estrone-sulfate and Alzheimer-Disease

To examine whether estrogen replacement therapy (ERT) affects clinical and cognitive responses to tacrine in women with Alzheimer's disease (AD).. A 30-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial of tacrine in which a subgroup of women were receiving ERT prior to randomization.. Women with mild to moderate-stage AD, at least 50 years of age, who were enrolled in the previously reported trial.. Randomized assignment to placebo or to one of three ascending-dosage regimens of tacrine: maximum dosages of 80 mg/d, 120 mg/d or 160 mg/d.. Alzheimer's Disease Assessment Scale-Cognitive Scale (ADASc), Clinician Interview-Based Impression of change (CIBI), Mini-Mental State Examination (MMSE), Caregiver's Impression of Change (CIC).. Of 318 women with evaluable data 14.5% were receiving ERT. Women completing the trial taking ERT and tacrine improved more than women not receiving ERT who were randomly assigned to tacrine or to placebo as assessed by the ADASc (p < 0.01), the CIBI (p = 0.02), the CIC (p = 0.006), and the MMSE (p = 0.07). They improved significantly on the ADASc (p = 0.01) using an intent-to-treat analysis.. Prior and continuing ERT may enhance response to tacrine in women with AD. Randomized trials are needed.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Cognition; Combined Modality Therapy; Double-Blind Method; Drug Administration Schedule; Estradiol; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Estrone; Female; Humans; Middle Aged; Nootropic Agents; Tacrine; Treatment Outcome

Seven women with senile dementia-Alzheimer's type (SDAT) were treated with conjugated estrogen [main content: estrone sulfate (E1-S)], at a dose of 1.25 mg/day over a 6-week period. A New Screening Test for Dementia developed by Japanese National Institute of Mental Health (NS) and the scores of Hasegawa Scale for dementia (HS) were performed every 3 weeks. Six women showed improvements in NS (P less than 0.05) and 5 women showed improvements in HS. Untreated women with SDAT did not show any improvement. Serum E1-S was measured by a direct radioimmunoassay. Serum E1-S was 911 +/- 156 pg/ml in 7 women with SDAT and lower than that of 7 normal women (1020 +/- 216 pg/ml). Following the treatment, serum E1-S increased to a level of 21.1 +/- 8.1 ng/ml. Estrone and estradiol-17 beta also increased. The results suggest a possibility for the future clinical use of estrogen for senile dementia, after careful clinical research trials including the side effects.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Estrogens, Conjugated (USP); Estrone; Female; Humans; Male; Reference Values

Estrone sulfate (E1-S) has been shown to be quantitatively the most important estrogen in peripheral blood. But, the physiological and/or pathological role of E1-S is not yet clarified. At present, we tried to clarify it using tissue cultures. In tissue cultures of human endometrium, secretory endometrium showed higher activity of estrone sulfatase (E1----E1-S) than proliferative endometrium. Progesterone added in the medium induced an increase of estrone sulfotransferase in the proliferative endometrium. The results suggest a reducing effect of estrogen by progesterone in secretory endometrium in physiological conditions. Estrogen dependent malignant tumors (breast cancer, endometrial cancer) have high estrone sulfatase. It converts E1-S to E1 (----E2) which are abundant in these tumors. Ishikawa cell line increased estrone sulfotransferase activity with progesterone, somewhat like the physiological conditions. From out study in vivo, there is a possibility of some ameliorative effects of E1-S on the central nervous system of patients with senile dementia (Alzheimer's type). Effects of E1-S on central nerves were investigated using tissue cultures.

Topics: Alzheimer Disease; Breast Neoplasms; Culture Techniques; Endometrial Neoplasms; Endometrium; Estradiol Dehydrogenases; Estrone; Female; Humans; Progesterone; Sulfatases; Sulfotransferases; Sulfurtransferases