Natural Menopause Relief Secrets

Power Of Hormones

The power of hormones program by Angela Bryne in a PDF form that outlines various ways of dealing with hormonal imbalance. Angela is a health Specialist, a researcher, writer and also a mother of three children. She was diagnosed with depression and sleeping disorder, conditions that motivated her to find ways of achieving optimal hormonal levels. Therefore, this book will help you learn various ways of treating your hormonal imbalance. Our whole body is managed by the endocrine system. Hormones are liquid chemical messengers that regulate major functions in our bodies. Important to note, they are responsible for dictating how the body perform various physiological functions. When hormones fail to function correctly, we end up having a hormonal imbalance. The human body functions optimally on different hormonal balance level. For this reason, it is prudent to always consider our hormonal levels and how they relate to each other. This is exactly why you need the Power of Hormones Guide by Angel. Read more here...

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Menopausal Status and the Androgen Milieu

The correlation between menopausal status and sexual health among diabetic women has been poorly investigated. Data seem to suggest, however, that the postmenopausal condition does not cause a significantly negative impact on women's sexuality particularly because of the diabetes mellitus itself (9, 23, 37, 38, 40). Similarly, the potential associations among the circulating androgen milieu total and free testosterone, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), and A4-androstenedione (A4A) and SF in diabetic women have been scarcely analysed, especially when studies adequately segregating both the type of diabetes and the pre- vs. postmenopausal population are considered. In contrast, several studies have analysed the concept that endogenous sex hormones may have a role in sex-dependent aetiologies of DM2, such that hyperandrogenism may increase risk in women while decreasing risk in men (55-63). In their comprehensive review, Ding et al. (56) reported that cross-sectional...

Dealing with Type Diabetes during Menopause

Menopause can be an even more difficult transition than the onset of menstrual periods for several reasons. Here are a few key changes associated with menopause i Estrogen, which makes the body more sensitive to insulin, declines during menopause, resulting in decreased insulin sensitivity. i The symptoms of menopause, such as hot flashes, sweating, and flushing, may be confused with symptoms of hypoglycemia. The way you manage this difficult time is no different from managing your diabetes at any other time insulin, diet, and exercise, along with lots of self-testing of the blood glucose. You have one other consideration during menopause, however the question of hormone replacement therapy. One question that may occur to you as you reach this passage from menstrual function to menopause is whether your T1DM needs to be as well-controlled at age 51 as it was at age 31. The answer is a definitive yes. You may have 30 or more years of life ahead of you, so you definitely don't want to...

Changes In Gonadal Hormones At Menopause

Menopause is defined as the cessation of menses for 12 months after the final menstrual period (1), and it results from the depletion of ovarian follicles with resulting loss of ovarian sex hormone production. The average age at which women in the USA and Western Europe undergo natural menopause is 50-51 years (2, 3). Women who undergo menopause before 40 years of age are considered to have premature ovarian failure (4). In 2001, the Stages of Reproductive Aging Workshop (STRAW) was convened in order to develop a useful staging system for reproductive aging in women and to revise the often-confusing nomenclature used to describe this process. The menopausal transition was The onset of the menopausal transition is marked by a shift from regular to irregular menstrual cycles (1). Marked hormonal fluctuations occur during the menopausal transition (5, 7). While FSH levels during the menopausal transition are higher than in the late reproductive phase, FSH levels may intermittently...

Getting through pregnancy and menopause

Starting with oral contraceptives, Chapter 16 takes you through preparing for pregnancy, getting through the pregnancy, and considering hormone replacement therapy during menopause. The surge of estrogens and progesterones that occurs every month in a menstruating female makes it even harder to control the blood glucose, so you find out the best ways to handle this tricky situation.

Going through Pregnancy and Menopause

Attaining tight control of T1DM before conception Getting through pregnancy safely Managing menopause and T1DM After the years when pregnancy is possible, the woman with T1DM has special challenges as she goes through menopause. Should she use hormone replacement therapy What are the special considerations for the woman with T1DM as she ages so that she can enjoy a high quality of life for many years I cover all these issues in this chapter.

Considering hormone replacement therapy

In recent years, medical experts have gone from recommending hormone replacement therapy (HRT) to all postmenopausal women, to condemning it as a source of all kinds of problems like heart attacks, to a more subtle reconsideration that's currently taking place, so I don't blame you if you're confused about this subject. Because these hormones have a definite effect on your blood glucose control, you need to understand what they do and whether they're for you. With the onset of menopause, you're at risk for some or all of the following symptoms Having T1DM along with menopause adds several other problems that make your blood glucose even more difficult to control they include Because all these symptoms seem to arise from a lack of the hormones estrogen and progesterone, it seems logical to replace them to reverse the problems. Hormone replacement therapy was the standard treatment for all these conditions up until 2002. It also was thought to protect women against osteoporosis and...

Symptoms Of Menopause

Characteristic symptoms of menopause include vasomotor instability (hot flashes and sweating), vaginal dryness, urinary incontinence, and sleep disturbance (3). The sleep disturbance is often due to hot flashes or night sweats that occur during sleep hours. Whether these symptoms differ in women with diabetes has not been systematically studied. Women with diabetes may attribute their menopausal hot flashes or sweats to hypoglycemia and inappropriately take in calories leading to weight gain. On the other hand, these women may also attribute sweating from hypoglycemia to menopause symptoms and not appropriately treat episodes of hypoglycemia. Urinary incontinence increases in frequency at menopause. In a study of over 1,000 postmenopausal women, there was no difference in urinary incontinence in women with diabetes as compared to those without. Severe incontinence was more common in women with diabetes although that may be in part explained by higher BMI (14).

Menopause and Diabetes Mellitus

Changes in Gonadal Hormones at Menopause Symptoms of Menopause Age of Menopause Changes in Body Composition at Menopause Risk of Diabetes in Postmenopausal Women Hormone Replacement Therapy Conclusion References Around the time of menopause, there are important changes in body composition and insulin sensitivity, which may impact both the risk for diabetes mellitus as well as glycemic control in individuals with established diabetes. Furthermore, these parameters may be affected by the use of hormone replacement therapy, a common treatment for menopausal vasomotor symptoms. Changes in body composition, beyond changes in weight, occur around the time of menopause, and these alterations in body composition have been correlated with changes in insulin resistance and glucose tolerance. Several studies have suggested that hormone therapy use reduces diabetes risk in postmenopausal women. Clinicians must keep these metabolic changes in mind when caring for postmenopausal women with and...

Risk Of Diabetes In Postmenopausal Women

The risk for diabetes increases with increasing age in both women and men. Whether menopause per se magnifies the risk for diabetes in women beyond that of age alone is not clear. The changes in body composition described earlier could contribute to increased diabetes risk following menopause. In addition, it is possible that hormonal changes that occur at menopause may affect diabetes risk. In the Multi-Ethnic Study of Atherosclerosis (MESA) study of 1,973 postmenopausal women of age 45-87 years, investigators found that higher levels of free testosterone were associated with a higher likelihood of impaired fasting glucose (IFG) but not diabetes. On the other hand, higher levels of estradiol were associated with both IFG and diabetes (45). In the Rancho Bernardo study, higher levels of free testosterone were predictive of the future development of DM2 independent of adiposity in older women of age 55-89 years (46).

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...

Effects of Changes in Body Composition on Insulin Sensitivity in Postmenopausal Women

The menopause-associated adverse changes in body composition are in turn associated with unfavorable effects on insulin sensitivity. It is well established that obesity, and particularly abdominal obesity, increases the risk of insulin resistance in the general population (40). These relationships have not been as extensively studied in postmenopausal women. Abdominal obesity has been shown to be independently associated with decreased insulin sensitivity (41) and glucose tolerance (42) in postmenopausal women. A secondary analysis of women participating in the Postmenopausal Estrogen Progestin Interventions (PEPI) study who were not taking estrogen revealed that increased BMI and waist-to-hip ratio were independently associated with increased glucose and insulin levels, both during fasting and after oral glucose (43). Furthermore, an interventional study of obese postmenopausal women with DM2 showed that exercise training led to improvements in insulin sensitivity, and these...

Effects of Menopause on Body Composition

Although weight gain is a common occurrence around the time of menopause, the bulk of the evidence suggests that this weight gain is a function of aging rather than a change in menopausal status (20). Yet several studies have demonstrated that several changes in body composition, beyond changes in overall body weight, are independently related to menopausal status (21-29). Changes in body composition, including the amount and distribution of body fat, are important predictors of cardiovascular risk. In particular, increased abdominal fat (also referred to as android or upper body fat) is associated with increased coronary heart disease risk, independent of body mass index (BMI) and traditional cardiovascular risk factors (30, 31). Cross-sectional studies have shown that postmenopausal women compared with premenopausal women have increased fat mass (21, 22, 29), increased abdominal fat (21-24), and decreased lean body mass (21, 25-27), independent of age. In addition, data from the...

Hormone Replacement Therapy and Diabetes

After menopause, if you use hormone replacement therapy, add these tests to your diabetes plan. Any tests that give abnormal results should be repeated more frequently. Have your A1C tested two to four times a year. This test tells you about your blood glucose levels over the long term. Have your cholesterol and triglyceride levels checked as recommended by your provider. The progesterone in hormone replacement therapy can sometimes cause cholesterol levels to rise.

Hormonal Replacement Therapy Womens Sexual Health and Diabetes

Upon natural menopause, sex hormones, physical and mental well-being and feelings for the partner are extremely relevant for women's sexuality. Even a significant lack of androgens, as more frequently occurs in surgical menopause, has a negative impact on women's desire and sexual responsiveness (126). Although menopause has been identified as a significant risk factor for SD among the general population (127-131), the same issue has been scarcely investigated among women with diabetes (19-26, 37, 38, 40, 41, 57, 58, 62). All the reports described earlier seem to support the idea that menopause per se should not be considered as an independent predictor of SD in diabetic women. Moreover, no studies have investigated the potential use of specific compounds for the treatment of SD among postmenopausal diabetic women, not even hormone replacement therapy. Local estrogen supplementation need not be withheld in postmenopausal women with diabetes. Indeed, vulvovaginal atrophy may be a...

HMG CoA Reductase Inhibitors

Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women. Ann Intern Med 1994 121(12) 936-941. 187. Gilligan DM, et al. Acute vascular effects of estrogen in postmenopausal women. Circulation 1994 90(2) 786-791.

Loss of Estrogen Protection in Diabetic Women

The mechanism by which DM2 abrogates the protective effect of estrogens in premenopausal women is incompletely understood. Increased CVD in diabetics has been linked to several factors, including enhanced platelet aggregation, hypercoagulability, decreased fibrinolysis, endothelial dysfunction, lipoprotein abnormalities, increased oxidative stress and inflammation, and enhanced vascular growth factor stimulation. Both hyperglycemia and insulin resistance hyperinsulinemia abrogate estrogen protection in premenopausal diabetic women by interfering with one or more of the earlier mechanisms. leads to rapid production of large amounts of NO, which causes various pathological effects including excessive vasodilation. In diabetic women reductions in estradiol receptor expression and the ability of estrogen to modulate iNOS contribute to diabetic vascular dysfunction (2). This impairment in estrogen modulation of both eNOS and iNOS activity appears to be related to abnormalities in receptor...

Obesity and the Abdominal Phenotype in PCOS

In humans, it is demonstrated that testosterone increases visceral fat in women. Female-to-male transsexuals treated with testosterone do in fact have an increase in visceral fat only when oophorec-tomized and thus eliminating the protective effects of estrogens (105). In addition, administration of androgens in postmenopausal women has been documented to increase visceral fat while reducing subcutaneous fat (106). This indicates that an increase in the testosterone to estrogen ratio in women causes accumulation of visceral adipose tissue, consistent with the important role of testosterone in determining the high prevalence of abdominal fat distribution pattern in hyperandrogenized women with PCOS.

The Metabolic Syndrome in PCOS

Due to the high prevalence of insulin resistance in PCOS, some recent studies used the NCEP ATP III criteria to assess the prevalence of the metabolic syndrome in PCOS women. Glueck et al. (95) studied 138 PCOS patients and found a prevalence rate of 46 , whereas, more recently, Apridonidze et al. (82) found a prevalence of 43 by retrospectively reviewing the medical charts of 106 PCOS women attending the Endocrine Clinic of Richmond, Virginia. Both these studies, therefore, described a prevalence of the metabolic syndrome in PCOS women nearly twofold higher than that reported in the general population investigated in the cited NHANES III report (96), matched for age and body weight. Apridonidze et al. (82) also described higher free testosterone and lower SHBG levels in those women with the metabolic syndrome compared with those without it, as well as a higher prevalence of acanthosis nigricans and a tendency toward a greater family history for PCOS. These results were in accordance...

Contemporary Endocrinology

Leonard Share, 1999 Menopause Endocrinology and Management, edited by David B. Seifer And Elizabeth A. Kennard, 1999 The IGF System Molecular Biology, Physiology, and Clinical Applications, edited by Ron G. Rosenfeld and Charles T. Roberts, Jr., 1999 Neurosteroids A New Regulatory Function in the Nervous System, edited by Etienne-Emile Baulieu, Michael Schumacher, 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

Diabetes Mellitus and Breast Cancer Risk

Two studies included all hospitalized patients diagnosed as diabetics in Denmark from 1977 to 1989 (n 55,010) 27 and in Sweden from 1965 to 1983 (n 80,005) 28 and both reported on elevated risk of breast cancer among diabetic patients (standardized incidence ratios 1.2, 95 CI 1.1-1.2 and SIR 1.3, 95 CI 1.2-1.4 respectively). However, the results of these studies should be interpreted with some caution use of hospitalization records and of former definitions of diabetes meant that both studies included patients with severe forms of type 2 diabetes compared to current definitions and did not exclude type 1 diabetes patients. In addition, both studies did not adjust properly for obesity. Michels et al. 29 reported on the association between type 2 diabetes and breast cancer in more than 6,000 participants of the Nurses' Health Study, which is a prospective population-based study. After adjustment of the HR for age, obesity, reproductive factors and benign breast disease, a modest but...

Summary and conclusions

Hyperinsulinemia may have a sex trait is not arbitrary, although major determinants are not adequately understood. Interestingly, sex-specific genes may therefore have a demonstrable impact on fetal growth and insulin resistance. There is no doubt that this topic should be subjected to a more intense investigation, taking into consideration different stages of women's lives, including the fertility period and menopause. Women, particularly those with the abdominal phenotype of excess body fat, are at risk for the metabolic syndrome, DM2, and, possibly, CvDs. This may be due to their specific hormonal condition, which is characterized by the presence of a relative hyperandrogenic status. Recent meta-analyzes have in fact shown the prevalence of DM2 to be associated with a modest increase of testosterone concentration in the general female population, although whether this also occurs for CvD susceptibility is still controversial.

Sexual Disorders Among Women with Type Diabetes Mellitus

Erol et al. (40) assessed the SF profile in 72 premenopausal DM2 women (mean age 38.8 years range 25-47) with no other systemic disease as compared with 60 age-matched healthy women. The FSFI was used to assess the prevalence of sexual disorders throughout the analysis. Overall, DM2 patients had a significantly lower FSFI total score than controls (29.3 6.4 vs. 37.7 3.5 p 0.05). Low sexual desire was the most frequently reported SD, being observed in 77 of the DM2 patients. Reduced lubrication (defined as vaginal dryness) was observed in 37.5 , whereas orgasm difficulties, vaginal discomfort (pain), and sexual dissatisfaction were reported by 49 , 42 , and 42 of the DM2 women, respectively. Similarly, Basson et al. (37) reported reduced lubrication in 47 of the DM2 women in their cohort, as well as a 31 rate for orgasm difficulties and a 42 rate of coital pain as compared with a 34 , 33 , and 26 prevalence among healthy controls (23, 37).

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...

Franks Et Al Hum Reprod 1997 12 2641-8

Holte J, Bergh T, Gennarelli G and Wide L (1994b) The independent effects of polycystic ovary syndrome and obesity on serum concentrations of gonadotropins and sex steroids in premenopausal women. Clin Endocrinol 41 473-81. Pasquali R and Casimirri F (1993) The impact of obesity on hyperandrogenism in polycystic ovary syndrome in premenopausal women. Clin Endocrinol 39 1-16. Pijl H, Langerdonk JG, Burggraaf J et al. (2001) Altered neuroregulation of growth hormone secretion in viscerally obese premenopausal women. J Clin Endocrinol Metab 86 5509-15.

Effects of HRT on Glycemic Control in Women with Diabetes

Women with diabetes were found to use HRT less commonly than women without diabetes (49). Yet studies have suggested neutral or beneficial effects of HRT on glycemic control among postmenopausal women with diabetes. Large observational studies have shown that glycemic control is improved in postmenopausal women with diabetes who use HRT compared with those who do not use HRT. One large study of women with diabetes aged 50 years included in the Northern California Kaiser Permanente Diabetes Registry found that HRT use was associated with an approximate 0.5 reduction in hemoglobin A1c (HbA1c), independent of age, ethnicity, obesity, education, exercise, disease duration, treatment type, and monitoring practices (50). Another study examining postmenopausal women with diabetes who participated in the Third National Health and Nutrition Examination Survey (NHANES III) found that current users of HRT had significantly lower HbA1c and fasting glucose levels than women who had never used HRT...

Mechanisms Underlying Endothelial Dysfunction in Diabetes

As discussed previously, hyperglycemia has also been shown to decrease estradiol-mediated NO production in women, perhaps contributing to the increased CVD risk in women than in men with diabetes. NO-dependent vascular tone and endothelial-dependent vasodilation are enhanced in nondiabetic premenopausal women than in men. The interaction between hyperglycemia and estradiol-mediated NO production has been well documented. Hyperglycemia decreases estradiol-mediated NO production from cultured EC (83). Men with DM2 do not appear to have reduced endothelium-dependent vasodilation beyond that observed with obesity alone in contrast to women with DM2. Thus, hyperglycemia appears to negate the protective effects of estradiol in part by decreasing vascular and perhaps platelet NO production.

Effects of HRT on Risk of Developing Diabetes

Although this reduction was not seen in all studies (60). In a post hoc analysis of the Heart and Estrogen Progestin Replacement Study (HERS), a large randomized, double-blind placebo-controlled study, the use of CEE and MPA in postmenopausal women with documented coronary artery disease (CAD) was associated with a 35 reduction in the new diagnosis of DM2 over 4.1 years vs. placebo. Of interest, the decrease in risk was primarily due to lower levels of fasting blood glucose as opposed to BMI or waist circumference (35). However, the study was designed to determine whether HRT was of benefit in reducing myocardial infarction and death from CAD, and the study demonstrated no reduction of CV risk. Women in the study on HRT had a significant increase in deep venous thrombosis than those on placebo (61), which makes this regimen undesirable for diabetes prevention. In the Women's Health Initiative (WHI), a large randomized placebo-controlled study of hormone replacement therapy (CEE and...

Antimicrobial treatment

Estrogen suppletion in postmenopausal women (oral or vaginal)) 61,60,62 Vaccines (both currently on halt) Urovac 66 An interesting possible preventive or treatment option is ingestion of cranberry juice. At first, the beneficial effect of cranberry juice was thought to be the result of acidification of the urine. More recently, in vitro studies have identified the inhibition of bacterial adherence to the uroepithelial cells as the most plausible mechanism of action 57 . Another possible preventive strategy is the oral or vaginal administration of lactobacilli. Lactobacilli are part of the commensal vaginal flora and are thought to protect against UTIs by competitive exclusion of uropathogens 58 . In a recent randomized trial, regular drinking of cranberry juice but not of lactobacillus GG drink reduced the recurrence of UTIs in women with E. coli infection 59 . In addition, several investigators have studied the influence of estrogen administration. Estrogen deficiency in...

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...

Diabetes And Minerals Vitamins And Dietary Supplements

This study evaluated the intake of various antioxidant vitamins found in foods and supplements to their relationship to coronary artery disease and overall mortality. This study evaluated close to 35,000 postmenopausal women (aged 55-69 years) with no history of cardiovascular disease for 7 years. Intake of vitamins A, E, and C were estimated by questionnaires and then correlated with

Procoagulant Activity

Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality in premenopausal women, and insulin resistance and compensatory hyperinsuli-nemia play a fundamental role in the etiology of this syndrome. This is another example of an organ, in this case the ovary, responding normally to hyperinsuli-nemia by increasing testosterone secretion in the face of muscle and adipose tissue insulin resistance. Indeed, in this instance, the ovary may be supersensitive to insulin stimulation. In any event, the primary clinical manifestations of PCOS (hirsutism, abnormal menstruation, and difficulty in conceiving) are secondary to increased insulin-stimulated testosterone secretion by the ovary. Women with PCOS are at increased risk to develop both type 2 diabetes and the dyslipidemia of syndrome X. Both of these changes suggest that insulin-resistant and hyperin-sulinemic women with PCOS will be at increased risk of CHD, and there is now evidence of enhanced atherogenesis in middle-aged...

The Metabolic Syndrome CardiovASCuLar Risk Factors And Cardiovascular Events In Women

Overall, the data support the concept that the prevalence of the metabolic syndrome may differ according to sex, and this may be particularly relevant for women, who physiologically undergo several vulnerable periods during their life, such as menopause. Menopause is in fact a typical physiological event in women, but its occurrence considerably changes their susceptibility to develop metabolic diseases and CvDs. Although the mechanisms responsible for these dramatic events are not completely understood, there is nonetheless evidence that changes in the hormone milieu, other than age, play an important role. Both these factors do in fact have an important regulatory function on metabolism and cardiovascular physiology. The emergence of the metabolic syndrome with menopause has been reviewed recently by Carr (38). In fact, the prevalence of the metabolic syndrome tends to increase with menopause and may partially explain the apparent acceleration in CvD after menopause. The transition...

Diabetes And CardiovASCuLar Risk Factors In Women

Obesity is one of the most important risk factors for DM2. In North America as well as in Europe and East Asia, the number of people considered overweight or obese is dramatically increasing (61), involving approximately half the population. Sex differences in weight are clearly influenced by geography and ethnic background. For example, data coming from the United States show that among whites and Mexican Americans, the prevalence is higher among men than among women. However, among black Americans, the prevalence of being overweight or obese is higher in women than in men (62). These figures are more or less similar in Canada (63). In Europe these trends are also similar, although the extent of this epidemic appears to be lower (61). In addition, obesity is also prevalent in many developing countries, with some geographical and ethnic differences. Collectively, prevalence rates appear to be similar for the two sexes, although available data suggest that countries reporting higher...

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...

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...

Effect of Insulin Resistance Treatment on Polycystic Ovary Syndrome Weight Loss

It has been established that HRT is beneficial in reducing osteoporosis and alleviating climacteric symptoms. HRT has also been shown to have beneficial effects on risk factors for CVD. However, data from recent clinical trials indicate that HRT, in the form of continuous combined CEE with MPA, has no cardioprotective effects and is not recommended for primary or secondary prevention of CVD in postmenopausal women. Data on HRT in postmenopausal women with diabetes are scarce but are of major importance, because these women are characterized by hyperandrogenicity, insulin resistance, and dyslipidemia and are at a higher risk for developing CHD. Evidence from the available data suggest that short-term unopposed oral estradiol has a beneficial effect on glucose homeostasis, lipid profile, and other components of the metabolic syndrome, which may be compatible with a reduced risk of CHD. The addition of a progestogen may attenuate some of these favourable effects. On the other hand, HRT...

Breast Cancer Risk and Diabetes Mellitus Type

The adipocytes, forming the belly fat, are now in the focus of metabolic research in oncology. Adipocytes produce adipocytokines, which are biologically active polypep-tides and act by endocrine, paracrine, and autocrine mechanisms most have been associated with MeS. Six adipocytokines - vascular endothelial growth factor, hepa-tocyte growth factor, leptin, tumor necrosis factor-a, heparin-binding epidermal growth factor-like growth factor, and interleukin-6 - promote angiogenesis. Obesity and insulin resistance, again, have been identified as risk factors for breast cancer and are associated with late-stage disease and poor prognosis 12 . However, the picture is not as clear as to be expected because a case-control study in Chile did not show any association between obesity and breast cancer at any age, although the same study revealed that insulin resistance was independently associated with breast cancer in postmenopausal women, but not in premenopausal women 13 . Another question...

Other intervention studies

In a single blind intervention study in Italy 120 menopausal (20-46 years old) obese women (BMI 30 kg m2) were randomly divided into two groups (Esposito et al., 2003). Women with impaired glucose tolerance or diabetes were excluded. In the intervention group the participants received detailed instructions how to reduce weight by 10 per cent by regulating diet and increasing physical activity. The methods to use included food diaries, personal goal setting, monthly small group sessions, and access to behavioural and psychological counselling. In the control group, women received general information about healthy dieting and physical exercise at baseline and in subsequent monthly visits but not specific individualized programme. The intervention had a beneficial effect on weight, fat distribution, and fasting plasma glucose after 2-year follow-up these indicators had decreased more in the intervention group (14 kg for weight, 0.08 for waist-hip ratio, and 9 mg dl for plasma glucose)...

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 type 1 diabetic women. FSD was not related to age, BMI, HbA1c, duration of diabetes, and diabetic complications. However, FSD was related to depression and the quality of the partner relationship (153). Recently, the prevalence of FSD in premenopausal women with the metabolic syndrome was compared to the general female population. Women with the metabolic syndrome had reduced mean full Female Sexual Function Index (FSFI) score, There is evidence to suggest that in men with diabetes, sexual dysfunction is related to somatic and psychological factors, whereas in women with diabetes, psychological factors are more predominant (153). The...

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...

Duration of Diabetes Diabetes Related Complications and Diabetes Control

Peripheral and autonomic neuropathies have been frequently associated with and are considered an important cause of erectile dysfunction in diabetic men. With the specific aim to assess whether peripheral neuropathy may be causally associated with the development of sexual disorders among diabetic women, Erol et al. (44) experimentally evaluated the genital and extragenital somatic sensory system using biothesiometry. In this case-control survey of 30 premenopausal diabetic women and 20 healthy sexually active women, women with diabetes showed a mean FSFI total score significantly lower than that of controls (23.6 vs. 38.3 p 0.0005). Moreover, for each genital and extragenital site, the mean biothesiometric values were significantly higher in diabetics, with the sensation at the vaginal introitus, the labium minora, and the clitoris the most deteriorated in diabetic women. A correlation was not found in women with diabetes, because the difference between women with or without SD was...

Where to Go from Here

Where you go from here depends on your needs. If you want a basic understanding of what T1DM is and isn't, head to Part I. If you or someone you know has a complication due to T1DM, skip to Part II. For help in treating T1DM using every available tool, turn to Part III. If you're thinking of becoming pregnant, are going into menopause, are elderly, or have a parent with T1DM, Part IV is your next stop. Likewise, go there if you want to know what your options are for school, work, and other activities, or if you want to know how to manage travel or illness. For a bird's-eye view of getting kids involved, key treatment strategies, the mythology that surrounds T1DM, and the latest discoveries, check Part V.

Epidemiological studies in favour of the iron hypothesis

The lower incidence of coronary heart disease in premenopausal women compared with men of the same ages and with postmenopausal women was shown to be due to the lower total body iron caused by menstrual blood loss (Sullivan 1989). In men, body iron assessed by ferritin concentration, rose after adolescence, while in women, ferritin began to rise only after the age of 45 years (Burt et al. 1993). The Framingham study showed that the risk of heart disease in women increased equally by natural or surgical menopause (Gordon et al. 1978 Hjortland et al. 1976 Kannel et al. 1976). In heterozygotes of familial hyperlipoproteinaemia, the premenopausal women had a lower risk of coronary heart disease than men (Ascherio & Hunter 1994 Slack 1969 Stone et al. 1974).

Dietary antioxidants and the prevention of CHD epidemiological evidence

Kushi et al. studied over 34000 postmenopausal women with no cardiovascular disease who in early 1986 completed a questionnaire that assessed, among other factors, their intake of vitamins A, E and C from food sources and supplements.38 After 7 years of follow-up, results suggested that in post-menopausal women the intake of vitamin E from food was inversely associated with the risk of death from coronary heart disease. This association was particularly striking in the subgroup of 21 809 women who did not consume vitamin supplements (relative risks from lowest to highest quintile of vitamin E intake, 1.0, 0.68, 0.71, 0.42 and 0.42 P for trend 0.008). After adjustment for possible confounding variables, this inverse association remained (relative risks from lowest to highest quintile, 1.0, 0.70, 0.76, 0.32 and 0.38 P for trend 0.004). By contrast, the intake of vitamins A and C was not associated with lower risks of dying from coronary disease.38 34000 postmenopausal women, followed up...

Increased cardiovascular risk

With the synergistic negative effect of obesity and PCOS on glucose tolerance (Dunaif, 1997). It has been reported that postmenopausal women with history of PCOS has a 15 per cent prevalence of type 2 diabetes which is much higher than in the general population (Dalhgren et al., 1992). In the presence of peripheral insulin resistance, pancreatic -cell insulin secretion increases but impaired glucose tolerance and type 2 diabetes mellitus develops when the compensatory increase in insulin secretion is no longer able to maintain euglycaemia. Ehrmann et al. (1999) recently documented that insulin secretory dysfunction in women with PCOS contributed significantly to the observed glucose intolerance with up to 40 per cent of women demonstrating either IGT or type 2 diabetes mellitus. Recently Norman et al. (2001) performed a follow-up study of women with PCOS seeking to establish the frequency of change of IGT and type 2 diabetes over an average period of 6.2 years. They reported 9 per...

Improvement of endothelial function

Endothelial dysfunction leads to defects in insulin-mediated glucose uptake. Blockade of vascular nitric oxide synthesis with L-arginine analogue also impairs endothelial dependent va-sodilation. Endothelial function improves with exercise, a low-fat, low-carbohydrate diet, and with use of statins and ACE inhibitors (Table 5) 29,59,67 . Angiotensin I blockade has not shown any improvement of endothelial dysfunction, but benefit has been noted with peroxisome pro-liferator activated receptor gamma (PPAR-y) stimulator, antioxidants, hormone replacement therapy, and L-arginine 66,68,69 . In addition, the ACE inhibitor quinapril significantly improved endothelial function in multiple studies, both in normotensive volunteers and in subjects with coronary artery disease 70-77 .

Prevention of Cardiovascular Outcomes in Type Diabetes Mellitus Trials on the Horizon

Clinical trials addressing the relationship between intervention to lower glucose and CV events are awaited with great interest. Furthermore, no outcomes studies have been conducted with insulin analogs or thiazolidinediones. Clinical practice is informed by the best available data, but epidemiologic studies can lead one astray, as was the case with hormone replacement therapy as a technique to reduce CVD 1 .

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).

Starting before birth

The lack of testosterone in the female also causes the brain to develop female sexual characteristics in a structure called the hypothalamus, which controls many of the body's glands, including ovaries in women and testicles in men. At puberty, the hypothalamus starts the monthly cycles that continue until menopause.

Living with Type Diabetes

Women and the elderly are two special populations when it comes to living with T1DM. In this part, I discuss how women can control their diabetes during menstruation, how a woman with T1DM should be in excellent control of her T1DM prior to conceiving a baby and throughout her pregnancy, and how menopause brings new considerations including whether or not to use hormone replacement therapy. I close this part with a chapter on the elderly population with T1DM and the unique problems that they face in treating their condition.

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.

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...

Gender Specific Differences in CVD

The disparity between the incidence of CHD in age-matched premenopausal nondiabetic women and men suggests that endogenous sex hormones such as estrogen, progesterone, and or both may have a significant influence on the vasculature. Specific estrogen receptors (ER) located in endothelial and vascular smooth muscle cells (VSMC) modulate vascular tissue function (6-8). Studies using postmortem coronary artery specimens obtained from pre- and postmenopausal women have linked expression of ER to reduced atherosclerotic changes in premenopausal women. This suggests that estrogen signaling through these receptors plays an important role in coronary protection from atherosclerosis. In this context, estrogen has been shown to increase endothelial nitric oxide synthase (eNOS) activity and associated increases in nitric oxide (NO) bioavailability. Since NO attenuates platelet aggregation, expression of endothelial cell (EC) adhesion molecules, and vascular smooth muscle cell (VSMC)...

Testosterone Substitution Therapy

Sexual desire, orgasm and satisfaction among postmenopausal women (65, 66, 69-74, 144), the Endocrine Society has recommended against both diagnosing androgen deficiency in women and against general use of testosterone by women, because of the paucity of data for long-term safety and effectiveness (65). A comprehensive Cochrane review of randomised trials that compared testosterone plus estrogen vs. estrogen alone both in pre- and in postmenopausal women showed that such a combination improved SF scores for postmenopausal women within the general population (69). No data are available on the efficacy of testosterone treatment without estrogen. Likewise, there are no specific studies regarding the potential use of either testosterone substitution or tibolone, a synthetic steroid with estrogenic, androgenic and progestogenic activity that is able to improve SF in postmenopausal women (23, 144, 145) for the treatment of SD among diabetic women.

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...

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).

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...

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...

Components of obesity treatment Behavioural lifestyle modification

Persons with BMI of 25.0-29.9 kg m2 who have two or more health risk factors are encouraged to consume a low-calorie diet and increase physical activity consistent with the US Surgeon General's recommendation for 30min or more per day most days of the week (NHLBI and NAASO, 2000 US Department of Health and Human Services, 1996). Behavioural lifestyle modification has comprised the cornerstone of weight loss treatment for decades, and typically involves group-led weekly meetings focusing on dietary change, activity increase and instruction in behaviour change techniques. Programme lengths have doubled from an average of 20 weeks in the 1980s to 40 or more weeks at present (Perri et al., 1989 Wing, 2002), with the active instructional phases most commonly lasting 16-26 weeks, and follow-ups typically extended to one or more years. Dietary recommendations include limiting calories to 1000-1800 kcal day, with no more than 20-30 per cent of calories from fat. Behaviour change strategies...

Facing Female Sexual Problems

Menopause can cause several of the same difficulties as diabetes-related sexual dysfunction, particularly the dry vagina and irregular menstrual function. You must rule out menopause before assuming that diabetes is the source of the problem. Unlike the case with men with diabetes, this is the only important abnormality that is known to cause sexual problems in women that may simulate the problems of diabetes. Most women who have problems with lubrication, whether due to diabetes or menopause, medicate themselves with over-the-counter preparations. These preparations fall into three categories Estrogen, which can be taken by mouth or placed in the dry vagina in suppository form, also may be useful for the menopausal woman.

Epidemiology Of Obesity

There is a large body of clinical data demonstrating a close relationship between body fat mass and the risk of diabetes. In contrast to other obesity-associated metabolic disturbances, the risk of diabetes increases already in the upper normal range of BMI. In the Nurses' Health Study, women in the upper normal range with a BMI between 23.0 and 24.9 kg m2 had a four- to fivefold increased risk of developing diabetes over a 14-year observation period compared to women with a BMI 22 kg m2 (2). In those with a BMI between 29.0 and 30.9 kg m2 the risk of diabetes was 27.6-fold higher than in the lean reference group. Almost two-thirds of newly diagnosed women with type 2 diabetes were obese at the time of diagnosis (2). Similar observations were reported for males in the Health Professionals' Study (3). Interestingly, a change in body weight strongly predicts the risk of diabetes. Weight gain from the age of 18 between 11.0 and 19.9 kg, which is the average range of weight change between...

Gender and cardiovascular risk in diabetes

In contrast mortality from heart disease in the general population is higher in men than women at all ages, and premenopausal women have a degree of cardioprotection as CHD rates remain low at this age. This premenopausal protection appears to be completely lost in young women with type 1 diabetes and CHD mortality rates are the same as for men. This accords with incidence data from Pittsburgh (Lloyd etal., 1996b), in which similar rates of new coronary artery disease events were found in males and females under 40 years, and from the WHO study (Morrish etal., 2001), which showed similar incidence rates for new myocardial infarctions in men and women. Even though the rates fall behind those of men in the older age groups, at all ages the rates in women with type 1 diabetes are higher than those for men in the general population. Women with type 2 diabetes appear to fare only slightly better and studies suggest that some of this survival advantage may also be lost. Data from

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. The cardiovascular effects of estrogen are certainly far more complex than was initially thought. Unraveling these effects remain a challenge for future research. Despite the disappointing outcomes from the clinical trials, there is considerable evidence to support the beneficial effects of estrogens in the early stages of atherogenesis (during the menopausal transition and the early years of postmenopause). In clinical practice it...

Epidemiologic Evidence Of The Relation Between Type Diabetes And Related Conditions To Mild Cognitive Impairment And

Diabetes has been related to a twofold higher risk of developing MCI among postmenopausal women (79). A multiethnic study in elderly from New York City found that diabetes was related to a doubling of the risk of cognitive impairment-no dementia (similar to MCI) with stroke, although the effect on cognitive impairment-no dementia without stroke was weaker after adjusting for demographic variables and the presence of Apo E-s(epsilon)4 allele (80). An Italian study showed a non-statistically significant increase of MCI with diabetes in an elderly population (81), while a Canadian study found that diabetes was related only to vascular cognitive impairment-no dementia (82). A study in New York City found that diabetes was related to a higher risk of both amnestic and non-amnestic MCI, underlining the importance of T2D for both AD-related and vascular cognitive impairment (83). A recent study from Olmstead County, MN, found that T2D itself was not related to MCI, but longer T2D duration...

Sex Hormones and Insulin Resistance

From the onset of menstrual cycles until menopause, every month a woman's reproductive system revolves around the task of ovulation releasing an egg ripe for fertilization. The follic-ular phase of the menstrual cycle begins the day your period starts and lasts for about 12 to 14 days until you ovulate, or release the egg. During the early part of this stage of the cycle, the female sex hormones estrogen and progesterone are at their lowest levels. Another hormone, follicle-stimulating hormone, is produced, which turns on estrogen production. This causes the ovary to release an egg midway through the cycle. After egg release, the luteal phase takes over. A second pituitary hormone, luteinizing hormone, triggers the ovary to produce estrogen and progesterone. These hormones cause the lining of the uterus to thicken, in preparation for a possible pregnancy. If fertilization does not occur, the ovary stops making estrogen

Isoflavones and coronary heart disease

The increase in coronary heart disease (CHD) incidence associated with decreased ovarian function at the menopause (McGrath et al., 1998 Bittner, 2002) is in part attributable to a less favourable blood lipid profile and arterial dysfunction. Replacement of the natural hormones by exogenous oestrogen and progesterone, in the form of hormone replacement therapy (HRT), has been consistently shown to decrease plasma concentrations of low-density lipoprotein (LDL)-cholesterol and increase concentrations of the beneficial high-density lipoprotein (HDL)-cholesterol (Erberich et al., 2002). As a result, HRT has been widely advocated as an effective means of delaying the progression of atherosclerosis in postmenopausal women. However, recent findings from long-term controlled intervention studies have proved disappointing, with no benefit, or increased incidence, of CHD reported in a number of well-controlled trials (Grady et al., 2002 Skouby, 2002 Kuller, 2003). This lack of efficacy has...

Maintaining your health after pregnancy

Women who have had gestational diabetes can use oral contraceptives with low levels of estrogen and progesterone to prevent conception. These drugs, along with hormonal replacement therapy after menopause, do not increase your risk of later diabetes. They may, in fact, decrease the risk and decrease blood glucose levels in those who have diabetes already. Women with type 1 and type 2 diabetes can use the same preparations. The story is similar for postmenopausal women. A study in Diabetes Care in October 2003 showed that the use of estrogens (with or without progestins) by women with diabetes resulted in a decrease in coronary artery disease. Because women with diabetes are at very high risk for coronary artery disease, this finding is an important one. Another large study reported that women on hormone replacement therapy have better control of their blood glucose than those not on such treatment. This information was reported in Diabetes Care in July 2001.

Genital Sexual Arousal Disorders Among Women with Diabetes

Caruso et al. presented the largest peer-reviewed series regarding the use of sildenafil in both diabetic (117, 118) and nondiabetic (119, 120) women complaining of genital sexual arousal disorder. They assessed whether sildenafil was effective in modifying clitoral blood flow in a group of 30 premenopausal women with DM1 as compared with 39 healthy premenopausal women. A direct comparison showed that the DM1 patients had significantly lower scores for the arousal, orgasm and frequency of sexual activity domains of the Personal Experience Questionnaire. Moreover, diabetic women suffered from dyspareunia more frequently than the healthy controls. Likewise, the baseline clitoral blood flow of the DM1 women was significantly lower than that of the control group. Each DM1 woman received a single oral dose of 100-mg sildenafil and underwent a translabial colour Doppler of the clitoral arteries 1 and 4 h after sildenafil absorption (117). At 1 h after the administration of sildenafil,...

Reproductive Hormones

Conversely, precocious puberty may lead to obesity. Children with idiopathic precocious puberty prior to treatment show no differences in regard to lean or fat mass. However, during long-term treatment with gonadotropin-releasing hormone (GnRH) children present a reduction of lean mass and increased fat mass which may lead to obesity (343). This may be due to a shortening of the prepubertal growing period and by the so-called menopausal effect of the treatment. In another study, both boys and girls with precocious puberty had BMI scores above the 85th percentile prior to and during treatment with GnRH. After treatment the scores still remained above the 85th percentile suggesting that children with precocious puberty are prone to obesity though treatment of precocious puberty itself did contribute to obesity (344).


CVD is the major cause of morbidity and mortality in Western societies. Although CVD is an uncommon cause of morbidity and mortality in premenopausal women, it is the most common cause of death among postmenopausal women (74). The pathophysi-ology of CVD involves atherosclerotic plaque development, inflammation and plaque disruption with development of overlying thrombosis. This can lead to vessel occlusion and organ ischemia with clinical sequelae (27,65). An established approach to prevent this condition is comprehensive risk reduction including both lifestyle measures and pharmacological interventions. Over the last decades, HRT was thought to be among these therapies with potential to reduce vascular disease in postmenopausal women (75,76).

With Diabetes

In addition to beneficial effects on lipids, HRT has also been shown to improve other risk factors for atherothrombosis in diabetic women. CRP, a cardiovascular risk marker, is known to be increased in patients with type 2 diabetes. Sattar and associates (159) in a 6-month, double-blind, placebo-controlled study reported that transdermal estradiol in conjunction with continuous oral norethisterone significantly reduced CRP concentrations in postmenopausal women with type 2 diabetes. This is in contrast to what was reported for oral HRT formulations in nondiabetic postmenopausal women (68). This beneficial effect on CRP is likely the result of the neutral effect of transdermal estradiol and the favorable effect of oral norethisterone. The same HRT regimen was also found to reduce factor VII activity and von Willebrand factor antigen levels. On the basis of these overall beneficial effects on inflammatory and thrombotic factors, the authors have suggested that HRT regimens based on 17...

What About Lipids

Treatments other than statins and fibrates, such as hormone replacement therapy in women (Robinson et al 1996) or fish oils (Friedberg et al 1998), have beneficial effects on lipids and therefore may reduce cardiovascular risk. Fish oils also have a beneficial effect on glycaemic control.

Gonadotropin Therapy

A second-line option for infertility treatment is direct gonadotropin therapy with either FSH or human menopausal gonadotropin (hMG). Because of the increased number of FSH-responsive follicles in polycystic ovaries, patients with PCOS are more at risk for OHSS and multiple gestations (82-84). A low-dose, step-up protocol has been developed, which yields an increased pregnancy rate while reducing the incidence of OHSS and multiple gestations (83, 85, 86). Treatment consists of employing a low starting dose, typically 50 or 75 international units (IU) per day, and using small incremental dose increases when necessary to initiate and continue follicular development, up to maximum of 225 IU (6, 85). Ultrasounds are performed every 3-4 days to monitor follicle development, and ovulation is triggered by intramuscular human chorionic gonadotropin (hCG) injection (85). Treatment is typically discontinued if more than three follicles develop to reduce the risk of OHSS and multiple gestations...

The Role Of Gender

This may be especially apparent in type 1 diabetes, where nephropathy generally develops after puberty but before menopause, after which many gender differences may be reduced. Nonetheless, recent studies have demonstrated an excess of diabetic nephropathy in African-American women with predominantly type 2 diabetes.31 However, an excess of cardiovascular mortality in men may bias this kind of survey.

Observational Data

Extensive observational data indicate that exogenous estrogen therapy appears to be cardioprotective. Investigators in a review of population-based, case-control, cross-sectional and prospective studies of estrogen therapy (with most using conjugated estrogens) and CHD, calculated that estrogen use reduces the overall relative risk of CHD by approx 50 (4). Observational studies comparing current hormone users with nonusers have shown consistent reductions in CHD risk ranging from 35 to 50 (76,77). A recent updated report from the Nurses' Health Cohort Study with 70,533 postmenopausal women followed up for 20 years, noted that overall, current use of ERT was associated with a relative risk of major coronary events of 0.61 (confidence interval CI , 0.52-0.71) when adjusted for age and the common cardiovascular risk factors (5). The findings from observational studies have been important in promoting the belief that HRT prevents CHD (77). Although the observational data are almost...

Hormone Regulation

Sex hormones may also affect secretion of adiponectin, because women have higher plasma levels of adiponectin than men, independent of body composition (14). Of the sex hormones, estrogen does not seem to account for the gender-related difference in adiponectin level, because premenopausal women have higher estrogen levels and lower adiponectin concentrations than postmenopausal females and estradiol levels actually have a strong negative correlation with serum adiponectin levels, females would be expected to have lower adiponectin concentrations than men (19). Testosterone may lower adiponectin levels by possibly inhibiting its secretion, however. In mice, removal of the testes led to an increase in adiponectin, although administration of testosterone reduced adiponectin levels (27). Although one study has demonstrated no association between adiponectin and free testosterone concentrations in women, this relationship remains to be explored in men (19).


CVD is the leading cause of death in women in the USA, and in the female diabetic population the situation is no different. Even though during the last decade, a considerable amount of knowledge has been gained into the pathophysiology of diabetic CVD, the clinical outcomes for women remain far from acceptable. Premenopausal women have been classically considered protected against CVD secondary to a hormonal effect unfortunately, in age-matched diabetic women this protective effect is blunted.

Whats a Foot Ulcer

Candida or other vaginal infections can happen to women regardless or their age, sexual activity, or hygiene. They occur more often after menopause because estrogen levels are lower. Estrogen helps to protect the vaginal lining. Infections are also more likely to occur just before your period, during pregnancy, or after you take antibiotics for another infection. Signs of a vaginal infection include the following


The mechanisms by which diabetes abolishes the cardiovascular protective effects of female sex hormones in premenopausal women are not well understood. In fact, the loss of the natural sex advantage in women with diabetes is independent of other diabetes-associated conventional risk factors. After adjusting for differences in hypertension, dyslipidemia, and obesity, the cardiovascular risk still remains higher in diabetic women Given the central role of the endothelium in modulating vascular tone, lipid peroxidation, smooth muscle proliferation, and monocyte adhesion and the beneficial effects of estrogen in maintaining vascular health, it was hypothesized that diabetes may compromise the effects of estrogen on endothelial function, thereby increasing the potential for premature atherothrombosis. Indeed, recent clinical studies provide direct evidence that premenopausal women with diabetes have a significantly impaired regulation of vascular tone. In a recent study Di Carli and...


The conclusions of the HERS and WHI trials were diametrically opposite to the overwhelming observational evidence that HRT could be cardioprotective in postmenopausal women, raising the question regarding in which the clinical truth is. Several explanations for this apparent discordance have seen suggested. Some discrepancies may be the result of methodological differences between the observational and clinical studies as


The incidence of CAD in premenopausal women is less than in age-matched males (181). One possible explanation is the effect of estrogen. Estrogen may have important effects on vascular function that are not totally explained on the basis of an improved lipoprotein profile (182). Diabetic women have the same cardiovascular risk as nondia-betic men, suggesting that they are denied the cardiovascular protection of estrogen enjoyed by other premenopausal women (182). Estrogen's possible beneficial effects include not only inhibition of platelet aggregation (183), but also its antioxidative effect and antiproliferative effects on vascular smooth muscle. Several investigators have demonstrated that estrogen improves endothelium-dependent vasodilation in ovariectomized animals (184,185) and postmenopausal women (186-188). The mechanism may be enhanced eNOS production (188,189) or, alternatively, suppression of a prostaglandin H synthase-dependent vasoconstrictor prostanoid (190). Lim and...


Current guidelines suggest work-up for anemia when hemoglobin (Hb) is less than 13.5 g dL in adult males and 11.5 g dL in premenopausal females (European Best Practise Guidelines, 2004). Two major studies currently investigate whether prevention of anemia by administration of EPO ameliorates cardiovascular surrogate markers and improves outcome.


Menopause is associated with changes in body composition, including an increase in total fat mass and abdominal obesity, and these changes may increase risk for DM2. This change in body composition does not appear to be explained solely by an increase in body weight. The risk for DM2 increases with menopause, though how much of this increase in risk is due to the hormonal changes of menopause vs. the increase in BMI with aging is not clear. Existing studies support a decrease in risk for DM2 with HRT. Given the increase in cardiovascular risk with HRT, however, it should not be used for this indication. The mechanism for this decrease in risk is unclear at present. Future studies are needed to define whether the symptoms and pattern of hormonal changes characteristic of menopause differ in women with DM2. Women with DM2 and their caregivers should be aware that menopause and its treatments may affect diabetes risk as well as glucose control in women with DM2.

With Type Diabetes

Our findings suggested that DM1 reproductive-aged women are at an increased risk for SD, with an endocrine milieu characterized by reduced estrogenic tone, adrenocortical androgen production, and low T3 T4. The role of the endocrine milieu in the pathogenesis of SD related to diabetes remains to be clarified. Moreover, our findings highlighted that investigations of the sexuality of pre-menopausal women with diabetes mellitus require examination of all the parameters in relation to the different phases of the menstrual cycle (85).



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