William Conners

Can testosterone therapy be offered to men on active surveillance for prostate cancer? Preliminary results

This report presents our experience with T therapy in a cohort of T-deficient men on active surveillance (AS) for Gleason 3 + 3 and Gleason 3 + 4 prostate cancer (PCa). A retrospective chart review identified 28 men with T deficiency who underwent T therapy (T group) for at least 6 months while on AS for PCa. A comparison group of 96 men on AS for PCa with untreated T deficiency (no-T group) was identified at the same institution. The AS protocol followed a modified Epstein criteria and allowed inclusion of men with a single core of low-volume Gleason 3 + 4 PCa. Mean age was 59.5 and 61.3 years, and mean follow-up was 38.9 and 42.4 months for the T and no-T groups, respectively. Of all 28 men in the T group, 3 (10.7%) men developed an increase in Gleason score while on AS. Of 22 men in the T group with Gleason 3 + 3 disease, 7 (31.8%) men developed biopsy progression including 3 men (13.6%) who developed Gleason 3 + 4 PCa. Of 6 men with Gleason 3 + 4 disease at baseline, 2 (33.3%) men developed an increase in tumor volume, and none developed upgrading beyond Gleason 3 + 4. All 96 men in the no-T group had Gleason 3 + 3 disease at baseline and, 43 (44.7%) developed biopsy progression, including 9 men (9.38%) with upgrading to Gleason 7 (3 + 4). Biopsy progression rates were similar for both groups and historical controls. Biopsy progression in men on AS appears unaffected by T therapy over 3 years. Prospective placebo-controlled trials of T therapy in T-deficient men on AS should be considered given the symptomatic benefits experienced by treated men.

Bone mineral density and response to treatment in men younger than 50 years with testosterone deficiency and sexual dysfunction or infertility.

PURPOSE Testosterone deficiency is a known risk factor for osteopenia and osteoporosis in older men. Less is known about the impact of testosterone deficiency on bone mineral density in younger men. MATERIALS AND METHODS We retrospectively reviewed the charts at an andrology/infertility clinic and identified 399 men younger than 50 years who underwent baseline dual energy x-ray absorptiometry and had total testosterone less than 350 ng/dl or free testosterone less than 1.5 ng/dl. Additional analysis was done in a subgroup of 75 men (18.8%) in whom dual energy x-ray absorptiometry was repeated after treatment at a mean ± SD of 30.4 ± 16.2 months. The determination of osteoporosis or osteopenia was based on T-scores (osteopenia less than -1.0 and osteoporosis less than -2.5) of the lumbar spine and left hip. RESULTS Of all 399 men 141 (35.3%) had bone mineral density consistent with osteopenia at the lumbar spine (137) and/or the total hip (19). In 11 men (2.75%) bone mineral density was consistent with osteoporosis at the lumbar spine. On multivariate analysis higher body mass index was independently associated with increased bone mineral density at the spine (p <0.0001) as well as the hip (p <0.001). Testosterone treatment in 43 men increased spine bone mineral density (p <0.001). Significant decreases in spine bone mineral density developed in 21 men treated with clomiphene citrate or anastrazole (p = 0.003). No significant change was noted in hip bone mineral density for any treatment. CONCLUSIONS More than a third of men younger than 50 years with testosterone deficiency and infertility or sexual dysfunction had decreased bone mineral density. Testosterone treatment increased bone mineral density while estrogen modulators such as clomiphene citrate or aromatase inhibitors decreased bone mineral density. These results suggest that dual energy x-ray absorptiometry may be warranted in young men with testosterone deficiency.

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer

PURPOSE Limited literature exists regarding the safety of testosterone therapy in men treated for prostate cancer. We present multi-institutional data on testosterone therapy in hypogonadal men with prostate cancer treated with radiation therapy. MATERIALS AND METHODS We retrospectively reviewed the records of hypogonadal men treated with testosterone therapy after radiation therapy for prostate cancer at 4 institutions. Serum testosterone, free testosterone, estradiol, sex hormone-binding globulin, prostate specific antigen, prostate specific antigen velocity and prostate biopsy findings were analyzed. RESULTS A total of 98 men were treated with radiation therapy. Median age was 70.0 years (range 63.0 to 74.3) at initiation of testosterone therapy. Median baseline testosterone was 209 ng/dl (range 152 to 263) and median baseline prostate specific antigen was 0.08 ng/ml (range 0.00 to 0.33). In the cohort the tumor Gleason score was 5 in 3 men (3.1%), 6 in 44 (44.9%), 7 in 28 (28.6%), 8 in 7 (7.1%) and 9 in 4 (4.1%). Median followup was 40.8 months (range 1.5 to 147). Serum testosterone increased to a median of 420 ng/dl (range 231 to 711) during followup (p <0.001). Overall a nonsignificant increase in mean prostate specific antigen was observed from 0.08 ng/ml at baseline to 0.09 ng/ml (p = 0.05). Among patients at high risk prostate specific antigen increased from 0.10 to 0.36 ng/ml (p = 0.018). Six men (6.1%) met criteria for biochemical recurrence. CONCLUSIONS Testosterone therapy in men following radiation therapy for prostate cancer was associated with a minor increase in serum prostate specific antigen and a low rate of biochemical recurrence.

Influence of baseline serum testosterone on changes in body composition in response to testosterone therapy.

INTRODUCTION The prognostic value of serum total testosterone (TT) prior to treatment has not been investigated. AIM This study was performed to determine how baseline TT influences changes in body composition in men undergoing testosterone therapy (TTh). MAIN OUTCOME MEASURES Response to TTh in a clinical population of men with symptomatic testosterone deficiency (TD). METHODS Retrospective case series of 58 men with TD were treated with TTh. All were naïve to previous TTh. Men were stratified into two groups: group 1 (N = 38) consisted of men with baseline TT > 300 ng/dL (10.4 nmol/L) and group 2 (N = 20) consisted of men with total TT < 300 ng/dL. Men in group 1 were diagnosed with TD on the basis of low values of free testosterone (FT) < 1.5 ng/dL (19.3 pmol/L). Dual-energy X-ray absorptiometry was performed at baseline and follow-up (6.9 ± 4 months) to assess regional and whole body. RESULTS At baseline, both groups had similar lean mass (LM) and fat mass (FM), but percentage of trunk FM and percentage of total FM were significantly higher in group 2. Both groups demonstrated similar increases in LM for arms, legs, and total body. Percentage of total FM significantly decreased in both groups. CONCLUSIONS Baseline severity of symptomatic TD influences body composition. Similar changes in LM and FM were seen with TTh regardless of baseline severity in TD. Men with TT > 300 ng/dL demonstrated significant positive changes in body composition. The similarity in objective response to TTh in these two groups provides support for the value of FT in the assessment of men with symptoms suggestive of TD.

The Evaluation and Management of Testosterone Deficiency: the New Frontier in Urology and Men’s Health

Testosterone deficiency (TD) is a common clinical condition that causes sexual and non-sexual symptoms. Low serum concentrations of testosterone also predict significant health outcomes, such as diabetes, metabolic syndrome, and increased mortality. Treatment with testosterone therapy (TTh) effectively improves symptoms, and also has a positive impact on body composition and bone density. Since there is no serum testosterone value that reliably identifies men who will respond to treatment from those who will not, healthcare providers must exercise clinical judgment in making the diagnosis of TD. Multiple formulations of TTh are available, each with advantages and disadvantages. Overall, TTh is relatively safe but the risks, such as erythrocytosis, makes long-term monitoring mandatory. The evidence does not support concerns regarding cardiovascular and prostate cancer risks.

Initial Clinical Experience With Testosterone Undecanoate Therapy (AVEED) in Men With Testosterone Deficiency in the United States

OBJECTIVE To report our initial experiences with testosterone undecanoate (TU 750) mg (AVEED) in men with testosterone deficiency. METHODS All patients receiving TU 750 mg at our center between July 1, 2014, and August 1, 2016, were identified. Clinical response was assessed through structured interviews and laboratory evaluations. Adverse events were documented, including increase in prostate specific antigen (PSA), increase in hematocrit (Hct), and the development of postinjection cough. RESULTS More than 2 injections were received by 147 men, with mean age 63.2 years. Mean baseline total testosterone (T) and free T were 305 ng/dL and 0.69 ng/dL, respectively. Nadir mean results during treatment were higher for total and free T, at 413.2 ng/dL and 0.81 ng/dL, respectively (P < .001 for each). Symptomatic improvement was reported by 97 of 147 patients (66.0%). Thirty patients (20.4%) discontinued therapy. Return of symptoms before the next injection was noted by 34%, managed by reduced interval between injections and/or supplemental injections of T cypionate. Three patients (2%) experienced transient cough immediately after TU injection, none requiring intervention. Mean Hct rose from 45.6% to 47.2%. Mean PSA rose from 1.7 ng/mL to 2.0 ng/mL. There were no strokes, myocardial infarctions, or deaths, and no new cases of prostate cancer. CONCLUSION This initial clinical experience with TU 750 mg provides evidence for good patient satisfaction and persistence with treatment, together with a favorable safety profile. Optimal dosing may be less than 10 weeks for some individuals.

MP89-06 PRESERVATION OF NORMAL CONCENTRATIONS OF PITUITARY GONADOTROPINS DESPITE ACHIEVEMENT OF NORMAL SERUM TESTOTERONE LEVELS IN HYPOGONADAL MEN TREATED WITH A 4.5% NASAL TESTOSTERONE GEL

up was carried out with quarterly semen analysis and hormonal profiles. Detection of sperm in ejaculate and achievement of pregnancy spontaneously or with assisted reproductive tecniques were the predetermined primary and secondary endpoints. RESULTS: The patients with regular follow-ups (135) had been selected out of the HH database with 250 patients and retrospectively investigated. During the treatment period(8-24 months), 94 (70%) patients had sperm appearance in their ejaculate. Out of the 72 married males with sperm appearing on their ejaculate, 40 patients (55%) obtained pregnancy spontaneously; 7 patients (%10) via assisted reproductive techniques. Forty one patients (%30) who had no sperm in their ejaculate yet are under routine control with hormonal treatment. CONCLUSIONS: The medical approach of males ,with hypogonadotropic hypogonadism and azoospermia, is a successful treatment modality both in terms of sperm presence in ejaculate and pregnancy rates.

Serum Concentrations of Sex Hormone–binding Globulin Vary Widely in Younger and Older Men: Clinical Data from a Men’s Health Practice

BACKGROUND The testosterone (T) status of a man is influenced by serum concentrations of sex hormone-binding globulin (SHBG). Specifically, tight binding of T to SHBG is believed to render the SHBG-bound T fraction biologically unavailable, meaning that interpretation of T levels in the clinical setting depends in part on knowledge of SHBG concentrations. Although SHBG levels have been reported in population studies, there is scant information for men presenting with clinical symptoms. OBJECTIVE To report SHBG values for a large cohort of men presenting to a mens health center. DESIGN, SETTING, AND PARTICIPANTS Medical records were reviewed for 1000 consecutive patients seen at our center with a reported SHBG value. SHBG concentrations were measured by a national clinical laboratory using an immunoassay run on a Beckman Coulter DXi system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Patients were age-stratified and data were plotted in the form of comparative histograms. RESULTS AND LIMITATIONS The mean age (±standard deviation) of the total cohort was 53.5±13.5 yr (range 17-91). The mean SHBG was 31.8±15.2nmol/l (range 6-109), with a nearly 20-fold difference from the lowest to the highest values. SHBG was >60nmol/l in 5.6% of the men. Patients were stratified according to age. A total of 535 patients were ≤54 yr old. In this younger cohort, the mean age was 40.52±7.9 yr (range 17-54) and mean SHBG was 27.7±13.3nmol/l (range 6-88), and 2.2% of patients had SHBG >60nmol/l. A total of 465 patients were ≥55 yr old. In this older cohort, the mean age was 64.8±7.23 yr (range 55-91) and mean SHBG was 36.6±15.8 nmol/l (range 11-109), and 9% of patients had SHBG >60 nmol/l. Mean SHBG was significantly higher in the older group (p<0.001). CONCLUSIONS A remarkably wide distribution of SHBG concentrations was observed in a clinical population of men presenting to a mens health center, among both younger and older men. Since SHBG concentrations greatly influence test results for hormones that bind to SHBG, recognition of this large interindividual variability should be considered in the clinical interpretation of these hormone results, particularly for T. Routine SHBG testing should be considered for men suspected of T deficiency. PATIENT SUMMARY Sex hormone-binding globulin (SHBG) levels vary widely among both older and younger men. This may impact the interpretation of test results for hormones that bind to SHBG, such as testosterone, since the portion that binds to SHBG is believed to not be biologically available.