Natural Menopause Relief Secrets

Holistic Hormone Balance

Every woman experiences hormonal imbalance at one point in life. The Holistic Hormone Balance is an essential guide that provides women with the information that they need to know on how to balance their hormones and reduce stress levels, fatigue, excessive weight gain, skin problems and increase desire in intimacy. In addition to that, the book provides women with steps to follow to identify any symptoms of hormonal imbalance and how to create an original and personalized treatment plan that works best for their body. A combination of natural hormone treatment has also been provided in the guide, making it easier for women to choose their best plan, that works best for them. Hormonal imbalance affects the female body and most of the time; they take the issue lightly, thinking that other people have more significant problems than theirs. Imbalance affects moods and creates discomfort in women. The frustration comes from the fact that they cannot do anything to change their situation, and always remain suffering in silence. The Holistic Hormone Balance book works towards helping women with hormone imbalance feel amazing again, by identifying the root cause of their problem and treating the symptoms when they occur. Read more here...

Holistic Hormone Balance Summary


4.6 stars out of 11 votes

Contents: Ebooks
Author: Graham
Official Website:
Price: $47.00

Access Now

My Holistic Hormone Balance Review

Highly Recommended

This e-book comes with the great features it has and offers you a totally simple steps explaining everything in detail with a very understandable language for all those who are interested.

My opinion on this e-book is, if you do not have this e-book in your collection, your collection is incomplete. I have no regrets for purchasing this.

Bone Density in Premenopausal Women

Hansen (9) evaluated 249 healthy premenopausal women whose average age was 39 years, measuring BMD at the distal forearm using SPA and at the PA spine and proximal femur using DXA (Hologic QDR-1000). In this study, no decline in BMD was seen at any site after age 30 and peak BMD appeared to be reached prior to age 30. Two other large cross-sectional studies have suggested that BMD in the proximal femur does decline in women prior to menopause. Rodin et al. (10) found a significant premenopausal decline in femoral neck BMD in a study of225 women who ranged in age from 18 to 52. Similarly, Bonnick et al. (11) found a decline in proximal femoral BMD after the age of 30 in a study of 237 premenopausal women ages 20 to 45. In this latter study, no increase in BMD in the spine or proximal femur was seen in any age group, suggesting that peak BMD in both regions was achieved prior to the age of 20. There was no significant change in spine BMD, again suggesting that spine BMD does not change....

Dissimilar BMDs Between Skeletal Sites at Peak and Prior to Menopause

Two hundred thirty-seven premenopausal women between the ages of 20 and 45 were evaluated with DXA (Lunar DPX) measurements of the PA spine and proximal femur to determine if differences exist in z-scores for the spine and proximal femur (11). The reference population for the calculation of the mean BMD and the SD were the 20- to 29-year-old women of the study population. Twenty to 24 of the 20 to 29-year-old women had differences in z-scores of more thanl between the lumbar spine and any of the three sites in the proximal femur (neck, Ward's, trochanter). In the 30- to 45-year-old women, however, this percentage increased to 32 to 46 . In the younger age group, the percentage of women having higher z-scores in the spine or higher z-scores in the proximal femur was roughly equally split. In the older age group, however, there was clearly a shift in percentages favoring a higher z-score in the spine. This appeared to be due to the earlier onset of bone loss from the proximal femur in...

Bone Density in Perimenopausal Women

Changes in spine BMD in pre-, peri- and postmenopausal women were evaluated in a longitudinal study by Pouilles et al. (13). The subjects were 230 Caucasian women ranging in age from 45 to 66 years. Menopausal status was determined by menstrual history and estradiol and LH levels. Based on these determinants, 71 women ages 45-51 were premenopausal throughout the study, 42 women ages 47-57 experienced menopause during the study and were considered perimenopausal, and 117 women were postmenopausal throughout the study. BMD in the PA spine was assessed using DPA. The women were followed for an average of 27 months. Bone loss in the premenopausal women averaged 0.8 per year. In the perimenopausal women, bone loss was 2.3 per year. In the postmenopausal women, bone loss was again 0.5 per year. The authors noted that approximately half the bone loss observed in the first 10 years after menopause was seen in the first 3 years after menopause. There was no difference in the rates of bone loss...

Dissimilar Spine and Femoral BMDs in Perimenopausal Women

Eighty-five Caucasian women between the ages of 45 to 60 who were within 6 months to 3 years past menopause underwent spine and proximal femur bone density testing using DXA (Lunar DPX) (15). These values were compared with reference values (mean and SD) from a group of 30 healthy women between the ages of 40 to 45. Thirty-nine women had both spine and femoral neck z-scores that were better than -1. Seventeen women had both spine and femoral neck z-scores that were both poorer than -1. Out of the 85 women, 22 (26 ) had dissimilar spine and femoral neck z-scores. Eight had spine z-scores that were better than -1 but femoral neck z-scores that were poorer than -1. Fourteen had femoral neck z-scores that were better than -1 but spine z-scores that were poorer than -1. In a similar study, Lai et al. (16) evaluated 88 Caucasian women, ages 44 to 59, who were within 5 years past menopause. BMD measurements of the lumbar spine and proximal femur were made using DXA (Hologic QDR-1000). The...

Hormone replacement therapy HRT gonadatropinreleasing hormone GnRH agonists estrogen

Epidemiological studies showing an increased prevalence of AD in postmenopausal females focused interest on the regulation of the hypothalamic-pituitary-gonadal (HPG) axis in AD. Additionally, females with high levels of endogenous estrogen were less prone to develop AD.42 The possibility that estrogen might serve as an AD preventive led to several preclinical studies examining its protective effects against amyloid toxicity and on cognitive performance. HRT was found not only to be ineffective in preventing AD in postmenopausal women over the age of 65 years in the National Institute of Health-sponsored Women's Health Initiative Memory Study, but increased the risk of dementia. Despite this finding, regulation of the HPG axis is still thought to be key in the development of AD, since AD patients show a twofold increase in gonadotropins, specifically luteinizing hormone in AD patients. Luteinizing hormone is thought to cause reactivation of the cell cycle in neurons leading to cell...

Estrogen Deficiency Postmenopausal

Ninety-three healthy women who had experienced a natural menopause 6 to 60 months earlier were followed prospectively for two consecutive 22-month periods (38). BMD was measured in the spine and proximal femur using DXA (Lunar DPX). The average decline in BMD in the spine was 1.46 per year (+2.6 to -6.9 ) in the first period and 1.28 per year (+2.8 to -5.3 ) in the second period. In the proximal femur, the average decline in the first period was 1.41 per year (+4.8 to -6.8 ) and 1.35 per year (+1.8 to -7.0 ) in the second. Individual rates of bone loss were not stable over time. Only 20-30 of women retained their initial classification as fast, intermediate, or slow losers during both observation periods. Of 24 women classified as fast losers during the first observation period, 5 remained fast, 12 became intermediate, and 5 became slow losers during the second period. The mean rate of loss in the fast loser group initially was -3.9 . Women who were originally classified as slow...

North American Menopause Society Recommendations

The North American Menopause Society (NAMS) published a comprehensive review of postmenopausal osteoporosis in the journal Menopause in 2002 (14). Included in the review were recommendations for bone density testing in the specific context of osteoporosis prevention and management. NAMS noted that measurement of BMD is the preferred method for diagnosing osteoporosis and that DXA is the technological standard for measuring BMD. NAMS stated that the total hip was the preferred region of interest to evaluate, particularly when measuring bone density in women over 60 because of the increased likelihood of degenerative calcification in the spine that would affect spine measurements.3 Nevertheless, spine measurements were described as useful in early postmenopausal women because of the faster rate of bone loss at that site compared to the rate seen at the proximal femur. Citing a report from the International Osteoporosis Foundation (IOF) published in 2000 (15), NAMS stated that they...

Medical guidelines for the prevention and management of postmenopausal osteoporosis

For risk assessment in perimenopausal or postmenopausal women who have risk factors for fractures and are willing to consider available interventions. 8. In younger postmenopausal women who have risk factors. (From Osteoporosis Task Force. American Association of Clinical Endocrinologists 2001 medical guidelines for clinical practice for the prevention and management of postmenopausal osteoporosis. Endocr Pract 2001 7 293-312.)


As the majority of patients who are suspected of having osteoporosis are close to the menopause or postmenopausal, it is necessary to have a clear understanding of how the menopause affects bone marker levels. The results of several studies suggest an increase of bone turnover at the time of menopause. Okano et al. 67 observed that bone markers are already elevated during the menopausal transition period, when menstruation is irregular and when rapid bone loss has already started. The results from this study suggested that changes in bone turnover may commence while menstruation is still regular, although the change is too small to reflect changes in spinal BMD. Perimenopausal changes have also been noted by others 68-70 . Hoshino et al. 71 reported that bone turnover was increased up to 4 years before the onset of menopause and increased significantly at the time of menopause. Interestingly, it is the peptide-bound crosslinks that appear to show the best discriminating power between...

Diet Menopause

Women going through menopause should increase intake of rich food sources of calcium, magnesium, and vitamins D and K to maintain integrity of the skeleton.23,24 In addition, high amounts of phosphorus (found in red meat, processed foods, and cola drinks) should also be avoided too much phosphorus in the diet accelerates loss of minerals from bones. Reducing sodium, caffeine, and protein intake can also help maintain body stores of calcium. To keep levels of blood fats in the healthy range, the saturated fat content of the diet should be reduced (by eating less meat, eggs, and whole-fat milk products).

Estimated Time To Complete

The utility of modern-day RA in predicting hip fracture risk was suggested by an analysis of data acquired during the first National Health and Nutrition Examination Survey (NHANES I, 1971-1975). During this survey, 1559 hand radiographs of Caucasian women were obtained with the older technique of photodensitometry using the Texas Woman's University wedge (27). During a median follow-up of 14 years that extended through 1987, 51 hip fractures occurred. Based on radiographic photodensi-tometry of the second phalanx of the small finger of the left hand, the risk for hip fracture per SD decline in bone density increased 1.66-fold. These films were then re-analyzed using RA with some compensation for the differences in technique. This re-analysis yielded an increase in the risk for hip fracture per SD decline in RA bone density of 1.81fold. Huang and colleagues (28) evaluated the utility of RA in the prediction of vertebral fractures. They followed 560 postmenopausal women, average age...

Preferred Form and Dosage Schedule

Villareal DT, Civitelli R, Chines A, et al. Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass. J Clin Endocrinol Metab. 1991 72 628. 8. Dawson-Hughes B, et al. Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Ann Intern Med. 1991 115 505.

Rationale for the Use of Aromatase Inhibitors in Cancer Treatment

Reticulum of placenta and granulosa cells of ovarian follicles. In three consecutive hydroxylating reactions, estrone and estradiol are synthesised from their precursors androstenedione and testosterone, respectively (Fig. 6). The final hydroxylating step in aromatisation does not require enzymatic action and is not product-sensitive. Aromatase is also present in peripheral tissues, including adipose tissue, liver, muscle, brain and breast cancer tissue. In the peri-menopausal period, the ovaries, as a result ofthe complete loss ofprimor-dial follicles, stop producing estrogens. This leads to a steady decline in ovarian estradiol production although serum estradiol concentrations can vary considerably. In post-menopausal women, approximate plasma estradiol levels are 20 pmol L, and most of the estradiol is formed by peripheral, extra-gonadal conversion of testosterone. As peripheral aromatase activity increases with age, peripheral estrogen production approximately doubles. Estrone is...

Rationale for the Use of Steroid Sulfatase Inhibitors in Cancer Treatment

The biologically inactive estrone sulfate (E1S) and dehydro-epiandrosterone-sulfate (DHEAS) are the most abundant circulating estrogenic precursors in the plasma of post-menopausal women 103 . Desulfation of inactive steroid-3-O-sulfates by estrone-sulfatase (STS) plays a key role in the regulation of levels of receptor-active estrogenic steroids (estradiol and androstenediol) in breast cancer cells (Fig. 9). There is strong evidence suggesting that estrone sulfatase (STS) and DHEA-sulfatase are the same enzyme 103 . Although the affinity of androstenediol for the ER is much lower than that of estradiol, the plasma concentration of androstenediol is 100-fold higher than that of estradiol and it is presumed that the amount of circulating an-drostenediol is sufficient to stimulate hormone-dependent breast cancer cells. In addition, the activity of the STS and the tissue concentration of estrone sulfate were found to be higher in tumour than in normal breast tissue 104 . This led to the...

Caveats and Qualifications

Are more likely to suffer from inflammatory pain that is often more intense and longer lasting than that in men (159-161). While there are a number of mechanisms that may contribute to this difference, evidence from both clinical and preclinical studies suggests that gonadal hormones, in particular estrogen, may be a critical factor. Its mechanisms of action are complex, as estrogen has been shown to influence structures relevant to nociception throughout the body. Timing, with respect to estrogen cycling or the sustained application of estrogen (as in the case of hormone replacement therapy), site of action, and dependent measures of nociception all appear to be important factors when assessing the impact of estrogen on specific aspects of nociceptive processing (120).

Rationale for the Use of Antiestrogens in Cancer Treatment

The effects observed after surgical oophorectomy and the discovery of steroid hormones and the steroid hormone receptors led to the concept that inhibition of steroid hormone receptor function by antagonists should prevent tumour growth. While the first anti-estrogen, tamoxifen, was found accidentally, a deeper understanding of the estrogen receptor as a transcription factor enabled more rational, SAR-based drug discovery. The introduction of the anti-estrogen tamoxifen has changed the treatment of all stages of breast cancer. It is still the method of choice not only for the treatment of advanced disease in pre- and post-menopausal women but also for prevention in women at high risk for developing breast cancer 141 . Tamoxifen has some interesting side effects that render this compound so unique that the term selective estrogen receptor modulator (SERM) was coined for this class of compounds. Although tamoxifen is an anti-estrogen, the drug is a partial estrogen receptor agonist with...

Pharmacology of Antiestrogens

These findings led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to design and launch the STAR trial (P-2, the Study of Tamoxifen And Raloxifene). The trial was designed to recruit a total of 22 000 post-menopausal women that are randomly assigned to receive either tamoxifen (20 mg day) or raloxifene (60 mg day) in a double-blind design and the results were reported recently 164 . Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of throm-boembolic events and cataracts but a non-statistically significant higher risk of non-invasive breast cancer. The risk of other cancers, fractures, ischemic heart disease and stroke is similar for both drugs. The novel SERMs, which include bazedoxifene and ospemifene (also known as deaminohydroxy-toremifene), are being investigated for the prevention and treatment of osteoporosis in post-menopausal women in phase III clinical trials 151,165 . The non-steroidal SERM...

Pharmacology of Progesterone Receptor Antagonists

To date, the results of five phase II clinical trials with PR antagonists in patients with metastatic breast cancer have been reported 191 . In post-menopausal women, two studies with mifepristone as second- or third-line treatment for metastatic breast cancer showed an objective response rate (complete response plus partial response) of 10 and 13 and stable disease in 54 and 40 of patients, respectively. A third study was conducted using mifepristone as first-line treatment. An objective response rate of 11 and a stable disease rate of 39 was reported 191 .

Estrogen and Apolipoproteins E and J in the Periphery

A considerable amount of data exists on estrogenic control of the blood-lipid profile and apoE levels. Estrogen replacement therapy (ERT) after natural or surgically induced menopause prevents elevations of total cholesterol and LDL-cholesterol, while maintaining high density lipoprotein (HDL)-cholesterol.6-10 Although ERT initially increases production of both HDL11 and LDL-cholesterol, ERT also increases the clearance of LDL6,12 and VLDL.13 One mechanism of faster clearance of postprandial lipids is an increase in hepatic LDL-receptor activity.14 However, HDL clearance does not appear to be affected by estrogen.6 Thus ERT shifts blood cholesterol and lipoproteins to a less atherogenic profile with a lower LDL HDL ratio. The risk of cardiovascular disease is correlated with earlier age of menopause, with the greatest risk if menopause occurs before 39 years the risk of cardiovascular disease is reduced by 2 for each year that menopause is delayed.15

Hormone Interference Estrogens and Progestins

Prior to the introduction of tamoxifen, high-dose estrogens such as diethyl-stilbestrol (DES) or ethinyl estradiol were generally considered the endocrine treatment of choice for post-menopausal women with breast cancer and for men with prostate cancer 221 . Subsequently, the use of estrogens declined, but data from recent clinical trials underline that these drugs have a similar efficacy as tamoxifen and are able to produce responses, even in patients who have received extensive prior endocrine therapy. However, the use of these agents is limited by their toxicity profile. The mode of action of high dose estrogens is still under discussion. Besides a negative feedback regulation of the hormonal cycle, cytotoxic effects and induction of apoptosis have been proposed 222 . A modification of the treatment schedule and new formulations like sulfamates, phosphates or esters, which avoid the primary liver passage of the estrogen, may lead to a renaissance of this very effective treatment...

Rationale for the Use of Inhibitors of Releasing Hormones in Cancer Treatment

Prostate cancer and breast cancer are both stimulated by steroid hormones. The synthesis of estrogens and androgens is initiated by gonadotropins. In pre-menopausal women, gonadotropin-releasing hormone (GnRH) is released from the hypothalamus in a pulsatile fashion and is carried by the portal veins directly to the anterior pituitary gland where it binds to GnRH receptors, stimulating the release of luteinising hormone (LH) and follicle stimulating hormone (FSH) (Fig. 17). The ligand-bound receptors cluster and are taken up into the pituitary cells. These inactivated G protein-coupled GnRH receptors are replaced by newly synthesised receptors on the cell surface, ready for the next pulse of GnRH. LH stimulates the ovaries to produce estrogens, including estradiol. This process is responsible for producing up to 90 of circulating estradiol, depending on the phase of the menstrual cycle. The aromatisation of androgens by the adrenal glands is responsible for the synthesis of the...

Background and Introduction

In 1896 George Beatson1 demonstrated that removal of the ovaries from premenopausal women could cause the regression of breast cancer. By the turn of the century it was established2 that about one-third of all premenopausal women with advanced breast cancer could benefit from oophorectomy and from that time, a principal strategy for the treatment and prevention of breast cancer has been either to block or to restrict the action of estradiol in its target tissue, the breast. However, the successful clinical development of the antiestrogenic drug tamoxifen did not initially focus on the therapy for breast cancer but evolved to this application by drawing upon expertise in several unrelated disciplines. Most of the early interest in antiestrogens was focused on reproductive endocrinology but it was clear from the beginning of clinical studies that the effects of the drugs on cholesterol biosynthesis would play a pivotal role in assessing safety considerations for long-term therapy....

Estrogen AD and Possible Mechanisms of Estrogen Induced Neuroprotection

Long-term use of ERT have the lowest risk.2 Gender differences were suggested as a possible explanation for the higher incidence of the familial AD in women that is also linked to the apoE-associated risk factor.5 In addition, Phillips and Sherwin32 showed that exogenous E2 maintains short-term memory in surgically-induced menopausal young women. Several levels of evidence demonstrated multiple sites of estrogen actions in the brain. The specific mechanism s by which estrogen reduces dementia are unclear, and they might be combined in order to be beneficial in improvement of clinical symptoms. Estrogen and several other estrogenic steroids which are contained in Premarin (the most common ERT drug) were also indicated as potential neurotrophins that increased survival and growth of hippocam-pal and cortical neurons in vitro.33 Direct actions of E2 and other estrogenic steroids on neurons occurred rapidly, suggesting involvement of membrane receptor(s) that mediate estrogen-induced...

Predicting rate of bone loss

If bone turnover markers could reliably predict the rate of bone loss, they would provide a cheap and easy way of screening women at high risk of developing osteoporosis. Unfortunately, there are major methodological problems that arise when trying to examine the association of bone markers with bone mineral density (BMD) in longitudinal studies 8 . For example, the magnitude of the error associated with BMD measurements over time (in the region of a few per cent) is similar to the annual changes that are seen in BMD. Therefore, it is difficult to make a valid assessment of the relationship between the rate of bone turnover and the subsequent rate of bone loss in individual postmenopausal women. Studies have previously given conflicting results 8-11 , but two recent studies suggest that bone markers cannot be used to predict the rate of bone loss. Yoshimura et al. 12 examined eight bone markers and their relationship with BMD change at the hip and femoral neck over 3 years in 400...

Predicting risk of fracture

One such study 20 found that, in women followed for 2 years, the formation markers (serum osteocalcin and BAP) were not predictive of hip fracture. However, baseline CTx and Dpd were higher in those patients who had subsequent hip fractures than in age-matched, nonfracture controls. This study showed that CTx and Dpd levels above the normal range were associated with a two-fold increase in hip fracture risk. A more recent study 21 also observed a significant relationship between CTx and fracture risk. In contrast to the earlier study, the authors of this study found BAP to be predictive of fracture as well. There is some disagreement as to the predictive value of bone markers. Tromp et al. 22 did not find any relationship between urinary NTx and osteoporotic fracture risk among 348 postmenopausal women over a 5-year period. Delmas 23 commented recently on the use of bone turnover markers in the assessment of fracture risk. He stated that the 'combination of a bone resorption marker...

Predicting response to treatment

Chesnut et al. 24 carried out a detailed analysis of the effect of hormone replacement therapy (HRT) on urine NTx levels and its value in predicting response to treatment. They observed a significant correlation between baseline NTx levels and lumbar spine BMD at 1 year. The percentage change in NTx at 6 months was also associated with an increase in spinal BMD. Furthermore, they demonstrated that the response to HRT in those subjects who had a low NTx at baseline (NTx level in the lowest quartile, which gave a value of less than 39 nmol bone collagen equivalents BCE mmol creatinine) was not significantly different from the placebo group. In contrast, in those subjects who had a high baseline NTx (NTx level in the highest quartile, greater than 69 nmol BCE mmol creatinine), the response to treatment was much greater, and, if no treatment was offered, these subjects had a 17.3 times greater risk of bone loss compared with the low turnover subjects. The authors suggest that the NTx...

Monitoring response to therapy

Hesley et al. 25 have investigated the effects of treatment with 17-0 oestradiol (0.05 mg day) on urinary Dpd excretion in 91 women who had recently undergone a surgical menopause. Despite the low number of subjects in this study, the results are in agreement with other studies that have shown that short-term changes in Dpd response to antiresorptive treatment are inversely correlated with long-term changes in BMD 37, 38 . In this study, the changes in Dpd at just 6 months were correlated (r 0.47, p 0.05), with changes in lumbar spine BMD at 6 months in the subgroup of patients on the 0.05 mg therapy. Additionally, urinary Dpd levels decreased into the premenopausal range in 95 (59 62) of those subjects taking HRT (dose ranged from 0.025 to 0.1 mg day). Delmas et al. 39 investigated the change in BAP, osteocalcin and CTx in response to different doses of transdermal 17 0-oestradiol patches in 569 women. They found that all markers decreased significantly after 3 and 6 months of...

Concerns about Tamoxifen

Much controversy surrounded the associations between tamoxifen use and the detection of endometrial cancer. However, it was possible to provide a reasonable picture of the actual incidence of endometrial cancer and provide a balanced view of the concerns. Reviews154-156 of the literature in the mid-1990s only identified about 400 cases of endometrial cancer associated with tamoxifen use worldwide. Millions of women had taken tamoxifen over many years. The increase in the incidence of endometrial cancer was found predominately in postmenopausal women and there was not a strong association between the duration of tamoxifen use and the risks of developing endometrial carcinoma. Based on the known long genesis of cancer in humans, it was inappropriate to suggest that the detection of endometrial cancer was caused by short courses of tamoxifen. It is also important to point out that DNA adducts were found to be absent from uterine samples of patients taking tamoxifen.157 Detection bias,...

Standardization of Dxa Bmd Results for the Femoral Neck Trochanter and Wards Area

In 2001, Lu et al. (13) developed equations for an sBMD for the femoral neck, trochanter, and Ward's area based on information obtained from studies of the same 100 women whose data was previously used to create formulas for the sBMD of the spine and total femur (10,12). The authors developed site-specific standardization formulas for the hip subre-gions. They compared the utility of the subregion formulas in reducing the disparity in BMD results among the three manufacturers' devices to that of the total femur standardization formulas developed previously when both sets of formulas were applied to the hip subregions. The authors applied the formulas to bone density data from a multicenter clinical trial involving 3139 postmenopausal women. Bone density data was acquired on 51 Hologic, 17 Lunar, and 2 Norland DXA scanners. Table 5-6 shows the difference between scanners for each subregion depending on whether no calibration, the total femur, or subregion calibration was used. The...

Current Chemoprevention

Based on a thorough review of all the available data, the FDA approved tamoxifen for the reduction of breast cancer incidence in high-risk pre- and postmenopausal women in 1998. However, the report that tamoxifen caused a small but significant increase in uterine sarcoma209 resulted in an industry request for a black box inclusion for tamoxifen from the FDA. Additionally, the IBIS-1 study noted an unacceptable increase in deaths from tamoxifen treated patients who inadvertently had surgery during the study acceptability of tamoxifen as a chemopreventive.210 This led to the development of IBIS-2 using an aromatase inhibitor to prevent breast cancer. Aromatase inhibitors have fewer side effects than tamoxifen and it is known that during adjuvant treatment, they reduce the incidence of contralateral breast cancer even more than tamoxifen.211-213 Another approach is the evaluation of the SERM raloxifene as a preventive for breast cancer in high-risk postmenopausal women. The Study of...

Tamoxifens Legacy A Menu of Medicines

Figure 7 The endocrine options in the early 1970s for the patient with metastatic breast cancer. Surgery to remove endocrine organs (ablative surgery) which secreted estrogenic hormones or their precursors. In the case of postmenopausal patients, additive high-dose estrogens, androgens, or progestins were standard therapy. Figure 7 The endocrine options in the early 1970s for the patient with metastatic breast cancer. Surgery to remove endocrine organs (ablative surgery) which secreted estrogenic hormones or their precursors. In the case of postmenopausal patients, additive high-dose estrogens, androgens, or progestins were standard therapy. The clinical success of tamoxifen encouraged an important re-evaluation of inhibitors for the aromatase enzyme system. In other words, block the synthesis of estrogens from androgen precursors. Early nonspecific inhibitors such as aminoglutethimide had many side effects, especially since there was a necessity to coadminister the drug with a...

Evolution of Antiestrogens to Raloxifene

We have obtained valuable clinical information about this group of drugs that can be applied in other disease states. Research does not travel in straight lines and observations in one field of science often become major discoveries in another. Important clues have been garnered about the effects of tamoxifen on bone and lipids so it is possible that derivatives could find targeted applications to retard osteoporosis or atherosclerosis. The ubiquitous application of novel compounds to prevent diseases associated with the progressive changes after menopause may, as a side effect, significantly retard the development of breast cancer. The target population would be postmenopausal women in general, thereby avoiding the requirement to select a high risk group to prevent breast cancer.

Raloxifene and Lipids

Estrogen increases HDL cholesterol levels and decreases LDL cholesterol levels in humans39,171 as well in animal models of atherosclerosis, partly because of estrogen receptor-mediated upregulation of the hepatic LDL receptor.172 In ovariectomized rats, raloxifene treatment has been shown to reduce serum total cholesterol concentrations,97,173 and this reduction correlates with the extent of raloxifene binding to the estrogen receptor.97,173 These results are not surprising for a 'nonsteroidal antiestrogen,' as the original observations for clomiphene analogs and tamoxifen show (see 8.08 Tamoxifen). Raloxifene may also have cardioprotective effects because of its antioxidant properties. This is important since oxidative modifications of LDL have been implicated in atherogenesisis.174 Raloxifene also appears to have a favorable effect on lipid parameters in postmenopausal women. In the published European trial,78 treatment with raloxifene in a dosage of 30, 60, or 150 mg day_ 1...

Bone markers and fracture risk

Several studies have shown that increased levels of bone turnover markers are associated with faster rates of bone loss in the subsequent years 1, 2 . For example, in a recent study of 305 untreated postmenopausal women 3 , the author found that baseline values of serum osteocalcin, serum procollagen type I N-terminal propeptide (PINP), serum and urinary C-terminal crosslinking telopeptide of type I collagen (CTx) and urinary N-terminal crosslinking telopeptide of type I collagen (NTx) were negatively correlated with the rate of bone loss at the forearm over the next 4 years. Interestingly, women whose marker levels exceeded mean values in premenopausal women by more than two SDs lost bone two to six times faster than those whose marker levels were normal. However, the most important issue from a clinical standpoint is the ability of bone turnover markers to predict fracture risk. years 4-7 . This predictive value is consistently in the order of a 2-fold increase in the risk of...

Preanalytical variability

Pregnancy and lactation menopausal status growth Most biochemical markers show significant diurnal variations, with the highest values in the early morning hours and lowest values during the afternoon and at night. Thirty years ago, Mautalen 26 demonstrated that the excretion of urinary hydroxyproline (OHP) follows a diurnal rhythm. Diurnal variation in pre- and postmenopausal women, as well as in men, has now been reported by several investigators for all biochemical markers of bone turnover 14, 20, 27-39 . Although some authors have reported diurnal changes as high as 100 of the daily mean 29 , most studies find amplitudes between 15 and 30 . Serum markers usually show less pronounced changes during the day than urine-based indices. This observation is also true for the new serum assays for the bone resorption markers such as serum NTx, serum CTx and BSP 20, 37 M.J. Seibel et al., unpublished data . Wichers and colleagues 35 , however, reported a daily amplitude of serum CTx of up...

Ehlers Danlos Syndrome

Were matched for age, menopausal status, and estrogen use. The mean L2-L4 BMD in the Ehlers-Danlos patients was 1.14 0.14 g cm2 compared to 1.21 0.15 g cm2 in the control group. This difference was not statistically significant. BMD in the femoral neck was 0.91 0.13 g cm2 in the Ehlers-Danlos patients and 0.99 0.12 g cm2 in the controls. This difference was statistically significant. However, after adjustment for body weight, height, and physical activity, the difference in BMD at the femoral neck was no longer significant.

Gluten Sensitive Enteropathy

In a study from Argentina, Gonzalez et al. (46) evaluated 127 consecutive postmenopausal women with osteoporosis, who had a mean age of 68. Osteoporosis was defined as at least one nontraumatic fracture and an L2-L4 and or femoral neck T-score below -2.5. Bone density was measured using a Lunar DPX. The Buenos Aires reference population was used to calculate T- and z-scores for the study populations. This reference database is reported as similar to the reference database for Caucasian women in the United States. The mean T-score for the osteoporotic population was -3.2 and -3.0 for spine and femoral neck, respectively. The prevalence of celiac disease in these osteoporotic women was compared to 747 women, with a mean age of 29, recruited for a population-based study. Screening for celiac disease was done using IgA and IgG antigliadin antibodies (AGA) in all patients. This was followed by antiendomysial antibodies (EmA) and total IgA in the patients testing positive for AGA....

Musculoskeletal System

The development of osteoporosis in middle-age men is uncommon except in male alcoholics, where decreased bone mass has been documented (Turner, 2000). In women, improvement in bone mass has been shown with moderate alcohol use, especially in postmenopausal women (Laitinen et al., 1993).

Zero population growth

Thus, Hill and Hurtado imply that a long-standing feature of human biology may have been not just the Malthusian possibility, but actual rapid increase, and a saw-tooth population history. They suggest that this may influence our ability to assess accurately the significant selective forces responsible for our biology and behaviour 'Perhaps trade-offs were not detected, and menopause not favored by kin selection, because the Ache were in a period of resource abundance'. There must also be implications for archaeologists' ideas about invention and 'intensification' as a response to population pressure.

Estrogen Hormone Replacement

The effects of cyclic hormone replacement therapy (HRT) with either transdermal estrogen or oral estrogen on BMD in the spine and proximal femur were compared to controls by Hillard et al. (126). Ninety-six Caucasian women between 6 months and 7 years postmenopausal participated in this study. Thirty women served as controls. Sixty-six women received either 0.05 mg transdermal 17-P estradiol continuously and 0.25 mg per day of norethisterone for 14 days of each cycle or oral conjugated equine estrogen 0.625 mg daily and 0.15 mg of dl-norgestrel daily for 12 days of each cycle. BMD measurements of the PA spine and proximal femur were obtained every 6 months for 3 years with DPA (Lunar DP3). In the control group, BMD in the spine declined by 4 and in the femoral neck by 5 at the end of 3 years. BMD increased at both sites in the two groups receiving some form of HRT with no significant difference between the two groups. The average increase in BMD at the spine in the transdermal...

Medroxyprogesterone Acetate

Thirty women receiving injectable depot medroxyprogesterone acetate for contraception for at least 5 years were evaluated by Cundy et al. (145). BMD was measured at the PA lumbar spine and femoral neck and compared to BMD in 30 premenopausal women and 30 postmenopausal women who served as controls. Compared to the premenopausal women, the women who received depot medroxyprogesterone had BMDs that were 7.5 lower in the lumbar spine and 6.6 lower in the femoral neck. Compared to the postmenopausal women, however, women who received depot medroxyprogesterone acetate had BMDs that were 8.9 higher in the lumbar spine and 4 higher in the femoral neck.

Primary Hyperparathyroidism

Among endocrine disorders inducing weight change, and theoretically weight loss, primary hyperparathyroidism (PHPT) must be mentioned. PHPT is a common endocrine disorder that predominantly affects post-menopausal women 43 . It is mostly caused by solitary adenomas of the parathyroid gland and is characterised by hypersecretion of parathyroid hormone (PTH) and consequently by hypercalcaemia. In addition to regu lating calcium concentrations, PTH exerts metabolic effects, including a stimulatory effect on lipolysis. This effect has been demonstrated both in animal and in human adipose tissue 44, 45 . However, PHPT is not commonly characterised by significant weight loss and there is contrasting evidence in the literature concerning this effect. For instance, it has been reported that PTH excess may promote weight gain by impeding cate-cholamine-induced lipolysis 46 . In a study by Grey et al., it was reported that post-menopausal women with mild untreated PHPT are markedly heavier than...

Guidelines from the European Foundation for Osteoporosis and Bone Disease

In contrast to the 1996 AACE guidelines, the EFFO guidelines do not direct the physician to perform a baseline measurement at the hip regardless of the reason for the measurement. The EFFO guidelines, like the ISCD guidelines, noted that the site of the measurement should be determined by the intent of the measurement. Although the EFFO observed that the hip may be less affected by changes of osteoarthrosis in the elderly and was the preferred site for a site-specific hip fracture risk assessment, they also observed that changes in BMD from therapeutic interventions were more likely to be documented in the spine. The EFFO also noted that the hip, wrist, or spine sites could be used for global fracture risk assessments in women around the time of menopause. Although the EFFO recommended scanning only one site initially, they acknowledged a. Premature menopause (

ACOG Recommendations for Bone Density Screening for Osteoporosis

In a press release (13) on February 28, 2002, the American College of Obstetricians and Gynecologists (ACOG) announced long-awaited recommendations for the use of bone densitometry. ACOG, like the NOF and AACE, recommended that all postmenopausal women 65 years of age and older be screened for osteoporosis. Similarly, they ACOG 2001 Recommendations for Bone Density Screening for Osteoporosis. Diseases and Conditions Associated with an Increased Risk for Osteoporosis in Which BMD Testing May Be Useful in Both Pre- and Postmenopausal Women ACOG 2001 Recommendations for Bone Density Screening for Osteoporosis. Diseases and Conditions Associated with an Increased Risk for Osteoporosis in Which BMD Testing May Be Useful in Both Pre- and Postmenopausal Women

US Preventive Services Task Force Recommendations

In September 2002, the US Preventive Services Task Force (USPSTF) issued recommendations for bone density testing when screening for postmenopausal osteoporosis (16). Like the recent guidelines from the NOF, AACE, NAMS, and ACOG that preceded the release of these recommendations, the USPSTF recommended that women age 65 and older be routinely screened for osteoporosis. Unlike previous guidelines that also recommended testing for postmenopausal women younger than age 65 who had risk factors for osteoporosis, the USPSTF limited their recommended for screening in younger postmenopausal women to those women ages 60 to 64 who were at high risk for osteoporosis. They made no comment on screening for postmenopausal women younger than age 60. The USPSTF also noted that there was no data to determine an upper age limit for screening. In making these recommendations, the USPSTF did not direct the clinician to use a specific bone density technology or skeletal site. They also noted that the risk...

Air and Water Pollutants

Establishing the fact that about two-thirds of all human cancers have an environmental cause and thus, theoretically at least, are preventable. This has led many people to believe that the environmental agents responsible for cancer are chemicals that we inhale or ingest. However, as Hig-ginson himself has reiterated,101,102 what he meant by the environment is the total milieu in which people live, including cultural habits, diet, exposure to various infectious agents, average age of menarche, number of children a woman bears, age of menopause in short, the cultural as well as the chemical environment.

Fat Mass and Distribution Changes Total Adipose Tissue

Little is known about age-related changes in body fatness in elderly adults. Most studies have documented increases up to 50-60 years of age, after which body fatness appears to stabilise 13-16 . In a cross-sectional survey, Baumgartner et al. 6 suggest that body fatness (in terms of both absolute FM and percent body fat) may be relatively stable in elderly men, but may decrease with age in elderly women. In their study, the distribution of body fat, as assessed by DEXA, did not appear to change with age beyond 65 years, leading to the conclusion that the accumulation of abdominal and visceral fat with age (in both men and women) occurs primarily in middle age, while FM remains constant or increases slightly in subsequent decades. In a longitudinal observation of body composition in older adults, as determined using hydrodensitometry, Hughes et al. 17 found an overall increase in adipose tissue in an older cohort, but this increase was attenuated with advancing age in women, whereas...

Can Crp Testing Improve On Standard Lipid Testing

The potential to improve cardiovascular risk prediction when used as an adjunct to lipid testing (8,30,31). In this regard, in the Women's Health Study, the area under the receiver-operator curve was significantly greater (p 0.001) when CRP testing was added to lipid screening, compared with lipid screening alone (8). Furthermore, when the relative risks associated with combined lipid and CRP testing were estimated, it was evident that increasing concentrations of CRP had additive predictive value at all lipid levels. Figure 4 shows the interactive effects of CRP and lipid testing among healthy men and women (32). Men and women with both CRP and lipid levels in the highest quintile are at markedly increased risk, but even among those with average or low lipid levels, CRP testing can identify individuals with high relative risks of future cardiovascular events. For instance, among postmenopausal women with LDL concentrations below 130 mg dL (the current National Cholesterol Education...

Comparing the performance of selfassessment questionnaires

Several studies (19-22) have compared the performance characteristics of the various indices. Cadarette and colleagues (19) compared the performance of the ORAI index to that of SCORE, ABONE, the 1998 NOF guidelines22 and the body weight criterion in a population of 2365 postmenopausal women age 45 and older who were participating in the CaMos study. These women were otherwise healthy women who had not taken HRT or any other bone-sparing agent or who had taken HRT for 5 years or more. The average age was 66.4 years and the average weight was 152 lb (69 kg). Bone density was measured at the femoral neck and T-scores were calculated using the manufacturer's reference data for Canadian women in which the mean and SD were 0.857 g cm2 and 0.125 g cm2, respectively.23 To compare the performance of the 1998 NOF guidelines to the risk indices, the authors converted the NOF guidelines to an index scoring system in which 1 point was awarded for age 65 or older, weight less than 127 lb (57.6...

Guidelines of the study group of the who for the diagnosis of osteoporosis

In an extensive report published in 1994 (3), a WHO study group composed of 16 internationally known experts in the field of osteoporosis proposed criteria for the diagnosis of osteoporosis based on a specific level of bone density. The focus of the WHO study group was the study of world populations rather than the diagnosis of osteoporosis in individuals. While endorsing the prior 1991 and 1993 Consensus Development Conferences' definition of osteoporosis, the WHO recognized that their proposed criteria did not include any assessment of microarchitectural deterioration. The WHO attempted to reconcile the prevalence of the disease that would be created depending on the level of bone density chosen with published lifetime fracture risk estimates. The study group noted that a cut-off value of 2.5 SD or more below the average value for healthy young women for bone density at the PA spine or proximal femur or for bone mineral content at the midradius would result in 30 of all...

Prognostic Characteristics

Published studies compare the stage and pathological characteristics of breast tumors occurring in young women with those occurring in older pre-menopausal women. In 1,703 patients treated at Institute Curie between 1981 and 1985, young age predicted for poorer survival 9 . The relationship between risk and age was a log-linear function, demonstrating a 4 decrease in the risk of recurrence and 2 decrease in the risk of death for every year of age. In multivariate analysis for survival and disease-free interval, young age was of independent prognostic significance when tumor size, nodal status, grade, hormone receptor status, loco-regional treatment, and adjuvant systemic therapy were all evaluated. Among 1,837 pre-menopausal women treated at the European Institute of Oncology between April 1997 and August 2000, 185 were aged less than 35 years at diagnosis. Young women were found to be more likely to have tumors that were estrogen receptor (ER)-negative (38.8 vs. 21.6 p

Adjuvant Endocrine Therapy

Amenorrhea may be important in the action of che-motherapeutic agents for pre-menopausal patients, with pre-menopausal women experiencing chemotherapy-induced amenorrhea demonstrating a better prognosis than those retaining their menstrual cycle 58-61 . RFS and OS appears to be improved by the induction of amenorrhea, but the optimal duration of the amenorrhea is unknown. The likelihood of becoming amenorrheic following adjuvant chemotherapy is dependent on age, with younger women less likely to become amenorrheic and, therefore, less likely to maximize on the benefits of the endocrine effect of adjuvant chemotherapy 62 . Suppression of ovarian functional, however, creates significant problems for very young women, including menopausal symptoms, psychological distress, and the need to adjust personal and family plans. In the 1998 Early Breast Cancer Trialists' Collaborative Group overview there were only 177 premenopausal women with ER-positive disease randomized to adju

Special considerations 1871 Fertility Issues

Young women are especially likely to have concerns regarding the potential effects of chemo- and endocrine therapy on their fertility. In patients with ER-positive tumors it is unclear whether there is any advantage to permanent menopause compared with reversible hormonal manipulation. Of patients aged less than 40 years treated with goserelin for 2 years at randomization, 90 had a return of menstrual function, and this did not adversely affect their outcome 65 . Chemotherapy can be cytotoxic to the ovaries and a proportion of pre-menopausal women receiving chemotherapy for early breast cancer will develop menstrual abnormalities and premature menopause, although younger women require higher cumulative doses of chemotherapy to develop gonadal failure 67 . The histological effect of chemotherapy is fibrosis and atrophy, resulting in a dose-related progressive and permanent depletion of primordial follicles 67, 68 . Increasing age at chemotherapy exposure is correlated with increasing...

Treating Epilepsy and the Menstrual Cycle Naturopathically

Naturopathic doctors have extensive training in the physiology of the menstrual cycle, which can serve to help female patients become more aware of how hormone levels can affect seizures. A healthy menstrual cycle should involve higher estrogen levels in the first half of the cycle and higher progesterone levels in the second half. When some women consistently have more seizures during days 16 to 28 of their cycle, a blood test can determine if a hormonal imbalance exists. Excess estrogen is the culprit in many medical conditions. Hormone replacement therapy is controversial, but N.D.s can help restore hormonal balance naturally by utilizing the following methods.

Lifetime Risk of Fracture

In 1992, Black et al. (11) proposed a method for calculating a woman's lifetime risk for hip fracture. The prediction was based on the woman's bone mass at menopause expressed as a percentile for her age, estimations of bone mass at subsequent ages and then estimating her risk for hip fracture at each age. The risk of hip fracture at each age was based on two factors the risk of fracture at a particular age derived from population-based data and the risk of fracture at a particular bone mass from prospective fracture trials. Based on a review of the literature at the time, an increase in relative risk for hip fracture of 1.65 for each SD decline in bone mass at the radius was used in the calculation of risk based on the level of bone mass. Using this method, the lifetime risk of hip fracture for a 50-year-old Caucasian woman whose midradial bone mass was at the 10th percentile was 19 . If her bone mass was at the 90th percentile, her lifetime risk of hip fracture was 11 . The gradient...

Remaining Lifetime Fracture Probability

The fracture incidence and bone loss rate data on which the RLFP model was originally based were derived from the Kuakini Osteoporosis Study. The original implementation of RLFP was based on measurements of bone mass at the calcaneus. Bone density measurements performed at other sites had to be converted to an equivalent calcaneal measurement. Using nomograms, the physician could find the calcaneal BMC on one scale and the patient's age on a second scale (19). By connecting the two values, the physician could find the RLFP on a third scale. RLFP predictions have now been recalculated for DXA measurements of the axial and appendicular skeleton and are available on the internet at After entering the patient's age, menopausal age, skeletal site measured, type of equipment used, and BMD, the RLFP calculation is presented as shown in Fig. 10-4. In this RLFP analysis, the RLFP was Age at Menopause 51

The Fracture Threshold

Ross et al. (22) proposed that the fracture threshold be defined as the BMC or BMD at which the risk of fracture doubled in comparison to premenopausal women. This recommendation was based on a prospective study of 1098 women who participated in the Kuakini Osteoporosis Study beginning in 1981. These women underwent BMC and BMD measurements at the proximal and distal radius and os calcis yearly with SPA and, beginning in 1984, lumbar spine BMD measurements with DPA. Four hundred eight women had spine films at baseline and were used to calculate spine fracture incidence during 4 years of follow-up. Spine fracture prevalence was calculated based on data from subjects who had fractures prior to the first bone density measurement. The authors looked at a variety of ways to define the fracture threshold and the BMC or BMD levels at the various sites that resulted. These considerations are shown in Table 10-10. They observed that the levels of BMC and BMD that corresponded to the 10th...

Historical Context

Cancer is a leading cause of death in Americans, second only to heart disease. While breast cancer kills the most women, many gynecological cancers are part of the overall cancer statistic. Ovarian cancer, the so-called whispering disease because of its insidious nature, is detected in one in 70 predominantly perimenopausal and postmenopausal American women and often metastasizes undetected. Risk factors include family history of ovarian and breast cancer, high dietary fat, delayed menopause, and no or late childbearing. The use of oral contraceptives appears to decrease risk. Ovarian cancer often presents itself with a cluster of three persistent and severe symptoms a swollen abdomen, a bloated feeling, and urgent urination. Other symptoms associated with the disease include gas pains, anorexia, backache, and indigestion. Unfortunately most women seek medical advice when their ovarian cancer is in the advanced stage because the symptoms might be associated with other gynecological...

Diseases of Bone Epidemiology and Diagnosis

Amongst the metabolic bone diseases, osteoporosis is by far the most frequent one. The World Health Organization defines osteoporosis as a BMD of 2.5 standard deviations (SD) or more below the mean for young healthy individuals. According to this definition, approximately 30 of all postmenopausal women and 20 of all men older than 60 years of age have osteoporosis. The incidence of osteoporosis and of osteoporotic fractures increases with age while only 4-5 of all women 60-70 years of age are found to have low BMD, this proportion rises to 50 in women aged 80 years or older. Similarly, according to the Dubbo Osteoporosis Epidemiological Study (DOES), the incidence of osteoporotic fractures is approximately 2000 per 100 000 person-years in the age group 60-70 years, but rises to almost 8000 per 100 000 person-years in women aged 80 years or more. One-third of women and one-sixth of men at age 90 years are estimated to have suffered a hip fracture.22 The pathogenesis of osteoporosis is...

Osteoporosis and Fracture Risk

Osteoporosis is a reduction in bone mass and bone microarchitecture leading to increased bone fragility and fracture risk. The most common cause of osteoporosis is increased bone turnover with excessive bone resorption (destruction) that exceeds bone formation. Among women, this is often caused by estrogen deficiency following menopause. A second large and independent contributor is glucocorticoid use. Later in life, a combination of vitamin D insufficiency, reduced 1,25(OH)2-vitamin D3 production and inadequate calcium nutrition contribute to bone loss in both men and women. Both menopause and glucocorticoid use cause an imbalance between the processes of bone resorption (removal) and formation, leading to bone loss. A woman can experience a loss of up to 5 of her bone mass per year during the first half decade postmenopause. There exists a correlation between the reduction in bone mineral density1-4 and or increased bone turnover5-7 with increased fracture risk.

CRP and cardiovascular risk in women

Most of the studies described earlier were carried out mainly or, exclusively, in men. Recently, however, the prognostic value of CRP was assessed in a nested study (122 women who suffered a first cardiovascular event - myocardial infarction, stroke, PTCA (percutaneous transluminal coronary angioplasty), CABG (coronary artery bypass graft) or cardiovascular death - and 244 age- and tobacco-matched controls) in apparently healthy postmenopausal women 50 . The authors observed that, after adjusting for other risk factors, women with cardiovascular events had significantly higher CRP levels than women without events at follow up - a result similar to that obtained in previous studies in apparently healthy men 45 . Recent observations from the author's group 51 have shown that women with chronic stable angina have significantly higher CRP concentrations than men, even after adjustment for other variables associated with gender. In agreement with the findings of other groups 52, 53 , the...

Clinical Use of Alendronate Fosamax

Alendronate (ALN) has had the most extensive clinical use to date in terms of the number of patients, over 4 million, and duration of monitored treatment, over 10 years. Its ability to reduce hip and other fractures is documented in large randomized placebo-controlled clinical trials, and 10 years of follow-up data are available from the extension of phase III ALN clinical trials.8 ALN is widely used for the treatment and prevention of osteoporosis in postmenopausal women and glucocorticoid-treated patients of both genders.9-16 ALN has been proven effective in significantly reducing the incidence of both vertebral and nonvertebral fractures, including those of the hip. The reduced risk of vertebral fracture is also associated with less height loss,17 as well as a significant reduction in the number of days where patients experience disability.18 Because ALN acts via a nonhormonal pathway, it has also been effectively used to increase bone mass associated with a number of different...

Regression to the Mean and Monitoring

In an article in the Journal of the American Medical Association in 2000, Cummings et al. (9) raised the issue of whether regression to the mean (RTM) invalidated serial bone density measurements in clinical practice. The statistical concept of RTM was explained in Chapter 3. Cummings et al. used bone density data from the Fracture Intervention Trial of alendronate in postmenopausal women as well as data from the Multiple Outcomes of Raloxifene Evaluation trial in postmenopausal women. They limited their analysis to data obtained during the first 2 years of each trial in women who were compliant with the medication. They analyzed bone density data at the proximal femur in women by treatment assignment (active medication versus placebo). The average change in bone density at the end of 1 year was calculated for each treatment assignment group. The women were then divided into subgroups based on their actual change in bone density during the first

Cytotoxic Chemotherapy

Compromise in peri-menopausal women with breast cancer who received adjuvant treatment. At least in part, this finding might have been a consequence of chemotherapy-precipitated menopause. In any case, the study of the cognitive effects of chemotherapy, and their potential reversal is a major priority in the management of older cancer patients.

Reporting the diagnosis

Such a statement is appropriate for a postmenopausal woman. If the study has been performed in a man, the statement should be amended to reflect that the WHO Criteria were originally intended to be used in postmenopausal women only. The controversy surrounding the use of the WHO Criteria in men was discussed in Chapter 9. Until this controversy is resolved, an amended statement should be used. Such a statement might read as follows When the World Health Organization Criteria for postmenopausal women are utilized,

Recommending evaluations for secondary causes of bone loss

The Canadian Panel's recommendation to comment on the z-score when it was less than -2 and to aggressively recommend an evaluation for secondary causes of bone loss is entirely appropriate. This was not listed in the top five elements of a report requested by primary care physicians but this is all the more reason that such statements should be included in densitometry reports. Statements reminding physicians to exclude secondary causes of bone loss are always appropriate in individuals with a low bone mass, regardless of the z-score. In postmenopausal women, estrogen-deficient bone loss is a diagnosis of exclusion. It is incumbent on the physician to prove that nothing else could have caused the apparent bone loss. In men, a search for secondary causes is equally important. Densitometrists may use the z-score to determine how aggressively to recommend such an evaluation, but the recommendation should always be made in some form. Statistically, a z-score of -2 or poorer is grounds for...

Mechanism of Action at the Tissue Level

Osteoporosis and other types of bone loss are associated with increased bone turnover and elevated levels of bone resorption. Osteoclastic bone resorption is a 2-week process that begins the bone remodeling process. Resorption itself can be effectively slowed or controlled by inhibiting osteoclast generation, reducing osteoclast activity, or both. ALN is one of the most effective inhibitors of bone resorption. ALN improvement of mechanical strength, reflected in a reduction in fracture risk, is caused by an increase in bone mass and mineralization (discussed above) as well as by an improvement in architecture, attributable to a reduction in bone turnover. A higher number of bone remodeling sites, where excessive osteoclastic destruction of bone takes place, leads to loss of bone tissue, formation of areas of stress concentration, and increased fracture risk. By reducing turnover, bisphosphonates reverse this condition. Effects on bone turnover can be estimated by measuring either...

Reporting serial studies

The patient underwent baseline and follow-up DXA studies of the PA lumbar spine on 2 5 02 and 2 10 03, respectively. A Lunar Prodigy, software version 6.7, was used for both studies. At baseline, the L2-L4 BMD was 0.945 g cm2. At follow-up, the L2-L4 BMD was 0.987 g cm2. This represents an absolute change from baseline of 0.042 g cm2 or 4.44 . The precision of L2-L4 PA lumbar spine BMD testing at this facility is 0.011 g cm2 in postmenopausal women with an average L2-L4 BMD of 0.904 g cm2. Therefore, the statistical confidence level for the change in bone density in this patient is 99 .

The Need For Pathway Biomarkers

A prospective study to assess patient outcome when treatment assignment is based on CYP2D6 genotyping has not yet been undertaken, but it is under consideration. For example, postmenopausal patients who are CYP2D6 poor metabolizers could be treated with aro-matase inhibitors rather than tamoxifen. The options for premenopausal women are more complicated because aromatase inhibitors are generally not recommended for their treatment, although use in combination with ovarian suppression by ovariectomy or suppression with LHRH agonist could be a possibility. On October 18, 2006, the FDA's Clinical Pharmacology Subcommittee of the Advisory Committee for Pharmaceutical Science recommended that the FDA revise tamoxifen's drug label to include a warning that postmenopausal women who are CYP2D6 poor metabolizers and are taking tamoxifen to treat breast cancer have an increased risk for breast cancer recurrence. The subcommittee also recommended that the label should include a...

Micronutrients Cramps

Boron enhances and mimics some effects of estrogen therapy in postmenopausal women. J Trace Elem Exp Med. 1992 58 237. 23. Villareal DT, et al. Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass. J Clin Endocrinol Metab. 1991 72 628. 28. Dawson-Hughes B, et al. Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Ann Int. Med. 1991 115 505.

Experimental Disease Models

One of the most significant current clinical trials involving the endocrine modulation of breast cancer is the Study of Raloxifene and Tamoxifen, or STAR. This is a large phase III, double-blind trial in which postmenopausal women are assigned to take tamoxifen (20mgday_ or raloxifene (60mgday_ for 5 years. The primary aim of this trial is to compare these two selective estrogen receptor modulators (SERMs) directly for efficacy and safety parameters with respect to breast cancer, coronary heart disease, and osteoporosis. In particular, the effects of long-term raloxifene therapy on preventing the occurrence of invasive breast cancer in postmenopausal women who are identified as being at risk for the disease will be investigated. Endocrine therapy has been practiced since the turn of the twentieth century. Pioneering studies by George Beatson in 1896 showed that surgical removal of the ovaries, the primary source of endogenous estrogen, from premenopausal women with metastatic breast...

Type 1 Diabetes Mellitus

Age at onset of 11 to 12 years, and the incidence is increasing. The disease is characterized by hyperglycemia and ketoacidosis. Chronic complications of type 1 diabetes include progressive atherosclerosis of arteries, which can lead to ischemic necrosis of limbs and internal organs, and microvascular obstruction causing damage to the retina, renal glomeruli, and peripheral nerves. These patients have a deficiency of insulin resulting from immune-mediated destruction of the insulin-producing P cells of the islets of Langerhans in the pancreas, and continuous hormone replacement therapy is needed.

American college of obstetricians and gynecologists guidelines for bone density measurements

All postmenopausal women 65 years of age or older. 2. Postmenopausal women under 65 years of age who have one or more risk factors. 3. All postmenopausal women who have sustained a fracture. 1. Pre- or postmenopausal women with diseases or conditions associated with an increased risk of osteoporosis.

Management of posttransplantation bone disease

Management of post-transplantation bone disease consists of measures to optimize BMD preoperatively and prophylaxis of bone loss during and after transplantation. Known risk factors for osteoporosis should be avoided where possible, vitamin D deficiency corrected and hormone replacement therapy advised for hypogonadal patients, both men and women. Transdermal preparations are preferable since they avoid first pass hepatic metabolism and both oestrogen and testosterone can be administered by this route. In those patients who receive glucocorticoids for their underlying disease, treatment with a bisphosphonate should be advised. In nonglucocorticoid-treated patients with evidence of osteoporosis prior to transplantation, appropriate treatment should be given according to age, gender and clinical circumstances. At present, there are no adequately powered randomized controlled trials in transplant cohorts with fracture as the primary end-point that have been reported. Because of the...

Gonadal Toxicity Following Malignancy Treatment

Unlike male germ cells, female germ cells proliferate only during prenatal life after birth, these progressively decrease in number due to apoptosis, and ovulation. Germ cells inside the female gonad do not proliferate, whereas the somatic cells do. Radiation and chemotherapy induce oocytes to undergo apoptosis, which reduces the number of germ cells,18 resulting in estrogen insufficiency. Therefore, when follicles are destroyed by cytotoxic therapy, the frequency of menses decreases and amenorrhea commonly occurs. Irreversible ovarian failure and menopause occur if the number of follicles falls below that is required for menstrual cyclicity.

Inulin and Bone Health

Osteoporosis is a condition characterized by a decrease in bone mass and density that causes the bones, especially in postmenopausal women, to become fragile and vulnerable to fracture. It is a growing global problem, which can be alleviated by dietary approaches. Calcium is a key factor in bone strength. By optimizing peak bone mass in early adulthood and by minimizing bone loss during the postmenopausal period, the risk, for example, of hip fracture can be significantly reduced. Improved calcium nutrition during development is critical and can reduce hip fracture rates later in life by around 50 (Coxam, 2005). Prebiotic inulin and fructooligosaccharides added to the daily diet of animals significantly increase calcium absorption in animals (e.g., Coudray et al., 2003 Mineo et al., 2001 Ohta et al., 1994 Remesy et al., 1993). This can increase mineralization and bone mineral density (Roberfroid et al., 2002b). In humans, a beneficial effect on calcium absorption is found in both...

Grandmothering age at maturity interbirth intervals and fecundity

In CM, aM is approximately invariant because longer life spans favour more advanced age at maturity. More time to accrue the benefits of increased production associated with growing longer before reproducing offsets the cost of delay. If gains from growing longer continue to pay off after menopause, as the grandmother hypothesis proposes, then a should be adjusted accordingly. It is. These authors found that the late age at maturity for humans (high a) combined with our long life spans (low M) result in an aM similar to that of the other great apes. The delay in maturity for humans is as predicted if the gains from growing longer before reproducing pay off throughout adulthood, during both childbearing and grandmothering years. The grandmother hypothesis combined with CM accounts for several distinctive features of human life history, including long life spans after menopause, late age at maturity, short interbirth intervals, and high fertility. Other hypotheses have been offered to...

Raloxifene and Breast Cancer Prevention

Figure 7 Study design for the Continuing Outcomes Relevant to Evista (CORE) trial. CORE is a multicenter, double-blind, placebo-controlled clinical trial. It is a follow-up to the MORE trial and its purpose is to evaluate the long-term efficacy of raloxifene in reducing the incidence of invasive breast cancer in postmenopausal women with osteoporosis who were previously treated with raloxifene for up to 4 years in the MORE trial. All MORE investigation sites were invited to participate in the CORE trial. From those investigators choosing to participate, all women in the MORE trial (n 7705 participants) were invited to participate in the CORE trial after their completion or discontinuation from the MORE trial, and 4011 of those women chose to participate. Of the 2500 MORE trial participants who chose not to enroll in the CORE trial, 1217 women were still participating in the MORE trial as of January 1, 1999. The remaining 1283 women had completed their participation in the MORE trial...

Artifacts in PA or AP Spine Densitometry

Cervical Manipulation Complications

In 1982, Krolner et al. (16) observed that osteophytes caused a statistically significant increase in the BMD in the AP spine when compared to controls without osteophytes. More recently, Rand et al. (17) evaluated a population of 144 postmenopausal women, aged 40 to 84 years, with an average age of 63.3 years, for the presence of osteophytes, scoliosis, and aortic calcification. These women were generally healthy women referred for the evaluation of BMD because of suspected postmenopausal osteoporosis. Table 2-5 lists the percentages of these women

Vertebral Morphometry and Fractures

In a second study, Ross et al. (35) evaluated 380 postmenopausal women with an average age of 65 who were participants in a multicenter trial of etidronate therapy for postmenopausal osteoporosis. In this study, the presence of one or two spine fractures at baseline increased the risk of future spine fractures 7.4-fold. Nevitt et al. (34) evaluated the effect of the number and location of prevalent spine fractures on future fracture risk using data from the Fracture Intervention Trial (FIT), a placebo-controlled, randomized trial of alendronate therapy in postmenopausal osteoporosis. Data from 6082 women were included in this analysis, roughly half of whom were receiving a placebo. Vertebral fractures at baseline were found in 1950 women. Four hundred sixty-two new vertebral fractures occurred in 344 women during an aver Lateral spine images, such as the image shown in Fig. 10-6, can be evaluated using Genant's semiquantitative method. Morphometric software can also be used to define...

Organochlorine Compounds Polycyclic Aromatic Hydrocarbons and Breast Cancer

An argument has been made that since PCBs and DDTs have been banned since the 1970s, these may not have been the correct chemicals to look at or exposure of female babies in utero may be the key factor here. While there may be some truth to these assumptions since organo-chlorines do persist in the environment and can remain in the body for more than a decade. However, a case-control study based on cohorts of women who donated blood in 1974, 1989, or both and who were matched on age, race, menopausal status, and month and year of blood donation showed that even after 20 years of follow-up after exposure to relatively high concentrations of DDE or PCBs there was no association with an increased risk of breast cancer.178 One might argue that a better way to assess risk is to look at damage to the target in the body to which environmental agents might bind. This was done in a study that looked at polycyclic aromatic hydrocarbon-DNA adduct levels in blood mononuclear cells of women who...

Hormonal regulation of bone remodeling

Sex hormones are major regulators of bone turnover and remodeling in both genders. Estrogens reduce bone loss by inhibiting the generation of new osteoclasts, reducing the activation frequency of the BMU and promoting apoptosis of mature osteoclasts via mechanisms that are not well understood. Some of the effects of estrogen seem to be mediated via the modulation of growth factors and cytokines, while others are associated with binding to at least two different estrogen receptors (ERa, ERb). A reduction in circulating endogenous estrogen levels, as occurs during and after menopause, has been shown to prolong osteoclast survival and stimulate the recruitment and hence generation of osteoclasts. The result is an increase in the activation frequency of the BMU, reflected in a high bone turnover state.14 While there is no doubt that androgens (i.e., testosterone, dihydrotestosterone) play a dominant role in male bone health, it also appears that circulating estradiol levels are important...

The Human Adipose Organ

The visceral depots are very similar to those described in small mammals. In overweight or obese individuals, the abdominal visceral depots tend to grow in men and in post-menopausal women. This type of fat accumulation is dangerous for its association with the diseases secondary to overweight and obesity (diabetes, hypertension, myocardial infarct). Not all fat depots respond identically to a negative energy balance. Indeed, the gluteo-femoral subcutaneous tissue of adult pre-menopausal women is known to be much more resistant to the slimming process than abdominal subcutaneous fat, whereas both depots behave similarly in post-menopausal subjects. This seems to be due to a combination of increased lipoproteinlipase activity and reduced lipolytic activity in the former area.

Association ofLpPLA2 With Cardiovascular Risk

The predictive role of Lp-PLA2 was assessed within the Women's Health Study (WHS), a large cohort ofmiddle-aged normocholesterolemic women (27) representing a low-risk population for CVDs. Using a nested case-control design that included 123 cases and 123 controls, investigators found that baseline concentrations of Lp-PLA2 were significantly higher among women who subsequently developed cardiovascular events (such as MI, stroke, or death owing to CHD) compared with those who remained free of vascular disease (mean of 1.2 vs 1.05 mg L, respectively p 0.016). However, although the RR in the top quartile compared with the bottom quartile was 1.73 (95 CI 0.87-3.44), it was statistically nonsignificant and decreased further to 1.17 (95 CI 0.45-3.05) after adjustment for various risk factors. This lack of association could be attributed to existing gender differences for Lp-PLA2. Indeed, several studies (28-30) have already reported on lower levels of Lp-PLA2 in women than in men, and...

Risk Factors and Cancer

Diet and obesity in adults account for 30 of all cancer deaths in the USA. Diet has been shown to play a significant role in the causation of cancer but little is known about how it plays its role as a carcinogen.15,18 Excessive fat in the diet raises the risk of colorectal and breast cancer and possibly prostate cancer. Adult obesity is associated with endometrial cancer, postmenopausal breast cancer, and cancers of the colon, rectum, and kidney.15,18 Obesity in concert with other risk factors such as low activity level, menopausal status, and predisposition to insulin resistance significantly increase the risk of cancer. While some methods of food preparation and preservation have been shown to increase the risk of various forms of cancers, certain classes of foods appear to contain protective substances against cancer including vegetables, whole grain products (fiber), and citrus fruits.12,15,18,20 Salt intake has been associated with risk of stomach cancer, but no other food...

Chemotherapy Regimens Mopp and MOPP derivatives

Long-term toxicities were of even more serious concern. Most patients experienced infertility after treatment with MOPP. Males had at least an 80 risk of permanent azospermia after MOPP, while 50 of females experienced gonadal failure.4748 The risk appeared lower with patients younger than 25 years of age however, accelerated early menopause seemed to be the case in every female who did recover her menses after treatment.46 At a time when sperm banking and oocyte cryopreservation were in their early stages, many young patients, though cured, experienced significant psychological repercussions due to their infertility.

Influence ofAge and Gender

Several noncardiac factors may influence the circulating levels of natriuretic peptides and potentially confound the relation to indices of cardiac function. Age has been shown to be an important determinant of circulating natriuretic peptide levels (216-218). Both increased release and decreased clearance may contribute to elevated circulating levels of BNP and NT-proBNP in advanced age, but the exact mechanisms remain to be elucidated. Subclinical reduction in renal function, increased LV mass, and LV diastolic dysfunction are factors that may be essential for the observed increments in BNP and NT proBNP levels with age. Population-based studies have convincingly shown that BNP and NT-proBNP levels not only increase with age but are also significantly higher in women than in men (216-218). The association between female gender and BNP may be owing to estrogen status, because BNP levels were found to be higher in women using hormone replacement therapy (217).

The osteoporosis selfassessment tool

Koh and colleagues (11) developed the original Osteoporosis Self-Assessment Tool for Asians (OSTA) based on a study of 860 non-Caucasian, postmenopausal women from eight Asian countries. Risk factors were captured from a self-administered questionnaire and bone density was measured by DXA in the proximal femur. Proximal femur T-scores were based on the manufacturer's reference data for Asian women. Statistical analysis was performed to determine which risk factors were independent predictors of BMD. The risk factors that were captured are listed in Table 8-9. These independent predictors were combined in a multivariable model from which risk factors were dropped one at a time until only statistically significant variables remained in the model. An index was developed from the variables in the final model to identify those women with a high probability of having a femoral neck T-score of -2.5 or less.

Endocrine Disorders Associated with Myofascial Pain

It is not uncommon to find dozens of patients who present with muscle pain, spasm, and TrPs that are secondary to a primary endocrine disorder. The two most common are hypothyroidism and menopause. It is a good practice to perform a confirmatory lab test, and if your suspicions are correct, the patient may need to see an endocrinologist. Menopause, secondary to estrogenic insufficiency may be difficult for the patient and associated with myofascial pain and TrPs, sweats, and hot flashes. On occasion, muscle pain, and or joint pain may be the primary complaints. Associated symptoms may include anxiety, weakness, depression, emotional difficulties, and loss of libido. These symptoms typically all improve with exogenous estrogen replacement. Male menopause, secondary to significant decreases in serum testosterone, may be associated with myofascial pain and TrPs, along with weakness and depression. Exogenous testosterone may relieve these symptoms.

Clinical Trial Issues

Males with prepubertal hypogonadotropic hypogonadism require the combined treatment with human chorionic gonadotropin (hCG) plus human menopausal gonadotropins to initiate sperm production and fertility. In those with a selective deficiency of GnRH, such as Kallmann's syndrome, pulsatile GnRH therapy has been shown to stimulate testosterone production and spermatogenesis.

Sexual Development Reproductive Patterns and Sexual Behavior

The duration of hormonal exposure appears to play a role in the susceptibility to breast cancer in women. The carcinogenic effects ofhormones were first demonstrated in animals. In 1932, Lacassagne reported the induction of mammary carcinomas in mice injected repeatedly with an ovarian extract containing estrogen. Later, he also showed that the synthetic estrogen diethyl-stilbestrol produced mammary tumors in susceptible strains of mice.76 Furthermore, ovariecto-mized mice and rats have a decreased frequency of breast cancer, whereas rodents subjected to increased levels of estrogen, progesterone, and prolactin have an increased frequency of breast cancer, although timing of exposure to individual hormones appears to be crucial.77,78 Similarly in humans, a role of hormones in the development of breast cancer has been deduced from the known risk factors associated with the disease. These factors include early age of menar-che, delayed age of first pregnancy, and delayed menopause,...

The Spectrum of Malnutrition

Nearly 30 of humanity - infants, children, adolescents, adults and older persons in the developing world - are currently suffering from one or more of the multiple forms of malnutrition. This remains a continuing travesty of the recognised fundamental human right to adequate food and nutrition, and freedom from hunger and malnutrition, particularly in a world that has both the resources and knowledge to end this catastrophe. The tragic consequences of malnutrition include death, disability, stunted mental and physical growth and as a result, retarded national socioeconomic development. Some 49 of the 10.7 million deaths each year among children aged under 5 in the developing world are associated with malnutrition. Iron-deficiency anaemia affects 2 billion people, especially women and children. Iodine deficiency is the greatest single preventable cause of brain damage and mental retardation worldwide 740 million are affected. PEM affects 150 million children aged under 5. Intrauterine...

Solid Tumors Incidence And Risk Factors

Decreased risk of breast cancer after alkylating chemotherapy exposure.45 The relationship was dose related, with decreasing breast cancer risk with additional cycles of chemotherapy. Other data suggest the risk of breast cancer is significantly reduced in women who had premature menopause the younger the age at menopause, the lower the risk of breast cancer.4 These studies do report that the radiation-related risk of breast cancer, however, does not diminish in the longest follow-up, again suggesting a need for lifetime surveillance and programs of patient and physician awareness.

Bone markers to monitor antiresorptive therapy

In this study, 569 postmenopausal women aged 40-60 years with a time since menopause shorter than 6 years were given either a placebo or transdermal oestrogen in a dosage of 25, 50 or 75 g twice a week for 28 days (continuous treatment) or 50, 75 or 100 g twice a week for 25 days per cycle (cyclic therapy). Bone mineral density (BMD) at the spine was measured at baseline and after 2 years using dual-energy X-ray absorptiometry (DXA). Women with a BMD increase versus baseline greater than 2.26 (i.e. twice the short-term coefficient of variation for DXA) were classified as treatment responders and women with a BMD decrease versus baseline of more than 2.26 as nonresponders. The table shows the sensitivity and the likelihood of a positive response obtained using a 3-month bone marker decrease cut-off associated with 90 specificity. 1 Riis, S.B.J., Hansen, A.M., Jensen, K., Overgaard, K. and Christiansen, C. (1996). Low bone mass and fast rate of bone loss at menopause equal risk factors...


This patient was typical, in that she presented with symptoms and signs of hyperthyroidism, which were quite mild. There is usually a goiter present, but the findings characteristic of Graves' disease (orbitopathy, dermopathy) are not seen. Features of a pituitary mass lesion (headache, visual field abnormalities) may occur in a minority of patients, and were not observed in this patient. Acromegaly is present in about 15 of cases, and amenorrhea galactorrhea in about 10 (1). Hypopituitarism, especially hypogonadism, may also be a presenting feature. In this patient, FSH and luteinizing hormone (LH) were appropriately elevated for her postmenopausal status. It should be stressed that this ratio is not valid in postmenopausal women, as was the case here, or in men with primary hypogonadism, because they will have high serum a concentrations resulting from high serum gonadotropin levels. Of course, pituitary MRI will show a mass lesion in 95 of TSHoma patients, and should be normal in...

Patenting Problems

In 1973, Nolvadex, the ICI brand of tamoxifen (as its citrate salt), was approved by the Committee on the Safety of Medicines in the UK for the treatment of breast cancer. Although tamoxifen was approved for the treatment of advanced breast cancer in postmenopausal women on 30 December 1977 in the US (ICI Pharmaceuticals Division received the Queen's Award for Technological Achievement in the UK on 6 July 1978), the patent situation was unclear. ICI Pharmaceuticals Division was repeatedly denied patent protection in the USA (with an exclusion of claims for a cancer treatment) until the 1980s because of the perceived primacy of the earlier Merrill patents229 and because no advance (that is, a safer, more specific drug) was recognized by the US Patent Office. In other words, the clinical development of tamoxifen advanced steadily for more than a decade in the USA without the assurance of exclusivity. This situation also illustrates how unlikely the usefulness of tamoxifen was considered...

Circadian variation

Compared with a 2-hour morning collection. A similar, but nonsignificant change was seen in men. The information on the circadian rhythm of collagen crosslinks in this study is limited by the study technique. Aoshima et al. 53 have reported that the urinary resorption markers, Dpd and CTx, were 37-55 higher at night compared with the day in nine premenopausal women and nine postmenopausal osteoporotic women. There are a few conflicting results in the literature, which are usually the consequence of variations in the study design. The general consensus, however, is that most markers tend to be higher in the early morning hours, with peak levels reported to occur between 05 00 and 08 00 49, 53 .


Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 1996 388 429-432. 6. Walsh BW, Schiff I, Riosner B et al. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. New England J Med 1991 325 1196-1204. 8. Schram JHN, Boerrigter PJ, The TY. Influences of two hormone replacement therapy regimens, oral oestradiol valerate and cyproterone acetate versus transdermal oestradiol and oral dydrogesterone, on lipid metabolism. Maturitas, 1995 22 121-130. 15. van der Schouw YT, van der Graaf Y, Steyerberg EW et al. Age at menopause as a risk factor for cardiovascular mortality. Lancet 1996 347 714-718. 17. Applebaum-Bowden D, McLean P, Steinmetz A et al. Lipoprotein, apolipoprotein, and lypolytic enzyme changes following estrogen administration in postmenopausal women. J Lipid Res 1989 30 1895-1906. 32. Phillips SM, Sherwin B. Effects of estrogen on memory function in...

Andre the Giant

Growth hormone was discovered in the 1920s. About thirty years later, scientists figured out how to remove growth hormone from the human pituitary gland. They gave it to children with growth hormone deficiencies and discovered it helped them grow. This discovery led to the development of growth hormone replacement therapy. The first growth hormone replacement therapy medicine was taken from the pituitary glands of dead bodies (cadavers). It was given through a shot (injection). Between 1958 and 1985, the medicine was used to treat more than 8,000 children with growth hormone deficiencies.

Complex Patenting

The reinvention of raloxifene is summarized as follows ''This invention provides new method for the treatment of bone loss comprising administering to a human in need of treatment an effective amount of a compound of Formula I.'' This is the generalization of the 2-phenyl-3-aroylbenzothiophene structure. The US patent no. 5,393,763 was a continuation of the application ser. no. 07 920,933 filed on July 28, 1992, which was abandoned. The chain of events that led to filing a patent application on July 28, 1992 is particularly interesting as the translational research published by the academic community had made the claim obvious for this class of drugs and for keoxifene in particular. In fairness, some of the relevant references were listed as 'other publications'96 in US patent no. 5,393,763. The Love publication144 on the bone-sparing effects of tamoxifen was a direct result of ongoing research at the University of Wisconsin Comprehensive Cancer Center that showed tamoxifen and...



The Stages Of A Woman’s Life Are No Longer A Mystery. Get Instant Access To Valuable Information On All The Phases Of The Female Body From Menstruation To Menopause And Everything In Between.

Get My Free Ebook