Toremifene Improves Lipid Profiles in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer: Interim Analysis of a Multicenter Phase III Study

Abstract

Purpose-Androgen-deprivation therapy (ADT) is associated with greater risk of incident coronary heart disease and hospital admission for myocardial infarction; treatment-related increases in serum lipids may contribute to greater cardiovascular disease risk. We evaluated the effects of toremifene, a selective estrogen-receptor modulator, on fasting serum lipid levels in men receiving ADT for prostate cancer.Patients and Methods-In an ongoing, multicenter, double-blind, placebo-controlled phase III fracture-prevention study, 1,389 men receiving ADT for prostate cancer were randomly assigned to receive toremifene (80 mg/d) or placebo. In this interim analysis of 188 patients, changes in fasting serum lipids from baseline to month 12 were compared between the placebo and toremifene groups.Results-Changes in serum lipids differed significantly between the groups. Mean (± SE) total cholesterol decreased by 1.0% ± 1.7% from baseline to month 12 in the placebo group and decreased by 8.1% ± 1.4% in the toremifene group (P = .001 for between group comparison). AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTAlthough all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. Low-density lipoprotein (LDL) cholesterol increased by 0.8% ± 2.5% in the placebo group and decreased by 8.2% ± 2.5% in the toremifene group (P = .003). In contrast, high-density lipoprotein (HDL) cholesterol decreased by 4.9% ± 1.2% in the placebo group and increased by 0.5% ± 2.2% in the toremifene group (P = .018). Triglycerides increased by 6.9% ± 4.2% in the placebo group and decreased by 13.2% ± 3.6% in the toremifene group (P = .003).Conclusion-Toremifene significantly decreased total cholesterol, LDL cholesterol, and triglycerides, and increased HDL cholesterol in men receiving ADT for prostate cancer.

Prevalence of Diabetes Mellitus and Metabolic Syndrome in Prostate Cancer Patients given Androgen Deprivation Therapy

“…27,34,35 Serum HDL decreased by ~5% in 12 months in one study. 36 There was no change in serum LDL in 3-6 months of therapy. 34,35 However, there was one study which showed a rise in LDL of 7% in the first 3 months.…”

Changes in blood glucose and cholesterol levels due to androgen deprivation therapy in men with non-metastatic prostate cancer

“…12 Conversely, a large, recent study showed a decrease in HDL and an increase in low-density lipoprotein (LDL), triglycerides and total cholesterol with 12-month use of ADT. 13 Prior studies have generally featured small sample sizes, and have not consistently accounted for patient medication use, smoking history, body mass index (BMI) and previous diseases.…”

Androgen deprivation therapy and risk for diabetes and cardiovascular disease in prostate cancer survivors

“…Toremifene significantly improved serum lipid profiles in postmenopausal women [40][41][42][43]. In an interim analysis of a large, multicenter, randomized, controlled study of men receiving ADT for prostate cancer, toremifene significantly decreased total cholesterol, LDL cholesterol, and triglycerides, and increased HDL cholesterol [44]. The beneficial effects of toremifene on lipid profiles provide a strong rationale to conduct exploratory analyses of cardiovascular outcomes when the ongoing fracture prevention study is completed.…”