TABLE 2.

Estrogens and Episodic Memory: Randomized, Double-Blind, Placebo-Controlled Trials in Postmenopausal Women^*

First author, publication year	Type of menopause	Experimental design	Mean age, years	Number of women	Mean duration	Hormone treatment	Episodic memory
							Verbala	Nonverbalb
Younger postmenopausal women (mean age less than 60 years)
Hackman, 197693	Both	Parallel	Range 29 to 68	18	6 months	Estrone (O)	NSc	—
Vanhull, 197694	Both	Parallel	58	26	3 months	Estriol (O)	—	NS
Sherwin, 198862	Surgical	Crossover	45	40d	3 months	E2 (IM); Other hormone treatments	E2 better	—
Phillips, 199263	Surgical	Parallel	48	19	2 months	E2(IM)	E2 better	NS
Polo-Kantola, 199895	Surgicale	Crossover	56	62	3 months	E2 ( TD)	—	NS
Linzmayer, 200196	Not reported	Parallel	57	49g	2 months E2 + P(O)g	E2 (O); E2 + P, most NSh	E2, NS;	NS
Dunkin, 200597	Both	Parallel	57	17	10 weeks	E2 (TD)	NS	NS
Joffe, 200658	Natural	Parallel	51	50	12 weeks	E2 (TD)	NS	NS
Maki, 200798	Natural	Parallel	52	180	4 months	CE + P(O)	NS	NS
Older postmenopausal women (mean age greater than 60 years)
Bender, 200199	Both	Parallel	81	52	9 months	CE + P(O)	NS	—
Grady, 2002100	Both	Parallel	67	1063	4 years	CE + P(O)	NS	—
Viscoli, 2005101	Both	Parallel	70	461	3 years	E2(O)	NS	NS
Wolf, 2005102	Surgicale	Parallel	64	35l	24 weeks	E2 (O); E2 + P (O)	NS	NS
Almeida, 200670	Surgicale	Parallel	74	115	20 weeks	E2(O)	NS	NS
Resnick, 200672	Natural	Parallel	71	1416	4 years	CEE + P (O)	Placebo betterm	NSm
Yaffe, 2006103	Natural	Parallel	67	417	2 years	E2 (TD)	NS	NS

^*Restricted to clinical trials reporting an objective measure of episodic memory and a mean treatment duration of at least one month. Table adapted with permission of the publisher from Henderson & Sherwin.⁶⁰

CE = conjugated estrogens; E2= estradiol; IM = intramuscular; NS = nonsignificant probability P>0.05; O = oral; P = progestogen (medroxyprogesterone acetate daily in Maki, Grady, Resnick and trimonthly in Binder; dienogest in Linzmayer); TD = transdermal.

^aVerbal episodic memory tasks were word-list recall (Dunkin, Joffe, Grady, Almeida, Resnick, Yaffe); paragraph recall (Sherwin, Phillips, Dunkin, Joffe, Maki, Wolf, Yaffe); associate learning (Phillips, Linzmayer, Dunkin, Bender, Wolf); a composite score emphasizing verbal memory (Hackman); common, numerical and total verbal memory (Linzmayer); and incidental recall of naming task items (Viscoli).

^bNonverbal episodic memory tasks were visual retention / visual reproduction (Vanhull, Phillips, Polo-Kantola, Linzmayer, Dunkin, Joffe, Maki, Resnick); manual labyrinth learning (Vanhull); a composite visuospatial memory score (Joffe); spatial location (Viscoli); face recognition (Almeida); associate learning (Wolf); and a visuospatial memory test (Yaffe).

^cCognition was assessed with Guild Memory Test, with six subtests that included tasks of verbal episodic memory. Subtest results are not provided; differences are implied to be nonsignificant. For the composite score, group differences are reported as significant; reanalysis of published data indicates no significant differences.

^dFour treatment groups of 10 women each: estradiol, estradiol plus androgen, androgen, placebo.

^eHysterectomy; oophorectomy status not reported.

^gThree treatment groups of 16 to 17 women each.

^hEstradiol plus progestogen was superior to placebo on associate learning, but comparisons with placebo were not significant on three other verbal memory tasks; estradiol alone and placebo were not significantly different on any comparison.

^lThree treatment groups of 10 to 13 women.

^mStatistical significance defined in this study as P<0.01. No significant between-groups differences after three years. After treatment for 1.4 more years, placebo was better for verbal memory (total word-list recall score, P<0.01); nonsignificant trends (0.01<P<0.05) favored placebo on two other verbal memory scores (short and long free delayed word-list recall) and hormone on a nonverbal memory task (visual retention).