Rapid effects of novel phytoandrogen adjuvant therapy (PAT) on metabolic health: a gender, age and BMI matched case-control study

Abstract

Background and Aim: The human androgen receptor (AR) is a key nuclear transcription factor that controls expression of genes involved in anabolism - such as musculoskeletal remodelling and body fat mobilisation to ATP energy production – processes which directly impact aspects of metabolic health. This study evaluates the adjuvant effects of orally administered AR-modulating phytoandrogens and suprahormonal lipidic augmenters (SuHLAs) combined with an integrative weight-healthcare regimen of polyvalent pharmacotherapy (hypoglycemic, lipid modifying and anti-inflammatory) and mild lifestyle intervention, over intervals of 2-4 weeks. Method: The total intention-to-treat (ITT) population consisted solely of women (N = 15) and were screened at baseline for metabolic health status, assessed via arterial blood pressure (BP), body fat (BF), lean muscle mass (LMM), body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). This gender matched ITT population were then stratified into two treatment groups that were age and BMI matched: 1) patients opting for a metabolic health program (control group, n = 5, mean BMI = 26.6 kg/m2, mean age = 45 years), and 2) patients treated with a metabolic health program plus phytoandrogen adjuvant therapy (PAT group, n=10, mean BMI = 26.5 kg/m2, mean age = 44 years). Results: After treatments averaging 2.8 weeks (control group) and 2.9 weeks (PAT group), mean systolic and diastolic BPs in the total ITT population were lowered by 5 mmHg and 4 mmHg respectively, from 116/79 ±4 mmHg to 111/74 ±2 mmHg (P =0.05). Mean BF showed negligible loss of 0.2% (P >0.05) in the control group, in contrast to a highly significant reduction of 0.8% in the PAT group (P 0.1). Both treatment groups showed comparable improvement in BMI, WC and WHR. The control group had mean reductions of -0.25 kg/m2 (BMI, P <0.05), -2 cm (WC, P <0.05) and -0.03 (WHR, P<0.05), while the PAT group showed reductions of -0.35 kg/m2 (BMI, P =0.01), -3 cm (WC, P =0.01) and -0.03 (WHR, P =0.01). Measured against the top WHR bracket, odds ratios (ORs) for WHR-associated risk for diabetes, hypertension or dyslipidemia (WHR ≥0.9, OR 5.4) in the control and PAT groups were lower by 19% (WHR =0.88 ±0.02, OR 4.38) and 48% (WHR =0.83 ±0.01, OR 2.81) respectively. Conclusion: Oral phytoandrogenic SuHLAs therapy can rapidly potentiate aspects of AR-mediated anabolism within a low intensity metabolic health program. Secondarily, in contrast to physiological androgens and anabolic steroids, phytoandrogenic modulators of the AR in this study did not aggravate arterial tension. This is the first casecontrol report on the pharmacologic use of true phytoandrogens (cognate ligands of the AR) and SuHLAs to aid metabolic competency.