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Surviving Perimenopause

To give you an even better idea of just what kind of useful and practical information youll find in Perimenopause: Have It, Live It, Love It!, heres a partial list of the topics covered extensively in this ebook: Learn about the 26 signs of perimenopause both common and not so common symptoms. Find out what your symptoms are Not telling you 18 perimenopause symptoms that are linked to other serious medical conditions. Learn how you can treat your symptoms Without the use of drugs and pills. Over 50 home remedies with recipes and instructions to help you cope with various perimenopause symptoms. What you need to prepare Before your visit to your doctor, including how to make sure your doctor listens to you and takes your symptoms seriously, and reaches the right diagnosis. Get tips and techniques to re-ignite your sex life. Its not too late to bring passion back to the bedroom. Perimenopause pregnancy? Get your facts straight whether you are trying to conceive or prevent a pregnancy. Make sense of the changes that are happening to your body and the ones that are happening inside your head. Learn techniques you can apply today to get better sleep and to overcome perimenopause insomnia. Discover what you can do now to prevent osteoporosis which attacks women after they hit menopause and is easily preventable only if you start now! Identify if you are estrogen deficient or estrogen dominant and find out which remedies work for each type. Determine whats actually causing your irregular periods, Pms and heavy bleeding. Learn how to tell when youll hit menopause. Understand medical jargon so you dont come out of a doctor consultation more confused than before you went in. Understand the link between hormonal changes in your body and your mood swings and depression. Find out what to expect when you have perimenopause the common and not-so-common transformations that can really affect the way you live. Get access to information that your doctor may not be telling you. Realize that you can do something about that weight youre putting on around your waist and thighs and why old dieting methods that worked for you in the past are next to useless now. Learn about the different kinds of tests your doctor may ask you to get and actually know what theyre for.

Surviving Perimenopause Overview


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Alternative Therapies to Hormone Replacement Therapy

Tibolone is a steroid hormone with a progestogen-like structure that is converted to estrogenic and androgenic derivatives in vivo. It improves menopausal symptoms and bone density and potentially has fewer side effects than conventional HRT. Limited human observational data on the cardiovascular effects of tibolone indicate that it reduces triglycerides and Lp(a) levels but also HDL and there is a suggestion that tibolone may not increase thrombotic risk (105). We must await data from clinical trials on definite clinical end-points to establish the vascular effects of tibolone.

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.

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.

Pr And The Normal Mammary Gland

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 lobuloalveolar development, and the underlying mechanisms mediating these effects are likely to include a number of molecular pathways, including those involved in cell cycle progression, growth factor activity, and differentiation. A proportion of the effects of P may be mediated by paracrine mechanisms, because there are emerging suggestions that ovarian hormones influence mammary gland biology by influencing the behavior of receptor-negative cells in the vicinity of cells that express receptors.

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.

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...

Sources of Estrogens in Women

After menopause, estrogen concentrations fall to levels that are equivalent to those in males (5-30 pg mL), and most of the estrogen is formed by extragonadal conversion of testosterone through aromatization, mainly in adipose tissue. E1 is the predominant estrogen in these women. The level of estrogen synthesis in extragonadal tissues increases as a function of age and body weight (10). In the circulation, estrogen binds to sex hormone binding globulin (SHBG) produced in the liver and, with less affinity, to albumin (11). Only about 2 -3 of estrogen is free. Changes in SHBG levels may influence the tissue availability of free estrogen and also free androgen because the latter also binds to SHBG. Estrogens themselves increase, whereas androgens and high insulin levels decrease SHBG levels. During the menopause, the drop of estradiol reduces SHBG levels, which in turn, results in decreased binding and an increased concentration of free androgens. Consequently, estrogens decrease to a...

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...

Data From Randomized Clinical Trials

It has been argued that the apparent early thrombotic risk might have been attenuated by a lower dose of estrogen at the initiation of therapy. Thus, the possibility that lower doses of estrogen may preserve an atherogenic benefit without increasing thrombotic events is an attractive hypothesis. Another criticism was that the HERS study only investigated the effect of one HRT (CEE + MPA) therefore, it is not known whether these results are applicable to all HRT preparations. However, a report from the Papworth Hormone Replacement Therapy Atlerosclerosis Study showed no benefit from transdermal estradiol alone or in combination with norethisterone in reducing CHD events in women with pre-existing disease (84).

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.

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. Another characteristic of postmenopausal women is androgenicity associated with low SHBG levels, which is also considered an important risk factor for insulin resistance and type 2 diabetes (120). In the Rancho Bernardo Study, SHBG was found to be inversely correlated with type 2 diabetes and impaired glucose tolerance (IGT) in postmenopausal women (130). In this regard, Andersson and associates (131) also reported that low SHBG levels were associated with type 2 diabetes in both men and women. Furthermore, they also reported...

Effects of HRT on Carbohydrate Metabolism in Women With Diabetes

Effects of Hormone Replacement Therapy on Carbohydrate Metabolism It is important also to note that in women with diabetes, the changes that accompany menopause may further deteriorate glycemic control and HRT may attenuate this effect. Indeed, in the studies conducted by Brussaard and associates (139) and Samaras and associates (144), HbAlc detrimentally increased in the placebo groups in postmenopausal women with type 2 diabetes, whereas in the same reports, and in others, HbAlc was significantly reduced with ERT (146). It appears that regarding glycemic control, low-dose HRT can be used in women with type 2 diabetes without undue concern. The recent North American Menopause Society (NAMS) consensus paper (147) advised that if oral ERT is used in women with type 2 diabetes, then only low-dose formulations should be prescribed. Beneficial effects on insulin sensitivity may be observed with HRT, although more work is needed in the area.

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.

Perspectives and conclusion

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. Collaborative Group on Hormonal Factors in Breast Cancer (1997). Breast cancer and hormone replacement therapy collaborative reanalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer. Lancet 350 1047-59. Kavanagh AM, Mitchell H and Giles GG (2000). Hormone replacement therapy and accuracy of mammographic screening. Lancet 355 270-4. Parazzini F, Braga C, La Vecchia C, Negri E, Acerboni S and Franceschi S (1997)....

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.

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.

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

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). 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 vascular disease in women than in men. In both sexes, low vitamin B6 conferred a twofold to threefold increased risk of vascular disease, independent of homocysteine. Folate levels lower than the 20th percentile were associated with a 50...

Genetic Considerations

Coagulopathies such as Factor V Leiden, a thrombophilia that predisposes to venous throm-boembolism and PE due to a very poor response to activated protein C, will increase clot formation in the heterozygote, but homozygotes are most severely affected. Therefore, transmission is both autosomal dominant and autosomal recessive. Testing for Factor V Leiden should be considered when a person has venous thromboembolism (VTE) meeting any of the following criteria onset before age 50, idiopathic VTE at any age, recurrent VTE, and venous thrombosis at unusual sites (e.g., cerebral, mesenteric, portal, and hepatic veins). Testing has also been recommended when VTE occurs during pregnancy, in the postpartum period, or in association with oral contraceptive use or hormone replacement therapy (HRT). Anyone with a strong family history should also be tested for Factor V Leiden.

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.

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

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 contrast, serum PTH levels increase progressively in the late slow phase of bone loss and are decreased by oestrogen...

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

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...

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...

Androgen Replacement in Hypogonadal Women

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 in libido and sexual fantasy. More recent reports suggest, in addition, that testosterone supplementation may improve energy and depression (23) (Table 1). The appearance of primary gonadal failure in healthy mature men prior to their eighth decade is relatively uncommon and is usually linked to...

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...

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.

Oestrogens in the management of incontinence

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. These findings have also been confirmed in the Nurse's Health Study which followed 39,436 postmenopausal women aged 50-75 years over a four year period. The risk of incontinence was found to be elevated in those women taking HRT when compared to those who had never taken HRT 251 . The most recent paper to be reported by the Women's Health Initiative (WHI) writing group has also studied the effect of oestrogens, with and without progestogens, on urinary incontinence 252 . In this study, 27,347 postmenopausal...

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 The threshold concept is useful in understanding the pitfalls of 'superovulation', in which daily injections of high doses of FSH are given as part of in vitro fertilization (IVF) treatment. The aim is to produce a cohort of eight or more mature follicles suitable for ultrasound guided oocyte retrieval. However, if the follicle pool is small (e.g. if the patient is near-ing menopause), then the yield of mature follicles will be disappointing, while if the follicle pool is large (e.g. if the patient has polycystic ovary syndrome), then there is a danger of over-response with hyper-stimulation syndrome.

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.

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.

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. Black cohosh is a herbaceous perennial plant native to North America, widely used to alleviate menopausal symptoms. There are four randomized controlled trials using black cohosh but only one of these was placebo controlled. Three trials have...

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

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...

Conclusions and Future Directions

There are several plausible explanations for the divergent findings from the clinical trials and the observational studies regarding the effect of HRT on CVD in postmeno-pausal women. Some discrepancies may be methodological in nature and others may have a biological basis related to the pleiotropic effects of estrogens and the characteristics of the study population. The later may be related to age, time since menopause, state of the arterial endothelium and stage of atherogenesis. Genetic factors may also contribute to the heterogeneity of the population.

Effects of thyrotoxicosis Bone Effects

Postmenopausal women are at high risk for losing bone density. Up to 3 of bone mass is commonly lost within each of the first 5 yr after menopause (37). It is estimated that 30 of Caucasian women in the United States have osteoporosis (38). Concomitant thyrotoxicosis, whether subclinical or overt, has been shown to exacerbate this risk for postmenopausal osteoporosis. In thyrotoxicosis there is an increase in both osteoblast and osteoclast activity. This results in increased bone turnover, as measured by increased urine, and serum N-telopeptide, and serum osteocalcin, with a net increase in bone resorption (39,40). In overtly

Gynaecologist Conclusion

We must not underestimate women's desire for a high quality of life in the menopause. Women will continue to demand HRT or a safe, effective alternative for their symptoms. It is, therefore, our duty to strive to provide the best therapy for women to achieve this goal. With every new study there appears to be a change in advice given by the regulatory agencies as to how we should advise our patients, leading to a great deal of confusion. Best practice should involve the following

Whats in a Name

In addition to its myeloablative effects, HDC is extremely toxic to other tissues with dividing cells, such as the gastrointestinal tract, the skin, and the hair follicles. Acute toxicities include cramping and dysfunction in the gastrointestinal tract, mouth sores, nausea, diarrhea, rashes, and fatigue. Total hair loss is very common but varies with the type of chemotherapy used. Severe organ toxicity is less common but can be fatal. The lungs are particularly sensitive to some drugs (e.g., vincristine in the Solid Tumor Autologous Marrow Program I regimen), and life-threatening interstitial pneumonitis can occur, resulting in fluid accumulation and reduced blood oxygen. Other severe adverse effects may include liver damage and inflammation of the bladder. Cardiac events occur more often with HDC. For these reasons, patients who underwent HDC ABMT were usually hospitalized for several weeks and sometimes for months if complications occurred. During hospitalization, patients were at...


Each month, under the influence of your reproductive hormones, one of your ovaries selects between 10 and 20 eggs to become possible candidates for release. The number of eggs decreases with age until menopause, when ovulation stops completely. The chosen eggs begin to mature within their own sacs, called follicles. In


Menopause, occupies only half of average adult life expectancy. Despite the enduring fertility potential, fathers older than 50 years are responsible for only *1 of births in developed countries. Communal procreative patterns are determined by the similarity of couple's age and the overwhelming age-restriction of female fertility. Nevertheless, fertility concerns of men cannot be disregarded at any set age particularly with increasing remarriage to younger women.

Androgen effects

Following the adage that when one's only tool is a hammer, remarkably soon all problems turn into nails, it is an understandable that androgen administration is proposed for older men. Such proposals long pre-date the first availability of testosterone (Hamilton 1937) with many bouts of rejuvenation quackery associated with the names of Brown-Sequard, Steinach and Voronoff into the early 20th century. Standard clinical endocrine practice includes replacement therapy for unequivocal hormonal deficiencies of the pancreas (insulin), thyroid (thyroxine), adrenal (glucocorticoid, mineralocorticoid) and gonads (oestrogen, androgen). Conversely, hormone replacement is not provided for other classical hormones such as prolactin, glucagon, somatostatin, calcitonin, calcitonin-gene related peptide and adrenalin, and other hormones (thyroid-stimulating hormone, LH, FSH, parathyroid hormone) are not replaced but substituted by simpler non-peptide end products. Generally, the criteria for a...

Subsequent fertility

Following either low- or high-risk chemotherapy treatment, fertility is usually maintained and regular menstruation restarts 2-6 months after the end of chemotherapy. However chemotherapy treatment does bring the average age of the menopause forward, by approximately 1 year for those treated with methotrexate and 3 years for those treated with EMA CO 17 .

Gender Bias

Age of disease onset is invariably later in female FSHD gene carriers, who are also more likely to exhibit a less severe form of the disease. 13 It has been suggested that female hormonal status somehow confers a mild protective effect. Consistent with this view, disease progression is markedly accelerated in female patients following menopause, which is often associated with a general decline in muscle strength.

What went wrong

The Heart and Estrogen progestin Replacement Study (HERS) was designed to determine whether hormone replacement therapy, known to lower LDL cholesterol and raise HDL cholesterol, would reduce the risk of coronary events. A fixed combination of conjugated estrogen (Premarin) and medroxyprogesterone (Provera) was evaluated in a placebo-controlled, long-term trial of about 2,800 postmenopausal women with established coronary heart disease. Based on the observed net mean reduction in LDL cholesterol (11 ) and mean increase in HDL cholesterol (10 ) at one year and the known statistical

With diabetes

Healthy postmenopausal women undergo changes in lipoprotein and carbohydrate metabolism and in the pattern of body fat distribution similar to those of patients with diabetes. In fact, a picture resembling the metabolic syndrome emerges with the menopause (12). Replacement therapy with estrogen can improve the adverse impact of meno

Follow up yrs

Surgical complications occur in approximately 10 of patients, including permanent diabetes insipidus, cerebrospinal fluid leaks, hemorrhage, secondary empty sella syndrome, meningitis, and sinusitis (Table 6). Approximately 20 of patients develop new hypopituitarism postoperatively, owing to surgical damage of the surrounding normal pituitary tissue (56), which may require life-long hormone replacement therapy. The incidence of complications is related to the experience of the neurosurgeon as well as the tumor size. Approximately 7 of patients experience tumor recurrence, as shown by 10-yr postoperative follow-up.

Research in progress

Prospective data from the Vancouver Ovulation and Bone Change Cohort (Prior et al 1996, 1990a) are still being collected as these women become perimenopausal or menopausal. Some of those women continue to keep quantitative basal temperature and Daily Perimenopause Diary (Prior 1999) records, and will potentially provide important comparisons of ovulation and experiences in premenopausal and perimenopausal cycles in relation to subsequent menopause and bone density. As an illustration, one year of ovulatory characteristics (analysed by the QBT least squares method Prior et al 1990b) are shown from the initial study and 10 years later in one woman (Fig. 5). This woman's initial cycles averaged 29.3 1.6 days in length and became two days shorter (27.0 1.5 days, P 0.0004). The changes in luteal phase length were even more dramatic with reduction from a mean of 11.2 2.0 to 5.4 2.7 days over the 10 years (P< 0.0001). Note that she had no normally ovulatory cycles in 1994 1995 even though...


One needs to weigh up the balance of waiting, and thereby possibly risking the development of cancer, versus performing an early oophorectomy and leaving the patient prematurely hypo-oestrogenic. One would then need to address the issue of hormone replacement therapy (HRT). There is some evidence to suggest that the prolonged use of HRT is associated with an increased risk of breast cancer. In an extended follow-up of the participants in the Nurses' Health Study, Colditz found that the risk of breast cancer was significantly increased among women who were currently using oestrogen alone (relative risk (RR), 1.32 95 CI, 1.14-1.54) or oestrogen plus progestins (RR, 1.41 95 CI, 1.15-1.74) when compared with postmenopausal women who had never used hormones. Women currently taking hormones, who had used such therapy for 5-9 years, had an adjusted relative risk of breast cancer of 1.46 (95 CI, 1.22-1.74). Those currently using hormones, who had done so for a total of 10 or more years, had a...

Egg Donation

Of course, you'd prefer to use your own eggs, but that's not always possible. It could be that you've already tried to use your eggs during IVF procedures but had poor results. Or perhaps you no longer have any viable eggs because of menopause, chemotherapy, radiation, or another medical condition. In some cases, you may carry a genetic defect that you don't want to pass along to your offspring. In any of these situations, receiving eggs from another woman may be the answer to your fertility concerns.


There are no objective tests (physical, biochemical or endocrine) to assist in making the diagnosis. Prospectively completed specific symptom charts are required (Fig. 41.1). This is partly because the retrospective reporting of symptoms is inaccurate and because significant numbers of women who present with PMS have another underlying problem such as the perimenopause, thyroid disorder, migraine, chronic fatigue syndrome, irritable bowel syndrome, seizures, anaemia, endometriosis, drug or alcohol abuse, menstrual disorders as well as psychiatric disorders such as depression, bipolar illness, panic disorder, personality disorder and anxiety disorder.


Women have no PMS before puberty, during pregnancy or after the menopause - these are times where ovarian hormone cycling has not begun or has ceased. Conversely, the use of progestagens in sequential hormone replacement therapy (HRT) provokes cyclicity in the negative mood and physical symptoms similar to those seen in PMS.

Genetic testing

Genetic testing for the presence of mutations in BRCA1 or BRCA2 is still relatively new, and individuals undergoing genetic testing carry a substantial stress burden. If the results of the test are positive they cannot, of course, indicate when the disease will develop, or indeed whether it will, as the genes do not have full penetrance. Also, sporadic breast cancer risk factors are still present for these women (e.g. age of menarche, menopause, pregnancy and age).


Seventy percent of Caucasians and Afro-Caribbeans suffer from hot flushes and sweats, the commonest menopausal symptoms. This compares to 10-20 of Japanese and Chinese women and may reflect cultural differences or may be diet related (e.g. isoflavone consumption in Asia). Hot flushes are thought to arise due to loss of oestrogenic induced opioid activity in the hypothalamus leading to thermo-dysregulation. It is thought that noradrenaline and serotonin mediate this activity hence the rationale for using the alpha agonist clonidine and the selective serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine as alternatives to HRT. Obese women are protected from these symptoms due to their production of large amounts of oestrone and their low sex hormone binding globulin levels which leaves more of the free active hormone. Other typical immediate menopausal symptoms include insomnia, anxiety, irritability, memory loss, tiredness and poor concentration. Mood disturbances can occur...

Long term

Osteoporosis, cardiovascular disease and dementia are three long-term health problems which have been linked to the menopause. Osteoporosis is predominantly a disease of women who achieve a lower peak bone mass than men and are then subjected to an accelerated loss of bone density following the menopause. The hypoestrogenic state leads to activation of the bone remodelling units with an excess of bone resorption relative to formation (Fig. 47.3) 6 . Women lose 50 of their skeleton by the age of 70 years, but men only lose 25 by the age of 90 years. The strength of bone is decreased to such an extent that by 70 years of age, 50 of women will have sustained at least one osteoporotic fracture. 20 Menopause 80 20 Menopause 80 Women are protected against cardiovascular disease before the menopause, after which the incidence rapidly increases reaching a similar frequency to men by the age of 70 years 7 . Surveys of menopausal women have shown that their perceived risk is that 4 will develop...

Endometrial Cancer

Menopause is the most effective protective factor against endometrial cancer, suggesting that female sexual hormones also play an important role in the etiology of this type of cancer (Pike et al. 2004). The risk for endome-trial cancer is increased primarily by exposure to estrogen unopposed by progesterone, suggesting that the two female hormones may have opposing effects, such that estrogen increases the risk, while progesterone has a protective effect for endometrial cancer (Cohen and Rahaman 1995). ERs and PRs are highly expressed in endometrial epithelium. The hormone receptor status of endometrial tumors constitutes an important indicator of response to therapy, and survival. Loss of ER expression is common and is associated with poor prognosis in endometrial cancer (Navari et al. 2000), while loss of PR is associated with more advanced disease. Since PGR is a downstream target of ER-mediated estrogen activity, these findings support the hypothesis that excessive estrogen...

Ovarian Cancer

As in the case of breast and endometrium, menopause is also the most effective protective factor against ovarian cancer (Pike et al. 2004). A high number of pregnancies can also reduce the risk of ovarian cancer. Studies performed on benign ovarian tumors, which have the same cell of origin as ovarian carcinomas, have shown that estrogen maybe an etiological factor for ovarian cancer through its growth stimulatory and anti-apoptotic effects, whereas progesterone appears to offer protection against ovarian cancer (Ho 2003 Zhou et al. 2002). All ERs and PRs are expressed at various levels in these tumors. The presence of both ERs and PRs in ovarian cancers is associated with a good prognosis (Leake and Owens 1990). About 80 of all ovarian tumors express ESR1, and about 50 express ESR2, and PGR. Loss of expression of ESR2 (Bardin et al. 2004) and PGR promoter A (Akahira et al. 2002) has been proposed to be an important event leading to the development of ovarian cancer. The methylation...

Why not HRT

There are a number of reasons why alternatives to HRT may be sought. The main reason is that an individual does not wish to use hormone therapy because they are concerned about the potential side effects and risks. There may be clinician concerns because of the personal or family history of the women, for example, cardiovascular disease, venous thromboembolism or breast cancer. It maybe deemed that an alternative preparation is actually a better choice than traditional HRT. While many more exist (over 200 ) focus here is on those preparations for which some trial evidence exists. The increasing use of complementary therapies has been confirmed by recent studies 68 of women attending a menopause clinic in London had ever tried an alternative treatment for symptoms and that 62 of these women were satisfied with the results 38 .

Useful web sites (the British Menopause Society site) (the medical and Healthcare Products Regulatory Agency) (the Premenstrual Syndrome website) (the National Osteoporosis Society) (the North American society) http European Menopause Society http European Medicines Agency (the International Menopause Society) National Centre for Complementary and Alternative Medicine. Alternative therapies for managing menopausal symptoms. http ourwork Current Problems in Pharmacovigilance Oct 2004 Review of the Evidence regarding Long term Safety of HRT (European Menopause Survey 2005, Organon International Website)


In women, oestrogen deficiency due to the menopause is the major cause of both the early rapid and late slow phases of age-related bone loss. In ageing men, oestrogen deficiency also appears to be the dominant cause and is due to age-related increases in serum SHBG and to impaired gonadal production of sex steroids. The role played by decreases in bioavailable testosterone in bone loss in


Shown to have beneficial effects on BMD for all postmenopausal women regardless of the time since menopause. There are no studies on risedronate and fracture incidence to date. Oral alendronate and intermittent intravenous etidronate or pamidronate have all been shown to be effective in prevention and treatment of glucocorticoid-induced osteoporosis (83-85). Calcitonin. Calcitonin is FDA-approved for the treatment of late postmenopausal osteoporosis. It has not been shown to be beneficial for prophylaxis in early menopause. Calcitonin decreases osteoclast formation, osteoclast attachment, and bone resorption. Use of nasal salmon calcitonin spray, 200 IU per d, resulted in a 33 reduction in new vertebral fractures in postmenopausal women with established osteoporosis (87). Calcitonin has also been noted to have an analgesic benefit, but the mechanism of its effect is unknown (88). Historically, the chronic use of calcitonin resulted in tolerance to calcitonin at initial doses (89)....


The actions of estrogens on the blood lipid levels of women have been studied for many years. Lipid levels are affected by the action of endogenous sex steroid hormones and hormone replacement therapy (HRT) on liver lipoprotein metabolism. In an analysis of several studies Mumford et al. found that total cholesterol and LDL levels were highest during the follicular phase of the menstrual cycle and were lower during the luteal phase. They found HDLs to be higher during the follicular and peri-ovulatory phases. In a meta-analysis of sex steroid use by transsexual individuals, Elamin et al. found a reduction in HDL in female to male patients After menopause it has been found that LDLs and triglyceride levels rise and HDL levels decrease. HRT appears to positively affect lipid levels by lowering total cholesterol, LDLs and raising HDLs, but negatively affects lipid levels by raising triglycerides (Mendelsohn and Karas 2005). Some controversy has arisen over the delivery method of HRT....

Urethral lesions

Outflow obstruction due to urethral stenosis or a stricture is rare in women. Such lesions usually present after the menopause and are found in the distal urethra. They are often the result of chronic urethritis or may follow fibrosis from repeated urethral dilatations or other surgery to the urethra. The most common symptoms are of voiding difficulties, but recurrent urinary tract infections may occur. Diagnosis can be made using uroflowmetry in conjunction with cystometry or by videocystourethrography. Urethral pressure profilometry or cystourethroscopy will help to localize the lesion. Urethrotomy, either Otis or open, is the treatment of choice, and local oestrogen therapy may be helpful in postmenopausal women.

Drug therapy

Combined oestrogen progestogens Oral contraceptives Hormone replacement therapy Medical therapies can be divided into two main classes non-hormonal and hormonal. The former includes nonsteroidal anti-inflammatory drugs and antifibrinolytics, and the latter progestogens, oral contraceptives, hormone replacement therapy, danazol, gestrinone and GnRH analogues (Tables 40.3 and 40.4). Non-hormonal treatment is taken during menstruation itself and should be a first line in primary care using either mefenamic acid or tranexamic acid both can be used together, but there are no good studies of the effect of the combination. Referral should be The main adverse effects associated with LNG-IUS are frequently occurring variable bleeding and spotting, particularly within the first few months of use. LNG-IUS is also sometimes associated with the development of ovarian cysts, but these are usually symptomless and show a high rate of spontaneous resolution. When compared with other medications and...



The menstrual cycle, pregnancy and the menopause are the most significant endocrine events which may influence pelvic floor fascia. Women often declare that prolapse symptoms are worse around the time of menstruation. This is thought to be secondary to higher progesterone levels increasing fascial elasticity. Recent studies have shown that women examined at the time of menstruation will have a higher stage of prolapse than at other times of the cycle. This has important implications when deciding on treatment. During pregnancy, prolapse symptoms will be more evident in the first trimester but diminish as the pregnant uterus enlarges out of the pelvis. During pregnancy many women develop stress incontinence of urine for the first time. Research has shown that fascial elasticity increases in pregnancy 5 and this probably results in diminished pelvic floor support and a tendency to stress incontinence. Women who develop stress incontinence of urine during pregnancy are more likely to...

Hormonal treatments

Hormonal treatments have traditionally attempted to mimic pregnancy or the menopause, based upon the clinical impression that the disease regresses during these physiological states. The treatments currently available -combined oral contraceptives (COCs), progestagens, danazol, gestrinone and gonadotrophin-releasing hormone (GnRH) agonists - have been extensively reviewed. Despite different modes of action, they all appear to induce atrophy and decidualization of peritoneal deposits by suppressing ovarian function. Peritoneal lesions decrease in size during therapy but reappear rapidly following therapy DIE responds in a similar manner (unpublished data). Endometriomas rarely decrease in size and adhesions will be unaffected.

Patient assessment

The diagnosis of the menopause can usually be ascertained from a characteristic history of the vasomotor symptoms of hot flushes and night sweats and prolonged episodes of amenorrhoea. Measurement of plasma hormone levels in patients with classical symptoms are unnecessary, expensive, time consuming and of little clinical significance. However, in the young patient or in a woman after hysterectomy, where the diagnosis is more difficult and the metabolic implications are serious, measurement of FSH levels may be helpful, in which case repeated measurements of 15 IU L or above may be regarded as climacteric. In patients still menstruating, persistent hot flushes and night sweats are suggestive of the climacteric, but in those patients with psychological symptoms the diagnosis may be more difficult even with an elaborate psychiatric history. In such cases it may be justified to give a trial of oestrogen therapy and monitor the response before discounting a hormonal aetiology.

Vascular tone

For some time a correlation between blood pressure and progression of retinopathy has been noted in epidemiologic studies demonstrating that lower blood pressures result in less diabetic retinopathy. This has now been confirmed by large randomized studies (Epidemiology of Diabetes Interventions and Complications (DCCT EDIC) Study Research Group 2005 The Diabetes Control and Complications Trial Group 1993 UK Prospective Diabetes Study Group 1998). It is well established that adolescent and premenopausal women have lower blood pressures than age matched males and that blood pressure in women rises after menopause. Systolic and diastolic blood pressures in men less than 60 years old are higher than in women by 6-7 and 3-5 mmHg (Dubey et al. 2002). Also blood pressure in women can be affected by the menstrual cycle, pregnancy and supplementation of estrogens (Mendelsohn and Karas 2005). While ERa and ERp both mediate important effects on blood vessels animal studies indicate that ERp...

Pedigree analysis

The cumulative risk of breast cancer according to decades from 29 to 79 years of age, based on age at diagnosis of one or two first- and or second-degree relatives with breast cancer. Predictions using the Claus model for women with one first-degree relative with breast cancer, one second-degree relative with breast cancer, and two first-degree relatives with breast cancer are shown in Table 8.1. Cumulative risk based on other combinations of relatives with breast cancer (mother and maternal aunt, mother and paternal aunt, and two second-degree relatives) are available in the publication by Claus et al. (1994). As an example, the risk of breast cancer by 79 years for a woman who is 35 years old at counselling and has an affected mother and an affected maternal aunt would be 0.37 and 0.18 according to whether the breast cancers occurred before or after menopause (Table 8.2). The risk of the same woman would be 0.22 even if the breast cancers occurred before menopause in two maternal...

Resistance Training

The incidence of coronary heart disease increases with age and after the menopause (BHFS, 2004). This coincides with an age-related decline in muscular strength and fat-free mass after the age of 50 (ACSM, 2001). RE has been shown to prevent decline in muscle strength and has shown favourable improvements in lean muscle mass (Pollock, et al., 1998).These benefits support the inclusion of RE within a comprehensive cardiac rehabilitation programme.

Alternatives to HRT

In December 2004, the European Medicines Agency ruled that HRT should no longer be used as a first line treatment for osteoporosis. This advice was mirrored by the MHRA in the UK who proclaimed that the long-term risks of HRT outweighed the benefits and that alternative preparations should be used for osteoporosis prophylaxis and treatment. The National Institute for Clinical Excellence (NICE) has recently carried out a technology appraisal for three of the main alternatives to HRT, bisphosphonates, raloxifene and parathyroid hormone. Treatment guidelines have been issued (Jan 2005 NICE website) but there is a delay in the advice regarding prophylaxis as it was only agreed to issue the latter advice after protests from the National Osteoporosis and British Menopause Societies. The most commonly employed alternatives to HRT for bone protection will now be considered.


ACE, angiotension converting enzyme AGE, advanced glycation end-products AR, androgen receptor Akt, serine threonine protein kinase CNV, choroidal neovascularization COX, cyclooxygenase CVD, cardiovascular disease DHEA, dehydroepiandrosterone DHT, dihydrotestosterone DIEP, Diabetes in Early Pregnancy Study E, estrogens E2, 17p-estradiol EDRF, endothelium-derived relaxing factor ETDRS, Early Treatment of Diabetic Retinopathy Study eNOS, endothelial nitric oxide synthase ER, estrogen receptor ERa, estrogen receptor alpha ERp, estrogen receptor beta ERE, estrogen-response element ERK, extracellular signal-regulated kinases FGF, fibroblast growth factor HAM, hypoandrogen metabolic syndrome HDL, high-density lipoprotein HLA, human leukocyte antigen HRT, hormone replacement therapy HSP, heat-shock protein HUVEC, human umbilical endothelial cells IDDM, insulin-dependent diabetes mellitus, type 1 ICAM, inter-cellular adhesion molecule LDL, low-density lipoprotein LH, luteinizing hormone MAPK,...