PD45-05 THE ROLE OF TESTOSTERONE SUPPLEMENTAL THERAPY IN OPIOID-INDUCED HYPOGONADISM: A COLLABORATIVE, PROSPECTIVE ANALYSIS

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control group, and comparisons of symptoms and hormone levels before and after commencement of CC and TST. The study is limited by its relatively small sample size and short follow-up (w 3.5 months). CONCLUSIONS: Testosterone supplementation and clomiphene citrate regimens are efficacious for improving both hypogonadal symptoms and serum total testosterone levels. Clearly, younger men appear to respond better following therapy for hypogonadism. Source of Funding: None

PD45-03 LONG-TERM TREATMENT WITH TESTOSTERONE UNDECANOATE INJECTIONS SUSTAINABLY IMPROVES ERECTILE FUNCTION AND METABOLIC CONTROL IN HYPOGONADAL MEN WITH TYPE 2 DIABETES MELLITUS (T2DM) Ahmad Haider*, Karim Sultan Haider, Bremerhaven, Germany; Gheorghe Doros, Abdulmaged Traish, Boston, MA INTRODUCTION AND OBJECTIVES: Erectile dysfunction in men with T2DM remains difficult to treat. We assessed effects of longterm treatment with testosterone undecanoate (TU) injections in hypogonadal with T2DM. METHODS: Cumulative, prospective, single-center, observational registry study of 340 hypogonadal men. 120 men (35.3%) had T2DM. All men received testosterone undecanoate injections for up to 7 years. All men were treated for their T2DM by their respective family physician. RESULTS: Mean age was 60.36
5.02 years. 4/120 men (3%) had normal weight, 9 (8%) were overweight, and 107 (89%) were obese. Testosterone levels rose from 10.0
1.28 nmol/L to trough levels (measured prior to the following injection) between 15 and 18 nmol/L. Weight decreased progressively from 110.37
14.28 to 89.38
9.33 by 21.36
0.73 kg. The proportion of weight loss was -18.24% in the obese, -13.64% in the overweight, and the men with normal weight gained 2.82%. Waist circumference decreased from 109.34
7.97 to 99.89
6.48 by 11.34 cm, BMI (kg/m2) from 35.57
4.5 to 29.09
2.91 (p<0.0001 for all). IIEF-EF increased steadily from 19.79
4.85 to 23.11
3.82 after 1 year and 25.2
3.75 after 7 years. Fasting glucose decreased from 113.45
14.53 to 95.93
2.56 mg/ dl, HbA1c from 8.02
0.86 to 5.9
0.45% (p<0.0001 for both). At baseline, 11% of patients were within HbA1c target of 7%, at the end of the observation time all patients completing 7 years of treatment had HbA1c 7%. At baseline, 4% of patients were within an HbA1c target of 6.5%, at the end of the observation time all but one patients completing 7 years of treatment had HbA1c 6.5%. Lipid pattern improved. The TC:HDL ratio declined from 4.9
1.18 to 2.52
0.56, the TG:HDL ratio from 4.84
1.34 to 2.49
0.54 (p<0.0001 for all). Systolic BP decreased from 160.48
13.89 to 137.41
7.37, diastolic BP from 96.03
10.65 to 77.17
5.98 mmHg (p<0.0001 for both). CONCLUSIONS: All changes were clinically meaningful and sustained for the full observation period, despite the fact that patient’s age increased by 7 years. T therapy seems to be highly effective in hypogonadal men with T2DM, improving both erectile function and metabolic parameters. Source of Funding: Bayer Pharma AG partially funded data entry and statistical analyses.

PD45-04 INCIDENCE OF PROSTATE CANCER AND EFFECTS ON PROSTATE-RELATED PARAMETERS UNDER LONG-TERM THERAPY WITH TESTOSTERONE UNDECANOATE INJECTIONS (TU) IN HYPOGONADAL MEN FOR UP TO 84 MONTHS: REAL-LIFE EXPERIENCE FROM AN OBSERVATIONAL REGISTRY STUDY Ahmad Haider*, Karim Sultan Haider, Bremerhaven, Germany; Gheorghe Doros, Abdulmaged Traish, Boston, MA INTRODUCTION AND OBJECTIVES: There are still concerns regarding prostate safety of testosterone replacement therapy (TRT). We

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investigated how long-term TRT with TU affected prostate-related parameters. METHODS: Prospective, longitudinal, registry study of 347 patients (mean age 57.32
7.12 years, min.: 32, max.: 69), with testosterone (T) levels  350 ng/dL (12.1 nmol/L) received TU 1000 mg injections at baseline, after 6 weeks and then every 12 weeks for up to 84 months (7 years). Prostate volume and residual voiding volume were measured by ultrasound at every or every other visit. IPSS was filled in at every visit and blood samples taken to measure PSA. Because prostatic diseases are closely associated with obesity, we also assessed anthropometric parameters and C-reactive protein (CRP). RESULTS: Registry participants contributed 1,806 personyears (21,678 person-months). Total T increased from 9.84
1.28 nmol/L to trough levels of approximately 16 to 17 nmol/L for the total observation period. Prostate volume increased from 28.98
10.4 to 30.87
12.06 ml (p<0.0001 vs baseline) by 2.46 ml. PSA increased from 1.73
0.94 to 1.79
0.93 ng/ml (p¼0.0151 vs baseline). 6/347 patients were diagnosed with prostate cancer following elevated PSA (> 4 ng/mL). Tumour stage was pT2a in four and pT1b in two men, Gleason score 3þ3 in five and 3þ2 in one patient, resp. They all underwent radical prostatectomy. The proportion was 1.7% with an incidence of 27.7 per 10,000 patient-years. The International Prostate Symptom Score (IPSS) decreased from 6.35
4.05 to 2.21
1.04 (p<0.0001) by 4.92 score points. The residual voiding volume decreased progressively from 46.82
22.71 to 15.22
5.4 ml (p<0.0001). Within the observation time, BMI dropped progressively from 33.18
5.35 kg/m2 to 28.42
2.95 kg/m2, with waist circumference declining from 105.77
8.6 cm to 97.74
7.05 cm. CRP decreased from 5.42
7.12 to 0.51
0.92 mg/dl (p<0.0001). The high baseline level of CRP results from the fact that 75 patients had inflammatory bowel diseases and/or psoriasis. CONCLUSIONS: The incidence of prostate cancer did not suggest an increased risk of prostate cancer in hypogonadal men on long-term TRT. Long-term treatment with TU did not negatively affect voiding function as measured by IPSS, or residual voiding volume. Part of these effects may be a result of parallel reduction in body weight and abdominal fat, as well as inflammation. Source of Funding: Bayer Pharma AG partially funded data entry and statistical analyses.

PD45-05 THE ROLE OF TESTOSTERONE SUPPLEMENTAL THERAPY IN OPIOID-INDUCED HYPOGONADISM: A COLLABORATIVE, PROSPECTIVE ANALYSIS Omer Raheem*, Joe Acevedo, David Sisul, T. Mike Hsieh, San Diego, CA INTRODUCTION AND OBJECTIVES: Chronic pain therapy is known to induce several endocrine changes and alter nociception. Available literature has shown limited data detailing the therapeutic strategies able to maintain testosterone level into eugonadal ranges and reduce nociception. The objective of this study is to identify the effect of testosterone supplemental therapy (TST) in men with chronic pain undergoing opiate therapy. We hypothesize that treatment of opiate-induced hypogonadism can reduce opiate requirement in men suffering from chronic pain. METHODS: Men with chronic pain recruited from a tertiary referrral pain center. Signs and symptoms of hypogonadism were assessed using the Androgen Deficiency in Ageing Males and International Index of Erectile Function questionnaires. Patient pain type, level of pain control based on the Visual Analog Scale (VAS) and morphine equivalent dose (MED) were recorded. Patients were screened for hypogonadism with luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), total testosterone (TT) and human binding globulin (HBG). Men with symptomatic hypogonadism (TT <300 ng/dL) offered TST. RESULTS: Twenty-seven men enrolled with mean follow-up of 6 months. Men screened were found to be androgen deficient on biochemical screening (TT<300 ng/dL). TST group consists of 11 patients while non-

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TST group consists of 16 patients. Mean patient age (55 and 54.4, p¼0.4) and BMI (28.5 and 31.9, p¼0.4) in TST and non-TST groups respectively. The most common etiology of pain was lumbar pain in the TST and non-TST groups (36% and 81% respectively). The methods of TST administration were 6 topical (55%), 3 implantable (27%) and 2 injectable (18%). Median VAS was 0 and 2 in the TST and non-TST groups (p¼0.02). TT was significantly higher after TST compared with the non-TST group (494 vs 242 ng/dL, p¼0.03). A total of 18% of men on TRT, have had a decrease in their MED (46.8 vs 71.5 in the TST and non-TST groups). CONCLUSIONS: This is the first report that TST may benefit men on chronic opioid therapy by reducing MED. It validates previous report on the prevalence of opiate-induced hypogonadism, TST’s effectiveness in correcting endocrine abnormalities and improves nociception in men during chronic pain therapy Table 1 Patients’ demographics and clinical data TST group (n¼11)

Non-TST group (n¼16)

P Value

55

54.4

0.4

Caucasian

10

14

Others

1

2

28.5

31.9

Variables Age, mean Ethnicity

Basic Metabolic Index (BMI), mean Location of pain Cervical spine

36%

6%

Lumbar spine

36%

81%

Groin

28%

13%

Visual Analog scale (VAS), Median (IQR)

0 (0-1)

2 (1-2)

Luteinizing hormone (LH) mIU/mL, mean

3.73*

4.31

0.7

Follicle-stimulating hormone (FSH) mIU/ mL, mean

4.23*

9.13

0.07

Estradiol (E2) mIU/mL, mean

25.1*

19.1

0.2

49*

52

0.1

Human Binding Globulin (HBG) mIU/mL Total Testosterone (TT) mIU/mL, mean

0.02

497.5*

242.4

0.03

Morphine Equivalent Dose (MED)

46.8

71.5

0.5

Duration of TRT months, mean

4.5

NA

TST: testosterone supplemental therapy; NA: not applicable; *indicates lab values post TST.

Source of Funding: The study was supported by a resident research grant from SMSNA.

PD45-06 LONG-TERM EFFECTS ON ERECTILE FUNCTION UPON TREATMENT UP TO 11 YEARS WITH TESTOSTERONE UNDECANOATE INJECTIONS (TU) IN HYPOGONADAL MEN WITH TYPE 2 DIABETES MELLITUS (T2DM): REAL-LIFE DATA FROM AN OBSERVATIONAL REGISTRY STUDY Aksam Yassin*, Yousef Al Mehmadi, Norderstedt-Hamburg, Germany INTRODUCTION AND OBJECTIVES: In men with T2DM, erectile dysfunction (ED) is difficult to treat. We investigated effects of long-term treatment with testosterone undecanoate (TU) injections in 77 hypogonadal with T2DM. METHODS: Cumulative, prospective, registry study of 262 hypogonadal men. 77 men (29.4%) had T2DM. All patients had presented with ED and were found hypogonadal (total Testosterone (T)  12 nmol/L (350 ng/dl). All men received TU for up to 11 years. T2DM had been diagnosed and was being treated by their respective family physicians. Results at the end of 8 years follow-up are reported. RESULTS: 9 of 77 men (12%) were overweight, and 68 (88%) were obese. Total T increased from 7.6 nmol/L to trough levels (measured prior to the following injection) between 17 and 20 nmol/L, free T from 150 to 400-500 pmol/L. Mean BMI decreased progressively from 34.66 to 27.78 kg/m2. Weight reduction was -18.24%. Waist circumference decreased from 115.03 to 96.47 cm (p<0.0001 for all). IIEF-EF increased steadily from 6.14 at baseline to 11.49 after 1 year, 14.46 after 2 years, 16.22 after 3 years, 16.73 after 4 years, and then remained stable at 17.05 after 5 years, 17.76 after 6 years, 17.35 after 7 years and 18.22 after 8 years.

Fasting glucose decreased from 146.26 to 83.72 mg/dl, HbA1c from 7.87 to 5.99% (p<0.0001 for both). C-reactive protein decreased from 1.63 to 0.74 mg/dl (p<0.0001) indicating a reduction in inflammatory activity. CONCLUSIONS: Despite the presence of T2DM and despite the aging process, long-term T therapy improved ED in hypogonadal men. All changes were clinically meaningful and sustained for the full observation period. Besides the direct effects of T on erectile tissue anatomy and physiology, weight loss and reduction of inflammation may have further contributed to the observed improvements. Source of Funding: none

PD45-07 A COMPARISON OF ESTRADIOL LEVELS AND GYNECOMASTIA RATES IN HYPOGONADAL MEN USING CLOMIPHENE CITRATE VERSUS TRANSDERMAL TESTOSTERONE Clarisse R. Mazzola*, Edoardo Miranda, Joseph Narus, John P. Mulhall, New York City, NY INTRODUCTION AND OBJECTIVES: Clomiphene citrate (CC) is recognized as a management strategy in men with hypogonadism (HG). Some concern exists regarding its ability to raise serum estradiol (E2) levels given its mechanism of action. Serum total testosterone (TT) may be converted to E2 by aromatase irrespective of which T replacement therapy (TRT) modality is used. This analysis was undertaken to compare serum E2 levels in men with HG using CC versus transdermal T (TDT). METHODS: Study population consisted of men with (i) HG (two early morning serum TT levels <300ng/dl) (ii) who were on either CC or TDT (iii) normal baseline E2 levels (iv) therapy for 6 months and (v) follow-up T and E2 levels. CC was commenced at 25 mg every other day and titrated up to 50mg daily to maintain men in the 500-600 ng/dl TT range. Likewise, TDT was titrated to achieve the same effect. All men were examined every 6 months for gynecomastia. RESULTS: 164 men on TDT, mean age ¼ 58
12 years and 142 men on CC, mean age ¼ 44
24 years were studied. Mean duration of treatment: CC 16 months; TDT 22 months. Significant improvements in mean TT levels were seen for both groups during treatment: CC 261 to 498 ng/dl (p<0.05), TDT 246 to 574 ng/dl (p<0.05); no significant difference between CC and TDT for baseline or treatment TT levels. Significant differences existed for LH levels in both groups during treatment: CC 2.4 to 7.8 (p<0.01); TDT 6.2 to 1.4 (p<0.01); significant difference between CC and TDT LH levels at baseline (p<0.01) and on treatment (p<0.01). Baseline E2 levels were similar for both groups (CC 19, TDT 22, p¼NS), however, end of treatment E2 levels were significantly increased in both groups (p<0.05) and in particular were significantly different in each group: CC 44pg/ml; TDT 31 pg/ml (p<0.05). Gynecomastia rates were: CC 4/142 (2.8%), TDT 6/164 (3.6%), p¼NS. CONCLUSIONS: While CC increased E2 levels to a significantly greater extent than TDT, the difference is likely not clinically meaningful. Gynecomastia rates were similar between both groups. Source of Funding: None

PD45-08 COMPARISON OF CLOMIPHENE CITRATE AND TRANSDERMAL TESTOSTERONE REPLACEMENT THERAPY IN THEIR INFLUENCE ON HORMONAL AND METABOLIC CHANGES IN THE TREATMENT OF HYPOGONADISM Daniel Lee, Long Island City, NY; Adrien Bernstein*, Alex Sarkisian, Matthew Wosnitzer, Ashley Winter, Darius Paduch, New York, NY INTRODUCTION AND OBJECTIVES: Recent studies have highlighted the possible modulation of cardiovascular risk factors by testosterone replacement therapy (TRT). Increased estradiol levels are known to potentially improve BMI and cholesterol levels and may improve glycemic control. We sought to compare serum cholesterol levels, BMI, and fasting glucose levels in men receiving clomiphene citrate (CC) or TRT for hypogonadism.