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Abstract
Context
Selective androgen receptor modulators (SARMs), because of their preferential muscle vs prostate selectivity, are being developed for muscle-wasting conditions. Oral SARMs suppress high-density lipoprotein cholesterol (HDL-C) but their effects on functional capacity and atherogenic potential of HDL particles are unknown.
Objective
To determine the effects of an oral SARM (OPK-88004) on cholesterol efflux capacity, HDL particle number and size, apolipoprotein particle number and size and HDL subspecies
Methods
We measured cholesterol efflux capacity (CEC); HDL particle number and size; APOB; APOA1; and protein-defined HDL subspecies associated with coronary heart disease (CHD) risk in men, who had undergone prostatectomy for low-grade prostate cancer during 12-week treatment with placebo or 1, 5, or 15 mg of an oral SARM (OPK-88004).
Results
SARM significantly suppressed HDL-C (P < .001) but HDL particle size did not change significantly. SARM had minimal effect on CEC of HDL particles (change + 0.016, –0.036, +0.070, and –0.048%/µmol-HDL/L–1 at 0, 1, 5, and 15 mg SARM, P = .045). SARM treatment suppressed APOAI (P < .001) but not APOB (P = .077), and reduced APOA1 in HDL subspecies associated with increased (subspecies containing α2-macroglobulin, complement C3, or plasminogen) as well as decreased (subspecies containing APOC1 or APOE) CHD risk; relative proportions of APOA1 in these HDL subspecies did not change. SARM increased hepatic triacylglycerol lipase (HTGL) (P < .001).
Conclusion
SARM treatment suppressed HDL-C but had minimal effect on its size or cholesterol efflux function. SARM reduced APOA1 in HDL subspecies associated with increased as well as decreased CHD risk. SARM-induced increase in HTGL could contribute to HDL-C suppression. These data do not support the simplistic notion that SARM-associated suppression of HDL-C is necessarily proatherogenic; randomized trials are needed to determine SARM’s effects on cardiovascular events.
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Details
1 Research Program in Men’s Health: Aging and Metabolism ; Claude D. Pepper Older Americans Independence Center, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts 02115 , USA
2 Department of Nutrition, Harvard TH Chan School of Public Health , Boston, Massachusetts 02115 , USA
3 Division of Metabolism, Endocrinology, and Nutrition, University of Washington , Seattle, Washington 98195 , USA
4 Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention, Department of Medicine, McGill University Health Centre , Montreal, Quebec QCH4A , Canada