Biologic Effects of Delta-8-Estrone Sulfate in Postmenopausal Women

Abstract

Objective: To determine in postmenopausal women the biological effects of delta-8-estrone sulfate, a novel estrogen component of Premarin (Wyeth-Ayerst, Philadelphia, PA).

Methods: An open-label, nonrandomized study of six healthy postmenopausal women was conducted. Each subject took 0.125 mg of delta-8-estrone sulfate daily for 8 weeks. Blood samples were collected at day 0 (baseline) and once a week for 8 weeks. Urine was collected on day 0 and at weeks 2, 3, 5, 6, 7, and 8. Serum gondotropins (follicle-stimulating hormone/luteinizing hormone), plasma binding proteins (corticosteroid-binding globulin/sex hormone-binding globulin), a marker for bone turnover (urinary n-telopeptide), and markers for cardiovascular effects (cholesterol, low-density lipoprotein_c, high-density lipoprotein_c, low-density lipoprotein oxidation, and rate of diene formation) were measured.

Results: Follicle-stimulating hormone levels decreased from 84.0 ± 8.5 to 67.0 ± 8.5 mlU/mL (P = .02), whereas luteinizing hormone levels did not change. Corticosteroid-binding globulin levels increased from 3.30 ± 0.16 to 4.10 ± 0.16 mg/dL (P = .02), and no change in sex hormone-binding globulin was noted. The n-telopeptide levels decreased an average of 31% from 40.7 ± 4.9 to 28 ± 7.0 nmol/L bone collagen equivalents/mmol/L creatinine (P = .03). Plasma diene concentration and diene production rate decreased by 34% and 40%, respectively; these changes were not significantly different from baseline values. In contrast, a significant (P = .03) 68% increase in the lag time for low-density lipoprotein_c oxidation (38.5 ± 5.5 minutes versus 64.8 ± 8.5 minutes) was observed. No significant change occurred in total cholesterol, high-density lipoprotein_c, and low-density lipoprotein_c.

Conclusion: Small doses (0.125 mg) of delta-8—estrone sulfate have profound estrogenic effects in postmenopausal women. The changes observed in n-telopeptide levels and the lag-time delay in oxidation of low-density lipoprotein_c indicate that this estrogen contributes toward the overall beneficial effects on bone and cardiovascular system associated with Premarin therapy.

Keywords

Delta-8—estrone sulfate oxidized low-density lipoprotein oxidation lag time n-telopeptide

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