5g gel, applied once daily to the upper arms, upper back or shoulders.

The SF-36 measures 8 domains of the QoL: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. Each domain is scored separately from 0 to 100 with higher scores representing better health-related QoL.

PCS questionnaire measures self-assessment of pain catastrophizing. This questionnaire consists of 13 items on past painful experiences and rate on 5-point scales ranging from 0 (not at all) to 4 (all the time). The PCS yields three subscale scores assessing rumination (range 0-16), magnification (range 0-12), helplessness (range 0-24), and a composite score (sum of three domains, ranging 0-52). Higher score represents worse painful experiences.

Sex hormone binding globulin was measured using immunofluorometric assays, with limits of quantification of 2.5 nmol/L.

Luteinizing hormone was measured using immunofluorometric assays, with limits of quantification of 0.05 U/L.

The pathophysiology of pain is measured by the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-Alpha).

Body composition was measured using dual-energy X-ray absorptiometry scan.

Serum total cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol levels were measured by enzymatic assays and standardized to the CDC using the Lipid Research Clinic protocol. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation.

All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The plasma glucose level were analyzed at baseline and at 60 and 120 min after glucose loading.

All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The insulin level were analyzed at baseline and at 60 and 120 min after glucose loading.

Insulin resistance was calculated using the homeostatic model assessment (HOMA) index: glucose * insulin / 22.5.

Total adiponectin was measured using an RIA kit with an interassay CV of 6.9-9.3% and an intra-assay CV of 1.8-6.2% (Millipore).

Leptin levels were measured using ELISA with an interassay CV of 2.6% to 6.2% and in intra-assay CV of 2.6% to 4.6% (Millipore, Billerica, MA, USA).

High-sensitivity C-reactive protein (Alpco Diagnostics) was measured using a high-sensitivity sandwich ELISA with an intra-assay CV of 5.6%

ISI is comprised of 7 items assesses a participant's perception of insomnia. Each item is rated on a 5-point scale from 0 (none) to 4 (very severe). Scores from the questions are summed to assign a total score ranging from 0 to 28, where higher score represents worse insomnia problem.

Total of all reporting groups

The Brief Pain Inventory (BPI) is a self-administered questionnaire that measuring chronic pain. The BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score assesses the severity of pain on a continuous scale from 0 (no pain) to 10 (severe pain). The pain interference score corresponds to the item on pain interference, ranging from 0 (does not interfere) to 10(completely interferes). The total score (ranging from 0-20) is the sum of the pain severity score and pain interference score. Higher scores represents severer and more interfering pain.

A digital pressure algometer at the trapezius muscle and the metacarpophalangeal joint of the thumb was used to measure pressure pain thresholds. Higher values represent a better tolerance of pressure pain.

Weighted pinprick stimulators are used to assess mechanical pain. Lower values represent better tolerance of pain.

Cold-pressor tests measure cold-induced pain and its sensation. Time was measured when a participant reached pain tolerance in cold water and after sensation. Higher values of time in Cold pain tolerance and lower values of time in Cold pain after-sensation (30 seconds) represent better tolerance of pain.

IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (range 1-30), orgasmic function (range 0-10), sexual desire (range 2-10), intercourse satisfaction (range 0-15), and overall sexual satisfaction (range 2-10). Each question was answered on a 6-point or 5-point scale from 0/1 to 5 (best) with a total possible score (sum of 5 domains) range of 5 to 75 with higher scores representing better function.

The SF-36 measures 8 domains of the QoL: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. Each domain is scored separately from 0 to 100 with higher scores representing better health-related QoL.

Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin. HOMA IR was calculated using the formula: glucose * insulin / 22.5

Of the completers, 64 men (36 in the testosterone arm and 28 in the placebo arm) had pre and post-intervention data on Adiponectin outcomes.

Of the completers, 64 men (36 in the testosterone arm and 28 in the placebo arm) had pre and post-intervention data on Leptin outcomes.

Of the completers, 64 men (36 in the testosterone arm and 28 in the placebo arm) had pre and post-intervention data on C-reactive protein outcomes.

PCS questionnaire measures self-assessment of pain catastrophizing. This questionnaire consists of 13 items on past painful experiences and rate on 5-point scales ranging from 0 (not at all) to 4 (all the time). The PCS yields three subscale scores assessing rumination (range 0-16), magnification (range 0-12), helplessness (range 0-24), and a composite score (sum of three domains, ranging 0-52). Higher score represents worse painful experiences.

Of the completers, 62 men (33 in the testosterone arm and 29 in the placebo arm) had pre and post-intervention data on PCS outcomes.

ISI is comprised of 7 items assesses a participant's perception of insomnia that specifically address the symptoms and consequences of insomnia, as well as the degree of distress caused by sleep quality. Each item is rated on a 5-point scale from 0 (none) to 4 (very severe). Scores from the questions are summed to assign a total score ranging from 0 to 28, where higher score represents worse insomnia problem.

Of the completers, 62 men (33 in the testosterone arm and 29 in the placebo arm) had pre and post-intervention data on ISI outcomes.

Placebo gel

Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.

A digital pressure algometer at the trapezius muscle and the metacarpophalangeal joint of the thumb was used to measure pressure pain thresholds. Higher values represent a better tolerance of pressure pain.

Weighted pinprick stimulators are used to assess mechanical pain. Lower values represent better tolerance of pain.

Cold-pressor tests measure cold-induced pain and its sensation. Time was measured when a participant reached pain tolerance in cold water and after sensation. Higher values of time in Cold pain tolerance and lower values of time in Cold pain after-sensation (30 seconds) represent better tolerance of pain.

IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (range 1-30), orgasmic function (range 0-10), sexual desire (range 2-10), intercourse satisfaction (range 0-15), and overall sexual satisfaction (range 2-10). Each question was answered on a 6-point or 5-point scale from 0/1 to 5 (best) with a total possible score (sum of 5 domains) range of 5 to 75 with higher scores representing better function.

All available data expressed as absolute values at week 14.

The SF-36 measures 8 domains of the QoL: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. Each domain is scored separately from 0 to 100 with higher scores representing better health-related QoL.

All available data expressed as absolute values at week 14.

PCS questionnaire measures self-assessment of pain catastrophizing. This questionnaire consists of 13 items on past painful experiences and rate on 5-point scales ranging from 0 (not at all) to 4 (all the time). The PCS yields three subscale scores assessing rumination (range 0-16), magnification (range 0-12), helplessness (range 0-24), and a composite score (sum of three domains, ranging 0-52). Higher score represents worse painful experiences.

All available data expressed as absolute values at week 14.

Total testosterone was measured in a CDC-certified laboratory using an LC-MS/MS method with a sensitivity of 2 ng/dL.

All available data expressed as absolute values at week 14.

Free testosterone was calculated using a law of mass action equation.

All available data expressed as absolute values at week 14.

Sex hormone binding globulin was measured using immunofluorometric assays, with limits of quantification of 2.5 nmol/L.

All available data expressed as absolute values at week 14.

Luteinizing hormone was measured using immunofluorometric assays, with limits of quantification of 0.05 U/L.

All available data expressed as absolute values at week 14.

The pathophysiology of pain is measured by the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-Alpha).

All available data expressed as absolute values at week 14.

Body composition was measured using dual-energy X-ray absorptiometry scan.

All available data expressed as absolute values at week 14.

Serum total cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol levels were measured by enzymatic assays and standardized to the CDC using the Lipid Research Clinic protocol. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation.

All available data expressed as absolute values at week 14.

All available data expressed as absolute values at week 14.

All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The plasma glucose level were analyzed at baseline and at 60 and 120 min after glucose loading.

All available data expressed as absolute values at week 14.

All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The insulin level were analyzed at baseline and at 60 and 120 min after glucose loading.

All available data expressed as absolute values at week 14.