[OR28-3] Lifestyle Modification Can Reverse Hypogonadism in Men with Impaired Glucose Tolerance in the Diabetes Prevention Program

Andrew A Dwyer, Lisa M Caronia, Hang Lee, David M Nathan, Frances J Hayes. Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Massachusetts General Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA; St Vincent's University Hospital, Dublin, Ireland.

Background: Testosterone (T) levels tend to be lower in men with obesity and type 2 diabetes than in age-and weight matched controls. We have previously shown that increasing insulin resistance is associated with a decrease in Leydig cell T secretion (1). However, limited interventional data have addressed causality.
Aim: To examine the impact of changes in body weight and insulin sensitivity on serum T levels in men.
Subjects: 891 men with impaired glucose tolerance (IGT) from the Diabetes Prevention Program (DPP), on no medications which interfere with T levels, who were randomized to lifestyle modification (n=293), metformin (n=305), or placebo (n=293).
Methods: Anthropometric variables (BMI, waist circumference), physical activity (MET hours/week), insulin sensitivity (homeostatic model assessment (HOMA-IR) and reproductive hormone levels (T, LH) were analyzed at baseline (BL) and 12 months.
Results: BL age was 53.9 ± 0.4 y (mean ± SEM) and BMI 31.9 ± 0.2 kg/m 2. Mean T levels were not significantly different among treatment groups at BL and in the group as a whole did not change (407 ± 5 vs 417 ± 5 ng/dL, BL vs 12 months). However, men randomized to lifestyle modification had a 15% increase in T levels (417 ± 8 vs 460 ± 7 ng/dL, P<0.0001) with no change in LH (3.1 ± 0.1 vs 3.1 ± 0.1 IU/L). T levels were unchanged in the other treatment groups. The overall prevalence of hypogonadal T levels (< 300 ng/dL) at BL was 23.7%; with lifestyle modification this decreased from 20.4 to 11.1% (P<0.05), but was unchanged with metformin (24.8 vs 23.8%) and placebo (25.6 vs 24.6%).
Reduction in body weight was greater with lifestyle modification than metformin (-7.8 vs -2.8 kg, P<0.0001) as was the decrease in HOMA-IR (7.0 ± 0.3 to 5.2 ± 0.2 with lifestyle modification vs 7.2 ± 0.2 to 6.0 ± 0.3 with metformin). Change in T levels correlated with changes in body weight (r=-0.32, P<0.0001), waist circumference (r=-0.13, P=0.001) and HOMA-IR (r= -0.13, P<0.0001). There was no relationship between change in T and physical activity.
Conclusions: (1) Almost 1 in 4 of this male DPP cohort with IGT has low T levels. (2) Lifestyle modification increases endogenous T levels and reduces the prevalence of hypogonadism by 46%. (3) The absence of an increase in LH suggests that enhanced Leydig cell responsiveness underlies the increase in T. (4) Reduction in body weight appears to play an important beneficial role in improving T levels in this population.

(1) Pitteloud N et al., J Clin Endocrinol Metab 2005;90:2636.

Sources of Research Support: Career Development Award, American Diabetes Association awarded to FJH.

Nothing to Disclose: AAD, LMC, HL, DMN, FJH

Date: Monday, June 25, 2012
Session Info: ORAL SESSION: Male Hypogonadism: Predisposition & Risks (11:15 AM-12:45 PM)
Presentation Time: 11:45 am
Room: Theater B

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