Natural Menopause Relief Secrets

Holistic Hormone Balance

Every woman experiences hormonal imbalance at one point in life. The Holistic Hormone Balance is an essential guide that provides women with the information that they need to know on how to balance their hormones and reduce stress levels, fatigue, excessive weight gain, skin problems and increase desire in intimacy. In addition to that, the book provides women with steps to follow to identify any symptoms of hormonal imbalance and how to create an original and personalized treatment plan that works best for their body. A combination of natural hormone treatment has also been provided in the guide, making it easier for women to choose their best plan, that works best for them. Hormonal imbalance affects the female body and most of the time; they take the issue lightly, thinking that other people have more significant problems than theirs. Imbalance affects moods and creates discomfort in women. The frustration comes from the fact that they cannot do anything to change their situation, and always remain suffering in silence. The Holistic Hormone Balance book works towards helping women with hormone imbalance feel amazing again, by identifying the root cause of their problem and treating the symptoms when they occur. Continue reading...

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What does menopause have to do with osteoporosis Are there different kinds of osteoporosis

Primary osteoporosis, although occurring in both men and women, is age-related and tends to occur mostly in women and about 10 years earlier than in men. This is because the rate of bone loss is different in women than men. Women rapidly lose bone in the four to eight years after menopause, and then continue with the slower rate of bone loss like men, who also experience bone loss over many years. Bone loss from primary osteoporosis is most common in the hip, but can affect all bones in the body. Menopause The time following menopause, when women rapidly lose bone and may develop osteoporosis. Estrogen-containing products used in the treatment of perimenopausal and menopausal symptoms. Estrogen taken for this purpose is called MHT (menopause hormone therapy). Sensations of heat, occurring during perimenopause and often well into post-menopause, that begin at the head and spread over the entire body. Sweating that occurs at night resulting from hot flashes during peri-menopause and...

Climacteric and Menopause

Nied by menopause, the cessation of menstruation (see insight 28.2). With age, the ovaries have fewer remaining follicles and those that remain are less responsive to gonadotropins. Consequently, they secrete less estrogen and progesterone. Without these steroids, the uterus, vagina, and breasts atrophy. Intercourse may become uncomfortable, and vaginal infections more common, as the vagina becomes thinner, less distensible, and drier. The skin becomes thinner, cholesterol levels rise (increasing the risk of cardiovascular disease), and bone mass declines (increasing the risk of osteoporosis). Blood vessels constrict and dilate in response to shifting hormone balances, and the sudden dilation of cutaneous arteries may cause hot flashes a spreading sense of heat from the abdomen to the thorax, neck, and face. Hot flashes may occur several times a day, sometimes accompanied by headaches resulting from the sudden vasodilation of arteries in the head. In some people, the changing hormonal...

Menopausal Cognitive Impairments

Many middle-aged women report that during menopause, whether naturally occurring or surgically induced, they experience for the first time a constellation of persisting symptoms that closely resembles ADD syndrome. They note significant declines in short-term memory, in the ability to screen distractions and to sustain attention, in the organization and prioritizing of tasks, and so on. Some of these women are very competent, well-educated professionals and business executives who until menopause have never experienced significant impairments of ADD syndrome. In addition, women who have been diagnosed before menopause with ADD often report that their ADD symptoms tend to worsen for several days each month at about the time their estrogen level is probably lowest. As they enter menopause, many of these women also report significant exacerbation of their long-standing ADD symptoms. Basic neuroscience research by Bruce McEwen (1991) suggests that estrogen plays an important role in the...

Have early menopause What does this mean for my bones and will I need treatment

Whether your early menopause (also called premature menopause) is caused by surgery, is for unknown reasons, or because of cancer treatments, your bones are at risk and you may need treatment. When you are trying to cope with the treatments for cancer, it's hard to think about your bones and the possibility of developing osteoporosis so early in life. But the fact is that when you stop having your menstrual periods for whatever reason, your risk of bone loss increases. When you experience a natural menopause around the average age of 51, you can expect to lose bone most rapidly in the 4 to 8 years following menopause (starting one year after your last period). There are several reasons why you might experience menopause much earlier than that and, therefore, need to cope with a larger stretch of your life without estrogen, an important hormone for bone growth. A very small percentage of women (1 ) experience natural menopause before the age of 40. It is not known why these people stop...

Perimenopausal Stage

Estradiol and testosterone parameters during the menopausal transition. The concentrations of estradiol and testosterone, their blood production rates, and their metabolic clearance rates are shown for women at various indicated phases of perimenopause. FSH, follicle-stimulating hormone. (Data from ref. 32.) Burger and associates (35) also conducted longitudinal studies of women through the menopausal transition. As found by others, they noted little, if any, change in total testosterone levels leading up to, during, and for several years after menopause. However, reductions in SHBG levels were observed in concert with the reduction in estradiol observed leading up to the menopause and thereafter. The net effect of declining SHBG levels in the face of unwavering levels of testosterone is to increase the free testosterone fraction by 80 over the interval beginning 4 years prior to menopause and ending 2 years after the menopause. If free testosterone levels are actually...

Correlation With Pathology

The adult female breast is a large, modified sebaceous gland that consists mostly of fat, fibrous septa, and glandular structures. The weight range for a normal, mature female breast is 30 grams to over 500 grams, depending on the woman's body habitus. The breast typically comprises 15 to 25 lobes that are divided into multiple lobules, each containing 10-100 terminal milk-secreting alveoli. Numerous tiny milk-transporting ductules combine to form a single lactiferous duct that exits each lobule. About 15 to 25 such ducts converge at the nipple. The composition of the breast varies from individual to individual and with age and other factors. Pregnancy, lactation, menstruation, and menopause all introduce characteristic changes in breast physiology. For example, in postmenopausal involution of the breast, the lobular and alveolar structures regress and the vascularity of the intervening connective tissue is reduced. Eventually only small, occasional islands of functional breast...

Auguste Ds case history

Auguste D. was admitted to the clinic in Frankfurt on November 25, 1901. The case history in the file reads as follows D., Auguste, wife of an office clerk, aged 51-and-a-half years. The patient's mother suffered convulsive attacks after menopause it seems that she did not lose consciousness and did not drop objects that she was holding in her hands. Her mother died at the age of 64 of pneumonia her father died at the age of 45. Three healthy brothers. No alcoholism or mental illness in the family history.

Examples Two Prognostic Studies in Breast Cancer

We consider the data of two studies of patients with node-positive breast cancer. The first, a clinical trial GBSG-2 study, n 686 patients, 299 events for event-free survival (EFS) is used to identify prognostic markers and to investigate the influence of different model-building strategies. This dataset was used previously for prognostic modelling for example, by Sauerbrei and Royston (1999) and Schumacher et al. (2006) and is available at The data of the second, smaller Freiburg-DNA study (n 139 patients, 76 events for EFS) are exclusively used to validate the results obtained in the GBSG-2 study. Prognostic markers evaluated in both studies were patient's age, menopausal status, tumour

Distribution in Tumors

In the Mainz experience, oxygen tensions measured in the normal breast of16 patients revealed a mean (median) pO2 value of 65 mmHg in 18 cancers of the breast (stages pT 1-4), the median pO2 was 28 mmHg. Six of 18 breast cancers exhibited pO2 values between 0 and 2.5 mmHg. Thirty-three percent of the tumors investigated contained hypoxic areas, and the proportion of pO2 readings between 0 and 2.5 mmHg ranged from 4 (in a T4 breast cancer) to 64 (in a T3 tumor). Furthermore, the oxygenation patterns did not correlate with the histological grades, menopausal status, tumor histology (ductal vs lobular), or extent of necrosis or fibrosis (49,56).

Regression models standard applications

BE(0.01) yields the same model as BE(0.05) when a linear effect is assumed, whereas only two markers (number of lymph nodes, progesterone receptor) were selected with BE(0.01) for categorised data (Table 2.2). Applying BE(0.157) in the latter situation, age and menopausal status were included in the selected model, but both markers were eliminated when assuming a linear effect. However, tumour size is now included. Assessing models by BIC, the smallest model would be preferred due to the large penalty term for additional markers the smallest AIC value was obtained with BE(0.05) for categorised covariates. However, in spite of the better fit, the categorisation can always be criticised because of some degree of arbitrariness and subjectivity concerning the number of cutpoints, the specific cutpoints chosen, and a loss of information see Royston, Altman, and Sauerbrei (2006) .

Summary assessment implication of the modelling strategy

Menopausal status p Number of covariates in the model, n denotes effective sample size n 299. t Except for menopausal status, which is binary grade coded 1,2,3. HR given without confidence intervals for better illustration only. *, ** Likelihood ratio test significant at significance level * a 0.05 and ** a 0.01. Menopausal status

Effect Of Estrogen Deficiency

Ovarian steroids are important in the normal maintenance of brain function in basal forebrain regions affected by AD. Estrogen promotes the growth of cholinergic neurons and protects against the formation of Ap (Simpkins et al., 1997 Jaffe et al., 1994). In guinea pigs, ovariectomy led to increased levels of Ap-peptides, Ap1-40 and Ap1-42, and this effect was reversible with exogenous estrogen treatment (Petanceska et al., 2000). Studies of postmenopausal women in the general population have shown that estrogen replacement therapy (ERT) may delay or prevent the onset of AD (Tang et al., 1996). Several studies have shown that women with DS experience menopause 4-5 years earlier, on average, than women in the general population, which may contribute to their high risk of AD (Carr and Hollins, 1995 Schupf et al., 1997). Cosgrave et al. (1999) found that earlier menopause is associated with earlier onset of AD, supporting the hypothesis that endogenous estrogen deficiency may accelerate...

Estrogen Replacement Therapy for Breast Cancer Survivors

Ninety percent of women will live to the climacteric age, compared to only 30 percent 200 years ago. Attrition and aging of ovarian follicles results in termination of the maturation of granulosa cells, which are responsible for estrogen production. Sources of estrogen in the pre-menopausal woman are several fold, including direct production of estradiol by the ovaries as well as the extraglandular aromatization in adipose cells of androstenedione created in the adrenal glands and ovary. The hallmark of menopause is a drop in ovarian production of estriol and testosterone. Peripheral aromatiza-tion of other steroids not produced by the ovaries is an additional source of estrogen in all women. However, this source is not sufficient in most women to prevent the symptoms characteristic of estrogen deprivation. Given the current population, 30 million women in the United States will spend approximately 40 percent of their lifetime in the post-menopausal period. These women have a lifetime...

Im 60years old Is it really worth it to start exercising now Will exercise at my age help prevent osteoporosis

Absolutely Exercising will help you no matter how old you are. Although exercise has been encouraged for many years as part of a healthy lifestyle, we are just beginning to quantify its positive effects on heart disease, obesity, diabetes, menopausal symptoms, and of course osteoporosis. It is never too late to incorporate regular exercise into your lifestyle. It's easy for us to say that we're too old to begin exercising at our age, but that is not true. If you don't already have osteoporosis or osteopenia, exercise is still important even though exercise alone doesn't prevent bone loss. When you are well past the first 4 to 8 years after menopause, during which the greatest amount of bone loss occurs, and if you don't have osteoporosis, you are less likely to develop osteoporosis. If you are only a few years into post-menopause, you may still lose enough bone to be diagnosed with osteoporosis later. Regardless of how many years you are past menopause, get moving And if you're a man,...

Benefits Versus Toxicity And Risks Of Therapy

The most common chronic chemotherapy toxicity is the cessation of menses and induction of menopause in premenopausal women. This is more common with 6 months of CMF (and CAF) than with AC x 4. In one study, amenorrhea was seen in 68 percent of women on CMF and 34 percent of women on AC.60 Symptomatic cardiomyopathy is a rare complication seen with doxorubicin-containing regimens. The risk is less than 1 percent with cumulative doxorubicin doses less than 350 mg M2.61 The cumulative dose with AC x 4 is 240 m2 with CAF, it is 360 m2. The risk is increased with age, left chest wall irradiation, and prior heart disease. Chemotherapy agents are carinogenic in experimental systems. Nev ertheless, the incidence of second malignancies has been low. The ECOG estimated the risk of secondary leukemia or myelodysplasia after its CMF adjuvant regimens to be less than 0.2 percent similar to that of the general population.62 Bonadonna could find no increased risk of malignancy in long-term follow-up...

Can I change any of my risk factors

You cannot change your age, gender, sex, race, fracture history, family history, menstrual history, time of menopause, genetic factors, and most medical conditions. You can, however, change some risk factors because most of them are related to lifestyle. Here's what you can do to lower your risk of developing osteoporosis or low bone mass Well, being black, I didn't really think it was a big problem for me. But my girlfriend just found out she has osteoporosis, and she has to take medication for it She told me to get tested, so I talked to my doctor about it. He said we don't need to test for it until after my periods stop, that the estrogen I have in my body helps protect my bones, but that after the estrogen goes down due to menopause, then I will need to be tested I asked what else I can do to protect my bones now and he said regular exercise, Vitamins C and D, and calcium. And he said it is good that I dont smoke. So I learned that I can be at risk, too

Are there blood and urine tests that can be used to determine if I have bone loss

By measuring the byproducts of bone breakdown (usually in the urine) and bone formation (usually in the blood), the rate of bone turnover can be determined. If bone turnover is very rapid, like it is in women following menopause, the quality of bone may be poor, thus increasing the risk for fracture. If bone turnover is very rapid, like it is in women following menopause, the quality of bone may be poor, thus increasing the risk of fracture.

Im worried that my daughter who is 40 will get osteoporosis How can she prevent this from happening to her

Women beginning midlife should make themselves aware of all the risk factors for developing osteoporosis. First, at the age of 40, unless she is one of the 1 who experience premature menopause (natural and total cessation of menstrual periods before the age of 40), she is likely to still be making the necessary estrogen to protect her bones. She should continue to take adequate calcium and Vitamin D for her age, which means 1,000 to 1,200 mg of elemental calcium and 400 IU of Vitamin D per day. This may mean assessing her diet and supplementing it if she does not get enough calcium through dairy products and other foods (see Table 4 in Question 48). If she smokes, she should stop. If she drinks excessive alcohol, she should stop that, too. Equally important, she should develop an exercise routine that puts the necessary stress on her bones for them to continue to remodel appropriately. Making exercise a habit is critical to keeping bones strong through midlife and beyond (see...

Adapting National Guidelines to Local Needs

'Among Group Health Cooperative women 40 years of age who completed the risk factor questionnaire by 1987 (n 55 875) but excluding women with a history of breast cancer (n-1 460) or for whom information was missing (n 1704). MRF, minor risk factors. Second-degree relative with breast cancer menarche age s 10 years or menopause s30 years previous negative breast biopsy. 'Among Group Health Cooperative women 40 years of age who completed the risk factor questionnaire by 1987 (n 55 875) but excluding women with a history of breast cancer (n-1 460) or for whom information was missing (n 1704). MRF, minor risk factors. Second-degree relative with breast cancer menarche age s 10 years or menopause s30 years previous negative breast biopsy.

Dysfunctional Uterine Bleeding

Pelvic infection, or some complication of pregnancy. It may occur at any age between menarche and menopause (Lewis and Chamberlain, 1990). Lewis and Chamberlain (2004) go on to explain that heavy or irregular bleeding without abnormal physical signs on ordinary examination will always suggest this diagnosis, but must never be taken for granted, as curettage may reveal that there is a local cause for the bleeding after all. In anovulatory cycles, which can occur for all women, normal amounts of oestrogen are secreted, but the egg may not ripen in the follicle. As an egg is not released, progesterone is not produced from the corpus luteum to counteract the proliferation of the uterine lining. In time the uterine lining outgrows its blood supply, and sloughs off at irregular intervals. Anovulation may be a result of inadequate signals, for example as a result of polycystic ovarian disease, or it may be pre-menopausal. It may also be caused by impaired positive feedback, for example in...

Asymmetric Division During Initiation of Oogenesis in Fetal and Adult Human Ovaries

It is now well documented that mammalian primordial germ cells in developing embryonic gonads originate from uncommitted (totipotent) somatic stem cells, and that their sex commitment is determined by local gonadal environment -signals produced by neighboring somatic cells (Alberts et al. 2002). Once committed to become female germ cells, these primordial germ cells are believed to multiply in human fetal ovaries and differentiate into definitive oocytes persisting until menopause. Yet the children born to women after the age of 35, but not before, are known to accumulate genetic alterations, which may originate from accumulation of alterations in persisting eggs. This indicates that until 35 years of age fresh oocytes and primary follicles are formed replacing aged ones in ovulatory ovaries. We observed that, even in midpregnancy human fetal ovaries, new germ cells are formed by asymmetric division of OSE stem cells (Bukovsky et al. 2005a, 2006). Such fetal oocytes associate with...

Combined Chemohormonal Therapy

The 1995 EBCTCG overviews looked at the relative benefits of adjuvant combined chemo-hormonal therapy versus single-modality treat-ment.19'31,38 There was a suggestion that in women aged 50 to 69 years, tamoxifen plus chemotherapy decreased the annual risk of death by 10 percent compared with tamoxifen alone.31 The issue was prospectively studied in newer trials. The NSABP, SWOG, and the International Breast Cancer Study Group, each found benefit in their studies of combined therapy versus tamoxifen alone in postmenopausal women 44-46 the National Cancer Institute (NCI) of Canada did not.47 While it is premature to suggest that all postmenopausal women with receptor-positive cancer should receive chemotherapy and tamoxifen certainly, it is appropriate in selected high-risk women under the age of 70 years. The best way to combine the two, simultaneously or sequentially, still remains unresolved. ized study in premenopausal women with hormone-sensitive, node-positive breast cancer....

Breast Reconstruction

Increased detection of breast cancer has paralleled improved techniques and availability of screening mammography, an increased female population, and the impact of changes in the age of childbearing, menarche, and menopause. Today, ductal carcinoma in situ (DCIS) represents 15 to 20 percent of all breast cancer cases 1 it is treated by either localized resection or total mastectomy. Genetic testing and better elucidation of risk factors has identified additional patients as potential candidates for prophylactic mastectomy. As many as 15 percent of patients undergoing breast conservation, and who require a proportionately large lumpec-tomy, attain poor esthetic outcome and may be better served in the longterm, by preoperative consideration of completion mastectomy and autologous reconstruction.2 Included in this group are patients with small breasts, proportionately large lesions, and centrally located lesions. These women, often having been diag

Multiple Routes to Impaired Executive Functions

These studies show that many impairments of executive function seen in ADD syndrome can occur in persons who did not have ADHD in their earlier years. For some, head injuries, the hormonal changes of menopause, or cognitive changes of old age create a cluster of impairments that looks very much like ADD without the lifespan history of symptoms. It seems likely that severe chronic substance abuse and a variety of other psychiatric or medical disorders may have similar damaging effects on executive functions. It also seems likely that external challenges like these would cause some individuals who have a lifelong history of ADD syndrome to experience a worsening of their ADD symptoms. I am suggesting that impairments of executive functions are a larger aspect of many psychiatric and learning disorders than has thus far been recognized. If accurate, this interpretation may have important implications for treatment of persons with other disorders. Perhaps some treatments demonstrated...

Microbiology And Pathogenesis

Normal variations in cervical-vaginal flora are related to the effects of age, pregnancy, and menstrual cycle (2). During early childhood, the normal flora is similar to that of adolescents or adults and includes Enterobacteriaceae and anaerobes. The prepubescent vagina is more supportive of growth of anaerobic bacteria, especially Bacteroides spp., than in adults (3). Also often recovered at that age group is S. epidermidis. In contrast yeasts and Gardnerella vaginalis are isolated in 10 of females (3). The microflora in females before puberty, during the child-bearing years, pregnancy, and after menopause are not uniform. Colonization with lactobacilli is low in prepubertal females and postmenopausal females and high in pregnant women as well as those in their reproductive years who are not pregnant.

Developmental View Of Womens Health And The Menstrual Cycle

Analogously, differential androgen production in men and women is implicated in central nervous system sexual differences evident in brain structure, physiology, and vascular patterns. Finally, the clinical observation that mothers, daughters, and sisters often resemble one another with respect to their ages at onset of menarche and at onset of menopause suggests that genetic and other early developmental factors may affect later events of sexual maturation. Further investigation is needed to understand the mechanisms that contribute to critical periods in sexual development. Dealing with reproduction issues such as contraception, pregnancy, miscarriage, infertility, premature menopause Physiologic, anatomic, and self-image changes associated with menopause In later adulthood, women experience physiological, anatomic, and emotional changes throughout their postreproductive years. Menopause ordinarily occurs in women aged 45 to 55, preceded by approx imately 2 years of...

Von Willebrands disease

Type I is the commonest form and is responsible for about 90 of cases all vWF (von Willebrand factor) multimers are decreased quantitatively, and the haemophilic part (VIII C) may also be decreased.The PT and PTT (partial thromboplastin time) are usually normal the bleeding time may be prolonged, but can be normal despite a history of bleeding. In addition, results may vary on different occasions for example, pregnancy and oestrogens may result in an increase in vWF, and the menopause may be associated with excessive menstrual bleeding. 4. Menorrhagia may increase in menopausal women with vWD, because of the decrease in oestrogen levels. Oestrogens generally increase vWF levels in the commonest type of vWD, therefore care should be taken to exclude a history of other bleeding in women requiring hysterectomy (Kadir et al 1998b).

Embryonic mammary gland development and establishment of a stem cell population

Uniquely, the human mammary gland undergoes a second involution at the menopause. At this point, there is regression of ducts as well as lobules, and adipose tissue replaces the glandular epithelium and interlobular stroma. As a result, there is a sparse scattering of atrophic acini and ducts through the tissue (1).

Vasomotor Instability

The menopausal state most commonly produces vasomotor instability and genital organ atrophy. Vasomotor symptoms affect 70 percent of postmenopausal women but only about 30 percent seek medical assistance. For 25 percent of menopausal women, these symptoms may persist for 5 years and may be lifelong in others. Vasomotor instability is more commonly termed hot flushes or hot flashes. The frequency, severity, or diurnal variation with which hot flushes occur can result in significant disruptions of sleep and daytime function. Menopausal symptoms are the most common side effect associated with the use of adjuvant chemotherapy for breast cancer, with approximately two-

Managing Age Related Disorders

OSTEOPOROSIS Diminished bone mass can be determined most conveniently with special X-ray machines (dual energy X-ray absorptiometry) or with ultrasound densitometry. Both procedures determine the density as g cm2, which is compared to normal values from a younger population and is used to estimate the likelihood of fracture. The first attempts to manage this disease involve a diet rich in calcium and vitamin D, along with regular weight-bearing exercises. Hormone replacement therapy has also been recommended, for men and women, but as discussed in a previous chapter, this approach can lead to dangerous side effects. An alternative drug therapy involves the use of bisphosphonates, antiresorptive drugs that are known to increase bone mass. The bisphosphonate, alendronate, was shown to decrease the incidence of vertebral and nonvertebral fractures by more than 50 percent in postmenopausal women. The major side effects are gastrointestinal, and the drug must be taken on an empty stomach...

Biomarker level determinations

The serum levels of CA125 generally reflect the volume of the disease. Elevated CA125 prior to surgery is useful for following the progress of the patient during and after treatment. CA15-3, CA19-9 and lipophosphatidic acid have been shown to have independent expression to CA125. Lactate dehydrogenase, human chorionic gonadotrophin and Alfa Feto Protein are used in the diagnosis of different types of germ cell tumours. Inhibin is performed only in post-menopausal women with granulose cell tumours.4

Exposure To Exogenous Or Endogenous Estrogen During Breast Cancer Development

The decision whether or not to take hormone replacement remains difficult for the post-menopausal woman because of conflicting risks and benefits and is even more difficult for the breast cancer survivor for whom there is even less data. One can therefore analyze situations in which women are inadvertently exposed to exogenous or endogenous estrogen at a time when they may have been harboring subclinical breast cancer. Does such exposure adversely affect survival outcome for these patients Such situations include those in which the diagnosis of breast cancer is made in postmenopausal women receiving ERT at the time of diagnosis or in whom the diagnosis is made in pregnancy or during lactation, or in those women

Principal investigations continued

Post-test probability of cancer was less than 1 for an asymptomatic post-menopausal woman with an endometrial thickness of less than 5 mm. However, other studies have found that the detection rate for endometrial cancer varies according to the cut-off for abnormality and noted that the median endometrial thickness varies between centres.8 Another large metaanalysis evaluated 9031 patients. Four studies used the cut-off of 5 mm. A positive test raised the probability of carcinoma from a pre-test 14 to a post-test 31 , while a negative test reduced it to 2.5 . The authors concluded that the ultrasound measurement could not be used alone to rule out endometrial cancer. The depth of invasion, size and location of the tumour are also important prognostic factors obtained from ultrasound. They are not used for official staging, but can guide decisions on treatment or the planned surgery. For instance, larger tumours, i.e. 2 cm, deeper invasion, i.e. 30 and lower uterine segment involvement...

In Vitro Fertilization

There are a number of different ovarian-stimulation protocols namely (1) human menopausal gonadotropin (hMG) or FSH, with or without clomiphene citrate, which was typically used in the early 1980s (2) the long, short, ultrashort, and microdose flare protocols using gonadotro-pin-releasing hormone (GnRH) agonists and hMG or FSH, which have gained widespread acceptance since the long protocol was first described in the mid-1980s and, more recently, (3) protocols using hMG or FSH followed by the addition of newer GnRH antagonists. The highest pregnancy and live-birth rates reported in all age groups and for all causes of infertility have been with the long protocol, which induces pituitary desensitization with GnRH agonist followed by ovarian stimulation with hMG or FSH and which is the most widely used protocol today (7).

Optimal Biologic Dose

Another example that demonstrates this concept is the use of the new aromatase inhibitor, anastrozole, for the treatment of metastatic breast cancer. Anastrozole, as opposed to its predecessor, aminoglutethimide, is a selective aromatase inhibitor that blocks the conversion of androstenedione to estrone. The drug is most effective in post-menopausal women with ER-positive tumors, in whom nonovarian sites of aromatase activity predominate (i.e., adipose tissue, liver, muscle) (21). During the development of anastrozole, several doses of drug were evaluated to determine the dose that most effectively suppresses estradiol levels (21). A daily dose of 1 mg anastrozole was optimal, and, even in the pivotal clinical trial, there was no advantage to higher daily doses of anastrozole in terms of ORR. These examples support the notion of seeking the OBD, rather than the MTD, to guide AI development.

Epithelial ovarian cancer

Ovarian cancer continues to frustrate. Clinicians are disadvantaged by the characteristics of unreliable, inconsistent symptomatology, which accounts for late presentation and poor associated survival figures. Even when the patient does present early, the preoperative diagnosis of ovarian cancer is frequently a difficult one to make. This is borne out by the fact that 50 of patients with this disease are initially referred to general physicians or general surgeons for investigation of symptomatology or ascites. The development by Jacobs et al (1990) of a scoring system, the risk of malignancy index (RMI), which incorporates the use of the serum CA125 level, pelvic ultrasound features and the menopausal status of the patient, has greatly eased this preoperative difficulty. The details of the calculation are shown in Figure 1 and the RMI has now been validated in clinical practice. Using this calculation to assess the nature of an abdominopelvic mass helps to confirm the diagnosis of...

Glucose Insulin and Potential Mechanisms of Vascular Stiffening

Increased arterial stiffening is a hallmark ofboth type 1 and 2 diabetes. The accompanying dyslipidemia, hypertension, visceral obesity and sedentary lifestyle also contribute to structural changes in the arterial wall. Premenopausal women may also have increased arterial stiffening compared to men, suggesting a role for estrogens. Fracture of elastin fibers and increased deposition of collagen associated with aging leads to gradual widening and decreased distensibility of the aorta and the consequent loss of its buffering capacity. These clinical features act through a variety of mechanisms, including insulin resistance, oxidative stress, endothelial dysfunction, and formation of AGEs and pro-inflammatory cytokines, to increase arterial stiffening and increase the risk of CVD. Fig. 1. Increased arterial stiffening is a hallmark ofboth type 1 and 2 diabetes. The accompanying dyslipidemia, hypertension, visceral obesity and sedentary lifestyle also contribute to structural...

Dietary Interventions

Epidemiologic observations of large international differences in the incidence of breast cancer have provided a basis for formulating hypotheses on a possible relation between diet and the development of cancer. The age-adjusted incidence of breast cancer varies from 22 per 100,000 in Japan to 68 per 100,000 in the Netherlands.116 The ratio of breast cancer mortality between the United States and Japan is 3 1 for premenopausal women and 8 1 for postmenopausal women.117 These important differences may possibly be related to fat intake and total calories in the diet. Clinical data collected from case-control studies have demonstrated a positive correlation between diets high in fat and meat and breast cancer.118-122 Experimental studies have shown that omega-6 polyunsaturated fatty acids (PUFAs) contained in high-fat diets promote both mammary tumorigenesis and cell proliferation in chemically induced mammary tumors, whereas omega-3 PUFAs, contained in fish oil, can inhibit these...

Palliative Therapy Against Overt Macroscopic Tumor And Potential Eradication Of Occult Microscopic Disease

Systemic therapy for overt advanced breast cancer began 100 years ago when Beatson observed shrinkage of locally extensive breast cancers after oophorectomy in premenopausal women.6 This phenomenon is based on the trophic effect of estrogen on approximately half of all breast cancers studied. Removal of the ovaries leading to a drop in endogenous estrogen levels in younger women can arrest cancer growth and result in regression. Another approach to depriving breast cancers of estrogen effects is to block estrogen binding to the protein, estrogen receptor (ER), in the breast cancer cell cytoplasm. The receptor-estrogen complex mediates much of the effect of the hormone on the cell, and blocking the interaction, such as by removing estrogen, leads to regression of the hormone-dependent cancer.7 Tamoxifen (Nolvadex) is the prototype competitive inhibitor of estrogen binding at its receptor. The ability to measure estrogen and progesterone receptors and thus predict responsiveness to...

Benefits and Risks of Mammography

The benefit of screening mammography has been called into question over the last decade. This occurred first for the application of screening mammography to premenopausal women (Fletcher et al., 1993), then more recently for the application of screening mammography to all age groups (Gotzsche and Olsen, 2000 Olsen and Gotzsche, 2001). In light of these criticisms, it is important to review the benefits and risks of screening mammography.

Prophylactic Oophorectomy andor Hysterectomy

It has been postulated that hysterectomy may have some secondary effects by affecting ovarian blood flow and ovulation. Schairer and colleagues evaluated 15,844 women undergoing surgery in the Uppsala health care region of Sweden and found a 50 percent reduction in breast cancer risk in those women who underwent bilateral oophorectomy prior to age 50 years, compared with the risk of the background population.146 Hysterectomy alone had no consistent association with change in breast cancer risk. In a case-control series from Italy, women who underwent premenopausal oophorectomy with hysterectomy or hysterectomy alone had reduced relative risk of developing breast cancer (0.8 and 0.7, respectively).147 However, given the importance of the ovarian function in maintaining cardiovascular and bone health, there are presently no indications for recommending these procedures as prophylaxis against breast cancer in any subset of patients.

Conclusion on the Role of Ovarian Surface Epithelium in Adult Human Ovaries

In human ovaries, the formation of new germ cells and follicles occurs at two occasions, during the second trimester of intrauterine life (fetal primordial and primary follicles) and during the prime reproductive period (follicular renewal). During all other periods of life (perinatal, childhood, and premenopausal), primary follicles with aging oocytes are preserved in the ovaries. While the preservation of primary follicles with aging oocytes until menarche does not represent a threat for the progeny due to the lack of ovulation, the premenopausal ovaries lacking follicular renewal may ovulate chromosomally aberrant oocytes, a source of chromosomal abnormalities in the progeny of mothers in advanced maternal age. Importantly,

Screening and Diagnostic Imaging

Mammography is currently the best available screening modality for early detection and diagnosis of breast cancer. Periodic examination of asymptomatic females with mammo-graphy has been shown to reduce breast cancer mortality.1 In accordance with the American Cancer Society recommendations, the available scientific data suggest a benefit from annual mammographic screening of all women beginning at the age of 40 years, combined with annual physical examination and monthly breast self examination.2 For women between 20 and 39 years of age, the ACS recommends a breast physical exam every three years and monthly breast self exam. Patients with a first-degree premenopausal relative diagnosed with breast cancer may consider beginning annual screening examinations 10 years prior to the age at which the relative was diagnosed, in an attempt to benefit from early detection.3

Radiotherapy For Locally Advanced Breast Cancer

When patients treated with orthovoltage radiotherapy were excluded from analysis, a survival benefit of approximately 10 percent was seen in the patients receiving chest wall radio-therapy.104 Recently, two prospective randomized studies reported results showing survival advantage from the addition of local-regional radiotherapy after mastectomy and chemotherapy for node-positive premenopausal breast cancer patients. Both studies show an improvement in survival of 8 to 10 percent.105,106 Both studies have shown a benefit to radiating all patients, regardless of the number of lymph nodes involved. Although patients with one to three nodes positive and four or more nodes positive both showed benefit from radiation in subgroup analysis, routine regional lymph node radiotherapy in all patients with positive nodes is not generally accepted practice (Table 13-5). Premenopausal patients with one to three positive nodes Inclusion of internal mammary nodes controversial Tumor less than five...

Prophylactic Mastectomy

The Society of Surgical Oncology has delineated categories of patients for whom prophylactic mastectomy may reasonably be considered on the basis of clinical features (and not including genetic testing results).144 For women with no history of breast cancer, the indications include atypical hyperplasia, family history of premenopausal bilateral breast cancer, and dense, nodular breasts associated with atypical hyperplasia. For women with a known unilateral breast cancer, the indications for considering contralateral prophylactic mastectomy include diffuse microcalcifications, LCIS, a large, difficult-to - evaluate breast, history of LCIS, and family history of early-onset breast cancer.

Characterization of mammary epithelial stem cells

Again, and for obvious reasons, in vivo DNA label retention studies cannot be carried out in women, but a method of implanting small pieces of intact normal breast tissue into immunodeficient mice to track mammary epithelial cells after administration of the label has been used (40). In this study, tissue was labeled intensively with 3H-dT for a period covering two S-phase durations and sampled at various time points afterward. The tissue was taken from adult premenopausal, but nonpregnant and nonlactating, women, so the study was analogous to that of Zeps et al., who used adult mice (38). Accordingly, 2 wk after 3H-dT injection, a population of LRCs was detectable that comprised less than 1 of the total population and expressed steroid receptors in addition to the p27KIP1 cyclin-dependent kinase inhibitor (CDKI), which is consistent with the conception of LRCs as a quiescent population.

Other Hormonal Approaches

Several other hormonal therapies have activity against metastatic breast cancer and have been evaluated as adjuvant therapy in early disease. Toremifene (Fareston) is a derivative of tamox-ifen with a similar mechanism of action and activity against disseminated disease.7 It is being evaluated in randomized trials against tamoxifen as adjuvant therapy in older women. Progestins lower endogenous estrogen levels in postmenopausal women and cause tumor regression in many women with advanced disease.7 Medroxyprogesterone has been studied as adjuvant therapy in randomized trials, with negative results.41,42 Aromatase inhibitors (AI) inhibit the enzyme that catalyzes the conversion of androgen to estrogen. They, too, lower serum (and intracellular) estrogen levels in older women and are effective hormonal therapies of metastatic breast cancer.7 Aminog-lutethimide, one of the first-generation aro-matase inhibitors, however, was no better than placebo in an adjuvant trial after surgery in...

Hepatic Osteodystrophy

The mechanism of metabolic bone disease in patients with liver disease is multifactorial. The liver is a source of factors involved in bone remodeling and these factors are reduced in chronic liver disease. Patients with liver disease have impaired osteoblast proliferation and thus decreased bone formation. The liver is a source of insulin-like growth factor (IGF)-1, which is important in bone remodeling. Animal data suggest that the decrease in IGF-1 in cirrhosis results in decreased bone formation. In humans, however, the correlation between IGF-1 and osteopenia is less clear. OPG is also produced by the liver, and reductions in this may result in increased osteoclast activity. In general cholestatic liver diseases are associated with lower BMD than noncholestatic liver diseases. In particular patients with PBC appear to have decreased BMD but this may also occur because patients are generally older, postmenopausal women. There are also data to suggest that patients with PBC or...

Arterial Stiffness and Coronary Artery Calcification

Finally, two larger studies (reported as abstracts) have reported strong associations between coronary calcification and cfPWV. First, in a study of 484 older adults (aged 70-96) from the Cardiovascular Health Study, the association between aortic stiffness (cfPWV) and both coronary and aortic calcification was evaluated. Among the older women (mean age 79 years), higher aortic stiffness was associated with higher quartiles of both coronary and aortic calcification after adjustment for age and mean arterial pressure 22 , The absence of an association among these older men may also be due to a survival bias. Second, in a cross-sectional analysis of 477 overweight postmenopausal women (aged 52-62) with no history of coronary heart disease, the prevalence of any coronary calcium was higher among those with higher levels of arterial stiffness (cfPWV) 23 . A 1-SD increase in cfPWV was associated with a 38 increase in odds of coronary calcification. These associations remained significant...

Patient Selection Study Eligibility

Proper conservative patient selection appears to be crucial to the success of APBI, yet clear boundaries of inclusion and exclusion criteria have yet to be fully tested. The goal of patient selection is to identify those patients without a significant risk of harboring microscopic disease outside the immediate vicinity of the lumpectomy cavity. To provide guidance for those practitioners offering APBI, selection criteria have been endorsed and published by the American Brachytherapy Society (ABS) and the American Society of Breast Surgeons (ASBS) (American Society of Breast Surgeons 2005 Arthur et al. 2002). These selection criteria were based on the early APBI published experiences, are conservative in nature and indicate that patients should only be treated with APBI if they present with infiltrating ductal histology the ASBS did include ductal carcinoma in situ (DCIS) as appropriate , lesions

Options for Hormonal Therapy

Rupting the cyclic release of FSH and LH from the pituitary. These drugs are efficacious in acne and hirsutism, and are available as injectable drugs or nasal spray. However, in addition to suppressing the production of ovarian androgens, these drugs also suppress the production of estrogens, thereby eliminating the function of the ovary. Thus, the patient could develop menopausal symptoms and suffer from hypoestrogenism. Headaches can also develop, as well as the occurrence of bone loss, due to the reduction in estrogen.

Medical History and Physical Examination in Patients With Possible Androgen Excess

Modified Ferriman Gallwey Score

The timing and pace of pubertal development and its relation to complaints of unwanted hair growth, hair loss, acne, and or obesity should be established. The onset and progression of these complaints should also be established. Drug or medication use and exposure or use of skin irritants should be elicited. A detailed menstrual history should be obtained, with an emphasis on determining whether evidence of ovulatory function (e.g., premenstrual molimina) is present. Change in skin pigmentation or texture, extremity or head size, and changes in facial contour should be noted. A detailed family history of endocrine, reproductive, or metabolic disorders should be obtained. A family history of similar hyperandrogenic signs and symptoms is a powerful clue to the inherited basis of the disorder, although a familial association can be noted for PCOS, HAIR-AN syndrome, NCAH, and IH patients. Clinicians should note that the etiology of hirsutism can often be suspected from the history alone....

Judgment Selecting the Optimal Technique for a Particular Patient

Similarly, patients who are offered balloon intracavitary brachytherapy have more favorable tumors in breasts that have a thick skin-cavity separation as determined by pretreatment ultrasound. The prescription point for the balloon catheter is only 1 cm beyond the balloon surface, in contrast to the prescription point for interstitial brachy-therapy at 2 cm or whatever distance the radiation oncologist and physics team choose. Despite one paper in the literature (Edmundson et al. 2002) implying that breast tissue is compressible, and the balloon can treat as much as 1.6 cm of breast tissue beyond the surgical margin, there are data from the University of Wisconsin indicating that interstitial consistently treats more breast tissue than the balloon catheter (Patel et al. 2005). Furthermore, the compressibility of breast tissue varies between premenopausal dense breasts and postmenopausal fatty breasts.

Senescence of the Organ Systems

Senescence Saladin

Organ systems do not all degenerate at the same rate. For example, from ages 30 to 80, the speed of nerve conduction declines only 10 to 15 , but the number of functional glomeruli in the kidneys declines about 60 . Some physiological functions show only moderate changes at rest but more pronounced differences when tested under exercise conditions. The organ systems also vary widely in the age at which senescence becomes noticeable. There are traces of atherosclerosis, for example, even in infants, and visual and auditory sensitivity begin to decline soon after puberty. By contrast, the female reproductive system does not show significant senescence until menopause and then its decline is relatively abrupt. Aside from these unusual examples, most physiological measures of performance peak between the late teens and age 30 and then decline at a rate influenced by the level of use of the organs. In women, the changes are more pronounced and develop more rapidly, over the course of...

Phase III Trial of Prone 3D Conformal APBI New York University

On the basis of the results of the pilot study, Formenti et al. conducted a study of 47 postmenopausal women with stage I T1N0 breast cancer, who refused to undergo 6 weeks of WBI, treated to 30 Gy in five 6-Gy fractions over 10 days (Monday, Wednesday, Friday, Monday, and Wednesday) (Formenti et al. 2004). Other eligibility criteria included

Crosssectional imaging

Uterine Carcinoma Mri

In approximately 90 of cases, endometrial cancer is well-differentiated adenocarcinoma which typically presents with postmenopausal bleeding. Histopathological diagnosis is usually confirmed by hysteroscopy and curettage, which despite a small false negative rate of 2-6 remains the 'gold standard' for differentiating benign from malignant endometrium. At presentation 75 of women have tumour confined to the endometrium (stage IA) for whom the 5-year survival rate is 80 following total hysterectomy (Creasman et al., 1987). The International Federation of Obstetrics and Gynaecology (FIGO) committee recommends staging by total hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy. Imaging aids detection of endometrial carcinoma and helps select those postmenopausal women with bleeding who need dilatation and curettage for histopathological diagnosis. It can provide preoperative information about depth of myometrial invasion, an important prognostic indicator. In endometrial...

Cut Off Points For Ca125

The serum value of 35 U ml, representing 1 of healthy female donors, is widely accepted as the upper limit of normal (Bast et al 1983). It should be noted that this is an arbitrary cut-off which may not be ideal for some applications of CA125. For example, in postmenopausal women or in patients after hysterectomy CA125 levels tend to be lower than in the general population, and lower cut-off points may be more appropriate (Alagoz et al 1994, Bon et al 1996). Approximately 83 of patients with epithelial ovarian cancer will have CA125 levels greater than 35 U ml (Bast et al 1983, Canney et al 1984). Unfortunately only 50 of patients with stage I disease have elevated levels, while raised levels are found in over 90 of patients with more advanced disease (Jacobs and Bast 1989). The incidence of CA125 elevation is lower in mucinous, clear cell and borderline tumours (Vergote et al 1987, Jacobs and Bast 1989, Tamakoshi et al 1996). Elevation of serum CA125 levels may also be associated...

Androgens and Sebum Production

Acne Vulgaris

The majority of potent androgens are produced by peripheral target tissues. For example, in postmenopausal women, 100 of active sex steroids are synthesized in peripheral target tissues from inactive steroid precursors while in adult men approximately 50 of androgens are locally made in intracrine target tissues 4 . The major androgens that interact with the androgen receptor are testosterone and dihydrotestosterone. Androgen receptors have been localized to the basal layer of the sebaceous gland and the outer root sheath keratinocytes of the hair follicle 5, 6 . Dihydrotestosterone is approximately 5-10 times more potent than testosterone in its interaction with the androgen receptor.

Thyroid and Parathyroid Disorders

Because of their location and small size, the parathyroids are sometimes accidentally removed in thyroid surgery. Without hormone replacement therapy, the resulting hypoparathyroidism causes a rapid decline in blood calcium levels and leads to fatal tetany within 3 or 4 days.

What about the new lowdose hormone patch Menostar estradiol that is used to prevent osteoporosis

Menostar (estradiol) was FDA-approved in 2004 for the prevention of postmenopausal osteoporosis. It is a dime-sized transdermal patch that delivers about 14 micrograms of estrogen per day. A new patch is applied every week. Because your body absorbs the estrogen from the patch through the skin, you can avoid the liver first-pass effect, meaning that the hormone is not metabolized through your liver. Instead, it can go directly into the bloodstream. The estrogen that is used in this patch is estradiol, one of the three estrogens made by the human body. Estradiol is the one in greatest abundance until menopause. Then levels drop off to near zero. Although estrone The blood levels of estrogen resulting from Menostar are high enough to preserve bone but not high enough to treat the vasomotor symptoms of menopause. If you need your symptoms treated, Menostar probably does not provide adequate estrogen levels for you to get relief. The levels of estrogen needed to effectively treat...

Estimating the Economic Burden of PCOS

The overall costs associated with the treatment and, if appropriate, the diagnosis of the various morbidities evident in the premenopausal women with PCOS are outlined in Table 3. This conservative estimate of the health care-related economic burden of premenopausal women with PCOS exceeded 4 billion annually in the United States alone. Approximately 40 of the burden is a result of the increased prevalence of diabetes associated with PCOS 30 arises from the treatment of the associated menstrual dysfunction AUB, 14 from the treatment of hirsutism, and 12 the provision of infertility services. Notably, the costs of the diagnostic evaluation of all patients accounted for a relatively small portion of the calculated economic burden, about 2 . The calculated economic burden of patients with PCOS during their reproductive years is about threefold that of hepatitis C ( 1 billion in 1998) (65) and about one-third that of morbid obesity ( 11 billion in 2000) (66).

Hormone Imbalance Theory

Processing Resources Theory Aging

One of the most dramatic age-related changes in humans is the loss of the ovarian cycle in females, generally referred to as the onset of menopause. Menopause usually occurs as women reach 50 years of age and is marked by a cessation in the development of ovarian follicles and, as a consequence, a dramatic drop in estrogen levels. Estrogen, aside from its role in reproduction, is important to female physiology for the maintenance of secondary sexual characteristics, skin tone, and bone development. Female mice and rats also go through menopause, although in these animals it is called diestrous, or the cessation of the estrous cycle. For gerontologists, the onset of menopause in mice and rats provides an experimental system which can be used to test the idea that the hypothalamus is an aging-clock that is, menopause or diestrous occurs because the hypothalamus stops releasing the necessary messenger molecules. When this happens, the reproductive system grinds to a halt. Many...

What types of medication are usually prescribed for osteoporosis

The North American Menopause Society (NAMS) advises that the following women receive prescription medication as part of their treatment for osteoporosis Postmenopausal women who sustain a fracture of a vertebra as a result of osteoporosis. Postmenopausal women whose T scores are lower than -2.5. Postmenopausal women with T scores lower than -2.0 with at least one additional risk factor for fracture. trying to break down old bone. Estrogen therapy (ET) is one of these types of medications and for post-menopausal women has been found to be very effective in the prevention of osteoporosis. ET is appropriate for preventing osteoporosis in postmenopausal women who are experiencing significant menopausal symptoms (see Questions 64-66). Other medications that fall into the group of drugs intended to prevent further loss by slowing down the breakdown of bone include bisphosphonates, calcitonin, and selective estrogen receptor modulators (SERMs). Questions 57 to 65 contain a full discussion of...

Biophysiological Factors

With menopause may result in mood changes which may be misattributed to psychological causes. On the other hand psychological changes may be misattrib-uted to hormonal changes. There are gender differences in return of diffuse physiological arousal (DPA) to baseline levels men take longer to return to baseline levels. These gender differences have implications for understanding and altering aggression among family members. Whenever physiological factors may be related to a problem as, for example, with seizures, depression, fatigue, or headaches, a physical examination should be required. Overlooking physical causes including nutritional deficiencies and coffee, alcohol, or drug intake may result in incorrect inferences.

What are isoflavones Are they effective for treating osteoporosis

Because isoflavones have been found to act like estrogen in the body, isoflavones are being studied not only for their effects on the hot flashes associated with menopause, but also for their effects on bone health. Several small studies have shown some promise in reducing bone loss and increasing bone mineral density without some of the side effects of estrogen observed in other scientific studies. For example, isoflavones don't seem to increase breast density, increase endometrial thickness, or exert the same negative effects on your heart health. Further study is needed to confirm the bone findings reported when isoflavone supplements are taken. Isoflavones are considered safe when taken with other medications, such as the prescription medications described in Questions 56 to 67.

Bilateral Breast Reconstruction

With improvements in breast cancer screening, a greater number of early breast cancers are being detected in young, premenopausal patients, many of whom have some degree of familial cancer history. Patients with young families present with the intent to absolve breast cancer risk for the benefit of their young ones and represent a new indication for either prophylactic or bilateral mastectomy. Breast cancer awareness has elevated the level of sophistication of all patients. Prosthetic and autologous reconstruction is a known entity that continues to become more reliable, safe, and esthetically satisfying. As this awareness becomes more apparent and outcomes improve, it is not surprising that an increasing number of susceptible women are at least questioning the option of bilateral ablation and immediate reconstruction.

What is Evista raloxifene What is a SERM and why is it effective in the treatment of osteoporosis

Evista (raloxifene) is the only FDA-approved selective estrogen receptor modulator (SERM) for the prevention and treatment of osteoporosis in postmenopausal women. You may be more familiar with tamoxifen, a SERM used in the treatment of breast cancer. A SERM binds with some estrogen receptor sites around the body. Although raloxifene is not a hormone, it has an estrogen-like effect in some body tissues such as bone and has an estrogen-blocking effect on other tissues such as breast and uterus. Evista increases bone mineral density, decreases the risk of fractures, and is FDA-approved for the prevention and treatment of osteoporosis in post-menopausal women. The dosage of Evista for both osteoporosis treatment and prevention is 60 mg per day taken as one tablet. Evista, unlike the bisphos-phonates, may be taken with or without food. In addition to Evista's positive effects on bone, it also decreases low-density lipoprotein (LDL) cholesterol (the bad cholesterol) as well as total...

The Evolution of Human Longevity

Although the age-related decline of reproduction in many mammalian species is sometimes referred to as menopausal, it is probably more appropriate to restrict the term menopause to describe the fairly sudden cessation of reproduction in human females. Clearly this is a programmed event, due to hormonal change, which is a much more distinct change than occurs in other mammalian species. Some have argued that the evolution of the menopause, occurring many years before final senescence and death, is hard to explain on evolutionary grounds because it has the effect of reducing reproductive potential. This view does not take account of a well established feature of evolution known as kin-selection, first recognised by the geneticist J.B.S. Haldane, and then developed much further by the evolutionary biologist W.D. Hamilton. Parents and children have 50 of their genes in common, as do siblings and 25 of a grandchild's genes are present in each grandparent. The care of children by parents...

A PMS Symptoms and Their Timing

The course and stability of PMS over time has not been systematically characterized. It has been observed that PMS can begin any time after menarche, but women most frequently seek treatment for their symptoms in their thirties. Symptoms are believed to remit with conditions, such as pregnancy, that interrupt ovulation. Women generally report that their symptoms worsen with age until menopause, when PMS usually ceases.

Coronary Artery Disease

Many epidemiological studies have found that postmenopausal women who use estrogen are at a much lower risk for coronary disease than are nonusers. Observational studies suggest a 50 percent reduction in the risk of coronary heart disease among healthy post-menopausal women taking oral estrogen.9 Hunt10 reported on a cohort of 4,544 women who had taken hormone replacement therapy continuously for at least 1 year at the time of recruitment. When compared with the general female population, mortality rates for ischemic heart disease among the cohort were significantly lower, with a relative risk of 0.41 and a 95 percent CI of 0.2 to 0.61. Bush11 evaluated a cohort of 2,270 women, 593 of whom were estrogen users. The age-adjusted relative risk of death from cardiovascular disease was 0.34, with the 95 percent CI of 0.12-0.81. Stampfer12 evaluated postmenopausal estrogen therapy and cardiovascular disease in the Nurses' Health Study, with a 10-year follow-up. Women currently using...

Which bones are affected by osteoporosis

Bisphos Fracture

Menopause hormone therapy (MHT) Type of treatment used for the relief of menopause symptoms also helps to prevent bone loss. In primary osteoporosis, women lose 5 to 10 of cortical bone and 20 to 30 of trabecular bone during the rapid bone loss occurring in the four to eight years following menopause. In contrast, men and women (after the faster postmenopausal bone loss) experience a slower rate of bone loss as a result of aging. Occurring slowly over many years, this type of bone loss accounts for about a 20 to 25 loss of both cortical and trabecular bone. Thus, women are at risk for much greater bone loss than men.

Background On Polycystic Ovarian Syndrome Among Adolacents

Steroid concentrations in peripheral and ovarian venous plasma of premenopausal women. The concentrations of androstenedione (A4), testosterone, estrone, and estradiol in peripheral blood, blood draining the ovary having either a dominant follicle and or an active corpus luteum, and in blood draining the contralateral ovary are shown for women having gynecological surgery. CL, corpus luteum. (Data from ref. 18.) Fig. 3. Steroid concentrations in peripheral and ovarian venous plasma of premenopausal women. The concentrations of androstenedione (A4), testosterone, estrone, and estradiol in peripheral blood, blood draining the ovary having either a dominant follicle and or an active corpus luteum, and in blood draining the contralateral ovary are shown for women having gynecological surgery. CL, corpus luteum. (Data from ref. 18.) Ovarian suppression in adult women because of the ingestion of oral contraceptive steroids is often accompanied by reductions in circulating levels of...

Selective Estrogen Receptor Modulators

Preclinical data have shown that raloxifene, an antiestrogen with no estrogen-agonist effect on the uterus, inhibits mammary carcinogenesis in a rat model of breast cancer in a manner similar to tamoxifen when raloxifene is used in combination with 9-cis retinoic acid.97 Clinical trials have been started in an attempt to establish the role of raloxifene in preventing osteoporosis in postmenopausal women, and preliminary results from two randomized clinical trials have recently become available. The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was specifically designed to evaluate the possibility of reducing the risk of fractures in post-menopausal women receiving raloxifene a markedly reduced risk of newly diagnosed breast cancer was demonstrated with raloxifene compared with placebo (0.21 versus 0.82 ).100 Jordan and colleagues recently reported the results of a multicenter, double-blind randomized trial conducted in about 12,000 women. Treatment with raloxifene was...

Facial Acne in Adults

- A postal survey was sent to 173 adult pre-menopausal women treated for acne between 1988 and 1996 in the USA 11 . 91 (52 ) answered all of them had received spironolactone at some point during the course of their treatment. The mean duration of acne was 20.4 years. Acne was reported to be persistent in 80 of the women and 58 of them had an ongoing need for treatment. In this selected population, acne in adult women was particularly persistent and desperately recurring.

Differential Diagnosis Of Polycistic Ovaran Syndrome

Healy DL, Burger HG, Mamers P, et al. Elevated serum inhibin concentrations in postmenopausal women with ovarian tumors. N Engl J Med 1993 329 1539-1542. 43. Regnier C, Bennet A, Malet D, et al. Intraoperative testosterone assay for virilizing ovarian tumor topographic assessment report of a Leydig cell tumor of the ovary in a premenopausal woman with an adrenal incidentaloma. J Clin Endocrinol Metab 2002 87 3074-3077.

Oophorectomy and Gonadotropin Releasing Hormone Analogue

The sporadic use of adjuvant oophorectomy after breast cancer surgery in younger women was continued by surgeons for many years in the hope of preventing recurrence. Randomized trials looking at its value date back 50 years.37 Unfortunately, these early trials suffer from the lack of hormone responsiveness of most breast cancers in premenopausal women and they predate our ability to predict responsiveness with hormone receptor measurements. The EBCTCG conducted overview meta-analyses of adjuvant oophorectomy in 1985, 1990, and 1995. The most recent overview encompassed 12 trials randomizing 2,100 women to surgical or radiation oophorectomy versus no castration.38 In women under the age of 50 years, oophorectomy resulted in an 18 percent relative decrease in recurrence, an 18 percent relative decrease in death, and, at 15 years after surgery, an absolute decrease of 6.3 percent in death from any cause, compared with women not getting the procedure (p .001).38 The relative benefit was...

Summary

Male-like hair growth and masculinization of women and the ambiguity of genders has fascinated mankind for millennia, frequently appearing in mythology and the arts. The earliest reports of androgen excess, beginning 400 years bc, focused on the appearance of male-like hair growth and features in women, often accompanied by menstrual cessation. The first etiologies identified as a cause of androgenization in the female were adrenal disorders, primarily adrenocortical neoplasms, but also eventually adrenal hyperplasia. The first report of a patient with nonclassic adrenal hyperplasia (NCAH) was made in 1957. The Achard-Thiers syndrome, which was originally reported in 1921 and was felt to primarily affect postmenopausal women, included the development of diabetes mellitus, hirsutism, and menstrual irregularity or amenorrhea in conjunction with adrenocortical disease. Androgen production by the ovary was not recognized until the early 1900s, with the first case of a patient with glucose...

The Role of Obesity

An example of the complexity of these relationships can be illustrated in two studies done by the same large group of collaborators (Nilsson et al, 2003 Lagergren et al, 2000). In a study published in 1999, the authors concluded that there was no relationship between body mass and GERD symptoms, and this applied to both severity and duration of reflux symptoms. In a more recent study, published in 2003, the authors reached a very different conclusion. In this study they reported a significant association between body mass and symptoms of GERD. They noted that the association was stronger in women, particularly in premenopausal women, and that the use of hormone therapy appears to strengthen this association. In the discussion of this article, the authors commented on their previous work and suggested that a paucity of males in that particular study biased the results toward negativity. Other epidemiological studies

Conclusions

In pregnancy, circulating levels of testosterone, A4, and DHT are all increased relative to those in nonpregnant women, although circulating levels of DHEAS at term are 50 or less than those in nonpregnant women. Interestingly, the maternal concentrations of DHEAS, A4, and testosterone have recently been shown to decrease with increasing maternal age in women in late gestation. The serum levels of testosterone and A4 are fairly stable for about 3 years prior to menopause, with a tendency to decline progressively thereafter. Alternatively, the age-associated declines in DHEA and DHEAS, consistent with the fact that these steroids are primarily of adrenal origin, are more related to age per se than to abrupt changes in ovarian function during the perimenopausal period. The steroidogenic defect that occurs in aging appears to be localized primarily to the zona reticularis of the adrenal. Although the role of the ovary in androgen production in postmenopausal women has been the topic of...

BAmyloid Protein 142

Relation of age at onset of menopause to age at onset of dementia. (Reproduced from Cosgrave et al., 1999, by permission of Blackwell Science Ltd.) Figure 3.3. Relation of age at onset of menopause to age at onset of dementia. (Reproduced from Cosgrave et al., 1999, by permission of Blackwell Science Ltd.)

Cohort Studies

As with other observational studies, retrospective cohort studies can be undertaken to evaluate preventive or therapeutic interventions, but there is again concern that those who had the intervention may differ in other ways from those who did not. A retrospective cohort study to determine whether calcium consumption reduces the risk for hip fracture illustrates the problem. People examined in the first National Health and Nutrition Examination Survey (NHANES I) of 1971-1975 had answered an extensive dietary questionnaire. Looker et al. (1993) related this information to the subsequent occurrence of hip fracture and found that higher calcium consumption was related to a lower hip fracture risk in women who were at least 6 years past menopause and who did not use hormone replacement therapy. However, the possibility remains that the women with higher calcium consumption differed from women with lower calcium in other ways that the investigators could not take into account because they...

Anatomy

Breast Anatomy Retromammary Space

Males and prepubescent females have only rudimentary glandular tissue. In the western world, a young woman's glandular tissue begins to proliferate early in her second decade, although maturation may be earlier or later. By the time a woman has completed puberty, her glandular tissue usually has developed to its maximum size. Hormonal variations related to menstrual cycles, pregnancy, and lactation cause the size of the glandular tissue to wax and wane. At menopause, glandular tissue gradually recedes, causing the breast to flatten somewhat, and become pendulous and less firm.

Osteoporosis

Bone mineral density (BMD) is a common criterion used to evaluate the onset of this very common disease, which affects more than 20 million people in North America alone. Women are four times more likely to develop osteoporosis than men. One out of every two women and one in eight men over 50 will have an osteoporosis-related fracture in her or his lifetime. Osteoporosis is caused primarily by hormonal changes that affect women and men as they approach their sixth decade. For women, this involves a dramatic drop in estrogen levels at menopause, and for men, a reduction in the levels of testosterone at a comparable age. Current treatments involve calcium and vitamin D supplements (at about 400 to 1,000 IU day for vitamin D). The preferred calcium source is milk, cheese, or yogurt. Hormone replacement therapy, involving estrogen for women and testosterone for men, has proved to be very effective. However, the effective dose was once believed to be low enough that cancer induction was...

The Menstrual Cycle

Historically, and for women as hunter-gathers, menarche occurred later and menopause earlier. It was also normal for lactation to continue for three to four years. As a result, women would have five to six children. Consequently, because of protracted amenorrhagia, women would experience only thirty menstruations in their lifetimes.

Fibroids

Fibroids are derived from single myometrial cells, though G - 6 PD type may vary between individual fibroids within the same uterus (West, 1998). It is thought that fibroid growth is dependent on ovarian hormones, as they do not occur prior to menarche and normally reduce in size following menopause. Fibroids appear to develop and be maintained in response to oestrogen, and progesterone may have a major role to play in the control of fibroid growth.

Colorectal Cancer

Calle and colleagues23 investigated the relationship between postmenopausal estrogen use and fatal colorectal cancer in a large prospective study of adults in the United States. Eight hundred and seventy-nine colon cancer case patients were compared to 421,476 noncase subjects. Ever use of ERT was associated with a significantly decreased risk of fatal colon cancer (RR 0.71 95 CI 0.61 to 0.83). Reduction in risk was strongest among current users (RR 0.55 95 CI 0.40 to 0.76) compared to former estrogen users. There was a significant trend of decreasing risk with increasing years of estrogen use among all users (p .0001). Those women who used estrogen for 1 year had a RR 0.81, whereas users of 11 years had a RR of 0.54 (95 percent CI 0.39 to 0.76). These associations were not altered in multivariate analyses controlling for age, race, parental history of colon cancer, body mass index, exercise, parity, type of menopause, age of menopause, oral contraceptive pill use, aspirin use, and...

Excessive hair

Hirsuties occurs most commonly after the menopause and may be present to some degree in normal women as a result of familial or racial traits. It may arise without any underlying hormonal disorder or as a result of virilising hormones. These causes are listed in the box on the right. In addition to androgens, a number of drugs can cause hirsuties. It is important to remember that hirsuties may be part of a virilising syndrome or polycystic ovaries. It is useful to measure the serum testosterone and oestrogen level, as well as urinary 17 oxosteroid concentrations.

Doxorubicin

The suggestion that doxorubicin-based chemotherapy was more effective than CMF in the palliation of advanced breast cancer11 led to the use of combinations containing the drug as adjuvant therapy particularly in poor prognostic groups, such as those with multiple positive nodes. The 1995 overview analyzed 11 CMF versus anthracycline (doxorubicin or epiru-bicin) polychemotherapy trials.19 At 5 years after surgery, anthracycline combinations decreased recurrence by an absolute 3.2 percent (p .006) and mortality by an absolute 2.7 percent (p .02). Individual trials themselves have been contradictory, but there are some general trends. The NSABP Protocol B15 showed that in node-positive women, a short four-treatment course of IV doxorubicin cyclophosphamide (AC) (see Table 12-1) was equivalent to the effect of classic CMF for 6 months.21 Furthermore, the AC regimen was effective and well tolerated in postmenopausal women. It is now widely used as an alternative to CMF for poor prognosis...

Cancer

Testosterone (ET ratio) in both men and women. Young women naturally have a high estrogen testosterone ratio (a lot of estrogen, very little testosterone), whereas young men have a low estrogen testosterone ratio (very little estrogen, a lot of testosterone). Estrogen levels drop dramatically in women after menopause, and men show a similar decline in the level of testosterone at a corresponding age. As a consequence, men and women approach a similar ET ratio throughout their sixth to ninth decades, a condition that is thought to influence the rate at which genetic instability occurs. In addition, many scientists believe the shift in the ET ratio is largely responsible for the weakening of the human immune system, leading to the increased occurrence not only of cancer but of many other diseases as well.

Results

To further complicate matters, the physiology of the breast, like that of many other organs, changes significantly with age. The most dramatic changes occur after menopause, when much of the glandular tissue atrophies and is progressively replaced with adipose tissue. Breast physiology also varies notably throughout the menstrual cycle 11 .

Alzheimers Disease

Subjects were initially free of Alzheimer's disease, Parkinson's disease, and stroke and were part of a longitudinal study of aging and health in a New York community. Overall, 158 (12.5 percent) reported taking estrogen after the onset of menopause. The age of onset of Alzheimer's disease was significantly later in women who had taken estrogen than in those who did not, 78 years versus 73 years. Even after adjustment for differences in education and ethnic origin, the relative risk of Alzheimer's disease was significantly reduced in estrogen users over nonusers 0.4, with a 95 percent CI of 0.22 to 0.85. Even among postmenopausal women who are not demented, ERT may help maintain cognitive function.17 Estrogen appears to have a specific effect on verbal memory skills in healthy postmenopausal women.1819

Endogenous Hormones

It is well established that menstrual factors resulting in exposure of the breast to increased numbers of ovulatory estrogen cycles over a lifetime, such as early menarche ( 50 years), and nulliparity can increase the risk of breast cancer.46,47 Conversely, bilateral oophorectomy at a young age and interruptions of the menstrual cycle in the form of multiple pregnancies may confer a protective effect.48 It is also well established that estrogen and progesterone exert proliferative effects on human breast tissue49,50 and that estrogen can promote mammary tumorigenesis in animal models as well as in in vitro tissue cultures.47-51 Postmenopausal obesity has been associated with increased breast cancer risk, and this relationship appears to be mediated by age-related variations in estrogen metabolism. In the post- menopausal woman, androstenedione, synthesized in the adrenal gland, is the principal estrogen precursor following the decline of ovarian function. Increased conversion of...

Ovarian Ablation

For premenopausal women with receptor-positive disease, medical or surgical castration is also an effective approach to hormonal therapy. The endocrinologic effect of castration is achieved by two analogs of gonadotropin-releasing hormone, goserelin and leuprolide, which suppress follicle-stimulating hormone and luteinizing hormone, and thus estrogen production by the ovary.62,63 Either agent will achieve the same benefit as oophorectomy, that is, a 45 percent likelihood of disease regression or stabilization, but require parenteral administration on a monthly or tri-monthly basis. Side effects are limited to pain at the injection site and menopausal symptoms such as hot flashes, mood swings, and dry skin. Once disease progresses after either medical or surgical castration, the alternate approach has little chance of benefit. Obviously, castration by either technique can only be of benefit to pre-menopausal patients, where the ovary is the primary site of estrogen production.

Preventive Therapy

It remains somewhat controversial whether osteoporosis is truly a complication of PBC. Although it is common among patients with PBC, this disease affects predominantly middle-aged women who are at risk for osteoporosis for other reasons. In any case, patients should be screened for osteopenia or osteoporosis using bone densitometry. All patients with PBC should take calcium and vitamin D, either as a supplement or as part of their regular diet. The bis-phosphonate etidronate has been shown to be safe in PBC, stabilizing bone loss in corticosteroid-treated patients. Caution should be used with these agents if patients have significant esophageal varices because of the risk of esophageal ulceration. Newer-generation bisphosphonates such as risedronate (Actonel) are likely safer, although no data specifically addressing this question are currently available. Other options include hormone replacement therapy, which has been shown not to worsen cholestasis in PBC but must be used with...

Endometrial biopsy

The largest study of the prognostic value of endometrial sampling involved a meta-analysis of 39 studies involving 7914 women. The results of endometrial sampling were compared to more invasive techniques, such as dilatation and curettage, hysteroscopy and hysterectomy. The detection rates for endometrial cancer were 99.6 in post-menopausal women and 91 for pre-menopausal women. The overall detection rate for atypical hyperplasia was 81 . The specificity for all sampling types was in the range 98-100 . An insufficient sample was returned in as many as 5 of patients.5 Therefore, endometrial biopsy might be an appropriate initial diagnostic test for ruling out endometrial cancer in symptomatic women. More invasive diagnostic methods may be considered in cases where the sample was inadequate. The overall grade for the patient's tumour is based on the worse sample obtained, whether from the biopsy, dilatation and curettage or hysterectomy specimen.

Effect Modification

Effect modification, sometimes called statistical interaction, also needs to be considered when studies are designed, analyzed, and interpreted. Effect modification is said to occur when the magnitude of the association between one variable and another differs according to the level of a third variable. For instance, obesity increases the risk for breast cancer in postmenopausal but not premenopausal women thus, menopausal status is a modifier of the effect of obesity on breast cancer. Asbestos appears to be a stronger risk factor for lung cancer among smokers than among nonsmokers in other words, smoking modifies the effect of asbestos on lung cancer risk. Detecting effect modification is an important component of the analysis of epidemiologic data.

Oocytes

Oocytes are retrieved after pituitary desensitization with a gonadotropin-releasing hormone agonist and follicle stimulation with a combination of human menopausal gona-dotropins (hMG) (Pergonal, Serono, Waltham, MA Humegon, Organon Inc., West Orange, NJ), and FSH (Gonal-F, Serono Follistim, Organon). Human chorionic gonadotropin (hCG) is administered when criteria (e.g., ultrasound, estradiol levels) for oocyte maturity are met, and retrieval is performed 35 h later by vaginal ultrasound-guided puncture. Under the inverted microscope at 100x, the cumulus-corona-cell complexes are scored as mature, slightly immature, completely immature, or slightly hypermature. Thereafter, the oocytes are incubated up to 4 h depending on their state. Immediately before micromanipulation, the cumulus-corona cells are necessarily removed for oo-cyte observation and accurately controlled by the use of the holding and or injecting pipette. Such removal involves oocyte exposure to M-HEPES containing 40 IU...

Future Directions

To determine whether PBI limited to the region of the tumor bed following lumpectomy provides equivalent local tumor control in the breast compared to conventional WBI in the local management of early-stage breast cancer, the first phase III randomized study of conventional WBI versus PBI opened in March 2005. This study includes patients with stage 0, I, or II breast cancer resected by lumpectomy with tumor size 60 Gy. If the patient is randomized to group 2, she will receive, as determined by her physicians in addition to patient preference, APBI via one of three modalities. The first two methods involve delivery of 34 Gy in 3.4 Gy fractions twice daily over 5-10 days using multicatheter brachytherapy or the

Estrogen Antagonists

The oldest and most widely prescribed estrogen antagonist is tamoxifen,52 but toremifene has also been approved for this indication. Raloxifene is currently marketed for prevention of osteoporosis and may also have some efficacy against metastatic breast cancer, although further study is clearly required.53 Tamoxifen appears to be effective for both pre- and post-menopausal women with advanced, receptor-positive disease.54 Common side effects of tamoxifen include hot flashes (particularly in perimenopausal women), disruption of menstrual cycles, and vaginal dryness or discharge.55 In addition, weight gain and mild fluid retention are frequent, with nocturnal leg cramps not uncommonly reported. Patients with bone metastasis may suffer a syndrome of tumor flare, typically 7 to 10 days after initiation of tamoxifen. This is seen in 1 to 3 percent of patients and consists of increased pain at sites of metastases it may lead to hypercalcemia. As this is predictive of subsequent response to...

Pregnancy Rates

Most early studies were of an observational nature and have also been reported in the context of large reviews (2,3). An unfortunate feature of many of the papers that describe laparoscopic treatment wedge resection is the poor characterization of the patients such that many appear to have been ovulating prior to treatment. Furthermore, as the polycystic ovary becomes more sensitive to either endogenous or exogenous FSH after LOD, many practitioners have taken a pragmatic approach by commencing ovarian stimulation with either clomiphene or gonadotropins if ovulatory activity is not immediately induced (30,31). The first RCT suggested that LOD was as effective as routine gonadotropin therapy in the treatment of clomiphene-insensitive PCOS (29). In this study 88 patients were randomized prospectively to receive either human menopausal gonadotropin, FSH, or LOD. There were no differences in the rates of ovulation or pregnancy between the two groups, although those treated with LOD had...

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Natural Cures For Menopause

Natural Cures For Menopause

Are Menopause Symptoms Playing Havoc With Your Health and Relationships? Are you tired of the mood swings, dryness, hair loss and wrinkles that come with the change of life? Do you want to do something about it but are wary of taking the estrogen or antidepressants usually prescribed for menopause symptoms?

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