Hormone Replacement Therapy and Risk for Neurodegenerative Diseases

Table 2

Randomized clinical trials of HRT and verbal memory.

Study (reference)	Hormone treatment used	Sample size	Age	Outcome measure	Overall findings
Bagger et al., [18]	E2 2 mg + varied progestins versus placebo for 2 years	261	54.1	Cognitive screening task	Followup study of women randomized 5, 10 and 15 years earlier to HRT or placebo during clinical trials. Logistic regression showed that for women who received HRT for 2-3 years, the relative risk for cognitive impairment was significant decreased by 64% compared to the never users. Long-term/current users of HT also demonstrated a decreased risk of 66% compared to the never users.
Joffe et al. [19]	E2 0.5 mg versus placebo for 12 months	52	40–60	Verbal memory; Functional MRI	Women on E2 had fewer perseverative errors during verbal recall when placebo-treated women. Women on E2 also showed greater retention of new information without interference.
LeBlanc et al., [20]	Estradiol 2 mg versus placebo for 2 months	32	53.26 (treatment) 52.08 (placebo)	Verbal memory	Women on estrogen therapy did not show higher cognitive performance on verbal memory tasks compared to women on placebo.
Maki et al., [21]	(CEE) + medroxyprogesterone acetate (MPA) versus placebo for 4 months	158	51.9 (treatment) 52.4 (placebo)	Verbal memory	Modest negative effects on verbal memory (short- and long-term recall) were found in the HRT versus placebo group.
Dumas et al. [22]	E2 2 mg versus placebo for 3 months	22	50-62 (younger) 70–81 (older)	Verbal memory	All women were administered the antimuscarinic drug scopaline (SCOP) or placebo. E2 pretreatment significantly decreased the anticholinergic drug-induced impairments on verbal memory task for the younger group only compared to the older group.
Tierney et al. [23]	E2 1 mg versus placebo for 2 years	142	61–87	Verbal memory	Women on E2 who scored at or above average showed less decline in delay verbal memory compared to women on placebo.
Silverman et al. [24]	17β-estradiol (E2) versus conjugated equine estrogen (CEE) versus CEE + P for 1 year	53	50–65	Verbal memory; FDG-PET	Women on E2 had significantly higher verbal memory than CEE and showed higher metabolism in Wernicke’s and auditory association. E2 was also associated with higher metabolism in mesial and inferior lateral temporal regions and inferior frontal cortex compared to PE.