Biomedical subjects

David J Handelsman

Publications and source records attributed to David J Handelsman.

60 records · Page 4Linked to original sources

PubMedDate not supplied

Induction of spermatogenesis by recombinant follicle-stimulating hormone (puregon) in hypogonadotropic azoospermic men who failed to respond to human chorionic gonadotropin alone.

A multicenter, open-label, randomized efficacy and safety study was performed with combined human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) (Puregon(R)) treatment to induce spermatogenesis in hypogonadotropic hypogonadal male patients. Patients were pretreated for 16 weeks with hCG to normalize testosterone levels. A total of 30 of 49 (61%) subjects had normalized testosterone levels but were still azoospermic after the hCG-alone phase. These patients were randomized into 2 treatment schemes with recFSH (2 x 225 IU recFSH per week [group A] or 3 x 150 IU recFSH per week [group B]), in combination with hCG for a period of 48 weeks. Total testosterone increased during the hCG-alone period from 1.08 and 1.22 ng/mL to 6.26 and 4.52 ng/mL for groups A and B, respectively. Combined gonadotropin treatment was effective in inducing spermatogenesis (sperm count >/=1 x 10(6)/mL) in 14 of 30 subjects (47%) and this was achieved after a median duration of treatment of approximately 5.5 months. Treatment time necessary for first sperm cells to appear in the ejaculate was related to the initial testicular volume. Subjects with a history of maldescended testes (11 of 30 subjects, 37%) showed a lower mean response to treatment as indicated by the relatively lower number of subjects reaching levels of at least 1 x 10(6) sperm cells per milliliter. Combined testicular volume increased during combined gonadotropin treatment from 11.4 to 24.0 mL. Although subjects with a history of maldescended testes had a lower starting testicular volume, subjects with and without a history of maldescended testes showed approximately the same relative increase in testicular volume. Total testosterone levels showed only a minor further increase during the combined gonadotropin treatment period. In conclusion, a weekly dose of 450 IU (3 x 150 IU or 2 x 225 IU) recFSH, in addition to hCG, was able to induce spermatogenesis in many hypogonadotropic azoospermic men who failed to respond to treatment with hCG alone.

Adult↗

PubMedDate not supplied

Men in Australia Telephone Survey (MATeS): a national survey of the reproductive health and concerns of middle-aged and older Australian men.

BACKGROUND: The Men in Australia Telephone Survey (MATeS) describes the prevalence of self-reported reproductive health disorders as well as related concerns and health behaviours among middle-aged and older Australian men. METHODS: A representative sample population (n=5990) of Australian men (>or=40 years) was obtained by contacting a random selection of households with unbiased sampling, stratified by age and state. A 20-min computer-assisted telephone interview was done to assess reproductive health and related knowledge and beliefs, sociodemographic factors, general health, and lifestyle factors. FINDINGS: A response rate of 78% (5990/7636) was achieved. 34% (1627/4737) of men surveyed reported one or more reproductive health disorder, all of which were most common in the oldest age group. Age-standardised prevalence of significant lower urinary tract symptoms was 16%, erectile dysfunction was 21%, and prostate disease was 14%. About 50% of participants reported having had a prostate cancer test whereas only 30% (300/1012) of men with erectile dysfunction sought medical help. Willingness to seek medical help for erectile dysfunction was related to age and ethnic origin. Although men aged 40-69 years expressed a moderate or high level of concern about prostate cancer and loss of erectile function, concern about reproductive health was less in the oldest age group (>or=70 years). INTERPRETATION: The high prevalence of reproductive health disorders and associated concerns in middle-aged and older Australian men draws attention to the need to develop appropriate services and education strategies specifically directed to improving reproductive health in these men.

Adult↗

PubMedDate not supplied

Muscle strength and ageing: methodological aspects of isokinetic dynamometry and androgen administration.

1. To evaluate interventions aiming to increase muscle strength in older men, it is necessary to use an objective and reproducible method to measure strength. The most reliable method to evaluate muscle strength is isokinetic peak torque (PT) measured by a dynamometer; however, raw PT varies with differences in body size and an optimal scaling for body physique to control confounding effects of body size is necessary to make the most valid comparisons. 2. The present study was designed to estimate the effects of age (part A) and androgen administration (part B) on muscle strength and to estimate reproducibility and evaluate various scaling methods in order to optimize comparisons of isokinetic PT measurements. 3. A single isokinetic exercise protocol was used to compare the muscle strength of 31 healthy men of two age groups (< 40 and > 60 years; part A) and change in strength due to administration of dihydrotestosterone (DHT; 70 mg/day) or placebo gel for 3 months in 35 healthy older (> or = 60 years) men (part B). 4. Muscle strength was assessed by a total of 16 PT measurements using a Cybex NORM dynamometer (Cybex, Ronkonkoma, NY, USA). Age-related differences in muscle strength were estimated by using PT evaluated as raw data or scaled by normalizing methods, including simple ratio (PT/weight), allometric PT (PT/weight(0.67)) and adjustment of PT by weight, height, body mass index and body surface area (BSA). The goodness-of-fit for various scaling methods was compared using the Akaike Information Criterion (AIC) as an objective measure of model-based entropy reduction. 5. The effects of DHT administration according to different scaling methods were estimated by eta-squared measure of effect size in treatment models. In part A, older men were weaker than younger men in five knee PT, consistently by all eight analysis models but not in shoulder PT. In part B, DHT treatment resulted in an increase one knee PT (dominant knee flexion at 120 degrees/s) with the difference consistent in all seven models. 6. The scaling model using BSA proved superior to other comparison models throughout both parts of the present study according to entropy minimization criteria (AIC) for goodness-of-fit of the model or eta-squares for treatment effect size. 7. We conclude that differences in muscle strength due to age or androgen administration in older men are restricted to a minority of lower limb contractions and that use of BSA scaling for PT values is considered the best scaling method for muscle strength comparisons in either cross-sectional or longitudinal studies.

Adult↗

PubMedDate not supplied

The present and future state of hormonal treatment for male infertility.

Although male factors contribute to over half of all cases of infertility, most infertile men are described as 'idiopathic oligo/asthenozoospermic' rather than diagnosed precisely; hence, specific medical treatment is not possible. One uncommon but treatable cause of male infertility is gonadotrophin deficiency in which gonadotrophin replacement therapy is highly effective at inducing spermatogenesis and fertility. Hormonal therapy is a logical approach for empirical drug therapy given the fundamental role of hormonal regulation in spermatogenesis. However, treatment with GnRH analogues, gonadotrophins, androgens, anti-estrogens, aromatase inhibitors, growth hormone- and prolactin-suppressing drugs is ineffective in unselected infertile men. Prolonged high-dose glucocorticoid therapy for sperm autoimmunity may improve pregnancy rates modestly, but the risks are generally unacceptable compared with IVF or ICSI. For these reasons, modern reproductive technologies, notably ICSI/IVF, have become the de-facto standard empirical treatment of male infertility, despite involving significant though infrequent risks to the fetus and mother. There remains a potential for hormonal methods to improve sperm quality or ultrastructure in subgroups of infertile men more responsive to hormonal manipulation or using novel protein or gene-targeted therapies or biochemical approaches based on post-hormonal receptor mechanisms that stimulate spermatogenesis. How such novel hormonal methods will develop in conjunction with improved ICSI/IVF or cloning technologies, and the potential role of adjunctive hormonal therapy remains to be clarified.

Androgens↗

PubMedDate not supplied

Optimal power transformations for analysis of sperm concentration and other semen variables.

The nongaussian (or nonnormal) distribution of sperm concentration, and variables deriving from it, is a common practical problem in the statistical evaluation of semen data. Yet it has been little studied, and its importance to data analysis, as well as to practical remedies, is not widely appreciated. Inappropriate use of the raw scale of measurement produces inflated estimates of mean and variance, leading to false-negative (underpowered) statistical comparisons and excessive sample size estimates. This study employs the Box-Cox family of power transforms to illustrate by a simple graphical method how to identify optimal power transforms for semen data variables. Using robust statistical methods, it is shown that the nongaussian distribution is due to right skewing rather than multimodality or influential outliers. The optimal power transform, typically in the region of 0.15 to 0.35 (most easily implemented as a cube-root transformation), usually performs better than the logarithmic transformation in normalizing the data. In addition, the power transformation has an important practical advantage over the logarithmic transformation in the appropriate handling of zeros (azoospermia), a regular and important features of such data sets in practice.

Humans↗

PubMedDate not supplied

Prostate epithelial expression of a novel androgen target gene.

To better understand the role of androgens in prostate development and disease it is important to characterize androgen-regulated genes in the prostate. Using suppression subtractive hybridization between congenitally androgen-deficient (hpg) and androgen-replaced hpg mouse prostates, we have cloned a novel androgen up-regulated gene from mouse prostate (AUMP). The messenger RNA sequence of AUMP consists of 805 nucleotides with an open reading frame of 408 base pairs. In non-hpg mice with normal androgen levels, AUMP is selectively expressed in the prostate, as shown by reverse transcriptase-polymerase chain reaction and Northern blot analysis of 9 organs. Depletion of androgens via castration of mature mice resulted in loss of AUMP expression, whereas testosterone replacement restored it. Tissue in situ hybridization localized AUMP expression to the luminal epithelial cells of the androgen-sufficient prostate. Database searches indicate that AUMP codes for a novel protein that shares approximately 65% similarity and 35% identity to palmitoyl protein thioesterase of human, rat, mouse, and bovine. A motif for protein-transport protein, which promotes translocation as well as integration of secretory proteins into membrane, is also present. Further efforts will be made to obtain the human homologue of AUMP that will enable evaluation of its role in normal and diseased human prostate.

Amino Acid Sequence↗