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. Read more here...

Womens Midlife Revolution Summit Summary


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Alternative Therapies to Hormone Replacement Therapy

SERMs are nonsteroidal estrogenic compounds with both estrogenic agonist (on bone and lipoproteins) and estrogenic-antagonist (on breast and endometrium) effects in use for the treatment of osteoporosis. Although SERMs have shown beneficial effects on some surrogate markers of CVD it is not known whether this will translate into clinical benefit. The recent secondary analysis of the osteoporosis prevention study, the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, suggested that there were no significant differences between raloxifene and placebo group regarding combined CHD and CVD events. Interestingly, however, in the subset with increased cardiovascular risk, the raloxifene group had a significantly lower risk of CVD events compared with placebo (99). The Raloxifene Use for the Heart Studyis currently testing the impact of raloxifene on cardiovascular endpoints in postmenopausal women. The results of this trial will provide information on the net clinical cardiovascular...

Effects of HRT on Endothelial Function in Postmenopausal Women With Diabetes

Endothelial dysfunction is the hallmark of diabetes and is regarded as an early manifestation of atherogenesis. In postmenopausal women with diabetes, multiple pathophysiological processes may contribute to endothelial dysfunction. These are diabetes- related, as a result of hyperglycemia and obesity insulin resistance and menopause-related as a result of loss of the protective effect of estrogen, as discussed earlier. Despite the importance of the endothelium, there is limited data on the effects of HRT on endothelial dysfunction in postmenopausal women with diabetes. In a recent study comparing healthy and diabetic postmenopausal women, Lim and associates (109) found that, although cutaneous vasodilation was impaired in postmenopausal women, it was able to be improved by HRT in nondiabetic subjects, but the improvement was less apparent in the diabetic cohort. However, the use of HRT in women with diabetes was associated with lower soluble ICAM levels, suggesting an attenuation in...

The ageing female reproductive axis II ovulatory changes with perimenopause

Perimenopause, a complex physiological transition for midlife women, begins with changes in experiences many years before cycles become irregular, oestradiol levels decrease or follicle-stimulating hormone levels increase. Erratic and average higher oestradiol levels as well as shorter luteal phase lengths and lower progesterone levels occur during perimenopause. These ovarian changes may be causally related to lower inhibin production but the dynamic prospective inter-relationships within women are not well documented. This review will first define perimenopause and then explore the limited published data on ovulatory characteristics in perimenopause. In addition, it will report preliminary prospective observational data on menstrual cycles and ovulation in initially ovulatory women followed through the perimenopause. Prospective data suggest that ovulation disturbances begin early in perimenopause and increase with irregular cycles. Combined with higher oestradiol levels...

Menopause demographics

Two hundred years ago only 30 of women lived through a menopause now, more than 90 will. Thus, the menopause transition and postmenopause is very much a condition of the 20th and 21st centuries. Life expectancy is now 82 years of age for a woman living in the UK. The majority of women can therefore expect to live over a third of their lives in a menopausal state (Fig. 47.1). Unfortunately, many of these postmenopausal women will have a progressively declining quality of life. Optimization of menopause health care should produce a rect-angularization of society where postmenopausal women remain at the peak of health.

Menopausal Ovarian Failure

Menopause results from what might be considered a preprogrammed failure of ovarian function and is due to the gradual depletion of ovarian follicles. Although this process actually begins in utero, physiologic estrogen secretory patterns are maintained in most women until somewhere between 40 and 60 yr of age. The first symptom of menopause is often vasomotor instability (hot flashes, warm flushes). These may begin after an interval of amenorrhea but usually surface earlier in the presence of irregular or even seemingly normal menstrual function. In most cases these episodes pass within 1-2 yr, but in a significant number of patients they may last for decades or disappear only to reappear years later. Although hot flashes are frequently considered a minor nuisance that will eventually pass, they may interfere significantly with normal REM sleep, thereby creating a state of relative sleep deprivation. Estrogen replacement therapy (ERT) represents the most effective approach to...

Menopause physiology

The menopause, from the Greek 'Menos' (month) and 'Pausis' (cessation) is defined as the last menstrual period. The diagnosis can only be made retrospectively after Age of menopause a minimum of 1 year's amenorrhoea. Although the menopause occurs at an average age of 51, the physiological changes which result in the final menstrual period (FMP) can start 10 years prior to this. Hormonal changes continue long after the FMP. This episode of dynamic neuroendocrine change is characterized by 'the climacteric' from the Greek 'Klimax' ladder, that is, the climb to the menopause. It may be associated with distressing clinical problems such as reduced fertility, menstrual irregularity and vasomotor symptoms. The intermediate sequelae of these changes are typically seen in the skin and urogenital tract and in the long term, in skeletal and cardiovascular pathology.


The urogenital tract and lower urinary tract are sensitive to the effects of oestrogen and progesterone throughout adult life. Epidemiological studies have implicated oestrogen deficiency in the aetiology of lower urinary tract symptoms occurring following the menopause with 70 of women relating the onset of urinary incontinence to their final menstrual period. Lower urinary tract symptoms have been shown to be common in postmenopausal women attending a menopause clinic with 20 complaining of severe urgency and almost 50 complaining of stress incontinence. Urge incontinence in particular is more prevalent following the menopause and the prevalence would appear to rise with increasing years of oestrogen deficiency. Some studies have shown a peak incidence in perimenopausal women whilst other evidence suggests that many women develop incontinence at least 10 years prior to the cessation of menstruation with significantly more premenopausal women than postmenopausal women being affected.

Contemporary Endocrinology

Thorner, 2000 Hormones and the Heart in Health and Disease, edited by Leonard Share, 1999 Menopause Endocrinology and Management, edited by David B. Seifer and Elizabeth A. Kennard, 1999 Emile Baulieu, Michael Schumacher, and Paul Robel, 1999 Autoimmune Endocrinopathies, edited by Robert Volp , 1999 Hormone Resistance Syndromes, edited by J. Larry Jameson, 1999 Hormone Replacement Therapy, edited by A. Wayne Meikle, 1999 Insulin Resistance The Metabolic Syndrome X, edited by Gerald M. Reaven and Ami Laws, 1999 Endocrinology of Breast Cancer, edited by Andrea Manni, 1999 Molecular and Cellular Pediatric Endocrinology, edited by Stuart Handwerger, 1999 Gastrointestinal Endocrinology, edited by George H. Greeley, Jr., 1999 The Endocrinology of Pregnancy, edited by Fuller W. Bazer, 1998 Clinical Management of Diabetic Neuropathy, edited by Aristidis Veves, 1998 G Proteins, Receptors, and Disease, edited by Allen M. Spiegel, 1998 Natriuretic Peptides in Health and Disease,...

Endocrinology of ageing

In men, several hormonal systems show a gradual decline in activity during ageing, represented by a decrease in their bioactive hormone concentrations. The 'andropause' is characterized by a gradual decline in serum total and bioavailable testosterone, due to a decrease in testicular Leydig cell numbers and in their secretory capacity, as well as by an age-related decrease in episodic and stimulated gonadotropin secretion (Vermeulen 1991). Both cross-sectional (Vermeulen 1991) and longitudinal (Morley et al 1997) studies have shown that in healthy males mean serum total testosterone (T) levels decrease by about 30 between age 25 and 75, whereas mean serum free T levels decrease by as much as 50 over the same period. The steeper decline of free T levels is explained by an age-associated increase in sexhormone binding globulin (SHBG) binding capacity (Vermeulen & Verdonck 1972). Conflicting results have been reported concerning the question of whether luteinizing hormone (LH)...

Estrogen Is Required For Breast Development And Tumorigenesis

In terms of biological activity, the most important circulating estrogen in women is estradiol (E2). From the advent of menarche until the menopause, E2 is synthesized and secreted in a cyclical manner by the ovaries under the control of the pituitary gonadotro-phins. The clinical and epidemiological evidence for an obligate role of estrogen in human mammary gland development and tumor formation is considerable. Observation of girls with estrogen deficiency through, e.g., gonadal dysgenesis or gonadotrophin deficiency, demonstrates that the steroid is strictly necessary (although probably not sufficient) for pubertal breast development (5). The incidence of BC in men is 1 of the incidence in women. Reducing exposure of the mammary gland to the fluctuating E2 levels of the menstrual cycle, through an early natural or artificially induced menopause, substantially lowers the risk of developing BC. Conversely, increasing exposure through early menarche, late menopause, or late age at...

Clinical consequences of the decline in activity of the hormonal systems

Andropause In most women, the period of decline in oestrogens during menopause is accompanied by vasomotor reactions, depressed mood, and changes in skin and body composition (increase in body fat and decrease in muscle mass). In the subsequent years, the loss of oestrogen is followed by a high incidence of cardiovascular disease, loss of bone mass and cognitive impairment (Lindsay et al 1996). Only recently has it become evident that oestrogens may not only play an important role in regulating bone turnover in women, but also in men. Smith et al (1994) described a male with a homozygous mutation in the oestradiol receptor gene who, even in the presence of normal T levels, had unfused epiphysis and marked osteopenia, along with elevated indexes of bone turnover. A few studies now have demonstrated significant relations between serum (bioavailable) oestradiol levels and bone mineral density in elderly men (Khosla et al 1998).

Life Span and the Aging Process

The aging process causes many changes, both visible and invisible. In humans, these changes take several forms. In the first two decades of life, from birth to adulthood, aging involves physical growth and maturation and intellectual development. These changes are fairly noticeable and relatively swift compared to the rest of the life span. After reaching physical maturity, humans begin to show subtle signs of physical aging that grow more pronounced over time. Long-term exposure to sunlight and the outdoors may begin to toughen the skin and produce wrinkles on the face and body. The senses change Sight, hearing, taste, and smell become less acute. Gradual changes in the eye cause many older adults to need glasses to read. Hair begins to thin and turn gray. Individuals with less active lifestyles often begin to gain weight, particularly around the waist and hips. Beginning in their 40s (or, rarely, in their late 30s), many women experience menopause, which marks the end of...

Ageing stress and the brain

In 1988 Joseph Meites described a neuroregulatory theory of ageing, emphasizing the integrative role of the nervous system for neuroendocrine axes and circadian rhythms (Meites 1988). As the brain aged, Meites proposed, so would the hypothalamus age, leading to menopause, andropause, somatopause and dysregulated circadian rhythms. Meites tested pharmacological strategies to augment hypothalamic neurotransmitter function, which he found could reverse these 'biomarkers of ageing', a result that comports with the age-associated decline of hypothalamic monoamine neurotransmitter systems (Rodriguez-Gomez et al 1995). Though it can be modified by recent insights, the general perspective of Meites that we endocrinologists are also neuroscientists remains valid. Ageing of the brain is an important factor in overall ageing and mortality.

Goals Of Clinical Trials

The objective of this study is to evaluate the efficacy and safety of the test drug under investigation with a placebo in the treatment of postmenopausal women with osteoporosis. investigation at dose y, frequency z, compared to a placebo, in the treatment of post-menopausal women with osteoporosis. 2. This trial is a randomized, double-blind, placebo-controlled trial conducted in x centers to evaluate the safety of the test drug under investigation at dose y, frequency z, compared to a placebo, in the treatment of postmenopausal women with osteoporosis.

Folate Deficiency And Chromosome Instability

Folate and or B12 deficiency in humans has been long associated with chromosomal instability and multiple chromosomal aberrations. Early cytogenetic studies of folate- or B12-deficient human lymphocytes or marrow cells revealed multiple chromosomal breaks and gaps, decondensed chromosomes, premature centromeric division, and centromeric spreading (31,32). Chronic folate deficiency is manifested in a futile cycle of uracil misincorporation during DNA replication and repair (5,6,12,33). Uracil misincorporation stems from a block in the folate-dependent methylation of dUTP to dTTP, resulting in the misinsertion of uracil in place of thymine (5,34). The misincorporation of uracil for thymine per se is not a premutagenic lesion because the DNA polymerase will insert the correct adenine base opposite either thymine or uracil (5,35). However, the presence of an active uracil glycosylase leads to site-specific abasic sites and single-strand breaks that represent significant premutagenic...

Clinical cancer genetic management

Careful annual physical examination of the thyroid and neck region, beginning at age 18 or 5 years younger than the earliest diagnosis ofthyroid cancer in the family (whichever is earlier), should be sufficient although a single baseline thyroid ultrasound in the early twenties might be considered as well. Surveillance for endometrial carcinoma (see Chapter 14) is recommended, perhaps beginning at the age of 35-40 years (no data for age at onset) or 5 years younger than the earliest onset case in the family. For premenopausal women, annual blind repel (suction) biopsies of the endometrium should be performed. In the postmenopausal years, uterine ultrasound should suffice.

Pr And The Normal Mammary Gland

PR can be detected in ECs of the breast at all stages of the menstrual cycle (40,43-45), and there is no evidence in the human that its levels change in the fluctuating hormonal environment of the cycle, despite the unequivocal evidence, derived from other target tissues, that PR expression is under hormonal control (11). The number of PR-positive cells in the breast must be subject to some degree of hormonal regulation, however In premenopausal women, PR is the predominant receptor, found in 12-29 of ECs, compared with ER, which is found in 4-10 of cells (45-47). Yet, in the relatively hormone-impoverished circumstance of postmenopause, ER expression is increased in the normal breast, and few cells are PR-positive (46). and is unchanged during the hormonal fluctuations in the ovarian cycle, but PR levels in the gland decrease upon functional differentiation of the mammary gland, during pregnancy, lactation, and after the menopause. P plays a role in mammary gland function and...

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Disease, suggesting that the dose-response curve would be steeper in the adjuvant (or early-stage) setting than in the metastatic setting. This appeared to be true for the CMF regimen in breast cancer treatment, but results differed for pre- and postmenopausal women (Hortobagyi 2000, p. 588).

Gender Ethnicracial And Life Span Considerations

Because early cervical cancer is usually asymptomatic, establish a thorough history with particular attention to the presence of the risk factors and the woman's menstrual history. Establish a history of later symptoms of cervical cancer, including abnormal bleeding or spotting (between periods or after menopause) metrorrhagia (bleeding between normal menstrual periods) or menorrhagia (increased amount and duration of menstrual bleeding) dysparuenia and postcoital bleeding leukorrhea in increasing amounts and changing over time from watery to dark and foul and a history of chronic cervical infections. Determine if the patient has experienced weight gain or loss abdominal or pelvic pain, often unilateral, radiating to the buttocks and legs or other symptoms associated with neoplasms, such as fatigue.

Evidence From In Vivo Studies With Humans

A folic acid depletion repletion study (baseline 195 g d depletion 5 wk 65 g d repletion 4 wk 111 g d followed by 20 d of > 280 g d) of nine postmenopausal women in a metabolic unit showed a significant increase in micronucleus frequency in lymphocytes following depletion and a decrease following repletion micronucleus frequency in buccal cells decreased after the repletion phase (27). The depletion phase in this study also resulted in increased DNA hypomethylation, increased dUTP dTTP ratio, and lowered NAD levels in lymphocytes (28). Other studies have shown that global DNA methylation in lymphocytes or colonic tissue is influenced by the extent of folate intake. The depletion-repletion study performed by Jacob et al. (28) with postmenopausal women in a metabolic unit showed more than a 100 increase in DNA hypomethylation after 9 wk on low-folate diet (56-111 g d) and a subse

Epidemiologic Studies

Data from epidemiologic studies, clinical trials, and in vitro studies of BC cell lines all provide support of the hypothesis that ER-negative cancers can arise from ER-positive cells. A vast amount of data from these epidemiologic studies suggest that the most important risk factor for BC development is the cumulative exposure to estrogen and possibly also P hormones (52). Such studies demonstrate that BC risk is increased with early menarche (53-56), late menopause (57,58), obesity in postmenopausal women (59, 60), hormone replacement therapy (meta-analysis performed in refs. 61-63), all of which lead to increased exposure to estrogen or progesterone. In addition, studies have shown that factors that decrease exposure to estrogen or progesterone reduce BC risk. Well-established factors associated with reduced incidence of BC include early first-term pregnancy (64), lactation (65,66), and increased physical activity (67,68). In addition, premenopausal women who have had bilateral...

System Reconstructive Procedures

The primary cause of cystoceles and rectoceles is a weakened vaginal wall. Factors that contribute to this loss of pelvic muscle tone are repeated pregnancies, especially those spaced close together, congenital weaknesses, and unrepaired childbirth lacerations. Obesity, advanced age, chronic cough, constipation, forceps deliveries, and occupations that involve much standing and lifting are also contributing factors. Lack of estrogen after menopause frequently aggravates the condition.

Familial ovarian cancer

Ovarian cancer is the fifth most common cancer in women (excluding skin) in the USA and UK. Since the prognosis of this neoplasm is largely determined by the stage of the disease at presentation, and approximately 80 of cases have spread beyond the ovary when first diagnosed, ovarian cancer accounts for a disproportionate number of deaths compared with other cancers of the female genital tract. A family history of ovarian cancer confers the highest known risk factor for developing the disease. Other risk factors include gonadal dysgenesis (Szamborski et al., 1981), early menarche and late menopause, whereas reducing the number of ovulation events either by use of an oral contraceptive or through pregnancy reduces the risk of ovarian cancer. The oral contraceptive pill appears to offer protection against the risk of developing both sporadic and familial cancer and continues to provide protection for some years after the contraceptive has been terminated (Anonymous, 1987).

Different basis for risk prediction

Menstrual and reproductive history, such as early age at menarche, late age at menopause, nulliparity or late age at first birth, as well as family history of breast cancer and history of benign breast disease, have been shown in epidemiological studies to increase the risk of breast cancer in women relative to those without these characteristics. Risk prediction models accounting for some of these factors have been developed. The Gail model was based on data from the Breast Cancer Detection and Demonstration Project - a large mammographic screening programme conducted in the 1970s (Gail et al., 1989). Risk factors accounted for included age at menarche (> 14, 12-13, < 12 years), number of breast biopsies and woman's age (0, 1, > 2 biopsies at < 50 or > 50 years), number of first-degree relatives with breast cancer (0, 1 or > 2) and woman's age at first live birth (< 20, 20-24, 25-29, > 30 years, or nulliparous). The calculation of breast cancer risk with the Gail...

Peroxisome Proliferator Activated Receptory Key Regulator of Adipogenesis and Insulin Sensitivity

PPAR-y was first identified as a part of a transcriptional complex essential for the differentiation of adipocytes, a cell type in which PPAR-y is highly expressed and critically involved (6). Homozygous PPAR-y-deficient animals die at about day 10 in utero as a result of various abnormalities including cardiac malformations and absent white fat (7-9). PPAR-y is also involved in lipid metabolism, with target genes such as human menopausal gonadotropin coenzyme A synthetase and apolipoprotein (apo)-A-I (10,11). Chemical screening and subsequent studies led to the serendipitous discovery that thiazolidinediones (TZDs) were insulin sensitizers that lower glucose by binding to PPAR-y. Used clinically as antidiabetic agents, the TZD class includes pioglitazone (Actos) and rosiglitazone (formerly BRL49653, now Avandia) (12,13). Troglitazone (ReZulin) was withdrawn from the market because of idiosyncratic liver failure. Naturally occurring PPAR-y ligands have been proposed, although with...

Analytical strategies

The groups can be defined on time, such as the summer college class of freshmen, or defined on specific requirements (e.g., fire fighters or workers, menopausal women, retired men aged 50 to 55). Thus, people are enrolled into a cohort and baseline data are collected on factors of interest to the study, such as their lifestyle and exposure to the substance. The range of people enlisted in prospective studies can be from 100 to 100,000, and as time passes, some individuals will develop the disease of interest.

Attenuate activity of the GHRP pathway in older men

GHRP2 is the most effective GHRP-receptor agonist available for investigational use in the human. GHRP2 synergizes with GHRH in stimulating GH secretion in healthy men (Fig. 4), and enhances oestradiol's drive of GH secretion in postmenopausal women (Evans et al 2000, Shah et al 1998a,b, 1999c, 2000). Other clinical studies show that GHRPs exert maximal acute stimulatory effects in mid-to-late puberty when sex-steroid hormone concentrations peak. Moreover, a single i.m. injection of testosterone in boys and brief oestrogen exposure in girls double GH stimulation by a near-maximally effective dose of the GHRP, hexarelin (Loche et al 1997). Thus, sex steroids may modulate GHRP-receptor effector activity in the human, as inferred recently in the postnatal rat and GH-transgenic mouse. Indeed, the promoter of the human GHRP-receptor gene contains a hemioestrogen-responsive element. Thus, we postulate that testosterone could act either pre- or...

The Ambivalent Commitment of Medicine to the Gold Standard

Ambivalence among many oncologists must be counted among the difficulties of organizing randomized trials. Belief in the value of trials may conflict with belief in the value of a treatment outside a trial. In 1991, Belanger et al. reported on a survey of 230 oncologists about the impact of clinical trials on their preferred methods of treating breast cancer. They found that preferred treatments for primary breast cancer and inflammatory breast cancer were supported by clinical trials that adjuvant chemotherapy for node-negative breast cancer was not based on consistent improvement in survival and that adjuvant chemotherapy for postmenopausal women with node-positive breast cancer was contrary to results from large randomized clinical trials. They suggested that even large randomized clinical trials may have a minimal impact on practice if their results run counter to belief in the value of the treatment (p. 7).

Distinctions in the actions of androgen and oestrogen on the GHIGF1 axis

The neuroendocrine mechanisms by which testosterone governs pulsatile GH secretion in the human have remained elusive, in part because of species differences in the nature of androgenic control of the GH IGF1 axis and in part due to the tripeptidyl control of this specialized axis (Giustina & Veldhuis 1998). Moreover, known actions of oestrogen are not necessarily equivalent to those postulated for testosterone. Notably, in clinical studies testosterone, but not oestradiol, consistently stimulates both GH and IGF1 production and elevates (non-pulsatile) GH secretion (Bellantoni et al 1991, Devesa et al 1991, Giustina & Veldhuis 1998, Karlsson et al 1990, Shah et al 1999b, van Kesteren et al 1996, Blumenfeld et al 1992, De Leo et al 1993). Thus, for example, the putative neuroendocrine mechanism of oestrogen's unleashing of GH secretion in postmenopausal women by way of reduced systemic IGF1 feedback cannot be facilely invoked to explicate testosterone's combined stimulation of...

Pharmacologic Highlights

Bile acid sequestrant resins (cholestyramine, colestopol) nicotinic acid (niacin) 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins such as levostatin, pravastatin, simvastatin, flu-vastatin, atorvastatin) estrogen in postmenopausal women Nicotinic acid (niacin), estrogen in postmenopausal women

Sources of Estrogens in Women

The estrogen compounds to which target tissues in women, including the vascular system, may be exposed are multiple and they arise from endogenous and exogenous sources. The naturally occuring estrogens 17 -estradiol (E2), estrose (E1), and estriol (E2) are C18 steroids and are derived from cholesterol in steroidogenic cells. In the premenopausal women, the primary source of estrogens are the ovaries. E1 and E3 are primarily formed in the liver from E2 (10). After menarche, when circulating E2 levels increase and begin to cycle, levels range from 10 to 80 pg mL during the follicular phase to 600 pg mL at midcycle. Following ovulation, progesterone is secreted from the luteinized cells during the luteal phase of the cycle. Progesterone has two main functions in the body, namely, transformation of the endometrium after estrogen priming (luteomimetic effect) and opposition to estrogen (anti-estrogenic effect), limiting proliferation of the endometrium. After menopause, estrogen...

Gonadotropins Follistim GonalF Bravelle [FSH and Repronex Menopur [FSH and LH

The other category is called urinary-based gonadotropins because these medications are made from the purified urine of menopausal women. Urinary-based gonadotropins fall into two types. The first type is almost as pure as the recombinant FSH and is sold under the brand name of Bravelle. The second type comprises nearly equal parts of FSH and LH. Brand-name examples of this type of gonadotro-pin are Repronex and Menopur. Some doctors prefer the pure FSH product, whereas others believe that LH helps the ovulation process.

Effects of Estrogen on Endothelial Function

The onset of menopause provides a natural model of estrogen deprivation in which the effects of the endogenous hormone on vascular function can be evaluated. In studies of changes in branchial artery diameter after reactive hyperemia, responses were greater in premenopausal than in postmenopausal women (31). Importantly, blood-flow responses to the NO donor glyceryl trinitrate (GTN) were similar in the two groups, indicating comparable vascular smooth muscle responses to NO. The responses in postmenopausal women were comparable to those observed in men (31). In agreement with these findings, sex hormone deprivation after ovariectomy or premature ovarian failure, is associated with a decline in endothelial-dependent vasodilation, whereas the response to GTN is unaltered (32,33). Another natural model of changes in estrogen levels is the menstrual cycle. In young women, endothelium-dependent vasodilation in the branchial artery paralleled serum estradiol levels, and furthermore, there...

Effects of Estrogen on Hemostatic Factors

Hepatic expression of the genes for several coagulation and fibrinolytic proteins are regulated by estogen through ERs (18). Elevated levels of fibrinogen, von Willebrand factor, and factor VII are thought to be important risk markers for ischemic heart disease. These factors have been reported to be increased in postmenopausal women (51). Use of HRT in postmenopausal women has been shown to decrease fibrinogen levels but also to decrease plasma concentration of the anticoagulant protein anti-thrombin III and protein S, and to increase factor VII activity (52). On the other hand, reduced fibrinolytic activity is associated with atherosclerosis and has been attributed to increased levels of the antifibrinolytic factor plasminogen activator inhibitor-1 (PAI-1) (53). Increased PAI-1 levels have been found in postmenopausal women, and a close relationship between low fibrinolytic activity, high PAI-1 and hyperinsulinemia has been observed in various populations (54). Even small doses of...

Effects of Estrogen on Lipids and Lipoproteins

Estradiol at plysiological levels has an antioxidant capacity that is independent of its effects on serum lipid concentrations. Thus, administration of 17 -estradiol in postmenopausal women can decrease the oxidation of LDL cholesterol, which could enhance endothelial NO bioactivity (62). This antioxidant effect may be as a result of ER-mediated changes in the expression of genes for enzymes that regulate the local production and degradation of superoxide. Recent evidence suggests that remnant lipoprotein particles (RLPs) are the most atherogenic particles among the triglyceride-rich lipoproteins. In particular, RLPs appear to be associated with impaired endothelial function and with severity of atherosclerosis and were identified as an independent risk factor for CVD in women (63). In this context, a recent randomized study demonstrates a favorable effect of HRT on lipoprotein remnant metabolism in postmenopausal women, without significantly affecting triglycerides (64).

Effects of Estrogen on Inflammatory Markers

Recent studies have indicated that oral estrogen therapy may increase levels of CRP in healthy postmenopausal women suggesting that estrogen may initiate or aggravate inflammation (67,68). In contrast, animal studies failed to demonstrate such proinflammatory effects of estrogen when given by subcutaneous implantation or injection (69). In this regard, a recent study in postmenopausal women showed that oral but not transdermal estrogen therapy increased CRP by a first pass hepatic effect (70). Additionally, although oral HRT may increase CRP it reduces other inflammatory markers including E-selectin vascular cell adhesion molecule-1, intercellular adhesion molecule (ICAM)-1, and soluble thrombomodulin (71), indicating that the increase in CRP after oral HRT may be related to metabolic hepatic activation and not to an increased inflammatory response. However, because CRP is a predictor of adverse cardiovascular prognosis and may be involved in the process of atherosclerosis, the route...

Anuja Dokras md phd and William I Sivitz md

PCOS affects 5-10 of premenopausal women (1). It is characterized by chronic anovulation and hyperandrogenism soon after puberty. Drs. Stein and Leventhal first described PCOS in 1935 in seven women with amenorrhea, hirsutism, and enlarged polycystic ovaries (2). These ovaries are classically associated with multiple 2-8-mm cysts in a peripheral location, as well as a hypervascular, androgen-secreting ovarian stroma that is typically increased in

Data From Randomized Clinical Trials

The first large clinical trial assessing HRT for secondary prevention in women with established coronary CHD was the Heart and Estrogen Progestin Replacement Study (HERS) (6). The HERS trial was a double-blind, placebo-controlled randomized study with combined continuous oral HRT (CEE 0.625 mg and medroxyprogesterone acetate MPA 2.5 mg daily) in almost 3000 postmenopausal women, mean age 66.7 years, with pre-existing CHD for more than 4.5 years. The study failed to demonstrate any overall differences in vascular events between the placebo and active treatment groups. There was an increase in the rate of coronary and thromboembolic events among HRT users in the first year of follow-up despite an improvement in lipid parameters. By the fourth year, the rate of vascular events in the HRT group was below that of the placebo group. However, recently published data from the extension of the HERS study to 6 years (HERS II) have shown that the trend toward reduction in cardiovascular events...

Monitoring Response to Treatment and Assessing Residual Disease

Monitoring chemotherapy response of breast cancer with DCE-MRI. 44-year old post-menopausal woman with a 4 cm, grade 3 invasive ductal cancer of the right breast with palpable ipsilateral axillary nodal enlargement. Rows depict T2-weighted anatomical images, early (100 seconds) subtraction images, transfer constant, relative blood volume (rBV) parametric images and relative signal intensity time curves (ROIs in whole tumour-green, normal tissue-red and fat-blue) at identical slice positions before and after two cycles of FEC (5-Fluorouracil, Epiru-bicin, Cyclophosphamide) chemotherapy. Transfer constant map (colour range 0-1 min-1) and relative blood volume (colour range 0-500 AU). With treatment, a reduction in the size of individual lesions is seen with a reduction in relative blood volume and transfer constant. This patient had a complete clinical and radiological response to treatment after 6 cycles of chemotherapy with pathology showing microscopic residual disease...

The State of the Vascular Endothelium

It appears that a woman's age and the number of years since menopause are potential factors modifying the influence of HRT on CHD. In this regard, in the Nurses' Health Cohort Study, the women ranged in age from 30 to 55 years at enrollment and almost 80 , commenced estrogen therapy within 2 years of menopause (5). In contrast, the mean age of participants was 63 years in the WHI and 67 years in HERS thus, these women had on average been postmenopausal for 10 years at the time of enrollment. In light of the above observations it is possible that HRT could be beneficial in younger women, before plaque complications set in, but may not inhibit progression from complicated plaques to coronary events in older women.

HRT and Genetic Factors

Thus the estrogen associated risk for thrombosis may be increased in the presence of the prothrombin 20210 G A variant, the factor V Leiden mutation or platelet antigen-2 polymorphisms (95-97). A common sequence variation of the ER gene is associated with the magnitude of the response of HDL cholesterol levels to HRT in women with coronary disease (19). The same ERP genotype is also related to changes in the levels of SHBG, another index of estrogen action (95). It is also interesting that in the HERS trial high levels of Lp(a), which is largely genetically determined, were an independent risk factor for CHD events in the placebo group. HRT lowered Lp(a) levels and the cardiovascular benefit of HRT was significantly related to the initial Lp(a) levels and the magnitude of the reduction in the level (98). It appears therefore, that genetic factors may also contribute to the net clinical effect of HRT regarding CVD in postmenopausal women.

Study Of Tam And Raloxifene Star

The STAR trial is a Phase III, double-blind trial that will assign eligible postmenopausal women to either daily TAM (20 mg orally) or raloxifene (60 mg orally) therapy for 5 yr. Trial participants will also complete a minimum of an additional 2 yr follow-up after therapy is stopped. The STAR trial's primary aim is to determine whether long-term therapy is effective in preventing the occurrence of invasive BC in postmenopausal women who are identified as being at high risk for the disease. Table 6 lists the eligibility criteria. The comparison will be made to the established drug, TAM. Its secondary aim is to establish the net effect of raloxifene therapy, by a comparsion of cardiovascular data, fracture data, and general toxicities, with TAM. It is clear that SERM is similar for TAM and ralaxifene, but the evaluation of the overall benefits of the agents will be an important new database on the new antiestrogen. The results from the STAR are anticipated by 2006. 1. Postmenopausal...

The Goal Of Prevention

Of antiestrogen use to hinder the development of primary disease. However, the issue will be critical over the next decade, because raloxifene is designed for indefinite use as a preventive for osteoporosis. It is only possible, at this point, to guess about the effectiveness of a long-term preventive strategy for postmenopausal women, because cardiovascular, bone, and cancer risks will all come into play for a woman's overall quality of life and, ultimately, longevity. Second, long durations of SERMs may be essential for true BC prevention during the promotion phase. The resolution of the competing effects of drug resistance and prevention can only be solved by large clinical trials or by an assessment of risk benefits of SERMs by a future generation of epidemiologists.

Population versus highrisk group screening

Screening before 50 years of age is controversial. Looking more closely at the effect of screening over the age of 50, the benefit seems to increase with age. In other words, screening with mammography seems effective after the menopause, but may have limited effect earlier. Moreover, the discussions on the effect of screening by mammography are statistical debates on whether or not it is beneficial to the group examined. Mammography every second year does not provide a guarantee against dying of breast cancer the individual women examined may not feel safe. When dealing with one young BRCA1-mutation-carrying woman, the issues surrounding her need for health are quite remote from the population-based cost benefit strategic thinking that underlies the screening programmes. Screening mammography may be very efficient at population level, but still inadequate for any given high-risk woman.

Effects of Estrogen on Risk Factors for Diabetes

The changes in lipid metabolism that occur with the menopause, including increased total and LDLC, triglycerides and Lp(a), and decreased HDL-C, resemble those of type 2 diabetes and the metabolic syndrome (12). Adverse changes in carbohydrate metabolism also emerge with the menopause including decreased insulin sensitivity and insulin secretion (128). These together with increased central adiposity contribute to the increased risk of CVD in postmenopausal women. The effects of estrogen on lipid parameters are discussed in detail in the first part of this chapter. A number of observational studies have also reported that estrogen improves insulin resistance in postmenopausal women, a factor that is predictive for the development of type 2 diabetes (125,129). Estrogen therapy also appears to prevent central fat distribution, a factor that is strongly associated with insulin resistance (126). Thus, estrogen can potentially prevent the insulin resistance associated with central obesity...

Effects of HRT on Carbohydrate Metabolism in Women With Diabetes

There is a degree of reluctance among health care professionals to prescribe HRT to women with diabetes. A community-based survey in London found that diabetic postmenopausal women were less than half as likely as the general population to be prescribed HRT (137). Doctors and health care professionals perceive HRT as detrimental for diabetic women because of fear about glycemic control as is also the case with the oral contraceptive pill (138). Yet there is no evidence that HRT results in deterioration of glycemic control in women with diabetes. Oral estradiol has been shown to improve glucose metabolism and insulin sensitivity in diabetic women (132,139), whereas transdermal estradiol was found not to affect glycemic control (140). The addition of norethisterone does not appear to adversely affect glycemic control, although it may reduce any benefit seen with oral 17 -estradiol alone. In women with IGT, Luotola and associates (141) reported that natural estrogen progestogen...

Effects of HRT on Lipids in Women With Diabetes

Serum lipid parameters show an overall beneficial change on HRT in postmenopausal diabetic women. Unopposed oral estradiol increases HDL-C and reduces LDL-C, whereas the addition of norethisterone may not alter this beneficial effect (132,148). Oral CEE 0.625 mg daily has been shown to reduce total and LDL-Cin women with diabetes, although increasing HDL-C (149). In one study, the increase in HDL-C was less than among nondiabetic women (150). Not all studies have shown an increase in triglycerides with oral CEE (149), although one showed a greater increase among women with diabetes Regarding Lp(a), no significant differences were found among the groups studied in the NHANES III survey. However, in a randomized controlled study combined continuous HRT (CEE + MPA) has shown beneficial effects on Lp(a) in postmenopausal women with type 2 diabetes (153). Also, a significant reduction in Lp(a) and triglycerides has been reported following treatment with tibolone (154).

HRT and Risk of Cardiovascular Disease in Women With Diabetes

CVD is the most common cause of death in type 2 diabetes. This increased risk is particularly apparent in women with diabetes in which the relative protection afforded by the female sex is lost (107). For women without diabetes, prospective cohort surveys such as the Nurse's Health Cohort Study, suggest that estrogen therapy decreases the risk of CHD in postmenopausal women who were initially healthy at the time of enrollment (5). However, data from the HERS and WHI clinical trials have questioned the validity of epidemiological evidence by reporting an increased risk of CHD among women assigned to HRT (6,7). With respect to the effect of HRT on the progression of atherosclerosis, Dubuison and associates (174) conducted a cross-sectional analysis and found that the beneficial effect of ERT HRT on carotid intima-media wall thickness a common measure of subclinical atherosclerosis was similar in diabetic and nondiabetic postmenopausal women. In the HERS trial, nearly 23 of the...

What screening tests are in use

Of the ovarian tumour markers, the most extensively studied is CA125. It is an antigenic determinant on a high-molecular-weight glycoprotein that is recognized by the mouse monoclonal antibody, OC125, developed using an ovarian cancer cell-line as an immunogen. CA125 was first discovered in 1981 (Bast et al.). Levels are raised in 50 of stage I ovarian tumours and in 90 of stage II ovarian tumours (Zurawski et al., 1988). CA125 levels may also be raised in a range of other physiological and pathological conditions, which may be gynaecological or non-gynaecological, benign or malignant (Table 14.1). This can cause particular problems in screening the high-risk population. Many of these women are premenopausal and the CA125 level may fluctuate with the menstrual cycle or maybe elevated by such conditions as endometriosis. Specificity using CA125 as a screening tool can be improved using serial determinations over time (Einhorn et al., 1992). An algorithm has been developed in...

Changes in circulating androgens

The significance of changes in androgen secretion is a neglected area of female reproductive ageing. One important study has documented a 50 fall in circulating total and free testosterone concentrations in normal regularly cycling women between the ages of 20 and 40 (Zumoff et al 1995). This has been postulated to reflect declining levels of adrenal androgen precursor secretion. Across the menopausal transition itself, studies from the authors' laboratory indicate that there is no significant change in the circulating concentrations of total testosterone, whilst there is a fall in sex hormone binding globulin and an increase in free androgen index (Burger et al 2000b). Studies from other investigators suggest that there may be a further increase in circulating androgen levels in the late 50s and 60s (Laughlin 2000). The precise consequences of these changes in androgen for womens' health in general are unknown. On the other hand, loss of androgen as may occur following ovariectomy...

Udaya M Kabadi md frcpc facp face

Prolactinoma is more common in women than in men. The clinical presentation of prolactinoma depends on the age and sex of the patient, the size of the tumor, and the duration of the hyperprolactinemia (11). Premenopausal women may present with menstrual dysfunction and or galactorrhea. Menstrual dysfunction includes amenorrhea, oligomenorrhea, menorrhagia, or normal periods with anovulation and thus infertility. Galactorrhea may be present in 30-80 of these women (11). They may also experience symptoms of estrogen deficiency including vaginal dryness, decreased libido, and dysparunia. Finally, osteopenia osteoporosis is also a concern owing to the lack of estrogen. Therefore, most of the premenopausal women manifest microadenoma, presenting with the classic symptoms of hyperprolactinemia early in the course of the disease. In contrast, postmenopausal women tend to manifest macroadenoma the delay in diagnosis during the earlier stage of the disease is caused by a lack of galactorrhea...

Calendar Time And Information Time

At the planning stage the sample size is usually calculated based on information regarding the expected difference between treatments, its corresponding variability, and the desired statistical power for a predetermined risk of type I error. After the study is initiated, patients are enrolled to receive the treatment for a fixed length of time until he or she reaches either the end of the study or the time of analysis with survival as one of the primary endpoints. The Postmenopausal Estrogen Progestin Interventions (PEPI), for example, is a trial funded by the U.S. National Institutes of Health to evaluate the effects of unopposed estrogen and combined estrogen-progestin therapy on four major cardiovascular disease risk factors in postmenopausal women (Espeland et al., 1995). These four risk factors include plasma HDL-cholesterol, systolic blood pressure, two-hour postoral glucose serum insulin, and plasma fibrinogen. Table 10.5.1 gives the five treatments to be assessed in the PEPI....

Perspectives and conclusion

Cauley JA, Norton L, Lippman ME, et al. (2001). Continued breast cancer risk reduction in postmenopausal women treated with raloxifene 4-year results from the MORE trial. Breast Cancer Res Treat 65 125-34. Chlebowski RT and McTiernan A (1999). Elements of informed consent for hormone replacement therapy in patients with diagnosed breast cancer. J Clin Oncol 17 130-42. Cobleigh MA, Norlock FE, Oleske DM and Starr A (1999). Hormone replacement therapy and high S phase in breast cancer. J Am Med Assoc 281 1528-30. Col NF, Hirota LK, Orr RK, Erban JK, Wong JB and Lau J (2001). Hormone replacement therapy after breast cancer a systematic review and quantitative assessment of risk. J Clin Oncol 19 2357-63. Colditz GA, Stampfer MJ, Willett WC, Hennekens CH, Rosner B and Speizer FE (1990). Prospective study of estrogen replacement therapy and risk of breast cancer in post-menopausal women. J Am Med Assoc 264 2648-53. Collaborative Group on Hormonal Factors in Breast Cancer (1997). Breast...

Screening for ovarian malignancy

Malignant ovarian tumours are the most common cause of gynaecological cancer related deaths in the Western Europe 4000 deaths occur every year in the UK from ovarian cancer. Transvaginal ultrasound is fundamental to any screening programme either as a single modality or in conjunction with serum tumour markers. An ovarian volume over 20 cm3 in pre-menopausal women and 10 cm3 in post-menopausal women is considered abnormal. The use of ultrasound screening for ovarian cancer is discussed in Chapter 55.

Clinical efects of ovulation disturbances

Flow and that progesterone progestin therapy is an effective treatment. Ovulation disturbances are related to rapid cancellous bone loss in regularly cycling, initially ovulatory premenopausal women (Prior et al 1990a) and cyclic medroxyprogesterone therapy increases bone density in women with menstrual cycle and ovulation disturbances (Prior et al 1994). It is probable, therefore, that ovulation disturbances in any phase of perimenopause, but especially phases C and D contribute to the increased bone loss that occurs at that stage of the transition (Okano et al 1998, Prior 1998). In summary, ovulation disturbances are probably of clinical as well as physiological consequence in the perimenopause and may relate to menorrhagia, VMS, mood disturbances and accelerated bone loss. Studies are needed to document this because therapy with cyclic progesterone or medroxyprogesterone may well be effective in symptomatic perimenopausal women.

Shideler n3 women 10 cycles

This three-part figure summarizes prospective data on ovulation disturbances during the perimenopause. The top section shows the proportion of three women experiencing three consecutive cycles that are normal (open bar) or showed ovulation disturbances (short luteal phase SLP and or anovulatory in black). MetcalPs data in women with irregular cycles are shown on the left (n 58) and on the right prospective data for 3 4 consecutive cycles in three women (see Fig. 4). The middle portion of the diagram shows prospective data drawn as percentage of ovulatory (open bar, includes SLP for Shideler data ) and anovulatory cycles (black bar). The bottom panel shows the percentage of sera with luteal levels of progesterone (Luteal Levels Prog, open bar) or low progesterone levels (Low Prog, black bar) during the 72 61 versus 6 0 months before the final menstrual flow from Rannevik data. mo, months. All data redrawn from published work (Metcalf 1979, Shideler et al 1989, Brown 1985,...

Introduction defining polycystic ovary syndrome and secondary amenorrhoea

Amenorrhoea is the absence of menstruation, which might be temporary or permanent. It may occur as a normal physiological condition such as before puberty, during pregnancy, lactation or the menopause, or as a feature of a systemic or gynaecological disorder. Primary amenor-rhoea may be a result of congenital abnormalities in the development of ovaries, genital tract or external genitalia or a perturbation of the normal endocrinological events of puberty (and these are described in Chapter 37). Furthermore, most of the causes of secondary amenorrhoea can also cause primary amenorrhoea, if they occur before the menarche.

Other Hormones Affecting Calcium Balance

Many of the systemic hormones directly or indirectly have an impact on calcium balance. Obviously, special demands are imposed on overall calcium balance during growth, pregnancy, and lactation. All of the hormones that govern growth, namely, growth hormone, the insulin-like growth factors, and thyroidal and gonadal hormones (see Chapter 44), directly or indirectly influence the activity of bone cells and calcium balance. The gonadal hormones, particularly estrogens, play a critical role in maintaining bone mass, which decreases in their absence, leading to osteoporosis. This condition is common in postmenopausal women. Osteoblastic cells express receptors for estrogens, which stimulate proliferation of osteoblast progenitors and inhibit production of cytokines such as interleukin-6 that activate osteo-clasts. Consequently in their absence osteoclastic activity is increased and osteoblastic activity is decreased, and net loss of bone results.

Hypothalamic causes of secondary amenorrhoea

Hypothalamic causes of amenorrhoea may be either primary or secondary. Primary hypothalamic lesions include craniopharyngiomas, germinomas, gliomas and dermoid cysts. These hypothalamic lesions either disrupt the normal pathway of prolactin inhibitory factor (dopamine), thus causing hyperprolactinaemia or compress or destroy hypothalamic and pituitary tissue. Treatment is usually surgical, with additional radiotherapy if required. Hormone replacement therapy is required to mimic ovarian function, and if the pituitary gland is damaged either by the lesion or by the treatment, replacement thyroid and adrenal hormones are required. Secondary hypogonadotrophic hypogonadism may result from systemic conditions including sarcoidosis, tuberculosis as well as following head injury or cranial irradiation. Sheehan's syndrome, the result of profound and prolonged hypotension on the sensitive pituitary gland, enlarged by pregnancy, may also be a cause of hypogonadotrophic hypogonadism in someone...

Genetic Considerations

The patient often appears thin and chronically ill. Her abdomen may be grossly distended, but her extremities are thin and even wasted. When you palpate the abdominal organs, you may be able to feel masses. During the vaginal examination, you may be able to palpate an ovary in postmenopausal women that feels like the size of an ovary in pre-menopausal women. An ovarian tumor may feel hard like a rock or pebble, may feel rubbery, or may have a cystlike quality. Palpation of an irregular, nodular (handful of knuckles), insensitive bilateral mass in the pelvis strongly suggests the presence of an ovarian tumor.

GnRH agonist analogues with and without add back

GnRH agonist analogues are extremely effective 11 . These are best administered by injected depot preparations (goserelin or leuprorelin) as compliance is virtually guaranteed. Remember that as these are agonist analogues missed nasal doses will result in incomplete suppression and even re-stimulation of cycles. Without add back there will usually be the distressing symptoms of menopause. With add back therapy (particularly tibolone) the analogues remain equally effective but menopause symptoms are eliminated 11 . It is difficult to know whether long-term use of this combination is justified either medically or economically. It is probably reasonable to use it in those women approaching the menopause and in the medium term in younger women.

Methods to avoid gestageninduced PMS

Continuous combined hormone replacement therapy. Standard preparations would not suppress ovulation and would also increase the incidence of uterine bleeding. The use of the continuous combined oral contraceptive ought to be effective but this has not been adequately researched. In this approach, oestrogen suppresses ovulation and avoids menopausal symptoms. The intrauterine progestogen provides endometrial protection without achieving systemic levels that would act on the central nervous system reintroducing the PMS symptoms. This combination would have the added benefit of improving any menstrual problems and would provide contraception. There is only limited evidence that exists for this combination - suppression of ovarian function with oestrogen has clearly been shown to eliminate the symptoms. The Mirena intrauterine system reduces the incidence of endometrial hyperplasia. Large-scale studies

Specific treatments for CPP evidence from randomized trials

Limited randomized controlled trial (RCT) evidence is available to guide treatment decisions in CPP. It is important to be clear as to whether treatment is directed towards an underlying condition such as adhesions or whether pain itself is the main focus. While hormonal therapy aims to achieve benefit in a non-specific manner by inhibiting ovarian activity, based on the observation that many patients with CPP experience resolution at the time of the menopause, psychological approaches aim to enhance coping skills and reduce pain-associated distress. Many proven treatments for chronic neuropathic pain such as low-dose tricyclic antidepressants and gabapentin are equally relevant in CPP where there are neuropathic

Primary Hyperparathyroidism

No calcimimetic drugs are currently commercially available and, therefore many patients must choose between an operation or no treatment. Drugs that inhibit bone resorption, such as bisphosphonates, can decrease hypercalcemia, but unfortunately PTH secretion may increase. Estrogens are an exception they increase bone density and may decrease serum calcium concentration slightly in postmenopausal women (25). In patients who do not undergo surgery, surveillance is necessary. Adequate hydration and ambulation are always encouraged. All diuretics should be avoided, and dietary intake of calcium should be moderate. Routine medical follow-up usually includes visits twice yearly with serum calcium measurements, yearly measurements of 24-h urinary calcium excretion, yearly bone densitometry, and yearly creatinine (17). Long-term survival in these patients is not adversely affected (26).

Cardiovascular Disease

In ischemic heart disease, there is a very marked gender difference Women die 10-15 yr, later than men and the death rate in women increases exponentially after the age of 50. In case of artificial menopause, the risk for atherosclerosis is two to three times higher than a menopausal age of 50 yr. The mortality figures for coronary heart disease vary from 50 to 200 per 100,000 inhabitants (male more than female) and for cerebrovascular disease, 100 per 100,000 inhabitants (female more than male). Fasting homocysteine levels are lower in women than in men. Levels of homocysteine show a positive association with age for both sexes. In the postmenopausal age category, female post-methionine-load homocysteine levels surpass the levels of men. Elevation of homocysteine (> 80th percentile of controls) appeared to be at least as strong a risk factor for vascular disease in women as in men, even before menopause. For post-methionine-load homocysteine, there is a 40 stronger association with...

Postoperative hormonal treatment

Compared to surgery alone or surgery plus placebo, postoperative hormonal treatment does not produce a significant reduction in pain recurrence at 12 or 24 months, and has no effect on disease recurrence similarly, it has no effect on pregnancy rates 27 . Prescribing hormone replacement therapy (HRT) after bilateral oophorectomy is advisable in young women but the ideal regimen is unclear. Adding a progestagen after hysterectomy is unnecessary but should theoretically protect against the unopposed action of oestrogen on any residual disease -causing reactivation or, in rare circumstances, malignant transformation. This theoretical benefit must be balanced against the risk of recurrent disease which is remarkably small and the increase in breast cancer risk reported to be associated with both tibolone and combined oestrogen and progestagen HRT.

Mineral And Phytate Concentrations And Ratios

Fractional Calcium Absorption from Calcium Carbonate as Influenced by Calcium Load and Phytate Calcium Molar Ratios in Healthy Premenopausal Women.3 TABLE 13.1. Fractional Calcium Absorption from Calcium Carbonate as Influenced by Calcium Load and Phytate Calcium Molar Ratios in Healthy Premenopausal Women.3

Clinical Implications of Thiazide Diuretics

These effects have been ascribed to its hypocalciuric action 13 , which causes calcium retention and reduces the turnover of bone. However, in many postmenopausal women and elderly subjects, urinary calcium excretion may be low due to impaired intestinal calcium absorption 13 . They may therefore

Who Might Benefit From Ovarian Tissue And Egg Freezing

All women are born with a limited supply of eggs. These eggs continue to dwindle in supply as we grow older. One recent study indicated that 98 percent of women are fertile through their early 20s. However, by their mid-30s, the percentage of those who are still fertile drops to about 70 percent. This biological clock phenomenon continues to tick until a woman reaches menopause and all of her eggs are depleted. Given that, the preservation of eggs and ovarian tissue by means of freezing can be of great benefit for many women who Are facing the loss of their ovarian function because of approaching menopause, disease, or planned complete hysterectomy

Female Sexual Dysfunction

Female sexual dysfunctions (FSD) include persistent or recurrent disorders of sexual interest desire, disorders of subjective and genital arousal, orgasm disorder, pain and difficulty with attempted or completed intercourse. The scientific knowledge on sexual dysfunction in women with diabetes is rudimentary. Sexual dysfunction was observed in 27 of women with type 1 diabetes. FSD was not related to age, BMI, HbAlc, duration of diabetes, and diabetic complications. However, FSD was related to depression and the quality of the partner relationship (71). Recently, the prevalence of FSD in premenopausal women with the metabolic syndrome was compared with the general female population. Women with the metabolic syndrome had reduced mean full female sexual function index score, reduced satisfaction rate, and higher circulating levels of C-reactive protein (CRP). There was an inverse relation between CRP levels and female sexual function index score (72).

Endocrine abnormalities and bone loss in women

This phase begins at menopause, can be prevented by oestrogen replacement, and almost certainly results from the cessation of ovarian function. Oestrogen acts through high affinity oestrogen receptors in osteoblasts and osteoclasts to restrain bone turnover, and when this restraint is lost at menopause, overall bone turnover increases and resorption increases more than formation. In addition, the increased activity of osteoclasts and their prolonged lifespan lead to trabecular plate perforation and to loss of structural elements, thus weakening bone out of proportion to the loss of bone density. The high rate of bone resorption increases skeletal calcium outflow, which leads to a partial suppression of parathyroid hormone (PTH) secretion and compensatory increases in urinary calcium excretion (Riggs et al 1998). The reason for the cessation of the rapid phase of As the rapid bone loss phase subsides, serum levels of PTH increase progressively throughout the remainder of life. Markers...

Endocrine abnormalities and bone loss in ageing men

Except after orchiectomy, men do not have an equivalent of the rapid phase of bone loss that women experience following menopause. After accounting for the absence of this phase, the patterns of late bone loss and of the increases in serum PTH and bone resorption markers in ageing men are virtually superimposable upon those occurring in women (Riggs et al 1998). In the past, it has been difficult to attribute male bone loss to sex steroid deficiency because men do not have an equivalent of menopause, and because serum total testosterone levels FIG. 3. Changes in serum testosterone (T) in ageing men. The left panel shows that serum total testosterone decreases only slightly in ageing men. Total T (p < 0.001), bioavailable T (P < 0.001). The right panel shows the changes in serum bioavailable testosterone, which decreased progressively with ageing. Values for premenopausal (Pre) and postmenopausal (Post) women are given for comparison. Error bars represent SEM. (With permission from...

The declining oocyte pool

A newborn female infant has over a million oocytes the oocyte cohort shrinks throughout life such that there are only a few thousand oocytes left as a woman enters her forties and few or none in the postmenopause. It is the depletion of oocytes which eventually leads to the cessation of menstruation, the cardinal sign of the menopause. There are two landmarks in the ovarian failure process. First, there is a marked decline in fertility with no cycle

Prediction of ovarian reserve

An FSH level of > 30 is regarded as being diagnostic of the menopause but can be misleading as levels can fluctuate if ovarian activity resumes as often does in the climacteric. Work is currently being conducted to develop an accurate predictive model for the menopause by combining FSH and Inhibin with anti-Mullerian hormone (AMH). There has been a great deal of publicity recently that follicular reserve can be predicted by measurement of ovarian volume 2 . The original work in fact took place over 10 years ago a nomogram was produced from measurement in over 2000 normally cycling women where the mean volume was estimated to be 3.57 cm3 3 . Further work is required to confirm the predictive value of this model but it is conceivable that a model could be developed which would combine both hormonal and sonographic measurements.

Premature ovarian failure

Premature ovarian failure is said to have occurred when menstruation ceases before the age of 40 years and early menopause before the age of 45 years. Although there are many causes of early ovarian failure, the main cause is spontaneous or idiopathic. The main identified genetic causes are Turner's syndrome and Fragile X. Recently, forkhead genes (FOX03A defect) have been discovered which lead to early follicular activation and thus premature depletion of the follicle pool. Other causes include FSH receptor polymorphisms, where follicles are present but unable to respond due to the loss of the FSH receptor. Fig. 47.2 Endometrial effects of perimenopause (a) Normal cycle (b) Unopposed oestrogen effect. From Kumar RJ (ed.) (2002) Blaustein's pathology of the female genital tract, 5th edn. New York Springer. Fig. 47.2 Endometrial effects of perimenopause (a) Normal cycle (b) Unopposed oestrogen effect. From Kumar RJ (ed.) (2002) Blaustein's pathology of the female genital tract, 5th...

Alternatives to HRT [3637 For Symptoms

There is little scientific evidence that complementary and alternative therapies can help menopausal symptoms or provide the same benefits as conventional therapies. Yet many women use them, believing them to be safer and 'more natural' especially following the current controversies regarding HRT. The choice of treatments is confusing and unlike conventional medicines, little is known about their active ingredients, safety or side effects or how they may interact with other therapies. They can interfere with warfarin, antidepressants and anti-epileptics with potentially fatal consequences. Some herbal preparations may contain oestrogenic compounds and this is of concern for women with hormone dependent disease such as breast cancer. There is also concern about contaminants such as mercury, arsenic, lead and pesticides. Legislation is soon to be introduced which will make it mandatory for herbal preparations to at least be registered with the MHRA. This will at least allow some control...

Androgen Replacement in Hypogonadal Women

Premenopausal circulating testosterone levels in women are approximately 10-fold lower than those seen in healthy men (22). They are maintained by the With a history of premenopausal pituitary, adrenal, or ovarian failure With postmenopausal complaints of reduced libido Adult men (presenting with) indirect production of testosterone from adrenal dehydroepiandrosterone (DHEA) and androstenedione and by the direct secretion of testosterone from the ovary. Adrenal DHEA secretion begins to decline in most women after the age of 30. This has been referred to as adrenopause and occurs at differing rates between individuals. Ovarian testosterone secretion declines by approximately 30 at menopause and then disappears almost entirely within the next decade. Although few studies have investigated the biologic effects of testosterone in women, several reports indicate that testosterone supplementation in ovariecto-mized women and some late menopausal patients results in a significant improvement...

Vegetarian Diets Ethics and Health

Some nutritionists claim that people with high metabolic needs, like pregnant or lactating women and children, face significantly higher risks of nutritional deficiency if they exclude both meats and dairy products from their diets. They claim, for instance, that (1) it is difficult for vegan women to get enough iron because iron from nonmeat sources is less efficiently absorbed than the iron available in meat (iron deficiency is a problem for women because menstruation removes iron from their systems monthly), (2) vegans cannot get enough vitamin B12 (deficiencies of which cause severe neurological damage) because the vitamin is produced by microorganisms in the digestive tracts of animals, and (3) it is particularly difficult for women to get enough calcium from a dairy-free diet (osteoporosis, a condition characterized by brittle bones, is a serious problem for postmenopausal women).

Proximal Colon Cancer

A large number of epidemiological studies suggest a hormonal basis for the pathogenesis of colorectal cancers. Evidence for the potential role of sex hormones in the etiology of colorectal cancer comes from several observations. Males and females differ in their incidence and mortality rates of colorectal cancer when localization of the tumor and the age of the patient at the time of diagnosis are taken in consideration. Age-adjusted colon cancer incidence rates are slightly higher for men than for women (Wingo et al. 1998). Also, the risk of colon cancer in family members afflicted by the hereditary colon cancer syndrome HNPCC is lower in women than in men (Froggatt et al. 1999). However, colon tumors that develop in the proximal part of the large intestine occur more frequently in older women (Butcher et al. 1985), whereas tumors of the distal colon are more common in men (Alley and McNee 1986). Parity and hormone replacement therapy (HRT) have also been shown to be inversely...

Clinical Use of erbBReceptors as Prognostic Factors

Using an enzyme-linked immunosorbent assay in fresh tissue samples, Kim et al. (372) found no EGFR overexpression (defined as EGFR level exceeding the 250 fmol mg protein) in a control group of 10 chronic cervicitis, but EGFR overexpression was found in 25 of 20 CIN II III samples. In 40 invasive cervical carcinomas, 72.5 showed EGFR overexpression. Lesions of 4 cm or more had significantly higher EGFR levels than those under 4 cm. There were no significant differences in EGFR levels when stratified according to clinical stage, histological cell type, age, or menopausal status. These data were confirmed by the IHC findings of Maruo et al. (336), who found no EGFR expression in normal cervical epithelium, but 75 of dysplastic and 50 of malignant tissues were positive. Large-cell nonkeratinizing and keratinizing carcinomas contained high levels of EGFR small-cell nonkeratinizing carcinomas lacked EGFR. Elevated expression of EGFR may be involved in the initial stage of tumorigenesis,...

Guidelines for Osteoporosis Screening

For risk assessment in perimenopausal or postmenopausal women who have risk factors postmenopausal women who have clinical risk factors for fractures (low body weight or strong family history of osteoporosis with vertebral or hip fractures) (9). The AACE recommendations for assessments of BMD are noted in Table 2.

Special Treatment Considerations

Hyperthyroidism, either as a primary disorder or iatrogenic from over-replacement with thyroid hormone, can cause accelerated bone loss (49-51). Thyroid function should be monitored (by TSH levels) and the hormone dose adjusted to achieve a normal TSH concentration in all individuals receiving thyroid hormone replacement therapy for nonmalignant conditions. Furthermore, patients with thyroid cancer on suppressive doses of thyroid hormone should have frequent evaluation of thyroid function and a baseline and repeat BMD every 1-2 yr until they are stable, and then again with clinical change. The monitoring of free thyroxine and TSH is to ensure that the lowest dose of thyroid replacement required to give adequate suppression of TSH is used.

Primary Nursing Diagnosis

If uterine cancer is detected early, the treatment of choice is surgery. A total abdominal hysterectomy (TAH) with removal of the fallopian tubes and ovaries, bilateral salpingo-oophrectomy (BSO) is generally performed. Common complications after a hysterectomy are hemorrhage, infection, and thromboembolic disease. Premenopausal women who have a BSO become sterile and experience menopause. Hormone replacement therapy may be warranted and is appropriate. In a total pelvic exenteration (evisceration or removal of the contents of a cavity), the surgeon removes all pelvic organs, including the bladder, rectum, and vagina. This procedure is performed if the disease is contained in the areas without metastasis. If the lymph nodes are involved, this procedure is usually not curative.

Expression of erbB Receptors and Clinical Outcome

Et al. (425) found overexpression of EGFR or erbB-2 in 2 15 (13 ) and 2 13 (15 ) endometrial carcinomas, respectively. The expression of both receptors was significantly higher in the malignant tissue than in the corresponding normal endometrium, but was also higher in premenopausal than in postmenopausal patients. A direct correlation between the ploidy status and the expression of EGFR and erbB-2 has been found. Esteller et al. (426) examined the amplification of erbB-2 and EGFR in 50 normal endometrial tissues, 10 adenomatous hyperplasias, and 50 endometrial carcinomas, using genomic differential polymerase chain reaction. No EGFR gene amplification was found in normal, hyperplastic, or malignant tissues, suggesting that mechanisms other than gene amplification could be responsible for the reported EGFR overexpression. Amplification of erbB-2 was found in 14 of endometrial carcinomas. None of the 50 endometrial normal tissues or the 10 adenomatous hyperplasias showed erbB-2 gene...

Oestrogens in the management of incontinence

A further meta-analysis performed in Italy has analysed the results of randomized controlled clinical trials on the efficacy of oestrogen treatment in postmenopausal women with urinary incontinence 248 . A search of the literature (1965-1996) revealed 72 articles of which only four were considered to meet the meta-analysis criteria. There was a statistically significant difference in subjective outcome between oestrogen and placebo although there was no such difference in objective or urodynamic outcome. The role of oestrogen replacement therapy in the prevention of ischaemic heart disease has been assessed in a 4-year randomized trial, the Heart and Estrogen progestin Replacement Study (HERS) 250 involving 2,763 postmenopausal women younger than 80 years. Overall combined hormone replacement therapy was associated with worsening stress and urge urinary incontinence, although there was no significant difference in daytime frequency, nocturia or number of urinary tract infections....

General therapeutic measures

All incontinent women benefit from simple measures such as the provision of suitable incontinence pads and pants. Those with a high fluid intake should be advised to restrict their drinking to a litre a day, particularly if frequency of micturition is a problem. Caffeine-containing drinks (such as teas, coffee and cola) and alcohol are irritant to the bladder and act as diuretics, so should be avoided, if possible. Anything which increases intra-abdominal pressure will aggravate incontinence, so patients with a chronic cough should be advised to give up smoking, and constipation should be treated appropriately. Pelvic floor exercises may be particularly helpful in the puerperium or after pelvic surgery. For younger, more active women who have not yet completed their family, a device or sponge tampon may be used during strenuous activity such as sport. Oestrogen replacement therapy for postmenopausal women is often beneficial as it improves quality of life as well as helps with the...

Polycystic Ovarian Syndrome and Insulin Resistance

Hyperinsulinemia and insulin resistance are thought to play a critical role in the pathogenesis of PCOS and are associated with a high risk for type 2 DM, hypertension, hyperlipidemia, and atherogenesis (Fig. 3). Obese, premenopausal women with PCOS have a 31 incidence of impaired glucose tolerance, and 7.5 develop overt diabetes (6,21). Hypertension is uncommon in young women with PCOS, but its prevalence increases to 40 in the perimenopausal period (22). Although hypertension is common in patients with insulin resistance, it is unclear whether this is secondary to direct sympathetic activation by insulin or to insulin resistance to insulin-mediated vasodilation (23). Approximately 5060 of women with PCOS have android obesity, with increased waist-hip ratio and an associated abnormal lipid profile high triglyceride and low-density lipoprotein (LDL) cholesterol and low high-density lipoprotein (HDL) and apolipoprotein A-I levels (24). Also, impaired fibrinolytic activity reflected by...

Incidence and death rates of thyroid cancer and lymphoma

About 17,000 new cases of thyroid cancer are diagnosed annually in the United States, making it about 14th in incidence among malignancies (6). It occurs at all ages but is most common among middle-aged and postmenopausal women (Fig. 1). The lifetime risk of developing thyroid cancer is about 1 (0.65 for women and 0.25 for men) (7), and death rates are less than 10 (1200 deaths occurred among 135,000 thyroid cancer patients in 1998) (6). However, both the incidence and mortality rates vary substantially among the different forms of thyroid cancer (Table 1) (8).

Step one ensuring monovulation

Hcg Molecular Structure

Such studies are of more than theoretical interest understanding the mechanisms regulating rate of entry into the pool of growing follicles should help to explain such common clinical problems as 'idiopathic' premature ovarian failure and early onset of menopause, as dotropins into the circulation, but have normal ovarian physiology. The results of a study of such a patient are shown in Fig. 35.3. The patient had Kallmann's syndrome with anosmia, primary amenorrhoea and hypogonadal hypogonadism. Ovulation induction was undertaken using two different preparations of gonadotropin. Treatment with both FSH and LH in the form of human menopausal gonadotropins (HMG) induces both normal follicle growth, monitored by transvaginal ultrasound (bottom panel) and oestradiol secretion (top left panel), leading to high luteal phase progesterone concentrations after an artificial LH surge with hCG injection. This indicates that successful ovulation and luteinization occurred. In contrast, treatment...

Urinary frequency and urgency

Cystitis Symptoms Women

Frequency and urgency are common symptoms in women of all ages which often coexist and may occur in conjunction with other symptoms such as urinary incontinence or dysuria. It is unusual for urgency to occur alone because once it is present it almost invariably leads to frequency to avoid urge incontinence and to relieve the unpleasant painful sensation. Bungay et al. 253 found that approximately 20 of a group of 1120 women aged between 30 and 65 years admitted to frequency of micturition and 15 of women from the same series reported urgency. In this study there was no specific increase in the prevalence of frequency or urgency with age or in relation to the menopause. For postmenopausal women, failure of adequate lubrication during sexual intercourse may be a problem so a lubricant gel or preferably oestrogen replacement should be prescribed 281 . For those women with a uterus who do not wish to suffer the recurrence of monthly withdrawal bleeds local oestrogen therapy using oestriol...

Management of secondary amenorrhoea

The diagnosis and consequences of premature ovarian failure require careful counselling of the patient. It may be particularly difficult for a young woman to accept the need to take oestrogen preparations that are clearly labelled as being intended for older postmenopausal women, while at the same time having to come to terms with the inability to conceive naturally. The short- and long-term consequences of ovarian failure and oestrogen deficiency are similar to those occurring in the fifth and sixth decade. However, the duration of the problem is much longer and therefore hormone replacement therapy is advisable to reduce the consequences of oestrogen deficiency in the long term. The HRT preparations prescribed for menopausal women are also preferred for young women. The reason for this is that even modern low dose combined oral contraceptive (COC) preparations contain at least twice the amount of oestrogen that is recommended for HRT, in order to achieve a contraceptive suppressive...

Ultrasound assessment of abnormal uterine bleeding

Endometrial Hyperplasia Fluid Cancer

POSTMENOPAUSAL BLEEDING Transvaginal ultrasound offers an opportunity to individualize the management of postmenopausal bleeding, and decrease the need for invasive testing. There is good evidence that women who present with postmenopausal bleeding in whom a TV ultrasound has demonstrated an endometrial thickness of < 4 mm have a very small risk of endometrial carcinoma 5 . The role of ultrasound in the assessment of women with abnormal pre- or peri-menopausal bleeding is not as clearly defined. The endometrial thickness alters with the different stages of the menstrual cycle. Endometrial polyps Thickness > 15 mm in postmenopausal woman highly suggestive of malignancy Local areas of necrosis may be seen

Examination and investigation of patients with PCOS and secondary amenorrhoea

Who was being treated with hormone replacement therapy (HRT) for primary amenorrhoea. In most cases, however, a history of secondary amenorrhoea excludes congenital abnormalities. A family history of fertility problems, autoimmune disorders or premature menopause may also give clues to the aetiology.

Absence of secondary sexual characteristics

In patients with hypogonadotrophic hypogonadism treat-mentshould be towards managing any avoidable problem or in the isolated GnRH deficiency hormone replacement therapy will need to be instituted to induce secondary sexual characteristic development. These patients can be informed that they are infertile and that ovulation induction in the future can be invoked using various fertility regimes. Hormone replacement therapy is essential and regimes exist for the induction of secondary sexual characteristics over 3-5 years. Oestrogen should be used alone for about 2 years, and then 2-3 years of gradual introduction of progestogens thereby establishing normal breast growth over a time frame that is equivalent to normal. Any attempt to accelerate breast growth by using higher doses of oestrogen will result in abnormal breast growth and this should be avoided at all costs. Patients with an XY dysgenesis or enzymatic failure should have gonadectomies performed to avoid malignancy.

Complementary therapies

Among the largest group of users of complementary therapies, middle age women, up to 33 of the population have used these preparations at any one time (European Menopause Survey 2005 43 ). It is estimated that the cost of complementary therapies amounts to 17 billion US dollars per annum. The majority of the costs are borne by the consumer as these are unlicensed preparations. These preparations are often used by women as they are perceived to be a safe alternative to traditional hormone therapies. However, the safety of a number of these preparations has been called into question. The current regulation of complementary and alternative medicine is inadequate and fragmented with only osteopaths and chiropractors currently regulated professions. phytoestrogens has stimulated considerable interest since populations consuming a diet high in isoflavones such as the Japanese appear to have lower rates of menopausal vasomotor symptoms, cardiovascular disease, osteoporosis breast, colon,...

Pelvic floor Figs 19 and 110

The vaginal wall consists of outer and inner circular layers of muscles which cannot be distinguished from each other. The epithelium contains no glands but is rich in glycogen in the premenopausal woman. The normal commensal, Doderleins bacillus, breaks down this glycogen to create an acid environment.

Karyotype and other tests

Woman Who Have Lost 100lbs With Pcos

Women with premature ovarian failure (under the age of 40 years) may have a chromosomal abnormality (e.g. Turner's syndrome 45X, or 46XX 45X mosaic or other sex chromosome mosaicisms) (Plate 39.1 facing p. 562). A number of genes have also been associated with familial POF, but are not assessed in routine clinical practice. An autoantibody screen should also be undertaken in women with a premature menopause, although it can be difficult to detect antiovarian antibodies many will have evidence of other autoantibodies (e.g. thyroid), which then indicates the need for further surveillance.

Female Reproductive Tract

Mammalian Ovary

Folliculogenesis begins in fetal life. Primordial germ cells multiply by mitosis. They begin to differentiate into primary oocytes and enter meiosis between the 11th and 20th weeks after fertilization. Primary oocytes remain arrested in prophase of the first meiotic division until meiosis resumes at the time of ovulation, which may be more than four decades later for some oocytes. Meiosis is not completed until the second polar body is extruded at the time of fertilization. Around the 20th week of fetal life, about 6 to 7 million oocytes are available to form primordial follicles, but the human female is born with about only 300,000 to 400,000 primordial follicles in each ovary. Oocytes that fail to form into primordial follicles are lost by apoptosis. The vast majority of primordial follicles remain in a resting state for many years. In a seemingly random process, some follicles enter into a growth phase and begin the long journey toward ovulation, but the vast majority of developing...

Epidemiology of chronic pelvic pain

Initial reports relied on estimates from hospital series, naturally unrepresentative of the general population. Some population sample survey data are available a US study reported the responses of women interviewed by telephone 1 . The age range of respondents was 18-50. 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 out of 5263 (14.7 ) were identified as suffering from chronic pelvic pain (CPP). 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 2 . Chronic pelvic pain was defined as recurrent pain of at least 6 months' duration, unrelated to periods, intercourse or pregnancy. For the survey, a 'case' was defined as a woman with CPP in the previous 3 months...

Low penetrancemodifier genes

CYP1A1 is a P450 gene and encodes aryl hydrocarbon hydroxylase, which catalyses the conversion of oestradiol to hydroxylated oestrogen. Some small studies have suggested that polymorphisms in this gene may be associated with an increased risk of breast cancer in some populations. In experimental systems, polychlorinated biphenyls (PCBs) can induce CYP1A1. In postmenopausal women, women heterozygous for an exon 7 point mutation and who had an increased exposure to PCBs were at an increased risk of breast cancer (Crofts et al., 1994 Moysich et al., 1999 Taioli et al., 1999).



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