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. More here...

Natural Female Hormone Balance Program Summary


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Menopausal Vasomotor Symptoms

In addition to its proven efficacy in PMDD, paroxetine (20 mg day) was shown to be effective in the treatment of postmenopausal hot flashes in breast cancer survivors with chemotherapy-induced ovarian failure in two open trials (Stearns et al. 2000 Weitzner et al. 2002) for a review, see Bordeleau et al. 2007) and in a double-blind study (Stearns et al. 2005). Paroxetine CR (25 mg day) was subsequently found to be efficacious in treating perimenopausal hot flashes in a placebo-controlled trial (Stearns et al. 2003). The drug's usefulness in this setting is underscored by recent concerns about the safety of hormone replacement therapy (HRT), hitherto the treatment of choice (H. D. Nelson et al. 2002). For clinicians and patients concerned about the long-term consequences of estrogen replacement in treating hot flashes, paroxetine provides a reasonable alternative.

Treatment Of Vasomotor Symptoms Of Menopause And Atrophic Vaginitis

Estrogens have been very useful in treating the hot flashes associated with early menopause, as well as atrophic vaginitis and other vaginal symptoms of inadequate estrogen production. The evidence that they result in enhanced mood and improved cognitive function in post-menopausal women is less clear, however, and more studies are needed to sort out the competing claims in these areas.102,103 Based on the results of the Women's Health Initiative (WHI) studies of HRT, however, the lowest effective doses should be used for as short of a duration as necessary for the management of postmenopausal symptoms (see below).

Menopausal Symptoms

One of the most disruptive and classic aspects of the menopause is the hot flash. In Western societies, it is the most common symptom of the menopause, although the prevalence is much lower in Japan 165,166 . This and the rarity of the problem in soybean-consuming populations have prompted investigations to determine whether phytoestrogens have a similar effect. Hormone replacement therapy (HRT) generally alleviates the hot flashes, as well as the vaginitis occurring at the menopause due to atrophy. More recently, postmenopausal HRT has been seen as a specific treatment for symptoms in the short-term and preventative therapy in the long-term 167 . Postmenopausal hormone therapy has both benefits and hazards, including a decreased risk of osteoporosis and cardiovascular disease and an increased risk of breast and endometrial cancer 168,169 . In a prospective study conducted by Grodstein et al. 170 , the relation between postmenopausal hormones and mortality was examined to provide a...

Sources of Estrogens in Human Breast Tissue

17 -Estradiol is biologically the most active estrogen in breast tissue. Circulating estrogens are mainly originated from ovarian steroidogenesis in premenopausal women and peripheral aromatization of ovarian and adrenal androgens in postmenopausal women 8 . The importance of ovarian steroidoge-nesis in the genesis of breast cancer is highlighted by the fact that occurring naturally or induced early menopause prior to age 40 years significantly reduces the risk of developing breast cancer 8, 44-46 . However, the uptake of 17b-estradiol from the circulation does not appear to contribute significantly to the total content of estrogen in breast tumors, since the majority of estrogen present in the tumor tissues is derived from de novo biosynthesis 47-50 . In fact, the concentrations of 17 -estradiol in breast cancer tissues do not differ between premenopausal and postmenopausal women, even though plasma levels of 17 -estradiol decrease by 90 following menopause 51 . This phenomenon might...

Increased Incidence of Female Breast Cancer

In women, the incidence of breast cancer has increased steadily over the past few decades in a number of countries including Finland, Denmark, USA and the UK.3i.39.4o in Finland, for example, the incidence rose from 25 per 100000 in 1953 to more than 40 per 100 000 in 1980. Although improved detection may be partly responsible, the underlying upward trend is estimated as about 1 per year since 1940. A number of factors that increase breast cancer risk have been identified, including diet, calorie intake and alcohol consumption, but lifetime exposure to oestrogens (age at menarche and menopause, use of contraceptive pill, etc.) is of major importance and environmental oestrogens might contribute to overall exposure and thereby to the rising incidence of the disease.

Nonsteroidal antiestrogens SERMs

The first discovered antiestrogen was clomiphene, but its development for the treatment for advanced breast cancer was discontinued because of concerns about potential side effects. In 1974, tamoxifen was the first antiestrogen to be approved for the treatment of advanced breast cancer (Great Britain) and in 1977 a similar approval was given by the FDA. Since then, tamoxifen has become the standard therapy for all types of ER-positive breast cancer. In the 1990s, it was also the first cancer chemopreventive agent approved by the FDA for the reduction of breast cancer in pre- and postmenopausal women with high risk.5 Tamoxifen also binds with high affinity to other targets, such as the microsomal antiestrogen

Steroidal antiestrogens

The SERMs, especially tamoxifen and toremifene, have been the preferred first-line hormonal therapy in estrogen-responsive postmenopausal breast cancer, but they have several disadvantages that are related to their partial estrogenic agonistic activity. These include tumor stimulation in some patients at the initial stages of the treatment (tumor flare) and increased hot flashes, endometrial cancer, and thromboembolism. These limitations stimulated the search for pure ER antagonists. which has been approved for the treatment of postmenopausal women with hormone-sensitive advanced breast cancer following prior endocrine therapy.15

Sex Differences in Insulin Resistance

Insulin resistance can vary between sexes and across a women's reproductive life cycle. For example, some studies have suggested that girls through adolescence are inherently more insulin resistant than boys, but this relationship is thought to reverse after puberty 3, 4 . In adults, fat distribution patterns favor the development of IR in men, as men are more likely to develop abdominal obesity. Abdominal fat tissue is a major source of free fatty acids and cytokines and is associated with IR 5 . Premenopausal adult women more frequently develop peripheral obesity with subcutaneous fat accumulation, whereas men and postmenopausal women are more prone to central or abdominal obesity. After the menopause, concentrations of lipoproteins as well as body fat distribution shift to a more male pattern 5 . Pregnancy is also a time of elevated peripheral IR for women. During pregnancy, there is an approximate 50 reduction in insulin sensitivity by the third trimester such changes are thought...

Steroid Sulfatase Inhibitors

It was previously mentioned that in postmenopausal women, who show the highest incidence of breast cancer, estrogens are produced in adipose tissues and in the breast by the action of aromatase on androstenedione. However, the clinical response to aromatase inhibitors is not as high as expected, and often it is not superior to the one obtained with antiestrogens or with other antihormones. Furthermore, there appears to be no relationship between the clinical response and the degree of suppression of circulating estradiol levels, which suggests that other factors besides the classical estrogens must be involved in tumor growth.33 Steroids with estrogenic properties can be biosynthesized by a route involving the steroid sulfatase (STS) enzyme, which regulates the formation of estrone by hydrolysis of estrone sulfate (E1S) and also controls the hydrolysis of dehydroepian-drosterone sulfate (DHEA-S) to dehydroepiandrosterone (DHEA). The latter compound can be reduced to 5-androstene-3p,...

Burning Mouth Syndrome

Summary This article discusses burning mouth syndrome (BMS), a condition that is characterized by a burning sensation in the tongue or other oral sites, usually in the absence of clinical and laboratory findings. Affected patients often present with multiple oral complaints, including burning, dryness, and taste alterations. Burning mouth complaints are reported more often in women, especially after menopause. Typically, patients awaken without pain but note increasing symptoms through the day and into the evening. Conditions that have been reported in association with BMS include chronic anxiety or depression, various nutritional deficiencies, type 2 diabetes, and changes in salivary function. However, these conditions have not been consistently linked with the syndrome, and their treatment has had little impact on BMS symptoms. Recent studies have pointed to dysfunction of several cranial nerves associated with taste sensation as a possible cause of BMS. Given in low dosages,...

Roles Of Estrogen In Angiogenesis

In premenopausal women, estrogen promotes angiogenesis in association with some diseases like Takayasu's arteritis and lupus erythematous.27 Together, the studies indicate that angiogenesis can be regulated by estrogen. A role for estrogen in angiogenesis is further supported by our studies on the rat pituitary that indicated estrogen as the sole etiological agent for the development of tumor angiogenesis during the development of estrogen-induced tumorigenesis.13 Some additional observations, such as inhibition of angiogenesis by antiestrogens, also support estrogen as a positive regulator of angiogenesis.107110

Sociodemographic factors

The mechanisms of gender differences in FMS are not fully understood. An interaction between biologic, psychological and sociocultural factors has been postulated 41 . Between puberty and menopause, adult women usually show lower responses of the hypothalamic-pituitary-adrenal axis (HPA) and autonomic responses than men of the same age 42 . Female gender is a risk factor for psychologic distress and some mental disorders (affective and anxiety disorder, PTSD) which are associated with FMS. Functional somatic syndromes

Depression And Reproductive Hormone Changes

In women with a previous episode of depression, times of rapidly changing gonadal steroid concentrations, such as those occurring premenstrually or postpartum, mark particularly vulnerable times for the occurrence of depressive symptoms. Several studies have shown that in women, a history of depression increases the risk of both postpartum blues and postpartum major depression (O'Hara 1986 O'Hara et al. 1991 Reich and Winokur 1970) and that hormonal changes occurring premenstrually may affect mood (Halbreich et al. 1984, 1986). When they were euthymic, 62 of women with a history of major depressive episodes reported the occurrence of premenstrual mood changes and biological symptoms typical of major depressive disorder. Other studies found a relationship between the rise in estrogen and testosterone levels and the rising incidence of depression in girls during adolescence (Angold et al. 1999). More recently in two epidemiological cohorts (Cohen et al. 2006 Freeman et al. 2006), there...

Reproductive Abnormalities in Depression

In depression, response to GnRH has been assessed by several groups. Some studies have reported a normal LH and FSH response to GnRH in pre- and postmenopausal women (Unden et al. 1988 Winokur et al. 1982). However, given the major differences in LH pulse amplitude and mean LH levels between follicular and luteal phases, it would be extremely difficult to observe a difference in basal LH secretion between major depression and control women without strict control of menstrual cycle phase. However, Brambilla et al. (1990) noted a decreased LH response to GnRH in both premenopausal and postmenopausal women, with lower baseline LH concentrations in postmenopausal depressed women. It may be that the increased secretion of LH following removal of the negative feedback of gonadal steroids in postmenopausal women unmasks a decrease in LH secretion that is not as easily observed in women with intact estrogen and progesterone feedback. Other studies examining depressed patients of both sexes,...

Growth Hormone And The Hypothalamicpituitarysomatotrophic Axis

Regulation make it difficult to extrapolate to humans from animal studies. It is well established, however, that the final common pathways for control of GH release from the pituitary are hypothalamic growth hormone-releasing hormone (GHRH) (stimulation) and somatostatin (inhibition). The wide variety of metabolic, endocrine, and neural influences that alter GH secretion do so primarily through effects on GHRH and or somatostatin. Neural influences may be mediated by noradrenergic, cholinergic, dopaminergic, 7 aminobutyric acid (GABA)-ergic, and serotonergic neurotransmission. Clear physiological regulatory roles, however, have only been well documented in humans for noradrenergic and cholinergic inputs. Dopamine, serotonin, and GABAergic drugs can alter GH release but do so in contradictory ways, depending on the experimental paradigm, leaving their roles as GH regulatory agents uncertain at present (Devesa et al. 1992 Muller 1987). In humans, GH is released by acute stress, but is...

Dilemma about Antioxidants

Most studies have been carried out in men. Knekt et al. (1996) found flavonoid intake to be significantly associated with reduced coronary risk in women. The risk was lowered non-significantly in men. It is well established that pre-menopausal women are relatively protected against coronary disease and that the protection may be due to circulating oestrogens which affect positively the LDL HDL (high-density lipoprotein) cholesterol ratio. The protection is lost in post-menopausal women. Could antioxidant protection by oestrogen be another factor in lowering risk in young women Shwaery et al. (1997) have reported that 17p-oestradiol protects LDL against copper-mediated oxidation in vitro. In another context, we showed many years ago that oestradiol inhibited ascorbic acid-catalysed oxidation of methyl linoleate (Kritchevsky and Tepper, 1964). White et al. (1997) have summarized results from other studies in which oestrogens influenced rates of LDL oxidation.

Vitamin E and Cardiovascular Disease

Observational studies have associated lower rates of heart disease with higher vitamin E intake. These studies held promise that vitamin E was protective against coronary heart disease.95 A study of 87,245 female nurses suggested that high intake of vitamin E from diet and supplements was associated with between 30 percent and 40 percent lower incidence of heart disease and that this was due primarily to vitamin E supplementation rather than intakes from food.96 Similarly, a reduction in heart disease-related mortality was observed in men and women in a smaller Finnish study.97 Intervention studies were undertaken to investigate these relationships. The Women's Angiographic Vitamin and Estrogen (WAVE) trial98 found no effects from supplements providing 400 IU vitamin E and 500 mg vitamin C twice a day in 423 postmenopausal women. One of the larger studies, the Heart Outcomes Prevention Evaluation (HOPE) Study, followed 10,000 patients at high risk for heart attack or stroke over 4.5...

Limitations to the current evidence

Although the meta-analyses in this chapter represent the best evidence regarding choice of intravenous fluid for resuscitation, one should be cautious in the application of their findings. Firstly, all of the meta-analyses pooled results from small randomised controlled trials. Most trials enrolled fewer than 100 patients per group. Most of the meta-analyses had fewer than 200 outcome events per comparison, which would be considered small and should be interpreted with caution.27 Previous instances, such as magnesium in the treatment of acute myocardial infarction and hormone replacement therapy in the prevention of coronary artery disease, in which subsequent large randomised controlled trials have contradicted the results of meta-analyses of small trials, highlight the danger of overinterpreting the findings of these systematic reviews.

YTocopheroi and Disease

A low y-tocopherol concentration and a high a- to Y-tocopherol ratio have been reported in patients with coronary heart disease (CHD) compared with controls (9,10) and in a population with a high incidence of CHD (11). These observations suggest that a serum tocopherol profile with low Y-tocopherol levels and a high ato Y-tocopherol ratio may be an indicator of an increased risk for CHD. In support of such a conclusion, Kushi et al. (12) reported that intake of dietary-derived vitamin E (i.e., mainly Y-tocopherol), but not supplemental vitamin E (a-tocopherol) was beneficial in reducing cardiovascular disease. Moreover, the same group recently arrived at a similar conclusion for postmenopausal women and death from stroke (13).

Effects of Perinatal Estrogen Exposure on Fertility and Cancer in Mice

Concerns have been raised regarding the reproductive and health hazards of chemicals in the environment that have potential endocrine disrupting effects. These concerns include increased incidences of breast, ovarian, and uterine cancer, endometriosis, fibroids, infertility, and early menopause in women in men, alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems have been suggested. Studies with the potent synthetic estrogen diethyl-stilbestrol (DES) have shown that exogenous estrogen exposure during critical stages of development results in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES is a potent environmental estrogen, studying its effects at low dose levels in an experimental animal model offers a...

Gender Dichotomy in AD Role of Sex Steroids

The part played by sex steroids, and estrogen in particular, in age-related cognitive decline and AD has gained prominence due to a number of lines of evidence suggesting that postmenopausal estrogen deficiency may contribute to both the benign cognitive decline 33-35 and the etiology of AD in women 36, 37 . These findings are supported by epidemiological and observational studies indicating that hormone replacement therapy (HRT) lessens the risk of AD in postmenopausal women 38-42 . It is interesting, however, that reports suggest HRT to be protective only when administered during a critical period,'' that constitutes the climacteric years. HRT is almost completely ineffective when given later during the postmenopausal years, during the latent preclinical stage of AD, the disease itself occurring much later in life 43-47 . The observed gender differences, in addition to the reported capacity of HRT to reduce AD risk in postmenopausal women, have led researchers to investigate a...

O Future Directions

A monoclonal antibody target for the treatment of osteoporosis is the RANKL, which is the essential mediator of os-teoclasts. As pointed out in the osteoporosis discussion, the loss of calcium by increased osteoclastic activity and decreased osteoclast apoptosis is opposed by a RANKL inhibitor, osteoprotegerin a 401-amino acid glycoprotein, and a member of the TNF superfamily. Rather than develop a pharmaceutically acceptable osteoprotegerin, a fully human monoclonal antibody, denosumab, that binds to the RANKL preventing its binding to RANK is being evaluated for the treatment of osteoporosis. The reported result is inhibition of all stages of osteoclast activity.17 It is important to keep a perspective when administering drugs that interfere with the immune system over long periods of time. RANKL is part of the normal bone remodeling process as well as with pathological bone loss. The key is balance, and this will require long-term studies in patients with post-menopausal...

Reduction of plasma lipid levels

A further inverse relationship between green tea consumption and serum cholesterol and triglyceride levels has been identified in another epidemiological study, also conducted in Japan. While ingestion of ten cups of green tea per day (estimated to contain 360-540 mg of epigallo-catechin gallate) did not lower total plasma cholesterol levels of post-menopausal women, male subjects were found to have decreased serum levels of both total cholesterol and triglycerides.17

Robert T Chatterton Jr and Villian Naeem

17beta-hydroxysteroid dehydrogenases (17beta-HSD), and the impact of estrogen sulfates (ES) on availability of estradiol (E2) to normal and tumor tissues were studied in postmenopausal women. Enzyme activities were measured using tritiated-steroid precursors. Tissues were obtained during surgery for invasive ductal carcinoma.

Proposition 1 VP Facilitates Memory Consolidation and Retrieval

Initial evidence relevant to proposition 1 was obtained from experiments with rats, which found that surgical removal of the intermediate posterior lobes of the pituitary gland led to abnormally rapid rates of extinction of a learned shuttlebox shock avoidance response (De Wied, 1965). The facilitated extinction could not be adequately accounted for by the associated disturbance in water metabolism, and it was corrected by replacement therapy with pitressin as well as purified LVP. Moreover, the normalization of extinction induced by posterior pituitary hormone replacement therapy was not mediated by a VP-induced release of ACTH (De Wied, 1965). An investigation of the effects of ACTH-like peptides and VP on intact rats showed that both delayed extinction on active avoidance tasks, but unlike ACTH, which needed to be present in the body for full effectiveness, VP prolonged extinction for weeks after termination of treatment (De Wied, 1971 De Wied and Bohus, 1966). Clearly, the...

Pathogenesis Behind These Associations

The exact mechanism(s) behind the association between obesity and some cancers is unknown. Obesity itself develops via complex mechanisms involving interactions between heredity and lifestyle changes that include nutritional and exercise considerations. Even the location of the fat deposits may provide clues as to the pathogenesis, as described below.38 The general thought is that augmented fat deposits lead to hormonal imbalances. For example, high levels of estrogens contribute to the proclivity toward cancer. The increased risk of breast cancer after menopause in obese women is believed to be due to increased levels of estrogens.39 Prior to menopause, the ovaries are the primary source of estrogen. After menopause, when ovaries stop producing estrogen, fat tissue becomes the primary source.39 Logic dictates that more fat leads to more circulating estrogens and, hence, an increase in risk. In an international study from three weight centers, blood samples were collected from almost...

Effects of soy consumption on plasma lipids

One trial involving hypercholesterolaemic postmenopausal women showed increased HDL-C and reduced non-HDL-C in subjects receiving 40 g of soy protein per day for six months. The soy supplements contained either 2.39 mg isoflavones g protein, or 1.39 mg isoflavones g protein. Patients in the group taking the low concentration of isoflavones had significantly improved blood lipid profiles before 24 weeks, while the other group did not show improvement until later in the study.32 content soy protein significantly decreased total and LDL-C levels in subjects with the highest baseline LDL-C concentrations.31 A study of premenopausal women found that subjects taking high isoflavone soy protein had lower LDL-C concentrations and lower ratios of total to HDL-C and of LDL-C to HDL-C than those women taking the low isoflavone soy protein.31 These studies support the view that the iso-flavone content of soy protein is responsible for the cholesterol-lowering capacity of soy products.28 In...

Clonidine Hydrochloride U Dose

Menopausal flushing (section Cautions must be withdrawn gradually to avoid severe rebound hypertension Raynaud's syndrome or other occlusive peripheral vascular disease history of depression interactions Appendix 1 (clonidine) Driving Drowsiness may affect performance of skilled tasks (e.g. driving) effects of alcohol may be enhanced Pregnancy may lower fetal heart rate, but risk should be balanced against risk of uncontrolled maternal hypertension avoid intravenous injection Breast-feeding manufacturer advises avoid present in milk

Differential Diagnoses

Like AFP and AO, BMS is a diagnosis of exclusion. Burning pain symptoms in the oral mucosa can be caused by systemic or local conditions, including anemia, vitamin B, folic acid, or iron deficiency, untreated diabetes, hormonal disturbances (menopausal complaints, estrogen deficiency), oral candidiasis, hyposalivation, Sjogren's syndrome, oral lichen planus, or systemic lupus.136,142 Furthermore, burning symptoms can be a side effect to some medications such as angiotensin-converting enzyme (ACE) inhibitors and also allergy to dental materials, dentures, toothpaste, etc., must be considered and excluded before a BMS diagnosis can be given.136,142

Contributing To Oxidative Stress In Ad

A very clear relationship between estrogens and AD has been established in epi-demiological studies showing that postmenopausal women who receive estrogen replacement therapy have a greatly reduced risk for developing AD (136,137), and by experimental studies showing that estrogen is neuroprotective (138). It has been known for many years that estrogen has beneficial effects in many organ systems susceptible to age-related oxidative damage including the cardiovascular system and nervous system. We (28) and others (139,140) have found that estrogens can protect neurons against various oxidative, metabolic, and excitotoxic insults. The data suggest that the neuroprotective action of estrogen is the direct result of its ability to suppress membrane lipid peroxidation (28). Estrogen can protect PC12 cells expressing mutant presenilin-1 against apoptosis induced by Ap and trophic factor withdrawal by a mechanism involving suppression of oxi-dative stress and preserved mitochondrial...

Nongenetic Risk Factors For Alzheimers Disease

Epidemiological studies have suggested that female gender is an independent risk factor for AD,76 even allowing for the increased proportion of women in the older, at-risk population, which is caused by their relative longevity, with a female male prevalence ratio in DAT of 2 1.76 In our study we also observed a higher prevalence of dementia among females, with a female male prevalence ratio in DAT of 1.7 1 (Table 35.6). Possible explanations for the higher prevalence of DAT among women could include unrecognized environmental influences, hormonal effects such as late effects of the menopause, or the use of estrogens by

Therapeutic Uses Of Estrogens

Another major use of estrogens is in HRT for postmenopausal women. For this use, a progestin is often included to oppose the effects of estrogens on endometrial tissue. HRT is covered in more depth later in the chapter. Treatment of Advanced, Inoperable Breast Cancer in Men and Postmenopausal Women and of Advanced, Inoperable Prostate Cancer in Men. Estrogens are used to treat inoperable breast cancer in men and in postmenopausal women, but estrogen therapy can actually stimulate existing breast cancers in premenopausal women. The selective ER modulator tamoxifen is reported to have fewer side effects hence, it is usually preferred. Estrogens have also been used to treat inoperable prostate cancer, but GnRH analogs are now generally preferred because of fewer unwanted side effects. Estrogens and Cancer. Many years of study have firmly established an association between estrogen use and increased risk of breast cancer. The risk is associated, however, with...


Several epidemiological studies have found significant inverse relationships between serum dehydroepiandrosterone sulfate (DHEAS) and cardiovascular morbidity and mortality of men, suggesting that dehydroepiandrosterone (DHEA) is a risk factor for CHD. However, DHEAS level was not linked to cardiovascular risk in postmenopausal women, and DHEA supplementation in women caused decreased HDLC levels.138 Another study found that plasma levels of DHEAS were decreased in patients with congestive heart failure in proportion to its severity, and that oxidative stress was associated with decreased levels of DHEAS.139

Division of Bone and Mineral Diseases Washington University School of Medicine St Louis Missouri

Estrogen is metabolized predominantly via two competing pathways, the 2-hydroxyl (nonestrogenic) and the 16a-hydroxyl (estrogenic) pathways. Studies have indicated that these pathways are important determinants of bone mineral density (BMD) in postmenopausal women. Women with predominant metabolism through the 2-hydroxyl pathway have accelerated postmenopausal bone loss and lower BMD compared to those with predominant 16a-hydroxylation who are protected from bone loss. Increased 2-hydroxylation has been observed in women with a positive family history of osteoporosis suggesting that the increased risk of osteoporosis in those with family history may, in part, be related to inherited differences in estrogen metabolism. Polymorphisms in the cytochrome P450 (CYP450) enzymes that metabolize estrogen are believed to result in alteration in the activity of these enzymes leading to differences in estrogen hydroxylation. It is the resulting estrogen tone'' generated from the variable...

Etiology Of Breast Cancer

With colon cancer and increasingly lung cancer, breast cancer constitutes the trias of major cancers in females in Western industrialized countries. In these countries, the life-time risk of breast cancer is around 10 for women, and about 30 of them turn out to be lethal. Most breast cancers become apparent in women after their menopause, but a significant fraction is diagnosed earlier. In Western countries, the mean age at menopause is now 50 yrs, and menopause takes place in almost all women between 45 and 55. In females aged 40-60 years, breast cancer is the most frequent lethal cancer. In most countries, its incidence is rising, although the increase in mortality has been checked. There are several explanations for this phenomenon, invoking earlier detection and better treatment ( 20.4). In any case, it is generally agreed that certain aspects of the Western life style favor the development of breast cancer. There is much less agreement on which aspects these are (Table 18.1)....

Recurrent infectious cystitis

Women frequently produce clean catch'' urine specimens that are still contaminated with vaginal secretions, as evidenced by squamous epithelial cells. Catheterized specimens are therefore recommended if repeated bouts of infectious symptoms occur. In cases of recurrent infection, repeat culture and test of cure cultures will aid in diagnosis and management. Further history should be elicited to determine the etiology if associated with intercourse, voiding following intercourse and prophylactic antibiotics may be used after coitus. Recurrent infections in peri- and postmenopausal women may benefit from vaginal estrogen cream by altering the vaginal pH and modifying the vaginal flora.102 Chlamy-dial infection is responsible for approximately 25 percent of cases of pyuria and urethritis in women with a sterile urine culture.101

Estrogens And Progestins

Estrogens and progestins are steroid hormones with numerous physiological actions. In women, these include developmental effects, control of ovulation, cyclical preparation of the reproductive tract for fertilization and implantation, and metabolic actions. Estrogens also have important actions in males, including effects on bone, spermatogenesis, and behavior. Estrogens and progestins are used in menopausal hormone therapy (MHT) and contraception in women. Estrogen- and progesterone-receptor antagonists also are available. Antiestrogens are employed in treating hormone-responsive breast cancer and infertility. The main use of antiprogestins has been for medical abortion. Selective estrogen receptor modulators (SERMs) with tissue-selective agonist or antagonist activities are increasingly available.

Concern About Carcinogenic Actions

The use of unopposed estrogen in postmenopausal women increases the risk of endometrial carcinoma by 5-15-fold, an increase that can be prevented if a progestin is coadministered with the estrogen. Randomized, clinical trials of estrogen-progestin and estrogen-only use in post-menopausal women have established a small but significant increase in the risk of breast cancer, apparently due to the medroxyprogesterone. In women without a uterus who received estrogen alone, the relative risk of breast cancer was insignificantly decreased. Thus, the data suggest that the progestin component in hormone-replacement therapy plays a major role in this increased risk of breast cancer. Importantly, the excess risk of breast cancer associated with menopausal hormone use apparently abates within 5 years after discontinuing therapy.

Metabolic And Cardiovascular Effects

Observational studies, clinical trials using surrogate markers of cardiovascular disease, and animal studies suggested that estrogen therapy in postmenopausal women would reduce the risk of cardiovascular disease. In randomized clinical trials, however, conjugated equine estrogens alone or in combination with medroxyprogesterone acetate (MPA) did not protect against coronary heart disease (CHD). It is unclear whether these results (single dose relatively older population) apply to other preparations, doses, and patient populations (e.g., women closer to age 50 who typically initiate hormone therapy for relief of vasomotor symptoms). Clearly, oral estrogens significantly increase the risk of thromboembolic disease in healthy women and in women with preexisting cardiovascular disease.

Other Potential Untoward Effects

The two major uses of estrogens are as components of combination oral contraceptives (see below) and for MHT. Historically, conjugated estrogens have been the most common agents for postmenopausal use (typically 0.625 mg day). In contrast, most combination oral contraceptives in current use employ 20-35 ,ug day of ethinyl estradiol. The effective dose of estrogen used for MHT is less than that in oral contraceptives when one considers potency. The doses of estrogens employed in both settings have decreased substantially in recent years and untoward effects have a lower incidence and severity than those reported in older studies. menopausal hormone therapy Established benefits of estrogen therapy in postmenopausal women include amelioration of vasomotor symptoms and the prevention of bone fractures and urogenital atrophy. The decline in ovarian function at menopause is associated with vasomotor symptoms, typically hot flashes. Treatment of vasomotor symptoms with estrogen is specific...

Pathways and Products of Estrogen Metabolism

Since ovarian activity is minimal after menopause, most circulating estrogen in postmenopausal women is derived just as in men from the aromatization of androstenedione to E1, which can be reversibly oxidized to E2. Although other relatively minor oxidative mechanisms exist 13 , the major metabolic pathway of E1 is irreversible hydroxylation at either the C-16a (active) or the C-2 (inactive) position 13, 14 (Fig. 1). The products of these two competitive

Antioxidants In Clinical

Although most of the previously mentioned compounds that have neuroprotective capacities with respect to oxidative cell death are still being studied at the level of preclinical research, employing cultured nerve cells or brain slice preparations and, therefore, in vitro, a validation of these very promising data is necessary. Future clinical trials will show whether the concept of antioxidants as preventive drugs or as therapy for neurodegenerative disorders, or AD in particular, will hold this promise. A first clinical trial employing vitamin E was recently successfully completed. There, in a multicenter clinical trial on AD patients suffering from a moderately severe impairment, vitamin E effectively slowed down the progression of the disease (90). Of course, it is still open as to whether the vitamin E effect is due to its antioxidant and neuroprotective capacity or due to other modu-latory functions of this compound. Nevertheless, this first success raises high hopes with respect...

Factors Influencing Estrogen Hydroxylation

May add to the already highly estrogenic state generated by increased aromatization of adrenal androgens in the adipocytes and the decreased SHBG production in obese women. The resulting hyperestrogenic environment is one of the mechanisms thought to be responsible for why obese women are at an increased risk for breast cancer but protected from osteoporosis 62, 63 . Increased physical activity may also push estrogen metabolism toward the inactive pathway and may account for the lower risk for breast cancer reported in women who exercise regularly 64, 65 . Even calcium intake may modulate estrogen metabolism. In a study of 175 post-menopausal women, we found that increasing calcium intake was associated with proportionate increases in the absolute levels of most urinary metabolites (with the exception of urinary E3) and total metabolites 66 . Moreover, dividing the average daily calcium intake into quartiles showed that levels of metabolites increase with increasing quartiles of...

Local Anesthetics

To painful site with total of 12 injection sites over four weeksa Candida - fluconazole 150 mg once a week for six weeks then once a month for six months Allergens - avoid agent (these patients should also avoid local creams and suppositories containing propylene glycol), hydroxyzine or other antihistamine, hydrocortisone 1 percent cream b.i.d., 5 percent aspirin cream q.i.d. Atrophy - topical estrogen vaginal cream, oral hormone replacement therapy Diet modification Low-oxalate diet with calcium citrate 400 mg p.o. t.i.d.

Biological Activity of Isoprostanes

Cultured aortic smooth muscle cells (Fukunaga et al., 1993a) and porcine and bovine, but not ovine, coronary arteries, with a potency twice that of PGF2a (Kromer and Tippins, 1996). 8-iso-PGF2a has also been shown to stimulate constriction of non-pregnant pre-menopausal human myometrial tissue in vitro (Crankshaw, 1995). 8-iso-PGF2a reduced coronary blood flow by 50 when administered to isolated, perfused guinea pig hearts (Mobert et al., 1997), and induced platelet shape change but not platelet aggregation (Pratico et al., 1995).

Role of Pharmacotherapy

Estrogen replacement therapy (ERT) may positively affect sexual function in a number of ways. Estrogens rapidly restore the superficial cell layer of the vaginal epithelium, reestablish elasticity, restore the balance in vaginal pH, improve mood, and increase blood flow to enhance lubrication. Short-term studies of estrogen replacement therapy have confirmed a benefit in some postmenopausal women with sexual dysfunction. However, not all studies have demonstrated positive results, possibly because women most likely to respond are those with symptoms of hypoestrogenism. Any short-term positive effect of oral estrogen may diminish in long-term use because of increasing sex hormone binding globulin (SHBG) levels, which lead to reduced estrogen and androgen bioavail-ability, and consequent decreased desire and activity. The increase in SHBG appears to be less significant in women who use non-oral delivery system for ERT. Vaginal estrogen is highly effective for treating genitourinary...

The Impact of Antipsychotics on Prolactin Elevation

Svestka et al. 26 reported one of the few studies with atypical antipsychotics where PRL was the primary outcome measure. Amisulpride and risperidone PRL levels increased significantly in 100 of female patients as early as the first week of treatment, whereas with quetiapine and zotepine, PRL levels were reduced as early as the first week after treatment. In the same study, olanzapine was associated with mild transient PRL elevation. In this study, PRL elevation did not correlate with age, menopausal status, efficacy of the antipsychotic, daily dose, serum lipids or blood glucose levels.

The intracellular ClC6 and ClC7 proteins

Bone degradation is carried out by a specialized osteoclast plasma membrane domain, the ruffled border, through acidification of the resorption lacuna. In fact, the ruffled border is formed by the exocytotic insertion of vesicles of late endosomal lysosomal origin, containing the H+-ATPase. ClC-7 colocalizes with the proton pump in this membrane and was suggested to function as a shunt for the efficient acidification (Jentsch et al. 2005a). This hypothesis is in agreement with the finding that ClC-7 knockout osteoclasts still attach to ivory but fail to acidify the resorption lacuna and are unable to degrade the bone surrogate (Kornak et al. 2001). Moreover, polymorphisms in the gene coding for ClC-7 have been associated with alterations in bone mineral density and bone resorption markers in post-menopausal women and have been found to modulate the phenotypes of patients affected by autosomal dominant osteopetrosis type II (Kornak et al. 2006).

Lipidregulating drugs

Individuals at high risk include those who already have atherosclerotic disease, those with diabetes mellitus aged over 40 years, and those with familial hyper-cholesterolaemia. The risk also increases with age those over 75 years are at particularly high risk, especially if they smoke or have hypertension. Preventative measures are also required for other individuals who may be at high risk of developing atherosclerotic cardiovascular disease those with a 10-year risk of cardiovascular disease1 of 20 or more stand to benefit most from drug treatment. The risk is assessed on the basis of lipid concentration as well as smoking status, blood pressure, gender, and age other risk factors, such as premature menopause, ethnicity, obesity, triglyceride concentration, chronic kidney disease, impaired glucose tolerance, and a family history of premature cardiovascular disease, should also be taken into account when assessing risk in individual patients.

Prospective Cohort Studies

In general, prospective cohort studies have not observed dietary or supplemental vitamin E intake to be significantly associated with gastric cancer risk.137 162164 166 Despite the fact that numerous case-control studies have found increased p-carotene intake from fruits and vegetables to be inversely associated with gastric cancer risk,96168 only one out of four prospective studies found a significant inverse association between p-carotene intake and gastric cancer risk.137 162164 164 In that study of 34,691 postmenopausal women, those whose intake of dietary a-carotene plus p-carotene was in the highest tertile had a risk of gastric cancer 70 lower than those whose intake was in the lowest tertile.164 However, only 26 cases of gastric cancer were identified during the 7-year follow-up period. Although the evidence for a protective effect of fruit and vegetable intake against gastric cancer is strong, the evidence that a-tocopherol or p-carotene play a role in that protective effect...

Brand Differentiation

During the past few years we have seen the traditional vitamin supplement companies offer customized products for men, women, smokers, joggers, osteoporosis, menopause and children. Look for the food industry to follow suit. The nutraceutical functional foods market will mature offering foods and beverages not only for improved lifestyle and performance, but also for those with risk factors for the major diseases and those afflicted with chronic conditions.

Overall Conclusions And Hypotheses

Finally, studies on steroid feedback can increase significantly our understanding of wider brain function. Thus, for example, E2 in its positive feedback mode stimulates a massive increase in the 5-HT2A receptor mRNA in the dorsal raphe nucleus and the density of 5-HT2A receptors in the cerebral cortex and nucleus accumbens. Estradiol-17p also induces a substantial increase in the amount of serotonin transporter mRNA in the dorsal raphe nucleus with a concomitant increase in the density of serotonin transporter sites in brain regions concerned with emotion and behavior. These findings may explain the powerful effects of E2 on mood and mental state the precipitous fall in plasma E2 concentrations has been implicated in the premenstrual syndrome, post-partum psychoses, and menopausal depression, and E2 has been postulated to delay the onset of schizophrenia in women.

Anticancer activity

Breast cancer is the leading cause of cancer-related death among females worldwide (Geyer et al., 2006 Parkin, 2001). Globally, more than 1.1 million females are diagnosed each year, representing around 10 of all newly diagnosed cancer cases (Anderson et al., 2006). The mortality rate for premenopausal breast cancer is almost four times greater in the Western world, compared with East Asia nation. In breast cancer etiology, genetics are thought to play a smaller role compared to environmental factors such as food diets. One important difference in the diet of East Asian populations compared to Western populations is higher amount of fish and marine algae consumption. As mentioned earlier, ancient tradition of marine algae consumption has made a large number of epidemio-logical researches showing the health benefit in females linked to marine algae consumption. Estrogen-dependent cancers such as breast, endometrial, and ovarian cancer are among the leading causes of morbidity and...

Beneficial and Adverse Effects of Dietary Estrogens on the Human Endocrine System Clinical and Epidemiological Data

Dietary estrogens, also known as phytoestrogens, represent a family of plant compounds which are of biological interest because they exhibit both in vivo and in vitro weak estrogenic and anti-estrogenic properties. Phytoestrogens appear to exert their physiological effects through a variety of possible mechanisms, such as their ability to bind to estrogen receptors and their actions on tyrosine kinases and growth factors. Phytoestrogens can be classified into three main categories consisting of isoflavones, lignans, and coumestans. A variety of commonly consumed foods contains appreciable amounts of these plant compounds which have been identified in various human body fluids, such as plasma, urine, bile, saliva, feces, breast milk, prostatic fluid and semen. Accumulating evidence from both clinical and epidemiologi-cal studies has suggested that dietary estrogens may potentially affect the human endocrine system. The existing evidence reviewed here will identify the current research...

Ginsengasian Panax ginseng Ginsana G115 Korean red ginseng

Promoted to improve vitality and well-being 200 mg PO daily. Ginsana 2 caps PO daily or 1 cap PO bid. Ginsana Sport 1 cap PO daily. Preliminary evidence of efficacy for erectile dysfunction. Efficacy unclear for improving physical or psychomotor performance, diabetes, herpes simplex infections, cognitive or immune function. American College of Obstetrics and Gynecologists and North American Menopause Society recommend against use for postmenopausal hot flashes. Not by prescription. 2- -

Epidemiology of chronic pelvic and vulvalperineal pain in women

Population data on pain prevalence in women are available. A US-based telephone survey interviewed respondents aged 18-50 years 21 17,927 households were contacted, 5325 women agreed to participate, and of these 925 reported pelvic pain of at least 6 months' duration, including pain within the past 3 months. Having excluded those pregnant or post-menopausal and those with only cycle-related pain, 773 5263 (14.7 ) were identified as suffering from chronic pelvic pain. A British population survey used a postal sample of 2016 women randomly selected from the Oxfordshire Health Authority register of 141,400 women aged 18-49 years 22 . Chronic pelvic pain was defined as recurrent pain of at least

Side Effects Of Hexaethyltetraphosphate

Hormone(s) (continued) pituitary, 891-894, 892t placental, 895 plasmakinins, 905-906 rDNA-derived, 908t, 910 recombinant, 134-136 somatostatin, 890, 894-895 thyroglobulin, 906 thyroid, 663 thyrotropin, 894 Hormone-related disorders, nonsteroidal therapies for. See Nonsteroidal therapies for hormone-related disorders Hormone replacement therapy (HRT) with androgens, 848-849 combined estrogen progestin, 846-847, 8461 estrogens in, 831 Hormone therapy, for bone disease, 708-710, 709 hPL. See Human placental lactogen HPMPC. See Cidofovir hPTH. See Teriparatide injection HPV. See Human papillomavirus vaccine HRT. See Hormone replacement therapy 5-HT1A antagonists, 515

Role of Estrogen Hydroxylation in Bone Density and Osteoporosis

The importance of estrogen metabolism in the pathogenesis of hormone-related diseases has come primarily from studies on breast cancer. For example, a lower circulating 2OHE1 16aOHE1 ratio is associated with an increased risk of breast cancer 67-70 , whereas high serum 16aOHE1 is a strong predictor of breast cancer risk 67 . In vitro studies showed that breast tissues obtained from women with breast cancer have increased 16-hydroxyl-ation. Furthermore, the addition of E2 to MCF-7 cell lines upregulates 16-hydroxylation with 2-hydroxylation unchanged. The ability of estrogen hydroxylation to alter hormonal status even among women in the reproductive age is likewise suggested by observation of frequent menstrual irregularities in young women with high 2-hydroxylated estrogens 71, 72 . What's more, estrogen metabolism may also be an important regulator of male hormonal status as well since high levels of 16aOHE1 and low 2OHE1 16aOHE1 ratio were associated with an increased risk of...

Aromatase Inhibitor Products

Anastrozole, was the first specific aromatase inhibitor approved in the United States. It is indicated for first-line treatment of post-menopausal women with advanced or metastatic breast cancer, for second-line treatment of postmenopausal patients with advanced breast cancer who have had disease progression following tamoxifen therapy, and for adjuvant treatment

Common Side Effects Associated with Antipsychotic Induced Hyperprolactinaemia

Smith et al. 22 followed up patients who had been stabilised on typical antipsychotics for at least 2 years measuring both PRL levels as well as gonadal hormones. Although the average dose of antipsychotics in chlorpromazine equivalents was only 384 mg, 75 of the females had PRL levels greater than the upper limit of normal, 36 had amenorrhoea, 32 oligomenorrhoea and 36 had apparent normal menstruation however, only 37 of these women were actually ovulating. Furthermore, this study showed that HPRL in women was correlated with the degree of suppression of the HPG axis. Howes et al. 28 found similarly high levels of intermittent anovulatory cycles (92 ) in a population of premenopausal females with a median exposure to antipsychotic of 3.3 years. Hankinson et al. 48 investigated the risk of breast cancer associated with high PRL by doing a series of epidemiological studies now well known as the US Nurse Health Study. This study cohort was establishes in 1976 with 121,700 US female...

Selective Estrogen Receptor Downregulators

FULVESTRANT Fulvestrant (faslodex) is the first FDA-approved agent in the new class of ER downregulators. Fulvestrant is approved for postmenopausal women with ER-positive metasta-tic breast cancer that has progressed despite antiestrogen therapy. Fulvestrant binds to the ER with an affinity 100 times that of tamoxifen its long, bulky side-chain at the 7 a position sterically hinders receptor dimerization, leading to increased ER turnover and disruption of nuclear localization. Unlike tamoxifen, which stabilizes or even increases ER expression, fulvestrant reduces the number of ER molecules in cells.

Dysesthetic Vulvodynia

Generally considered a diagnosis of exclusion, it presents commonly in perimenopausal and postmenopausal women as nonspecific superficial vulvar burning or perineal discomfort with intermittent, deep, aching pain. Patients deny entry dyspareunia. Physical examination is normal, with no tenderness on palpation. Pudendal nerve tenderness, hyperesthesiae, or hypoesthesiae in a saddle distribution extending from the mons pubis to the upper inner thighs and posteriorly across ischial tuberosities may be noted on examination.187 The etiology may be secondary to an aberration in cutaneous nerve perception (pudendal nerve distribution S2-S4) at either the central or peripheral level. Tricyclic antidepressants starting at 10 mg q.d. to 40-60 mg q.d. may be of benefit in this condition.188 Topical 5 percent lidocaine may provide additional benefit. Other reported treatments, although of unproven effectiveness, include acupuncture, pelvic floor muscle, physical therapy, TENS, regional nerve...

O Diseases Of Bone Tissue Utilizing Approved Drug Therapies

Bisphosphonate Binding

Osteoporosis has been considered a disease of aging, but inflammation may be an important variable. Calcium flux favors bone mineralization through adolescence. Bone resorption and deposition are in balance in adults and become negative beginning in the late 50s. Loss of calcium from bone increases relative to calcium deposition onto bone increases with menopause. The importance of estrogen is shown by it acting directly on osteoblasts and possibly inhibiting osteo-clasts. The loss of estrogen production results in a significant alteration of the osteoblast-osteoclast ratio because of increased osteoclastogenesis and decreased osteoclast apopto-sis. The role of estrogen on osteoblast function has led to the development of selective estrogen receptor modifiers (SERM) Associated with menopause and the loss of estrogen is an increase in the production of proinflammatory cytokines including interleukin-1 (IL-1), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6). Paralleling this...

Osteoporosis Prevention And Treatment104106

Epiandrosterone Pathway

Osteoporosis is an enormous public health problem, responsible for approximately 1.5 million fractures in the United States each year. Because of the prevalence of osteoporosis, especially in older women, the prevention and treatment of this condition have received much attention. Prior to menopause, a good diet and exercise are essential for young women, to decrease the risk of osteoporosis later in life. After menopause, supplemental estrogens can have a positive effect relative to osteoporosis. Estrogens mainly act by decreasing bone resorption, so estrogens are better at preventing bone loss than restoring bone mass. Estrogens taken after menopause (often with a supplemental progestin) have been unequivocally shown to greatly decrease the incidence and severity of osteoporosis, especially when combined with good nutrition and exercise. The long-term use of estrogens plus a progestin for preventing osteoporosis, however, should be carefully evaluated in light of the WHI studies...

Agents Affecting Mineral Ion Homeostasis And Bone Turnover

Calcium absorption and excretion In the U.S., -75 of dietary calcium is obtained from milk and dairy products. The recommended adequate daily intake value for calcium is 1300 mg in adolescents, 1000 mg in adults, and 1250-1500 mg in postmenopausal women typical intake is only -50 of these values.

Serm And Antiestrogen Products

Tamoxifen, A-dimethylethanamine (Nolvadex), is a triphenylethylene SERM used to treat early and advanced breast carcinoma in postmenopausal women. Tamoxifen is used as adjuvant treatment for breast cancer in women following mastectomy and breast irradiation. It reduces the occurrence of contralateral breast cancer in patients receiving adjuvant tamoxifen therapy. It is also effective in the treatment of metastatic breast cancer in both women and men. In premenopausal women with metastatic breast cancer, tamoxifen is an alternative to oophorectomy or ovarian irradiation. Tamoxifen can be used preventa-tively to reduce the incidence of breast cancer in women at high risk. Antiestrogenic and estrogenic side effects can include hot flashes, nausea, vomiting, platelet reduction, and (in patients with bone metastases) hypercalcemia. Like all triphenylethylene derivatives, it should be protected from light. Toremifene Citrate, USP. Toremifene, N-di-methylethanamine...

Compounds Acting on Glucose Absorption

Insufficient data are available on the long-term safety of high-fibre supplements. People at risk of deficiencies, such as postmenopausal women, the elderly, or growing children, may require supplements of calcium and trace minerals. People with upper gastrointestinal dysfunction risk bezoar formation and should be cautioned against a diet high in fibre of the leafy vegetable type. Careful attention must be paid to insulin doses because hypoglycaemia can appear if there is a radical change in fibre intake without appropriate reduction in insulin dose. Care must be exercised in the use of novel fibres, including wood celluloses, because little is known of their safety and efficacy.

Implications of Estrogens in Human Breast Carcinogenesis

Although 67 of breast cancers are manifested during the postmenopausal period, a vast majority, 95 , are initially hormone-dependent 14 . This indicates that estrogens play a crucial role in their development and evolution. It has been established that in situ metabolism of estrogens through aromatase-mediated pathway is correlated with the risk of developing breast cancer 66-69 . A recent finding that expression of estrone sulfatase is inversely correlated with re The receptor-mediated activity of estrogen is generally related to induction of expression of the genes involved in the control of cell cycle progression and growth of human breast epithelium 144 . The biological response to estrogen depends upon the local concentrations of the active hormone and its receptors. The level of ER expression is higher in breast cancer patients than in control subjects and is related to breast cancer risk in postmenopausal women 145 . It has been suggested that overexpression of ER in normal...

Gonadotropin Evidence Based Hypothesis for AD High Gonadotropin vs Low Estrogen

Dependent on secondary hormonal changes in gonadotropins such as luteinizing hormone (LH). In support of this hypothesis, the levels of gonadotropins including LH are highest during perimenopause and early menopause 72 , when HRT has been observed to be most successful in preventing dementia 73, 74 . The balance of this feedback loop can shift during menopause (and andro-pause'') and result in an increase in the production of gonadotropins such as LH and FSH. In postmenopausal women, changes mediated by decreased action of estrogen 76 result in large increases in the concentration of serum LH and FSH 77 . Likewise, men (but to a lesser degree than women) also experience an increase in these hormones as their reproductive function declines during andropause 78 . Surprisingly, despite these well-documented hormonal changes, the effects of loss of negative feedback and consequent increased circulating gonadotropins on the aging brain remain largely unexplored. This may be because these...

Recombinant therapeutic hormones

Post-menopausal FSH, along with hCG, is utilized medically to treat various reproductive disorders, such as anovulatory infertility. FSH preprations traditionally have been extracted from the urine of post-menopausal women, while hCG is purified from the urine of pregnant women. Urine is hardly an ideal source of any therapeutic agent, rendering attractive production of recombinant forms of gonadotrophins. Gonal F, for example, is a recombinant FSH preparation produced in Chinese Hamster Ovary cells which gained marketing approval in the EU in 1995 and the USA in 1997.

Selective Estrogen Receptor Modulators And Antiestrogens

Tamoxifen has seen extensive use in treating primary breast cancers that are ER dependent.52,53 For premenopausal women with metastatic disease, tamoxifen is an alternative and adjuvant with oophorectomy, ovarian irradiation, and mastectomy. Tamoxifen use, however, is not problem free. Tamoxifen increases the incidence of endometrial polyps, hy-perplasia and carcinoma, and uterine sarcomas. The risk of endometrial cancer resulting from tamoxifen is, however, much lower than the modest but highly significant reductions in morbidity and mortality of breast cancer. 54 Because

Steroid Hormonal Factors in Populations with Different Risk for Prostate Cancer

Menopausal women with the A2 allele had higher circulating estradiol and progesterone levels than women homozygous for the A1 allele, and circulating levels of DHEA and androstenedione, but not testosterone, were increased in post-menopausal women. Lunn et al. 153 reported frequencies of the A1 A1 and A1 A2 genotype of between 40 and 44 and frequencies of the A2 A2 genotype between 16 and 17 in both African American and European American men, resulting in an A2 allele frequency of 0.36-0.38. In Asians (Taiwanese), however, the frequency of the A1 A1 genotype was 24 , that of the A1 A2 genotype 49 , and that of the A2 A2 genotype 27 , resulting in an A2 allele frequency of 0.52. The frequency differences between the Asians and the American groups were statistically significant, and are possibly related with the low prostate cancer risk in Asian men.

Phytoestrogens And Carcinogenesis

Despite the adverse effects of naturally occurring phytoestrogens, these compounds also exhibit beneficial effects.146 Both epidemiological and experimental studies have shown that the consumption of phytoestrogen-rich diets may reduced the risk of cardiovascular diseases, menopausal disorder, osteoporosis, as well as breast and prostate cancers,146152-15 suggesting that their use may be worthwhile.155 There are two principal categories of phytoestrogens, isoflavones and lignanes. Isoflavones and flavones, represented by genistein, luteolin, and daidzein, are produced by leguminous plants (soybean, alfalfa), while lignanes are found in high concentration in linseed.146 The commonly available lignanes are enterolactone and enterodiol. These phytoestrogens From the results of several independent studies, flavonoids could be considered valuable as anticancer therapeutic agents. With the use of soy phytoestrogens and the avoidance of hormonal replacement therapy (HRT), encouraging results...

Ra Expression in the Normal Breast and Breast Cancer

In the progression to breast cancer, cells increase their level of ERa expression, and ERa levels seen in breast cancer are consistently higher than those seen in normal breast (Panahy et al., 1987 Silvistrini et al., 1979). Increased ERa expression is seen in the earliest stages of ductal hyperplasia, and increases even more with progressing atypia - in cases of atypical ductal hyperplasia and in low to intermediate grade ductal carcinoma in situ (DCIS), most of the ductal epithelium stains ERa-positive (Allred et al., 2001 Shoker et al., 1999b). Another early change observed in the progression to malignancy is the loss of the inverse relationship between ERa expression and cell proliferation, especially as ERa expression becomes more widespread (Shoker et al., 1999a). Atypical ductal hyperplasia (ADH) and low grade CIS demonstrate strong ERa-positivity, with immunohistochemical analysis revealing contiguous ERa-positive cells in a majority of the lesion (Roger et al., 2000 Shoker et...

Antioxidants In Neuroprotection In Vitro

There are numerous links between the female sex hormone estrogen and neurode-generative diseases in general and AD in particular. It is well known that women are twice as likely to develop AD than men (42,43) and that the loss of estrogens during menopause may play a role in an age-associated cognitive decline (44). Increasing the level of estrogens by estrogen replacement therapy may lower the risk of getting AD for postmenopausal women (45,46). Estrogen is a steroidal compound that binds to cognate receptors upon penetration of the cellular membrane, and these activated estrogen receptors comprise transcription factors that translocate into the nucleus. There estrogen receptors bind to estrogen-responsive elements in the promoter regions of certain target genes activating the transcription of these genes. It is known that estrogen affects neurons through this estrogen receptor-dependent hormonal effect by activating the transcription of certain receptors of neurotrophins such as...

Other Possible Benefits

Cardiovascular Disease and Atherosclerosis. Coronary heart disease and other cardiovascular diseases are multifactorial conditions risk factors include raised serum cholesterol, high blood pressure and smoking. The rates of coronary heart disease vary depending on geographical location, sex, age and dietary practice. Thus, the incidence of cardiovascular disease in general is lower in Asian than Western countries. For example, in 1986, age-standardised mortality rates for coronary heart disease for men and women (40-69 years old) in the USA were approximately 300 and 100 per 100000 respectively and, in Japan, 50 and 15 per 100000 respectively.80 Rates are also known to be lower in vegetarians than omnivores. These diseases contribute significantly to mortality. In the UK, for example, coronary heart disease accounts for 30 and 23 of mortality in men and women, respectively. i7 The finding that the incidence of cardiovascular disease is lower for premenopausal women than men of similar...

Negative Feedback In The Hypothalamicpituitarygonadal Axis

For most of the reproductive life, plasma gonadotropin levels are kept within a relatively low range by the negative feedback of gonadal steroids and, in the case of FSH, inhibin (for review see Steinberger and Ward, 1987). Gonadectomy in several species including man is followed by a massive increase in gonadotropin release, and this occurs naturally after menopause in the human female (Fink, 1977). The administration of gonadal steroids suppresses plasma gonadotropin concentrations. Within the bandwidth allowed by the HPG comparator, gonadotropin secretion is pulsatile. In the human female, the frequency (ca. one pulse per 1 to 4 h) and amplitude of the gonadotropin pulses change during the menstrual cycle (Yen et al., 1972). Pulsatile release plays an important signaling role in that it permits frequency, as well as amplitude modulation, and also prevents receptor downregulation.

Clinical Significance Of Estrogen Feedback And The Lhrh Selfpriming Effect

The negative feedback of female sex steroids is best exemplified by the massive increase in plasma gonadotropin concentrations that follows the menopause (Fink, 1977). Androgen negative feedback in man is best illustrated by the testicular feminization syndrome in which the absence or defect in the androgen receptor results in a significant increase in the mean plasma concentrations of LH and the frequency of LH pulses (Boyar et al 1978). The negative feedback action of E2 and progesterone underpins the extensive use of the most widely used chemical contraceptive, the pill . Gregory Pincus, about 40 years ago, established the method of inducing reliable contraception in women by administration of estrogen and progesterone. Several different modes and dosages of administration have been

Treatment For Osteoporosis

Hormone, hormone therapy, and recently developed receptor activator of nuclear factor-kB ligand (RANKL) inhibition. Estrogen agonists antagonists in combination with estrogen for prevention and treatment of osteoporosis have also been studied (Stovall and Pinkerton, 2008). Bazedoxifene for the prevention of postmenopausal osteoporosis (Gennari et al., 2008), parathyroid hormone (Black et al., 2003 Finkelstein et al., 2003 Horwitz etal., 2010 Neer et al., 2001), estrogen therapy (Eskridge et al., 2010 Genant et al., 1997 Lindsay, 1987 Lindsay and Tohme, 1990), hormone therapy (Engel et al., 2011 Pentti et al., 2009), and recently developed RANKL inhibitory (McClung, 2006, 2007) treatment options are currently available for osteoporosis treatment. Among this bisphosphonates are the primary drugs used to both prevent and treat osteoporosis in postmenopausal women. Bisphospho-nates taken orally, once a week or once a month, include alendronate (Fosamax), ibandronate (Boniva), and...

Estrogen and Depression

Because of increased incidence of depression at critical hormonal transition phases such as postpartum and perimenopause, much speculation has taken place about estrogen's role as a precipitant. Recent studies have found increased incidence of depressive symptoms and major depression during the menopause transition (Cohen et al. 2006 Freeman et al. 2006). The initial findings of Freeman et al. (2004) in regard to estrogen were that both high and low estrogen levels were associated with depression. More recently, the data suggest that variability in estrogen levels may drive depression. A model of differential sensitivity to estrogen has been proposed for premenstrual dysphoric disorder (PMDD) and also by Cohen et al. (2006) to explain the findings of increased depression during the menopause transition. Increased FSH, suggesting ovarian aging, and overall low or variable estrogen were also found to be strongly associated with depression (Freeman et al. 2006). And in the Freeman et al....

Functional Foods And Disease Prevention

Though it is a focus of a narrow audience to look for products focusing heart health, products with low saturated fats and cholesterol are admired by the majority of the consumers. In the same arena, o-3 fatty acids are still maintaining its recognition among consumers having identified its effects including protection against cardiovascular disease, various inflammatory and autoimmune conditions, and enhanced cognitive health. In recent years, there was concentration toward products targeting the women population composed of active ingredients capable of fighting against bone-related complications, pregnancy, or menopause-related issues. Wider coverage in research is given for phytoestrogens and phy-tosterols available in this category of products among other phytochemicals. Further, soy protein inclusions are getting highly recognized by women population due to their ability to reduce the risk of heart diseases by lowering blood cholesterol levels, promoting bone health, and easing...

Coronary Heart Disease

Coronary heart disease (CHD) is a multifactorial disease, for which the main established risk factors are raised serum cholesterol, raised blood pressure and smoking. The proportion of both men and women who are hypertensive steadily increases with age. Compared with men, serum cholesterol levels are lower in women up to the age of 50 years. After the menopause, levels of serum cholesterol in women exceed those of men. In women, therefore, the relative importance of CHD as a cause of death steadily increases with age, whereas in men, its importance declines after 55-64 years of age 181 . CHD accounts for 23 of deaths in women in the UK, and 30 of deaths in men, although rates have been falling since the late 1970s. Rates are low in Far East countries, such as Japan, and also declining 181,182 . Postmenopausal estrogen replacement has been shown to decrease lipoprotein (a) Lp(a) 183, 184 . The synthetic anti-estrogen, tamoxifen, has also been shown to beneficially alter serum lipid and...

Potential Adverse Effects of Dietary Estrogens

Despite the hypothesized beneficial effects of phytoestrogens in human cancer, two reports suggest that caution may be necessary at this stage. In one study, 29 women took 60 g soybean (containing 45 mg isoflavones) for 14 days and demonstrated a significant increase in the proliferation rate of breast lobular epithelium 271 . In an earlier study, Petrakis et al. 156 evaluated the influence of the long-term ingestion of commercial soy protein isolate on breast secretory activity. It was hypothesized that the features of nipple aspirate fluid (NAF) of non-Asian women would be altered so as to resemble those previously found in Asian women. Both pre- and post-menopausal white women ingested 38 g of soy protein isolate containing 38 mg of genistein daily. Unfortunately, the findings did not support their hypothesis. Compared to baseline values, a 2- to 6-fold increase in NAF volume ensued during ingestion of soy protein isolate in all premenopausal women. This 6-months pilot study...

Effects of soy consumption on vascular function

One trial found that dietary soy protein supplementation over three months significantly improved distal pulse wave velocity in normo-tensive male and postmenopausal female subjects, following reduction in the extent of vasoconstriction in peripheral resistance vessels. Although the trial showed that soy supplementation improved blood pressure and lipid status, it did not improve vascular function, and produced a decline in endothelial function in male subjects.38 After oestrogen therapy postmenopausal women have improved large artery function, enhanced brachial artery FMD and restoration of normal vasomotion.38,41 Impaired brachial artery FMD is positively associated with coronary artery endothelial dysfunction and with cardiovascular risk factors.38 Dietary soy could improve vascular function, hence reducing CVD risk, through oestrogenic mechanisms.38 Although some studies show beneficial results, others show uncertainty concerning the effects of soy isoflavones on vascular...

Possible Causes for Concern

In adults, a few areas may require further study. For example, there is a report of soya consumption causing an increased incidence of hyperplastic epithelial cells in the nipple aspirate fluid of pre- and postmenopausal women.i2i This could constitute a risk factor for breast cancer. Also, the use in herbal medicine of particular plants emphasises that these species have the potential to cause physiological changes. Consequently, the increasing public interest in the use of herbal medicines could lead to unintended (adverse) effects, particularly as most In a 1996 review, the Committee of Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) estimated the intake of isoflavones from soya-milk to be approximately 4 mg kg day over the first 4 months of life. This is greater than that associated with hormonal effects in premenopausal women, but the COT nonetheless supported the existing Department of Health's advice that

Potential Health Benefits of Dietary Estrogens

Both clinical and epidemiological data suggest that dietary estrogens may have a beneficial effect on the human endocrine system. Breast cancer, prostate cancer, colon cancer, menopausal symptoms, heart disease, and osteoporosis share a common epidemiology in that they are rare in Far Eastern populations eating traditional diets containing soybean products compared with Western populations. However, with Westernization and loss of traditional eating patterns, the pattern of disease incidence is also changing in these countries. Cross-sectional studies have shown higher phytoestrogen levels in the urine and plasma of populations at lower risk of these diseases 28, 91 . This section will focus on the beneficial role which phytoestrogens may play in breast cancer, prostate cancer, colon cancer, endogenous hormones, the menstrual cycle, menopausal symptoms, cardiovascular disease, and osteoporosis.

Pharmacotherapy Of Anxiety

Superior to fluoxetine, and both duloxetine and venlafaxine also may be effective) fibromyalgia peptic ulcer and irritable bowel syndrome hot flashes of menopause chronic fatigue cataplexy tics migraine and sleep apnea. These disorders may have some psychobiological relationship to mood or anxiety disorders.


The effect of oral magnesium supplementation has been studied in osteoporosis. In fact, significant reductions in serum and bone magnesium have been described in several studies on post-menopausal women with osteoporosis. Recently, dietary magnesium has been observed to be positively associated with bone mineral density (BMD) in a community-based study in elderly men and women.89 Despite this, epidemiological studies relating magnesium intake


Women with bipolar disorder (BD) may have unique risk factors for insulin resistance (IR). Specific periods in a woman's reproductive timeline, specifically pregnancy and after the menopause, may represent times of increased IR. Moreover, women with BD demonstrate higher rates of obesity compared to men with BD, suggesting a sex-specific vulnerability to metabolic sequelae in BD. Additional contributors to metabolic sequelae, such as psychotropic medication, dysregulation of the hypotha-lamic-pituitary-adrenal axis, and genetic influences common in BD, may also manifest differently between the sexes. Several studies have suggested that women with BD may have more menstrual cycle irregularities than women in the general population. It has been hypothesized that such irregularities may be due to endocrinological disorders, such as polycystic ovarian syndrome or to hypo-thalamic-pituitary-adrenal axis dysfunction, both of which are also be associated with IR. Women treated with valproate...

Therapeutic Uses

The major therapeutic use of clonidine (catapres, others) is in the treatment of hypertension (see Chapter 32). Clonidine also has apparent efficacy in the off-label treatment of a range of other disorders reducing diarrhea in some diabetic patients with autonomic neuropathy treating and preparing addicted subjects for withdrawal (see Chapter 23) ameliorating some of the adverse sympathetic nervous activity associated with withdrawal, and decreasing craving for the drug. Transdermal administration of clonidine (catapres-tts) may be useful in reducing the incidence of menopausal hot flashes.


Kushi, L.H., Folsom, A.R., Prineas, R.J., Mink, P.J., Wu, Y., and Bostick, R.M. (1996) Dietary Antioxidant Vitamins and Death from Coronary Heart Disease in Postmenopausal Women, N. Engl. J. Med. 334, 1156-1162. 26. Yochum, L.A., Folsom, A.R., and Kushi, L.H. (2000) Intake of Antioxidant Vitamins and Risk of Death from Stroke in Postmenopausal Women, Am. J. Clin. Nutr. 72, 476-483.


However, epidemiological data are conflicting in finding a relationship between calcium intake and bone health, although racial and other confounding factors may complicate the picture. A weak but positive relation between calcium intake and bone mass was found in a study conducted in the USA.15 There is strong evidence for the importance of an adequate calcium intake in the prevention of bone loss associated with aging and or menopause, in the reduction of risk fracture16 and of a close positive relation between calcium intake and bone mass.17 Absorption efficiency for calcium at the recommended dietary allowance can vary from 10 to almost 60 in postmenopausal women of the same age18 and there is convincing evidence of a decreased absorption efficiency for calcium with age.19 Calcium insufficiency due to low calcium intake and reduced absorption can translate into an accelerated rate of age-related bone loss in older individuals. Among the homebound elderly and persons residing in...


Environmental triggers for RA have not been clarified, despite extensive searches for infectious organisms. Many patients blame their RA on a stressful event though this is unlikely to be causal, there is increasing evidence that stress may modify the immune system and be associated with exacerbations of RA. Hormones clearly play a role in RA. Before the menopause, there is an excess of females affected but this gender difference disappears after the menopause. Pregnancy usually results in amelioration of symptoms though a postpartum flare is often seen. Finally, the contraceptive pill may be weakly protective against RA.

Meal Composition

It has been suggested that dietary fat is a prime contributor to the development of obesity 46 . For any given body mass index, mortality is higher if fat is distributed centrally (visceral adiposity) compared with a more generalized pattern of distribution 52 . This has renewed interest in the factors that control adipose tissue distribution in addition to adipose tissue mass and function 53 . Although men tend to progressively increase abdominal fat deposits with increasing total adiposity at each age, a tendency to develop different obesity phenotypes throughout the lifespan occurs more clearly in women, particularly after the menopausal age 54 . The response of the HPA axis to a high-lipid protein meal or high-CHO meal in obese women depends on their pattern of body fat distribution and that the activation of

Ongoing trials

The Harvard Women's Health Study (WHS) is a chemoprevention trial designed to evaluate the risks and benefits of low-dose aspirin, p-carotene and vitamin E in the primary prevention of cardiovascular disease and cancer in healthy postmenopausal women in the United States (Buring and Hennekens, 1993a,b). Begun in 1992, the WHS has enrolled approximately 40,000 female nurses, ages 45 and older, without a history of either disease. Participants are randomized to treatment or placebo groups for 2 years


The estrogens are synthesized by the action of the enzyme aromatase on androstenedione or testosterone (Fig. 25.5). They are normally produced in relatively large quantities in the ovaries and the placenta, in lower amounts in the adrenal glands, and in trace quantities in the testes. In post-menopausal women, most estrogens are synthesized in adipose tissue and other nonovarian sites. About 50 to 350 g d of estradiol are produced by the ovaries (especially the corpus luteum) during the menstrual cycle. During the first months of pregnancy, the corpus luteum produces larger amounts of estradiol and other estrogens the placenta produces most of the circulating hormone in late pregnancy. During pregnancy, the estrogen blood levels are up to 1,000 times higher than during the menstrual cycle.

Syndrome X

Syndrome X is the combination of anginal chest pain, abnormal exercise testing, and normal coronaries on angiography. It appears to be more prevalent in women,66 who tend to complain of symptoms after the menopause. Despite presenting angina on exertion and nearly 50 percent cases also at rest, only 40 percent benefit from sublingual nitrates during an episode of pain.66 However, in a follow up of up to seven years, no acute coronary events or deterioration of cardiac function were found in a study that included 99 patients.66

Breast Cancer

Carcinoma of the breast is a major lethal cancer in females in the Western world, on a par with lung and colon cancer. Most cases occur in postmenopausal women, but a significant number of younger women are afflicted, often in families with a hereditary predisposition. Known risk factors include the length of the life-time exposure to estrogens, ionizing radiation, cigarette smoking, and a high-fat diet. Like normal breast tissue, many breast cancers remain dependent on estrogens and gestagens for growth and survival and therefore respond to hormone depletion. Hormone depletion in premenopausal women is achieved by surgical removal of the ovaries. In addition, and generally in postmenopausal women


In the general female population, prevalence is estimated at approximately 10 percent and with infertile women it is 15-25 percent, and 28-74 percent of women undergoing diagnostic laparoscopy for CPP.27,28,29 In the past decade, the incidence has increased, perhaps reflecting delayed childbearing but also the increasing use of laparoscopy and greater awareness of subtle endometriotic lesions.30 Endometriosis may present in any age group (from adolescents to postmenopausal women on hormonal therapy), however most diagnoses are made in women in their thirties or forties.31 Endometriosis has been suggested by


Teriparatide is a recombinant form of parathyroid hormone, which is used for the treatment of osteoporosis in men and postmenopausal women. The N-terminal region possesses 34 amino acids, which are identical to the biologically active region of the 84-amino acid sequence of human parathyroid hormone. It has been shown to act on osteoblasts to stimulate new bone growth and improve bone density.

Natural Cures For Menopause

Natural Cures For Menopause

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

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