Hormone replacement makes sense for some menopausal women

Contents:

Cognitive Changes After Menopause: Influence of Estrogen

It is still unknown whether it may also induce the growth of new cancers. Use of estrogen alone for at least five years, may be associated with a slightly increased risk of breast cancer according to the Nurses' Health Study. Recent publications showed a significant decrease in the incidence of breast cancer in this group , a surprising finding which may be related to the type of estrogen used in the WHI study conjugated equine estrogen. The study is ongoing but clarification of this discrepancy has not been forthcoming.

Women who had never received hormones in the past in WHI did not have a significant risk over the 5. Many studies have not shown an increased risk of breast cancer with estrogen use. A large meta-analysis of 51 epidemiologic studies involving more than , women from 21 countries showed that HT increases the risk of breast cancer and that risk increases with longer use That is, for every 1, women who began using HT at age 50 and continued using it for 5, 10, or 15 years, an additional 2, 6, or 12 cases of breast cancer would be expected to occur.

However, another review showed that at doses of 0. Data from the Iowa Women's Health Study showed no increased risk of breast cancer in women who had used HT versus those who had not taken hormones Additionally, when researchers went back and analyzed data from women who had developed breast cancer, they found that HT, in a very small number of women, was associated with cancer with a favorable prognosis This finding is supported by other studies which have shown that women who use HT are less likely to have metastatic disease, and have a longer life expectancy than women who have not used HT The findings of these studies suggest that rather than acting as a carcinogen, estrogen may act as a mitogen.

However, one possible explanation for these findings is that women on HT are more likely to be seeing a doctor regularly and to undergo regular breast examinations and mammograms. Data from the Nurses' Health Study showed a survival advantage for women taking estrogen at the time their breast cancer was diagnosed.

The increased survival rate was associated with a lower frequency of late-stage disease and undoubtedly reflects earlier diagnosis in estrogen users However, other evidence suggests that estrogen users develop better differentiated tumors and that surveillance or detection bias is not the only explanation for better survival , A number of recent studies have aroused concern over the effect of menopausal HT on breast tissue density. In women not on HT, breast density has been found to be an independent risk factor for breast cancer Hormone therapy has been found to increase breast density, with the greatest increase in women on conjugated estrogen and progesterone Although an association between breast density and breast cancer has not been seen in women on HT, there has been some concern that mammograms may be less effective in women on HT with greater breast density.

However, Rutter et al. Therefore, until this issue is better understood, it may be advisable for women to discontinue HT for two weeks before a mammogram exam, especially in the case of prior problematic mammograms. Evidence suggests, however, that estrogen plus progestin may have an impact on breast cancer. This risk amounted to approximately 8 more women per 10, being diagnosed with breast cancer compared to those on placebo It is important to note, however, that the average age of women in this study was It is important to note though, that women taking estrogen only had a significantly lower increase in risk compared with women taking both an estrogen and progestogen.

It is an important to recognize that this was an observational study only and hence has a larger potential area for error. Although there is some evidence that combination therapy may increase risk of breast cancer above that of estrogen alone, neither a protective, nor a detrimental effect has been demonstrated convincingly, particularly for younger, healthier women.

London Trio No. 1 - Flute 1?
Hormone replacement makes sense for some menopausal women | Science News.
Cognitive Changes After Menopause: Influence of Estrogen;
Estrogen and the Brain.
History of Computer Graphics: DLR Associates Series?
Hormone replacement therapy: Uses, types, and alternatives!
?

One study interviewed nearly women with and without breast cancer and found a significant correlation between use of continuous combined replacement therapy and breast cancer However, the risks were higher in thin women than in heavier women which may confound the results. Also, it is possible that the use of cyclic therapy could provide the additional risk, and HT was generally given at higher doses that are rarely used today.

One hypothesis to explain this observation is that HT may promote the development of slow-growing tumors or discourage the development of more aggressive tumors. It has also been posited that better screening of these women leads to lower mortality rates. The argument that menopausal HT should not be given to women who have a personal history of breast cancer may seem reasonable based on evidence that breast cancer is a hormone responsive tumor.

However, while women with a first-degree relative mother, sister, or daughter who has or had premenopausal breast cancer are at increased risk by virtue of their family history alone, their risk of breast cancer is not thought to be increased further by HT use. Eighty percent of women who develop breast cancer do not have a family history. This is supported by the findings of Rebbeck et al. HT use did not negate the observed reduction in cancer risk. Interestingly, studies of breast cancer survivors showed that women using HT had a lower risk of recurrence compared to survivors not using HT , Breast cancer incidence is thought to increase after hormone use and since WHI there has been much interest on the role of the progestin in combination with estrogen in contrast to the use of estrogen alone 13, 14, In general most studies that have shown a small increase have shown more of an effect with the combination 26 and nurse health and collaborative study.

This has led to speculation as to the role of progestin, and to the minimization of progestin use despite the well-recognized and significant risk of endometrial cancer with the use of unopposed estrogen. Some recent studies suggest the progesterone and dydrogesterone may be safer than other progestins but no randomized studies examine this question In general, some effect is seen with treatment duration and some studies show an effect although small. WHI reported an increase in breast cancer risk in the combined therapy arm in subjects who had used hormones prior to enrollment but only after 5 years A later paper from the WHI study however suggested that the risk was higher in women who initiated therapy soon after menopause within 3 to 5 years However, in this study, a much larger group of women who were recently menopausal had been on HT and the effect was more pronounced in the less rigorous observational arm.

In general the effect takes several years to appear and is small. When hormones are discontinued the effect starts to decline within one year All of this confusing and contradictory data suggests that the combined HT may be acting as a promoter in susceptible women with undiagnosed subclinical cancer and the promoter effect may disappear with discontinuation of therapy. This may also explain the overall drop in breast cancer seen with the Seer Surveillance, Epidemiology and End Result cancer registries database report.

This report showed a drop in breast cancer rates after when women stopped hormone therapy after the WHI publications This effect has not been seen universally and the trend was actually seen prior to the reports. In fact there has been a drop in many different cancer rates, possibly due to earlier detection and earlier treatment However this effect was not seen in WHI.

Both combined hormone use and estrogen alone lead to denser breasts and more abnormal mammograms , This effect is rapidly reversible and stopping hormones 10 to 30 days before a mammography may decrease abnormalities requiring follow up One group of women who benefit from hormone therapy is the women with BRAC 1 and 2 mutations who undergo oophorectomy as prophylaxis. Use of HT does not appear to place them at risk for the genetically determined breast cancer and will improve quality of life It will also prevent the effects of estrogen deprivation at a young age.

The effects of stopping hormones are contradictory depending on the study. Breast cancer prognosis does not appear to be influenced by the high hormone levels during pregnancy, nor has oral contraceptive use been shown to increase breast cancer risk. These observations may allay some of the fear regarding the use of exogenous hormones after menopause. Data on ovarian cancer has not shown a consistent risk with use of hormone therapy. There is possible weak association with long term at least 10 years of therapy but data are inconclusive for recommendations Its use does not adversely affect the risk of cancer in BRCA mutations Other studies too, including HERS and a meta-analysis of 15 case-controlled studies found no significant association In , 38, cases of endometrial cancer were diagnosed, and 6, women died of the disease.

The mean age at diagnosis is 61 years, with most cases occurring in women 50 to 59 years old. Estrogen alone causes endometrial hyperplasia and a two to three-fold increase in the risk of endometrial cancer. However, the addition of progestogen reduces this risk to lower levels than those seen in women not on HT , Thus, the addition of a progestational agent to postmenopausal estrogen therapy is now standard for women with an intact uterus. While there have been some reports that the risk of endometrial cancer may be slightly increased even with the combined therapy, most studies have not confirmed this.

Women in the WHI study on combined therapy showed no difference in endometrial cancer rates compared to women on placebo Recent research has focused on the use of lower doses of estrogen and a progestogen in HT to reduce the risk of endometrial cancer The dose of progestogen given depends on several factors, including the number of days given each month, the amount of estrogen given, the individual needs of the patient, and her ability to tolerate the medication.

Side effects of progestogen can include anxiety, irritability, depressed mood, acne, bloating, fluid retention, headaches, breast tenderness, and bleeding problems. The inability to tolerate these effects is the main reason for poor compliance or discontinuation of HT. Despite being one of the major causes of cancer-related mortality in women, colon cancer is often overlooked by patients in their risk assessment of HT. In addition, reports from the WHI study showed that the combined estrogen plus progestin therapy was associated with a decrease in the incidence of colon cancer compared to women on placebo 6 fewer cases per 10, women on HT This was not found with estrogen alone At present; however, although the evidence that HT may be beneficial in reducing the risk of colon cancer should be considered, there is insufficient evidence to warrant recommending long-term HT solely for this purpose.

Review ARTICLE

"Controversial Issues in Climacteric Medicine" Series 3rd Pisa. Workshop ''HRT in Climacteric HRT: Hormone Replacement Therapy. IGF Insulin-like . preserve the brain endocrine function and respon- siveness. Indeed. Hormone replacement is still an important therapeutic modality for women with symptoms and quality of life issues which deserves further study, and should thrown the use of HT into question in both the medical and lay communities. . function(60) Current recommendations include the use of hormone.

The existence of estrogen receptors in the hippocampus, a part of the brain essential to learning and memory, has been known for some time. Several mechanisms may account for the effects of estrogen on the brain. Firstly, estrogen increases levels of choline O-acetyl-transferase, the enzyme needed to synthesize acetylcholine, a neurotransmitter thought to be critical for memory Studies on healthy middle-aged and elderly postmenopausal women have supported the theory that estrogen may help to maintain aspects of cognitive function , Data also suggest that estrogen therapy may enhance short- and long-term memory , Additional effects of estrogen on neural function include: A recent review of clinical trials of hormone therapy suggest that there is a clear difference between the effects of estrogen therapy and estrogen plus progestin There is modest support for the beneficial effect of estrogen alone on verbal memory in women under 65, and possibly surgically menopausal, while a harmful effect is seen with estrogen plus progestin in women over Conjugated estrogen with medroxyprogesterone acetate may also have some detrimental effect on younger women.

Estrogen alone appears to be neutral in women over Thus the age of initiation of therapy and the use of progestins are important when evaluating possible effects on verbal memory At present there is no combination which appears to be neutral to verbal memory and there is suggestion of some harm even with micronized progesterone Hot flashes appear to relate to memory dysfunction, and some of the cognitive improvement on hormone therapy may relate to the treatment of the hot flashes For every five years after the age of 65, the prevalence of Alzheimer's disease doubles in the population.

As the population ages over the next 20 years, these numbers are expected to increase. According to epidemiologic evidence, there is reason to believe that estrogen deficiency may contribute to Alzheimer's disease. Low body weight is associated with low levels of circulating estrogens in postmenopausal women.

Women who suffer from Alzheimer's disease tend to have lower body weights than women without the disorder Incidences of Alzheimer's disease are low or its expression is delayed in postmenopausal women with high levels of endogenous estrogenic steroids or those receiving long-term HT. One explanation for estrogen's apparent protective effect may involve neurotransmission. Estrogen acts as a trophic factor for cholinergic neurons in vitro. Cholinergic depletion is the most prominent neurotransmitter deficit in Alzheimer's disease.

However, while HT does show promise in preventing or delaying the onset of the disease, a recent study showed no benefit of either 0. Most likely, estrogen may merely delay the deterioration seen in Alzheimer's patients. The effect of HT on different subtypes of dementia could not be determined because the number of cases was too small. It must be noted, however, that because the WHIMS participants were all 65 or older, these results may not apply to women who initiate HT at a younger age. The results of the Cache County Study serve to further confuse the issue.

In this prospective study of incident dementia in older women mean age For current users with more than 10 years of therapy the HR was 0. Interestingly, in past users, reductions were present in all age groups and showed a duration effect HR 0. The Nurses' Health Study showed a twofold increase in the risk of pulmonary embolism among postmenopausal women who were current estrogen users.

The recent findings of the WHI study confirmed these findings for women on combined estrogen plus progestin therapy. Women on this treatment suffered 8 more pulmonary emboli per 10, than women on placebo Although estrogen use has been associated with an increase in the relative risk of venous thromboembolism VTE , the absolute risk remains low, as VTE occurs infrequently in this setting.

Women on combined estrogen-progestin therapy in the WHI study suffered 18 cases of more venous thromboembolism than women on placebo. It does, however, show that patients should be screened for a history of idiopathic thrombosis as this has been a consistent finding Some epidemiologic studies have found an increased risk of gallstones among women who use HT. Estrogen has been shown to increase cholesterol saturation of bile, alter bile acid composition, and decrease bile flow.

Each of these effects can enhance gallstone formation. Data from the Nurses' Health Study 54, postmenopausal women monitored for eight years showed that current HT users were more likely to have undergone cholecystectomy than nonusers relative risk, 2. This risk tends to increase with long-term therapy and with high doses of estrogen Because many women gain weight as they age, a common fear is that HT will exacerbate this problem. However, this is unconfirmed by prospective studies. Attention to diet with reduced fat intake and regular aerobic exercise for weight maintenance should be recommended to all postmenopausal women.

Data from WHI also showed an attenuation of increases in weight seen with age in the combined hormone treated arm This suggests there may be some beneficial effect to HT on the normal increases that are seen in postmenopausal women and that the effect may protect against the increase in central obesity seen in hypoestrogenic menopausal women. A decrease in the incidence of diabetes, and lower insulin levels suggestive of better insulin sensitivity may be related to this attenuated weight gain. Some studies have shown a small reduction in the incidence of this eye disorder among users of HT , It is thought that skin may be an important target organ for reproductive hormones.

In postmenopausal women, dermal collagen decreases, and skin becomes thinner. Applying estrogen cream to the skin after menopause improves the external appearance of facial skin. In addition, systemic HT increases dermal collagen and limits age-related skin extensibility. To date, of the eleven clinical trials that examined the effect of HT on collagen levels, only one failed to demonstrate efficacy Furthermore, results from a recent study indicates that estrogen also increases skin thickness HT has also been shown to accelerate cutaneous wound healing, both microscopically and macroscopically, in postmenopausal women This study also showed delayed repair of acute incisional wounds in ovariectomized young female rodents; the delay was reversed by the topical application of estrogen.

The risk of tooth loss increases after menopause. Osteoporosis, as well as estrogen deficiency, could both be contributing to this effect. Data from the Nurses' Health Study indicate that the risk of tooth loss may be decreased in women with a history of estrogen therapy Several treatments have recently become available and have FDA approval for relief of vasomotor symptoms.

A progestin is not necessary as this combination offers endometrial safety , Another SERM ospemifene has been approved for the treatment of postmenopausal vulvovaginal atrophy Another treatment consists of a Swedish pollen extract femal, which has been shown to be effective in a small study for a composite of menopausal symptoms including vasomotor symptoms, fatigue and quality of life Over the years, doses of estrogen in hormone therapy have been decreasing: Today, a CE dose of 0.

The goal of hormone therapy is to reduce menopausal symptoms e. Use of the lowest clinically effective dose of HT for relief of menopause-related symptoms and for prevention of osteoporosis is now recommended. The benefit-risk ratio of hormone therapy for each woman is influenced by the severity of her menopausal symptoms and their impact on quality of life, her current age, age at menopause, time since menopause, cause of menopause, and baseline disease risks. Generally appropriate indications include also treatment or prevention of osteoporosis in women who are not candidates for or cannot tolerate other osteoporosis therapies including bisphosphonates or teriparatide.

Absolute contraindications for systemic HT include hormone-related cancer, active liver disease, history of hormone-induced venous thromboembolism, history of pulmonary embolism not caused by trauma, vaginal bleeding of unknown etiology, and pregnancy. Relative contraindications include chronic liver disease, severe hypertriglyceridemia, endometriosis, history of endometrial cancer, history of breast cancer, coronary artery disease. Guidelines for hormone use are reviewed in the statement of the North American Menopause Society and recently by the Endocrine Society Considerable confusion has developed as a result of the numerous transdermal preparations which have appeared on the market.

The effective dose depends on the delivery rate and the surface area applied so that there is much variation in terms of estradiol delivered to the blood stream. The following charts attempt to present equivalent doses. Lower doses take longer weeks for effective relief, and it is important to individualize therapy.

Most preparations take a full 12 weeks for maximum effect although standard therapy provides relief sooner weeks. There is also much debate as to the safety of oral vs. One study suggests that venous thromboembolism may be lower with transdermal products, but the doses compared were not equivalent Another study shows a decreased risk of stroke in women on transdermal preparations with higher doses of both oral and transdermal estrogen showing significant effect One study suggests progesterone may be associated with a lower risk of breast cancer than progestins but this again awaits further study These preparations offer no advantage over regulated and tested preparations approved by the FDA, and their risk is equivalent to commercial compounds.

Claims that they are safer are misleading particularly since they have not been studied and one of the estrogens used, estriol, has no safety or efficacy data. In general initiation of treatment of the symptomatic newly menopausal women will provide benefit which greatly outweighs risk and provides protection from bone loss.

Older women who continue to be symptomatic may. Although the decision to treat menopausal women rests on individualized risk vs. In general, hormone treatment is being used for symptoms. These include vasomotor symptoms and vulvovaginal atrophy. There are, however, a variety of symptoms which make up the menopausal syndrome and are not strictly classified as vasomotor or vulvovaginal symptoms and are distressing to the patient and may also be a consideration for treatment Some patients can endure two hot flashes a day while others who are in stressful or public jobs cannot.

Patients are usually uncomfortable and distressed by more than two hot flashes per day. In particular the patient who wakes at night two or more times and suffers from sleep deprivation is usually in need of treatment. Patients suffering from five to seven hot flashes a day are experiencing moderate to severe symptoms and should be offered treatment.

The physician should help the patient make a quality of life decision and advise these patients on the low risks associated with treatment particularly for a few years. Some patients may be experiencing bone loss and hormone therapy is ideal for this type of patient. Some of the estrogens on the market are also approved for prevention of osteoporosis and data shows they are very effective and prevent fractures.

A patient on hormone therapy does not need a second drug for prevention of bone loss. If bone loss is occurring on hormone therapy a secondary cause should be searched for such as vitamin D deficiency, over treatment with thyroid hormone or hyperparathyroidism. Patients with mood issue may have problems with progestins and micronized progesterone or a vaginal delivery system may be better tolerated. Estrogens should be started first and a progestin added after a few weeks.

Patients with migraines also have special tolerability issues and fluctuations of hormone levels which may be triggering the headaches may persist or be aggravated initially by hormone treatment. A transdermal patch may be the best option and a progestin should be started after a trial of treatment with estrogen. The issue of duration of hormone treatment will arise.

Two to five years is usual. The small risk of breast cancer is also important to review with the patient. This risk surfaces after 5 years of use and did not surface at all with estrogen alone therapy after 7 seven years. This interval does not apply to patients with premature menopause who have been shown to be at risk for osteoporosis and premature heart disease if they are not replaced. All patients need a yearly mammogram and the increase in density can be avoided by stopping hormones for two weeks prior to the mammogram if she can tolerate it.

Some patients stay on hormone therapy long term because of mood or other issues or they are in the unfortunate 10 percent who continue to suffer form vasomotor symptoms or cannot tolerate other drugs for osteoporosis. Patients with severe mood issues may require antidepressants. Recent data has shown the efficacy of low doses for vasomotor symptoms and many are available. However the patient with severe symptoms may prefer a standard dose which may be lowered after 6 months when symptoms are well controlled.

Lastly, vaginal estrogens are an excellent option for patients with symptoms of vaginal atrophy and do not have the risks associated with systemic use. In particular, recurrent urinary tract infections and or vulvovaginitis are a hallmark of genitourinary estrogen deficiency which can be easily relieved or prevented with the use of vaginal estrogen. Treatment with hormone therapy is very individualized and quality of like may be greatly improved its use.

When therapy is discontinued, a return of symptoms is common although generally in a milder form. Unfortunately there is little data to guide the physician but many clinicians slowly taper doses over several months. When assessing risk vs. The normal menopause transition. Clinical observations on the use of an ovarian hormone: Am J Med Sci. Overview of estrogen replacement therapy: Proc Soc Exp Biol Med.

Menopause and Hormone Replacement - Endotext - NCBI Bookshelf

Postmenopausal estrogen for treatment of hot flashes: Steroid and gonadotropin levels in women during the peri-menopausal years. Factors associated with age at natural menopause in a multiethnic sample of midlife women. Vasomotor flushes in menopausal women. Am J Obstet Gynecol. Options for hormone therapy in women who have had a hysterectomy.

Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. Global consensus statement on menopausal hormone therapy. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women.

Hormone replacement therapy and risk of breast cancer: Postmenopausal hormone therapy and mortality. Postmenopausal hormone use and secondary prevention of coronary events in the nurses' health study. Prospective study of exogenous hormones and risk of pulmonary embolism in women. Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab.

The impact of hormone therapy on health-related quality of life: Breast cancer and hormone-replacement therapy in the Million Women Study. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis. Risk for new onset of depression during the menopausal transition: Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: Freeman EW, Sherif K. Prevalence of hot flushes and night sweats around the world: Management of menopausal symptoms. Ann N Y Acad Sci.

Commonly used types of postmenopausal estrogen for treatment of hot flashes: Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Comparison of Alora estradiol matrix transdermal delivery system with oral conjugated equine estrogen therapy in relieving menopausal symptoms. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: Health Qual Life Outcomes.

Related Ratings

Symptoms during the perimenopause: Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance. Effects of estrogens on sleep and psychological state of hypogonadal women. Depression and its influence on reproductive endocrine and menstrual cycle markers associated with perimenopause: Psychologic distress and natural menopause: Am J Public Health.

Depressive symptoms during the menopausal transition: Hormones and menopausal status as predictors of depression in women in transition to menopause. Predictors of first lifetime episodes of major depression in midlife women. A longitudinal analysis of the association between menopause and depression. Results from the Massachusetts Women's Health Study. A population-based study of depressed mood in middle-aged, Australian-born women. A longitudinal evaluation of the relationship between reproductive status and mood in perimenopausal women. Sex hormones and mood in the perimenopause.

Female psychopathologic profile during menopausal transition: Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care. Depressed mood during the menopausal transition and early postmenopause: A cross-sectional evaluation of perimenopausal depression.

Factors associated with early menopause. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: Lack of efficacy of estradiol for depression in postmenopausal women: Panay N, Studd J. Progestogen intolerance and compliance with hormone replacement therapy in menopausal women. Sex steroids and affect in the surgical menopause: Affective changes with estrogen and androgen replacement therapy in surgically menopausal women. A study of European womens' experience of the problems of urogenital ageing and its management.

Vulvar transepidermal water loss TEWL decay curves. Effect of occlusion, delipidation, and age. Advances in the treatment of menopausal symptoms. Womens Health Lond Engl. Treatment of atrophic vaginitis with topical conjugated equine estrogens in postmenopausal Asian women. Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: Treatment of urogenital atrophy with low-dose estradiol: Management of symptomatic vulvovaginal atrophy: The role of androgen in the maintenance of sexual functioning in oophorectomized women.

Lifetime risks of hip, Colles', or vertebral fracture and coronary heart disease among white postmenopausal women. Hormonal determinants and disorders of peak bone mass in children. Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause. Characterization of perimenopausal bone loss: J Bone Miner Res.

Questions and answers for estrogen and estrogen with progestin therapies for postmenopausal women updated http: In Alzheimer disease, cognitive loss begins insidiously and progresses gradually over a period of about a decade. An early and consistent feature of Alzheimer disease is impairment in episodic memory.

Most Alzheimer patients also have problems with language, attention, visuospatial skills, abstract reasoning, and judgment. Behavioral symptoms such as apathy, depression, agitation, or delusions are sometimes seen as well. Key histopathologic features of Alzheimer disease are neurofibrillary tangles, found within nerve cell bodies, and neuritic plaques, found in the neuropil between cell bodies.

Tangles are composed largely of tau protein. The pathogenesis of Alzheimer disease is unknown, although it is apparent that different genetic and nongenetic factors contribute to the characteristic clinical and pathologic picture. Early-onset Alzheimer disease, in which dementia symptoms emerge before about age 60, is often transmitted as an autosomal dominant disorder. The risk of early-onset and late-onset Alzheimer disease is influenced by polymorphic variations in the gene that encodes apolipoprotein E, a lipid transport protein. The clinical relevance of these biologic effects is not fully known.

The relation between hormone usage and Alzheimer risk has been addressed in a large number of observational studies and in 1 primary prevention trial. This body of clinical research has led to important conclusions regarding hormone therapy and dementia, although some important clinical issues remain unsettled. Protective associations of hormone therapy are reported from a number of studies. These include the Leisure World retirement community [relative risk estimate RR , 0.

The interpretation and clinical relevance of these reported associations is challenged by seemingly discrepant findings from the WHIMS trials. Women were generally healthy, but there is suggestion that these volunteers were somewhat less healthy eg, higher prevalence of obesity than women in the general population.

One hundred eight women developed dementia during the course of the 2 WHIMS trials during mean follow-up periods of about 5 years. Because the trials were halted prematurely, the number of incident cases of dementia was less than anticipated, and separate outcomes were not reported for Alzheimer disease or other specific dementia types. In the estrogen-progestogen trial, the risk of dementia among women in the active treatment group was twice that of women in the placebo group.

The increased risk in these populations represents about 2 additional cases of dementia per women per year of hormone use. Women with lower cognitive scores at the time of enrollment, and older women, were much more likely to develop dementia during the course of the trials.

The increase in dementia risk became apparent within a few years after treatment allocation. Women in the WHIMS trials who had used hormone therapy in the past were significantly less likely to develop Alzheimer disease or another form of dementia than women who had not used hormone therapy; prior use did not modify effects of randomized treatment allocation during the WHIMS trials.

In general, women who use hormone therapy are better educated, enjoy better health, and engage in healthier lifestyles than nonusers. Such differences might account for protective associations seen in most observational studies. WHIMS participants differed from many women in observational studies, particularly including the age at which hormone therapy was initiated and used. Thus, most hormone use in observational studies occurred at a relatively young age, close to the time of menopause.

Endotext [Internet].

Am J Clin Nutr. If you do choose HRT, see your physician regularly and consider bioidentical rather than synthetic hormones. Please review our privacy policy. E2 1 mg PO. If symptoms are controlled, continue HT.

In contrast, all hormone use during the WHIMS trials occurred only after age 64, remote from the time of menopause. It is unknown whether estrogen effects on Alzheimer risk are modified by age of use or by use during a critical window close to the time of menopause. Estrogen has been considered as a potential treatment for women with dementia due to Alzheimer disease. Results of several randomized, double-blind, placebo-controlled trials—while not fully congruent—have been disappointing. Perhaps most encouraging was an 8-week trial of 20 women treated with transdermal estradiol or placebo.

In contrast, 4 somewhat larger clinical trials found no important effect on a variety of clinical and functional measures. These included a week trial of 36 women, a week trial of 47 women, a month trial of women, and a week trial of women. Some neurons express progesterone receptors. In the laboratory setting, different estrogens affect neuronal function differently; the same is true for different progestogens.

Although progesterone is neuroprotective in some experimental models, limited observational data raise the possibility that the progestogen component of combined hormone therapy could affect cognition deleteriously. They exert tissue-specific estrogenic effects by inducing unique conformational changes in the estrogen receptor.

Two well-known SERMs are tamoxifen, used in breast cancer prevention, and raloxifene, used in osteoporosis prevention. Within the brain, agonist or antagonist profiles of tamoxifen and raloxifene differ from each other. For women with osteoporosis, cognitive outcomes were examined in ancillary studies of the Multiple Outcomes of Raloxifene Evaluation trial.

Raloxifene had no effect on overall cognitive function in this large clinical trial, 43 but at higher doses raloxifene reduced the likelihood that study participants would develop cognitive impairment. Neurologic effects of SERMs are an increasingly important area of consideration as newer compounds are developed and marketed. Although much remains to be learned, considerable progress has been made in understanding cognitive effects of estrogen after menopause.

Clinical implications of current evidence are summarized in Table 3. Cognitive changes and menopause: There is no approved indication for estrogen for the treatment or prevention of cognitive aging or Alzheimer disease. National Center for Biotechnology Information , U. Author manuscript; available in PMC Sep 1. Henderson , MD, MS. The publisher's final edited version of this article is available at Clin Obstet Gynecol.

New Study Eases Long-Held Fears About Hormone Replacement Therapy

See other articles in PMC that cite the published article. Abstract The natural menopause is not associated with substantial cognitive change. Alzheimer disease, cognition, estrogen, memory, menopause, selective estrogen receptor modulators. Estrogen and the Brain About 40 million American women have reached the menopause.

Estrogen and Cognition in Midlife Functional brain imaging studies demonstrate that estrogen modulates neural activity during performance of cognitive tasks. Estrogen and Cognition Later in Life Results of observational research involving older women are not fully consistent in delineating putative cognitive effects of hormone therapy in the late postmenopause. Table 1 Hormone therapy in older postmenopausal women without dementia: Open in a separate window.

No between-group differences on memory tasks 3 years after randomization; better digit span performance in placebo group, but no differences on other non-memory tasks. Other comparisons were nonsignificant, and the magnitude of significant differences was small. Alzheimer Disease Dementia is a symptom with multiple causes. Hormone Therapy and Dementia Risk The relation between hormone usage and Alzheimer risk has been addressed in a large number of observational studies and in 1 primary prevention trial. Estrogen and Alzheimer Disease Therapy Estrogen has been considered as a potential treatment for women with dementia due to Alzheimer disease.

The Role of Progestogen Some neurons express progesterone receptors. Clinical Implications Although much remains to be learned, considerable progress has been made in understanding cognitive effects of estrogen after menopause. Table 3 Cognitive changes and menopause: Dementia risk may be elevated if WHIMS clinical trial findings in older women generalize to this younger group.

Alzheimer risk may be reduced if observational findings of protective associations are valid. Limited clinical trial evidence. Footnotes Conflicts of Interest: Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks. Estrogen exposures and memory at midlife: Endogenous estrogen is not associated with cognitive performance before, during, or after menopause.

Cognitive function across the life course and the menopausal transition in a British birth cohort. A longitudinal study of cognition change during early menopausal transition in a rural community. Memory functioning among midlife women: Effects of estrogen on memory function in surgically menopausal women.

Hormone Replacement Therapy and Neurological Function (Controversial Issues in Climacteric Medicine)

Popular Posts

Cognitive Changes After Menopause: Influence of Estrogen

Review ARTICLE

Menopause and Hormone Replacement - Endotext - NCBI Bookshelf

Related Ratings

Endotext [Internet].