leuprolide and Cognition-Disorders

In the 1990s, estrogens were thought to protect the aging brain. Large randomized controlled studies, however, showed that estrogens did not treat dementia symptoms and even increased risk for dementia in older women. These findings contrast with earlier positive findings, including a wealth of cell culture and animal data all suggesting that estrogens could be a prophylactic treatment for dementia. Observational data had also suggested a significantly decreased risk for dementia in women who had been treated with estrogens for menopausal symptoms in midlife. This review discusses the "Critical Window", Healthy Cell Bias' and "Limited Duration" hypotheses, and forms of bias (healthy user, recall and survivor bias) and potential mediators (e.g., body mass, genetics) to attempt to explain the differences seen between the studies. On the basis of limited data, we conclude that estrogens only have limited positive effects on some tests for a number of months regardless of age. These effects were seen in recently menopausal women, but also in women with dementia, who are at least 15 years past the average age of menopause. In addition, after a longer period of time, treatment may confer risk, especially in older women. From this it would follow that longer term treatment with estrogens to maintain cognitive function is not indicated for older women. Whether there still is a case to treat surgical menopausal women with estrogens for a longer or shorter period of time remains to be tested.

Topics: Aged; Aged, 80 and over; Animals; Brain; Cardiovascular Diseases; Cognition Disorders; Comorbidity; Confounding Factors, Epidemiologic; Dementia; Estrogen Replacement Therapy; Female; Humans; Leuprolide; Male; Menopause; Menopause, Premature; Middle Aged; Models, Biological; Obesity; Prevalence; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors

To investigate the effects of different management strategies for non-localized prostate cancer on men's quality of life and cognitive functioning.. Men with prostate cancer were randomly assigned to one of four treatment arms: leuprorelin, goserelin, cyproterone acetate (CPA), or close clinical monitoring. In a repeated-measures design, men were assessed before treatment (baseline) and after 6 and 12 months of treatment. A community comparison group of men of the same age with no prostate cancer participated for the same length of time. The men were recruited from public and private urology departments from university teaching hospitals. All those with prostate cancer who were eligible for hormonal therapy had no symptoms requiring immediate therapy. In all, 82 patients were randomized and 62 completed the 1-year study, and of the 20 community participants, 15 completed the study. The main outcome measures were obtained from questionnaires on emotional distress, existential satisfaction, physical function and symptoms, social and role function, subjective cognitive function, and sexual function, combined with standard neuropsychological tests of memory, attention, and executive functions.. Sexual dysfunction increased for patients on androgen-suppressing therapies, and emotional distress increased in those assigned to CPA or close clinical monitoring. Compared with before treatment there was evidence of an adverse effect of leuprorelin, goserelin, and CPA on cognitive function.. In deciding the timing of androgen suppression therapy for prostate cancer, consideration should be given to potential adverse effects on quality of life and cognitive function.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cognition Disorders; Cyproterone Acetate; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Quality of Life; Sexual Dysfunction, Physiological; Stress, Psychological

To report the first systematic investigation of the cognitive effects of luteinizing hormone-releasing hormone (LHRH) analogues in male patients, as LHRH analogues have been associated with memory impairments in women using these drugs for gynaecological conditions.. Eighty-two men with extraprostatic prostate cancer were randomly assigned to receive either continuous leuprorelin, goserelin (both LHRH analogues), cyproterone acetate (a steroidal antiandrogen) or close clinical monitoring. These patients underwent cognitive assessments at baseline and before starting treatment (77), and then 6 months later (65).. Compared with the baseline assessments, men receiving androgen suppression monotherapy performed worse in two of 12 tests of attention and memory; 24 of 50 men randomized to active treatment and assessed 6 months later had a clinically significant decline in one or more cognitive tests but not one patient randomized to close monitoring showed a decline in any test performance.. Pharmacological androgen suppression monotherapy for prostate cancer may be associated with impaired memory, attention and executive functions.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cognition Disorders; Cyproterone Acetate; Drug Combinations; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms

Treatment of women with uterine myomas with GnRH agonists results in symptoms of hypoestrogenism which can be prevented by concurrent "add-back" estrogen administration. We took advantage of these induced endocrine changes to investigate their effects on cognitive functioning in young women with myomas. Nineteen women with uterine myomas were tested before treatment. They all received the GnRH agonist, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks and were then randomized to receive LAD plus estrogen or LAD plus placebo every 4 weeks for 8 additional weeks. Levels of all sex hormones decreased after 12 weeks of LAD treatment (P < 0.01), and only estradiol (E2) levels increased (P < 0.01) following 8 weeks of subsequent treatment in the group that received LAD plus E2. Scores on neuropsychological tests of verbal memory decreased from pretreatment to 12 weeks posttreatment with LAD (P < 0.05). These memory deficits were reversed in the group that received LAD plus E2 for 8 weeks coincident with an increase in plasma E2, whereas memory scores remained depressed in the group that received LAD plus placebo. These findings are consistent with those from studies on surgically menopausal women and strongly suggest that estrogen serves to maintain verbal memory in women. These results provide support for the efficacy of add-back estrogen regimens in women treated with GnRH agonists and also imply that estrogen may be important for maintaining memory in the postmenopause.

Topics: Adult; Cognition Disorders; Delayed-Action Preparations; Estradiol; Female; Humans; Leiomyoma; Leuprolide; Memory Disorders; Uterine Neoplasms

Meningiomas are the most common type of benign brain tumor, and the incidence of meningioma in women is more than twofold higher than in men. Several studies have demonstrated that hormones are somehow related to the growth of meningiomas.. A 72-year-old man with benign meningioma underwent tumor resection and had no recurrence for 18 years. He was found to have prostate cancer, and he received hormonal therapy with a luteinizing hormone-releasing hormone (LHRH) agonist. Two years later, he developed severe cognitive dysfunction and gait disturbance. Gadolinium-enhanced brain magnetic resonance imaging revealed a large recurrent mass and obstructive hydrocephalus. Staged resection was performed and stereotactic radiation therapy was administered against the residual tumor. His symptoms improved after endoscopic third ventriculostomy for obstructive hydrocephalus and his residual tumor remains stable.. This is the first report of a case in which an LHRH agonist promoted the growth of a pre-existing meningioma. We suggest that patients with a history of meningioma who are receiving LHRH agonist treatment should be closely monitored.

Topics: Aged; Antineoplastic Agents, Hormonal; Cognition Disorders; Disease Progression; Gadolinium; Gait Disorders, Neurologic; Humans; Ki-67 Antigen; Leuprolide; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Meningioma; Neoplasm Recurrence, Local; Neoplasm, Residual; Prostatic Neoplasms; Radiosurgery

Cognitive difficulties following treatment for breast cancer are frequently reported. Breast cancer treatments also disrupt the function of ovarian and glucocorticoid hormone systems, both of which can affect cognition.. To assess the influence of glucocorticoid and ovarian disruption on cognitive dysfunction, survivors of breast cancer treated with the GnRH agonist Lupron were compared with healthy controls on their glucocorticoid response to a physiological stressor, and their performance on various measures of cognition including working memory, verbal paired associate memory, and narrative recall.. The results indicated no significant glucocorticoid response to the stressor in Lupron-treated survivors, while the controls showed significantly elevated cortisol levels. Cognitive testing showed a general impairment of narrative recall in breast cancer survivors relative to controls, irrespective of stress treatment. When tested on an emotional narrative, controls exposed to post-training stress showed a significant enhancement of emotional recall and a significant relationship between cortisol release and subsequent memory. In contrast, post-training stress produced no cognitive enhancement in survivors, and memory performance in this group showed no relationship to cortisol levels.. These results suggest that a disruption of the enhancement of memory by stress may contribute to cognitive difficulties following breast cancer treatment.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Case-Control Studies; Cognition; Cognition Disorders; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leuprolide; Memory; Neuropsychological Tests; Pituitary-Adrenal System; Saliva; Stress, Psychological; Survivors

Declining levels of estrogen in women result in increases in gonadotropins such as luteinizing hormone (LH) through loss of feedback inhibition. LH, like estrogen, is modulated by hormone replacement therapy. However, the role of post-menopausal gonadotropin increases on cognition has not been evaluated. Here, we demonstrate that the down-regulation of ovariectomy-driven LH elevations using the gonadotropin releasing hormone super-analogue, leuprolide acetate, improves cognitive function in the Morris water maze and Y-maze tests in the absence of E2. Furthermore, our data suggest that these effects are independent of the modulation of estrogen receptors alpha and beta, or activation of CYP19 and StAR, associated with the production of endogenous E2. Importantly, pathways associated with improved cognition such as CaMKII and GluR1-Ser831 are up-regulated by leuprolide treatment but not by chronic long-term E2 replacement suggesting independent cognition-modulating properties. Our findings suggest that down-regulation of gonadotropins is as effective as E2 in modulating cognition but likely acts through different molecular mechanisms. These findings provide a potential novel protective strategy to treat menopause/age-related cognitive decline and/or prevent the development of AD.

Topics: Animals; Aromatase; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cognition Disorders; Disease Models, Animal; Down-Regulation; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Fertility Agents, Female; Gonadotropins; Leuprolide; Maze Learning; Menopause; Mice; Mice, Inbred C57BL; Ovariectomy; Reaction Time; Receptors, AMPA; Receptors, Estrogen; RNA, Messenger; Serine

The study investigated the neuropsychological status of women with induced hypoestrogenism.. An ABA design was employed in which neuropsychological measures were repeated prior to, during, and after induction of hypoestrogenism with leuprolide acetate.. The study took place in a medical school affiliated in vitro fertilization clinic.. Leuprolide acetate was administered to all subjects as part of in vitro fertilization.. Eighteen women receiving in vitro fertilization treatment underwent neuropsychological testing before, during, and after treatment with leuprolide acetate and gonadotrophins. The neuropsychological test battery was selected on the basis of previous patients' symptomatic complaints during periods of hypoestrogenism with leuprolide acetate.. Depending upon the tests administered, some individuals showed significant cognitive deficits during therapy particularly in the areas of memory, fine motor coordination, and two-point discrimination. Two of the 18 subjects showed very substantial neuropsychological sequelae including memory gaps and disturbances in a variety of neuropsychological test performances. However, in terms of group statistics, only two-point discrimination and delayed recall memory test performance proved significant. Not all measures were sensitive for the group, as many tests displayed a balance between individuals who showed practice effects and those who showed detrimental effects.. For a substantial portion of individuals, hypoestrogenism can result in statistically significant or clinically noteworthy problems with memory, dexterity, and two-point discrimination.

Topics: Adult; Cognition Disorders; Estrogens; Female; Fertilization in Vitro; Humans; Leuprolide; Memory Disorders; Motor Activity; Neuropsychological Tests