Effect of pulsed electromagnetic field therapy on prostate volume and vascularity in the treatment of benign prostatic hyperplasia: a pilot study in a canine model.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a result of urogenital aging. Recent studies suggest that an age-related impairment of the blood supply to the lower urinary tract plays a role in the development of BPH and thus may be a contributing factor in the pathogenesis of BPH. The canine prostate is a model for understanding abnormal growth of the human prostate gland. We studied the efficacy of pulsed electromagnetic field therapy (PEMF) in dogs to modify prostate blood flow and evaluated its effect on BPH. METHODS: PEMF (5 min, twice a day for 3 weeks) was performed on 20 dogs affected by BPH. Prostatic volume, Doppler assessment by ultrasonography, libido, semen quality, testosterone levels, and seminal plasma volume, composition and pH were evaluated before and after treatment. RESULTS: The 3 weeks of PEMF produced a significant reduction in prostatic volume (average 57%) without any interference with semen quality, testosterone levels or libido. Doppler parameters showed a reduction of peripheral resistances and a progressive reduction throughout the trial of the systolic peak velocity, end-diastolic velocity, mean velocity, mean, and peak gradient of the blood flow in the dorsal branch of the prostatic artery. The pulsatility index and the resistance index did not vary significantly over time. CONCLUSIONS: The efficacy of PEMF on BPH in dogs, with no side effects, suggests the suitability of this treatment in humans and supports the hypothesis that impairment of blood supply to the lower urinary tract may be a causative factor in the development of BPH.

The role of hormones and aromatase inhibitors on breast tumor growth and general health in a postmenopausal mouse model.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer in women in the United States. Approximately 70% of breast cancers are diagnosed in postmenopausal women. Major clinical trials and experimental studies showed that aromatase inhibitors are effective against postmenopausal breast cancer. Despite their effectiveness in reducing tumor recurrence, aromatase inhibitors have adverse effects on the cardiovascular system and increase osteoporosis and bone fractures. Our study is aimed at investigating the role of natural steroid hormones on serum cardiovascular and bone resorption markers in an established mouse model mimicking postmenopausal breast cancer. METHODS: Ovariectomized nude mice were transplanted with MCF-7 breast cancer cells constitutively expressing aromatase. The mice were treated with different combinations and doses of steroids, [estrogen (25 pg, 40 pg, 100 pg), progesterone (6 ng) and testosterone (50 ng)] along with dehydroepiandrostenedione (100 ug). Serum levels of HDL, LDL/VLDL, free and total cholesterol, total and bone specific alkaline phosphatase and triglycerides were analyzed after 5, 10 and 15 months. RESULTS: Free cholesterol and LDL/VLDL levels in serum were reduced in groups mimicking estrous cycle and menstrual cycle hormones treatment. HDL cholesterol was increased in all the hormone treated groups except the estrous cycle-mimicking group. Bone specific alkaline phosphatase was decreased in menstrual cycle levels of estrogen and progesterone treatment. CONCLUSIONS: All together our results show that use of natural hormones in appropriate combinations have beneficial effects on cardiac and bone toxicity, along with better tumor reduction than current treatments.

Restoration of Reproductive Hormone Concentrations in a Male Neutered Dog Improves Health: A Case Study.

This case study reports on the use of hormone therapy to treat a dog with a range of physical and behavioral signs that began after gonadectomy. A male mixed breed dog neutered at 7 months of age presented at 1 year with health issues impacting quality of life. Reduced mobility, limping, rapid weight gain, and fear of unfamiliar people were treated over the next 3 years with trials of pain medication, joint supplements, thyroxine, antidepressant, and significant diet restrictions. Frequent carprofen administration and daily joint supplements reduced limping, but mobility was still poor. Weight stabilized on a strict diet but fear and anxiety responses to strangers continued to worsen. Hormone restoration therapy was initiated when the dog was almost 4 years of age. Weekly subcutaneous administration of testosterone cypionate (0.5 mg/kg) significantly reduced pain and increased muscle mass, thereby improving mobility. However, supraphysiologic concentrations of luteinizing hormone were not reduced with testosterone therapy so a gonadotropin-releasing hormone agonist was implanted. After hormone restoration, appetite was reduced, and anxiety and fear behaviors became manageable. The testosterone and gonadotropin-releasing hormone agonist treatment was easily administered, had no known side effects, and the owners were pleased with the outcome.

Reversibility of Vasalgel™ male contraceptive in a rabbit model.

BACKGROUND: Development of a non-hormonal long-acting reversible contraceptive for men could have a significant impact on reducing unintended pregnancies. Vasalgel™ is a high molecular weight polymer consisting of styrene-alt-maleic acid (SMA) dissolved in dimethyl sulfoxide being developed as a reversible male contraceptive device. It forms a hydrogel when implanted into the vasa deferentia, which prevents the passage of sperm. Previous studies in the rabbit have proven its efficacy, durability and rapid onset. This study evaluates the capacity to restore sperm concentrations in ejaculates after a reversal procedure. METHODS: Sodium bicarbonate was injected into the vasa deferentia after fourteen months of azoospermia following the injection of two device variations (Vasalgel 100 and Vasalgel 80). Semen samples were then collected for six months and sperm characteristics were compared to baseline levels. Samples of vasa deferentia were obtained for histological examination. RESULTS: Spermatozoa were present in all subject ejaculates after the reversal procedure. Sperm concentration and sperm motility were similar to baseline levels after reversal, while sperm forward progression was significantly lower and normal acrosomes were not observed. Forward progression percentages increased linearly during six months of semen collection, however, normal acrosomes were not observed at the conclusion of the study. Histologically, several vasa deferentia were clear of the device and contained an intact epithelial lining. A smaller proportion of tissues contained residual test material. A secondary intraluminal inflammatory response was seen occasionally in the tissues containing residual material. There was no difference between the two device variations for studied parameters. CONCLUSIONS: Vasalgel's prevention of sperm transport for 14 months was reversed through an intravasal injection of sodium bicarbonate. Post-reversal sperm concentrations and motility returned to baseline levels during the six-month follow up. Residual material in the vas lumen or compromised epididymal and vas deferens function may be resulting in reduced forward progression and loss of acrosomes during transit through the vas. Reduced forward progression and the lack of normal acrosomes strongly suggest impaired sperm function.

CONTEXTE: Le développement d'une contraception réversible, de longue durée et non hormonale pour les hommes pourrait avoir un impact significatif sur la réduction du nombre de grossesses non désirées. Le Vasalgel ™ est un polymère de haut poids moléculaire constitué d'acide styrène-alt-maléique (SMA) dissous dans du diméthylsulfoxyde, en cours de développement comme moyen réversible de contraception masculine. Une fois injecté dans les canaux déférents, il forme un hydrogel qui fait obstacle au passage des spermatozoïdes. De précédentes études chez le lapin ont prouvé son efficacité ainsi que la rapidité et la persistance de son effet. La présente étude a évalué la capacité de restauration de la concentration de spermatozoïdes dans les éjaculats obtenus après une procédure de réversion. MATÉRIEL ET MÉTHODES: Du bicarbonate de sodium a été injecté dans chaque canal déférent après quatorze mois d'azoospermie secondaire à l'injection de deux formulations du produit testé (Vasalgel 100 et Vasalgel 80). Des échantillons de sperme ont ensuite été recueillis pendant six mois et les caractéristiques des spermatozoïdes comparées aux valeurs de départ. Des échantillons de canal déférent ont été prélevés pour analyse histologique. RÉSULTATS: Des spermatozoïdes furent retrouvés dans les éjaculats de tous les animaux après la procédure de réversion. La concentration de spermatozoïdes et le pourcentage de spermatozoïdes mobiles après réversion étaient similaires aux valeurs de départ, mais le pourcentage de spermatozoïdes à mobilité progressive directionnelle était significativement moindre que celui des valeurs de départ, et aucun acrosone normal n'a été observé. Les pourcentages de spermatozoïdes à mobilité progressive directionnelle ont augmenté linéairement durant les six mois de recueil du sperme ; cependant, aucun acrosome normal n'a été retrouvé à la fin de l'étude. Au plan histologique, de nombreux canaux déférents ne contenaient plus aucune trace du produit testé et étaient bordés par un épithélium intact. Une plus faible proportion d'échantillons contenait des traces du produit testé. On a occasionnellement observé une réaction inflammatoire secondaire dans la lumière des canaux contenant des résidus de produit testé. Il n'a été retrouvé aucune différence entre les deux formulations du produit testé pour les paramètres étudiés. CONCLUSIONS: L'obstacle au transport des spermatozoïdes pendant 14 mois réalisé par le Vasalgel™ a été supprimé par une injection intra canalaire de sodium de bicarbonate. Après la réversion, la concentration de spermatozoïdes et le pourcentage de spermatozoïdes mobiles reviennent à leur valeur de départ durant les six mois de suivi. La présence dans la lumière du canal de résidus du produit testé, ou une altération des fonctions épididymaire et déférentielle, pourraient entraîner la réduction de la mobilité progressive directionnelle et la perte des acrosome durant le transit des spermatozoïdes dans les canaux. La réduction de la mobilité progressive et l'absence d'acrosomes normaux suggèrent fortement une altération de la fonction spermatique. MOTS-CLÉS: Contraception masculine, Polymère, Réversibilité, Contraception réversible de longue durée, Acide styrène-alt-maléique (SMA).

The contraceptive efficacy of intravas injection of Vasalgel™ for adult male rhesus monkeys.

BACKGROUND: Options for male contraception are limited. The purpose of this study was to use a nonhuman primate model to evaluate Vasalgel™, a high molecular weight polymer being developed as a contraceptive device for men. METHODS: Sixteen adult male rhesus monkeys received intravas injections of Vasalgel, consisting of 25% styrene maleic acid in dimethyl sulfoxide. After a one-week recovery, males were returned to outdoor group housing, which included at least 3 and up to 9 intact, breeding females with a successful reproductive history. RESULTS: Treated males have had no conceptions since Vasalgel injections. All males were housed with intact females for at least one breeding season and seven have been almost continually housed with females for 2 years. Complications were minor and included one incident of incorrect placement of Vasalgel into the vas deferens and the development of a sperm granuloma in one animal. Three unilateral vasectomies were performed, one was necessary for incorrect placement of Vasalgel, the other two were elective. CONCLUSIONS: Intravas injection of Vasalgel in sexually mature adult male rhesus monkeys was effective in preventing conception in a free-living, group environment. Complications were few and similar to those associated with traditional vasectomy.

Azoospermia in rabbits following an intravas injection of Vasalgel ™.

BACKGROUND: Vasectomy is currently the only long-acting contraceptive option available for men, despite increasing demand and potentially significant positive impacts on human health of additional male contraceptive options. Vasalgel ™ is a high molecular weight hydrogel polymer being developed as a non-hormonal long-acting reversible male contraceptive. Vasalgel consists of styrene-alt-maleic acid dissolved in dimethyl sulfoxide, which is distinct from styrene-alt-maleic anhydride materials previously studied. METHODS: The goal of the study was to determine the contraceptive efficacy of two test articles with different levels of styrene maleic acid (100 %, and 80 % acid/20 % anhydride). The test articles were injected bilaterally in the vasa deferentia of mature male rabbits. Post-implantation analyses of semen parameters were completed over a 12 month period and compared to baseline measures of sperm concentration, motility and forward progression. RESULTS: Both test articles were effective in blocking the passage of spermatozoa through the vasa deferentia in the 12 subjects completing the study. A significant decrease in sperm concentration occurred following implantation of the test material, with no measurable sperm concentration except for a few samples in one animal that were markedly oligospermic. Vasalgel produced a rapid onset of azoospermia, with no sperm in semen samples collected as early as 29-36 days post-implantation, and was durable over a 12 month period. CONCLUSION: This study indicated that Vasalgel is an effective non-hormonal long-acting male contraceptive in a rabbit model.

Alcohol diluent provides the optimal formulation for calcium chloride non-surgical sterilization in dogs.

BACKGROUND: Surgical castration is widely used to sterilize male dogs, but has significant impacts on time to perform the operation, recovery of the animals as well as cost, which can limit population control programs. Previous research has shown intratesticular injection of calcium chloride dihydrate (CaCl2) in saline to be a promising alternative to surgery. However, long-term azoospermia was not maintained at dosages low enough to avoid side effects. In the search for an optimized formulation, the current investigation is the first study on long-term sterilization effects of intratesticular injection of CaCl2 in either lidocaine solution or alcohol in dogs. CaCl2 at 20% concentration in lidocaine solution or alcohol was administered via intratesticular injection to groups of 21 dogs each. The treated animals were examined at 2, 6, and 12 months for sperm production, blood levels of testosterone, and side effects; at time zero and 12 months for testicular size and semen volume. The experimentally treated animals were compared to a control group receiving saline injection only. RESULTS: Testicles of dogs treated with CaCl2 in either diluent significantly decreased in size. After administration of CaCl2 in lidocaine solution, sterility was achieved for at least 12 months in 75% of treated dogs. However, optimal long-term contraceptive effectiveness was achieved with CaCl2 in alcohol, which resulted in azoospermia over the 12-month study period. Testosterone levels significantly decreased following treatment with CaCl2, and sexual activity disappeared. Although testosterone returned to baseline levels by 12 months for the group treated with CaCl2 in lidocaine, dogs injected with CaCl2 in alcohol had a 63.6% drop in testosterone level, which remained at the low end of physiological range throughout the study. No adverse effects were noted. CONCLUSIONS: A single, bilateral intratesticular injection of 20% CaCl2 in 95% ethanol was a reliable method for induction of sterilization in 18-28 kg male dogs in this study. The approach showed long-term efficacy and reduced sexual behavior. This chemical method of sterilization might provide an effective, efficient alternative to surgical castration that can have positive impacts on dog welfare.

A dose-finding, long-term study on the use of calcium chloride in saline solution as a method of nonsurgical sterilization in dogs: evaluation of the most effective concentration with the lowest risk.

BACKGROUND: Canine overpopulation is a global issue with serious health and welfare implications. Nonsurgical methods of sterilization could yield positive impacts on this problem, but no long-term data on such methods are available. The objective of the current investigation was to determine the effects of intratesticular injections of calcium chloride dihydrate (CaCl2) in saline in dogs over a one year period. Five concentrations (0%, 10%, 20%, 30%, 60%) of CaCl2 in saline were administered via intratesticular injection to groups of 10 dogs each. Total sperm count and motility, blood levels of testosterone, and side effects were examined at 0, 2, 6, and 12 months post-injection (PI). Testicular size and semen volume were examined at 0 and 12 months PI. RESULTS: Total sperm count, semen volume and testosterone showed significant dose-dependent decreases upon treatment with 10%-60% CaCl2 compared with either the control group (0% CaCl2) or baseline for each treatment group. Azoospermia was achieved for at least 12 months PI in 60% and 80% of treated dogs after administration of a 10% and 20% CaCl2, respectively. Treatment with 30% or 60% CaCl2 resulted in azoospermia in 100% of dogs, but more side effects were observed, while no side effects were noticed at lower doses. For each treatment group, testosterone levels had decreased an average of 35%-70% at 6 months following treatment. However, testosterone levels rebounded by the 12-month time point in all groups except the highest dosage group (60% CaCl2), which remained at the low end of physiological range throughout the study. Sperm motility dropped to zero or near zero in all dogs treated with CaCl2. Testicular size was significantly smaller at 12 months PI for all groups when compared to baseline. CONCLUSIONS: This first long-term study confirms reports of the efficacy of CaCl2 sterilization. However, at dosages free of adverse events, calcium chloride in saline may not provide permanent sterilization as previously believed. Future work should explore optimized solvents to increase the permanence of the well-tolerated 20% formulation.