Natural Menopause Relief Secrets

Natural Female Hormone Balance Program

Joan Atman with the help and inspiration from Dr Stephanie put down this book. Dr Stephanie is the mastermind behind this helpful guide. He is a nutritionist and a medical practitioner who has been very active in this case. Joan Atman is an international Life coach and Energy medicine specialist. The Natural Female Hormone Balance program is a 28 day Hormone reset Detox program for female. It is a very easy and gentle program that is designed by the author to support the female body detox and eventually regain the normal hormonal balance. All the tips and the dietary changes discussed in the program will kick start the body's natural ability to balance hormones. This eventually helps your body look and feel incredible. The full program contains 6 modules designed to lead you step by step through the Hormone reset Detox program. This program is available in PDF formats. The author has also included some video and audio tutorials. You can download the program and print or just download the PDF file, the Videos and the Audio. Read more here...

Natural Female Hormone Balance Program Summary


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The writer presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this book are precise.

When compared to other ebooks and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

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...

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...

Use of Any Type of Postmenopausal Hormone Therapy

Most studies of postmenopausal hormone therapy and breast cancer have found a small increase in the risk of breast cancer associated with ever use (Fig. 6.10), with an overall average risk of breast cancer in ever-users compared to never-users of 1.14 (95 CI 1.09-1.49). Further examination of breast cancer risk according to the pattern of use of postmenopausal hormone therapy shows that this excess risk is largely confined to current and recent users and among these women the risk increases with increasing duration of use (Fig. 6.11). Indeed, in current users and those who ceased use less than 5 years previously, the RR of breast cancer is estimated to increase by 2.3 (95 CI 1.1 -3.6 ) for each year of use. In contrast, women who have ceased use 5 or more years previously do not appear to be at any overall increase in risk, nor does their risk increase with increasing duration of use of postmenopausal hormone therapy. This pattern of increasing breast cancer risk with increasing...

Comparison of Risks According to Type of Postmenopausal Hormone Therapy Used

Table 6.1 Relative Risk (RR) of Breast Cancer by Time Since Last Use, Duration of Use, and Type and Dose of Postmenopausal Hormone Therapy Mainly Used Table 6.1 Relative Risk (RR) of Breast Cancer by Time Since Last Use, Duration of Use, and Type and Dose of Postmenopausal Hormone Therapy Mainly Used Type and Dose of Postmenopausal Hormone Therapy Since the collaborative reanalysis, three studies have published new results on breast cancer risk according to type of postmenopausal hormone therapy used. The first, which is an extended follow-up of a large cohort within the Breast Cancer Detection Demonstration Project15 (a U.S. breast cancer screening program), with over 2000 cases of breast cancer, has shown that the risk of breast cancer is increased both in recent users of estrogen-only therapy (RR 1.2, 95 CI 1.0-1.4) and in recent users of combined therapy (RR 1.4, 95 CI 1.1-1.8). However, when the trend in breast cancer risk with increasing duration of use was estimated separately...

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...

Project Title Premenopausal Risk Factors For Coronary Heart Disease In Black White Women

Summary Premenopausal black women have a 2- to 3-fold greater rate of coronary heart disease (CHD) than premenopausal white women. The purpose of this study was to provide greater insight into the reasons for this difference, which are currently unclear. We compared CHD risk factors in 99 black and 100 white, healthy, premenopausal women, aged 18 to 45 years, and of relatively advantaged socioeconomic status. Compared with white women, black women had a higher body mass index (32.0 _ 9.2 vs 29.0 _ 9.4 kg m2, p 0.021), and higher systolic (124 _17 vs 115 _ 14 mm Hg, p

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 creams...

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.

The Relationship Between HRT and Risk of Lobular Carcinoma

As a result ofthe observations described above, attention has been paid to potential risk factors that may be more strongly related to ILC risk than to IDC risk. In particular, there is a growing interest in the relationship between combined E and P HRT (CHRT) and ILC risk. Two main observations have driven this research. First, CHRT use in the USA increased over the same time period that ILC rates increased and IDC rates remained constant. From 1982-1992 the number E and P prescriptions increased 2.3-fold and 4.9-fold, respectively (24). Among controls from a recent USA multi-center case-control study of postmenopausal women spanning 1994-1998, 45 were current HRT users (25). Second, CHRT use has been shown to be associated with an elevated BC risk in numerous studies, and more recently in the Women's Health Initiative (WHI), a randomized controlled trial. The pooled analysis conducted by the Collaborative Group on Hormonal Factors in Breast Cancer of 51 observational studies found...

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 Antiestrogenic Activity of Progestins Good or Bad Significance

Vitro, since R5020, a pure progestin, inhibited the E-induced growth of MCF7 cells (8). However, proposals concerning mechanism ofthis anti-estrogenic activity have varied with time Induction of 17P-OH-steroid dehydrogenase (9), increase of inactive E-sulfates (20), down regulation ofthe ER, and inhibition of transcription of ERE-controlled genes by squelching of limiting receptor co-factors (21). The decrease in the ERa level in mammary glands, after progestin treatment of pre-menopausal women with a benign breast disease was demonstrated in a population of 67 women by two fine needle biopsies performed before and after a 20-30 days treatment with lynestrenol, i.e., a nor-testosterone progestin routinely used in France to treat benign breast disease in the 1980s. In the 20 women receiving only placebo, the ERa concentration measured by immunohistochemistry was not altered, while in the 47 women receiving lynestrenol, the ERa level was markedly reduced by this treatment in all...

Project Title Aging Estrogen Hsps And Myocardial Ischemia

Summary (Adapted from the Investigator's abstract) The heat shock proteins (HSPs) are an important family of endogenous, protective proteins found in all tissues. In the heart, HSP72, the inducible HSP70, is increased by ischemia and is cardioprotective. Overexpression of other HSPs also protects against cardiac injury. Aging results in a decreased heat shock response in male rats the effect on females in unknown. Women have less cardiovascular disease than men, but postmenopausal women have an increased incidence of heart disease. Although some of estrogen's protective effects can be explained by changes in lipoprotein profiles, other, unknown factors are involved. Studies in the Principal Investigator's laboratory have shown that estrogen increases levels of HSPs in male rat cardiac myocytes. We hypothesize that, as estrogen increases HSP expression and estrogen protects against CV disease, the decrease in estrogen with aging is associated with a decrease in HSP expression, and...

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...

Association of 16aHydroxylated Estrogens with Breast Cancer Risk

Mation of 16a-hydroxylated estrogen metabolites might be associated with increased risk of developing breast cancer. Their initial studies showed that 2- and 16-hydroxylation of estradiol was minimally affected by age and did not differ between premenopausal and post-menopausal women.129 However, when these enzymatic activities were compared between breast cancer patients (n 33) and matched controls (n 10), 16-hydroxylation was associated with increased risk of breast cancer, whereas the competing 2-hydroxylation pathway was either neutral or associated with decreased risk.135 The investigators suggested that the breast cancer patients had an increased extent of 16a-hydroxylation prior to the onset of the disease, unless the increase was a consequence of the cancer itself. In a subsequent study, using a murine mammary tumor model, Bradlow and associates136 reported a close correlation between the extent of tumor incidence and 16a-hydroxylation, but not 2-hydroxylation, of estra-diol....

The 216aHydroxylated Estrogen Breast Cancer Risk Hypothesis

On the basis of the studies described above, which showed that increased formation of 16a-hydroxylated metabolites relative to 2-hydroxy-lated estrogen metabolites may be associated with an elevated risk of breast cancer, it was hypothesized that a low urinary 2-hydroxyestrone to 16a-hydroxyestrone ratio should be inversely associated with breast cancer risk.144 Development of a competitive-type enzyme immunoas-say (EIA) method for quantifying these metabolites in urine145 allowed the hypothesis to be tested rapidly and relatively inexpensively in a large number of samples. This assay was used in the study by Kabat and associates,144 who measured the metabolites in spot urine from breast cancer cases (n 42) and controls (n 64), including both premenopausal and postmeno-pausal women. Although the 2-hydroxyestrone to 16a-hydroxyestrone ratio was not associated with breast cancer overall, the ratio in the post-menopausal group was significantly lower in the cases (n 23) compared to the...

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...

Risk Factors and Neurocognition

Various hormones are known to have a direct biological influence on the brain while potentially promoting diseases that affect cognitive function. In that regard, low levels of estrogen and androgens (Sherwin, 2003, 2006) and both low and high levels of thyroid hormones (Smith et al, 2002) have been related to poorer cognitive function. Hormone therapy in post-menopausal women may help prevent cognitive decline (Sherwin, 2003). Numerous studies have revealed associations between higher resting cortisol levels and lowered levels of cognitive performance, particularly on tests of learning and memory (Lupien et al, 2005). It has also been noted that stress-induced cortisol elevations are associated with decreased cognitive performance (Kirschbaum et al, 1996).

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) Most ofthe studies of expression in normal ducts and lobules, as well as in-situ neoplasia, are immunohistochemical studies focused on the ERa, although the potential cross reactivity for the much more recently discovered is not currently clear (11). Normal terminal duct-lobular units express ERa approximately 90 ofthe time, and in perhaps a third ofthese the expression is quite limited and only seen in a minority of cells. During the childbearing years (12), the number of positive cells varies with the menstrual cycle and is much higher during the follicular phase....

The Nature of Subsequent Invasive Carcinoma

Although not widely accepted or utilized in clinical decision making, it is quite evident that there are some important associations between hormonal manipulation and the nature of the subsequently developing invasive BC (34). Simply, many BCs, particularly in the post-menopausal age range (35), are of low grade, low

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...

Established Coronary Disease

Colleagues (2002) found that scores on the Cook Medley scale were an independent risk factor for recurrent events in postmenopausal women. Denollet and Brutsaert (1998) found that anger was one of several negative emotions conferring excess risk in MI patients. There have been some negative studies, however (e.g., Frasure-Smith and Lesperance, 2003), other researchers have observed the effect only under certain conditions. For example, two studies (Angerer et al, 2000 Boyle et al, 2004) found some hostility measures to be predictive while others were not, and Boyle and colleagues (2005) observed a stronger effect in younger patients. Although the picture painted by the literature is not completely clear, it is highly probable that hostility does convey increased risk of future coronary events in those with established disease. The exact conditions and aspects of hostility that maximize that risk are yet to be established.

Sexual incentive properties of odors

A favorite odor source in human pheromone studies is sweat collected from the armpits. We can probably all agree that the odor produced by non-deodorized armpits is strong and salient, but everyday experience insinuates that it is not particularly attractive to potential sex partners. Nevertheless, there are those who have tried to show that armpit sweat is a positive sexual incentive. A concoction with a composition purportedly similar to underarm secretions was provided to 36 women. They were instructed to apply the concoction under the nose, on the cheeks and behind the ears at least once every other day for 6 weeks. Subjects recorded their sexual activities in a diary and they were also interviewed a few times during the study. The concoction was found to increase the frequency of sexual intercourse and formal dating. The authors concluded that the concoction acted as a sex attractant, enhancing the women's sexual attractiveness (McCoy and Pitino, 2002). In the language of...

William R Miller Introduction

There is compelling evidence that estrogens (Es) both increase risk of developing breast cancer (BC) and maintain the growth and progression of established tumors (1). Recently, drugs have been developed which specifically and potently block E biosynthesis (aromatase inhibitors). These agents now occupy a central role in the treatment of postmenopausal patients with BC, and are being considered as preventative agents in women at high risk ofthe disease. The success ofthese drugs is founded on (A) The peripheral production of Es in postmenopausal women. (B) The key role of aromatase in the pathway of E synthesis. (C) The unique endocrinology of postmenopausal BCs. (D) The evolution of different types of aromatase inhibitors. (E) The mechanisms whereby Es initiate and promote BC. Therefore, the objectives of this chapter are to review (i) the pivotal role of aromatase in maintaining E within the breast and its tumors, and agents which have been developed as inhibitors of this enzyme,...

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.

Endocrinology of Aromatase Inhibitors

These effects on peripheral aromatization translate into decreased levels of Es in the circulation. Thus, daily anastrozole (1 mg), letrozole (2.5 mg), and exemestane (25 mg) reduce circulating E in postmenopausal women to levels often below the detection amount ofcurrent assays (21,28). Additionally, differences in potency between inhibitors that are apparent on whole body aromatase can also be detected at the level of circulating Es. Thus, exemestane will reduce E levels in patients relapsing on the first-generation inhibitor aminoglutethimide (29).

Western Heads East a tangible example of what is possible

A receptivity survey for probiotic products among pre-menopausal female students in an African university, showed that 82 of participants stated they would welcome probiotic products in capsular form for vaginal instillation or as daily oral form to improve vaginal health 64 . Over one third of the women indicated they would use probiotic products as part of their daily self-care and 39 said they were willing to buy probiotic products for vaginal instillation, while 82 preferred yogurt or milk-based food forms of the products. This showed that lack of progress was not due to a different viewpoint on the merits of probiotics, but rather more likely a result of lack of knowledge and availability of products.

Differences Between SERMs and Aromatase Inhibitors

SERMs and aromatase inhibitors are often thought of as being equivalent however differences in mechanism of action may lead to variations in biological and clinical effects. For example, aromatase inhibitors reduce endogenously synthesized Es in contrast, SERMs generally do not inhibit synthesis, and E levels remained unaltered (60), or, in the case of pre-menopausal women, may increase (61, 62). This difference may be important because metabolites ofnatural Es can have influences independent of ER (63). Although aromatase inhibitors reduce levels of Es synthesized endogenously, they will not diminish the activity of exogenous Es and adrenal androgens that interact with the ER (64-66). In contrast, SERMs will interfere with ER signaling irrespective of ligand. However, as the third generation aromatase inhibitors appear more effective than tamoxifen (67-71), it is unlikely that exogenous Es are responsible for the induction and growth of most BCs (64).

Aromatase Inhibitors and Prevention of Breast Cancer

0.007. compared with an expected 85 cases with no treatment,) (79). Aromatase inhibitors also have not been successful in premenopausal women (80-82) because of the high levels of aromatase activity in the premenopausal ovary and compensatory feedback loops (13). However, the new aromatase inhibitors may be sufficiently powerful to produce effective blockade, but they are not yet used routinely in premenopausal women Pilot chemoprevention studies which target high risk women, using third generation aromatase inhibitors are being planned or underway. One study has identified a small cohort of women with either DCIS or benign breast disease who were treated for 3 months with letrozole, the primary objective being to measure surrogate biomarkers of BC risk, and bone and lipid metabolism (83). The WISE trial aims to recruit women at risk on account of high circulating Es and randomize to either letrozole (1 year) or placebo. The National Institute of Canada is conducting double blind,...

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).

Anthropometric Factors

The data on breast cancer risk and height have been relatively consistent in demonstrating an increase in risk with increased adult height. A pooled analysis of seven prospective cohort studies of height and breast cancer risk reported relative risks for breast cancer, after adjusting for other risk factors, of 1.02 per 5 cm of height among premenopausal women 95 confidence interval (CI) 0.96-1.10 and 1.07 among postmenopausal women (95 CI 1.03-1.12).29 The relationship between greater height and risk of breast cancer is hypothesized to be due to the influence of growth hormone, insulin-like growth factor-I (IGF-I),30 or possibly in utero influences on ductal stem cells.31 The relationship between weight and breast cancer risk is dependent on age. In premenopausal women, high body weight does not increase the risk of breast cancer. Pooled results have shown an inverse association between risk of breast cancer in premenopausal women and body weight.29 Compared to women weighing less...

The Insulin Like Growth Factor Family

Epidemiological studies have begun to investigate the role of circulating IGFs and IGFBPs, as well as polymorphisms in the genes that encode them, in the etiology of breast cancer. Most studies have focused on the association with serum of plasma levels of IGF-I, IGFBP-3, or their ratio, which is a proposed proxy for biologically active IGF-I. Hankinson et al.65 found a markedly increased risk of premenopausal breast cancer relative risk (RR) 7.28, 95 CI 2.40-22.0 for women with the highest levels of plasma IGF-I but no association among post-menopausal women. Risk of breast cancer was also elevated among premenopausal women with a high ratio of IGF-I to IGFBP-3 (RR 2.46, 95 CI 0.97-6.24) compared to those with a low ratio. Studying this pathway presents important challenges to understanding the role of IGFs in carcinogenesis. In this complex family, risk of cancer could be mediated through any of the members, the IGFs, the receptors, or the binding proteins, or through interactions...

Dietary Fat and Fiber

Many case-control studies of fat consumption and breast cancer have found only small differences between cases and controls, generally no larger than the differences in total caloric consumption. However, Howe and colleagues68 combined 12 large case-control studies representing populations with a wide range of dietary habits and underlying rates of breast cancer to study the diet-breast cancer relationship. They found that the breast cancer risk of post-menopausal women was positively associated with both total fat intake (RR 1.46 for 100 g day, p 0.0002) and saturated fat intake (RR 1.57 for highest quintile of intake, p 0.0001). Nonetheless, cohort studies that have examined total fat, saturated fat, or vegetable fat69-72 have found little or no difference in breast cancer risk over a wide range of fat intakes.73 There have been several attempts to demonstrate a reduction in serum estrogen levels following dietary interventions that reduce fat or increase fiber intake.75 A recent...

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...

Dietary antioxidants and the prevention of CHD epidemiological evidence

Kushi et al. studied over 34000 postmenopausal women with no cardiovascular disease who in early 1986 completed a questionnaire that assessed, among other factors, their intake of vitamins A, E and C from food sources and supplements.38 After 7 years of follow-up, results suggested that in post-menopausal women the intake of vitamin E from food was inversely associated with the risk of death from coronary heart disease. This association was particularly striking in the subgroup of 21 809 women who did not consume vitamin supplements (relative risks from lowest to highest quintile of vitamin E intake, 1.0, 0.68, 0.71, 0.42 and 0.42 P for trend 0.008). After adjustment for possible confounding variables, this inverse association remained (relative risks from lowest to highest quintile, 1.0, 0.70, 0.76, 0.32 and 0.38 P for trend 0.004). By contrast, the intake of vitamins A and C was not associated with lower risks of dying from coronary disease.38 34000 postmenopausal women, followed up...

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. Over 60 epidemiological studies worldwide have examined breast cancer risk in relation to either hormonal contraceptive use or post-menopausal hormone therapy. There have been collaborative reanalyses of data on breast...

Fertility Enhancing Drugs

Women who undergo treatment for infertility can be exposed to a variety of hormonally active drugs, including clomiphene citrate, human menopausal gonadotrophin, and gonadotrophin-releasing hormone. Studies examining the relationship between use of fertility drugs and breast cancer risk have been hampered by small numbers of women and the inability to adequately control for all important confounding factors. Bearing this in mind, their findings have been generally reassuring, showing no significant increase in the risk of breast cancer in infertile women treated with fertility drugs compared to infertile women who did not receive such treat-ment.24-27 However, a recent study reported a significant, transient excess of breast cancer in the 12 months following ovulation stimulation for in vitro fertilization compared to the general female population,25 and there remains considerable uncertainty about the effect of fertility drugs 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...

Materials and Methods

A validated food frequency questionnaire (24), which included questions on reproductive, medical, and anthropometric factors. In the cross-sectional study, self-reported information was used to classify women's menopausal status and hormone use (HRT). The majority of subjects (n 208) donated an overnight urine specimen, while those ofthe cross-sectional study (n 97) only a spot urine sample.

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...

Colin D Clyne Evan R Simpson

Recent models of estrogen insufficiency have challenged traditional concepts of estrogen ac-tion.1-3 Studies of humans with natural mutations in the genes that encode the estrogen receptor4 or cytochrome P-450 aromatase5 and of estrogen receptor and aromatase knockout mouse models6-11 have revealed hitherto unexpected roles for estrogen in both males and females. For example, the critical role of estrogen in the spermatogenic process12 suggests that this hormone might more appropriately be termed an androgen in this context.13 Additionally, in postmenopausal women (as in men), estrogen no longer functions as a circulating endocrine hormone rather, it is produced in a variety of ex-tragonadal sites (e.g., adipose tissue or bone), where it acts locally as a paracrine, autocrine, or intracrine factor.2,3,14 This has great significance for our understanding of the biology of estrogen-dependent diseases such as breast cancer.

Synthesis Of Estrogens

Estrogens are synthesized from C19 precursors produced by the ovary (in premenopausal women), the adrenal cortex (in postmenopausal women and men), or the testis (in men). The first step in the pathway, common to the synthesis of all steroid hormones, is cleavage of the choles terol side chain to yield pregnenolone (Fig. 8-1).15 This reaction is catalyzed by the cholesterol side chain cleavage enzyme (P450scc) and requires 22-hydroxylase, 20a-hydroxylase, and 20 22 lyase activities,16 all of which occur at a single active site.17 The C21 steroids pregnenolone and progesterone are then converted to the C19 androgens dehydroepiandrosterone and an-drostenedione by 17a-hydroxylase (P450c17). These are two-step reactions that require 17a-hydroxylase and c17,20-lyase activities, both of which are characteristic of P450c17.18 The final step in estrogen synthesis is catalyzed by P450 aromatase (P450arom), which converts an-drostenedione and testosterone to estrone and 17j6-estradiol,...

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 primary follicles is gonadotropin-dependent (Macklon and Fauser, 1999), many of the newly formed primary follicles in older females cease development or become atretic,...

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 the neutral video only in the left middle frontal gyrus. Under estrogen replacement therapy, these women displayed more enhancement of blood flow in the left thalamus, medial frontal and right cingulate and parahippocampal gyri in response to the pornographic video than in response to the neutral one. When given testosterone in addition to estrogen, blood flow enhancement was larger in...

Inhibition Of Aromatase

Inhibition of estrogen action is generally the first-line adjuvant therapy for patients with metastatic estrogen receptor (ER)-positive breast cancers. Recent trials have demonstrated superiority of aromatase inhibitors such as anas-trozole over traditional estrogen receptor antagonists in this setting,66 and there is therefore much interest in the development of more effective aromatase inhibitors, both as treatment and as preventive agents.67 Estrogen receptor antagonists and aromatase enzyme inhibitors inhibit estrogen action in a global fashion, particularly in bone tissue and this inhibition may cause osteoporosis.68 Although this might be of less consequence in advanced postmenopausal breast cancer, the effects of estrogen deprivation in bone of young postmenopausal women could be significant. In addition, other sequelae of estrogen deprivation with anti-estrogen therapy for breast cancer such as hepatic steato-sis69-71 and cognitive impairment,72,73 have been described. For...

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. Although we know a good deal about the development of sex-related behaviors at puberty (Baum, 1979), surprisingly few studies have examined pubertal or menopausal changes in other behaviors that appear to be...

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 Phytoestrogens and Postmenopausal Activity 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...

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.

Management of the Unaffected Carrier

Alternative methods of imaging are being assessed in the high-risk population in the hope that they may provide an alternative to mam-mography. Mammography may be less effective in the younger population because breast tissue in premenopausal women is more dense. In addition, there is some concern that the radiation dose associated with mammography may cause tumor progression in gene carriers. The value of magnetic resonance imaging in screening for breast cancer is being evaluated in a U.K. study of known BRCA1 2 carriers or women at 50 genetic risk.23 Ovarian screening is more controversial because it has not been proven to be of benefit. It is currently offered on the basis of local availability, although the UKCGG has recommended that it should be offered only as part of a clinical trial.21 When it is available, women are screened annually by transvaginal ultrasonogra-phy from the age of 35, usually together with measurement of serum CA125 antigen. In a pilot study of 21,935...

Project Title Impact Of Chd Risk Perception On Health Behaviors And O

Summary (Applicant's abstract) The overall goal of the proposed study is determine if perceived risk of heart disease among postmenopausal women enrolled in the Observational Study (OS) of the Women's Health Initiative (WHI) in the New York Clinical Center, differs by race, and if risk perception is related to health behaviors. The applicant's long-term career goals are to become an independent investigator with special scientific interest in determining the key psychosocial contributors to racial and gender disparity in heart disease morbidity and mortality. In the proposed study, the first phase will be to develop and pilot test a methodologically sound instrument that measures perceived risk of heart disease. The second phase will be to administer this instrument to 300 White, African-American and Hispanic women at higher risk of heart disease because of smoking status, hypertension, diabetes or high cholesterol (requiring pills) and to determine the relationship of risk perception...

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

Lifespan in an anovulatory state, as compared to humans (50 ) (Tardif et al, 1992 Bellino and Wise, 2003), making it difficult to study postmenopausal changes. Additionally, researchers face high costs to obtain and care for these animals (expensive due to the cost involved in maintaining them for 20+ years), the supply is limited, and there is a higher risk of loss of data due to age-related illness or death. Thus, two models have been developed to alleviate these challenges the intact, aged, and the ovariectomized, young monkey. 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...

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

How Ovarian Steroids Affect Mammographic Density

The association between ovarian steroids and mammographic density parallels what is known about the effects of ovarian steroids and breast cell proliferation.43 Breast cell proliferation is higher in pre- than postmenopausal women and higher in women in the luteal than in the follicular phase of the menstrual cycle. In short, high estrogen progesterone levels are associated with high amounts of breast cell proliferation.

Using Hormonal Strategies To Improve Mammographic Density And Sensitivity Of Screening Mammograms

It is possible that the benefit of such hormonal strategies varies substantially. It is clear that not everyone who takes a GnRHA regimen has a reduction in density,36 just as not everyone who starts EPRT has an increase.51 The biological or genetic predictors of mammographic density changes with hormonal alterations are currently unknown. Thus, in the absence of such predictive markers, the best clinical approach currently to improve the screening benefit in a young woman with dense breasts would be to simply test whether a temporary endogenous hormone reduction will result in a reduced amount of density on her mammogram. For premeno-pausal women, a reversible approach, such as a GnRHA-based regimen, ought to be attempted first. Women with a substantial reduction in mammographic density with a GnRHA-based regimen may be more likely to benefit from ta-moxifen treatment or early oophorectomy than women who do not have density reduction with such hormonal manipulation. Postmenopausal...

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

Lacassagnes Prevention Principle A Target And An Estrogen Antagonist

Were conducted exclusively on postmenopausal women with advanced breast cancer,3,4 and not until 1977 was it suspected that tamoxifen was more effective in ER-positive breast cancer.46 Tamoxifen is currently used as a palliative therapy in the treatment of pre- and postmenopausal patients with ER-positive, advanced breast cancer. Adjuvant therapy revolutionized the treatment of breast cancer and is now used after breast surgery to destroy undetected mi-crometastases in a woman's body. The general principles derived from the use of tamoxifen as a therapy for breast cancer serve as the basis for consideration of tamoxifen as an estrogen antagonist in the prevention of breast cancer.

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

Information from Human Studies

Wismer Fries et al (2005) reported that children who had lived in orphanages with limited social contact for an average of 17 months before being adopted showed lower overall urinary vasopressin levels for 4 days and lower urinary oxytocin during a game involving lots of mother-child touching compared with age-matched children who had always lived with their parents. Adult men who experienced early parental separation have also failed to show normal inhibition of cortisol following intranasal oxytocin administration (Meinlschmidt and Heim, 2007), while adult women who had experienced childhood abuse or neglect had lower oxytocin levels in their cerebrospinal fluid (Heim et al, 2008). Together, these studies suggest that central oxytocin and vasopressin pathways may show long-term effects of early life events involving parental attachment. In young unmarried adults, higher plasma oxytocin levels were linked to stronger attachment to their parents and to lower...

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...

Conclusions and Future Research Directions

With our greater understanding now of the factors that likely contributed to the findings in the WHI trial, any conclusions about the prophylactic benefit of ERT HRT for cardiovascular risk in perimenopausal or healthy postmenopausal women are precluded. Consequently, with the appreciation in the field of behavioral medicine for identifying individual difference characteristics that predict both disease risk and response to intervention, we have reached a new dawn in research related to ERT HRT in peri- and postmenopausal women. Future

Biological Basis For Tamoxifen As A Breast Cancer Preventive

Tamoxifen produces partial agonist action in the rat uterus,56 but until the late 1980s there was little information about its actions in the normal human uterus. It is now clear that a variety of en-dometrial changes occur in unselected populations of women.110 The most significant finding is an increase in the stromal component, rather than endometrial hyperplasia.111,112 Laboratory data suggesting that tamoxifen has the potential to encourage the growth of preexisting disease harbored in the uterus67,68 provoked an intense investigation of the rates of endometrial cancer detection in women using adjuvant tamoxifen treatment for breast cancer. It is clear from the results of the tamoxifen prevention trial106 that ta-moxifen does not cause an excess of endometrial cancer in premenopausal women but does increase risk by three- to fourfold in post-menopausal women. This is consistent with the fact that women harbor four to five times the level of endometrial cancer than is detected...

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. ers have found no relationship between abortion and breast cancer.131,132 Studies of the effect of lactation on breast cancer risk have also been in-conclusive,133,134 but recent studies have suggested that a long duration of lactation...

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).

Identification of Candidates for Chemoprevention

Come from studies of white women thus, little is known about the impact of ethnic diversity. Finally, with the exception of women with predisposing genetic mutations, the majority of women with risk factors will not develop breast carcinoma. A recent study of the fraction of breast cancer cases in the United States attributable to risk factors152 found that fewer than 50 of women who develop the disease have any identifiable risk factors. Family history of breast cancer accounted for only 9 of cases, while relatively minor risk factors, such as later age at first birth and nulliparity, were seen in 29 of cases. In a similar study, Seidman et al.153 noted that only 21 of breast cancer cases in women aged 30-54 and 29 of cases in women aged 55-84 occurred in women with at least one of 10 common breast cancer risk factors. The majority of women had minor risk factors, which increase the RR of breast cancer only twofold, and most had only a single risk factor. This level of increased risk...

Royal Marsden Pilot Study

Acute toxicity was low for participants in the pilot study, and compliance remained correspondingly high 77 of women on tamoxifen and 82 of women on placebo remained on medication at 5 years.163 There was a significant increase in hot flashes (34 vs. 20 , p 0.005), mostly in premenopausal women vaginal discharge (16 vs. 4 , p 0.005) and menstrual irregularities (14 vs. 9 , p 0.005). At the most recent follow-up, 320 women had discontinued tamoxifen and 176 had discontinued placebo prior to the study's completion.160 In contrast, tamoxifen exerted antiestrogenic or estrogenic effects on bone density, depending on menopausal status. In premenopausal women, early findings demonstrated a small but significant (p 0.05) loss of bone in both the lumbar spine and hip at 3 years. In contrast, postmenopausal women had increased bone mineral density in the spine (p 0.005)

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.

Comparisons Of Longterm Effects Of Diagnosis And Treatment By Cancer Site Breast Cancer And Hodgkins Disease

We found no significant changes in marital partner status or in employment status in the breast cancer group. With regard to the SF-36 subscales, social function improved over time. We did not find differences in sexual activity or reporting of sexual problems even though by now most women were menopausal (75 due to treatment) and there were fewer children at home. There were significant decreases in the size of one's social network and emotional support. In multivariate analyses, less reduction in emotional support predicted better QOL.

Methodological issues in the hunt for human obesity genes

Obesity is defined as an excess of body fat, which can be measured directly using dual energy X-ray absorptiometry and isotopic dilution techniques. However, these are costly and their limited availability makes it difficult to perform such measurements in large numbers of subjects. In some studies fat mass has been measured indirectly using bioelectrical impedance or skin-fold thickness both of which correlate reasonably well within the normal range but less so in the very lean or the obese. The most commonly used marker of adiposity is BMI (weight in kg height in m2) which is a measure of heaviness that can be performed in large epidemiological studies and correlates reasonably well with body fat content. Body fat distribution provides an additional risk that is not given by simply the amount of body fat. Abdominal fat mass, for example, can vary significantly within a narrow range of total body fat or BMI. Furthermore, within a given BMI, men have on average twice the amount of...

Study Of Tamoxifen And Raloxifene

The STAR trial is a phase III, double blind trial that is assigning eligible postmenopausal women to either 20 milligrams daily tamoxifen or 60 milligrams daily raloxifene therapy for 5 years. Trial participants will complete a minimum of 2 additional years of follow-up after therapy is stopped. The STAR trial's primary aim is to determine if long-term raloxifene therapy is effective at preventing the occurrence of invasive breast cancer in high-risk postmenopausal women. It will additionally compare cardiovascular data, fracture data, and general toxicities for raloxifene and ta-moxifen. It is clear that the activation or suppression of various target sites is similar for ta-moxifen and raloxifene, but evaluation of the comparative benefits of the agents will provide an important new clinical database for raloxifene in postmenopausal women. Premenopausal women at risk for breast cancer are currently ineligible for the STAR trial. Although there is extensive information about the...

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

Breast cancers are thought to arise from the epithelial cells of the terminal duct lobular unit (TDLU). Studies of cell proliferation rates of the TDLU are therefore of substantial interest to our understanding of the factors that influence breast cancer risk. Repetitive cell proliferation is central to the risk of many common human cancers, and factors that increase cell proliferation in a tissue may result in malignant transformation by increasing the probability of converting DNA damage, however caused, into stable mu-tations.6-10 In the postmenopausal human breast, the rate of TDLU cell proliferation is low compared to the premenopausal breast.11,12 This low rate of cell proliferation is consistent with the small change in breast cancer risk seen during the postmenopausal years. The steeply rising premenopausal breast cancer rates are consistent with the measured higher breast ep ithelial cell proliferation rates and vary associated with the phase of the menstrual cycle,...

Gonadotropinhormonereleasing Hormone Analogues

Native GnRH produced by the hypothalamus controls the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the pituitary and, thence, gonadal steroid hormone production. Inhibition of GnRH action can be achieved either with recently introduced antagonists or with agonists that desensitize GnRH receptors. Potent synthetic agonists of GnRH administered to pre-menopausal women produce a transient rise in FSH LH release followed by a sustained suppression. Reduction in serum estradiol and serum progesterone to oophorectomized levels by GnRH agonists has been demonstrated in numerous reports and has led to their use in the treatment of hormone-responsive metastatic breast cancer in premenopausal women.19 The role of ovarian ablation in the adjuvant therapy of early breast cancer remains unsettled, and studies evaluating GnRH analogues continue. Adjuvant studies in hormone receptor-positive premenopausal breast cancer patients show a benefit similar to...

Gonadotropinhormonereleasing Hormone Analogues In Combination

Use of GnRH analogues in premenopausal women is predictably associated with hypo- The effect of protracted GnRH analogue treatment on BMD has prompted consideration of several strategies to combat the loss of bone density. A logical choice is addition of a SERM such as tamoxifen, which is known to have protective effects on BMD.23 The use of tamoxifen combined with a GnRH analogue is also of interest because of the known chemopreventive effects of tamoxifen.24 Bisphosphonates are important agents in the management of osteopenia in postmenopausal women. A study testing the combination of a GnRH analogue and a bispho-sphonate has also been proposed. While either approach may ultimately prove useful in reducing the loss of BMD, the tolerance of women to hypoestrogenic symptoms, which will not be alleviated by these approaches, remains to be evaluated. Analogues of GnRH are associated with greater symptoms than tamoxifen alone in the adjuvant setting,25 and control of these symptoms may...

GH Administration for Age Related Osteoporosis

Only a small number of studies have evaluated the effects of GH administration on bone density in women with postmenopausal osteoporosis and elderly men. The sample sizes of these studies have typically been small and overall fail to demonstrate a positive effect of GH on bone density. Aloia et al. (49) performed a series of three studies evaluating the effectiveness of GH in the treatment of post-menopausal osteoporosis. The first of these included eight patients who received pituitary-derived human GH for up to 12 mo (49). Bone resorption increased as measured by urine hydroxyproline, and bone density of the radius decreased. A subsequent study compared 24 mo of combination treatment with GH and calcitonin to calcitonin alone in 25 post-menopausal women, and showed a deleterious effect of the addition of GH on radial bone density (50). The third study compared a regimen of alternating GH and calcitonin to calcitonin alone in 14 women over 24 mo, and showed no significant difference...

Gonadotropinhormonereleasing Analogues With Addback Sex Steroids

Low-dose hormone-replacement therapy, as proposed by Pike et al.,1 will reduce the hypo-estrogenic symptoms of a GnRH analogue. While there is greater hormone exposure than would occur with a GnRH agonist alone, the overall reduction in hormone exposure compared to remaining premenopausal is substantial with reductions in estrogen exposure of 60 and in progestogen exposure of 75 . As the add-back low dose should permit long-term use, protracted reductions in hormone exposure would be possible. The predicted reductions in breast cancer incidence are less than with a GnRH analogue alone (Table 13.1) but remain substantial. As will be discussed below, the dose of add-back proposed is similar to that used as hormone-replacement therapy in postmenopausal women however, the schedule of progestin administration differs. The add-back will, of course, have an effect on breast cancer risk. The effect of the add-back on breast cancer risk is consistent with that reported from studies of...

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).

Isabell A Schmitt Milana Dolezal Michael F Press

Breast cancer is the most common malignancy in women, and treatment is challenging. The potential role of hormonal therapy in breast cancer treatment was first demonstrated by George Beatson more than 100 years ago, when he showed that two of three premenopausal women with metastatic breast cancer responded to ovarian ablation.1 Subsequently, Huggins and Bergenstal2 demonstrated that postmenopausal women with metastatic breast cancer responded to ovariectomy and adrenalectomy. Despite the usefulness of hormonal ablation in some women, only approximately 30 of unselected women with metastatic breast cancer responded to the treatment.3 Thus, there was a need to distinguish those women whose breast cancers were hormone-dependent from those whose cancers were hormone-independent. Jensen and collaborators4 demonstrated that patient responsiveness to endocrine manipulative management was correlated with the uptake of estrogen in the breast cancer tissue. The first results showed that uptake...

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...



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