Natural Menopause Relief Secrets

Women's Midlife Revolution Summit

The Women's Midlife Revolution Summit is an online event that presents a wonderful opportunity for women to learn, bond and share in the privacy of their homes. The interviews of the day will be online viewable for 24 hours for absolutely FREE, starting at 10:00 am. And every day for eleven days, there will be another set of experts videos releasedfor 24 hours for FREE viewing. This will be 11 days packed with knowledge, experience, inspiration, and wisdom as Arnold interviews 22 female professionals, releasing two new interviews per day over this 11-day period. Female nutritionists, doctors, herbalists, holistic therapists, authors, life coaches, entrepreneurs, hormone experts, and physical trainers have all been gathered to lend credence to the joy of seasoned womanhood. Registration is free. You will be required to fill a registration form. After filling the form you will receive an email to click on a link to confirm your participation. Then 3 days before the event starts, you will receive the Playbook for this event, which you can download.You can join the talks easily on your PC, Tablet, Laptop or Cellphone. It is time to shed light on the myths and lies women are told about aging and let women reclaim their power. More here...

Womens Midlife Revolution Summit Summary


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Implications For Soy As A Complementary Hormone Replacement Therapy

Accumulating evidence suggests that significant interactions occur between plasma estradiol and soy isoflavones that may decrease risk factors for cardiovascular disease. In 1997, Wagner and coworkers reported on a study with cynomolgus macaque females with preexisting diet-induced coronary artery atherosclerosis.67 Both soy and estradiol reduced aortic cholesterol ester content but more importantly, as shown in Figure 13.13, the soy and estradiol combination resulted in a greater reduction in cholesterol ester concentration than with either treatment alone (soy protein X estradiol interaction, p 0.02). Similarly, as mentioned earlier in the chapter, a significant (p < 0.05) interactive effect of soy and estradiol on vascular reactivity of postmenopausal monkeys has also been reported.47 Important interactions have also been described between changing plasma estra-diol concentrations of premenopausal women and the extent to which relatively high doses of soy isoflavones (129 mg day)...

Postmenopausal Women With Advanced Breast Cancer

Implementations of aromatase inhibitors either as monotherapy or in sequence with tamoxifen for adjuvant therapy has challenged our algorithm for endocrine treatment of postmenopausal women in the metastatic setting. Previously, for patients being treated with tamoxifen (or not having adjuvant endocrine therapy) first-line treatment in metastatic disease should mean treatment with one of the new third-generation aromatase inhibitors, anastrozole, letrozole, or exemestane. Alternatively, patients

Premenopausal Women With Metastatic Breast Cancer

For premenopausal patients, we are left with three potential options for first-line therapy tamoxifen monotherapy, treatment with an LH-RH analogue, or the two treatment options administered in concert. Considering further treatment for premenopausal women, a natural choice should be treatment with a third-generation aromatase inhibitor. While we are left with an open question in adjuvant therapy regarding duration of treatment with an LH-RH analogue (85), based on the fact that metastatic breast cancer remains noncurable and, thus, patients responding to ovarian ablation may be candidates for subsequent aromatase inhibition, it seems reasonable to advocate permanent ovarian ablation (radiological or surgical) for those patients obtaining a clear response to treatment with an LH-RH analogue. Subsequently, such patients may be treated according to the principles outlined for postmenopausal women above.

Hormone Replacement Therapy

The beginning of menopause is marked by the last menstrual cycle. This is the result of declining ovarian func tion and reduced synthesis of estrogens and progesterone. Estrogen production in postmenopausal women is usually only about 10 of that in premenopausal women. Almost no progesterone is synthesized in postmenopausal women. Hormone replacement therapy (HRT) generally refers to the administration of estrogen-progestin combinations. Estrogen replacement therapy (ERT) consists of the use of an estrogen alone, usually in the form of conjugated equine estrogens or an estrogen transdermal patch. The four most common symptoms associated with menopause are vasomotor disorders, or hot flashes urogenital atrophy osteoporosis and psychological disturbances. A varying proportion of women may have one or more of these symptoms. One in four postmenopausal women have osteoporosis. Osteoporosis, a decrease in bone mass, constitutes the most serious effect of menopause. It has been estimated...

Pharmacogenetic Interactions in Hormone Replacement Therapy

Combined estrogen and progesterone therapy, whether in the form of oral contraceptive pills (OCP), in premenopausal, or hormone replacement therapy (HRT), in postmenopausal women, is associated with an increased risk for VTE. Although the absolute risk of pulmonary embolism (PE), or deep vein thrombosis (DVT), is low in healthy young women, users of OCP have a three- to sixfold increased risk of VTE compared with the nonusers (43). Traditionally, the estrogen content has been implicated as the cause for increased VTE risk. However, third generation OCP containing < 50 ug of estrogen and synthetic progesterones, desogertrel or gestodone, are associated with a higher risk of VTE than second generation OCPs containing levonorgestrel and norgestrel, supporting a combined hormonal risk model (44). Based on a recent meta-analysis, the increase risk of VTE among HRT users was estimated to be 2.14, compared with the controls (45). The Women's Health Initiative study randomized 16,1809...

Age and Menopause

To date, there are no studies evaluating the role of estrogen replacement initiated at the start of menopause in prevention of genital prolapse. However, because age has been shown to be a strong risk factor in the development of pro lapse, it can be assumed that estrogen deficiency, which will occur in all women in the menopausal years, may contribute to weakening of the supports (epithelium, connective tissue, muscle). This may be a key factor in the development and progression of prolapse, explaining the increased incidence of prolapse in the postmenopausal years. Estrogen receptors have been identified throughout the nuclei of the connective tissue and smooth muscle cells of the bladder trigone, urethra, vaginal mucosa, levator ani muscle stroma, arcus tendineus, and the uterosacral ligaments. The collagen content of the pelvic floor is also estrogen dependent. In biochemical analysis of pelvic floor tissue, it has been demonstrated that there is a reduction in total collagen...


Several menopause-related changes in sexual function occur that have been described in the literature diminished sexual responsiveness, dyspareunia, decreased sexual activity, decrease in sexual desire, and a dysfunctional male partner. Sarrel29 described the underlying cause of biological changes that occurred with sexual dysfunction to be estrogen deficiency. The postmenopausal ovary has been shown to be responsible for up to 50 of the testosterone believed to be associated with libido. Many clinicians believe that a combination of both estrogen and testosterone is required to improve female sexual function. The effect of menopause on vaginal physiology has been described. There is a pronounced decrease in pelvic blood flow. This in turn results in a thinning of the vaginal mucosa and loss of the normal microbial environment. With the loss of estrogen, there is change in the integrity of the vaginal tube, making it less compliant for coitus. Lubrication is also compromised because...

The menopause

As a human is unlikely to be self-sufficient until aged 14, the menopause may be thought of as timed to precede death by this number of years. The menopause heralds a sharp drop in oestrogen levels, leading to a loss of subcutaneous fat, an ageing appearance, and thinning of the vaginal mucosa leading to dyspareunia, both of which may lower libido. Freedom from contraception and raised levels of luteinizing hormone-releasing hormone may have the opposite effect. Hallstrom (8) reported on the sexual activity of 586 subjects aged 38 to 54. He found that the loss of libido was due more to the menopause than to age, but social factors also played a part. Hawton et a .(9) selected and age-matched 34 menstruating women with 34 who had ceased. Age had more effect than the menopause. McCoy and Davidson1,' followed 43 women through their menopause and found a slight decrease in interest, coital frequency, and responsiveness.

Continence Abnormalities

Menopause is noted to be a risk factor for the development of altered fecal continence. Some preliminary studies have shown a plethora of estrogen receptors in the sphincters of women, and have shown a subjective improvement in fecal incontinence with estrogen therapy.34'35 Aging is also a significant risk factor for fecal incontinence. The prevalence of fecal incontinence is between 9 and 17 in women 75 years or older. The incidence is higher in women (8 1) probably because of a history of obstetric injury and the loss of estrogen.36

Descriptive Epidemiology

Breast cancer incidence has increased over the past 30 years in the U.S.6 This trend is thought to reflect increased diagnosis due to mammographic screening,7 and perhaps also to secular trends in the prevalence of obesity and hormone replacement therapy (HRT) use by postmenopausal women.8 Over the same period, breast cancer mortality rates have declined, reflecting earlier breast cancer detection and treatment, and improvements in breast cancer therapies.9

Female Sexual Dysfunction

Female sexual dysfunction is a generalized term for abnormalities in the normal female sexual cycle. It is a highly prevalent problem affecting anywhere from 30 to 50 of women in all age groups. The National Health and Social Life survey of 1749 women found that 43 complained of sexual dysfunction.20 Only recently have the problems involved with female sexuality gained recognition by clinicians. There are risk factors associated with female sexual dysfunction including age, menopause, previous surgery, mental and physical health, and availability of a partner.

The hypothalamicpituitarygonadal axis

In view of the remarkable gender differences in the prevalence rate of depression, the relatively high rates of postpartum depression, as well as the reduction in libido that is so characteristic of depression, it is plausible to posit a reduction in HPG axis activity in depressed patients. Therefore it is somewhat surprising that so little research has been conducted on HPG axis activity in depression and other psychiatric disorders. Indeed, a comprehensive database on this extraordinarily important area is simply not available, but the field has recently been reviewed. (3D A series of older studies documented no differences in basal gonadotrophin levels in depressed patients when compared to controls. The gonadotrophin-releasing hormone ( GnRH) stimulation test has only been administered to a relatively small number of depressed patients although the results revealed a blunted or normal response, no firm conclusions can be drawn from this limited data set. Indeed, such studies...

Biological Explanations For The Sex Ratio In Depression

Direct evidence linking hormone status to depressive disorder has some face validity oestradiol and progesterone seem to modulate the neurotransmitter and neuroendocrine systems, including those involving monamines, and there are transitions in women's lives characterized by hormonal shifts that may also be associated with mood disturbance (childbirth and the menopause).

Clinicopathological Features Of Brca1related Breast Cancer

The relevance of estrogen ERa to the etiology of BRCA1 -associated tumors has been a long-standing clinical conundrum. BRCA1 -associated tumors are largely ERa-negative (6) and their gene expression profile resembles that from basal epithelial cells in the mammary gland (94, 95). On the other hand, prophylactic oophorectomy, which removes the major source of circulating estrogen in premenopausal women, significantly reduces risk of breast cancer in BRCA1 -mutation carriers (96, 97). Consistent with the findings in human (96, 97), oophorectomy decreases the incidence of mammary tumor formation in the MMTV--BRCA1'' mouse model (98). In addition, tamoxifen has been shown to be effective in reducing the risk of contralateral tumors in BRCA1 -mutation carriers (99). Epidemiological evidence also suggests that hormonal exposure and obesity in adolescence, which are well-known risk factors for sporadic breast cancer, can significantly affect breast cancer onset for BRCA1 -mutation carriers...

Stressresponsive hormones

Stress-responsive hormones, including but not limited to adrenal corticosteroids and catecholamines, have a myriad of effects on various aspects of the immune response in both down- and upregulatory fashion.(23) Often hormones affect immunity in an 'inverted U-shaped' way, being suppressive at either abnormally high or abnormally low levels. As mentioned above, the hypothalamic-pituitary-adrenal axis, itself triggered by immunological as well as psychological events, is immunoregulatory, and both corticotrophin-releasing factor and ACTH have direct effects on immunity in addition to those via induction of release of cortisol. Growth hormone increases T- and NK-cell functions in aged animals. Prolactin antagonizes glucocorticoid-induced immune suppression. Gonadal hormones affect immunity. NK cell activity is higher in the luteal phase of the menstrual cycle (which should influence surgeons in the timing of cancer surgery in premenopausal women). Cellular immunity is depressed during...

Preventing AD and future treatments

A number of factors such as non-steroidal anti-inflammatory drugs, hormone replacement therapy, and the antioxidant vitamin E, might be of some use in strategies to prevent AD. Prevention could be primary before any signs of the disease or secondary after some manifestation of the process. Primary preventive measures would have to be directed at either the entire population or to groups at risk (identified by family history or genotype, for example), and therefore would have to be entirely benign and almost cost-free to be acceptable. Secondary prevention, possibly in those with memory impairments not amounting to dementia (minimal cognitive impairment), is a more realistic prospect rendering the determination of the very earliest signs of disease or evidence of a prodromal state a high priority. A biological marker for AD would have immense utility in both clinical practice and in clinical trials. Markers suggested have included platelet membrane fluidity and measurement of amyloid,...

Etiology And Risk Factors

Reports from epidemiological studies of protective effects of certain prescribed medication, non-steroidal anti-inflammatory drugs, hormone replacement therapy (HRT) and cholesterol-lowering therapies are now being investigated in randomized controlled trials. The randomized controlled trial of HRT in postmenopausal women indicated, against expectation, that it increased rather than lowered the incidence of dementia.

Physiologic Correlates Of Malignancy

Cells are required for the repair of defects during ovulation. Hence, ovulatory events could promote tumor progression by stimulating the proliferation of ovarian surface epithelial precursor cells. Consistently, early menarche, late menopause, nulliparity, and the use of fertility-stimulating drugs is associated with increased risk for ovarian carcinoma. In contrast, multiple pregnancies, prolonged breast-feeding, and the use of contraceptives decrease the risk.

Hormonal Risk Modulation in PTEN Mutant Cells

Estrogens and progestins have a reciprocal effect on endometrioid endometrial cancer risk. Epidemiological studies of endometrial cancer risk factors show a 2-10-fold increased cancer risk in women exposed to estrogens without opposing effects of progestins (6,43-45). The protective effects of progestins are evident in women using combined oral contraceptives, as they have a 0.5-0.7 endometrial cancer risk relative to controls (46,47). Risk modulation occurs through interaction of these systemically administered agents with the target endometrial tissue. Identification of a very high baseline frequency of endometrial mutagenic events, such as PTEN-mutated endometrial cells in up to 43 of otherwise normal premenopausal women (latent precancers, discussed earlier) (22), has renewed the focus on endocrine risk modifiers, rather than mutagenesis rates, as the rate limiting event. Progestin treatment of a type known to reduce endometrial cancer risk causes preferential involution of...

The Role Of Aromatase And Other Oestrogen Producing Enzymes In Mammary Carcinogenesis

Abstract There is a large and compelling body of epidemiological and experimental evidence that oestrogens are the fuel behind the aetiology of breast cancer. The local biosynthesis of oestrogens especially in postmenopausal women as a result of the interactions of various enzymes is believed to play a very important role in the pathogenesis and development of hormone-dependent breast carcinoma. The over-expression of such enzymes seems to be associated with the development of a more aggressive disease and associated with poor outcome and increased local and distant recurrences. In this chapter we shed light on CYP19 gene expression, aromatase enzyme activity and its role in mammary carcinogenesis. In addition, other oestrogen producing enzymes such as 17beta hydroxy steroid dehydrogenase 1, 2 and steroid sulphatase and their role in breast cancer development are discussed in details. The understanding of the mechanisms that regulate these enzymes is crucial to the development of new...

Medications for Stress Urinary Incontinence

Pharmacologic therapy of stress urinary incontinence (SUI) is directed toward enhancing urethral sphincteric function, especially during times of increased intraabdominal pressure such as coughing or lifting. Appropriate function of the intrinsic and extrinsic urethral sphincteric musculature, along with appropriate urethral support, as well as integrity of the urethral mucosa and submucosal vascular plexus are the key components of the delicate female continence mechanism. The extrinsic muscular support of the urethra is dependent on intact pelvic floor musculature and its innervation. Physiotherapeutic approaches to SUI are discussed in Chapter 12-2. The urethral mucosal and vascular factors are dependent on estrogen availability. In menopausal women, there is a prompt reduction in blood flow to the urethral submucosa and thinning of the urethral mucosa. Usage of local estrogen cream is discussed in Chapter 11-1.

Cerebral Blood Flow Changes

A lower incidence of stroke and vascular events in premenopausal women has been well documented, as has an increase in these events in women after menopause.7 Although indirect effects of estrogens on cardiac risk factors such as estrogen's lipid-lowering effect are partially responsible, direct effects of estrogen on the blood vessel wall may play an important role. These direct vascular effects of estrogens may also underlie much of the hormone's neuroprotection after brain injury. One component of autoregulation is the myogenic response, which is the constriction or dilation of vascular smooth-muscle cells in response to increases or decreases in transmural pressure. An important modulator of the myogenic response is EDRF or nitric oxide (NO ). Interestingly, the myogenic tone of rat cerebral arteries has been shown to differ between males and females and this difference appears to result from estrogen enhancement of NO production.44, 49-51 It has been shown that the vascular...

Epidemiology And Classification

Thyroid cancer occurs at all ages but is most common among middle-aged and postmenopausal women and in older men (7). According to reproductive status, the female to male incidence ratio varies, from being almost one in childhood, increasing to three from puberty to menopause, and declining to 1.5 by 65 years of age. Overall death rate is less than 10 (7).

The Impact of Physical Activity on Health

Specifically focusing on women, The Women's Health Initiative Observational Study, which includes 73,743 postmenopausal women 50 to 79 years old, reported in 2002 that increasing PA resulted in a reduced relative risk for coronary artery disease. Each increasing quintile of energy expenditure lowered the risk of coronary artery disease from 1.0, 0.73, 0.69, 0.68, and 0.47. These findings were consistent across all races, ages, and BMIs 9 . Physical activity has a positive impact on the health of obese patients whether or not weight loss occurs. One study divided premenopausal women into four groups diet weight loss, exercise weight loss, exercise without weight loss, and control group. After 14 weeks, the data showed women in both the diet weight loss group and the exercise weight loss group lost weight. However, CRF improved only in the two exercise groups, and reduction in both total and abdominal fat occurred only in the exercise weight loss group 21 . Another study has shown a...

Gender Dimorphism in Trauma Patients

Plays a significant role in the outcome of trauma patients (Schroder et al., 1998 Eachempati et al., 1999 Offner et al., 1999 Oberholzer et al., 2000 McGwin et al., 2002 Bowles et al., 2003 George et al., 2003a, 2003b Gannon et al., 2004). Recently, a retrospective analysis of more than 150,000 blunt or penetrating trauma patients (George et al., 2003a, 2003b) suggested that after blunt trauma, male patients had a significantly higher risk of death as compared with female patients. In addition, these findings suggested that premenopausal women had a survival advantage in blunt trauma patients however, the opposite pattern prevailed in patients with penetrating trauma (George et al., 2003a, 2003b). Similarly, findings from a prospective analysis of septic patients suggested significantly more deaths in males compared with females (Schroder et al., 1998). Consistent with these findings, another study (Wichmann et al., 2000) concluded that while the overall mortality was not different...

Hormonally Mediated Events

Menopause may cause uncomfortable symptoms in many women and can be controlled to a great extent by HRT. Some of these symptoms, hot flashes, fatigue, and bone thinning (leading to osteoporosis) can intensify symptoms and problems related to MS. Osteoporosis has been linked to the treatment of MS with steroids, and this condition may worsen during the peri-menopausal or menopausal state of life. Unfortunately, there is some controversy in the medical community about the benefit risk ratio of HRT and women should consult their personal physician and gynecologist to discuss the pros and cons of these medications. There are other reasons your physician might suggest HRT for a person with MS, as they can reduce post-menopausal complications that include osteoporosis, weight gain, fatigue, vaginal dryness, diminished libido, increased cardiovascular disorders, and decreased exercise tolerance.

Relationship Of Hormones And Molecular Genetic Alterations

These studies suggest that the mechanism by which tamoxifen increases the incidence of endometrial carcinoma is through the same pathogenetic pathways that give rise to sporadic cancer. Given these results, tamoxifen may act as an initiator of tumori-genesis through estrogen agonistic activity in the endometrium, according to the suggestions made by clinical trials and laboratory studies (26,28-32). An immunohistochemical study of endometrial epithelial proliferation in postmenopausal women showed increased staining with MIB-1 in tamoxifen-exposed benign endometrium compared to nonexposed endometrium. This further supports the idea that tamoxifen exposure results in increased epithelial proliferation (29). Thus, tamoxifen may act to increase the proliferation of a subset of cells, thereby increasing the likelihood of mutations.

Physical Activity for Obese Patients

Similar positive health benefits from walking were found in postmenopausal women, with a lower risk of hip fractures by 6 for each hourly increase in walking per week 30 , and in premenopausal women who maintained weight loss and decreased waist circumference with walking 2 to 3 hours per week 31 .

Studies That Have Changedor Could Change Practice

Cost-effectiveness studies showed that some commonly used treatments were within the range of accepted cost-effectiveness ratios but some were not. Postmastectomy radiation in premenopausal women improved survival at a cost of 24,900 LY. Capecitabine docetaxel in metastatic breast cancer, compared to docetaxel alone, improved survival by 3 months29 at a cost-effectiveness ratio30 of approximately 3,700 LY (Canadian), well within accepted standards of treatment. In this study, utility was not included but the magnitude of survival benefit would likely offset the negative effects of toxicity associated with capecitabine. Of note, the alternative strategies of sequential therapies were not tested, so no conclusion can be drawn. A more expensive initial strategy, autologous stem cell transplant for myeloma instead of melphalan and prednisone, had longer survival that offset the cost, so the incremental cost-effectiveness was acceptable. One recent study31 looked at cost-effectiveness...

The Insulinlike Growth Factor1 Ligand In Breast Cancer Management

Abstract The insulin-like growth factor-1 (IGF-1) system plays an important role in normal human development and is also a potent mitogen which can stimulate the development and progression of breast cancer cells. This review aims at looks at how measuring IGF-1 levels may be used in the clinical management of breast cancer patients. Many studies have shown that IGF-1 acts synergistically with oestrogen to stimulate breast cancer cells. Case-control studies have also shown that premenopausal women with high levels of serum IGF-1 have a high risk of developing breast cancer later in life which does not apply to postmenopausal women with correspondingly high serum levels. Serum IGF-1 levels can therefore potentially be used as biomarkers for predicting breast cancer risk while some studies have started using serum IGF-1 levels as a response bio-marker for chemopreventive drug trials. Measuring IGF-1 ligand expression in breast cancer tissue is not consistently associated with better or...

Gonadal responses to critical illness

Luteinizing hormone is secreted in a pulsatile fashion by the pituitary gland and stimulates testicular secretion of testosterone in men. Testosterone levels fall promptly within 24 h of the onset of severe illness, but there is no compensatory rise in gonadotropins. Instead there is a fall in levels which persists for the duration of illness. In postmenopausal women, severe illness is also associated with relatively low concentrations of gonadotropins which correlate directly with outcome. These findings are compatible with an illness-induced hypogonadal syndrome.

Predisposing and trigger factors

Migraine, in particular, is said to be subject to certain physiological and external environmental factors. While predisposing factors increase susceptibility to attacks, trigger factors may initiate them. The two may combine. Attempts to control migraine by managing either are often disappointing. A few predisposing factors (stress, depression, anxiety, menopause, and head or neck trauma) are well recognized but not always avoidable or treatable. Trigger factors are important and their influence is real in some patients, but generally less so than is commonly supposed. Dietary triggers are rarely the cause of attacks lack of food is a more prominent trigger. Many attacks have no obvious trigger and, again, those that are identified are not always avoidable. Diaries may be useful in detecting triggers but the process is complicated as triggers appear to be cumulative, jointly overflowing the threshold above which attacks are initiated. Too much effort in seeking triggers causes...

Agonistssupraphysiological doses of hormone

This approach is epitomized by the use of gonadotrophin-relating hormone agonists (GnRHa or LHRHa). The gonadotrophins LH and FSH provide the stimulus for gonads to produce steroid hormones in turn their synthesis and release from the pituitary is regulated by the hypothalamic factor GnRH (or LHRH). Highly potent agonist analogues of GnRH have been synthesized by introducing unusual amino acids into the native peptide. When administered for short periods they cause a rapid release of gonadotrophins, but in the long term these agonists down regulate gonadotrophic receptors and desensitize the pituitary. As a result circulating gonadotrophins fall, the trophic drive to the gonads is abolished, and circulating sex hormones are reduced to castration levels. Depot formulations of LHRH agonists are available so that a single injection can maintain effective medical castration over prolonged periods. The use of GnRH analogues in pre-menopausal women with breast cancer and men with prostate...

Inhibition of steroidproducing enzymes

This approach is best illustrated by inhibitors of aromatase or 5a-reductase activity. The aromatase enzyme converts androgens to oestrogens and is the last step of the synthetic cascade. Its inhibition represents the most specific method of blocking oestrogen production. Because oestrogen biosynthesis can occur in non-endocrine tissue such as adipose tissue and malignant tumours themselves (particularly in post-menopausal women), aromatase inhibitors have the potential to suppress oestrogen levels beyond that achievable by surgical ablation of classical endocrine organs. Two major types of inhibitors have been developed Early type II inhibitors such as aminoglutethimide were neither potent nor specific, inhibiting other steroid-metabolizing enzymes that had a similar cytochrome p450 prosthetic group. Triazole drugs (anastrozole, letrozole, vorozole) are 2000-fold more potent than aminoglutethimide and have differential affinity towards aromatase cytochrome p450 with highly selective...

Disorders of sexual desire

In men, the biological component underlying sexual desire is circulating levels of testosterone and, more specifically, bioactive or free testosterone. Schiavi et al.(23) found that men with hypoactive sexual desire had significantly lower levels of testosterone than matched controls. In women, however, hormone-behavioural relationships are more difficult to identify because baseline levels of androgens are substantially lower and less variable than men's and thus more difficult to measure. Measurement is further complicated in women because endocrine profiles are considerably altered during periods of menstruation, pregnancy, lactation, and the menopause. Schreiner-Engel and Schiavi(24) failed to find significant differences in mean levels of free testosterone in young women with hypoactive sexual desire compared to matched controls.

Psychotherapysexual counselling

Clinician has expanded to include helping men couples, regardless of the aetiology of the dysfunction, make use of these new interventions. Thus, the clinician provides assistance in overcoming the resistances to utilizing medical treatments that may help patients and partners develop a satisfying sexual relationship. (43> Sometimes attitudinal or psychological resistances need to be worked through prior to beginning a medical intervention. If not overcome, these forces can render the best-intentioned treatment efforts ineffectual. The therapist can also help the couple to cultivate a romantic ambience and engage in conversations that will physically and psychologically prepare them to become lovers again. Frequently the therapist can also assist the couple in accepting the changes that may have occurred in their lives, for example menopause, disability, illness, or other life stresses.

Disorders of sexual arousal in women

Typically, female arousal disorders are diagnosed in women with complaints of diminished lubrication or painful intercourse. There is considerable ambiguity regarding this diagnosis because, with the exception of postmenopausal women in whom diminished lubrication is a normal physiological change, symptoms of female arousal disorder are frequently subsumed under desire and or orgasmic disorders ( Table 4). Additionally, the definition of female sexual arousal disorder reflects the overemphasis of physical function (lubrication and pelvic vasocongestion) over psychological excitement and or pleasure. The correlation between physical and mental arousal is at best inconsistent and often puzzling. For instance, Palace (48> evaluated the effects of heightened autonomic arousal, noting that it significantly increased both physiological and subjective sexual arousal. These findings indicate that heightening autonomic arousal in an actual sexual setting might be useful for increasing sexual...

[3 Site Specific Fluorescent Labeling of Estrogen Receptors and Structure Activity Relationships of Ligands in Terms of

The estrogen receptor (ER) is a ligand-regulated transcription factor that belongs to the nuclear receptor (NR) superfamily and acts as a dimeric species. There are two subtypes of ER, ERa and ERb, which are both mainly regulated by the endogenous estrogen, estradiol (E2). ER modulation is involved in the development and regulation of reproductive, cardiovascular, and bone health, in addition to controlling various aspects of cognitive function.1 In addition to maintaining homeostasis in many tissues, an excessive activity of ER has been correlated with the development and proliferation of certain breast and uterine carcinomas.2 In clinical settings, ER activity is modulated with exogenous estrogen and antiestrogen ligands as hormone replacement therapy (HRT) and as anticancer agents.3

Clinical Utility of Testing

Homozygous carriers is increased 80- to 100-fold. VTE risk increases due to interaction between Factor V Leiden and other genetic disorders such as AT, PC, or PS deficiency. Genetic and clinical risk factors also interact to compound the risk of VTE. For example, VTE risk increases 30-fold among heterozygous Factor V Leiden women carriers receiving oral contraceptives, 7- to 16-fold during pregnancy or the puerperium, and 13- to 15-fold for postmenopausal women carriers receiving estrogen replacement therapy.22 Factor V Leiden carriers also may be at increased risk for VTE after surgery. The incidence of VTE among Factor V Leiden carriers also varies by age, ranging from 2 to 3 per 1,000 person-years for ages 15 to 30 years, to 7 to 11 per 1,000 person-years for age 60 years and older. However, compared to that for patients with AT, PC, or PS deficiency, the lifetime probability of developing VTE is considerably less for Factor V Leiden heterozygotes. Only 2.4 of Factor V Leiden...

Pessaries for Genital Prolapse

Advances in gynecologic surgery and anesthesia over the last several decades have reduced the need for pessary usage in the treatment of prolapse and incontinence. However, the recent increase in the elderly population requiring conservative treatment of prolapse and incontinence has led to a resurgence of pessary use.5 In addition, there remains a very acceptable role for therapeutic use of a vaginal pessary in the premenopausal patient. In a recent survey administered to members of the American Urogy-necologic Society, 77 of the respondents used pessaries as a first-line therapy for prolapse, and only 12 reserved pessaries for women who were not surgical candidates. In addition, 92 of the physicians surveyed believed that pessaries relieved symptoms associated with pelvic organ pro-

Vaginal Vault Prolapse Surgery

Identification of weakness of vaginal vault support is crucial for the surgical correction of vaginal prolapse. In the presence of a large cystocele or enterocele, accurate identification of a prolapsed vaginal apex can be challenging, even to an experienced examiner. However, it is not uncommon to see a patient referred with recurrent vaginal prolapse after an anterior and posterior repair who likely had preexisting vaginal vault prolapse before the initial reparative procedure. Recent estimates have calculated that approximately 14 of women in their peri- and post-menopausal years may have uterine prolapse. Of those who have been hysterectomized, approximately 38 will have some form of prolapse. It is estimated that 10 of this age group of women will have vaginal vault prolapse.

Surgical Approaches

We will typically perform an abdominal sacro-colpopexy in a patient with advanced prolapse in which the vaginal apex reaches significantly above the ischial spines on vaginal examination, for whom maintaining normal sexual activity is very important, someone who will require another abdominal procedure for their vaginal prolapse such as an abdominal paravaginal repair, and someone with significant vaginal wall scarring, large apical fascial defects, or significant foreshortening of the vaginal canal. Vaginal approaches are typically performed in post-menopausal women for whom sexual activity may not be as important and in whom other reconstructive procedures can be appropriately performed vaginally. Obliterative procedures are performed in elderly women who are not, and will not, be sexually active, and who request the least invasive procedure for advanced vaginal prolapse. Laparo-scopic approaches are reserved for surgeons request laparoscopic skills adequate enough to...

Fibrocystic Breast Disease

Most premenopausal women experience fibro-cystic breast disease characterized by tenderness, sometimes painful breasts, and small lumps that can be felt. It may be part of PMS and is associated with an excess of estrogen. If the lump is tender or painful, it is likely a cyst and not a tumor. Avoiding coffee and any foods or drugs containing caffeine can reduce symptoms signifi

Lipids And Lipoproteins

It seems clear, based on current evidence, that soy protein as a part of a diet or as a supplement exerts beneficial effects on plasma lipids and lipoproteins, but the magnitude of the beneficial effects is uncertain. The uncertainty probably relates to a number of poorly understood variables that relate to differences in metabolism among human and nonhuman primates and lower animals, and the effects of intervening variables, such as stage of the menstrual cycle and perhaps plasma concentrations of nonovarian-derived estrogens. In this brief review we attempt to put these various issues in the context that is possible based on current knowledge. Since soy supplements are more widely used by postmenopausal females than by males, the majority of the studies have focused on females. Our group conducted and reported on several studies comparing the effects of diets containing casein lactalbumin (C L) and isolated soy protein on the plasma lipids and lipoproteins of surgically...

Clinical Significance

The primary utility of genetic testing for RET mutations is to confirm the diagnosis of MEN2, to provide predictive risk-assessment testing for family members, and to facilitate prenatal diagnosis of MEN2. Early detection of a pathogenic RET mutation improves the prognosis for presymptomatic individuals by offering an opportunity for therapeutic intervention prior to advanced disease, metastasis, or both.45-47 There is reduced morbidity and mortality achieved by increased clinical monitoring, prophylactic thyroidectomy (followed by thyroid hormone replacement therapy plus autotransplantation of the parathyroids), or both.1,37 This can be a very effective treatment to prevent disease metastasis. Resected thyroid tissue from children and adults with positive genetic findings demonstrates C cell hyperplasia or microscopic foci of malignancy in the absence of biochemical screening abnormalities or clinical symptoms.47 Thus, genetic testing for RET mutations is a more sensitive and...

Conclusions And Potential Clinical Relevance

Given the current use of melatonin as a popular over-the-counter jet lag and sleeping aid, it is important to understand the potential for cardiovascular effects in people self-administering melatonin. Possible interactions with estrogen are additional considerations for women taking melatonin during puberty, childbearing years and hormone replacement therapy after menopause. In addition, defining the role of mela-tonin in vascular regulation may lead to novel approaches for treating migraine, stroke and cardiovascular disease.

Epidemiological Studies

Adlercreutz et al.7 first showed in 1982, in a small number of subjects, that postmenopausal Finnish women with breast cancer (n 7) had a lower urinary mammalian lignan excretion compared to healthy controls (n 20), suggesting that the lignans are associated with a reduced risk of breast cancer. More studies, detailed in Table 19.1, have since been conducted, utilizing larger sample sizes and either urinary or serum lignans levels, or lignan intake as biomarkers, to determine if the lignans are associated with breast cancer risk. From 1997-2002, three case-control studies11-13 showed negative association between urinary lignans or lignan intake and breast cancer risk, while a case-control study14 showed no association between lignan intake and breast cancer risk in pre- and postmenopausal women. In another case-control study, when both pre- and postmenopausal women were combined, there was a significant negative association between serum lignans and breast cancer risk.15 A prospective...

Management of glandular cell abnormalities

When a Pap smear is performed during menstruation, endometrial cells may be present. However, endometrial cells on a Pap smear performed during the second half of the menstrual cycle or in a post-menopausal patient may indicate the presence of polyps, hyperplasia, or endometrial adenocarcinoma. An endometrial biopsy should be considered in these women.

Estrogen and Progesterone

Estrogen and progesterone may exert a protective effect on the upper airway, preventing premenopausal women from developing sleep apnea (19). The role of hormone replacement therapy (HRT) in sleep-disordered breathing was examined in a cohort of 2852 women who were 50 years of age or older and participated in the Sleep Heart Health Study. The prevalence of sleep-disordered breathing (AHI of 15 or more) among hormone users was approximately half the prevalence among nonusers (19). The inverse association between hormone use and sleep-disordered breathing was evident in various subgroups and was particularly strong among women 50 to 59 years old. An earlier study showed that postmenopausal women had a significantly higher mean AHI compared with premenopausal women, and this significant difference persisted even after adjusting for body mass index and neck circumference (20). The effects of HRT on OSA should be taken into consideration when weighing the risk to benefit ratio of HRT for...

Background Information Epidemiology

Vulval carcinoma occurs most frequently in elderly women, peaking in incidence in the sixth and seventh decades, but with 30 of cases arising in premenopausal women. There are approximately 900 new cases per year in the UK. The American Cancer Society estimates the incidence of vulval cancer in the USA will be 3800 new cases in 2002, with 800 deaths expected. Symptoms of vulval malignancy include a mass, pruritus, pain and discharge. Human papilloma virus (HPV) infection is believed to predispose to malignant transformation in the vulval epithelium. Women presenting with invasive squamous carcinoma often have a history of vulval intraepithelial neoplasia (VIN) with histological evidence of viral infection in the vulval epithelial cells. As with the relationship between cervical intraepithelial neoplasia and invasive cervical carcinoma, there is postulated to be a progression from low grade VIN (dysplasia) to high grade VlN (carcinoma In situ) with eventual development of invasive...

Prescription Drug Data

Both generic and proprietary names are used so the ability to differentiate between product types is available. The total amount of drug dispensed is also entered together with the dosing instructions, thus allowing the duration of any prescription to be calculated. Community prescribing data have been entered for selected medications from January 1989 (notably non-steroidal anti-inflammatory drugs, ulcer healing drugs, lipid-lowering drugs and hormone replacement therapy) and all prescribed medications from January 1993. MEMO now has records of 15 million prescriptions dispensed in Tayside up to December 1996.

Influence of Gender on Arteriolar Function in Hypertension

Females prior to menopause are much less susceptible to hypertension and other cardiovascular diseases than males, indicating that gender has a protective effect in these disorders and that female sex hormones can offset some of the alterations in arteriolar function that may occur with hypertension in males. For example, flow-induced arteriolar dilation is significantly reduced in male spontaneously hypertensive rats compared to females, because of the loss of the nitric oxide (NO)-mediated portion of the response. This impairment of the NO-mediated component of flow induced dilation results in a maintained elevation of wall shear stress in the male rats, suggesting that female sex hormones play an important role in maintaining NO-dependent vasodilator responses and in preserving the regulation of arteriolar shear stress by nitric oxide. Arteriolar dilation in response to increases in perfusate flow is also impaired in isolated gracilis muscle arterioles of ovariectomized female...

Variation In Prescribing And Medication Compliance

Prescribing may vary by patient factors that are independent of need or disease severity. For example, the variation of use of hormone replacement therapy by socio-economic status independent of need (Evans et al., 1997a). Compliance to labelled medication direction or therapy is a related issue. By assessing how patients collect dispensed medication, in terms of numbers of prescriptions dispensed and intervals between them, and linking to outcome data sets, patient compliance or non-compliance to medication can be studied. For example, a study in diabetes showed that adolescents in Tayside who have brittle diabetes are often non-compliant with insulin (Morris et al., 1997b).

Clinical evaluation of PMS

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

Lactation Introduction

Breast milk is widely acknowledged to be the most complete form of nutrition for infants. Breastfeeding poses multiple benefits for infants including health, growth, immunity, and development. Specific infant benefits of breastfeeding include decreased episodes of diarrhea, respiratory infections, and ear infections. Breastfeeding poses multiple maternal benefits as well, including a reduction in postpartum bleeding, earlier return to prepregnancy weight, reduced risk of premenopausal breast cancer, and reduced risk of osteoporosis 34 . In order to encourage breastfeeding, the Health and Human Services Healthy People 2010 initiative targets increasing the percentage of mothers who breastfeed to 75 in the early postpartum period, 50 at six months, and 15 at one year 35 . Professional medical organizations encourage breastfeeding as well 36, 37 . The American Academy of Pediatrics (AAP) considers breastfeeding to be

Ovulation suppression

Ovarian suppression with GnRH agonists induces menopause. PMS symptoms will be relieved, but patients experience menopausal side effects, including irritability, insomnia, hot flashes, and vaginal dryness. To prevent osteoporosis, add-back therapy with estrogen and progesterone is required.

Clinical Studies ofMLT and Breast Cancer

In addition to the studies in the rat model, the effects of MLT have also been investigated in human breast cancer. It has been reported that the nocturnal rise in MLT levels is significantly reduced in women with ER-positive breast tumors compared to women with ER-negative breast tumors and healthy age-matched controls (24). Another clinical study assessing pineal function in patients with breast cancer found that post-menopausal women with advanced breast cancer have diminished urinary levels of MLT compared to healthy controls (25). Based on these data, it has been suggested that depressed MLT secretion may be a predisposing factor for the development of breast cancer in humans (26). It has also been reported that a two-fold higher MLT level is associated with breast tumors with a low proliferative index compared to those with a high index, suggesting that hypersecretion of MLT may predict a more favorable prognosis (27). Clinical trials investigating the combined effects of MLT...

Red wine polyphenolics

The well publicized French paradox means that when in France one can eat and drink with abandon without fear of becoming obese. Red wine consumption has often been cited as the protective factor in this phenomenon. The good news is that there may well be a scientific basis for this happy situation. Pal et al. (2004) studied the impact of acute consumption of red wine polyphenolics in postmenopausal women. They found that red wine polyphenolics attenuate postprandial chylomicron and chylomicron remnant levels in plasma, possibly by delaying absorption of dietary fat.

Central nervous System symptoms

In elderly menopausal women, estrogens may retard the progression of dementia, especially Alzheimer's disease. B. Sexual function. Libido may decrease at the time of the menopause. The use of testosterone with estrogen may induce a positive effect on mood and overall sense of well-being, particularly in women who have had their ovaries removed.

Estrogenic and Antiestrogenic Effects

The factors that dictate what response a phytoestrogen will produce are actually complex, but in general, phy-toestrogens possess weak estrogenic activity as compared to estrogen, and they compete with estrogen for estrogen receptors in a cell's nucleus. In addition, they can occur at much higher plasma concentrations than estrogen. Therefore, when estrogen levels are low (as in postmenopausal women), they have the potential to produce estrogenic effects. At least one human study using moderate isoflavone doses (140 milligrams per day, from soy concentrate) noted a slight but significant es-trogenic effect in postmenopausal women. Using the same reasoning, when estrogen levels are high (as in premenopausal women), we would expect genistein or other phytoestrogens to produce antiestro-genic effects. The effects of genistein on premenopausal women, however, are still uncertain. Mild estrogenic effects from genistein have been reported in some human studies, and two studies have noted...

Therapeutic options

Contraindications to hormone replacement therapy Family or individual history of breast cancer estrogen dependent neoplasia undiagnosed genital bleeding and a history of or active thromboembolic disorder. B. Hormone replacement therapy should be considered to relieve vasomotor symptoms, genital urinary tract atrophy, mood and cognitive disturbances, and to prevent osteoporosis and cardiovascular disease. It also may be considered to help prevent colon cancer, Alzheimer's disease, and adult tooth loss.

Estrogen replacement therapy

All postmenopausal women without contraindications should consider ERT. Contraindications include a family or individual history of breast cancer estrogen dependent neoplasia undiagnosed genital bleeding and 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 .

Hereditary Breast Ovarian Cancer

Breast cancer is also a component of the rare Li-Fraumeni syndrome in which germ-line mutations of the p53 gene on chromosome 17p have been documented.61 First reported by Bottomley et al.,62 this syndrome is characterized by pre-menopausal breast cancer in combination with childhood sarcoma, brain tumors, leukemia and lymphoma, and adreno-cortical carcinoma. A germ-line mutation in the p53 gene has been identified in more than 50 of families exhibiting this syndrome, and inheritance is autosomal dominant with a penetrance of at least 50 by age 50. Although highly penetrant, the Li-Fraumeni gene is thought to account for less than 1 of breast cancer cases.63 not, however, eliminate the risk for primary peritoneal cancer, which is estimated to range from 1.9 to 10.7 .85 Furthermore, premenopausal women choosing this option must consider the long-term consequences of surgically induced menopause. Similarly, prophylactic mastectomy does not completely eliminate the risk of subsequent...

Schizophrenia and paranoid disorders

When viewed across the lifespan, the incidence of schizophrenia shows strong age-group differences. (33) In males, the incidence rises steeply in adolescence, reaching a peak in the early twenties and then steadily declines to old age. Females show a similar rise in young adulthood with a subsequent drop, but there is also a second peak around the time of menopause. This second peak may occur because oestrogen delays the onset of schizophrenia in some vulnerable women. In younger adults, males have a higher incidence of schizophrenia, whereas in later life females have the higher incidence.

Hormonal Influences on the Pelvic Floor

Reproductive hormones, especially estrogen, have a significant impact on pelvic floor function. Hormonal changes that occur during a woman's lifespan impact many aspects of female physiology. With the onset of menopause, it becomes evident that estrogen sensitivity is greatest in the central nervous system and the genital tissues. The most frequently occurring initial symptoms of estrogen deprivation include hot flushes, mood changes, and emotional irritability. These central nervous system symptoms are promptly reversible with systemic estrogen replacement. More prolonged duration of estrogen deprivation will lead to other known consequences such as osteoporosis and urogenital atrophy. It is estimated that 80 of postmenopausal women have hot flushes, and that not all women will develop osteoporosis. However, urogenital atrophy occurs universally. Interestingly, many women with urogenital atrophy are asymptomatic.1 Many treatments are currently available for prevention of and therapy...

Chapter References

Hawton, K., Gath, D., and Day, A. (1994). Sexual function in a community sample of middle aged women with partners effects of age, marital, socio-economic, psychiatric, gynaecological, and menopausal factors. Archives of Sexual Behavior, 23, 375-95. 10. McCoy, N and Davidson, J. (1985). A longitudinal study of the effects of menopause on sexuality. Maturitas, 7, 203-10. 19. Sherwin, B., Gelfand, M., and Brender, W. (1985). Androgen enhances sexual motivation in females a prospective cross-over study of sex steroid administration in the surgical menopause. Psychosomatic Medicine, 47, 339-51.

Symptomatology of Urogenital Atrophy

Typical symptoms of vaginal atrophy include vaginal dryness, vaginal irritation, as well as loss of vaginal caliber and depth in more advanced degrees of atrophy. The initial symptoms of vaginal atrophy can be promptly reversed with local estrogen therapy. However, the more long-term effects of urogenital atrophy such as loss of vaginal caliber and depth are less likely to be readily reversible. This has recently become a clinically important issue, because male erectile dysfunction can be treated pharmacologically, whereas the female partners' advanced urogenital atrophy has not been taken into account. Any attempt at sexual intercourse after a long hiatus of inactivity in a post-menopausal woman can result in sexual dysfunction and even vaginal trauma including lacerations upon attempted penetration. It is thus critical that both partners be considered when initiating erectile dysfunction therapy in the male. larization. It is estimated that the urethral submucosal vascular plexus...

Impact on Nerve Function

One of the proposed reasons for differences in urogenital symptomatology seen in postmenopausal women may have to do with the effect of estrogen on nerve function. Treatment of postmenopausal sexual dysfunction has demonstrated that systemic and local estrogen therapy improves clitoral, perineal, and vaginal sensation. Thus, there is likely a neurotrophic effect of estrogen on nerve conduction and function. On a systemic basis, this is best demonstrated in the effect of hypoestrogenism on short-term memory. Systemic estrogen supplementation has a positive impact on memory, which is likely attributed to a direct neuronal effect.

Hormonal Impact on Colorectal Function

Very few data are available regarding the impact of estrogen deprivation after menopause on colorectal function. Many of the changes in colorectal function, such as increased incidence of hemorrhoids and weakening of the anal sphincter are thought to be age-related, rather than caused by hormonal changes. However, estrogen receptors have been found in the external anal sphincter, and there is some anecdotal evidence that local estrogen therapy may be useful in the treatment of hemorrhoids.8

Few Words Regarding Womens Health Initiative

Recent reports regarding the adverse effects of combination hormone replacement therapy found during the Women's Health Initiative (WHI) trial have further fueled the controversy regarding the usage of estrogen therapy in postmenopausal women. The WHI is a National Institutes of Health-funded study beginning in 1993 evaluating the influence of postmenopausal management on cardiac disease, breast and colon cancer, and fractures. The study intervention groups included a low-fat diet group, calcium and vitamin D supplementation group, conjugated equine estrogens-alone group, combined conjugated equine estrogens and medroxyprogesterone acetate group, and a placebo group. The findings reported in 2002 demonstrated an increased risk of deep venous thrombosis, stroke, myocardial infarction, and breast cancer in women in the combination estrogen progestin group. There was a reduction in colon cancer and risk of bone fractures. The adverse changes were only seen in the combination hormonal...

Pathology Of Endometrial Carcinoma

The most common EC variant is the endometrioid type, with an indolent biological behavior. The aggressive serous, papillary, and clear cell types of EC fortunately are rarer. Other types of ECs include pure squamous, mixed adenosquamous, mucinous, and mixed types. It is the endometrioid type carcinoma that is often preceded by endometrial precursor lesions, such as complex and atypical endometrial hyperplasia. Type I cancers (prototype endometrioid carcinomas) (Fig. 4) are often well differentiated, typically slow-growing cancers with usually excellent prognosis. Type I ECs (approx 80 of all ECs) tend to occur in perimenopausal or recently postmenopausal women with preceding endometrial hyper-plasia and other indications of excessive estrogenic effects unopposed by progesterone. Endometrioid tumors may show glandular, solid, or villoglandular histological patterns. Occasional morules of benign squamous metaplasias can be seen. Predictably, these tumors have high estrogen receptor (ER)...

Conservative Treatment

Cholinergic medication to relax the detrusor muscle and prevent spasms is used. Estrogen is used routinely in postmenopausal women to promote healing. In the last few years, we have been successful in managing small VVFs with cystoscopic fulguration with and without fibrin glue injection. The same principles of conservative management are followed after the procedure.

Natural Estrogens And Progestins

The ovary is the major site of estrogen and progestin biosynthesis in nonpregnant premenopausal women. In pregnant women, the fetoplacental unit is the major source of estrogens and progestins. Peripheral sites of estrogen synthesis include the liver, kidney, brain, adipose tissue, skeletal muscle, and testes. Progesterone is secreted in small amounts by the testes and adrenal gland. The combined estrogen and progestin production by all of these peripheral sites amounts to 10 or less of ovarian synthesis in normal premenopausal women. In postmenopausal women, ovarian steroid synthesis declines and peripheral estrogen biosynthesis accounts for all estrogen produced, both in postmenopausal women and in males.

Cardiovascular Complications

Mild hypertension and fluid retention frequently occur in oral contraceptive users. Systolic blood pressure is elevated 5 to 6 mm Hg diastolic blood pressure increases are on the order of 1 to 2 mm Hg. Hypertension is not commonly a problem in postmenopausal women receiving conjugated estrogens.

Prevalence Of Overweight And Obesity

The observed association between obesity and colorectal cancer is generally more consistent and stronger for men than for women and for colon cancer than for rectal cancer.33 Some studies found that WHR is a strong predictor (of the same strength as BMI) of colorectal cancer risk, especially for women.36,42,44,52-55 The association is also generally stronger and more consistent for cancer of the distal colon than the proximal colon.36,39,40,52,54-58 A meta-analysis of 13 studies on BMI and colon cancer found that the observed associations were of similar strength for cohort and case-control studies, and that the pooled estimates were statistically significant for both male and female but larger for men than for women.34 Excess weight early in life appears to be at least as important as recent excess weight in relation to colorectal cancer risk.40,45,54,56,58 One large population-based case-control study found that estrogen modifies the association between BMI and colon cancer risk...

Preparation For Pregnancy

Menstruation continues in most women until about age 50. At this time, a woman no longer ovulates. Most of a woman's follicles have either matured and ruptured or degenerated. Without follicles, the ovaries cannot secrete enough estrogen and progesterone to continue the menstrual cycle, and menstruation ceases. This stage is called menopause (MEN-uh-PAWZ).

Iron Deficiency Anemia

Iron is a constituent of hemoglobin, and iron deficiency will lead to a decrease in hemoglobin synthesis. Since iron is conserved by the body, deficiency usually results from acute or chronic loss of blood or insufficient iron intake during physiological stress. Infants, children, and premenopausal women require more iron than do men because of the increased demand that occurs during growth, pregnancy, and loss of blood during menstruation. In tropical climates, bleeding due to an infestation by the hookworm parasite is a common cause of iron deficiency.

Multipurpose Databases

Failure of clarity at this stage could doom the study from the onset. Investigators interested in a particular hypothesis can often be mesmerised by the apparent abundance of information available to them. They should keep in mind that it is crucial to restrict themselves to appropriate comparisons. Thus if one is looking at the effect of, say, hormone replacement therapy on osteoporosis, the relevant outcome measure available in such databases is generally a fracture. However, not all fractures are relevant. Indeed, most are irrelevant to the hypothesis, as they will have an obvious and sufficient cause, such as a road traffic or other accident, an underlying neoplasm or pre-existing bone disease. Similarly, not all exposures to hormones are relevant. For example, it would seem unlikely (biologically implausible) that a single prescription for such treatment would be relevant to the outcome of interest. Trained epidemiologists are used to thinking of chance, bias and confounding as...

Mechanism of Action

Soy isoflavones appear to act as selective estrogen receptor modulators in that they can occupy and block the (3-estrogen receptor. In premenopausal women with normal estrogen levels, soy therefore would have an overall antiestrogen (estrogen blocking) effect, whereas in postmenopausal women lacking estrogen, a weak estro-genic effect would be observed. Soy may also increase the excretion of bile acids and lower cholesterol.

Comment on difference in approach to genderspecific cancers using MRS and MRSI

Reinhold, I. Khalili, Postmenopausal bleeding value of imaging, Radiol. Clin. N. Am. 40, 527-562 (2002) 55 S. Ciatto, S. Cecchini, G. Gervasi, A. Landini, M. Zappa, E. Crocetti, Association of endometrial thickness assessed at trans-vaginal ultrasonography to endometrial cancer in postmenopausal women asymptomatic or with abnormal uterine bleeding, Radiol. Med. 104, 437442 (2002).

Therapeutic Use of Androgens in Women

Female hypogonadism, especially prepuberal, may be an indication for androgen therapy. Androgens are necessary for normal pubic hair induction and long bone growth in both sexes. In prepuberal females with hy-popituitarism in whom all other hormonal deficiencies (estrogen, progesterone, thyroid, adrenal, and growth hormone) have been corrected, normal sexual development and long bone growth are not complete without androgen hormone replacement. Estrogen administration during adolescence is necessary for the development of the breast, the gynecoid pelvis, and other female characteristics. However, maximal long bone growth and development of axillary and pubic hair will not occur without small amounts of androgen replacement. The use of methyltestosterone (Android) and di-ethylstilbestrol in combination has been demonstrated to be very effective in inducing complete secondary sexual development in these females. Finally, low doses of androgens have been used to facilitate impaired...

Reproductive and Developmental Toxicology Carole A Kimmel PhD Judy Buelke Sam

Gametogenesis Males And Females

Agents that interfere with the development of the reproductive system and the normal hormonal patterns necessary to regulate development may alter the intricate processes involved in a number of different ways. For example, the normal structure of the ovaries, uterus, oviducts, cervix, and vagina can be altered during development, resulting in interference with fertility and pregnancy. This was the case with the drug diethylstilbestrol (DES), a potent synthetic estrogen used in the 1950s and 1960s to prevent spontaneous abortion. Unfortunately, the drug was not effective in preventing labor but had profound effects on the development of the reproductive system in both boys and girls exposed before birth and produced a rare form of cancer (vaginal adenocarcinoma) in females not detected until after puberty (28). Synthetic androgens and antiandrogens also alter the structure of reproductive organs by interfering with the normal hormonal milieu during development. For example, ethinyl...

Sources and medical uses of folliclestimulating hormone luteinizing hormone and human chorionic gonadotrophin

Although the human pituitary is the obvious source of human gonadotrophins, it also constitutes an impractical source of medically useful quantities of these hormones. However, the urine of post-menopausal women does contain both FSH and LH activity. Up until relatively recently, this has served as the major source used medically, particularly of FSH. Menotrophin (human menopausal gonadotrophin) is the name given to FSH-enriched extracts from human urine. Such preparations contain variable levels of LH activity, as well as various other proteins normally present in urine. As much as 2.5 l of urine may be required to produce one dose (75 IU, 7.5 mg) of human FSH (hFSH).

Relation Between Sleep Apnea and Insomnia

Looking at the reverse picture, what is the prevalence of SDB in insomnia patients Research shows that these numbers are similarly high. Guilleminault et al. (37) documented SDB in 83 of 394 postmenopausal women complaining of chronic insomnia using PSG studies with pressure transducer and esophageal manometry. The SDB was classified mainly in the low AHI range. Similarly, Lichstein et al. (38) reported sleep apnea in 29 to 43 of a recruited sample of older individuals with

Prostaglandin H Synthases1 and 2 in ECs

Although PGHS-1 is expressed constitutively by a number of EC types, its expression is also controlled by transcriptional regulation. For example, upregulation of PGI2 synthesis in intrapulmonary vessels rises markedly during late fetal life, because of a developmental increase in PGHS-1 expression that occurs via estrogen stimulation of the estrogen receptor. This may also have implications for PGHS-1 expression in pre- and postmenopausal women where risk of vascular disease increases with decreased estrogen levels, and estrogen replacement is associated with decreased cardiovascular risk.

Use of Inhibitors of Sex Steroid Synthesis

Anastrozole, and exemestane, work best in postmenopausal women (Brodie and Njar, 2000 Arora and Potter, 2004). Furthermore, formestane and exam-estane have been shown to be effective in breast cancer patients with advanced disease (Brodie and Njar, 2000 Arora and Potter, 2004). A number of other inhibitors such as 7a-substituted androstenediones evaluated clinically are exemestane, atemestane, and 10-propagylandrostenedione (Brodie and Njar, 2000 Arora and Potter, 2004).Although both atemestane and 10-propagylandrostenedione are potent aromatase inhibitors and highly effective in lowering estrogen levels in breast cancer patients, only exemestane currently remains an available treatment option.

Effects of mediumchain triglycerides on energy expenditure

Consequently, longer studies to assess the impact of MCT on EE were undertaken. White et al. (1999), fed 12 non-obese, premenopausal women a diet containing 40 of energy as fat, either in the form of butter and coconut oil or beef tallow, over 14 days. On day 7, mean BMR and PP EE values were significantly greater with the MCT diet than with the LCT diet. On day 14, PP total EE was still greater with the MCT diet, but not

Case Study IV Tamoxifen and Breast Cancer

Overall, this trial showed that tamoxifen use was associated with fewer ER+ breast cancers in pre- and postmenopausal women with a high-risk profile.61 However, there is a cautionary note for sexually active premenopausal women taking tamoxifen, because tamoxifen was initially developed as a fertility drug.65 Also, results from the Breast Cancer Prevention Trial showed that tamoxifen does not increase the risk of other cancers (besides endometrial), but may increase the risk of cataracts. Similar findings to the Breast Cancer Prevention Trial have appeared in other trials (Table 23.4), such as the Italian Randomized Trial of Tamoxifen and The International Breast Cancer Intervention Study 1.66'67 Preliminary analysis of the Italian study revealed no difference between the tamoxifen and placebo groups68 however, by the end of the trial, women in the tamoxifen arm did have a lower risk of breast cancer.66 On the other hand, the Royal Marsden Hospital Tamoxifen Chemoprevention trial...

Estrogen and Lupus Human and Animal Studies

Tion of these immune complexes triggers inflammation, culminating in widespread tissue damage (Abdou et al., 1981). Gender is a strong risk factor for SLE since this disease primarily affects women in the reproductive years and the female-to-male susceptibility ratio can be as high as 13 1 (Rider and Abdou, 2001). SLE has been associated with situations where levels of gonadal hormones are changing such as during pregnancy, postpartum period, menopause, and during estrogen administration. The first onset of the disease is unlikely to occur before puberty or after menopause. Pregnancy has been associated with flares of lupus (Wilder, 1998). SLE disease activity fluctuates with the menstrual cycle (Bruce and Laskin, 1997) and lessens after menopause (Mok et al., 1999). The flares of lupus have been reported to increase during in vitro fertilization when levels of female hormones, particularly estrogen, are clinically manipulated (Guballa et al., 2000). Further, although not unequivocal,...

Mammographic Density and Breast Cancer

Epithelium and stromal tissues that are strongly related to risk of breast cancer appear radiologically dense, whereas fat appears radiologically lucent.93 The proportion of the mammographic image occupied by radiologically dense tissue is a composite measure of breast tissue composition. At present, the role of mammographic density in breast cancer etiology is not clear.94 However, it has been established that mammographic density is an independent predictor of breast cancer risk, with associated relative risks between 4 and 6 for the highest vs. the lowest quartile of mammographic density. Evidence suggests that the magnitude of the increase in breast cancer risk is greater than that associated with nearly all other breast cancer risk factors after adjustment for age, body mass index (BMI), age at menarche, breast cancer family history, parity, menopausal status, and HRT use.93,95

Supplemental Reading

Treatment of postmenopausal osteoporosis. N Engl J Med 1998 338 736-746. Neer RM et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in post-menopausal women with osteoporosis. N Engl J Med 2001 344 1434-1441. Nelson HD et al. Postmenopausal hormone replacement therapy Scientific review. JAMA 2002 288 872-881.

Indian Girl Ka 664266

Bostick RM, Kushi LH, Wu Y, Meyer KA, Sellars TA, and Folsom AR. Relation of calcium, vitamin D, and dairy food intake to ischaemic heart disease mortality among postmenopausal women. Am J Epidemiol 1999 149 151-61. Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, and Bostick RM. Dietary antioxidant vitamins and death from coronary heart disease in post-menopausal women. New Engl J Med 1996 334 1156-62.

Mechanisms Underlying Low Grade Inflammation During Aging

A second potential mechanism resides in endocrine changes during aging. In aging, dysregulation of secretion of hormones that come under the regulation of the HPA axis may occur. This may have impact on the regulation of cortisol secretion. Cortisol is important as an anti-inflammatory agent. The effect of aging on glucocorticoid (GC) sensitivity of pro-inflammatory cytokine production was examined in elderly men, testosterone-treated elderly men, and young controls. Stress-induced increases in cortisol did not differ significantly between experimental groups, but GC sensitivity increased significantly in young controls and testosterone-treated elderly men, whereas a decrease was found in untreated elderly men. As the increase in GC sensitivity after stress serves to protect the individual from detrimental increases of pro-inflammatory cytokines, the disturbed mechanism in elderly men may result in enhancement of inflammation. The decrease in sensitivity is linked to decreased...

The Molecular Basis Of The Tissue Specificity Of Brca1associated Tumors

In addition to dysregulated transcriptional activity of ERa, prolonged estrogen exposure is also a well-documented risk factor for breast cancer (68, 74-78). Ovaries, specifically ovarian granulosa cells, are the primary source of estrogen in premenopausal women. This explains why early menarche and late menopause are associated with increased risks of breast cancer (79). Aromatase (Cyp19) is expressed in a restricted number of steroidogenic tissues including ovaries. The enzyme catalyzes the conversion from androgen to estrogen, the rate-limiting step in estrogen biosynthesis (80). Recently published work from our laboratories suggests that expression of BRCA1 in ovarian granulosa cells is inversely correlated with that of aromatase during steroidogenesis (81). Importantly, small interfering RNA (siRNA)-mediated knockdown of BRCA1 or its partner BARD1 resulted in elevated aromatase expression and its enzymatic activity in ovarian granulosa cells (81). In an independent study, Dubeau...

Pharmacologic Therapy Of Obstructive Sleep Apnea Drugs that Increase Respiratory Drive See Also Chapter

The prevalence of sleep apnea increases after menopause, suggesting that female hormones may play a protective effect on sleep-disordered breathing (83). Medroxyprogesterone (Cycrin , Provera ) is a respiratory stimulant and has been used to treat OSA by increasing central neural drive to the pharyngeal muscles. Strohl et al. (84) demonstrated improvement in 4 9 patients with OSA in an uncontrolled study of note, three of the four subjects who improved were hypercapnic suggesting that they may have had an element of obesity-hypoventilation syndrome in addition to OSA. Subsequent studies, however, have not been as impressive, with mild to no improvement of OSA after treatment with progesterone (85,86), even in postmenopausal women (87). Furthermore, the combined use of estrogen and progesterone does not appear to be effective (88).

Reproductive Endocrine Function Ovarian Dysfunction

Alkylator therapy (e.g., busulfan, melphalan, or thiotepa) are at particularly high risk of developing ovarian failure (Thibaud et al. 1998 Sklar 1999). Furthermore, even if female patients recover ovarian function after treatment is completed, a significant proportion of these patients are at risk of experiencing premature menopause in the future (Byrne et al. 1992). Radiation-induced ovarian failure is also common in female cancer survivors. As with chemotherapy, pre-pubertal ovaries seem to be more resistant to damage from irradiation than post-pubertal ovaries. Radiation doses above 1000-2000 cGy can, however, cause irreversible ovarian damage in young girls (Stillman et al. 1981 Wallace et al. 1989a) therefore, young females who receive abdominal, pelvic, or spinal irradiation for tumors such as neuroblastoma have a high risk of ovarian failure (Shalet et al. 1976 Stillman et al. 1981 Wallace et al. 1989a Wallace et al. 1989b). Moreover, we can extrapolate that the concomitant...

On Adult Presentations

Diminishes with time, however, and both sexes achieve a similar incidence by age 50 (43). A study of OSA incidence and its risk factors found the risk for sleep apnea in men increased only marginally with age, while it increased very significantly in women the OR (confidence interval) for increased AHI per 10-year increase was 2.41 in women (1.78-3.26) and only 1.15 (0.78-1.68) in men (43). A study of Hong Kong women found a 12-fold rise in the prevalence of sleep apnea in women between the fourth and sixth decades (31). There is a large amount of literature to support the role of menopause in modulating this increased risk for sleep apnea in women around the age of 50 (44-46). In general, men and women are present with the same constellation of sleep-related symptoms and complications (47). Women with OSA may be slightly older, more obese, more likely to use sedatives, and complain of insomnia and depression (48).

Tumors of the Lacrimal

Epidemiology Keratoconjunctivitis sicca as a result of dry eyes is one of the most common eye problems between the ages of 40 and 50. As a result of hormonal changes in menopause, women are far more frequently affected (86 ) than men. There are also indications that keratoconjunctivitis sicca is more prevalent in regions with higher levels of environmental pollution.

Testicle Shrinkage Treatment

Very Small Testicular Size

If you are approaching menopause, discuss your options for hormone replacement therapy (HRT). Menopausal symptoms, your potential for developing osteoporosis, and your risk for developing cardiovascular disease should be part of this discussion.

Ablation of endocrine glands

In men and premenopausal women the major sites of steroid hormone synthesis are the gonads. Castration decreases circulating testosterone in males by over 95 and oestrogens in premenopausal women by 60 (relative to follicular phase levels).These endocrine effects produce benefits in about 80 of men with metastatic prostate cancer and in 30-40 of unselected premenopausal women with advanced breast cancer. Oophorectomy is rarely beneficial in postmenopausal women because the postmenopausal ovary produces little oestrogen. These response rates represent the gold standard against which to compare other forms of endocrine therapy. Hypophysectomy and adrenalectomy have been used in postmenopausal women with breast cancer. Whilst these may produce benefit in about one-third of cases, the procedures do have significant morbidity and lack specificity, removing other classes of hormones in addition to sex steroids. The irreversible nature of surgical ablation of endocrine organs, when all...

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