Study «Alhola P, Tuomisto H, Saarinen R, ym. Estrogen + p...»1
Population: 16 perimenopausal (45–51 years) and 16 postmenopausal (aged 58–70 years) women. Mean time since menopause in the postmenopausal women was 12.0 years (SD = 4.5).
Inclusion criteria: No history of cardiovascular (stabile hypertension and treated hyperlipidemia accepted), neurological, endocrinological, or mental disease; no malignancies; no use of medication affecting the central nervous system; no abuse of alcohol or medications; no smoking or excessive consumption of caffeine (>five cups of coffee a day). Before the study, depression was rolled out by The Beck Depression Inventory and cognitive impairment by The Mini-mental State Examination.
Study design and interventions: Randomized, controlled study. Cognitive measurements included tests of: 1) controlled cognitive processing and attention, 2) verbal attention, 3) auditory attention, 4) shared attention, 5) working memory, 6) verbal functions, 7) verbal episodic memory, 8) visuomotor functions, and 9) visual episodic memory.
After the baseline cognitive measurement, the subjects were randomized to receive either oral menopausal hormone therapy (MHT) or placebo (PL) for six months. In the premenopausal women, the MHT was cyclic EPT (2 mg estradiol valerate for 16 days and 2 mg estradiol valerate + 1 mg norethisterone for 12 days, and in the postmenopausal women, it consisted of continuous combined EPT (2 mg estradiol valerate + 0.7 mg norethisterone). In case of previous MHT, the women conformed to a 12-month washout period.
After three months, the women visited the research unit, where compliance for research drug and possible side-effects were checked in an interview, and blood samples were taken to control estradiol (E2) and follicle stimulating hormone (FSH) -levels.
Results: In premenopausal women, at sixth months, cognitive attention, when compared to baseline, improved with MHT, but declined slightly with PL in the two-choice reaction time task (p=0.049), while PL was associated with better performance in tests of shared attention (p=0.024) and auditory attention (p<0.05). In postmenopausal women, use of MHT was associated with improved performance in verbal episodic memory (p=0.024) and a minor decline in auditory attention (p=0.025).
Conclusions: MHT, with estradiol valerate and norethisterone, in healthy women showed only minor effects on attention around the menopausal transition and on memory in postmenopause.
Study «Alhola P, Polo-Kantola P, Erkkola R, ym. Estrogen ...»2
Population: 62 healthy postmenopausal women, 60 (97%) women participated in this follow-up. At the follow-up, the subjects were aged between 53 and 72 years (mean 62.4 years, SD 4.4).
Study design: A prospective, single-blind, 6-year follow-up study based on the population of a randomized, double-blind, crossover trial to measure effects of short-term (3 months) MHT on cognition.
After the baseline intervention trial, the women were free to choose whether they continued MHT: 18 women discontinued immediately (nonusers), 21 women continued to use MHT (continuous users), and 21 women used MHT discontinuously during the 6 years (irregular users). The MHT used in this study was unopposed estrogen (estradiol).
Cognitive tests included a conprehensive test battery. Verbal skills were measured with Similarities and Digit Span from the Wechsler Adult Intelligence Scale (WAIS) and naming time of 20 objects. Episodic memory was assessed with recall of 20 objects, 30 Paired Word Associates (30-PWA), and the Benton Visual Retention test (Form C). Delayed recall of the 20 objects and the 30 PWA was asked after 60 minutes. Visuomotor performance was evaluated with Digit Symbol and Block Design from the WAIS. Cognitive processing and attention were measured with the CogniSpeed software, including the Simple reaction time, 2-Choice reaction time (2-CRT), 10-Choice reaction time (10-CRT), Subtraction, Verification, Vigilance, Stroop (color-meaning congruence and incongruence tasks), and Recognition of numbers and letters. Reaction times in milliseconds for correct responses, and error rates were recorded. The Paced Auditory Serial Addition Test was used to measure auditory attention The trained psychologist who conducted neuropsychological tests was blinded to the subjects' use of HT.
Results: In most of the variables, the changes between baseline and follow-up were similar in all three groups. In 4 of 45 variables, performance changed differently in the groups (20 objects naming time p=0.032, immediate recall p=0.021, and delayed recall p=0.049, 30-PWA immediate recall, correct p=0.027). The change in continuous users differed from that of nonusers and irregular users in the 20 objects task (naming time, immediate and delayed recall, all p values ≤ 0.001). Naming time improved in nonusers, but had become slightly longer in irregular users and more so in continuous users. The number of recalled objects (immediate and delayed recall) increased in nonusers and irregular users, whereas in continuous users, the numberdid not change. In the 30-PWA (immediate recall, correct), the change was different between nonusers and irregular users (p=0.018). The performance of nonusers had improved, but there was no change in irregular users. Continuous users had improved their performance slightly. In CogniSpeed tasks of processing speed and accuracy, the subjects made only few errors, except in the verification task of working memory. The change did not differ between the groups in any error rates. In the Vigilance task of sustained attention, the omission rates did not change. The subjects were able to detect nearly 100% of the targets both at baseline and at follow-up
Conclusions: All women had well-maintained cognitive performance. In fact, cognitive performance was well maintained, even if 6 years had passed and some women were older than 70 years. Long-term HT did not affect cognition, either for better or for worse.
Study «Espeland MA, Shumaker SA, Leng I, ym. Long-term ef...»3
Population: 1,326 postmenopausal women, who had begun treatment in two randomized placebo controlled clinical trials of hormone therapy when aged 50–55 years. The clinical trials in which they participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate (MPA) over an average of 7.0 years.
Study design: Cognitive testing was conducted an average of 7.2 years following the end of the trials, when women had mean age 67.2 years, and repeated one year later. Cognitive testing was administered by telephone and included measures of global (primary outcome) and domain-specific cognitive functions (verbal memory, attention, executive function, verbal fluency, and working memory).
Results: Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean [95% confidence interval] intervention effect of 0.02 [−0.08,0.12] standard deviation units (p=0.66). Similarly, no overall differences were found for any individual cognitive domain (all p>0.15). Pre-specified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of −0.17 [−0.33, −0.02] and −0.25 [−0.42, −0.08], respectively, however this may be a chance finding.
Conclusions: Initiating hormone therapy during the menopause and maintaining therapy during several years, does not affect cognitive function, either in the short or longer term. CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50–55 years.