Natural Menopause Relief Secrets

Holistic Hormone Balance

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

Holistic Hormone Balance Summary

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Menopausal Symptoms

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

Postmenopausal Dyspareunia

Recurrent pain during intercourse occurring for the first time within or subsequent to the menopausal transition is typically attributed to vulvovaginal and urogenital atrophy (also referred to as atrophic vaginitis) (83). These conditions are manifestations of tissue aging, cytological changes, and chemical transformations within the vagina, urethra, and bladder, which result from declining levels of endogenously produced estrogens at menopause (84,85). Both the DSM-IV-TR (3) and the ICD-10 (4) specifically mention this problem but do not classify it as dyspareunia. In the DSM-IV-TR, it would be termed a sexual dysfunction due to a general medical condition, whereas in the ICD-10, it is classified as postmenopausal atrophic vaginitis. These classifications and descriptions appear to be based on clinical experience since there is, in fact, very little systematic research evidence to support a strong link between declining estrogen levels, vulvovaginal atrophy, and recurrent pain...

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.

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...

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.

Menopause and Obesity in Women

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

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...

Age at Menopause

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

Menopause

Inhibition of serotonin reuptake and possible oestrogenic activity provide a theoretical basis for its use in pre- and postmenopausal women with mild to moderate depression (Ofir et al 2003, Takeuchi et al 1991). Constituents in licorice may bind to oestrogen receptors, enhance osteoblast function and attenuate vascular injury and atherosclerosis (Choi 2005, Somjen et al 2004a, b) suggesting a possible role in the prevention of bone disorders and cardiovascular diseases in postmenopausal women.

The menopause

Epidemiological studies do not demonstrate any increase in major psychiatric morbidity in women of menopausal age. However, mild to moderate depression or anxiety may develop at this time of life perhaps secondary to hormone changes, perhaps reactive to physical symptoms, or perhaps reflecting life changes such as children leaving home, death of parents, and awareness of ageing. Again, a variety of treatments has been used (http www.clinicalevidence. especially hormone replacement therapy (HRT) progesterone alone is 'beneficial', but oestrogen alone or in combination with progesterone causes 'improved menopausal symptoms but increased risk of breast cancer, endometrial cancer, stroke, and venous throm-boembolism after long term use', and there is a 'trade-off between benefits and harms'. Antidepressants are of 'unknown effectiveness'.

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...

The Clinical Significance of FAS

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

Age Gender Ethnicity and Geography

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

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...

Estrogen Receptor and Normal Cell Cycle in Breast Tissue

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

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).

Estrogen replacement therapy

Postmenopausal women without contraindications should consider ERT. Contraindications include a family or individual history of breast cancer estrogen dependent neoplasia undiagnosed genital bleeding or a history of or active thromboembolic disorder. 2. ERT should be initiated at the onset of menopause. Conjugated estrogens, at a dose of 0.625 mg per day, result in increases in bone density of 5 .

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,...

Lymphovascular Supply

Clinical features related to uterine pathology are most commonly those of abnormal uterine bleeding. In premenopausal patients this may take the form of menorrhagia (heavy periods), dysmenorrhoea (painful periods) or a variety of other forms of abnormal uterine bleeding. In postmenopausal patients, the most common symptomatology is postmenopausal bleeding. This should always be taken seriously and uterine malignancy excluded. Other symptomatologies related to uterine pathology include a palpable abdominal or pelvic mass, pain within the pelvis or abdomen (often deep seated), a feeling of fullness within the abdomen and uterine prolapse. Uterine pathology may also be associated with symptoms such as constipation, urinary frequency or infertility.

Clinical Investigations

Ultrasound scan transvaginal ultrasound scan is often performed in patients with abnormal uterine bleeding and other symptomatology related to the uterus. This may show focal lesions or diffuse thickening of the endometrium or myometrium. The endometrial thickness can be measured and related to the menopausal status of the patient. Endometrial sampling usually sampling of the endometrium to provide material for histology is necessary for a definitive pathological diagnosis, especially in cases of abnormal uterine bleeding such as postmenopausal bleeding. In some centres, endometrial brushings with cytological examination is carried out but this is rare. Previously, the most common means of sampling the endometrium was by dilatation and curettage (D & C). This requires a general anaesthetic and is performed as an inpatient procedure. However, pipelle endometrial biopsies can now be performed as an outpatient procedure without the need for a general anaesthetic. Histological sampling...

Colorectal cancer epidemiology

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

Influence of Age and Sex on Metal Toxicity

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

Concentration Of Estrogens And Their Sulfates In Normal And Pathological Breast

Estrogen sulfotransferase activity is very high in both physiological and pathophysiological conditions. It is well established that EXS is quantitatively the most important form of circulating estrogen during the cycle (Honjo et al., 1987 Nunez et al., 1977) as well as in postmenopausal women (Noel et al., 1981 Roberts et al., 1980). Different studies agree that the plasma levels of unconjugated estrone and estradiol are similar in normal women and in breast cancer patients (for a review, see Pasqualini and Chetrite, 1996), although Thomas et al. (1997) reported a strong positive relationship between breast cancer susceptibility and increased serum estradiol concentration. However, the concentration of E1S is significantly higher in the follicular phase of premenopausal breast cancer patients than in normal women (Pasqualini et al., 1996). In breast cancer tissues, most authors agree that the concentrations of unconjugated estrogens are found at high levels (Bonney et al., 1983...

Materials and Methods

Samples of ECA tissue were collected from women (ages 39 to 69) who underwent total abdominal hysterectomy. Normal endometrium was obtained from patients undergoing surgery for reasons other than the endometrium pathology. We examined 21 normal endometrium (6 post and 15 premenopausal) and 19 malignant endometrium samples 10 in stage greater than IA and 8 greater than IC, according to International Federation of and Gynecology and Obstetrics (FIGO) 1988 criteria .

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

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

Clinical evaluation

Ninety percent of patients with endometrial cancer have abnormal vaginal bleeding, usually presenting as menometrorrhagia in a perimenopausal woman or menstrual-like bleeding in a woman past menopause. Perimenopausal women relate a history of intermenstrual bleeding, excessive bleeding lasting longer than seven days or an interval of less than 21 days between menses. Heavy, prolonged bleeding in patients known to be at risk for anovulatory cycles should prompt histologic evaluation of the endometrium. The size, contour, mobility and position of the uterus should be noted. B. Patients who report abnormal vaginal bleeding and have risk factors for endometrial cancer should have histologic evaluation of the endometrium. Premenopausal patients with amenorrhea for more than six to 12 months should be offered endometrial sampling, especially if they have risk factors associated with excessive estrogen exposure. Postmenopausal women with vaginal bleeding who either are not on hormonal...

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...

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 inconclusive,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...

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...

Cardiovascular Effects

In a double blind, placebo-controlled, randomised trial of red clover-derived isoflavones (43.5 mg day), with 205 women aged between 49 and 65 years, active treatment had no significant effect on total cholesterol or HDL- and LDL-cholesterol levels or triglycerides (Atkinson et al 2004b). A single-blind, randomised crossover study of 21 healthy premenopausal women (aged 18-45 years) found that tablets containing 86 mg day isoflavones for two menstrual cycles did not significantly change total cholesterol, HDL- or LDL-cholesterol or triglyceride levels (Samman et al 1999). Another study of postmenopausal women with mild to moderate hypercholesterolemia also found red clover did not significantly affect plasma lipids (Howes et al 2000). A recent double-blind, randomised parallel study found that 86 mg day purified isoflavones derived from red clover also had no effect on cholesterol homeostasis or insulin resistance in 25 premenopausal women (Blakesmith et al 2003). However, there have...

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 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...

The Opgranklrank System

OPG binds to RANKL leading to inhibition of the osteoclastic activation (see Figure 58.1) (Khosla et al., 2001). OPG Knock-out mice develop arterial wall calcification as well as osteoporosis (Min et al., 2000). Reversal of these abnormalities is observed in OPG transgenic restoration (Min et al., 2002). Furthermore, intravenous injection of recombinant OPG protein reverses the osteoporotic phenotype observed in OPG-deficient mice (Min et al., 2000). Also, in a randomized, double-blinded, placebo-controlled study, a single subcutaneous injection of OPG was found to be effective in reducing bone turnover in postmenopausal women, highlighting its potential as a therapeutic agent for osteoporosis (Bekker et al., 2001).

Cardiovascular Disease

There are many potential mechanisms by which soy may improve cardiovascular outcomes, including reduction in total cholesterol, LDL, HDL, triglycerides, lipoprotein a, blood pressure, C-reactive protein, homocysteine, endothelial function, systemic artery compliance, and oxidised LDL (Balk et al 2005). A review by the North American Menopause Society suggests that the most convincing health effects of soy can be attributed to the actions of isoflavones on lipids, with studies finding statistically significant reductions in LDL and triglycerides, as well as increases in HDL (Greenwood et al 2000). It is unclear how soy exerts its beneficial effects on lipid metabolism or Soy 1107 Although it has been suggested that there is no evidence of beneficial effects of phyto-oestrogens on blood pressure, arterial compliance or oxidation of LDL-cholesterol, there may be beneficial effects on endothelial function and homocysteine concentrations in postmenopausal women (Cassidy & Hooper 2006)....

Osteoporosis Prevention

The clinical data suggest that approximately 80 mg day isoflavones are needed to derive skeletal benefits, whereas limited epidemiologic data among Asian populations generally suggests that lower amounts are efficacious (Messina et al 2004). The relationship between usual soy food consumption and fracture incidence was studied in 24,403 postmenopausal women aged 40-70 years who had no history of fracture or cancer in the Shanghai Women's Health Study. During a mean follow-up of 4.5 years a statistically significant association was found between soy or isoflavone consumption and fracture risk, with the association being more pronounced among women in early menopause (Zhang et al 2005). A recent systematic review found 31 studies that evaluated the effect of soy on markers of bone health however, few of these were long term studies and they involved a wide variety of interventions making overall conclusions difficult. Of the 5 studies longer than 1 year, no consistent effect was seen on...

Division H Of Meiosis

Annulate Lamellae

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

Longlived Monkeys Have Life Spans Proportional To Human Centenarians

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

Recommended Resources

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

Physical Exercise and Body Weight

Physical exercise is known to be associated with reduced breast cancer risk in the general population, although the degree of protection afforded in relation to the amount and intensity of exercise is not entirely clear (41). The relationship between body weight and breast cancer risk is more complex, with an interaction repeatedly observed with menopausal status. A pooled analysis of data from seven prospective cohort studies has confirmed that while being overweight increases breast cancer risk among postmenopausal women by around 25 , obesity is associated with protection from breast cancer in premenopausal women (49). Only two studies have investigated weight-related factors among BRCA1 and BRCA2 mutation carriers. In a study including just 104 Ashkenazi Jewish carriers of one of three ancient mutations, King et al. (7) found evidence that physical exercise during teenage years was associated with reduced breast cancer risk among BRCA1 and BRCA2 mutation carriers (RR 0.63 p 0.03),...

Genisteine And Isoflavones

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

Possible Mechanisms Responsible For Hypertension

Whether RAS activity changes with age in men and women is somewhat controversial. James and colleagues (1986) reported from serial analyses that plasma renin activity (PRA) was higher in men than in age-matched women, that PRA was higher in postmenopausal women than in premenopausal ones, and that in white men, PRA did not decrease with age. Blood pressure becomes more salt sensitive with aging in both men and women (Weinberger and Fineberg, 1991), which suggests that RAS activity and Ang II do not respond appropriately in the presence of salt in aging individuals. Endothelin is a potent vasoconstrictor that when infused chronically leads to increases in blood pressure (Wilkins et al., 1995). Endothelin has been shown to be up-regulated during Ang II infusion (Alexander et al., 2001). Therefore, if aging is associated with activation of the RAS, then the increased synthesis of endothelin could play a role in the Ang II mediated increase in blood pressure with aging. In postmenopausal...

Anatomical And Morphological Relationships Of The Female Reproductive System

Corpus Hemorrhagicum

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

Chromosomal Instability A New Paradigm for Estrogeninduced Oncogenesis

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

Clinical Considerations

Rectal Nerve Block

Pelvic relaxation is the weakening or loss of support of the pelvic organs because of damage to the pelvic diaphragm, urogenital diaphragm, transverse cervical ligament, uterosacral ligament, or pubocervical ligament. It may result in cystocele (prolapse of the urinary bladder into the anterior vaginal wall), rectocele (prolapse of the rectum into the posterior vaginal wall), or uterine prolapse (prolapse of the uterus into the vaginal vault). Pelvic relaxation may result from multiple childbirths birth trauma increased intraabdominal pressure because of obesity, heavy lifting, or chronic cough or menopausal loss of muscle tone. Clinical signs include a heavy sensation in the lower abdomen that is exacerbated by heavy lifting or prolonged standing increased

Age at Onset and Resolution

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

Controversies and Discrepancies Concerning Progestin Action on Mammary Glands

Progestin Pathway

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

What is Your Diagnosis

Calcium Breast Mass

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

Identification of a Second HS Locus to Chromosome

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

Evidence for Ovarian Senescence in Rhesus Monkeys

Female Lifespan Ovarian Reserve

The number of potentially viable oocytes available to the reproducing female depends on the size of the primordial follicle population within the ovary. In humans, primarily due to follicular atresia and secondarily because of follicular recruitment, the numbers of primordial follicles decrease dramatically from birth to the onset of menopause. At the end of the reproductive lifespan, the ''ovarian reserve'' of viable follicles and oocytes is essentially depleted, and the ovary is said to be senescent (Faddy and Gosden, 1996). Concomitantly, ovulatory activity ceases and levels of estrogen decrease markedly. As a result, FSH secretion increases strikingly because of diminished negative feedback from estrogen (Walker, 1995). Bioactive FSH retrieved from postmeno-pausal women's urine was in high demand for a number primary follicles is gonadotropin-dependent (Macklon and Fauser, 1999), many of the newly formed primary follicles in older females cease development or become atretic,...

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...

Ovarian Germ Cell Tumors

Embryonic Cyst Ovary

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

Nonhuman Primate Models Old World Monkeys

Osteogenesis Imperfecta Life Expectancy

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...

Vulvar Vestibulitis Syndrome

Vulvar Vestibulitis Treatment

Vulvar vestibulitis syndrome is believed to be the most common form of painful intercourse in premenopausal women (10), affecting an estimated 12 in the general population (8). Women with vulvar vestibulitis typically experience a severe sharp, burning pain localized at the entrance of the vagina (i.e., the vulvar vestibule) (14). This pain occurs upon contact, through both sexual and nonsexual stimulation (10,14). Approximately half of the women with vulvar vestibulitis syndrome have primary vestibulitis, that is, they have experienced the pain from their first intercourse attempt, whereas the other half of the sufferers develop the pain after a period of pain-free intercourse, termed secondary vestibulitis (29,30).

Lack of Association between HS and Endocrinopathies

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

Age Related Changes in Fat Distribution

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

Genetic Models Of Hypertension

Female SHR A model of postmenopausal hypertension. The elucidation of mechanisms responsible for postmenopausal hypertension has been stunted by lack of an animal model (Reckelhoff and Fortepiani, 2004). Most of the studies in postmenopausal women have been correlative. Sheep, rabbits, nonhuman primates, rats, and mice have been used as models of various meno-pausal changes. However, to our knowledge, there have been few studies in which a naturally occurring animal model of postmenopausal hypertension has been described. The female SHR is an exception to this. Throughout their reproductive lives, female SHR have mean arterial pressures that are 25 to 30 mm Hg lower than male SHR, although they are quite hypertensive compared to normotensive rats (Reckelhoff and Fortepiani, 2004). When female SHR stop estrous cycling at 10 to 12 months of age, the blood pressure begins to increase such that by 16 months of age, the mean arterial pressure is similar or even higher than in males of...

Typical vs Atypical Ischemia

Relatively uncommon unless they are postmenopausal, or affected by atypically high cholesterol levels or diabetes mellitus. Accelerated atherosclerosis, even in women with adequate ovarian hormonal function, can occur with hypercholesterolemia, diabetes mellitus, and rarely hypo-thyroidism with myxedema. We are not informed of this patient's menstrual history, a critical piece of information that is often not investigated during acute presentations with serious complaints in emergency rooms. However, it is reasonable to assume that at age 45 she was not postmenopausal. Moreover, she did not have a history of diabetes mellitus or hypertension. However, her physical examination did reveal a diffusely enlarged thyroid gland, but she had no complaints or physical signs of significant hypo or hyperthyroidism. Her serum cholesterol was low, which may even be secondary to hyperthyroidism, but it certainly rules out hypercholesterolemia. Despite this, she had a positive family history, with...

Sexual aversion disorder

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

Genetic Testing Complexitieswhere To Start

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

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 postmenopausal 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...

Comparison with Other Risk Factors

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

Aging Of The Reproductive System In Females

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

Is Absent or Impaired Genital Responsiveness a Valid Diagnostic Criterion

In a recent study we investigated whether pre- and postmenopausal women with sexual arousal disorder are less genitally responsive to visual sexual stimuli than pre- and postmenopausal women without sexual problems (42). Twenty-nine women with sexual arousal disorder (15 premenopausal and 14 postmenopausal), without any somatic or mental comorbidity, diagnosed using strict DSM-IV criteria, and 30 age-matched women without sexual problems (16 premenopausal and 14 postmenopausal) were shown sexual stimuli depicting cunnilingus and intercourse. Genital arousal was assessed as vaginal pulse amplitude (VPA) using vaginal photoplethysmography. We found no significant differences in mean and maximum genital response between the women with and without sexual arousal disorder, nor in latency of genital response. The women with sexual arousal disorder were no less genitally responsive to visual sexual stimuli than age- and menopausal status-matched women without such problems, even though they...

David J Bentrem V Craig Jordan

In 1896, George Beatson1 demonstrated that the removal of ovaries from premenopausal women with metastatic breast cancer could cause regression of the disease and improve the prognosis however, by 1900 Stanley Boyd2 established that only one in three patients would respond and only for 1 year. Despite this disappointment, a link was established between an In the 1950s and 1960s, it became clear that adrenalectomy, with glucocorticoid support, improves the prognosis of some postmenopausal women with advanced breast cancer.8 In fact, about one-third of the women responded, approximately the same proportion as pre-menopausal women after oophorectomy. The reason for the apparently arbitrary responses was not resolved until the discovery of the estrogen receptor (ER),9 and the subsequent application of this knowledge to predict the hormone responsiveness of a patient's tumor to endocrine ablation.10 Only patients whose tumors had high levels of ER were likely to respond to endocrine...

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

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

Cognitive Function

Although not all studies have consistently shown benefits of soy on cognitive function, there have been a number of double-blind RCTs showing that soy improves memory and frontal lobe function in young volunteers (File et al 2001) and postmenopausal women (Duffy et al 2003, File et al 2005). In one 6-week double-blind trial in 50 postmenopausal women, 60 mg day total isoflavone equivalents significantly improved non-verbal short-term memory and performance on tests of frontal lobe function with no effects on long-term memory, category generation, or sustained attention (File et al 2005). Similarly, another double-blind controlled trial of 33 postmenopausal women found that 12 weeks' supplementation with the same supplement significantly improved recall of pictures, sustained attention, learning rule reversals and planning at 12 weeks without affecting menopausal symptoms, self-rating of mood, bodily symptoms or sleepiness (Duffy et al 2003). A further double-blind, randomised,...

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

Medical Letter In Reference To Erical Dysfunction

Measuring the menopause genital changes a critical account of laboratory procedures past and for the future. Menopause Rev 1999 1V 49-57. 43. Caruso S, Intelisano G, Lupo L, Agnello C. Premenopausal women affected by sexual arousal disorder treated with sildenafil a double-blind, cross-over, placebo-controlled study. Int J Obstet Gynaecol 2001 108 623-628. 44. Kaplan SA, Reis RB, Kohn IJ, Ikeguchi EF, Laor E, Te AE, Martins AC. Safety and efficacy of sildenafil in postmenopausal women with sexual dysfunction. Urology 1999 53 481-486. 55. Kokcu A, Cetinkaya MB, Yanik F, Alper T, Malatyalioglu E. The comparison of effects of tibolone and conjugated estrogen-medroxyprogesterone acetate therapy on sexual performance in postmenopausal women. Maturitas 2000 36 75-80. 56. Wu MH, Pan HA, Wang ST, Hsu CC, Chang FM, Huang KE. Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy. Climacteric 2001 4 314-319.

Inhibition Of Aromatase

Adipocytes 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...

BS2 Intermediate Course of the Disease

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

Treatment of acute DVT

Trauma, or major medical illness) from which they have fully recovered. Their risk of recurrence when anti-coagulants are discontinued at 3 months is estimated to be less than 5 in the next year and somewhat lesser in subsequent years. These patients should be encouraged to have prophylactic anti-coagulants if exposed to a high-risk state and, in general, should be encouraged to seek alternatives to oestrogens for contraception or post-menopausal use. Moderate-risk patients are those without inherited or acquired thrombophilia who had a thromboembolic event in association with a minor risk factor, such as, oestrogen use or long distance travel. Their risk of recurrent thrombosis after 6 months of anti-coagulants is likely to be less than 10 in the year after stopping anti-coagulants, provided that the precipitating risk factor is avoided they should be treated with anti-coagulants for 6 months. If, however, the precipitating factor cannot be avoided (e.g., oestrogens) they should be...

Terminology and Definitions

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

Identifying Psychosocial Barriers to Success

There are a variety of bio-psychosocial obstacles to be recovered that contribute to treatment complexity. All of these variables impact compliance and sex lives substantially, in addition to the role of organic etiology (20). There are multiple sources of patient and partner psychological resistance, which may converge to sabotage treatment (i) What is the mental status of both the patient and the partner and how will this impact treatment, regardless of the approach utilized What is the nature and degree of patient and partner psychopathology (such as depression) What are the attitudinal distortions causing unrealistic expectations, as well as endpoint performance anxiety (ii) What is the nature of patient and partner readiness for treatment When and how should treatment begin, and be introduced into the couple's sex life What is his approach to treatment seeking What should be the pacing of intimacy resumption The average man with ED waits 2-3 years, before seeking...

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...

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)

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...

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...

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...

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...

Pharmacological Toxicological Effects 51 Endocrine Effects

Although many products containing ginseng are marketed specifically for postmenopausal women, a recent review concluded that there is insufficient evidence that ginseng is effective for treatment of menopausal symptoms (11). In vitro, Siberian ginseng extract, but not P. ginseng extract, binds to estrogen receptors. Both extracts have affinity for progestin, glucocorticoid, and mineralocorticoid receptors (32). A recent study reported that a morning evening formulation containing ginseng and other constituents relieved menopausal symptoms, but no placebo control was included so it is difficult to tell whether the effect was caused by the formulation or a placebo effect (33). However, two studies have also suggested that administration of ginseng (or a combination of ginseng and G. biloba) has no effect on cognition (and mood). Hartley and colleagues evaluated the effects of a 6- or 12-week course of a ginkgo ginseng combination product (Gincosan ) on the mood and cognition of...

Association of Osteoporosis and CVD

In another study of 236 premenopausal women aged 45 to 57 years, followed for nine years, the progression of atherosclerotic calcification of the aorta and metacarpal bone loss was demonstrated (Hak et al., 2000). In this prospective study, a cross-sectional analysis was also performed in postmenopausal women showing a graded inverse relationship between the extent of aortic LBMD was associated with increased mortality form CVD (Browner et al., 1991 von der Recke et al, 1999). In the study of osteoporotic fractures research group (Browner, 1991), 9704 ambulatory women aged 65 years and older were prospectively followed. LBMD at the proximal radius was strongly associated with increased mortality from stroke (relative risk 1.74 95 CI 1.12-2.70). This association was not confounded by other risk factors for stroke such as age, hypertension, diabetes, smoking, or previous history of stroke (Browner et al., 1991). Another study involved two populations of healthy women one group...

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...

Inflammation on Pap smear

(HGSIL) or invasive cancer therefore, persistent inflammation is an indication for colposcopy. 6. Atrophy with inflammation is common in post-menopausal women or in those with estrogen-deficiency states. Atrophy should be treated with vaginal estrogen for 4-6 weeks, then repeat Pap smear.

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...

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

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

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...

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.

Female Reproductive System Disorders

Menopausal hot flushes According to one randomised, double-blind placebo-controlled study EPO supplementation significantly reduces the maximum number of night-time flushes, although other symptoms failed to respond. The study used a dose of four capsules daily (each containing 500 mg EPO and 10 mg vitamin E) over 6 months (Chenoy et al 1994). A position statement of the North American Menopause Society (2004) concluded that evidence was lacking to warrant the use of EPO in the treatment of vasomotor symptoms of menopause.

What conditions are often missed

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

Activation And Regulation Of Sexual Response Processing of Sexual Information

A surprising finding from our studies was the ease with which healthy women become genitally aroused in response to erotic film stimuli. When watching an erotic film depicting explicit sexual activity, most women respond with increased vaginal vasocongestion. This increase occurs within seconds after the onset of the stimulus, which suggests a relatively automatized response mechanism for which conscious cognitive processes are not necessary. Even when these explicit sexual stimuli are negatively evaluated, or induce little or no feelings of sexual arousal, genital responses are elicited. Genital arousal intensity was found to covary consistently with stimulus explicitness, defined as the extent to which sexual organs and sexual behaviors are exposed (66). This automatized response occurs not only in young women without sexual problems, but also in women with a testosterone deficiency (67), in postmenopausal women (68,69), and in women with sexual arousal disorder (42). Such responses...

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.

Urogenital Infections

Probiotics are widely used to decrease the frequency of recurrent bacterial vaginosis and candidal vulvovaginitis, and have undergone clinical testing that supports this use. They are administered both orally and intravaginally. Additionally, lactobacilli play a significant role in the prevention of UTIs. One study using intravaginal administration of probiotics such as Lactobacillus GR-1 and B-54 or RC-14 strains twice weekly for 2 weeks and then monthly for 2 months demonstrated that treatment resulted in 45 less UTIs than placebo and improved the maintenance of normal flora (Reid & Burton 2002). A significant reduction in UTI rate was also reported in a randomised double-blind study involving 55 premenopausal women (Reid 2001 b). The study investigated the effectiveness of treatment for 1 year with a weekly suppository containing either 0.5 g L. rhamnosus GR-1 and L. fermentum B-54 or a Lactobacillus growth factor. Treatment resulted in the UTI rate decreasing by 73 and 79 ,...

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...

Specific interventions

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

Neoplastic Conditions

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

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