulatory problems, to avoid standing in 1 position for prolonged periods, avoid heat which is a vasodilator, avoid obesity, excercise regularly, wear appropriate footgear, and follow other good health practices.
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PMID:[Estrogens and vascular thrombosis]. 692 85

The 3 main methods of oral contraception (OC) are: 1) the sequential method, reproducing the hormonal sequence of the normal cycle; with this method the estrogen component is the one which inhibits ovulation; 2) the combined method, using estrogen and progesterone agents, and whose effectiveness is practically absolute; 3) the minipill, or low-dose progestin method. Other methods include the use of medroxyprogesterone acetate, which is 100% effective but has too numerous side effects, and the morning after pill. Estrogens utilized for OC are mestranol and ethinyl estradiol, while progestational agents can be derived from the natural progesterone, such as medroxyprogesterone, chlormandinone, and megestrol or from nor-19 testosterone. The minipill entails much fewer side effects than regular estroprogestational drugs, such as lower risk of thromboembolitic and metabolic processes; it does cause, however, a number of serious anomalies in the menstrual cycle. OC with low-dose progestin agents are recommended for women with pathologic antecedents, such as diabetes, cardiopathy, and hyperlipidemia.
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PMID:[Pills and minipills]. 1226 67

Epidemiological studies clearly indicate that combined oral contraceptives (OCs) increase risks of vascular thromboses. The risk of myocardial infarct is increased by 3 for combined OC users aged 30-39 and by 5 for those aged 40-44. Risks of deep phlebitis and cerebral thromboses are also 5 times greater in OC users. The effects of OCs on serum lipid levels depend on the dose and type of estrogens and progestin. Ethinyl estradiol causes an increase in triglycerides and HDL cholesterol, while progestins tend to increase total cholesterol and decrease HDL cholesterol. Low-dose combined OCs have slight or no effect on cholesterol, HDL cholesterol or triglycerides. Moderately dosed combined OCs elevate triglycerides but their effects on total cholesterol and HDL are moderate. High dose combined OCs increase triglyceride and cholesterol levels. The combined effects of the estrogen and progestin in high dose pills usually increase HDL cholesterol, but there is some doubt as to whether the increase is beneficial. Although all combined OCs have deleterious effects on serum lipids, only persons predisposed to hyperlipidemia are truly at risk. Young women using OCs require systematic control, of serum lipid and lipoprotein levels. Low-dose formulations are generally preferable. Standard or high dosed OCs can cause disturbances of glucose metabolism in predisposed women, but risks of patent diabetes are small. Glucose intolerance developed during pill use is not always reversible. The risk appears more serious with pills containing estranes or norgestrel than with those containing pregnanes. Low-dose pills entail less deterioration than higher dosed pills. Low-dose progestin-only pills also have deleterious effects. OCs interfere with glucose metabolism in part by creating an effect of peripheral insulin resistance and in part by diminishing the insulin-secreting capacities of the islets of Langerhans. All OCs are contraindicated in women with histories of gestational diabetes or glucose intolerance. Insulin-dependent diabetes in adolescents is a relative contraindication. Regular surveillance is required of weight and blood sugar for normal women using OCs. Estrogens have been the major factor identified in variations of coagulation factors and fibrinolysis in OC users. Platelet aggregation has been less well studied. OCs should be avoided in case of hypercoagulative states of platelet hyperaggregation.
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PMID:[Metabolic risks of oral contraception]. 1228 76

The major side effects due to estrogens in oral contraceptives are summarized, (thromboembolism, hypertension, diabetes, lipid metabolism, liver function) 2 retrospective studies on thromboembolism are reviewed. Estrogens decrease bile flux in the liver, which can become manifest as jaundice or pruritus, and may be the cause of abnormal synthesis of proteins by the liver. Glucose tolerance decreases and insulinemia rises in 30% of users after 2 years and in 80% after 5 years, often revealing latent diabetes or causing obesity. Plasma fatty acids and triglycerides increase, and in the predisposed, hyperlipidemia may appear. Hypercoagulability results from increased synthesis of clotting factors by the liver and thromboembolism may become more likely because of hypertension, obesity and lesions in the veins. Hypertension seems due to increased output of angiotensinogen by the liver and aldosterone by the adrenal. A British retrospective study on less than 10% of known thromboembolism cases implicates estrogen doses above 50 mcg, but found several contradictions.
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PMID:[Are estrogens responsible for incidents observed under combined estrogen-progestagen treatment?]. 1230 14

This review consists of an explanation of the significance and sources of blood lipids and lipoproteins and an evaluation of the effects on triglycerides, cholesterol, and phospholipids of estrogens and progestagens taken combined or separately by normal or hyperlipidemic subjects. Normal blood contains alpha and beta lipoproteins (binding cholesterol and phospholipids) in morning, and chylomicrons (with dietary triglycerides) and prebeta-lipoproteins (with endogenous triglycerides) after a meal. Estrogens or combined pills raise triglycerides to 1.5 gm per 100 ml, the upper range of normal limits, due to an elevation of heavy prebeta-lipoproteins (0-12 SF). Th is elevation may be related to decreased lipoprotein lipase (post-heparin-lipolytic activity) seen in women taking estrogen. Heightened triglycerides have been observed in mixed and endogenous hyperlipidemia and types 1, 4, 5 (Frederickson classification), but not essential or type 2 hyperlipidemia. Progestogens lower triglycerides and raise lipoprotein lipase in normal subjects and in those with endogenous hyperlipidemia type 5. Results of studies of total cholesterol are variable: androgenic progestogens decrease cholesterol, but other progestagens increased it in some studies. A norethisterone and ethinyl estradiol combination has been shown to raise high- and very high-density lipoproteins, cephalin and lecithin, but to depress lyso-le cithin. Besides altered lipoprotein lipase, these lipoprotein changes c ould be due to elevated insulin, cortisol, thyroxin, or growth hormone, or their protein carriers.
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PMID:[Study of metabolism of circulating lipids during oral contraception]. 1230 67


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