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Surviving Perimenopause

To give you an even better idea of just what kind of useful and practical information youll find in Perimenopause: Have It, Live It, Love It!, heres a partial list of the topics covered extensively in this ebook: Learn about the 26 signs of perimenopause both common and not so common symptoms. Find out what your symptoms are Not telling you 18 perimenopause symptoms that are linked to other serious medical conditions. Learn how you can treat your symptoms Without the use of drugs and pills. Over 50 home remedies with recipes and instructions to help you cope with various perimenopause symptoms. What you need to prepare Before your visit to your doctor, including how to make sure your doctor listens to you and takes your symptoms seriously, and reaches the right diagnosis. Get tips and techniques to re-ignite your sex life. Its not too late to bring passion back to the bedroom. Perimenopause pregnancy? Get your facts straight whether you are trying to conceive or prevent a pregnancy. Make sense of the changes that are happening to your body and the ones that are happening inside your head. Learn techniques you can apply today to get better sleep and to overcome perimenopause insomnia. Discover what you can do now to prevent osteoporosis which attacks women after they hit menopause and is easily preventable only if you start now! Identify if you are estrogen deficient or estrogen dominant and find out which remedies work for each type. Determine whats actually causing your irregular periods, Pms and heavy bleeding. Learn how to tell when youll hit menopause. Understand medical jargon so you dont come out of a doctor consultation more confused than before you went in. Understand the link between hormonal changes in your body and your mood swings and depression. Find out what to expect when you have perimenopause the common and not-so-common transformations that can really affect the way you live. Get access to information that your doctor may not be telling you. Realize that you can do something about that weight youre putting on around your waist and thighs and why old dieting methods that worked for you in the past are next to useless now. Learn about the different kinds of tests your doctor may ask you to get and actually know what theyre for.

Surviving Perimenopause Overview


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Menopausal Symptoms

The natural oestrogen-receptor activity of soy is popularly considered an alternative to controversial HRT for postmenopausal women (Sliva 2005). A recent analysis of 17 trials, however, found mixed results for the effects of soy isoflavone extracts on menopausal symptoms (Nelson et al 2006). Although some data seem to support the efficacy of isoflavones in reducing the incidence and severity of hot flushes, many studies have not found any difference between the isoflavone recipients and the controls. Inadequate data exist to evaluate the effect of isoflavones on bone mass and vaginal dryness (Greenwood et al 2000).

Menopause and Obesity in Women

There are relatively few data on changes in adiposity and fat distribution associated with menopause in women. This is an important issue because of the relationships that have been noted between obesity and cardiovascular disease (5), and obesity and certain cancers (56,57) in postmenopausal women. As noted above, body weight reaches its maximum in women very near the time of menopause, and there is an increase in relative adiposity for any given weight or BMI. While some studies find that the increase in weight accompanying menopause is more related to age than menopause itself (58,59), others have noted specific menopause-related increases in BMI, overall adiposity, central adiposity and intra-abdominal adiposity (60-64). A recently published longitudinal study that followed 35 women aged 44-48 for 6 years (65) found that those women who experienced menopause during the period of follow-up lost significantly more FFM ( 3 vs. 0.5 kg), and had greater increases in fat mass (FM 2.5...

Managing Menopausal Symptoms

This chapter deals with menopause-associated symptoms including hot flashes, night sweats, sleep disturbances, and vaginal symptoms. Other symptoms that accompany the perimenopause transition but are related to other life events or aging, including sexual dysfunction and mood disturbances, are discussed. The options for managing these changes include menopause hormone therapy, both systemic and local, as well as complementary therapies and nonhormonal therapies for each of the symptoms.

Hormone Replacement Therapy

It is well established that women who use hormone replacement therapy (HRT) are at a slightly increased risk of breast cancer and that risk increases with duration of use (by 2-3 per year of use), but decreases when use is ceased (38). Rebbeck et al. have reported that use of HRT in mutation carriers who had undergone a bilateral prophylactic oophorectomy (BPO) did not significantly alter the reduction in breast cancer risk associated with BPO. These data suggest that short-term HRT does not negate the protective effect of BPO on subsequent breast cancer risk in BRCA1 orBRCA2 mutation carriers. In addition, theNarod-led collaboration have reported that HRT use by carriers does not appear to adversely influence their risk of ovarian cancer (OR 0.93 95 CI 0.56-1.56) (39). Despite these encouraging results, additional research on the use of HRT and its role in breast cancer risk among women with BRCA1 or BRCA2 mutations is warranted.

Age at Menopause

Early menarche and late menopause increase the number of ovulatory cycles during which a woman is exposed to high levels of estrogen. It has been estimated that women who experience natural menopause (as defined by cessation of periods) before the age of 45 have only one-half the breast cancer risk of those whose menopause occurs after the age of 55.23 Artificial menopause, by either bilateral oophorectomy or pelvic irradiation, also markedly reduces breast cancer risk. The effect appears to be slightly greater than that of natural menopause, probably because surgical removal of the ovaries causes an abrupt cessation of hormone production, whereas some hormone production continues for a few months or years after a natural menopause.


The climacteric or menopause, the cessation of menstruation, occurs by age 50 in most women and marks the end of the childbearing years. Some women manage to give birth during their fifties and even sixties, but for most, the period of fertility ends sometime during the fifth decade. Associated with menopause is a sharp drop in the production of estrogen The degree of vasocongestion of the breasts, clitoris, and vagina is also affected, and vaginal lubrication is reduced with menopause. The decreased acidity of vaginal secretions also increases the likelihood of infection. These changes in the vagina may result in pain and discomfort during sexual intercourse and an aching, burning sensation afterward. A minority of meno-pausal women experience these symptoms to any great degree, and they can, of course, be treated (Corby & Solnick, 1980). For example, vaginal irritation can be treated with a water-based lubricant such as K-Y, and by enhancing lubrication by means of estrogen...

The menopause

Again, a variety of treatments has been used (http www.clinicalevidence. especially hormone replacement therapy (HRT) progesterone alone is 'beneficial', but oestrogen alone or in combination with progesterone causes 'improved menopausal symptoms but increased risk of breast cancer, endometrial cancer, stroke, and venous throm-boembolism after long term use', and there is a 'trade-off between benefits and harms'. Antidepressants are of 'unknown effectiveness'.

Contemporary Endocrinology

Menopause Endocrinology and Management, edited by David B. Seiferand Etienne-Emile Baulieu, Michael Schumacher, and Paul Robel, 1999 15. Autoimmune Endocrinopathies, edited by Robert Volp , 1999 14. Hormone Resistance Syndromes, edited by J. Larry Jameson, 1999 13. Hormone Replacement Therapy, edited by A. Wayne Meikle, 1999 12. Insulin Resistance The Metabolic Syndrome X, edited by Gerald M. Reaven and Ami Laws, 1999

Telomerase And T Cells

Our data on estrogen effects in T cells in vitro are reminiscent of an earlier study in which we documented the reversal of some of the age-related T cell changes in postmenopausal women treated with hormone replacement therapy (Porter et al., 2001). In another set of preliminary experiments with small molecule activators of telomerase, we have shown a significant enhancement of telomerase activity in T cells from both healthy and HIV-infected persons (Fauce et al., manuscript in preparation). Thus, therapeutic approaches that are based on telomerase modulation would seem to be promising candidates for clinical interventions in the elderly that are aimed at reversing or retarding the process of replicative senescence in T cells. The major question to be addressed is whether the process of replicative senescence, characterized so extensively in cell culture, has any relationship to events within the immune system during normal human aging. As will be described below, this certainly...

Hormonal Carcinogenesis

An important concept related to human studies of hormonal carcinogenesis has evolved from observations such as those of Thomas et al.17 that mean differences in circulating sex steroid levels associated with increased cancer risk are typically not large. Pike18 made the critical observation that the age-specific incidence curve of breast cancer, as well as endometrial and ovarian cancers, fit the log incidence log age model of Cook et al.19 once an effect of menopause was figured into the model. Based on such a model, small differences in serum hormone levels, since they are present virtually constantly, over a lifetime can be shown mathematically to predict

Christopher I Li Introduction

In addition, there are different histologic types of BC. The two most common are invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), which account for approximately 80 and 5-15 ofall BCs, respectively (2, 3). In this chapter a summary of the pathologic, clinical, and epidemiologic characteristics of ILC, in contrast to IDC recent work investigating associations between hormone replacement therapy (HRT) use and risks of ILC compared to IDC and the accumulated evidence supporting the role of progesterone (P) in the etiology of BC in general, and ILC in particular are presented.

Henri Rochefort Majida Esslimani Sahla and Dany Chalbos Introduction

The assumed role of progesterone and progestins on mammary glands and human breast carcinogenesis has varied between laboratories and countries and is still controversial. Progestins inhibit estrogen (E) action in cell lines and provide protection against the mitogenic effect of Es in endometrium, which is why they are required to overcome the mitogenic activity of E in hormone replacement therapy (HRT) of non-hysterectomised postmenopausal women. The effect of progestins on mammary carcinogenesis is much less clear since molecular and cellular studies diverge according to laboratories (1-2), and it was even proposed that progestins protect against breast cancer (BC) (3). The results of a large randomised NIH clinical trial in USA (4) involving post-menopausal women treated with medroxyprogesterone acetate (MPA) and the E conjugate, Premarin, vs placebo indicate that this association increases the risk of BC by 30 , as previously shown in several observational studies also attained...

History of venous thromboembolism

Oral contraceptives and hormone replacement therapy Compared with oral contraceptives, there have been fewer studies on the relationship between the use of post-menopausal hormone replacement therapy and VTE. The doses of oestrogen used for post-menopausal replacement are much lower than those used for contraception, and the route of administration is sometimes different (transdermal vs. oral). Yet, several studies have shown a 2- to 4-fold increased risk of thrombosis associated with hormone replacement therapy.56,57 Perhaps the lower risk associated with the low oestrogen dose of hormone replacement therapy is neutralised by the higher baseline risk of post-menopausal women due to their older age, in comparison with women of child-bearing age who use oral contraceptives. The high-risk (Table 4) category includes patients with the most severe forms of thrombophilia, including anti-thrombin deficiency, homozygous protein C or protein S deficiency, homozygous factor V Leiden,...

The Clinical Significance of FAS

Moreover, FAS staining in BC was generally greater in pre-menopausal patients than after menopause. These results indicated that progestins also induced FAS expression in vivo, in both malignant and non malignant mammary gland cells, and suggested that FAS is a marker of responsiveness to progestins. Based on the dominant paradigm concerning progestins in BC in France, we initially proposed that FAS is a differentiation marker First, in normal mammary glands, FAS is known to be mostly active during lactation to produce milk lipids (30). Secondly, we observed high accumulation of lipid droplets in R5020-treated T47D cells with

Age Gender Ethnicity and Geography

Whereas a malignant glioma can occur at any age, the average age of onset for glioblastoma is 62 yr (2). In general, gliomas affect males 40 more frequently than females (6). According to a recent study, this greater incidence of glioblastoma in males becomes evident around the age of menarche, is greatest around the age of menopause, and then decreases, suggesting a possible protective effect provided by female hormones (7), though such a protective effect is merely speculation.

Breast Cancer Susceptibility And Other Risk Factors

An important and largely unresolved question is the relationship between genetic and lifestyle risk factors for breast cancer. The combined analysis by the Collaborative Group examined the effect of several important risk factors on the familial risk of breast cancer, including parity, age at first full-term pregnancy, and ages at menarche and menopause. In each case, they found that the relative risks conferred by these risk factors were similar in women with and without a family history (1). These results imply that such risk factors can be assumed to multiply the familial risks of breast cancer (an assumption made in the Tyrer et al. and Gail models). It also suggests that such risk factors are largely independent of genotype. Whether this is true for specific susceptibility genes, in particular BRCA1 and BRCA2, is less clear however. Several studies have examined the effects of these risk factors in BRCA1 2 carriers but many of the results are contradictory, perhaps reflecting...

Protection of the Patient

In normal pelvic films, gonadal protection may obscure the region of interest in women. The female fertile phase ends with menopause, which makes gonadal protection less important. The law states that men need protection where appropriate. G. E.'s old chief used to put it this way Every man up to the age of 60 gets gonadal protection. Older men get it if they request it but they get a piece of sweet chocolate with it.

Natural Models Of Alzheimerlike Pathology

Rhesus monkeys are Old World monkeys with a maximum life span of approximately 40 years they reach puberty at 3-4 years of age, and females go through menopause at approximately 25 years of age (Walker, 1995). Age-related cognitive decline is well-documented in rhesus monkeys, but a dementia-like state has not been reported. Rhesus monkeys develop senile plaques with age, usually in their early-mid 20's (Walker and Cork, 1999). These lesions are cytologically and biochemically similar to human plaques, except that the abnormal neurites that surround the core are devoid of tau filaments. Indeed, although primates can manifest tau abnormalities in brain, fully formed neurofibrillary tangles have not yet been detected in any nonhuman primate, including the apes. Squirrel monkeys. In addition to widely varying phenotypes and lifespans, nonhuman primates show species-specific patterns of age-associated lesion development in brain. Squirrel monkeys are small, New World...

BS2 Intermediate Course of the Disease

The process usually burns out with more or less fibrous sequelae, but the ending of the inflammatory process is unpredictable. Frequently menopause brings relief in women, but the association is not constant, and the end may come after or before the menopause. For men it is similarly unpredictable.

Estrogen Receptor and Normal Cell Cycle in Breast Tissue

PR mediates the mitogenic effect ofprogesterone which further stimulates proliferation (4). This latter effect has now been demonstrated epidemiologically in that hormone replacement therapy (HRT) after menopause has only a mild effect on BC risk if it involves estrogen only (7), whereas the addition of progestins adds significantly to the likelihood of later BC development in the post-menopausal woman (8-10)

Tyrercuzick International Breast Cancer Intervention Study

The personal risk factors incorporated into the IBIS model are the ages at menarche, first childbirth and menopause, parity, height, and body mass index, and two diagnoses associated with increased risk, namely atypical hyperplasia and lobular carcinoma in situ. Both these diagnoses are known to be associated with at least a fourfold increase in risk in the general population (35,36). Some risk factors have not yet been included. These are the administration of exogenous hormones such as the oral contraceptive pill and hormone replacement therapy and the presence of ductal carcinoma in situ.

Estrogen Progesterone and Androgen Receptors

Reproductive and homeostatic systems, respectively. The sex steroid receptors ER, PR, and AR direct transcription of genes involved in sexual development, differentiation, and specification (Tables 3.4, 3.5). As a result of their growth-promoting activities in these processes, these receptors are pharmacologically targeted in a number of neoplastic reproductive tissues. Receptors ERa and ERjS are predominantly expressed in reproductive tissues, as well as in vasculature, cardiac muscle, and bone. Their activity is subject to estradiol availability, which is regulated by hormonal cascades generated from the ovary and other steroidogenic tissues. Confirmation of the role of ERs in the regulation of the reproductive tract was achieved by targeted deletion of ERa and ERjS alleles in transgenic mice, which develop normally but are infertile or suffer ovarian dysfunction, respectively.296,297 In addition to reproductive maintenance, specialized roles for ERs include regulation of bone...

Clinical evaluation of premenstrual syndrome

The differential diagnosis includes hypothyroidism, anemia, perimenopause, drug and alcohol abuse, and affective disorders. Common alternative diagnoses in patients complaining of PMS include affective or personality disorder, menopausal symptoms, eating disorder, and alcohol or other substance abuse. A medical condition such as diabetes or hypothyroidism, is the cause of the symptoms in 8.4 , and 10.6 have symptoms related to oral contraceptive (OC) use.

Sites of Estrogen Production

The major sites ofE production differ in pre- and postmenopausal women. Before the menopause, the ovary is mainly responsible for circulating levels of E. However, peripheral synthesis of E is of greater importance in postmenopausal women when ovarian E biosynthesis ceases. The postmenopausal ovary along with the adrenal cortex produces substantial amounts of androgen (2,3) that can be used as substrate for synthesis of E at peripheral sites such as fat (4), skin (5), muscle (6), liver (7), and BC (8), all of which possess aromatase activity.

Specific interventions

Coronary heart disease (CHD) includes history of myocardial infarction, unstable angina, stable angina, coronary artery procedures, or evidence of clinically significant myocardial ischemia. CHD risk equivalents include clinical manifestations of non-coronary forms of atherosclerotic disease, diabetes, and > 2 risk factors with 10-year risk for hard CHD > 20 . Risk factors (RF) include age (male > 45 years, female > 55 years or premature menopause without hormone replacement), positive family history for premature CHD (in first-degree relatives < 55 years and first-degree female relatives < 65 years), cigarette smoking, hypertension (blood pressure > 140 90 mmHg or taking antihypertension drugs), HDL < 40 mg dl (1.0 mmol l). If HDL cholesterol is over > 60 mg dl (1.6 mmol l), subtract one risk factor from the total (adapted from Dub 2000 and Schambelan 2002). Coronary heart disease (CHD) includes history of myocardial infarction, unstable angina, stable angina,...

Regulatory Status

The German E Commission has approved St. John's wort for internal consumption for psychogenic disturbances, depressive states, sleep disorders, and anxiety and nervous excitement, particularly that associated with menopause. Oily Hypericum preparations are approved for stomach and gastrointestinal complaints, including diarrhea. Oily Hypericum preparations are also approved by the Commission E for external use for the treatment of incised and contused wounds, muscle aches, and first degree burns (96).

Terminology and Definitions

The term andropause indicates a particular type of hypogonadism that is related to aging in men and is said to consist of the following diminished sexual desire and erectile function, decrease in intellectual activity, fatigue, depression, decrease in lean body mass, skin alterations, decrease in body hair, decrease in bone mineral density resulting in osteoporosis, and increase in visceral fat and obesity (24). The word andropause is an attempt to draw a parallel in men to the experience of menopause in women. Whereas menopause occurs abruptly, andropause is said to occur quite slowly. As well, menopause is associated with the irreversible end of reproductive life, whereas in men spermatogenesis and fertility continue into old age. In the opinion of some observers, trying to equate the two is rather questionable (23). The existence of andropause is a subject of controversy partly because of great difficulty distinguishing this syndrome from age-related confounding variables such as...

What conditions are often missed

Menopausal symptoms can also be overlooked as we focus on a particular symptom. Some important pitfalls are given in Table 15.3 . Lead poisoning Malnutrition (unsuspected) Menopause syndrome Migraine (atypical variants) Paget's disease Pregnancy (early) Seizure disorders Tourette's syndrome Urinary infection

Gillian K Reeves Emily Banks Timothy Ja

The importance of endogenous hormones in the etiology of breast cancer is evident from the strong relationships between breast cancer risk and certain aspects of a woman's reproductive history, such as age at menarche, age at first birth, and age at menopause.1 More recently, the risk of developing breast cancer among post-menopausal women has also been shown to increase substantially with increasing levels of circulating estradiol,2 thus providing more direct evidence for the role of hormones in the development of the disease. The relationship between endogenous hormones and breast cancer risk leads naturally to the question of whether exogenous hormones, such as oral contraceptives and postmenopausal hormone therapy, might also have an effect on breast cancer risk.

Cardiovascular Complications

Patient characteristics associated with cardiac long-term and late effects are older age and preexisting cardiac disease. Premature menopause from cancer Chemotherapy, particularly alkylating agents like cyclophosphamide, can induce infertility and, in women, premature menopause, with its attendant problems of hot flashes, mood swings, vaginal dryness, and urinary incontinence. Cyclophosphamide is commonly used in breast cancer, but management of the menopausal symptoms is complicated by the fact that hormone replacement therapy is considered contraindi-cated in patients with a history of breast cancer. Consequently, other treatments must be used for hot flashes, such as antidepressants.52 This example illustrates the importance of both recognizing the symptoms related to ovarian failure in a cancer patient in which it would be otherwise unexpected, and having knowledge of the oncologic considerations of the therapies being chosen. Bone health can be impaired in many ways. Premature...

Theoretical Issues

Two mutually informing analytic frameworks have been central to much recent fertility research the life course and the proximate determinants frameworks. The biological nature of fertility determines the structure of each framework. In fact, both frameworks rest on very straightforward observations. The life course perspective adopts a sequential model because children tend to be born one at a time, not in lots (Namboodiri 1972 198). Moreover, because women are biologically restricted to having children only between menarche and menopause, fertility may be considered as an irreversible, time-limited sequence.

Estrogen and its Receptors

Estrogens and estrogen receptor (ER) have been implicated in the pathogenesis and progression of ovarian cancer based on epidemiological and experimental observations (41-43). Even though estrogens plus progestins taken as an oral contraceptive during the premenopausal period in women are protective, when used in postmenopausal years as hormone replacement therapy, estrogens may increase the risk of ovarian cancer (7). Although no difference in risk was observed in women who had used estrogens continuously supplemented by progestins, an elevated risk of epithelial ovarian cancer in women who had used estrogen, either unopposed or combined with sequential progestins, was observed in an epidemiological study (41).

Aging General Characteristics

Aging in the rhesus monkey has many similarities to human aging. The incidence of cancer, type 2 diabetes, and other diseases increase in the rhesus monkey similar to humans. In addition, diseases and clinical conditions, such as osteoporosis, that occur in aging women also occur in the rhesus female. Changes that occur during aging fall into two categories those associated with declining physiological function and those contributing to a disease state (Hadley et al., 2005). Obvious signs of aging in nonhuman primates and humans include loss of posture due to muscle loss (sarcopenia). Recent evidence has directed new attention to the important role of immune system function as a central element in a possible range of health-related issues and disease states that emerge as the individual ages (Nikolich-Zugish and Messaoudi, 2005). In addition, visual and auditory systems undergo an age-related decline, similar to humans (Torre and Fowler, 2000 Roth et al., 2004). Similarly, there is...

Frequency Of Infertility

Comprises artificial insemination, in vitro maturation (IVM) of oocytes, in vitro fertilization (IVF), embryo culture and embryo transfer. For presumptively infertile women aged up to about 37, the outcome of clinical IVF (in this general context meaning IVF together with embryo culture and transfer) is good, with an average of about 32 of treatment cycles in the United States resulting in a live birth (Wright et al., 2003). But for women approaching 40 or over, the efficiency of IVF drops sharply, to only about 5 after the age of 42 (Wright et al., 2003). Similarly, the incidence of natural conceptions falls progressively towards the age of 40, prior to overt menopause. The reasons for this precipitous drop in fertility are not well understood, but a decline in the ability of the uterus to support pregnancy does not seem to be a primary factor, in view of the number of births to women over 40 carrying a surrogate embryo made with oocytes from younger women. The quality of oocytes and...

Hellevi Peltoketo Veli Isomaa Debashis Ghosh Pirkko Vihko

Estrogen and steroid metabolism in the target or surrounding cells therefore determine the availability of estrogens in breast tissue. The ovary is the single primary source of estradiol (E2) in the circulation of premenopausal women, but circulating estrone (E1) and androgens originating from the adrenal gland are also converted to E2 in peripheral tissues such as adipose tissue and muscles, including smooth muscle cells of the vena cava.15-18 Breast adipose and epithelial cells also contain enzymes needed for the production in situ of E2 from circulating precursors,7,16 which may further enhance estrogen action in the tissue. After menopause, in particular, estrogen biosynthesis in peripheral tissues has a major role in estrogen action.19 Finally, nutriment may contain compounds with estrogenic and or antiestrogenic effects.20

Neoplastic Conditions

Malignant tumours primary malignant ovarian neoplasms are of surface epithelial, germ cell or sex cord-stromal type. Surface epithelial tumours are most common and these are serous, mucinous, endometrioid, clear cell, transitional or undifferentiated carcinomas in type. Borderline neoplasms (tumours of low malignant potential) also occur and these may be one of any of the morphological subtypes described, most commonly serous or mucinous. These are neoplasms with malignant nuclear characteristics but in which there is no evidence of stromal invasion. Ovarian surface epithelial adenocarcinomas are most common in middle-aged and elderly women, in nulliparous women and those with an early menarche and late menopause. The oral contraceptive pill is protective. It has been suggested than women who are exposed to ovulation-inducing drugs are at increased risk of the development of ovarian carcinoma. Women with BRCA1 or BRCA2 gene mutations are at increased risk of the development of both...

Effects of sex steroid hormones on behavior over the lifespan

Most of the data reviewed in this chapter concern effects of sex steroid hormones on adult behavior, resulting either from organizational effects of early hormonal exposure during the fetal or neonatal periods or from activational effects of sex steroid hormones in adulthood. However, sex steroid hormone levels change dramatically both in children as they mature and enter puberty, and in women when the activity of the reproductive axis declines at menopause thus, one would expect to see accompanying changes in behaviors modulated by sex steroid hormones at these times. One would also predict that sexually dimorphic areas of the brain that are dependent on adult levels of sex steroid hormones for maintenance of the dimorphism would change in morphology over puberty and menopause. In the past few years, a number of studies have examined how cognitive functions change in women as they enter menopause and how steroid hormone replacement therapy affects cognitive function. Although some...

Colorectal cancer epidemiology

Figure 17.1a demonstrates that colorectal cancer is more common in males than in females and in both sexes the incidence rate increases with advancing age. This difference in sex incidence may partly be explained by evidence from a number of case-control and cohort studies which demonstrated an association between hormone replacement therapy (HRT) and colorectal cancer, with the majority of these suggesting a protective effect (Giacosa et al., 1999). Accumulating evidence implicates obesity as a risk factor for colorectal cancer (Giacosa et al., 1999), and a positive association may exist between colorectal cancer and diabetes (La Vecchia et al., 1997). Not surprisingly, smoking has also been suggested as a significant risk factor (Giovannucci, 2001). Many studies have elucidated precise dietary and other variables responsible for the observed

Influence of Age and Sex on Metal Toxicity

Adult women before menopause lose iron with menstrual blood, and there is a high prevalence of low iron stores in this population group. Because it is known (cf Chapter 23) that persons with low iron stores have an increased gastrointestinal uptake of cadmium, women often accumulate more cadmium than men. Higher blood cadmium values have been reported among women than men in many epidemiological studies.

Agerelated Changes in Hormones and Their Receptors in Animal Models of Female Reproductive Senescence

Traditionally, the onset and progression of menopause in humans has been attributed to ovarian follicular decline. Because the follicles are the primary source of circulating estrogens, these age-related changes lead to a number of symptoms such as hot flashes, mood swings, irritability, and depression, as well as increased risk of osteoporosis, cardiovascular disease, and age-associated diseases. Recent research indicates that along with the ovarian changes at menopause, the hypothalamic and pituitary levels of the reproductive axis also undergo significant changes during reproductive aging. Indeed, current research suggests a neural, as well as hormonal, mechanism involved in the menopausal process. A number of animal models are available to study these processes, most commonly the nonhuman primates and rodents, and to a lesser extent, avian systems. Here, we will discuss Old and New World monkey models, rats, mice (wild type, transgenic, and genetically modified), and birds as...

Clinical evaluation

Ninety percent of patients with endometrial cancer have abnormal vaginal bleeding, usually presenting as menometrorrhagia in a perimenopausal woman or menstrual-like bleeding in a woman past menopause. Perimenopausal women relate a history of intermenstrual bleeding, excessive bleeding lasting longer than seven days or an interval of less than 21 days between menses. Heavy, prolonged bleeding in patients known to be at risk for anovulatory cycles should prompt histologic evaluation of the endometrium. The size, contour, mobility and position of the uterus should be noted.

Role Of Mammographic Density

Mammographic sensitivity is lower in women with mammographically dense breasts.11,12 The differences in sensitivity and false-positive rate observed in women below and above age 50 parallel the decrease in mammographic density observed with increasing age between 35 and 55.14,15 Very dense mammographic patterns especially appear to change to lower-risk patterns during the perimenopausal period (age 45-55).14 There is, of course, no abrupt change in the positive predictive value of mammogram at age 50,16 but, rather, a gradual increase. This decrease in mammographic density and increase in sensitivity is most likely an effect of menopause and not age per se.17,18

QOL in Long Term Survivors of Breast Cancer

Eleven of the 16 studies discussed physical domain QOL outcomes for long-term survivors.2,4,32,41,43,46-51 Generally, survivors report lower physical domain QOL than healthy controls and poorer physical functioning.4,41,43,49 Arm pain, including swelling, loss of sensation, weakness, and stiffness, are common.4,32,48,50,51 Survivors also report fatigue,2,46 with one study finding that younger survivors report the lowest levels of vitality.51 Physical problems associated with treatment induced menopause are also common.2,32 One study shows that physical functioning was predicted by age at diagnosis,48 while another found that older age in general is related to worse physical domain QOL.47 Another study found that physical health was most affected among women who were both diagnosed with lymphoma and treated with chemotherapy.2

Risk Factors For Breast Cancer

Breast cancer is clearly related to endogenous hormones, and numerous studies have linked breast cancer risk to age at menarche, menopause, and first pregnancy. Although the absolute age-specific incidence of breast cancer is higher in postmenopausal than premenopausal women,125 the absolute rate of rise of the curve is greatest up to the time of menopause, then slows to one-sixth of that seen in the pre-menopausal period. Further support for the promotional role of estrogen in breast cancer comes from observations that early menarche,126 late menopause,127 nulliparity, and late age at first birth128 all increase the risk of breast cancer development. An increased number of ovu-latory cycles is suggested to be the common mechanism of increased risk. The effects of exogenous hormones in the form of oral contraceptives and hormone-replacement therapy (HRT) on breast cancer risk have been studied extensively. Overall, there is no convincing evidence of increased risk with use of oral...

Interactions among Risk Factors

The interactions between a family history of breast cancer and other risk factors have been examined, often with conflicting results. Data from the Nurses Health Study149 show that women with known risk factors, such as age at menarche or menopause, parity, age at first birth, alcohol use, the presence of benign breast disease, and a mother or sister with breast cancer, develop disease at rates equivalent to women with a family history alone. In contrast, Anderson and Badzioch150 and Brinton et al.151 reported that hormonal factors further modulate risk in women with a family history of breast cancer, although the effect varies with the factor under study. Studies of the interaction between HRT and other known risk factors also have variable results, depending on the risk factor under study. In a meta-analysis of 16 published studies, Steinberg et al.143 found that the effect of HRT did not differ among parous and nulli-parous women and those with or without benign breast disease...

Fertility and Aging Men An Introduction to the Male Biological Clock

The levels of sex hormones in men decline with age. The roughly 1 per year decline in testosterone levels after age 30 has been termed andropause, or ''symptomatic hypogonadism in the aging male.'' Rhoden and Morgentaler estimate that between 2 and 4 million men in the United States alone suffer from hypogonadism, but only 5 of men are getting treatment for their symptoms. or as sudden as that associated with menopause, but it can be equally significant for fertility and overall well-being. Recently, there has been a lot of interest in declining testosterone levels in men. The roughly 1 per year decline in testosterone levels after age 30 has been termed andropause and is associated with a plethora of congenital and acquired disease-syndromes (McLachlan, 2000).

Pharmacological Toxicological Effects 51 Endocrine Effects

Although many products containing ginseng are marketed specifically for postmenopausal women, a recent review concluded that there is insufficient evidence that ginseng is effective for treatment of menopausal symptoms (11). In vitro, Siberian ginseng extract, but not P. ginseng extract, binds to estrogen receptors. Both extracts have affinity for progestin, glucocorticoid, and mineralocorticoid receptors (32). A recent study reported that a morning evening formulation containing ginseng and other constituents relieved menopausal symptoms, but no placebo control was included so it is difficult to tell whether the effect was caused by the formulation or a placebo effect (33). A 44-year-old woman who had experienced menopause at age 42 experienced three episodes of spotting associated with use of Fang Fang ginseng face cream (Shanghai, China). Interestingly, these episodes of bleeding were associated with a decrease in follicle-stimulating hormone levels and a disor

Osteoporosis Prevention

Pharmaceutical HRT is sometimes used for preventing loss of bone following menopause however, a growing number of users are concerned about the increased risk of breast cancer associated with long-term HRT. As such, phyto-oestrogens have been used as an alternative to prevent osteoporosis. Most research has focused on soy isoflavones, although there is some evidence that red clover-derived isoflavones may also be of benefit.

Epidemiological Basis For Considering Gonadotropinhormonereleasing Hormone Analogues

Of early menopause or surgical oophorectomy on breast cancer risk. Epidemiological studies clearly demonstrate that early menopause, whether natural or artificial (bilateral oophorec-tomy), substantially reduces breast cancer risk. The large case-control study of Trichopoulos et al.2 showed that artificial menopause below age 35 is associated with a breast cancer relative risk of 0.36 (a 64 reduction). Feinleib3 noted in his large cohort study that among 1278 women with artificial menopause before age 40, six had breast cancer compared to an expected incidence of 24.0, a 75 reduction. Hirayama and Wynder's4 epidemiological study found that the relative risk of breast cancer was 0.56 for women with bilateral oophorectomy for women who were oophorectomized before age 37, the relative risk was 0.41 (i.e., a 59 reduction). What is of key importance is the magnitude of the benefit and the consistency of these findings. Menopause before age 35 is associated with a 60 -75 reduction in breast...

Breast Cell Proliferation And The Estrogen Plus Progesterone Hypothesis

The effect of menopause or oophorectomy on breast cancer risk is thus predictable in light of these effects of estrogen and progesterone on breast epithelial cell proliferation. Cessation of ovarian function reduces cancer risk by eliminating the breast mitogen progesterone and reducing estrogen levels.

Association of Osteoporosis and CVD

LBMD was associated with increased mortality form CVD (Browner et al., 1991 von der Recke et al, 1999). In the study of osteoporotic fractures research group (Browner, 1991), 9704 ambulatory women aged 65 years and older were prospectively followed. LBMD at the proximal radius was strongly associated with increased mortality from stroke (relative risk 1.74 95 CI 1.12-2.70). This association was not confounded by other risk factors for stroke such as age, hypertension, diabetes, smoking, or previous history of stroke (Browner et al., 1991). Another study involved two populations of healthy women one group early after menopause with a mean age of 50 years and another later after menopause with a mean age of 70 years. In this study (Von der Recke, 1999), each decrease of one SD in bone mineral content was associated with a 2.3-fold increased risk of dying from CVD within 17 years of menopause. Elderly women (over 70 years of age) had a 1.8-fold increase of such a risk. These data...

Cardiovascular Disease

There are many potential mechanisms by which soy may improve cardiovascular outcomes, including reduction in total cholesterol, LDL, HDL, triglycerides, lipoprotein a, blood pressure, C-reactive protein, homocysteine, endothelial function, systemic artery compliance, and oxidised LDL (Balk et al 2005). A review by the North American Menopause Society suggests that the most convincing health effects of soy can be attributed to the actions of isoflavones on lipids, with studies finding statistically significant reductions in LDL and triglycerides, as well as increases in HDL (Greenwood et al 2000). It is unclear how soy exerts its beneficial effects on lipid metabolism or Soy 1107

Postmenopausal Dyspareunia

Attempts to lessen the pain through the use of water-based lubricants and topical estradiol cream had not been successful, and she did not wish to try systemic hormone replacement therapy for fear of developing breast cancer. A detailed sexual history revealed that Brenda had suffered from intermittent pain during intercourse for at least 15 years but had never complained about it, and that Alexander had always had difficulties with ejaculatory control. Over the past 4 years, Brenda reported difficulty getting sexually aroused, diminished lubrication, postcoital bleeding, and less interest in sex. Their current sexual frequency was less than once every 3 months, a frustrating situation for Alexander, who had hoped that their youngest child leaving home in the previous year would result in more frequent sexual activity. In the previous 5 years, the couple had also experienced significant life stressors including the sudden death of Brenda's mother and major financial problems....

Division H Of Meiosis

Ovulation of a single ovum each month requires only about a total of 400 oogonia over the 30-40 year period of reproductive fertility. At the time of menopause the number of viable oogonia in the ovary is virtually zero. These events are summarized in Figure 13-3. It is interesting that the ovum that is ultimately fertilized is the product of an intense selection procedure there is a ratio of atresia to selection of 1000 1. Figure 13-4 presents a schematic diagram of a single

Longlived Monkeys Have Life Spans Proportional To Human Centenarians

Post-reproduction expected from primate patterns. Hammer and Foley (1996) use body and raw brain volume estimates from fossil crania to predict early hominid longevity using a multivariate regression of log body weight and brain volume. Estimates based on regressions ofanthropoid primate subfamilies, or limited to extant apes, indicate a major increase in longevity between Homo habilis (52 to 56 years) and H. erectus (60 to 63 years), occurring roughly 1.7 to 2 million years ago. Their predicted life span for small-bodied H. sapiens is 66 to 72 years. From a catarrhine (Old World monkeys and apes) comparison group, Judge and Carey (2000) predict 91 years when contemporary human data are excluded from the equation. For early hominids to live as long or longer than predicted was probably extremely rare the important point is that the basic Old World primate design resulted in an organism with the potential to survive longer than a contemporary mother's ability to give birth. Notably,...

Vasomotor Symptoms

Quality of life in menopause encompasses more than just absence of symptoms. It includes enjoyment of life, participation in meaningful relationships, work, and play (Matthews and Bromberger, 2005). Although most women in Western societies report hot flashes and night sweats, for most of these women such symptoms do not affect quality of life. In fact, data from the Melbourne Women's Mid-life Project show that well-being increases across the menopause transition (Dennerstein et al., 2003). Lifestyle changes are recommended first for vasomotor symptoms. These include weight reduction for women who are significantly overweight it has long been considered that women who were obese had fewer vasomotor symptoms because of elevated estrone levels from aromatization of adipose tissue to androgens than to estrone. However, new evidence shows that the occurrence of VMS in obese perimenopausal women may be due to the increased heat insulation afforded by greater adiposity, leading to more hot...

Recommended Resources

North American Menopause Society http Menopause http Alternatives in menopause by herbalist Susan Weed http Mayo Clinic Menopause page http www.mayo Planned Parenthood Menopause page http WebMD Menopause page http default.htm

Genisteine And Isoflavones

Estrogen plays a role in the central nervous system through binding estrogen receptors located in the brain and exerting neuroprotective and neurotrophic properties 58 . Epidemiological studies suggest that postmenopausal women using estrogen replacement theraphy (ERT) have a decreased risk of developing dementia. Although ERT alleviates the symptoms associated with menopause and has a positive effect on bones, ERT in postmenopausal women has been linked to a higher incidence of cervical and breast cancer 59 . Consequently the selective estrogen receptor modulators (SERMs) compounds that exert tissue-specific estrogenic effects may provide the benefits of ERT without the risks. Groups of natural SERMs are the soy-derived phytoestro-gens, which are structurally similar to estrogen and may serve as an alternative to ERT.

Models of Hypertension in Aging

All forms of hypertension studied to date are caused by a defect in the handling of sodium and water by the kidney. There is a shift to the right in the pressure-natriuresis relationship (higher blood pressure) in which a hypertensive individual must increase blood pressure in order to excrete a normal sodium load. There are sex differences in blood pressure control in humans and animals, with males having higher blood pressure than females. However, blood pressure increases in some women after menopause. The mechanisms that play a role in hypertension, and have been studied extensively, include the renin-angiotensin-aldosterone system, endo-thelin, oxidative stress, the sympathetic nervous system, androgen estrogen ratio, and obesity.

Possible Mechanisms Responsible For Hypertension

Androgens estrogens In experimental settings, many in vitro, estradiol has been shown to have a variety of effects that should be cardiovascular protective. However, despite the potential of estradiol to combat cardiovascular disease, large clinical trials on the effect of hormone replacement therapy (HRT) in post-menopausal women do not support these findings (The Writing Group for the PEPI Trial, 1995 Burry, 2002). Furthermore, HRT doesn't always result in a reduction in blood pressure in post-menopausal women, and even if it does so, the reduction is not dramatic. Proponents of the beneficial role of estradiol in cardiovascular disease cite the use of progesterone in HRT as possibly negating the positive effects of estradiol. However, in women who have experienced surgical menopause, estrogen replacement therapy (ERT) was also not successful in reducing blood pressure (Powledge, 2004). Thus reductions in estradiol that occur at menopause do not fully explain the progressive...

Anatomical And Morphological Relationships Of The Female Reproductive System

Ligaments Female Reproductive System

The adult human ovary is 4-5 cm in length and is almond-shaped. Structurally each ovary consists of the cortex (outer) and medulla (inner) zones (see Figure 13-2). Just below the surface layer of connective tissue is the germinal epithelium, which is the site of generation of the follicles. Each primary follicle contains one central germ cell or oogonium, which is surrounded by a layer of epithelial cells. Surrounding the follicular cells, but separated by a basement membrane, are the theca externa and theca interna cells (see insert box of Figure 13-3). The medulla comprises the central region of the ovary, which is devoid of follicles. The normally functioning ovary undergoes, over a 4-5 decade interval, a series of profound changes that are essential for female development, puberty, reproduction, and menopause.

Chromosomal Instability A New Paradigm for Estrogeninduced Oncogenesis

Human sporadic breast cancer (BC) comprises > 90 of all BC cases whereas familial BC is less than 10 (1). Despite its likely multifactorial origin, there is now pervasive evidence from epidemiological and animal studies, developed over the past several decades, that the causation of human sporadic BC primarily involves female sex hormones, particularly estrogens (Es) (1-8). This view is consistent with long standing epidemiological data relating extended exposure to Es and elevated BC risk, such as early first menarche, late age at menopause, nulliparity, late age at full-term pregnancy, and absence of lactation (5, 6). These BC risk factors are all related to pre-menopausal women. Moreover, all ofthe well-established BC risk factors are associated with elevated circulating E levels. Even lesser risk factors such as obesity and alcohol ingestion are known to significantly increase serum E concentrations in women (9, 10). These earlier studies are buttressed by results of the recent...

Age at Onset and Resolution

Early menarche, although cases have been published in which the two co-occur. Similarly, there is a tendency for the disease to burn out after menopause in women. Patients with continuously active disease after the age of 50 (mostly men), however, regularly appear, and for some the disease may even have started at that age.

Controversies and Discrepancies Concerning Progestin Action on Mammary Glands

Progestin Pathway

There is a relatively high consensus among laboratories on the mitogenic effect of Es on the mammary gland, and coherence between in-vitro studies on cell lines, and in-vivo epidemiological data, even though the detailed mechanism is not yet fully understood. By contrast, the effects of progestins after menopause, i.e., whether good or bad, have been extensively debated according to the laboratory and country involved. This is mostly due to the fact that different progestins are being used and that most controlled clinical studies have been conducted using MPA, which is rarely prescribed in Europe. In Europe, and particularly in France, at least 15 different preparations are used, varying in their structure (natural progesterone, synthetic pregnanes, 19 nor-pregnane, and 19 nor-testosterone derivatives), and in their mode of administration (continuous or discontinuous, per os or transparenteral) (10). Consequently, the receptors interacting with progestins are not only the two PR...

What is Your Diagnosis

Calcium Breast Mass

In older women, new fibroadenomas are a rarity and are always very suspect. On physical examination, the fibroadenoma is usually a very mobile lesion. As it may grow rapidly and occasionally reaches a spectacular size, patients are often frightened. The mammogram displays the fibroadenoma as an oval and smoothly marginated mass, frequently speckled with coarse calcifications that may remind you of popcorn (Fig. 12.3a). Sonographi-cally the appearance of a fibroadenoma is compatible with a solid mass that shows a rather homogeneous internal echo without any dorsal echo shadowing and also a smooth contour (Fig. 12.3b). If the appearance of the lesion is not that clear-cut or if there is suspicion otherwise, an ultrasound-guided core needle biopsy is rapidly performed, which usually ends the diagnostic uncertainty.

Identification of a Second HS Locus to Chromosome

The apparent hormonal influence of HS made the oestrogen receptor-a a good candidate gene. HS symptoms usually begin post puberty and the average age of onset is early to mid-twenties. There have only been a few reports of prepubertal HS and these cases have usually been associated with precocious puberty or a hormonal imbalance 42 . Women are significantly more frequently affected by the disease then men and also often describe a premenstrual flare of the disease 25 . Symptoms tend to improve after the menopause 61 . There were however no obvious differences in hormone levels between patients and controls 2 suggesting that any hormonal influence may take place at the receptor level.

Evidence for Ovarian Senescence in Rhesus Monkeys

Female Lifespan Ovarian Reserve

The number of potentially viable oocytes available to the reproducing female depends on the size of the primordial follicle population within the ovary. In humans, primarily due to follicular atresia and secondarily because of follicular recruitment, the numbers of primordial follicles decrease dramatically from birth to the onset of menopause. At the end of the reproductive lifespan, the ''ovarian reserve'' of viable follicles and oocytes is essentially depleted, and the ovary is said to be senescent (Faddy and Gosden, 1996). Concomitantly, ovulatory activity ceases and levels of estrogen decrease markedly. As a result, FSH secretion increases strikingly because of diminished negative feedback from estrogen (Walker, 1995). Bioactive FSH retrieved from postmeno-pausal women's urine was in high demand for a number This study (Nichols et al., 2005) illustrates that in several important respects, the rhesus monkey is an appropriate model for studying age-related loss of fertility in...

Ovarian Germ Cell Tumors

Embryonic Cyst Ovary

Mature teratomas are cystic in 80 of cases (Figure 4-7) and solid in the remaining 20 of cases. Mature solid teratomas occur in younger women and must be distinguished from immature teratomas, with which they share many features. Cystic teratomas represent the most common ovarian GCT. These teratomas can be diagnosed during a woman's entire reproductive life and even after menopause.

Nonhuman Primate Models Old World Monkeys

Studies in intact, aged macaques and baboons focus primarily on the perimenopausal period, when menstrual cycle variability increases, fecundity decreases, and hormonal status first changes. Humans and OWMs show very similar changes in urinary estrogen and progestin profiles once they begin perimenopause. However, there are a few differences in the timing of the hormonal transition to perimenopause middle-aged women show a period of increase in FSH and decrease in inhibin A along with a cyclically high level of estrogen prior to onset, whereas rhesus monkeys do not (Bellino and Wise, 2003). Hence rhesus monkeys show a more immediate transition to perimenopause, whereas the human transition is more gradual. In both humans and OWMs, the onset of perimenopause is accompanied by declines in estrogen and progesterone levels, and a shorter follicular phase is observed during the menstrual cycle. In accordance with this, LH FSH levels increase, partly due to the release from negative...

Lack of Association between HS and Endocrinopathies

HS usually begins after puberty when the apocrine glands are fully developed. A few cases have been reported in children, as clinical manifestations of premature adrenarche or early puberty 11, 12, 15 . This represents in fact the strongest evidence for an influence of andro-gens on HS. However, HS is more common in women and usually affects premenopausal women, although it may appear after menopause 3 . The rare incidence of HS in post-menopausal women does not stand in favour of a role for androgens, since hyperandrogenism after the menopause has yet to be demonstrated. On the other hand, improvement during and re

Age Related Changes in Fat Distribution

Intra-abdominal fat accumulation, known to be independently related to the metabolic concomitants of obesity (39-44), has also been demonstrated to be greater at any given BMI or BF in older individuals (45-47). While the accumulation of intra-abdominal fat with aging may be progressive in men, it appears to greatly accelerate in women following menopause (62,48). Although there are racial ethnic differences in fat distribution (see Chap. 3), relatively little is known about how these are affected by aging. It appears that African-American women have greater central fat distribution than Caucasian women before menopause (50) but that the slope of the increase with age is not different between the two groups. Of interest, NHANES I also noted that central adiposity conferred relatively less risk for cardiovascular disease in black women (51). This finding agrees with earlier reports that central adiposity was not a strong risk factor for the development of non-insulin-dependent diabetes...

Sexual aversion disorder

There are a number of reasons that people lose interest in sexual intercourse. It is normal to experience a loss of desire during menopause directly after the birth of a child before or during menstruation during recovery from an illness or surgery and during such major or stressful life changes as death of a loved one, job loss, retirement, or divorce. These are considered normal causes for fluctuations in sexual desire and are generally temporary. Changing roles, such as becoming a parent for the

Genetic Testing Complexitieswhere To Start

Unaffected woman who presents for risk assessment due to concern regarding her maternal family history of breast cancer. She tells you she is certain she will one day develop breast cancer since both her mother and maternal grandmother had breast cancer. After assessing the pedigree, it is clear that the paternal side is more concerning for strong genetic risk due to a mutation in BRCA1 or BRCA2. A common misconception is that risk for female cancers can only be transmitted through the maternal side. Although the maternal side includes two generations of women with breast cancer, the ages of onset, well past menopause, are not highly suggestive of risk due to BRCA1 or BRCA2. In addition, there are many at-risk women on the maternal side who have been cancer-free there is no ovarian or other cancers suggesting an inherited cancer syndrome, there are no rare tumors or any individuals with multiple primary cancers. In contrast, the paternal side includes two women with breast cancer...

Comparison with Other Risk Factors

An additional feature of mammographic density, which sets it apart from other risk factors for breast cancer, is that it appears to be modifiable. Mammographic density is known to regress with age, attributed to the hormonal changes associated with menopause. There is evidence that hormone replacement therapy can preserve or increase mammographic density in peri- and postmenopausal women 16 . It has also been shown that a hormonal contraceptive that suppresses ovarian function can result in a significant reduction in mammographic density in just a 1-year interval 17 . It is not yet known whether the reduction in density also reduces breast cancer risk. Nevertheless, the observation that a strong risk factor for breast cancer can be altered gives hope for the development of potential preventive strategies.

Aging Of The Reproductive System In Females

The rhesus monkey (Macaca mulatta) has been a biomedical model for reproductive studies in women since the early 1900s (Heape, 1900). Female rhesus monkeys are pubertal by 2.5 to 3.5 years of age and exhibit menstrual cycles approximately 28 days in length, similar to humans. Furthermore, rhesus monkeys experience a reproductive decline much like that of human menopause around 24 years (Gilardi et al., 1997 Bellino and Wise, 2003). Urinary hormone profiles demonstrated that, like women, menopause in rhesus monkeys is associated with amenorrhea, low urinary estrogen conjugates, and irregular patterns of urinary concentrations of progesterone metabolites (Gilardi et al., 1997). Urinary FSH levels also increase in postmenopausal rhesus monkeys (Shideler et al., 2001). about the mechanism that initiates menopause. Age alone is not a reliable predictor of menopause, but endocrine disturbances often precede noticeable irregularities in menstrual cyclicity. Few longitudinal studies have...

Breast And Ovarian Analysis Of Disease Incidence And Carrier Estimation Algorithm Boadicea

Nongenetic risk factors, e.g., parity, breast feeding, and age at menopause may be possible when the contribution of these factors to the overall risk to BRCA carriers has been more comprehensively assessed by long-term studies such as Epidemiological Study of Familial Breast Cancer (EMBRACE) (27).

Cognitive Function

Supplementation with the same supplement significantly improved recall of pictures, sustained attention, learning rule reversals and planning at 12 weeks without affecting menopausal symptoms, self-rating of mood, bodily symptoms or sleepiness (Duffy et al 2003). A further double-blind, randomised, placebo-controlled trial in healthy postmenopausal women aged 55-74 years found that 6 months' supplementation with 110 mg day total isoflavones significantly improved category fluency compared with baseline scores and the placebo group responses at 6 months (Kritz-Silverstein et al 2003). In contrast to these studies a double-blind, randomised, placebo-controlled trial of 202 healthy postmenopausal women aged 60-75 years found that 25 g day of soy protein containing 99 mg of isoflavones for 12 months did not affect cognitive function, BMD or plasma lipids (Kreijkamp-Kaspers et al 2004).

Physiological Aging

Animal model are similar to those seen in people. Equally relevant are reproductive changes with age, which include testis and ovary changes as well as the onset of reproductive senescence such as age of menopause. Many age-related changes and pathologies can also be studied and compared to human aging. A few parameters of interest include, but are not limited to, fat deposits, hormonal levels such as those of growth hormone, insulin and insulin-like hormones, and dehydroepiandrosterone (DHEA), atherosclerotic lesions, osteoporosis, arthritic changes, changes in reaction times with age, changes in senses, and the presence of cerebrovascular -amyloid protein (Finch, 1990). There are also examples of comparative studies aimed at specific age-related pathologies, and readers should consult other chapters in this book.

Uterine Cancer

Trends in uterine cancer incidence and mortality are influenced by factors that alter circulating estrogen and progesterone levels, including hormone replacement therapy and oral contraceptives. Risk of uterine cancer will increase if endometrial tissue is exposed to estrogen that is unopposed by progestogen.15,39,40 Thus, estrogen-replacement therapy (ERT), in which estrogen is given to postmenopausal women without any progestogen, increases uterine cancer risk. In the United States, a doubling of estrogen prescriptions (ERT) to treat menopausal symptoms beginning in 1966 resulted in the epidemic of endometrial cancer that ended in the late 1970s,41 when progestogens were increasingly added to ERT to reduce or possibly eliminate this risk. Rates peaked in 1975 among white women of all ages and African-American women under the age of 50 years rates peaked among African-American women over 50 years old 2 years later in 1977. As a result of the epidemic, ERT for menopausal symptoms...


Independent risk factors for venous thromboembolism include increasing age, male gender, surgery, trauma, hospital or nursing home confinement, malignancy, neurological disease with limb paralysis, and central venous catheter transvenous pacemaker, prior superficial vein thrombosis and varicose veins. Among women, risk factors include pregnancy, oestrogen-containing oral contraceptives, and hormone replacement therapy. About 30 of VTE surviving cases develop recurrent venous thromboembolism within 10 years.

Policy Matters

Some individuals worry, for example, that ''artificially'' extending human lives would cheapen our existence, whereas others point out that the modern medical enterprise has already drastically increased lifespans with no ill effects on society. Other subjects that the site has explored include the paucity of older people included in clinical trials the wisdom of using human growth hormone to combat symptoms of aging despite data suggesting that the substance curtails lifespan and how we might improve our flu-combating measures. It has discussed nanotech-nology, hormone replacement therapy, guidelines for keeping bones strong, and chronic pain, as well as age-related voice changes and hearing loss. SAGE Crossroads ponders such topics in News and Views articles as well as through Webcasts in which experts debate and discuss such matters.


It Is suggested that the effects of A. racemosa may be due to dopaminergic activity, because black cohosh extract BNO 1055 displayed dopaminergic activity with a D(2)-receptor assay (Jarry et al 2003). Considering that dopaminergic drugs reduce some symptoms (e.g. hot flushes) associated with menopause, this theory is feasible however, further studies are required to explain why black cohosh is devoid of the typical side-effects associated with dopaminergic drugs (Borelli & Ernst 2002).

Concluding Remarks

Foot note added in proof Since this review was completed (June 2003) results of a cohort of a million of British post menopausal women taking hormone replacement therapy with different preparations Beral V and the MWS group (2003) Breast cancer and hormone-replacement therapy in the Million Women Study, Lancet 362 419-427 confirmed the adverse effect of progestins on breast, including the progestins currently used in Europe


Foods rich in calcium and vitamin D, or daily supplements of these and other substances (e.g., estrogens, fluoride, vitamin K, magnesium, growth hormones) are prescribed treatments for osteoporosis. Preventive treatments include hormone replacement therapy and progesterone, and a program of exercises that place stress on the long bones (walking, jogging, dancing, bicycle riding). Also recommended is that the intake of alcohol and certain drugs, as well cigarette smoking, be controlled.

Dong quai

Historical note Dong quai is an aromatic herb commonly used in TCM. Its reputation is second to that of ginseng and is regarded as a 'female' remedy, or women's ginseng. Used in combination with other herbs, dong quai is used to treat numerous menstrual disorders and menopausal symptoms, as well as abdominal pain, migraine headache, rheumatism and anaemia (Murray 1995). Dong quai (Angelica sinensis) is closely related to the European Angelica archangelica, a common garden herb and the flavouring in Benedictine and Chartreuse liqueurs.

Functional Problems

Surgical long-term and late effects usually result from damage to, or removal of, tissue and organs in the course of cancer surgery. Much of the time the effects are expected (e.g., menopausal symptoms following hysterectomy for ovarian cancer), while in other cases they are unintended (e.g., dumping syndrome after a partial gastrectomy). For example, surgery may leave the head and neck cancer patient without a voice or the ability to swallow, or may have resulted in the loss of a limb for a sarcoma patient. Physical, occupational, and speech therapists are among the mul-tidisciplinary specialists that can greatly help cancer survivors with these disabilities optimize their function and activity.


Given that andropause ADAM PADAM is purported to be one form of hypo-gonadism, the phenomena described under Assessment above in this chapter, applies here as well. Low sexual desire is usually seen as a symptom of andropause ADAM PADAM. To explain the desire change, a great deal of emphasis has been given to laboratory values, especially alterations in T. However, the typical history has received much less attention. Only one study of aging men seems to have examined various manifestations of sexual desire. Schiavi et al. reported on 77 volunteer couples who responded to an announcement concerning a examination of factors contributing to health, well-being, and marital satisfaction in older men. Three groups of men were compared 45 -54, 55 -64, and 65 -74. The following were conclusions related to the issue of sexual desire (i) sexual interest, responsiveness, and activity was noted even among the oldest men (ii) increasing age was associated with ED, but not with HSDD or PE...

Chest Radiation

Pelvic radiation can damage fertility. Primary or adjuvant radiation for cancers of the pelvis will render most women infertile, even if ovaripexy (surgically moving the ovaries out of the radiation field) is performed, likely due to the scatter of radiation outside of the intended field.40 Unfortunately, there is often insufficient time to stimulate and harvest ova prior to therapy. Radiation doses to the ovaries as low as 20 Gy induces premature menopause in women under 40 years, and as


Postmenopausal hormone therapy is taken here to refer to the use of preparations containing estrogen(s), with or without progestagen(s), around the time of the menopause, primarily for the relief of menopausal symptoms. Use of such therapy has increased dramatically in the last decade such that by 1998 around one-third of women aged 50-64 in England were estimated to be using it.13 In addition, recent estimates suggest that between 20 and 30 of women aged 45-64 in many developed countries, other Since use is most common around the time of the menopause and usually continues for a few years, the time of peak use is when a women is in her early 50s. Postmenopausal hormone therapy use is consistently more common in women who have had a surgical rather than a natural menopause. The relationship between hormone use and other factors varies from country to country in general, users have a lower body mass index and a more favorable cardiovascular risk profile than nonusers.


Of circulating ovarian hormones at the menopause, it might reasonably be expected that while women are using such therapy the beneficial effects of the menopause on breast cancer risk will be delayed. To a certain extent, this is borne out by the data in that current or recent use of postmenopausal hormone therapy increases the risk of breast cancer by about 2.3 per year of use, which is comparable to the 2.8 increase in risk estimated to apply for each year later that menopause occurs.5 It is perhaps less clear what this analogy with the effects of delayed menopause should predict about the risk of breast cancer in past users, but the majority of the data suggest that the excess risk of breast cancer associated with long duration of use declines with increasing time after cessation of use.

Disease Specific

Reproductive counseling regarding sexual function and fertility is often overlooked given the patient's potentially terminal disease but all patients should be educated regarding sexual and reproductive issues. Many female patients may experience premature menopause, irregular menstrual cycles, and infertility. Infertility can be permanent, particularly in men and women over the age of 40. Patients need to be educated regarding their prognosis so that they can make informed decisions regarding future childbearing. Males may choose to bank sperm prior to undergoing treatment. Females may chose to undergo egg retrieval but this requires considerably more time and expense and therefore the need to initiate therapy as soon as possible may not provide enough time to retrieve viable eggs (8). Patients should be counseled to use reliable contraception and that it is important to avoid pregnancy during chemotherapy and radiation. A waiting period following treatment is recommended for women...


Rats and mice undergo estrous cycles, as opposed to menstrual cycles in humans. Thus the process by which reproductive aging occurs in rodents is sometimes called estropause, and it shares some similarities, as well as some differences, with human menopause. The rodent estrous cycle is four to five days long, consisting of four phases proestrus, estrus, diestrus I (sometimes referred to as metestrus), and diestrus II (see Figure 43.2). In rodents, estrous cyclicity can be tracked by observing daily vaginal cytology. Through this methodology, researchers have determined that rodents begin to show irregular cycles at middle age (9-12 months), as defined by prolonged cycles, most commonly with additional days of cornified vaginal cells, interspersed with the normal four- to five-day rhythm. As aging occurs, these animals transition into an acyclic, anestrus status, in which persistent estrus is observed and ovulation has ceased (Rubin, 2000). In accordance with humans, rodents begin to...

Web Sites

The North American Menopause Society, http A scientific organization presenting information and current research on menopause and its management. The Endocrine Society, An international scientific organization, consisting of basic researchers and clinicians, that supports research in all areas of endocrinology, including menopause. JOURNAL ARTICLES AND REVIEWS Bellino, F.L. and Wise, P.M. (2003). Nonhuman primate models of menopause workshop. Biol Reprod 68(1), 10-18. Burger, H.G., Dudley, E.C., Robertson, D.M., and Dennerstein, L. (2002). Hormonal changes in the menopause transition. Rec Prog Horm Res 57, 257-275. A comprehensive review of human studies encompassing hormonal changes that accompany the onset and progression of menopause.

Gender Differences

These observations might indicate a demographic crossover in which women are better off than men in younger old age and men, although fewer in number, are functionally better off in extreme old age. The underlying reasons why women generally live longer than men and are, at least before menopause, significantly less likely to develop heart disease and stroke are unclear. Estrogen, which might be a powerful antioxidant, has been implicated as an important reason. However it has been noted that premenopausal women who undergo hysterectomy but not oophrectomy experience an increased risk for vascular disease that is similar to men (Kiechl, 1997). Another possible reason is that women, because of menses, are relatively iron-deficient compared to men for a 30- to 40-year period. Iron is a crucial catalyst in mitochondrial production of free radicals as a byproduct of metabolism. Perhaps a reduction in available iron leads to less free-radical production. For example, iron deficiency has...

Red clover

Historical note Red clover has been used for a long time as an animal fodder as well as a human medicine. Traditionally, it is considered an alternative remedy with good cleansing properties useful in the treatment of skin diseases such as psoriasis, eczema and rashes. A strong infusion was used to ease whooping cough and other spasmodic coughs due to measles, bronchitis and laryngitis. It was recommended for 'ulcers of every kind, and deep, ragged-edged, and otherwise badly-conditioned burns. It possesses a peculiar soothing property, proves an efficient detergent, and promotes a healthful granulation'. Combined with other herbs, red clover was recommended for syphilis, scrofula, chronic rheumatism, glandular and various skin affections (Felter & Lloyd 1 983). Interestingly, red clover was not traditionally used for the treatment of menopausal symptoms.


MENOPAUSE PSYCHOLOGICAL AND PSYCHOSOMATIC SYMPTOMS Another study investigated a fixed combination of isopropanolic black cohosh (Remifemin standardised to 1 mg triterpene glycosides) and ethanolic SJW (standardised to 0.25 mg total hypericin) in 301 women with menopausal symptoms with pronounced psychological symptoms (Uebelhack et al 2006). The double-blind, randomised study found that 16 weeks of herbal treatment produced a significant 50 reduction in the Menopause Rating Scale score compared to 20 with placebo and a significant 42 reduction in the HDS score compared to only 13 in the placebo group.

T Levels And Aging

The decline in T levels with aging when associated with symptoms and signs of androgen deficiency has been called andropause. This association also has been referred to as androgen deficiency in the aging male (ADAM), partial androgen deficiency in the aging male (PADAM), aging-associated androgen deficiency (AAAD) or late-onset hypogonadism. The term andropause is inaccurate because men do not have menses and because androgen secretion gradually decreases, and usually is

Endocrine Changes

Although men do not experience a dramatic decline in sex steroid levels in midlife akin to the female menopause, there is a steady decline with aging. Around a third of men aged 70 years and over has levels of testosterone in the range that would normally be regarded as hypogonadal. Levels of the major adrenal androgen dehydroepiandrosterone also decline steadily with age. This decrease in androgen status is accompanied by, but does not entirely cause, increased fat mass, decreased muscle mass and decreased bone mineral density. Decreased androgen status often is seen particularly in patients with diabetes and is a common feature of poorly controlled diabetes, even in the young. The decline in testosterone status with aging and obesity is due partly to loss of function and number of Leydig cells. There is also a central component with reduced hypothalamic release of gonadotrophin releasing hormone (GnRH), The role of sex steroids and replacement therapy with these is even more...

Figure 2221

An abrupt transition between this squamous epithelium and the mucus-secreting columnar epithelium of the cervical canal, the endocervix, occurs in the transformation zone that during the reproductive age of the woman is located just outside the external os. Before puberty and after menopause the transfor


The age-related decrease in GH secretion is associated with changes in functional capacity, body composition, and hormonal status which mimic those observed in adults with GH deficiency. These changes have raised questions similar to those focused around the decline in sex steroids with aging or menopause, including whether there is a net benefit in reversing this decline if so, how and who should be treated. Since the aging pituitary remains responsive to GHRH (41), GHRH has come under study both as a potential probe for assessing the status of the GH axis and as a potential therapeutic agent as an alternative to GH administration.