Natural Health Remedies for Andropause

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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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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Changes in womens sexual behavior at menopause

The preceding brief review of research on variations in sexual behaviors during the menstrual cycle did not offer much support for the hypothesis that ovarian hormones are closely involved in the control of sexual behaviors in women. The consequences of menopause, surgical or natural, for these behaviors do not seem to be more impressive than those of the menstrual cycle. The lack of effect of ovariectomy on sexual behavior in women was described many years ago (Filler and Drezner, 1944 Werner, 1946 Kinsey et al., 1953) and has later been confirmed in a number of studies. Likewise, menopause does not seem to be associated with any particular decline in sexual activity. As always, questionnaire and self-report studies have given conflicting results and conclusions of such studies range from no effect (e.g. Kinsey et al., 1953) to a substantial decline (Dennerstein et al., 2002). Sexual activity is known to diminish with increasing age and this fact may explain the notion held by some...

The Menopause Determining Female Reproductive Stage

Women do not start or end reproductive function at a particular chronological age. The menopause transition, like puberty, is a dynamic period with respect to the reproductive axis, and a multidimensional process because in addition to changes in hormonal factors, it represents a time of change associated with family and personal relationships, work status, and self-concept. It was only recently that a staging system and nomenclature for healthy women who age spontaneously to a natural menopause was developed out of The Stages of Reproductive Aging Workshop (STRAW) (Soules et al, 2001). The relatively wide age range (42-58 years) for complete reproductive failure (menopause) in normal women underscores the importance of relying on criteria other than age to determine reproductive status. The STRAW criteria for reproductive staging are primarily based on the characteristics of the menstrual cycle and secondarily on follicle-stimulating hormone (FSH) levels. The anchor for the staging...

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.

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...

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

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...

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.

Controversies and Discrepancies Concerning Progestin Action on Mammary Glands

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...

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

Ovarian Germ Cell Tumors

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.

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...

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...

Project Title Cardiac Estrogen Receptors And Mi Mouse Models

Summary Ischemic cardiovascular disease, specifically myocardial infarction (MI), is the leading cause of morbidity and mortality in Western society. There are clear gender-based differences in cardiac function and electrophysiology that influence the two major sequelae following MI heart failure (NF), and susceptibility to arrhythmias. In women, MI is uncommon prior to menopause and postmenopausal estrogen replacement therapy decreases its incidence. These beneficial effects of estrogen have been attributed previously to indirect effects on classic risk factors. However, estrogen is now recognized to have direct effects on cardiovascular cells that are central to its beneficial effects on cardiovascular disease. Estrogen's effects are mediated by receptors that act as ligand-activated transcription factors. Two such receptors are currently known, ERALPHA, and the recently discovered ERbeta. We have developed and reported a series of novel murine models that provide unique tools for...

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).

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 epidemiological 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...

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.

Project Title Cvd Risk Health In Postmenopausal Phytoestrogen Users

Summary (Adapted from Investigator's Abstract) In the United States, heart disease is the leading cause of death in postmenopausal women. Estrogen replacement therapy is beneficial for heart disease risk factors as well as for bone density. However, a large proportion of postmenopausal women are not compliant with therapeutic regimens. Phytoestrogens are naturally occurring compounds found in plants and soy products that have estrogenic effects, and may represent an alternative treatment for the prevention of heart disease and osteoporosis in postmenopausal women. However, few intervention trials have examined the extent to which it is possible to improve heart disease risk factors, bone density, and quality of life in postmenopausal women through use of a dietary supplement of Phytoestrogen. The proposed randomized, double-blind, placebo controlled study is designed to determine the acceptability and benefits of use of a dietary supplement of Phytoestrogen (genistein) versus placebo...

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).

Hormones and sexual behavior in women

The endocrine control of sexual behavior in the human female has been the subject of a substantial amount of research. Undoubtedly, among the primates there is no species that has attracted as much attention as Homo sapiens. There are several good reasons for this. One is that disorders of the reproductive system are rather common, and one treatment for some of these disorders is ovariectomy. The considerable number of women who have been subjected to ovariectomy, from the early fertile age until well into menopause, has allowed researchers to evaluate the behavioral consequences in a rather large number of individuals. Another reason is that ovarian function ceases at a relatively young age in the human. Many women can expect to live 30 years or more after the ovaries have stopped producing the typical ovarian hormones, estrogens and progesterone. In many respects, the endocrine changes associated with menopause are similar to those occurring after ovariec-tomy. In fact, it has...

The role of androgens in women

Since plasma androgen concentrations are not reduced during menopause, we should expect pre- and menopausal women to have the same level of sexual behaviors, provided that other factors that might affect sexual activity are excluded. In view of the lack of effect of menopause on the genital response to sexual incentives, we must conclude that this prediction is confirmed. The marginal importance of phase of the menstrual cycle, ovariectomy and menopause all suggest that androgens rather than estrogens are crucial for sexual behaviors in women. The large inhibitory effects of adrenalectomy combined with ovariectomy, and its reversal by androgen replacement, gives further support to the notion that androgens are important. I conclude by suggesting that women are more similar to other primates than to rodents with regard to the endocrine control of sexual behaviors, nothing else.

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...

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).

Colorectal Cancer Background and aetiology

In 1972, Burkitt described the relationship between diet and incidence of bowel cancer he hypothesised that a diet rich in fibre was associated with regular bulky stools and reduced bowel carcinogenesis, perhaps by reducing exposure of colonic mucosa to dietary carcinogens. It does seem likely that the combination of high fibre and low fat may be protective against bowel cancer. Protection against colorectal carcino-genesis is also derived from dietary supplements of calcium and folate and evidence from the Nurses Health Study (North America) suggested that oestrogen in the form of hormone replacement therapy (HRT) lowers the incidence of colorectal neoplasia. There has been interest in the potential influence of non-steroidal anti-inflammatory drugs in colorectal carcinogenesis. Cyclooxygenase (COX)-2 inhibition appears to have potent effects on the colonic mucosa, increasing apoptosis and reducing cellular proliferation. It is also likely that these drugs function through...

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...

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...

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...

Evidence for Ovarian Senescence in Rhesus Monkeys

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...

Central nervous control of sexual behavior in the human female

The third study (Archer et al., 2006) I would like to mention has a more interesting design. Women in surgical menopause (mean age when the study was performed was 50 years) were exposed to pornographic video fragments and to neutral videos as controls. The women were first untreated, then they were give estrogen replacement therapy and finally estrogen + testosterone. They were exposed to the videos under each of these treatment conditions. A group of pre-menopausal women was also used (mean age 43 years). When the menopausal women were untreated, the pornographic video enhanced blood flow more than

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

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

Consumption of soybean and reduced incidence of disease

The structure of soybean isoflavonoids is uniquely similar to that of estrogen (17) and may account for their weak ability to act as agonists at estrogen receptors (38). Many have speculated that soybean isoflavonoids may be useful for the treatment of somatic, mood, and cognitive disturbances associated with the onset of menopause (39). Diet supplementation with soybean phytoestrogens has been reported to ameliorate hot flashes and other symptoms of menopause (40-43). Soybean isoflavonoids may also have potential in natural chemoprevention therapies against long term health problems associated with menopause, particularly for osteoporosis (44-47). After menopause, the ovaries stop producing estrogen. Because estrogen positively affects the metabolism of calcium, lack of sufficient estrogen can lead to bone loss and osteoporosis (48). Hormone replacement therapy (HRT) can reduce bone loss and the risk of osteoporosis in postmenopausal women, but unfortunately appears to also increase...

Epidemiological studies in favour of the iron hypothesis

The lower incidence of coronary heart disease in premenopausal women compared with men of the same ages and with postmenopausal women was shown to be due to the lower total body iron caused by menstrual blood loss (Sullivan 1989). In men, body iron assessed by ferritin concentration, rose after adolescence, while in women, ferritin began to rise only after the age of 45 years (Burt et al. 1993). The Framingham study showed that the risk of heart disease in women increased equally by natural or surgical menopause (Gordon et al. 1978 Hjortland et al. 1976 Kannel et al. 1976). In heterozygotes of familial hyperlipoproteinaemia, the premenopausal women had a lower risk of coronary heart disease than men (Ascherio & Hunter 1994 Slack 1969 Stone et al. 1974).

Clinical Characteristics of Homozygous Individuals

The onset of puberty is usually delayed without affecting fertility. IGHD women of Itabaianinha tend to have a lower number of children (2.0 vs. an average of 5.5), probably due to delayed age of first intercourse and to the necessity of performing caesarean sections because of cephalic pelvic disproportions, but have normal menopause timing and symptomatology. Their hormonal profiles are similar to unaffected women, apart from decreased serum prolactin (PRL) level.146 Low-PRL concentration has also been reported in some individuals with the E72X mutation, suggesting a possible interference of the GHRHR mutation with PRL secretion, as PRL gene transcription is cAMP-activated and cAMP concentration is increased by GHRHR activation (Ref. 120 and references therein). Nevertheless, the Itabaianinha IGHD women are able to nurse their children.

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...

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...

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

Carcinoma Of The Breast Introduction

Breast cancer accounts for approximately 24 of all malignancies occurring in the female population in industrialised western societies and 18 of deaths in women due to malignant disease. In the UK there are approximately 117 cases per 100 000 women (34 000 new cases per annum). Thus, 1 at least 12 women will develop breast cancer during their lifetime and the incidence is rising by approximately 2 per annum. Breast cancer rarely occurs in women under the age of 25 years. Thereafter, the incidence increases steadily until at the time of the menopause, where the incidence plateaus out. After the menopause there is again a steady increase in

Estrogen Deprivation Increases Risk for Depression and Medical Illness

While the most common symptoms associated with progressive ovarian failure and estrogen deprivation during the menopause transition are vasomotor (e.g., hot flushes), perimenopausal women are also at increased risk for clinical depression. While most women will not suffer from clinically significant depressive symptoms during the menopausal transition, longitudinal studies in community samples have consistently documented an increased risk for clinically significant depressive symptoms or major depressive episodes during the menopause transition, with odds ratios generally ranging from 1.3 to 4.0 (e.g., Cohen et al, 2006 Freeman et al, 2009). That the fluctuations in hormones during the menopause transition contribute to the development of depression in vulnerable women is supported by the work of Freeman (2006) who showed that greater variability in estra-diol levels, and not the estradiol levels per se, was associated with both higher depressive symptoms and diagnosed major...

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...

Of Physiological Stress Mechanisms in the Oldest

Endocrine mechanisms are also considered to be important linking pathways through which behavioral factors exert their impact on health. With aging, and especially after menopause, levels of sex steroid hormones, such as testosterone, estradiol, and dehydroepiandrosterone sulfate (DHEA-S), decrease. Whereas in younger age groups, high levels of sex hormones have sometimes been shown to be unfavorably associated with behavioral factors such as depression, in aging populations low sex hormone levels have been linked with late-life depression (Morsink et al, 2007).

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.

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.

Confounding Factors in Neuroendocrine Research

Factors are age, sex, pubertal stage (in adolescents), phase of the menstrual cycle intake of oral contraceptives menopause (in women), ethnicity, weight, smoking, caffeine alcohol or drug intake, strenuous exercise, and history of endocrine immune hepatic or psychiatric disorders. In terms of the study setting, one may want to standardize time of day, food intake, and in case of multiple blood collections, allow for enough time between first venipuncture and subsequent hormone analysis, as an endocrine stress response may occur. Sleep disorders and shift working may distort circadian endocrine rhythms (for an overview, see Heim and Ehlert, 1999 Kudielka et al, 2007).

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...

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...

The Problem of Causal Inferences

To some extent, the problem here relates to different standards for claiming causality in social psychology (B& K) and in medicine (MacArthur). In observational studies in social psychology, a causal association is assumed to exist and if the data do not refute that assumption, the causal assumption remains viable. In medicine inferences of causality usually require RCTs. To understand why this is so, consider the inference drawn from the observational study in 1985 that use of hormone replacement therapy (HRT) protects against heart disease (Stampfer et al, 1985), later refuted by an RCT that showed that the use of HRT increased the risk of heart disease, as well as that of breast cancer. (Writing Group for the Women's Health Initiative Investigators, 2002). After the 1985 study, many women began and continued HRT with the hope of avoiding the most common cause of death in women heart disease. Following the 2002 study and the subsequent sudden decrease in use of HRT, cancer rates...

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...

Project Title Surveillance And Analysis Of The Unc Alumni Heart Study

Summary (investigator's abstract) The UNC Alumni Heart Study continues to examine the impact of hostility on health behaviors and psychological status at midlife to test the prospective associations of hostility with coronary heart disease (CHD) events and other health outcomes. The Specific Aims of the proposed research are 1 To better understand the dynamic interrelationships of psychosocial and behavioral risk factors of the adult life span, we will map the trajectories of hostility, depression, smoking, body mass, exercise patterns, and alcohol consumption using multiple assessments from age 19 to age 60. It is predicted that a significant proportion of the change in risk behavior will be due to trajectories of hostility and depression, operating singly and in combination over time. 2 To test the prospective associations of hostility, depression, and other psychosocial variables (e.g., social support and job strain) with coronary events and mortality observed while the cohort is...

Recommended Resources

North American Menopause Society http www.meno-pause.org Menopause http www.menopausejournal.com Alternatives in menopause by herbalist Susan Weed http www.menopause-metamorphosis.com Mayo Clinic Menopause page http www.mayo clinic.com Planned Parenthood Menopause page http WebMD Menopause page http my.webmd.com default.htm

The Influence of Environmental Factors on Psychiatric Symptoms

Changing patterns of contact with medical providers may also exert effects on psychological adjustment during an RCT. For example, the transition from active treatment to early survivorship (i.e., re-entry phase) can be a particularly distressing time for cancer patients (Stanton et al, 2005). This difficult adjustment period is thought to be in part due to the loss of a safety net. Patients typically have less frequent contact with health-care providers following active treatment and they might receive less support from family and friends as they transition back to their normal lives. Continued side effects from treatment (e.g., fatigue, menopause, sexual dysfunction, lymphodema) are often unexpected and can also contribute to this difficult transition. There is some evidence that most patients do not experience significant psychiatric distress during the re-entry phase (Costanzo et al, 2007) and only a subset of patients experience adjustment difficulties. However, preliminary...

Isoflavones and coronary heart disease

The increase in coronary heart disease (CHD) incidence associated with decreased ovarian function at the menopause (McGrath et al., 1998 Bittner, 2002) is in part attributable to a less favourable blood lipid profile and arterial dysfunction. Replacement of the natural hormones by exogenous oestrogen and progesterone, in the form of hormone replacement therapy (HRT), has been consistently shown to decrease plasma concentrations of low-density lipoprotein (LDL)-cholesterol and increase concentrations of the beneficial high-density lipoprotein (HDL)-cholesterol (Erberich et al., 2002). As a result, HRT has been widely advocated as an effective means of delaying the progression of atherosclerosis in postmenopausal women. However, recent findings from long-term controlled intervention studies have proved disappointing, with no benefit, or increased incidence, of CHD reported in a number of well-controlled trials (Grady et al., 2002 Skouby, 2002 Kuller, 2003). This lack of efficacy has...

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...

The high cost of the imposed association between sexual behavior and reproduction

The emphasis on penile-vaginal procreative sex as the only acceptable sexual activity has led to a reduction in the quality of life for numerous groups besides lesbians and gays. One of the largest is menopausal women. In menopause, reproduction is not possible and sexual activity cannot be legitimate. Thus, those menopausal women taking either religion or biology seriously felt obliged to abandon sex and move out of the conjugal bedroom. Their poor husband was also forced to abandon sex, since it would be sinful to have sex with a non-fertile woman. He could at least find a solution to this dilemma by taking a younger woman as mistress, but the solution could only be partial since he then committed the mortal sin of adultery. In fact, having sex with his wife would have had a lesser cost, since Saint Augustine determined that sexual activity without the goal of reproduction is only a venial sin. The husband's predicament is probably that his wife refuses to commit any sin at all,...

EEG and the Effects of Hormone Treatment

The administration of hormone replacement therapy (HRT) offers the promise of normalization of function, but EEG ERP has been used to determine whether general brain state or cognitive function indeed improved with treatment. Schneider and colleagues (2005) examined the effects of growth hormone (GH) replacement deficiency on the sleep EEG, using polysomnography in growth hormone-deficient patients. Results showed that the values for the obtained sleep parameters were similar to those for Golgeli and colleagues (2004) examined the effects of growth hormone (GH) replacement therapy on cognitive function in women with Sheehan's syndrome. Sheehan's syndrome is also known as postpartum hypopituitarism, a pituitary hormone deficiency as a result of life-threatening blood loss during or after childbirth. At baseline, amplitude and latencies of auditory oddball ERPs of patients showed longer latencies than those of controls. After 6 months of hormone replacement therapy, patients showed...

Potential endocrine causes of hypoactive sexual desire disorder

In Chapter 5, I made clear that adequate blood concentrations of androgens are necessary for maintaining a functional central motive state in both men and women. Therefore, it is not startling that several studies have determined blood androgen concentrations in women diagnosed with hypoactive sexual desire disorder. Early studies failed to detect any difference between women reporting an adequate level of desire and those diagnosed with hypoactive desire disorder (Stuart et al., 1987 Schreiner-Engel et al., 1989). In contrast, a group of women with life-long hypoactive sexual desire disorder were found to have a lower free testosterone blood concentration than controls (Riley and Riley, 2000). This is a very interesting observation, suggesting that the life-long variant of desire disorder can be attributed to reduced reactivity of the central motive state because of insufficient androgen stimulation. Later studies have extended these findings. Premenopausal, regularly cycling women...

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

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...

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...

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.

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

Acknowledgement

Weiss LK, Burkman RT, Cushing-Haugen KL, et al (2002) Hormone replacement therapy regimens and breast cancer risk(1). Obstet Gynecol 100 1148-1158. 24. Daling JR, Malone KE, Doody DR, et al (2002) Relation of regimens of combined hormone replacement therapy to lobular, ductal, and other histologic types of breast carcinoma. Cancer 95 2455-2464.

Osteoporosis

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.

Reproductive factors

It is now 100 years since George Beatson, a Glasgow surgeon, first reported that removal of the ovaries of a young female could reverse the progress of recurrent breast cancer, and there is now unlimited evidence that deprivation of oestrogens in both pre- and post-menopausal women can alter the progress of the disease. In young women, oestrogens are secreted by the thecal cells of the ovary, but following the menopause, oestrogens are synthesized from precursors of adrenocortical origin in liver and fat through the action of aromatase enzymes. Active ovarian function is a necessary prerequisite for the development of breast cancer. Women who have an artificial menopause before the age of 35 years have one-third the incidence of breast cancer compared to women whose ovaries remain intact until their natural menopause. The younger the age at menarche and the older that at menopause the greater is the risk of breast cancer, this being related to the number of ovarian cycles during the...

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.

Background

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.

Implications

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...

Rodents

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 www.menopause.org A scientific organization presenting information and current research on menopause and its management. The Endocrine Society, www.endo-society.org 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.

Fibroadenomas

Fibroadenomas are the commonest benign tumours to arise in the breast and are most often seen in women under the age of 35 years. They comprise approximately 10 of symptomatic breast lumps. In older women, particularly after the menopause, they are quite uncommon. In the latter age group they can undergo involution and become calcified. Large, rapidly growing fibroadenomas may occur in girls and young women.

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...

Hormonal factors

Data has accumulated from different epidemiological studies that a prolonged exposure to oestrogens may increase the risk of subsequently developing breast cancer. Therefore, the following have been shown to increase the relative risks of developing breast cancer early menarche, delayed menopause, late age of birth of first child and nulliparity.

Chemotherapy

Hormone therapy has the advantage of less severe side effects than chemotherapy. Hormone therapy would be indicated in patients who were unfit for chemotherapy and also in those with disease present in multiple sites and with bone metastases. Responses to hormonal therapy have been reported in up to 60 of patients whose tumours have a high level of OR. Response rates are unlikely in OR negative tumours or in patients with hepatic metastases. If patients have been taking tamoxifen as adjuvant therapy before the development of metastatic disease then only 20-30 will respond to second-line hormonal manipulation, for example using medroxyprogesterone or aromatase inhibitors. It is also important to remember that even if patients demonstrate no response to first-line hormonal therapy, 20 will respond to second-line hormonal treatment. A further 10-15 may show a response to third-line hormonal treatment. In pre-menopausal women ovarian ablation (e.g. oophorectomy or radiation-induced...

Testosterone Decline

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).

Sleep Continuity

To PSG, actigraphy- and PSG-assessed sleep efficiency values did not differ. Race ethnicity and menopausal symptoms were significant effect modifiers in these analyses, which suggests that sample characteristics influence diary, actigraphy, and PSG-based estimates of sleep continuity.

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...

Aging

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.

Bleeding

Bleeding pattern is the first change a woman will experience as she approaches the perimenopause transition. The reproductive-age-cycling woman will have predictable menses after ovulation because the cascade of hormonal events leads to a menstrual bleed after 14 days in the luteal phase of the cycle. When a woman reaches the perimenopause period, her supply of follicles secreting estradiol is decreased to a point that not every cycle is ovulatory. Circulating inhibin-B levels drop in response to the decreased number of follicles present in the ovary, leading to a rise in follicle stimulating hormone (FSH) levels. The increased FSH helps the ovary to produce near normal (premenopause levels) estradiol levels until just before the actual menopause. However, ovulation does not always occur under such circumstances, causing longer or shorter intervals between menses. When ovulation fails to occur, these cycles are characterized by absence of progesterone production, further contributing...

Vaginal Symptoms

During the menopause transition, women may experience vaginal symptoms including vaginal dryness, itching, and dyspareunia (painful intercourse). These vaginal changes result from changes in the serum estradiol levels that drop precipitously just before the last period. The end organ response to this drop in estradiol results in less estrogen effect on the mucus membranes that line the vaginal wall. During the reproductive years the vaginal wall is composed of a highly estrogenized superficial layer beneath which is the intermediate layer, and beneath that is the basal layer. This bottom-most layer is exposed when estradiol levels drop at menopause. When this happens the vagina loses elasticity and moisture, blood vessels are closer to the surface, and with time atrophy occurs. It is hypothesized that for some women who maintain an active sex life, blood flow to the pelvis keeps the vaginal supple and can prevent symptoms. Many women, though, experience itching and pain, and are...

Mood Disturbances

The majority of studies from large literature searches indicate no associations between the menopause stage and mood symptoms, development of mental disorders, or general mental health (Haney, 2005). Two cohort studies report increased incidence of depressive symptoms among peri- and postmenopausal women (Freeman et al., 2004 Maartens, Knottnerus, and Pop, 2002). Data from studies of prevalence rates for mood symptoms have wide ranges and are similar across the menopausal stages (Haney, 2005). Periods of reproductive hormonal change (premenstrual, postpartum, and perimenopause) may constitute times of particular risk to women with regard to depressive illness. Since perimenopause is a time of great change for women in many arenas including important hormone changes, some women will be at risk for affective disorders during this period. Treatment of mood disturbances that accompany the transition through the menopausal stages is important given the morbidity associated with untreated...

Estrogen Signaling

Ovarian hormones have dichotomous effects when applied to the biology of the breast. On one hand, prolonged exposure through early menarche, belated menopause, or postmeno-pausal hormone replacement therapy increases the risk of breast cancer. On the other hand, an early full term pregnancy can significantly reduce breast cancer risk to humans (51), and in rodents pregnancy levels of estrogen and progesterone will impart a significant protection against carcinogen induced breast cancer (52,53). The context and duration of the signaling is likely to be the important determinant in the effects of estrogen. There is no doubt, though, that estrogen remains one of the critical hormones that regulate both normal and malignant development of the mammary gland.

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