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Earlier and more frequent sexual activity and the significant risk of pregnancy have increased the need for contraception among young adolescent girls. The problem for the physician is to choose a contraceptive method which will not affect future fertility or the psychological and biological maturity of adolescents. Condoms, diaphragms, and spermicides are quite effective if used correctly; they have no deleterious side effects, and they provide protection against sexually transmitted diseases. They appear to be well-adapted to the sporadic sexual activity of adolescents. The efficacy of combined oral contraceptives (OCs) is also high. Side effects depend on the synthetic estrogen component and are dose dependent. Absolute contraindications to OC use in women of any age include thromboembolic disease, cerebral vascular accidents, severe cardiac or hepatic disorders, breast or genital cancer, pregnancy, undiagnosed genital bleeding, and pituitary adenoma. Relative contraindications include hypertension, diabetes, hyperlipidemia, obesity, history of hepatitis, migraines, epilepsy, asthma, renal insufficiency, cystic breast disease, and mammary fibroadenomas. Combined OCs do not seem to interfere with subsequent maturation of the hypothalamopituitary axis. The frequency of ovulatory cycles in adolescents who have discontinued pill use is the same as that in adolescents who have never used pills. However, estrogens accelerate the process of maturation in the bones, so combined OCs should never be prescribed for girls who have not terminated their growth. Minidose OCs containing 30-45 mcg of ethinyl estradiol aggravate the relative hyperestrogenism of adolescents and are associated with menstrual problems, functional ovarian cysts, and breast problems. They should only be prescribed for adolescents with regular sexual activity, no less than 3 years following menarche, with regular ovulatory menstrual cycles and no history of breast disorders. Otherwise, a standard-dose combined pill with 50 mcg EE should be selected. Continuous dose progestin minipills depend on peripheral effects such as modifications in the cervical mucus for their contraceptive effects. They are associated with frequent menstrual problems, functional ovarian cysts, and extrauterine pregnancies. They may be indicated for adolescents with regular sexual activity but with contraindications to combined OCs. Trimonthly injections of medroxyprogesterone acetate have major effects on endocrine metabolism and should be used only for adolescents with severe mental problems. IUD efficacy is high but they may be less well tolerated by adolescents than by older women and the risk of infection may be heightened. They should only be used for adolescents with absolute contraindications to use of hormonal contraceptives who have no history of genital infections.
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PMID:[Choosing contraception for adolescents]. 1228 May 85

The main concern of physicians prescribing oral contraceptives (OCs) is the possibility of cardiovascular accidents, not because of their number but of their seriousness. Cardiovascular risk affects primarily women over 35. A 1986 survey of 600 physicians indicated that avoiding cardiovascular risk was their main objective when prescribing pills, with avoidance of modifications in lipid and glucose metabolism virtually as great a concern. Less than 50% were concerned with functional symptoms such as spotting which can be managed by therapeutic adjustments. Numerous cofactors participate in cardiovascular risk, including family history, life style, and intercurrent illness. The frequency of vascular accidents is only slightly higher among OC users than in the control population. Numerous Anglo-Saxon studies have found the risk of deep venous thrombosis to be multiplied by 4 or 5 for OC users and of superficial thrombosis to be multiplied by 2 or 3. Age and obesity play no role in the increased risk for OC users, smoking has a minor role, and family history and bed rest are the only major cofactors. Risk of venous thrombosis under OC use does not depend on duration of use and disappears the month after termination of use. The synthetic estrogen is primarily responsible because of the modifications it produces on coagulation factors. OC use increases the risk of coronary accidents by 3 or 4. 3 hypotheses have been advanced to explain the pathogenic mechanism: classic atherogenesis, alteration of the intima, or immunological factors. Atheromatous arterial accidents are related to age, smoking, problems of glucose or lipid metabolism, and blood pressure. The factors have a synergistic effect on each other. Risks increase with duration of use and dose level, and depend also on the biochemical properties of the estrogen and progestin. Some accidents in young women about 30 years old show no relation to duration of use or dose. The only elements differentiating the women involved are smoking, family histories of vascular accidents, and intense headaches in the days before a cerebrovascular accident. They seem to be associated not with atherogenesis but with thickening of the intima secondary to a proliferation of smooth muscle cells with subendothelial fibrosis. 90% of OC users experiencing vascular accidents have been found to have anti-ethinyl estradiol antibodies, compared to 30% of users never having vascular accidents and no nonusers. The practical import of this finding remains undetermined. Under some circumstances the causes of headaches should be investigated and OC use should be terminated. Careful attention to patient selection and development of new progestins with fewer androgenic and metabolic effects should reduce cardiovascular risks from OCs to a minimum. The new synthetic progestin gestodene has given very satisfactory results in a triphasic formulation and should be on the market soon.
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PMID:[Combined contraceptives and cardiovascular risk]. 1231 99

Epilepsy in women raises special reproductive and general health concerns. Seizure frequency and severity may change at puberty, over the menstrual cycle, with pregnancy, and at menopause. Estrogen is known to increase the risk of seizures, while progesterone has an inhibitory effect. Many antiepileptic drugs induce liver enzymes and decrease oral contraceptive efficacy. Women with epilepsy also have lower fertility rates and are more likely to have anovulatory menstrual cycles, polycystic ovaries, and sexual dysfunction. Irregular menstrual cycles, hirsutism, acne, and obesity should prompt an evaluation for reproductive dysfunction. Children who are born to women with epilepsy are at greater risk of birth defects, in part related to maternal use of antiepileptic drugs. This risk is reduced by using a single antiepileptic drug at the lowest effective dose and by providing preconceptional folic acid supplementation. Breastfeeding is generally thought to be safe for women using antiepileptic medications.
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PMID:Epilepsy in women. 1240 23

Elderly women with the lowest serum estrogen levels are at the greatest risk of bone loss and fractures, but it is controversial whether the ovaries contribute to estrogen production after menopause, and therefore, whether bilateral oophorectomy in postmenopausal women might have adverse skeletal effects. To address this potential problem, we estimated long-term fracture risk among 340 postmenopausal Olmsted County, MN, women who underwent bilateral oophorectomy for a benign ovarian condition in 1950-1987. In over 5632 person-years of follow-up (median, 16 years per subject), 194 women experienced 516 fractures (72% from moderate trauma). Compared with expected rates, there was a significant increase in the risk of any osteoporotic fracture (moderate trauma fractures of the hip, spine, or distal forearm; standardized incidence ratio [SIR], 1.54; 95% CI, 1.29-1.82) but almost as large an increase in fractures at other sites (SIR, 1.35; 95% CI, 1.13-1.59). In multivariate analyses, the independent predictors of overall fracture risk were age, anticonvulsant or anticoagulant use for > or = 6 months, and a history of alcoholism or prior osteoporotic fracture; obesity was protective. Estrogen replacement therapy was associated with a 10% reduction in overall fracture risk (hazard ratio [HR], 0.90; 95% CI, 0.64-1.28) and a 20% reduction in osteoporotic fractures (HR, 0.80; 95% CI, 0.52-1.23), but neither was statistically significant. The increase in fracture risk among women who underwent bilateral oophorectomy after natural menopause is consistent with the hypothesis that androgens produced by the postmenopausal ovary are important for endogenous estrogen production that protects against fractures.
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PMID:Fracture risk after bilateral oophorectomy in elderly women. 3026 33

We studied the role of estrogen in the gender differences in insulin resistance observed in the apoB/BATless mouse, a model of obesity, insulin resistance, and hyperlipidemia. Ovariectomized apoB/BATless mice were more obese and more insulin-resistant than sham ovariectomized apoB/BATless mice. Estrogen replacement by subcutaneous pellet reversed the obesity, lowered plasma insulin levels, and normalized both glucose tolerance and insulin sensitivity associated with ovariectomy. The apoB/BATless mouse should be a good model to delineate the molecular mechanisms whereby estrogen protects against insulin resistance.
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PMID:Ovariectomy leads to increased insulin resistance in human apolipoprotein B transgenic mice lacking brown adipose tissue. 1280 87

Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor- (subscript)3(/subscript), basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.
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PMID:Etiology and pathogenesis of uterine leiomyomas: a review. 1282 76

Low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP), has recently been linked to obesity, insulin resistance syndromes such as polycystic ovary syndrome (PCOS), and an increased risk of cardiovascular disease. Because the insulin sensitizer metformin has been shown to improve metabolic disturbances in PCOS, it was of particular interest to examine serum CRP levels during metformin therapy. Twenty nonobese women [body mass index (BMI) </= 25 kg/m(2)] and 32 obese women (BMI >/==" BORDER="0"> 27 kg/m(2)) with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months) or ethinyl estradiol (35 micro g)-cyproterone acetate (2 mg) oral contraceptive pills. The serum concentrations of CRP were significantly higher in obese than in nonobese subjects at baseline [4.08 +/- 0.53 (SE) vs. 1.31 +/- 0.28 mg/liter; P < 0.001] and correlated to BMI and to a lesser extent waist-hip ratio, suggesting that the elevated CRP levels may be related to obesity and not only to PCOS itself. During metformin treatment, serum CRP levels decreased significantly from 3.08 +/- 0.7 mg/liter to 1.52 +/- 0.26 mg/liter at 6 months in the whole study population (P = 0.006) and especially in obese subjects. In contrast, the treatment with ethinyl estradiol-cyproterone acetate increased serum CRP levels from 2.91 +/- 0.68 mg/liter to 4.58 +/- 0.84 mg/liter (P < 0.001). Whether this effect is related to estrogen action in the liver or whether it reflects increased inflammation process and possible risks for cardiovascular disease remains unclear. The decrease of serum CRP levels during metformin therapy is in accordance with the known beneficial metabolic effects of this drug and suggests that CRP or other inflammation parameters could be used as markers of treatment efficiency in women with PCOS.
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PMID:Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome. 1455 35

Stroke morbidity increases with age. That is the reason why it affects especially the middle aged and elderly. Life expectancy is longer for females than males by 10 years, that is why stroke is a major problem in women. Women die twice more frequently from stroke than men (16% vs. 8%). Stroke risk factors are basically the same in spite of gender. The most important are hypertension, diabetes, dyslipidaemia, atrial fibrillation, coronary heart disease, previous stroke, smoking, alcohol abuse, obesity and lack of physical activity. Their impact, however, is different in males and females. Women with diabetes, atrial fibrillation, myocardial infarction, obese, drinking excessive amounts of alcohol and smoking are more likely to suffer of stroke than males with the same burden. A less favourable outcome after stroke has been observed in female patients--higher mortality rates and disability. It is possible that poor prognosis is related to a drop in blood estrogen concentration after menopause. Estrogen replacement therapy has not proved to be beneficial in preventing stroke and improving outcome. There are several specific conditions: pregnancy, migraine in women associated with the occurrence of stroke.
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PMID:[Does gender exert influence on stroke?]. 1456 Jul

Estrogens, acting through its two receptors, ESR1 (hereafter designated ER alpha) and ESR2 (hereafter designated ER beta), have diverse physiological effects in the reproductive system, bone, cardiovascular system, hematopoiesis, and central and peripheral nervous systems. Mice with inactivated ER alpha, ER beta, or both show a number of interesting phenotypes, including incompletely differentiated epithelium in tissues under steroidal control (prostate, ovary, mammary, and salivary glands) and defective ovulation reminiscent of polycystic ovarian syndrome in humans (in ER beta-/- mice), and obesity, insulin resistance, and complete infertility (both in male and female ER alpha-/- mice). Estrogen agonists and antagonists are frequently prescribed drugs with indications that include postmenopausal syndrome (agonists) and breast cancer (antagonists). Because the two estrogen receptors (ERs) have different physiological functions and have ligand binding pockets that differ enough to be selective in their ligand binding, opportunities now exist for development of novel ER subtype-specific selective-ER modulators.
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PMID:Estrogen receptor beta in health and disease. 1603 96

This review presents a comprehensive, evenhanded evaluation of the evidence from experimental, in vitro and human studies associating environmental and therapeutic factors with risk of colorectal cancer. Life styles correlated with the greatest increase in colorectal cancer risk are the ones that typify a diet rich in fat and calories, alcohol drinking and tobacco smoking, and low intake of vegetable, fruits and fibers, referred to as a "western diet," as well as sedentary style (i.e., no- or low-exercise). This kind of life style has also been associated with other chronic diseases (other cancers, obesity, dyslipedemia, diabetes, hypertension cardiovascular, and hypertension). The evidence does not implicated red meat as a risk factor, and fiber has been shown to protect against colorectal adenomas and carcinomas. Calcium, vitamin D, folate, and some antioxidant vitamins and minerals (gamma-tocopherol and selenium) have protective effects, and daily exercise for > or =30 min results in a significant decrease in risk. Estrogen use (hormone replacement therapy) substantially reduces colorectal cancer risk in postmenopausal women. Nonsteroidal anti-inflammatory drugs (e.g., aspirin) in excessive doses is protective, especially in high risk populations, but the side effects of its use and cost incurred due to its continued intake over long periods must be carefully scrutinized before any recommendations are made for the general public.
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PMID:Effect of diet, life style, and other environmental/chemopreventive factors on colorectal cancer development, and assessment of the risks. 1629 19


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