Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation.

Hormone replacement therapy (HRT) in postmenopausal women suppresses the increase in bone resorption expected as circulating levels of endogenous estrogen decline. We tested the hypothesis that bone lead content might remain elevated in women on HRT. Fifty six women who at recruitment were on average 35 years postmenopausal were placed on calcium supplementation. Six months later 33 of these women were prescribed either low dose or moderate dose hormone replacement in addition to the calcium supplementation. After approximately 4 years of hormone replacement, lead content was measured at the tibia and calcaneus by in vivo fluorescence excitation, and lead concentrations were measured in serum, whole blood, and urine. Women not taking hormones had significantly lower lead concentrations in cortical bone compared to all women on HRT (p = 0.007). Tibia lead content (mean +/- SD) for women on calcium only was 11.13 +/- 6.22 microgram/g bone mineral. For women on HRT, tibia bone lead was 19.37 +/- 8.62 micrograms/g bone mineral on low-dose HRT and 16.87 +/- 11.68 micrograms/g bone mineral on moderate-dose HRT. There were no differences between groups for lead concentrations measured in trabecular bone, whole blood, serum or urine. Hormone replacement maintains cortical bone lead content. In women not on HRT, there will be a perimenopausal release of lead from bone.     

Medical issues and hormone replacement therapy

The debate surrounding postmenopausal hormone replacement therapy (HRT) has become more contentious in the past decade. The relationship between HRT and venous thrombotic events has been confirmed, although the absolute risk is small. Evidence of a relationship between breast cancer and HRT is stronger. Randomized controlled trials reveal an association with cardiovascular events in women with known heart disease, a possibly diminished overall quality of life due to HRT, and worsening of urinary incontinence. There is also some evidence associating HRT with ovarian cancer. However, longitudinal studies continue to demonstrate over the long term that HRT use is associated with fewer cardiovascular events and a reduced risk of developing dementia. Future studies may show that a lower daily dose of HRT can reduce the risks while still providing benefit.     

HRT and breast cancer

Research on hormone replacement therapy (HRT) in the 21st century has been dominated by the findings of the Women’s Health Initiative (WHI) and Million Women Study (MWS). Clinical practice has changed accordingly. Both studies confirm an increase in the risk of breast cancer among women using combined HRT (oestrogen and progestogen) when compared with women who have never used HRT. The risk among women using oestrogen-only preparations of HRT, according to the MWS, is increased, but to a lesser extent than for women using combined HRT. In contrast the WHI Study suggests that oestrogen alone is not associated with an increased risk of breast cancer. Despite these different findings most evidence-based guidelines from professional organizations still advise use of HRT only for the relief of menopausal symptoms and only short term. Routine use of unopposed oestrogen for women with a uterus is being discussed but is still not recommended. New data have also led to the recommendation that HRT is contraindicated for women who have had breast cancer. More research is needed on the contribution of progestogens to the increased risk of breast cancer and on the safety of different routes of administration of both oestrogen and progestogen.     

妇女围绝经期与绝经后内分泌变化及HRT研究进展（综述）

女性进入围绝经期后,由于卵巢功能减退雌激素不足使女性在心理及生理上发生明显变化,性激素替代疗法（HRT）可以调整月经、缓解围绝经期症状、预防泌尿生殖道萎缩与骨折、降低早期心脑血管意外发生等。且早期开始使用HRT风险很低,长期使用需要针对个体全面分析可能发生的危险因素,决定是否使用或如何使用HRT。     

Cigarette smoking, sex hormones and bone density in women

It is known that among women over the age of 65, bone mineral density is lower, and the risk of hip fracture higher, in smokers than non-smokers. We report a study in 1334 health pre- and postmenopausal women aged 35–64 years, to determine whether this effect can be attributed to lower oestrogen levels in smokers. Among 676 premenopausal women forearm bone density was no lower in smokers (95% confidence interval 1% lower, 4% higher). Among 543 postmenopausal women who had not used hormone replacement therapy (HRT) for more than a year there was no statistically significant difference, but the lower confidence interval was consistent with a lower bone density in older smokers (by 8% at age 55–59, 16% at age 60–64). Measurements in 194 postmenopausal women not taking HRT showed that oestrone and oestradiol were similar in smokers and non-smokers, as were cortisol and FSH, LH and prolactin. Meta-analysis of the present study and previous studies confirmed significantly higher levels in smokers of the androgens DHEAS (by 37%) and androstenedione (by 34%). Oestrogens were no lower in smokers, and the lower confidence limit excluded more than a trivial effect of smoking in lowering oestrogen. These results indicate that the recognised lower bone density in elderly smokers cannot be explained by an effect of smoking on oestrogen, since in premenopausal women bone density is no lower in smokers and in postmenopausal women oestrogens are no lower in smokers. The data suggest a balance between higher androgen levels but lower rates of conversion of androgens to oestgrogens in smokers. The effect of smoking on bone may be due to impaired response of bone and other target organs to oestrogen, or to actions independent of oestrogen.     

Do perceptions of risk and quality of life affect use of hormone replacement therapy by postmenopausal women?

BACKGROUND: Although the understanding of the health impact of hormone replacement therapy (HRT) is incomplete, even less is known about the attitudes, perceptions, and motivations of women faced with the decision to use HRT. The purpose of this study was to evaluate the relation between HRT use and women's perceptions of the risk and benefits associated with HRT use. METHODS: A written questionnaire was administered to 387 women, aged 45 years and older, responding to a health plan invitation for free bone mineral density screening. Women were asked to estimate the lifetime probability of developing breast cancer, uterine cancer, osteoporosis, and myocardial infarction when taking HRT and when not taking HRT. Women rated their quality of life in their current state of health, with breast cancer, with uterine cancer, with osteoporosis, and after myocardial infarction. RESULTS: HRT users perceived a greater risk reduction using HRT compared with HRT nonusers for osteoporosis (-34.9% vs -17.8%, P <.001) and myocardial infarction (-20.7% vs -8.4%, P <.001). HRT nonusers perceived a greater risk increase using HRT compared with HRT nonusers for breast cancer (16.5% vs 3.3%, P <.001) and uterine cancer (9.2% vs 0.6%, P =.004). HRT users estimated a greater quality-of-life reduction compared with HRT nonusers for osteoporosis (-31.0 vs -24.5, P =.006). CONCLUSIONS: Regardless of whether they used HRT, women in this study overestimated their risk for all four diseases. HRT users perceived greater benefit and less risk using HRT than nonusers. The results of our study show that continuing efforts are needed to help women understand the risks and benefits of HRT.     

Postmenopausal hormone-replacement therapy discredited,except in healthy women shortly after menopause

Results from the Women's Health Initiative randomized trial in 16,608 healthy postmenopausal women have revealed more risks than benefits in terms of invasive breast cancer and cardiovascular disease rates in patients treated for more than 5 years with a combination of conjugated oestrogens and progestin compared with placebo. Hormone-replacement therapy (HRT) is more effective in healthy women (maintaining vascular health) than in older women with atherosclerosis (restoring endothelial dysfunction). The initiation of HRT in patients at risk of a cardiovascular event results in an increased rate of cardiovascular complications and has not been proven beneficial in the long term. The point at which HRT is started after menopause plays a crucial role in the effectiveness of hormones on the vascular system: it is uncertain whether HRT initiated shortly after menopause can delay clinical signs of atherosclerotic disease.     

Advances in hormone replacement therapy: making the menopause manageable

The importance of the results of some large, randomized controlled trials (RCTs) on Hormone Replacement Therapy (HRT) has modified the risk/benefit perception of HRT. Recent literature review supports a different management. The differences in age at initiation and the duration of HRT are key points. HRT appears to decrease coronary disease in younger women, near menopause; yet, in older women, HRT increases risk of a coronary event. Although HRT is a recognized method in the prevention and treatment of osteoporosis, it is not licensed for the prevention of osteoporosis as a first-line treatment. The effectiveness of low and ultra-low estrogen doses has been demonstrated for the treatment of vasomotor symptoms, genital atrophy and the prevention of bone loss, with fewer side-effects than the standard dose therapy. Further research, however, is needed to determine the effect both on fractures, as well as on cardiovascular and breast diseases. Newer progestins show effects that are remarkably different from those of other assays. The effectiveness of testosterone at improving both sexual desire and response in surgically and naturally postmenopausal women is shown by the testosterone patch. The intention, dose and regimen of HRT need to be individualized, based on the principle of choosing the lowest appropriate dose in relation to the severity of symptoms and the time and menopause age.     

Osteoporosis management: physicians' recommendations and womens' compliance following osteoporosis testing.

Physicians use several pharmaceutical agents (e.g., hormone replacement therapy [HRT], calcitonin, bisphosphonates, calcium, and vitamin D) to manage osteoporosis. However, relatively little research has examined how physicians employ these agents in osteoporosis management. Additionally, researchers have not examined compliance with these treatments following the measurement of bone mass. Using a mail survey, we examined physicians' recommendation of, and women's compliance with, osteoporosis treatment modalities (stratified by fracture risk at the femoral neck and age) following bone mass measurement. We found that physicians recommended non-HRT treatment more often than HRT treatment to women with an increased risk of fracture, and women's acceptance of recommended treatments was relatively high following the measurement of bone mass.     

Dietary iron positively influences bone mineral density in postmenopausal women on hormone replacement therapy

The associations of dietary intakes of iron and calcium on change in bone mineral density (BMD) were examined over 1 y in healthy nonsmoking postmenopausal women (mean age 55.6 +/- 4.6 y) stratified by hormone replacement therapy (HRT) use (HRT, n = 116; no HRT, n = 112). BMD was measured at lumbar spine L(2)-L(4), trochanter, femur neck, Ward's triangle, and total body using dual-energy X-ray absorptiometry at baseline and 1 y. Mean nutrient intakes were assessed using 8-d diet records. All women received 800 mg/d of supplemental elemental calcium. Regression analyses examined the effects of iron and calcium intakes on BMD change adjusting for years past menopause, baseline BMD, weight change, exercise, and energy intake. The interaction of iron with calcium on BMD change was assessed using tertiles of iron and calcium intake and estimated marginal mean change in BMD. Iron was associated (P < or = 0.05) with greater positive BMD change at the trochanter and Ward's triangle in women using HRT. Calcium was associated (P < or = 0.05) with BMD change at the trochanter and femur neck for women not using HRT. In women using HRT in the lowest tertile of calcium intake, change in femur neck BMD increased linearly as iron intake increased. In women not using HRT, BMD increased in the women in the highest tertile of calcium intake. We conclude that HRT use appears to influence the associations of iron and calcium on change in BMD.     

Use of HRT and the subsequent risk of cancer

At least 20 million women in developed countries are estimated to be currently using hormone replacement therapy (HRT). Almost 100 epidemiological studies have reported on the relationship between the use of HRT and the risk of cancer of female reproductive organs, namely the breast, uterus or ovary. Cancer at these sites is common and there are a priori reasons why the use of hormonal therapy to 'replace' the endogenous production of ovarian hormones after the menopause might increase the risk of these cancers. The available evidence indicates that the risk of breast cancer or endometrial cancer is increased while women are using HRT, the risk increasing with increasing duration of use. Most of the evidence about these cancers relates to use of HRT preparations containing oestrogens alone. The limited evidence about combination therapy, with oestrogens and progestogens, suggests that, compared to oestrogens alone, the effect on the breast is similar, but the effect on the endometrium is diminished, the diminution in risk being greater the more days each month that progestogens are used. The effect of HRT on breast cancer wears off after use ceases and has disappeared largely, if not wholly, within 5 years, whereas the effects on endometrial cancer take longer to wear off, if at all. The breast and endometrial cancers that are diagnosed in HRT users are less aggressive clinically than cancers in never-users but, as yet, there is little reliable information about the relationship between use of HRT and mortality from these cancers. For other cancer sites, the existing data about the effects of HRT are inconclusive. The longer the period of use of HRT, the greater the excess incidence of cancer of the breast and endometrium is likely to be. Use of HRT for short periods of time should have little effect on the incidence of these cancers. The cumulative excess incidence in 1000 women who used HRT for 10 years, beginning at age 50, is estimated to be six for breast cancer, 42 for endometrial cancer in women with an intact uterus using oestrogen therapy alone and about 20 for endometrial cancer in women with an intact uterus using oestrogen-progestogen combinations. The estimate for combined therapy is based on small numbers and may well vary with the type of preparation used. The overall balance between the excess incidence of these cancers and other effects of HRT needs to be evaluated carefully and will require more reliable data than exist at present.     

Hormone replacement therapy acceptability to Nottingham post-menopausal women with a risk factor for osteoporosis.

In Nottingham we have assessed the acceptability of oral hormone replacement therapy (HRT) for an at risk group of post-menopausal women for osteoporosis. One hundred post-menopausal women between the ages of 50 and 70 years who had sustained a distal radial fracture were offered oral HRT. There was a 36% overall uptake of HRT with 9% of patients unable to take HRT because they had medical contraindications. The uptake in the 50-55 year age group was 54%. We conclude that in prospective studies of HRT for osteoporosis up to 50% of patients may not wish to take HRT and therefore study design should allow for this level of uptake.     

Osteoporosis Management: Physicians' Recommendations and Womens' Compliance Following Osteoporosis Testing

ABSTRACT

Physicians use several pharmaceutical agents (e.g., hormone replacement therapy [HRT], calcitonin, bisphosphonates, calcium, and vitamin D) to manage osteoporosis. However, relatively little research has examined how physicians employ these agents in osteoporosis management. Additionally, researchers have not examined compliance with these treatments following the measurement of bone mass. Using a mail survey, we examined physicians' recommendation of, and women's compliance with, osteoporosis treatment modalities (stratified by fracture risk at the femoral neck and age) following bone mass measurement. We found that physicians recommended non-HRT treatment more often than HRT treatment to women with an increased risk of fracture, and women's acceptance of recommended treatments was relatively high following the measurement of bone mass.     

激素替代治疗绝经后阴道出血53例临床分析

目的：探讨激素替代治疗对绝经后妇女子宫内膜的影响及临床监测方法。方法：选用1995年1月至1999年12月收治的激素替代治疗的绝经后阴道出血53例，并选用同同期未经激素替代治疗的绝经后道出血60例为对照组，均有完整的B超和病理及随访资料。结果：激素替代治疗组和非激素替代治疗组的子宫内膜癌的发生率分别是5.66％和8.33％，差异无显著意义。炎症的发生率分别为1.89％和16.67％，差异有显著意义。结论：激素替代治疗可有效改善围绝经期妇女的更年期症状，短期内使用完全有效，而5年以上的长期使用则需严密的监测。     

Hormone replacement therapy: characteristics of users and non-users in a British general practice cohort identified through computerised prescribing records.

STUDY OBJECTIVE--To assess the feasibility of recruiting a cohort of women, including long term users of postmenopausal hormone replacement therapy (HRT), through computerised general practice prescribing records, and to compare clinical and demographic characteristics of users and non-user controls. DESIGN--Cross sectional analysis of questionnaire data. SETTING--Subjects were recruited through 17 general practices in the Oxfordshire, south west Thames, and north west Thames regions that contributed to the VAMP Research Database. PARTICIPANTS--A total of 2964 women aged 45-64 years were identified. Altogether 1482 were long term (> 1 year) users of HRT and 1482 were non-user controls: 1037 (70%) of the users and 819 (55.3%) of the controls agreed to participate and provided questionnaire data. MAIN RESULTS--Users of HRT were more likely to have undergone hysterectomy than controls. Most women with a history of hysterectomy used unopposed oestrogen, while those with intact uteri generally used a combination of oestrogen and a progestagen. Among women who had undergone hysterectomy, HRT users did not differ significantly from controls over a range of demographic and clinical characteristics but they were more likely to be past users of oral contraceptives. Among women with intact uteri, users were similar to controls in terms of reported clinical characteristics, but were of higher social class and were more likely to be past users of oral contraceptives and to have had a mammogram after the age of 50. Compared with the general population, all categories of women recruited to the study were of higher social class and exhibited more health conscious behaviours. CONCLUSIONS--Electronic general practice prescribing records provide a feasible and efficient method for recruiting women to a cohort of HRT. Women who agreed to participate in this study were not representative of the general population, emphasising the importance of internal controls in such a study. Among participants, HRT users who had not undergone hysterectomy showed evidence of better health than non-users on some dimensions. In the whole sample, however, there were no appreciable differences in social class and self reported health indicators between users and controls.     

The Women's international study of long-duration oestrogen after menopause (WISDOM): a randomised controlled trial

Background  

At the time of feasibility work and final design of the trial there was no randomised control trial evidence for the long-term risks and benefits of hormone replacement therapy. Observational studies had suggested that long term use of estrogen was likely to be associated, amongst other things, with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer. Concomitant use of progestogens had been shown to protect against endometrial cancer, but there were few data showing how progestogen might affect estrogen actions on other conditions. Disease specific risks from observational studies suggested that, overall, long-term HRT was likely to be beneficial. Several studies showed that mortality from all causes was lower in HRT users than in non-users. Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women. The WISDOM trial was designed to compare combined estrogen and progestogen versus placebo, and estrogen alone versus combined estrogen and progestogen. During the development of WISDOM the Women's Health Initiative trial was designed, funded and started in the US.     

绝经与认知功能障碍

认知功能障碍泛指各种原因导致的各种程度的认知功能损害。老年女性出现认知功能的衰退不仅与年龄、遗传易感等因素相关,还可能与女性绝经后内源性雌激素缺乏有关。雌激素对于神经功能的保护作用已在诸多实验室研究和动物研究方面获得支持,但在临床应用激素补充治疗(hormone replacement therapy,HRT)时其疗效与预期并不完全一致。这可能与HRT启用的时机有关。目前认为,在围绝经期的窗口期开始HRT,会形成一个长期对痴呆的保护作用。     

Dietary Protein Intake above the Current RDA and Bone Health: A Systematic Review and Meta-Analysis

Dietary intake of protein is fundamental for optimal acquisition and maintenance of bone across all life stages; however, it has been hypothesized that intakes above the current recommended dietary allowance (RDA) might be beneficial for bone health. We utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines when preparing and reporting this systematic review and meta-analysis. A literature search strategy through April 11, 2017, was developed for the following 3 databases: PubMed, Ovid Medline, and Agricola. Included studies were those randomized controlled trials and prospective cohort studies among healthy adults ages 18 and older that examined the relationships between varying doses of protein intake at or above the current U.S. RDA (0.8 g/kg/d or 10%–15% of total caloric intake) from any source on fracture, bone mineral density (BMD)/bone mineral content (BMC), and/or markers of bone turnover. Twenty-nine articles were included for data extraction (16 randomized controlled trials [RCTs] and 13 prospective cohort studies). Meta-analysis of the prospective cohort studies showed high vs low protein intakes resulted in a statistically significant 16% decrease in hip fractures (standardized mean difference [SMD] = 0.84, 95% confidence interval [CI], 0.73, 0.95; I² = 36.8%). Data from studies included in these analyses collectively lean toward the hypothesis that protein intake above the current RDA is beneficial to BMD at several sites. This systematic review supports that protein intakes above the current RDA may have some beneficial role in preventing hip fractures and BMD loss. There were no differences between animal or plant proteins, although data in this area were scarce. Larger, long-term, and more well-controlled clinical trials measuring fracture outcomes and BMD are needed to adequately assess whether protein intake above the current RDA is beneficial as a preventative measure and/or intervention strategy for osteoporosis.

Key teaching points: ? ? Bone health is a multifactorial musculoskeletal issue, and optimal protein intakes are key in developing and maintaining bone throughout the life span.

? ? Dietary protein at levels above the current RDA may be beneficial in preventing hip fractures and BMD loss.

? ? Plant vs animal proteins do not seem to differ in their ability to prevent bone loss; however, data in this area are scarce.

? ? Larger, long-term RCTs using women not using hormone replacement therapy (HRT) are needed to adequately assess the magnitude of impact that protein intakes above the RDA have on preventing bone loss.