Thyroid hormones and cognitive functioning in healthy, euthyroid women: a correlational study.

Thyroid hormones (THs) play a critical role in differentiation, growth, and metabolism of animal and human organ systems, including the brain. Although associations between normal levels of THs and cognitive functions in healthy elderly individuals have been reported, the findings are inconsistent, possibly due to differences in study designs. Because thyroid disease occurs more frequently in women, the goal of the present study was to examine the relationship between levels of THs and performance on neuropsychological tests in 122 healthy, euthyroid women whose mean age was 51 years.

Estrogen and cognitive functioning in women: lessons we have learned.

Extant research findings allow several conclusions regarding the relationship between estrogen and cognitive functioning across the female life span. First, performance on tests of verbal memory fluctuates in concert with physiological changes in ovarian hormone production during the menstrual cycle and during pregnancy and the postpartum period. Estrogen therapy (ET) prevents the decrease in verbal memory when administered immediately following the surgical removal of both ovaries in premenopausal women.

Hormones and cognitive functioning during late pregnancy and postpartum: a longitudinal study.

This longitudinal study investigated the possible influence of estradiol (E₂), progesterone (P), testosterone (T), cortisol (CORT), and prolactin (PRL) levels on cognitive functioning during late pregnancy and the early postpartum period. The performance of 55 pregnant women on a battery of neuropsychological tests, tested once during the third trimester of pregnancy and once during the early postpartum period, was compared with that of 21 nonpregnant controls matched for age and education. Women in the pregnancy group had significantly lower scores than the controls during both the pre- and postpartum visits on tasks of verbal recall and processing speed.

Differential effects of estrogen and micronized progesterone or medroxyprogesterone acetate on cognition in postmenopausal women.

Objective: To investigate possible differential effects of the coadministration of conjugated equine estrogen (CEE) and a placebo (CEE + PL), CEE and medroxyprogesterone acetate (CEE + MPA), or CEE and micronized P (CEE + MP) on aspects of cognitive functioning in naturally postmenopausal women.

Design: Double-blind, randomized, controlled trial.

Setting: Gynecologic screening occurred at a university hospital, and neuropsychological testing took place in a university laboratory.

Sex steroid hormones and cognitive functioning in healthy, older men.

The precise impact of age-related changes in hormone levels on cognition in men is still unclear due to differing study designs and contradictory findings. This study was undertaken to examine the relationship between endogenous sex hormone levels and cognitive functioning in healthy older men using a comprehensive battery of neuropsychological tests and measurement of serum sex hormone levels. Verbal learning and memory, visual-motor processing, spatial abilities, working memory and attention, and levels of testosterone and estradiol were evaluated in 54 healthy older men.

A randomized controlled trial of estrogen treatment in men with mild cognitive impairment.

This randomized, placebo-controlled, cross-over study investigated whether estrogen treatment would have a beneficial effect on tests of verbal memory in men with mild cognitive impairment (MCI). Forty-three men newly diagnosed with MCI were administered a battery of neuropsychological tests before randomly receiving 12 weeks of treatment with estrogen or placebo followed by a 12 week cross-over treatment. A significant improvement in the total score, and in two subscale scores of the Buschke Selective Reminding Test occurred following estrogen treatment compared to both pretreatment and post-placebo scores (p<0.

Estrogen therapy: is time of initiation critical for neuroprotection?

According to the 'critical period' hypothesis, which attempts to explain the observed discrepancies in the studies on estrogen and cognition, estrogen therapy effectively decreases cognitive decline in aging women when it is initiated around the time of menopause but not when it is started decades later. Here, I review studies in which the timing of the initiation of estrogen therapy was provided, to determine whether their findings support the 'critical period' hypothesis. The vast majority of the reviewed studies support the idea that early but not late initiation of estrogen therapy might prevent or delay cognitive decline in aging women.

A randomized controlled trial of add-back estrogen or placebo on cognition in men with prostate cancer receiving an antiandrogen and a gonadotropin-releasing hormone analog.

The effects of testosterone (T) and estradiol (E(2)) on cognition in men are confounded in extant studies. This randomized, placebo-controlled trial was undertaken to investigate the possible effects of E(2) on cognition in older men. Twenty-five men with prostate cancer (mean age: 71.

Brain aging modulates the neuroprotective effects of estrogen on selective aspects of cognition in women: a critical review.

Although there is now a substantial literature on the putative neuroprotective effects of estrogen on cognitive functioning in postmenopausal women, it is replete with inconsistencies. The critical period hypothesis, posited several years ago, attempts to account for the discrepancies in this literature by positing that estrogen treatment (ET) will protect aspects of cognition in older women only when treatment is initiated soon after the menopause. Indeed, evidence from basic neuroscience and from the animal and human literature reviewed herein provides compelling support for the critical period hypothesis.

The clinical relevance of the relationship between estrogen and cognition in women.

Randomized controlled trials (RCTs) and observational and longitudinal studies provide positive, albeit, inconsistent evidence that estrogen might protect against cognitive decline in postmenopausal women. The fact that the Women's Health Initiative Memory Study (WHIMS), the largest RCT to date, failed to find that estrogen therapy (ET) had a protective effect against cognitive aging led to the formulation of the critical period hypothesis which holds that ET will effectively protect against memory decline when it is initiated around the time of menopause but not when considerable time has elapsed since the menopause. Evidence from basic neuroscience, and from rodent, nonhuman primate, and human studies that supports this theory is presented.

Surgical versus natural menopause: cognitive issues.

Objective: Women who undergo both natural and surgical menopause experience the loss of cyclic ovarian production of estrogen, but hormonal and demographic differences distinguish these two groups of women. Our objective was to review published evidence on whether the premature cessation of endogenous estrogen production in women who underwent a surgical menopause has deleterious consequences for cognitive aging and to determine whether consequences differ for women if they undergo natural menopause. Studies of estrogen-containing hormone therapy are relevant to this issue.

Testosterone levels and cognitive functioning in women with polycystic ovary syndrome and in healthy young women.

We investigated the possible influence of testosterone (T) on cognitive functioning in women with polycystic ovary syndrome (PCOS), an endocrine disorder associated with elevated levels of free testosterone (free T). Performance on a battery of neuropsychological tests in 29 women with elevated free T levels due to PCOS was compared to the performance of 22 age- and education-matched, healthy control women with free T levels in the normal female range. Women with PCOS had significantly higher levels of free T (estimated by the free androgen index) and demonstrated significantly worse performance on tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory than the healthy control women.

Effects of the pharmacologic manipulation of testosterone on cognitive functioning in women with polycystic ovary syndrome: a randomized, placebo-controlled treatment study.

In a previous study, we found that women with polycystic ovary syndrome (PCOS), an endocrine disorder characterized by chronic hyperandrogenism, performed more poorly than healthy, matched controls on a number of neuropsychological tests, in particular tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory. This randomized, placebo-controlled trial was undertaken to investigate whether pharmacologic manipulation of free testosterone (free T) levels in women with PCOS might affect their performance on cognitive tests. Nineteen women with PCOS completed a battery of neuropsychological tests before and after 3 months of treatment with either an anti-androgen (cyproterone acetate) plus estrogen or with a placebo.

Effects of treatment with leuprolide acetate depot on working memory and executive functions in young premenopausal women.

The goal of this study was to assess the influence of sex steroid hormone suppression on performance on tests of prefrontal cortex (PFC) and working memory function (WM) in premenopausal women. Twenty-five women were treated with leuprolide acetate depot (LAD), a gonadotropin releasing hormone (GnRH) analog that chemically suppressed ovarian function as treatment of various benign gynecologic disorders. Performance on tests of PFC and WM of the LAD-treated women was assessed at pretreatment baseline and, again, following 4 weeks of treatment and their performance was compared to that of 25 healthy, control participants matched on age, education, and general intelligence.

Surgical menopause, estrogen, and cognitive function in women: what do the findings tell us?

Randomized, controlled trials of estrogen treatment found protective effects of estrogen therapy (ET) on verbal memory in healthy, 45-year-old surgically menopausal women given 17-beta estradiol immediately after surgery. However, no effect was found when conjugated equine estrogens were given to older women years after their surgical menopause. These findings suggest that there is a critical time for the initiation of estrogen following the menopause with regard to its protective effect on memory as well as a specificity of the effect on verbal memory.

Estrogen and memory in women: how can we reconcile the findings?

Although several randomized controlled trials (RCTS) of surgically menopausal women have provided evidence that estrogen protects aspects of memory, many cross-sectional and longitudinal studies, including those from the RCT, the Women's Health Initiative Memory Study (WHIMS), have reported inconsistent information with regard to the relationship between estrogen and aspects of cognitive function. Although numerous reasons could be offered to explain these discrepancies in research findings, recent evidence from rodent, nonhuman primate, and human studies consistently suggests that one possibility may be critical to our understanding of the estrogenic effect on memory. Results of these animal and human studies indicate that the initiation of estrogen treatment at the time of menopause, or soon after ovariectomy (OVX), provides a window of opportunity for the preservation of memory in females whereas the administration of the hormone following a considerable delay in time after OVX has little or no beneficial effect on cognition.

Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study.

Context: The Women's Health Initiative Memory Study (WHIMS) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older. The effect of estrogen-alone therapy, also evaluated in WHIMS, on cognition has not been established for this population.

Objectives: To determine whether conjugated equine estrogen (CEE) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate (CEE plus MPA).

Steroid hormones and cognitive functioning in aging men: a mini-review.

The decrease in testosterone (T) production in aging men has been well documented. Because the majority of circulating estradiol (E2) in men arises through aromatization of T, levels of E2 decrease as well with increasing age. It is also clear that some proportion of men develop impairments in aspects of cognition, particularly in explicit memory and language abilities with normal aging.

Estrogen and cognitive functioning in women.

Research in basic neuroscience has provided biological plausibility for the hypothesis that estrogen replacement therapy (ERT) would protect against cognitive aging in healthy women. The weight of the evidence from randomized controlled trials of estrogen and cognition in women shows that this hormone preferentially protects verbal memory in postmenopausal women, whereas findings from observational studies are less consistent and show a more diffuse effect of estrogen on a range of cognitive functions. There is fairly consistent evidence from epidemiological studies that ERT significantly reduces the risk of Alzheimer's disease (AD) in women.

Estrogen and cognitive aging in women.

The steady increase in female life expectancy has attracted attention to the importance of preventing cognitive aging and Alzheimer's disease (AD) in women. Evidence from randomized, controlled trials and from cross-sectional and longitudinal studies shows that estrogen-replacement therapy preferentially protects against a decline in verbal memory in healthy postmenopausal women and decreases the risk of AD. Although results are not consistent across studies, they indicate that treatment with estrogen during the postmenopausal years might protect against cognitive aging in women during the latter part of their life.

Estrogen and cognitive functioning in men with mild cognitive impairment.

Although men do not experience an abrupt cessation of gonadal hormone production at midlife as do women, levels of testosterone (T) decrease gradually with aging. Because estradiol (E2) arises mainly from the conversion of T in men, the availability of E2 also decreases with increasing age. In randomized clinical trials, E2 replacement therapy has been shown to maintain aspects of cognition in postmenopausal women, specifically with regard to verbal memory.

Randomized clinical trials of combined estrogen-androgen preparations: effects on sexual functioning.

Objective: To review the randomized controlled trials of the efficacy of combined estrogen-androgen (E-A) preparations on sexual functioning in postmenopausal women.

Patient(s): Naturally and surgically menopausal women.

Main Outcome Measure(s): Changes in aspects of sexual functioning.