Ann J. Conway

Young's syndrome. Obstructive azoospermia and chronic sinopulmonary infections.

We studied 29 men with Youngs syndrome, a combination of obstructive azoospermia and chronic sinopulmonary infections. Men with this syndrome have only mildly impaired respiratory function and normal spermatogenesis; the azoospermia is due to obstruction of the epididymis by inspissated secretions. The diagnosis is based on the occurrence of chronic sinopulmonary infections, persistent azoospermia, normal spermatogenesis, and characteristic epididymal findings, as well as exclusion of cystic fibrosis and the immotile-cilia syndrome. The sperm themselves appear to be normal in Youngs syndrome. Pregnancies had occurred in five couples; in three paternity was documented by genotyping. Thus, improved microsurgical and medical therapy might restore fertility. We suggest that Youngs syndrome has a prevalence comparable to that of Klinefelters syndrome and is a common cause of both chronic sinopulmonary infection and azoospermia.

Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study

To determine serum concentrations, intra‐individual variability and impact of age‐related co‐morbidities on serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2) and estrone (E1) in older men.

Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome.

BACKGROUND The induction of spermatogenesis and fertility with gonadotropin therapy in gonadotropin-deficient men varies in rate and extent. Understanding the predictors of response would inform clinical practice but requires multivariate analyses in sufficiently large clinical cohorts that are suitably detailed and frequently assessed. DESIGN, SETTING, AND PARTICIPANTS A total of 75 men, with 72 desiring fertility, was treated at two academic andrology centers for a total of 116 courses of therapy from 1981-2008. OUTCOMES Semen analysis and testicular examination were performed every 3 months. RESULTS A total of 38 men became fathers, including five through assisted reproduction. The median time to achieve first sperm was 7.1 months [95% confidence interval (CI) 6.3-10.1]) and for conception was 28.2 months (95% CI 21.6-38.5). The median sperm concentration at conception for unassisted pregnancies was 8.0 m/ml (95% CI 0.2-59.5). Multivariate correlated time-to-event analyses show that larger testis volume, previous treatment with gonadotropins, and no previous androgen use each independently predicts faster induction of spermatogenesis and unassisted pregnancy. CONCLUSIONS Larger testis volume is a useful prognostic indicator of response. The association of slower responses after prior androgen therapy suggests that faster pregnancy rates might be achieved by substituting gonadotropin for androgen therapy for pubertal induction, although a prospective randomized trial will be required to prove this.

An analysis of testosterone implants for androgen replacement therapy

To review 13 years of experience using fused crystalline testosterone implants for androgen replacement therapy in order to identify pattern of usage (including continuation rates) and adverse events emerging during therapy and factors associated with adverse events including implant extrusions.

Long-Term Effects of Dihydrotestosterone Treatment on Prostate Growth in Healthy, Middle-Aged Men Without Prostate Disease: A Randomized, Placebo-Controlled Trial

BACKGROUND Benign prostatic hypertrophy increases with age and can result in substantially decreased quality of life for older men. Surgery is often required to control symptoms. It has been hypothesized that long-term administration of a nonamplifiable pure androgen might decrease prostate growth, thereby decreasing or delaying the need for surgical intervention. OBJECTIVE To test the hypothesis that dihydrotestosterone (DHT), a nonamplifiable and nonaromatizable pure androgen, reduces late-life prostate growth in middle-aged men. DESIGN Randomized, placebo-controlled, parallel-group trial. (Australian New Zealand Clinical Trials Registry number: ACTRN12605000358640) SETTING: Ambulatory care research center. PARTICIPANTS Healthy men (n = 114) older than 50 years without known prostate disease. INTERVENTION Transdermal DHT (70 mg) or placebo gel daily for 2 years. MEASUREMENTS Prostate volume was measured by ultrasonography; bone mineral density (BMD) and body composition were measured by dual-energy x-ray absorptiometry; and blood samples and questionnaires were collected every 6 months, with data analyzed by mixed-model analysis for repeated measures. RESULTS Over 24 months, there was an increase in total (29% [95% CI, 23% to 34%]) and central (75% [CI, 64% to 86%]; P < 0.01) prostate volume and serum prostate-specific antigen level (15% [CI, 6% to 24%]) with time on study, but DHT had no effect (P > 0.2). Dihydrotestosterone treatment decreased spinal BMD (1.4% [CI, 0.6% to 2.3%]; P < 0.001) at 24 months but not hip BMD (P > 0.2) and increased serum aminoterminal propeptide of type I procollagen in the second year of the study compared with placebo. Dihydrotestosterone increased serum DHT levels and its metabolites (5α-androstane-3α,17β-diol and 5α-androstane-3β,17β-diol) and suppressed serum testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels. Dihydrotestosterone increased hemoglobin levels (7% [CI, 5% to 9%]), serum creatinine levels (9% [CI, 5% to 11%]), and lean mass (2.4% [CI, 1.6% to 3.1%) but decreased fat mass (5.2% [CI, 2.6% to 7.7%]) (P <0.001 for all). Protocol-specific discontinuations due to DHT were asymptomatic increased hematocrit (n = 8), which resolved after stopping treatment, and increased prostate-specific antigen levels (n = 3; none with prostate cancer) in the DHT group. No serious adverse effects due to DHT occurred. LIMITATION Negative findings on prostate growth cannot exclude adverse effects on the natural history of prostate cancer. CONCLUSION Dihydrotestosterone treatment for 24 months has no beneficial or adverse effect on prostate growth but causes a decrease in spinal but not hip BMD. These findings have important implications for the wider use of nonsteroidal pure androgens in older men. PRIMARY FUNDING SOURCE BHR Pharma.

Effects of androgen deficiency and replacement on prostate zonal volumes.

BACKGROUND AND OBJECTIVES Androgens play a key role in prostate development and disease. However the effects of androgen deficiency and replacement on the prostate during mid‐life are not well understood, and there is no information on their effects on prostate zonal volumes. This study aimed to define the effects of androgen deficiency and androgen replacement therapy on prostate zonal volumes (central, peripheral & total) using planimetric prostate ultrasound with particular emphasis on the central zone of the prostate, the most hormonally sensitive and fastest growing region of the prostate and the zone where nodular benign prostate hyperplasia originates.

Hypothalamic‐pituitary adrenal function in end‐stage non‐alcoholic liver disease

Abstract Patients with end‐stage liver disease have significant mortality often associated with intercurrent episodes of bleeding or sepsis. Intact adrenal function is essential in such situations. In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic‐pituitary adrenal function was evaluated in patients with end‐stage liver disease awaiting transplantation.

Hypothalamic-pituitary-testicular function in end-stage non-alcoholic liver disease before and after liver transplantation.

OBJECTIVE Gonadal dysfunction is common in chronic liver disease, but most of the previous studies have been restricted to men with alcohol‐Induced liver disease. We have evaluated hypothalamic‐pituitary‐testicular function In patients with end‐stage non‐alcoholic liver disease before and at 6 and 12 months after hepatic transplantation.

Testicular function and glycemic control in diabetic men. A controlled study

Summary:  We have investigated testicular function in 28 insulin‐dependent diabetic men under the age of 50 years and 119 age‐matched controls. Diabetics had reduced testicular volume, semen volume, total and total motile sperm output while plasma LH and FSH levels were elevated. Reduction in semen volume and impotence were more common in long‐standing complicated diabetes. Glycosylated hemoglobin (GHb) levels were positively correlated with plasma LH levels (r = 0.46, p < 0.02) but there was no direct correlation of glycemic control and spermatogenesis. The differences in testicular function were due to decreased spermatogenesis and could not be explained by other forms of testicular pathology or the presence of diabetic neurovascular complications. We conclude that the function of the hypothalamic pituitary testicular axis is impaired in diabetic men, that this impairment is at least partly related to the degree of preceeding glycemic control and that multiple levels of the axis may be dysfunctional.

Extrusion of testosterone pellets: a randomized controlled clinical study

It has previously been shown that testosterone implantation is an effective and well accepted form of androgen replacement therapy, but that pellet extrusion was the most frequent side‐effect. The present study aimed to reduce the extrusion rate.