Randomized clinical trial: effect of low-dose flutamide on abdominal adipogenic function in normal-weight women with polycystic ovary syndrome

Abstract

To examine whether low-dose flutamide administration to normal-weight women with polycystic ovary syndrome (PCOS) reduces abdominal fat deposition, attenuates accelerated lipid accumulation in newly formed adipocytes derived from subcutaneous (SC) abdominal adipose stem cells (ASCs), and/or alters glucose-lipid metabolism. A double-blind, placebo-controlled randomized clinical trial. An academic medical center. Twelve normal-weight women with PCOS and 12 age- and body mass index-matched controls. Women underwent circulating hormonal and metabolic determinations, intravenous glucose tolerance testing, total body dual-energy roentgenogram absorptiometry, and SC abdominal fat biopsy. Interventions were repeated in women with PCOS after 6-month administration of flutamide (125 mg orally daily) vs. placebo. Clinical parameters and lipid accumulation in newly formed adipocytes derived from SC abdominal ASCs invitro were compared between controls and the women with PCOS receiving flutamide vs. placebo. Serum luteinizing hormone and androgen levels as well as lipid accumulation in newly formed SC abdominal adipocytes were greater in the women with PCOS than controls. Flutamide vs. placebo reduced percent android fat, lowered serum log low-density lipoprotein and log non-high-density lipoprotein levels, and increased fasting circulating glucose levels. In all women with PCOS, changes in percent android fat positively correlated with serum log non-high-density lipoprotein and log low-density lipoprotein levels, with correlations influenced by serum free testosterone levels. Flutamide vs. placebo also attenuated lipid accumulation in newly-formed PCOS SC abdominal adipocytes invitro relative to controls, which was unrelated to serum lipid levels. Low-dose flutamide administration to normal-weight PCOS women reduces preferential abdominal fat deposition, attenuates accelerated lipid accumulation in newly-formed adipocytes derived from SC abdominal ASCs invitro, and alters glucose-lipid homeostasis. NCT01889199 (URL, clinicaltrials.gov; date of registration, 6/28/2013; enrollment date of first subject, 6/28/2013).