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For women beyond the desire for childbearing, the contraceptive options are discussed as appropriate for the age and in light of risks and benefits. Reeducation and careful history taking are important. A pregnancy for a woman 40 years places a woman at greater risk for an elective abortion and greater risk of maternal mortality from abortion; low dose contraceptive use can have beneficial effects for menopausal women. Methods are grouped as contraceptive steroids (combination pills, progestin-only pills, oral preparations, implants, and injections), IUDs, barrier methods (diaphragms, cervical caps, vaginal sponges, spermicides, and contraceptive film), condoms, sterilization, and natural family planning. Empowering women means providing current scientific information and urging women to examine their lives, and to review how and why contraceptive choices were made, and the consequences of the choices. Sexually transmitted disease counseling is appropriate for women in new relationships. A positive attitude toward menopause needs to be conveyed. Combination pills at the lowest dose possible are recommended for women 35 years who are healthy, nonsmoking (or smoking 15 cigarettes/day), blood group O, and able to derive benefits from the pill. Benefits include a 30% reduction in uterine fibroids and protection against endometrial cancer, and decreased risk of ectopic pregnancy, pelvic inflammatory disease (PID), and iron deficiency anemia. Multivitamin use with the pill is recommended due to reduced liver stores of vitamin A. Women 40 years with a parent dying of cardiac disease 50 years or with a history of hypertension, diabetes, or hyperlipidemia are not suitable candidates. 35 mcg preparations are recommended for women 35-45 years, and 20 mcg for women over 45 years. Progestin-only pills are recommended for those with contraindication to estrogen, but have a higher pregnancy rate. IUD use among older women may be difficult due to cervical or pelvic surgery; there is a higher incidence of PID and ectopic pregnancy with IUD use. Barrier methods are more successful for older women due to the changing vaginal anatomy. Vasectomy is the safest sterilization procedure.
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PMID:Contraception for midlife women. 159 31

The relation between history of several medical conditions and procedures and risk of breast cancer was evaluated in data from a hospital-based case-control study of 2663 cases of breast cancer and 2344 controls with acute conditions unrelated to any of the established or potential risk factors for breast cancer. Whereas previous diagnosis of diabetes mellitus, thyroid disease, hypertension at any age, hyperlipidaemia, cholelithiasis, pelvic inflammatory disease and physician-diagnosed subfertility were unrelated to cancer risk, history of severe obesity in postmenopausal women (odds ratio [OR] 1.4), benign breast disease (OR 1.8) and history of breast biopsies (OR 2.4) were associated with significant risk elevation. Conversely, lifelong history of menstrual irregularities (OR 0.6) seemed to confer some protection against onset of breast cancer. This study supports the hypothesis that, unlike endometrial cancer, breast cancer risk is not enhanced by medical conditions known or suspected to be linked with female hormones, with the exception of benign breast disease and severe overweight in postmenopausal women.
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PMID:Breast cancer risk and history of selected medical conditions linked with female hormones. 214 95

As is obvious from the previous discussions, obesity is associated with a wide variety of changes in endocrine parameters (Table 1). Some of these changes, such as the reduction in SHBG without change in serum free testosterone levels, reflect merely laboratory abnormalities that may influence interpretation of diagnostic tests but have no important physiologic relevance. Other abnormalities have major clinical impact, such as hyperestrogenemia-endometrial carcinoma and hyperlipidemia-coronary artery disease. In some cases, endocrine changes in obesity are beneficial--that is, hyperestrogenemia leading to lower incidence of osteoporosis. In other cases, such as the profound suppression of growth hormone output in obesity, the physiologic relevance is unknown. Several endocrine changes in obesity, such as the impaired response of many hormones (growth hormone, prolactin, vasopressin, corticotropin) to insulin-induced hypoglycemia and elevated endorphin levels, suggest hypothalamic dysfunction. Furthermore, the failure of all of these abnormalities to be normalized after weight reduction raises the possibility of an underlying disorder leading to both endocrine dysfunction and obesity, rather than the endocrine dysfunction being simply a consequence of the obesity. Successful elucidation of the pathogenesis of obesity, which might then lead to much needed specific treatment modalities, may be advanced if we can solve some of these puzzles.
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PMID:Endocrine aspects of obesity. 264 1

Current research on lipid alterations and the risk of ischemic cardiopathy is reviewed, and the relationship of such cardiopathy to exogenous hormonal treatment is examined. Most large epidemiological and intervention studies have focused on men. Men and women share some risk factors, including high serum cholesterol levels, adverse lipoprotein profile, smoking, hypertension, diabetes, obesity, advanced age, and according to some studies sedentary life style. Additional factors that may affect women more than men are elevated serum triglyceride levels, natural or surgical menopause, use of oral contraceptives (OCs), and possibly hormonal substitution therapy. Studies have revealed a characteristic female profile of lipids and lipoproteins that follows a predictable course with age and menopause. Average total cholesterol and LDL cholesterol are higher in men than in premenopausal women, but women's levels rise after menopause until they eventually exceed those of men. According to epidemiological study and clinical trials over the past 2 decades, the principal determinants of serum lipid levels and hyperlipidemia are similar for both sexes and include diet, smoking, physical exercise and other habits, and genetic factors. Lipid levels in women are also affected by endogenous estrogens, high-dose OCs, estrogen replacement therapy, and menopause. Several studies have shown that high serum concentrations of total and LDL cholesterol and relatively low levels of HDL cholesterol are correlated with development of atherosclerotic lesions and increased cardiovascular risk in men, and that lowering cholesterol reduces the risk. Thus far there are no conclusive studies demonstrating the benefits of reduced cholesterol levels for women, but studies that included women along with men suggested that they share the benefits. Low levels of HDL cholesterol and elevated serum triglyceride levels appear to be important predictors of ischemic cardiopathy in women. The coronary risk in former OC users does not appear to be higher than that of women who never used OCs. It is likely that the lower-dosed formulations now in use will mitigate the risk. The adverse effect of OCs on lipid levels appears to be related to the androgenicity of the progestin. Most of the progestins used in combined pills are related to the 19-nortestosterone group which tends to decrease HDL level and increase LDL and triglyceride levels. Many studies have demonstrated that postmenopausal use of estrogens alone result in a decrease in LDL and an increase in HDL levels. Most but not all studies have shown that hormonal substitution reduces risks of coronary disease. But the longterm effects of estrogen/progestin use, now recommended to avoid increased risk of endometrial cancer, are not known.
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PMID:[Women and ischemic cardiopathy]. 269 94

Mechanism of action, indications, side effects and contraindications of oral contraceptive agents (OCA) are reviewed. OCA can be divided into two groups: consecutive and combined agents. Combined OCA contain both estrogens and gestagens and are taken for 3 weeks, while consecutive OCA contain only estrogens and are taken for 2 weeks followed by 1 week of combined OCA until the onset of menstruation. Biological activity of synthetic gestagens is estimated by a dosage which results in a delay of menstruation by 2 weeks. Gestagens norethindrone and norethynodrel were shown to be equally effective, while ethinodiol diacetate and norgestrel were 15-30 times more effective. Estrogen component of OCA is represented by ethinyl estradiol or mestranol. Combined OCA are more effective than consecutive OCA; probability of undesirable pregnancy during administration of combined OCA does not exceed 0.2%. The most frequent side-effects of OCA include nausea, headache, uterine hemorrhage, and changes in libido. OCA can affect the endocrine and reproductive systems. Major endocrine effects of OCA include changes in the cortisol metabolism in the adrenal glands, increase in the level of thyroid-binding globulin in the thyroid gland, changes in the glucose metabolism in the pancreas, inhibition of the luteinizing hormone releasing hormone in the hypothalamus with simultaneous decrease in the production of pituitary gonadotropins and inhibition of the ovulation. The most serious side-effects of OCA include cholelithiasis, thrombophlebitis, thromboembolism, liver adenoma, and myocardial infarction. Absolute contraindications to the use of OCA include hypertension, hyperlipidemia, breast or endometrial cancer, pregnancy, cardio-vascular diseases, liver diseases, and kidney insufficiency.
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PMID:[Principles of the use of oral contraceptive preparations]. 307 80

The author presents a hypothesis that the complex of endocrine and metabolic disturbances arising long before the development of endometrial carcinoma determines the biological peculiarities of the tumor, its clinical course, and the prognosis of the disease. On the basis of a prospective study of 366 patients with endometrial carcinoma, the author postulates that there are two different pathogenetic types of endometrial carcinoma. The first pathogenetic type of the disease arises in women with obesity, hyperlipidemia, and signs of hyperestrogenism: anovulatory uterine bleeding, infertility, late onset of the menopause, and hyperplasia of the stroma of the ovaries and endometrium. The second pathogenetic type of the disease arises in women who have no signs stated above or these signs are not clearly defined. The frequency of the first pathogenetic type in the studied group of women was 65%, whereas the frequency of the second type was 35%. The peculiarities outlined above which are characteristic of the first pathogenetic type of the disease determine the development of highly and moderately differentiated tumors (82.3% G1 and G2), superficial invasion of the myometrium (69.4%), high sensitivity to progestogens (80.2%), and favorable prognosis (85.6% 5-year survival rate). In patients who have the second pathogenetic type of endometrial cancer when endocrine and metabolic disturbances are absent or occult, poorly differentiated tumors arise (62.5% G3), a tendency to deep invasion of tumor into the myometrium is observed (65.7%); high frequency of metastatic spread into the pelvic lymph nodes (27.8%); decrease of sensitivity to progestogens (42.5%); and doubtful prognosis (58.8% 5-year survival rate) are noted.
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PMID:Two pathogenetic types of endometrial carcinoma. 682 61

Indications and complications of estrogen replacement therapy are discussed in this edited transcription of a conference held at the UCLA School of Medicine. Although many of the symptoms of loss of ovarian function can be corrected by estrogen replacement therapy, several potentially harmful side effects are associated with the administration of estrogen. Hot flashes, the most common menopausal symptom for which women seek treatment, may continue over extended periods of time and the loss of ovarian feedback signals. Several types of evidence indicate that hot flashes are centrally rather than peripherally mediated disturbances, and it now appears that the hypothalamic factors which stimulate pulsatile release of luteinizing hormone play an integral role in initiation of hot flashes. The fact that the extent of estrogen deficiency differs among postmenopausal women may explain why all women do not have hot flashes. The effects of body size on estrogen production and plasma protein binding appear to be significant variables modulating the extent of estrogen deficiency and hypothalamic function. Other studies suggest that calcitonin and gonadal steroids are linked in the pathogenesis and treatment of osteoporosis, but the mechanism of action of estrogen replacement therapy in the treatment of osteoporosis has not been elucidated. Most investigations have failed to show the presence of estrogen receptors in bone. It is likely that the term osteoporosis includes heterogeneous skeletal disorders and that both sex hormones and calcemic hormones are important in pathogenesis. Further research is required on the possible effect of estrogen replacement therapy in decreasing relative risk of arteriosclerotic heart disease. Vaginal atrophy is an accepted indication for estrogen replacement, but its use for skin indications should not be recommended until a beneficial cosmetic effect is shown. Complications of estrogen replacement include endometrial cancer, breast cancer, hypertension, hyperlipidemia, and gallbladder disease, the latter 3 apparently resulting from hepatic action of estrogen replacement therapy. Because of the enhanced hepatic action of orally administered estrogen, other routes of administration are being explored. Additional research is needed to define the risk-benefit ratio of estrogen replacement therapy.
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PMID:Estrogen replacement therapy: indications and complications. 682 55

Recent cohort and case control studies of low-dose combined oral contraceptives (COCs) containing the new generation of progestogens have allowed classification of adverse effects into those which are rare but serious and should be considered risks and those which are more frequent but are less of a threat to health. Low-dose COCs continue to affect coagulation in a complex way, but the risk is less than with the older preparations, and it can be minimized by screening women for a personal or familial history of early or unusual thrombosis and for levels of protein C, S, and antithrombin III. Women with true migraine with focal signs should also avoid using COCs. The relative risk of myocardial infarction (MI) may increase from 4:1 in women with one risk factor (age, smoking, hypertension, hyperlipidemia, and diabetes) to 20:1 with two risk factors and 128:1 with three or more risk factors. In the absence of all risk factors, a recent study indicated that the relative risk of MI with COC use was 1.9 for current and past use. COC use also causes a slight increase in hypertension in most women, especially those who are older or have a family history of hypertension. While the COC can affect carbohydrate and lipid metabolism, the new generation of progestogens has reduced these effects. The COC may accelerate presentation of gallbladder disease in predisposed women. The COC protects against benign breast disease but may increase the risk of breast cancer and cervical cancer slightly. There is a strong link between hepatocellular adenoma and COC use, but the incidence is low. Return to fertility after use has not been a problem. Both estrogenic adverse effects (nausea, dizziness, irritability, weight gain, bloating) and progestogenic adverse effects (vaginal dryness, acne, hirsutism, weight gain, depression, loss of libido) can occur in 50% of women, but these generally disappear after a few months of use. In conclusion, the low-dose, third generation COCs are associated with minimal risks in the absence of other risk factors and have many beneficial effects such as the prevention of ovarian and endometrial cancer; a decrease in pelvic inflammatory disease and ectopic pregnancies; and protection from anemia, primary dysmenorrhea, functional ovarian cysts, and benign breast disease as well as from the morbidity and mortality associated with pregnancy.
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PMID:The combined oral contraceptive. Risks and adverse effects in perspective. 776 40

Obesity is associated with the development of some of the most prevalent diseases of modern society. The greatest risk is for diabetes mellitus where a body mass index above 35 kg/m2 increases the risk by 93-fold in women and by 42-fold in men. The risk of coronary heart disease is increased 86% by a 20% rise in weight in males, whereas in obese women the risk is increased 3.6-fold. Elevation of blood pressure, hyperlipidaemia and altered haemostatic factors are implicated in this high risk from coronary heart disease. Gallbladder disease is increased 2.7-fold with an enhanced cancer risk especially for colorectal cancer in males and cancer of the endometrium and biliary passages in females. Endocrine changes are associated with metabolic diseases and infertility, and respiratory problems result in sleep apnoea, hypoventilation, arrhythmias and eventual cardiac failure. Obesity is not a social stigma but an actual disease with a major genetic component to its aetiology and a financial cost estimated at $69 billion for the USA alone.
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PMID:Obesity as a disease. 924 38

Polycystic ovary syndrome (PCOS) is the most common endocrine condition of premenopausal women and has significant metabolic abnormalities that could have an impact after the menopause. Diabetes mellitus, hyperlipidemia and hyperinsulinemia could potentially affect health in this era of life. Endometrial cancer, due to unopposed estrogen action, is more common where progestins have not been given for menstrual dysfunction. Preventive management earlier in life will avoid postmenopausal problems in PCOS.
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PMID:Polycystic ovary syndrome and implications for the menopause. 1191 Jun 67


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