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PubMed2005

The ontogeny of the urogenital system of the spotted hyena (Crocuta crocuta Erxleben).

Studies were conducted to elucidate the importance of androgen-mediated induction of the extreme masculinization of the external genitalia in female spotted hyenas. Phallic size and shape; androgen receptor (AR) and alpha-actin expression; and sex-specific differences in phallic retractor musculature, erectile tissue, tunica albuginea, and urethra/urogenital sinus were examined in male and female fetuses from Day 30 of gestation to term. Similar outcomes were assessed in fetuses from dams treated with an AR blocker and a 5alpha-reductase inhibitor (antiandrogen treatment). Clitoral and penile development were already advanced at Day 30 of gestation and grossly indistinguishable between male and female fetuses throughout pregnancy. Sex-specific differences in internal phallic organization were evident at Gestational Day 45, coincident with AR expression and testicular differentiation. Antiandrogen treatment inhibited prostatic development in males and effectively feminized internal penile anatomy. We conclude that gross masculinization of phallic size and shape of male and female fetuses is androgen-independent, but that sexual dimorphism of internal phallic structure is dependent on fetal testicular androgens acting via AR in the relevant cells/tissues. Androgens secreted by the maternal ovaries and metabolized by the placenta do not appear to be involved in gross masculinization or in most of the sex differences in internal phallic structure.

Androgen Antagonists↗
PubMed1997

Benign prostatic hyperplasia.

Benign prostatic hyperplasia is a common and costly disease that affects older men. This article reviews the underlying histopathologic changes that cause benign prostatic hyperplasia. The symptoms and systematic evaluation of the patient are described, along with the current therapeutic options for treatment.

Adrenergic alpha-Antagonists↗
PubMed1995

Benign prostatic hyperplasia: pathophysiology and pharmacological treatment.

Recent studies have confirmed that alpha-blocker therapy and antihormonal therapy are effective and safe treatment modalities in patients with symptomatic benign prostatic hyperplasia. New data suggest that the clinical response to medical therapy lasts for at least 3 years without any increase in side effects during this period.

Adrenergic alpha-Antagonists↗
PubMed2001

Minimally invasive procedures as an alternative to medical management for lower urinary tract symptoms of benign prostatic hyperplasia.

Data are reviewed relating to the safety and efficacy of minimally invasive transurethral microwave thermotherapy and medical management in patients with lower urinary tract symptoms of benign prostatic hyperplasia. Recent evidence is summarized indicating more pronounced long-term beneficial effects of microwave treatment. alpha-Blockade, however, offers the advantage of more rapid action than microwave treatment. Neoadjuvant and adjuvant alpha-blocker therapy can accelerate symptom and flow rate improvement in patients receiving microwave treatment. Compared with medical management, microwave treatment possesses greater versatility, allowing patients with severe baseline symptoms and small prostate sizes to be treated with a high probability of success.

Adrenergic alpha-Antagonists↗
PubMed2003

Chronic prostatitis.

PURPOSE OF REVIEW: This review covers recent developments in the classification, epidemiology, aetiology, diagnosis and treatment of patients diagnosed with chronic prostatitis (NIH classification types II, IIIa/IIIb and IV prostatitis) in the period of review (2001-2002). RECENT FINDINGS: Recent studies highlight some of the problems with the 1995 NIH classification. Epidemiological studies have confirmed that "prostatitis" is common, with a prevalence of 10-15%. Associations of prostatitis include benign prostatic hyperplasia, sexually transmitted disease, lower urinary tract symptoms, stress, and reduced sunlight exposure. Elevated levels of cytokines in the seminal plasma and prostatic secretions have been detected in men with chronic prostatitis compared with normal individuals, suggesting an active inflammatory process in the male genital tract. This inflammatory reaction may be mediated by an adaptive immune response directed against a genital tract antigen(s) (autoimmunity). Increased levels of bacterial 16S ribosomal DNA in the prostates of men with chronic prostatitis compared with controls are compatible with the notion that a bacterial inflammatory event initiates an auto-immune process; however, the role of bacteria in the continuation of symptoms is unknown. SUMMARY: The aetiology of chronic pelvic pain syndrome is still not certain, although an auto-immune process is favoured. Further research is required to determine the putative auto-antigen, the immune responses of patients, the role of bacteria in the inflammatory process, and the patients' pain response to genitourinary insults. As yet no diagnostic tests (other than to eliminate other pathology) and few treatments for chronic prostatitis can be recommended on the basis of scientific evidence.

Adult↗
PubMed2004

Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia.

PURPOSE: We reviewed the physiological and pathogenic role of dihydrotestosterone (DHT), evidence for the beneficial effects of decreasing DHT through 5alpha-reductase inhibition and the effects of altering the androgen balance with these agents. MATERIALS AND METHODS: A review of the relevant literature was done using published studies identified from the MEDLINE database. RESULTS: The androgens DHT and testosterone have complementary roles in male physiology. Each is mediated through the intracellular androgen receptor. It has been hypothesized that DHT may provide an amplification mechanism for testosterone, which could be a beneficial adaptation in men with low circulating testosterone. The recognition of the central role of DHT in benign prostatic hyperplasia (BPH) has changed the way the disease is viewed and has led to the introduction of 5alpha-reductase inhibitors, which can prevent and retard the progression of BPH by suppressing DHT synthesis. The 5alpha-reductase inhibitors decrease prostate volume. In doing so they improve symptoms and urinary flow, and decrease the risks of acute urinary retention and the need for BPH related surgery. The predominant drug related adverse events with 5alpha-reductase inhibitors are reproductive events, that is typically decreased libido, impotence and ejaculatory dysfunction. These events occur in a minority of men and tend to decrease with a longer treatment duration. CONCLUSIONS: DHT appears to have an obligatory role in the development of BPH. The role of 5alpha-reductase inhibitors in the treatment of BPH has been firmly established with an adverse events profile that is suitable for long-term use.

5-alpha Reductase Inhibitors↗
PubMed2005

A population based study of incidence and treatment of benign prostatic hyperplasia among residents of Olmsted County, Minnesota: 1987 to 1997.

PURPOSE: The treatment of benign prostatic hyperplasia (BPH), a common problem faced by aging men, has changed dramatically during the last decade. While BPH has long been considered a surgical condition, the advent of less invasive therapies makes the evaluation of the use of these various treatments important. Thus, this population based study was undertaken to describe the incidence and treatment for BPH from 1987 to 1997 among residents of Olmsted County, Minnesota. MATERIALS AND METHODS: We identified all Olmsted County men with a new diagnosis of BPH from 1987 to 1997 through the Medical and Surgical Indices made available through the Rochester Epidemiology Project. Overall year and age specific incidence rates were calculated for diagnosed BPH and by treatment type (surgical, minimally invasive, pharmacological, watchful waiting) assuming all men of the Olmsted County population to be at risk. Temporal changes in incidence were analyzed by Poisson regression. RESULTS: From 1987 to 1997, 2,330 cases of BPH were identified representing an age adjusted, corrected incidence for BPH among male residents of Olmsted County of 854.7 per 100,000 men. While the incidence of BPH increased from 1987 to 1992, coinciding with the introduction of serum prostate specific antigen testing, and subsequently decreased through 1997, the overall incidence of BPH decreased during the 10-year period for the entire cohort (p =0.002). Although the incidence of watchful waiting appeared to increase in the mid 1990s, significant decreases in age adjusted incidence were observed for the period overall (p <0.001). Significant decreases in surgical treatments were observed (p <0.0001). In contrast, there were significant increases in the age adjusted rates of pharmacological treatments during the 10 years (p <0.0001). No significant differences in incidence patterns of treatment type over time were observed by age group. CONCLUSIONS: The introduction of serum prostate specific antigen testing as a screening tool for prostate cancer along with the advent of less invasive alternatives, including pharmacological therapy, have had a significant impact on the incidence of diagnosed BPH in the last decade.

Adrenergic alpha-Antagonists↗
PubMed2002

Exposure to naturally circulating androgens during foetal life incurs direct reproductive costs in female spotted hyenas, but is prerequisite for male mating.

Among all extant mammals, only the female spotted hyena (Crocuta crocuta) mates and gives birth through the tip of a peniform clitoris. Clitoral morphology is modulated by foetal exposure to endogenous, maternal androgens. First births through this organ are prolonged and remarkably difficult, often causing death in neonates. Additionally, mating poses a mechanical challenge for males, as they must reach an anterior position on the female's abdomen and then achieve entry at the site of the retracted clitoris. Here, we report that interfering with the actions of androgens prenatally permanently modifies hyena urogenital anatomy, facilitating subsequent parturition in nulliparous females who, thereby, produce live cubs. By contrast, comparable, permanent anatomical changes in males probably preclude reproduction, as exposure to prenatal anti-androgens produces a penis that is too short and has the wrong shape necessary for insertion during copulation. These data demonstrate that the reproductive costs of clitoral delivery result from exposure of the female foetus to naturally circulating androgens. Moreover, the same androgens that render an extremely unusual and laborious process even more reproductively costly in the female are apparently essential to the male's physical ability to reproduce with a normally masculinized female.

Androgen Antagonists↗
PubMed2006

Validation of scalp coverage scoring methods for scalp hair loss in male pattern hair loss (androgenetic alopecia).

BACKGROUND: Global evaluation of hair loss in male subjects affected by androgenetic alopecia has been proposed as a means for monitoring changes over time, including placebo-controlled drug efficacy studies. Because of the potential impact of subjectivity (e.g. placebo effect) of clinical investigators, global photographs (GPs) have been introduced as a more objective record. Examination of paired before and after pictures and rating on a seven-point scale (from greatly decreased -3 to greatly increased +3) have been historically introduced by United States of America (US) experts. METHODS: Based on published GPs and original GPs obtained at our clinical research facility, we developed a training set in order to allow European Union (EU) observers to practice and compare with ratings by the US experts. RESULTS: After training with the seven-point scale, there was a positive correlation between three US and three EU ratings (n=52 paired images from 35 different subjects, r=0.795). The results of a test-retest evaluation was performed on 18 paired images from the initial image collection by the three EU experts. Correlation r=0.806 and identical scores in 78% of cases documents a reproducibility similar to the single one US expert published data (119 subjects, retest correlation 0.76 with 75% identical duplicate ratings). Seventeen subjects taken from a placebo-controlled trial had GPs at 6 and 12 months. The average difference between an efficacious drug treatment and the placebo were almost similar in the US (0.833) as in the EU (0.689) expert panels. We also trained the EU experts in performing the scalp coverage scoring (SCS), a novel system for the global evaluation of scalp hair in vivo and on GP. SCS was performed on single images (randomised as to time and treatment) taken from the same set of 17 paired GPs. This showed a between-group difference of 0.055 at 6 months and 0.201 at 12 months, i.e. 5% improved coverage in favour of the active group. CONCLUSION: After completion of our study, US and trained - calibrated EU experts seem equally valuable in comparing before-after GPs. SCS can also be used on GPs and may support the clinical investigator during inclusion of test subjects and for real-time efficacy evaluation during the trial.

Alopecia↗
PubMed1994

5 alpha-reductase inhibitors and prostatic disease.

5 alpha-Reductase inhibitors are a new class of substances with very specific effects on type I and type II 5 alpha R which may be of use in the treatment of skin disease, such as male pattern baldness, male acne and hirsutism, as well as prostatic hyperplasia and prostate cancer. At least two types of 5 alpha R inhibitors with a different pH optimum have been described. cDNA encoding for both the type I and the type II enzyme has been cloned. Most of the orally effective 5 alpha R inhibitors belong to the class of 4-azasteroids. The radical substituted in the 17 position of the steroid ring seems to be related to species specific variations and to the types of 5 alpha R enzymes in different species and organ systems. 5 alpha R inhibitors lead to a decrease of plasma DHT by about 65% while there is a slight rise in plasma testosterone. The decrease of tissue DHT in the ventral prostate of the intact rat, the dog and in humans is more pronounced and amounts to about 85%. There is a reciprocal rise of tissue T in these systems. The application of an inhibitor of 5 alpha R type II leads to a shrinkage of BPH in men by about 30%. In the rat a similar shrinkage accompanied by a significant decrease of total organ DNA occurs. This decrease, however, is not as pronounced as can be achieved with castration.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Transrectal ultrasound versus magnetic resonance imaging in the estimation of prostatic volume.

OBJECTIVE: To establish which method of determining prostatic volume (transrectal ultrasound [TRUS] or magnetic resonance imaging [MRI]) and which calculation formula give the most exact and least variable results; to determine the size and the source of the variability: and to establish which method is the more sensitive to drug-induced changes in prostate volume. PATIENTS AND METHODS: Prostatic size was estimated by TRUS and MRI in 21 patients treated medically (either active treatment or placebo) for benign prostatic hyperplasia. Each patient was examined at baseline, and after 3 months and 6 months of treatment. Prostatic volume was calculated at every visit using different formulae proposed in the literature. RESULTS: With some of these formulae, including the classical ellipsoid formula, there was a strong correlation (r > 0.8) between TRUS and MRI volume estimates. For others the correlation was much weaker, suggesting unreliability. MRI gave a significantly larger volume than TRUS because of larger values for the cephalocaudal and anteroposterior diameters. For patients on placebo the visit-to-visit variability of the prostate volume was 10-12% of the mean volume, whether calculated by TRUS or MRI. Part of this variability was apparently due to natural variation of prostate size. CONCLUSION: The classical ellipsoid formula is adequate for determining prostate volume. MRI and TRUS give different volumes. Visit-to-visit variability is similar for both methods and is partly due to real, natural variation. MRI is better able than TRUS to detect drug-induced changes in prostate volume.

Double-Blind Method↗