1.  Peer Reviewed Title: Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Author: Lue Y; Wang C; Cui Y; Wang X; Sha J; Zhou Z; Xu J; Wang C; Hikim AP; Swerdloff RS Source: Biology of Reproduction. 2009 Mar;80(3):484-92. Abstract: Prior studies have demonstrated that combined treatment of testosterone with a progestin induces a more rapid and greater suppression of spermatogenesis than testosterone treatment alone. We hypothesized that the suppressive effects of the combination of testosterone undecanoate (TU) injections plus oral levonorgestrel (LNG) on spermatogenesis may be mediated through a greater perturbation of testicular gene expression than TU alone. To test this hypothesis, we performed open testicular biopsy on 12 different adult healthy subjects: 1) four healthy men as controls; 2) four men 2 wk after TU treatment; and 3) four men 2 wk after TU + LNG administration. RNA isolated from biopsies was used for DNA microarray using the Affymetrix Human Genome U133 Plus 2.0 oligonucleotide microarrays. Gene expression with >or=2-fold changes (P < 0.05) compared with control was analyzed using the National Institutes of Health Database for Annotation, Visualization, and Integrated Discovery 2008 resource. The TU treatment altered the gene expression in 109 transcripts, whereas TU + LNG altered the gene expression in 207 transcripts compared with control. Both TU and TU + LNG administration suppressed gene expression of insulin-like 3; cytochrome P450, family 17, subfamily A1 in Leydig cells; and inhibin alpha in Sertoli cells; they increased proapoptotic transcripts BCL2-like 14, insulin-like growth factor-binding protein 3; and they decreased X-linked inhibitor of apoptosis protein. In comparison with TU treatment alone, TU + LNG treatment upregulated insulin-like 6 and relaxin 1, and downregulated RNA-binding protein transcripts. We conclude that TU + LNG administration induces more changes in testicular gene expression than TU alone. This exploratory study provided a novel and valuable database to study the mechanisms of action of hormonal regulation of spermatogenesis in men and identified testicular-specific molecules that may serve as potential targets for male contraceptive development. Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | MEN | MALE CONTRACEPTION | PROGESTERONE | SPERMATOGENESIS | TESTIS | TESTOSTERONE | CONTRACEPTION RESEARCH | LEVONORGESTREL | Developed Countries | North America | Americas | Demographic Factors | Population | Contraception | Family Planning | Progestational Hormones | Hormones | Endocrine System | Physiology | Biology | Reproduction | Genitalia, Male | Genitalia | Urogenital System | Androgens | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents Document Number: 341724 |
| 2. Peer Reviewed Title: Male contraception: what is on the horizon? Author: Blithe D Source: Contraception. 2008 Oct;78(4 Suppl 1):S23-S27. Abstract: Male contraception remains an important area of research. Methods can inhibit sperm production or can be targeted to inhibit sperm functions such as motility, orientation or interaction with the egg. Hormonal methods appear to be safe and effective in proof of concept studies but efforts are underway to improve delivery options or lead time until full efficacy is achieved. Nonhormonal methods are based on numerous targets that impact sperm production or function. Several agents that inhibit the sperm-specific or testis-specific targets have been identified and studies in animals have shown promising results. (author's) Language: English Keywords: GLOBAL | MALE CONTRACEPTION | CONTRACEPTIVE AGENTS, MALE | SPERMATOGENESIS | OBSTACLES | CONTRACEPTION RESEARCH | Contraception | Family Planning | Contraceptive Agents | Reproduction | Organization and Administration Document Number: 328204 |
| 3. Peer Reviewed Title: Approaches to the identification of new nonhormonal targets for male contraception. Author: Kopf GS Source: Contraception. 2008 Oct;78(4 Suppl 1):S18-S22. Abstract: Fertility control is a global health issue with major personal and societal impact. Although, currently, there are several different options for contraception, the technologies behind these are antiquated, and the options for male-based contraception (i.e., withdrawal, condom and vasectomy) are inadequate. The genomic, proteomic and bioinformatic revolutions have provided new tools and new targets for contraceptive development, and the results of such approaches have identified gene products that play critical roles in male reproduction, thus expanding the array of potential targets for novel and innovative male-based contraceptives. This article will review the types of targets being considered in the development of nonhormonal male contraceptives and the technologies used to identify and validate these targets. (author's) Language: English Keywords: GLOBAL | LITERATURE REVIEW | MALE CONTRACEPTION | CONTRACEPTION RESEARCH | RESEARCH AND DEVELOPMENT | SPERMATOGENESIS | GENETIC TECHNIQUES | Contraception | Family Planning | Technology | Economic Factors | Reproduction | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health Document Number: 328205 |
| 4. Peer Reviewed Title: Male hormonal contraception: so near and yet so far [editorial] Author: Liu PY; McLachlan RI Source: Journal of Clinical Endocrinology and Metabolism. 2008 Jul;93(7):2474-2476. Abstract: Finding a life partner and starting a family are near-universal human desires. Fulfilling these expectations requires effective planning because child rearing imposes major life demands; consequently, fertile couples practice family planning to avoid unintended pregnancies and space and limit desired pregnancies to best fit their personal desires and financial resources. For these reasons, broadening contraceptive choice to allow men and women the option to share family planning responsibilities satisfies important individual and societal needs. To this end, generating male-directed contraceptive methods, vasectomy and condoms, is an important objective because the two currently available methods are not widely acceptable because vasectomy is not easily reversible, whereas condoms have limited user efficacy. (excerpt) Language: English Keywords: GLOBAL | CRITIQUE | MALE CONTRACEPTION | DRUGS | CONTRACEPTIVE AGENTS, MALE | ADMINISTRATION AND DOSAGE | CONTRACEPTIVE AGENTS, SIDE EFFECTS | SPERMATOGENESIS | TESTOSTERONE | DESOGESTREL | Contraception | Family Planning | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraceptive Agents | Reproduction | Androgens | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female Document Number: 328308 |
5.  Title: Screening of "y" chromosome microdeletions in Iranian infertile males. Author: Malekasgar AM; Mombaini H Source: Journal of Human Reproductive Sciences. 2008 Jan-Jun;1(1):2-9. Abstract: It has been hypothesized that microdeletions of Yq may account for a significant proportion of men with infertility. Three nonoverlapping regions, referred to as "azoospermia factors" (AZFa, b, c from proximal to distal Yq) have been defined as spermatogenesis loci and deletions in these regions have been shown to be pathogenically involved in male fertility associated with azoospermia or severe oligospermia. The aim was the evaluation the frequency of Y chromosome microdeletions in Iranian population. Fifty infertile men were selected. Semen analysis was done and on the basis of the mean sperm count, all patients were categorized into azoospermia and oligozoospermia, groups. Blood samples were obtained for DNA extraction and chromosomal analysis. Genomic DNA was extracted from blood lymphocytes and amplified by sequence tagged sites-polymerase chain reaction (STS-PCR) method to determine the presence of microdeletions in AZF locus. A total of 34 STS primers including two controls were selected toidentify microdeletions of Y chromosome on each subject. 26/50 cases (52%) showed deletion of at least one of the STS Marker. Totally 41 microdeletions was observed. A total of 17 cases (34%) had deletion in one STS. Four Oligospermia cases (8%) had deletion in 2 STS site. Three azoospermia cases (6%) had again deletion in 2 STS site, but in different STS. One case had three deletions in three STS site and finally one individual had seven deletions in AZF locus. The overall frequency of Y chromosome microdeletions observed in the present study was found to be 26/50 (52%). Comparison of our data with the result of other investigators world wide shows that the incidence of Yq microdeletions in Iranian population is much higher than international frequency. Our data agree with other studies regarding microdeletions of AZFc, but for microdeletions of AZFa (14.6%) our results is much higher and differ significantly with many studies. (author's) Language: English Keywords: IRAN | RESEARCH REPORT | CLINICAL RESEARCH | GENETIC TECHNIQUES | MEN | INFERTILITY | CHROMOSOME ABNORMALITIES | SPERMATOGENESIS | SPERM COUNT | SPERMATOZOA | Developing Countries | Middle East | Research Methodology | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Demographic Factors | Population | Reproduction | Neonatal Diseases and Abnormalities | Diseases | Laboratory Procedures | Germ Cells | Genitalia | Urogenital System | Physiology | Biology Document Number: 325574 |
| 6. Title: Advances in male contraception. Author: Page ST; Amory JK; Bremner WJ Source: Endocrine Reviews. 2008;:[59] p. Abstract: Despite significant advances in contraceptive options for women over the last 50 years, world population continues to grow rapidly. Scientists and activists alike point to the devastating environmental impacts that population pressures have caused including global warming from the developed world and hunger and disease in less developed areas. Moreover, almost of half of all pregnancies are still unwanted or unplanned. Clearly, there is a need for expanded, reversible, contraceptive options. Multicultural surveys demonstrate men's willingness to participate in contraception, and their female partners to trust them to do so. Notwithstanding their paucity of options, male methods including vasectomy and condoms account for almost a third of contraceptive use in the United States and other countries. Recent, international, clinical research efforts have demonstrated high efficacy rates (90-95%) for hormonally-based male contraceptives. Current barriers to expanded use include limited delivery methodsand perceived regulatory obstacles, stymieing introduction to the marketplace. However, advances in oral and injectable androgen delivery are cause for optimism that these hurdles may be overcome. Non-hormonal methods, such as compounds that target sperm motility, are attractive in their theoretical promise of specificity for the reproductive tract. Gene and protein array technologies continue to identify potential targets for this approach. Such non-hormonal agents will likely reach clinical trials in the near future. Great strides have been made in understanding male reproductive physiology; the combined efforts of scientists, clinicians, industry and governmental funding agencies could make an effective, reversible, male contraceptive an option for family planning over the next decade. (author's) Language: English Keywords: GLOBAL | RESEARCH REPORT | LITERATURE REVIEW | MALE CONTRACEPTION | RESEARCH AND DEVELOPMENT | SPERMATOGENESIS | CONTRACEPTIVE AGENTS, MALE | TESTOSTERONE | CONTRACEPTIVE EFFECTIVENESS | CONTRACEPTIVE SAFETY | CONTRACEPTIVE AGENTS, SIDE EFFECTS | Contraception | Family Planning | Technology | Economic Factors | Reproduction | Contraceptive Agents | Androgens | Hormones | Endocrine System | Physiology | Biology | Safety | Public Health | Health Document Number: 326425 |
| 7. Title: Effects of environmental and occupational pesticide exposure on human sperm: A systematic review. Author: Perry MJ Source: Human Reproduction Update. 2008 May-Jun;14(3):233-242. Abstract: Relatively recent discoveries of the hormone disrupting properties of some pesticides have raised interest in how contemporary pesticide exposures, which primarily take the form of low level environmental or occupational exposures, impact spermatogenesis. The objective of the present review was to summarize results to date of studies examining pesticide effects on human sperm. Outcomes evaluated included sperm parameters, DNA damage and numerical chromosome aberrations (aneuploidy (disomy, nullisomy) or diploidy). Studies investigating sperm in men environmentally and/or occupationally exposed to any types of pesticides were included in the review. The targeted literature search over the last 15 years showed a range of pesticide classes have been investigated including pyrethroids, organophosphates, phenoxyacetic acids, carbamates, organochlorines and pesticide mixtures. None of the studies involved acute exposure events such as chemical accidents. There were 20 studies evaluating semen quality, of which 13 studies reported an association between exposure and semen quality; 6 studies evaluating DNA damage, of which 3 reported an association with exposure; and 6 studies assessing sperm aneuploidy or diploidy, of which 4 reported an association with exposure. Studies varied widely in methods, exposures and outcomes. Although suggestive for semen parameters, the epidemiologic evidence accumulated thus far remains equivocal as to the spermatotoxic and aneugenic potential of pesticides given the small number of published studies. This question warrants more investigation and suggestions for future studies are outlined. (author's) Language: English Keywords: GLOBAL | RESEARCH REPORT | LITERATURE REVIEW | SEMEN | SPERMATOZOA | SPERMATOGENESIS | HEALTH | ENVIRONMENT | PESTICIDES | EXPOSURE | OCCUPATIONAL HEALTH | CHROMOSOME ABNORMALITIES | Seminal Vesicles | Genitalia, Male | Genitalia | Urogenital System | Physiology | Biology | Germ Cells | Reproduction | Ingredients and Chemicals | Risk Factors | Neonatal Diseases and Abnormalities | Diseases Document Number: 325850 |
| 8. Title: Human exposure to endocrine disrupters and semen quality. Author: Phillips KP; Tanphaichitr N Source: Journal of Toxicology and Environmental Health, Part B. 2008 Mar;11(3-4):188-220. Abstract: Reproductive pathology in the male represents about 20% of infertility cases. Male infertility may be attributed to a number of causes, including genetic and congenital abnormalities, infection, multisystemic diseases, varicocele, and others; however, a significant number of cases are idiopathic. Global declines in semen quality were suggested to be associated with enhanced exposure to environmental chemicals that act as endocrine disrupters as a result of our increased use of pesticides, plastics, and other anthropogenic materials. A significant body of toxicology data based upon laboratory and wildlife animals studies suggests that exposure to certain endocrine disrupters is associated with reproductive toxicity, including (1) abnormalities of the male reproductive tract (cryptorchidism, hypospadias), (2) reduced semen quality, and (3) impaired fertility in the adult. There is, however, a relative paucity of studies designed to measure exposure to endocrine disrupters on semen quality parameters(sperm concentration, motility, morphology). An overview of the human semen quality literature is presented that examines the role of endocrine disrupters including organochlorines (OC), dioxins, phthalates, phytoestrogens, and chemical mixtures (pesticides and tobacco smoke). (author's) Language: English Keywords: GLOBAL | RESEARCH REPORT | LITERATURE REVIEW | MEN | INFERTILITY | SEMEN | EXPOSURE | TOXICITY | ENDOCRINE EFFECTS | SPERMATOGENESIS | Demographic Factors | Population | Reproduction | Seminal Vesicles | Genitalia, Male | Genitalia | Urogenital System | Physiology | Biology | Risk Factors | Endocrine System Document Number: 326098 |
| 9. Title: Cigarette smoking and reproductive function. Author: Soares SR; Melo MA Source: Current Opinion in Obstetrics and Gynecology. 2008 Jun;20(3):281-291. Abstract: The purpose of review was to perform a systematic review of the literature on the relationship between cigarette smoking and reproductive function. Whenever possible, this review is focused on the most recently published studies (mainly the past 2 years). Nevertheless, in many instances older literature was too relevant not to be taken into account. Tobacco compounds exert a deleterious effect on the process of ovarian follicle maturation. This effect is expressed by worse in-vitro fertilization parameters in cycles performed on women with smoking habits. Also, uterine receptiveness is significantly altered by the smoking habit. In men, cigarette smoking reduces sperm production, increases oxidative stress, and DNA damage. Spermatozoa from smokers have reduced fertilizing capacity, and embryos display lower implantation rates. Even in-utero exposition to tobacco constituents leads to reduced sperm count in adult life. A strong body of evidence indicates that the negative effect of cigarette smoking on fertility comprises fairly every system involved in the reproductive process. Couples in reproductive age should be strongly discouraged to smoke. (author's) Language: English Keywords: GLOBAL | RESEARCH REPORT | LITERATURE REVIEW | TOBACCO USE | REPRODUCTIVE HEALTH | OVARIAN EFFECTS | SPERMATOGENESIS | SPERMATOGENESIS BLOCKING AGENTS | FERTILITY DETERMINANTS | Behavior | Health | Ovary | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology | Reproduction | Contraceptive Agents, Male | Contraceptive Agents | Contraception | Family Planning | Fertility | Population Dynamics | Demographic Factors | Population Document Number: 326577 |
| 10. Title: Mutation screening and association study of the TSSK4 gene in Chinese infertile men with impaired spermatogenesis. Author: Su D; Zhang W; Yang Y; Deng Y; Ma Y Source: Journal of Andrology. 2008 Jul-Aug;29(4):374-378. Abstract: The testis-specific serine/threonine kinase (TSSK) family is a specific kinase group with exclusive or dominant expression in testis and involvement in spermatogenesis and male infertility. TSSK4 is a newly identified member of the TSSK family. In order to investigate the possible relationships between variations, including mutations and polymorphisms of the TSSK4 gene and impaired spermatogenesis in humans, mutation screening of this gene in 372 patients with azoospermia or severe oligospermia and 220 controls was performed. In total, 4 novel single nucleotide changes including c.679G>A, c.987+108G>A, c.-155C>G and c.765C>A were discovered. The latter 2 variations were found only in patients, not in controls. Bioinformatics analysis suggested that allele A of c.765C>A could decrease the activity of pre-mRNA splicing of TSSK4. The frequency of allele A of c.679G>A was significantly higher in controls than in patients. On the contrary, allele A of c.987+108G>A was remarkably increased in patients compared with controls. Our investigation of TSSK4, a potentially important testicular gene, in Chinese infertile and control men identified the association of some single nucleotide polymorphisms in this gene with male infertility. (author's) Language: English Keywords: CHINA | RESEARCH REPORT | DATA ANALYSIS | MEN | INFERTILITY | SPERMATOGENESIS | SCREENING | GENETICS | LABORATORY PROCEDURES | Asia, Eastern | Asia | Developing Countries | Research Methodology | Demographic Factors | Population | Reproduction | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Biology | Laboratory Examinations and Diagnoses Document Number: 327340 |
| 11. Title: Evidence that chronic hypoxia causes reversible impairment on male fertility. Author: Verratti V; Berardinelli F; Di Giulio C; Bosco G; Cacchio M Source: Asian Journal of Andrology. 2008 Jul;10(4):602-606. Abstract: Aim: To evaluate the effect of chronic hypoxia on human spermatogenic parameters and their recovery time. Methods: Seminological parameters of six male healthy mountain trekkers were evaluated in normoxia at sea level. After 26 days exposure to altitude (ranging from 2 000 m to 5 600 m, Karakorum Expedition) the same parameters were again evaluated after returning to sea level. These parameters were once again evaluated after 1 month and then again after 6 months. Results: Sperm count was found to be lower immediately after returning to sea level (P = 0.0004) and again after a month (P = 0.0008). Normal levels were reached after 6 months. Spermatic motility (%) shows no reduction immediately after returning to sea level (P = 0.0583), whereas after 1 month this reduction was significant (P = 0.0066). After 6 months there was a recovery to pre-hypoxic exposure values. Abnormal or immature spermatozoa (%) increased immediately after returning to sea level (P = 0.0067) and then again after 1 month (P = 0.0004). After 6 months there was a complete recovery to initial values. The total number of motile sperm in the ejaculate was found to be lower immediately after returning to sea level (P = 0.0024) and then again after 1 month (P = 0.0021). After 6 months there was a recovery to pre-hypoxic exposure values. Conclusion: Chronic hypoxia induces a state of oligospermia and the normalization of such seminological parameters at the restoration of previous normoxic conditions after 6 months indicate the influence of oxygen supply in physiological mechanisms of spermatogenesis and male fertility. (author's) Language: English Keywords: ITALY | RESEARCH REPORT | CLINICAL RESEARCH | MEN | REVERSIBLE STERILIZATION | SPERMATOGENESIS | ALTITUDE | OXYGEN | SPERM COUNT | MALE CONTRACEPTION | TIME FACTORS | SPERM IMMOBILIZING AGENTS | Developed Countries | Europe, Southern | Europe | Research Methodology | Demographic Factors | Population | Sterilization, Sexual | Family Planning | Reproduction | Environment | Inorganic Chemicals | Ingredients and Chemicals | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraception | Population Dynamics | Spermicidal Contraceptive Agents | Contraceptive Agents Document Number: 327405 |
| 12. Peer Reviewed Title: Prolactinoma presenting as a failed vasectomy reversal. Author: Templeton AW; Pobi KK; Turco J; Nangia AK Source: Fertility and Sterility. 2007 Nov;88(5):1438.e3-1438.e5. Abstract: The objective was to present a case of prolactinoma presenting as a failed vasectomy reversal. A case report was used for the design of the study. The setting was a University-affiliated teaching hospital. A 46-year-old male with severe oligospermia after bilateral vasovasostomy and his 31-year-old female partner who had normal cycles were the patients examined. The interventions were bromocriptine, carbegoline, and l IVF. The main outcome measures were correction of hyperprolactinoma, improved semen analysis, and pregnancy achieved by assisted reproductive technologies. Semen analysis showing low volume (0.65 mL) and severe oligospermia (16 sperm) with zero motility on presentation. Endocrine evaluation showed prolactin of 650 ng/mL, T 0.37 ng/mL, and FSH 2.0 mIU/mL. A head CT scan showed a 1.2 cm pituitary adenoma. This was managed initially with bromocriptine, but due to side effects he was switched to carbegoline. In 1 month his PRL decreased to 16.9 ng/mL. Testosterone and FSH normalized. Repeat semen analysis after 5 months showed a volume of 4.5 mL and a concentration of 15 million/ mL with 1% motility. Antisperm antibodies were positive. Because of antisperm antibodies and oligoasthenospermia, intracytoplasmic sperm injection with ejaculated sperm and, later, testicular extraction, were attempted without success. Donor sperm was eventually used. This is the first reported case of prolactinoma as a cause of infertility after vas reversal and demonstrates that not all cases of suspected failed vasectomy reversals are due to recurrent obstruction. (author's) Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | MEN | EXAMINATIONS AND DIAGNOSES | SPERMATOGENESIS | PROLACTIN ANALYSIS | VASECTOMY | STERILIZATION REVERSAL | PITUITARY GLAND | NEOPLASMS | INFERTILITY | Developed Countries | North America | Americas | Demographic Factors | Population | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Reproduction | Prolactin | Pituitary Hormones | Hormones | Endocrine System | Physiology | Biology | Male Sterilization | Sterilization, Sexual | Family Planning | Reversible Sterilization | Diseases Document Number: 322120 |
| 13. Title: Drug insight: recent advances in male hormonal contraception. Author: Amory JK; Page ST; Bremner WJ Source: Nature Clinical Practice. Endocrinology and Metabolism. 2006 Jan;2(1):32-41. Abstract: As there are limitations to current methods of male contraception, research has been undertaken to develop hormonal contraceptives for men, analogous to the methods for women based on estrogen and progestogens. When testosterone is administered to a man, it functions as a contraceptive by suppressing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. Since these hormones are the main stimulatory signals for spermatogenesis, low levels of LH and FSH markedly impair sperm production. After 3--4 months of testosterone treatment, 60--70% of men no longer have sperm in their ejaculate, and most other men exhibit markedly diminished sperm counts. Male hormonal contraception is well tolerated, free of serious adverse side effects, and 95% effective in the prevention of pregnancy. Importantly, male hormonal contraception is reversible, with sperm counts usually recovering within 4 months of the discontinuation of hormone treatment. Because exogenous testosterone administration alone does not completely suppress sperm production in all men, researchers have combined testosterone with second agents, such as progestogens or gonadotropin-releasing-hormone antagonists, to further suppress secretion of LH and FSH and improve suppression of spermatogenesis. Recent trials have used combinations of long-acting injectable or implantable forms of testosterone with progestogens, which can be administered orally, by injection or by a long-acting implant. Such combinations suppress spermatogenesis to zero without severe side effects in 80--90% of men, with near-complete suppression in the remainder of individuals. One of these testosterone and progestogen combination regimens might soon bring the promise of male hormonal contraception to fruition. (author's) Language: English Keywords: UNITED STATES OF AMERICA | LITERATURE REVIEW | MALE CONTRACEPTION | SPERM COUNT | HORMONES | SPERMATOGENESIS | PROGESTERONE | FERTILITY DECLINE | North America | Americas | Developed Countries | Contraception | Family Planning | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Endocrine System | Physiology | Biology | Reproduction | Progestational Hormones | Fertility Changes | Fertility | Population Dynamics | Demographic Factors | Population Document Number: 309792 |
| 14. Title: [Varicocele (concepts and generalities)] Varicocele (conceptos y generalidades). Author: Esquivel Vindas LF; Rivas Rauda F Source: Revista Medica de Costa Rica y Centroamerica. 2006 Jul-Sep;63(576):99-104. Abstract: A varicocele is a dilatation of the testicular vein and the pampiniform venous plexus within the spermatic cord. They may be detected in 20% of the men population, left-sided lesions predominate and is the most common cause of infertility. Studies have shown that varicocele causes progressive duration-dependent injury to the seminiferous epithelium and testicular function over time. Is associated with testicular hypotrophy, an abnormal gonadotropin axis, histologic changes, abnormal spermatogeneses, and infertility. Alteration of testicular temperature is the most widely pathophysiologic mechanism for the alteration of testicular function secondary to varicocele. The diagnosis is generally made by physical examination, but we can use too the high-resolution color-flow Doppler ultrasonography, venography, thermography, MRI or Scintigraphy. The most common complications from varicocelectomy are hydrocele, varicocele recurrence, and testicular artery injury. The incidence of these complications can be reduced with the microsurgical inguinal or subinguinal approach. Overall, varicecelectomy results in significantly improved semen parameters in 60% to 80% of men and pregnancy rates of 20% to 60%. (author's) Language: Spanish Keywords: LITERATURE REVIEW | CLINICAL RESEARCH | MEN | TESTIS | INFERTILITY | PHYSICAL EXAMINATIONS AND DIAGNOSES | ULTRASONICS | HISTOCHEMICAL EFFECTS | SPERMATOGENESIS | COMPLICATIONS | MALE UROLOGIC SURGERY | BODY TEMPERATURE | VASCULAR DISEASES | SEMEN | Research Methodology | Demographic Factors | Population | Genitalia, Male | Genitalia | Urogenital System | Physiology | Biology | Reproduction | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Cytologic Effects | Diseases | Urogenital Surgery | Surgery | Treatment | Seminal Vesicles Document Number: 308808 |
| 15. Peer Reviewed Title: Identification of ten novel genes involved in human spermatogenesis by microarray analysis of testicular tissue. Author: Lin YH; Lin YM; Teng YN; Hsieh TY; Lin YS Source: Fertility and Sterility. 2006 Dec;86(6):1650-1658. Abstract: The objective was to identify novel genes that are down-regulated in the testicular tissue of infertile men. Design: Prospective study. Setting: University-based reproductive clinics and genetics laboratory. Patients: Nine patients with normal spermatogenesis, and 15 patients with maturation arrest (MA) or Sertoli cell-only syndrome (SCOS). Intervention: Testicular samples of patients with the same histology were pooled for complementary DNA (cDNA) microarray analysis. Main Outcome Measure: Novel, down-regulated genes. In total, 300 genes were significantly down-regulated in SCOS or MA samples, and 10 novel sterility-related genes were identified. Of the 10 novel genes, 6 genes (Hs.126780, Hs.553658, Hs.274135, Hs.268122, Hs.531701, and Hs.171130) encode proteins with predictable functional domains, and all these functional domains are believed to correlate with spermatogenesis and/or spermiogenesis. Conversely, the other 4 genes (Hs.351582, Hs.407480, Hs.552781, and Hs.355570) do not encompass known functional domains. Two genes (Hs.407480 and Hs.552781) lack mouse orthologues. Most novel genes showed a testis-specific expression pattern in both mice and humans. Reverse transcription-polymerase chain reaction (RT-PCR) showed three distinct types of developmental stage-dependent expressions of message ribonucleic acid (mRNA) for these novel genes in murine testes. These 10 novel genes provide targets to elucidate novel pathways involved in human spermatogenesis. (author's) Language: English Keywords: TAIWAN | RESEARCH REPORT | PROSPECTIVE STUDIES | GENETIC TECHNIQUES | MEN | SPERMATOGENESIS | INFERTILITY | TESTIS | LABORATORY PROCEDURES | Asia, Eastern | Asia | Developed Countries | Studies | Research Methodology | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Demographic Factors | Population | Reproduction | Genitalia, Male | Genitalia | Urogenital System | Physiology | Biology Document Number: 310575 |
| 16. Peer Reviewed Title: Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Author: Liu PY; Swerdloff RS; Christenson PD; Handelsman DJ; Wang C Source: Lancet. 2006 Apr 29;367(9520):1412-1420. Abstract: Hormonal methods for safe, reliable, and reversible contraception based on the suppression of spermatogenesis could soon become available. We have investigated the rate, extent, and predictors of reversibility of hormonal male contraception. We undertook an integrated multivariate time-to-event analysis of data from individual participants in 30 studies published in 1990-2005, in which sperm output was monitored every month until recovery. The primary outcome was the time for the sperm concentration to recover to a threshold of 20 million per mL, an indicator of fertility. We undertook univariate and multivariate analyses, using Kaplan-Meier and Cox's methods. 1549 healthy eugonadal men who were white (n=965), Asian (almost all Chinese men; n=535), or of other origins (n=49) and aged 18-51 years underwent 1283.5 man-years of treatment and 705 man-years of post-treatment recovery. These data represented about 90% of all published data from individuals using androgen or androgenprogestagen regimens. The median times for sperm to recover to thresholds of 20, 10, and 3 million per mL were 3.4 months (95% CI 3.2-3.5), 3.0 months (2.9-3.1), and 2.5 months (2.4-2.7), respectively. Multivariate Cox's analysis showed higher rates of recovery with older age, Asian origin, shorter treatment duration, shorter-acting testosterone preparations, higher sperm concentrations at baseline, faster suppression of spermatogenesis, and lower blood concentrations of luteinising hormone at baseline. The typical probability of recovery to 20 million per mL was 67% (61-72) within 6 months, 90% (85-93) within 12 months, 96% (92-98) within 16 months, and 100% within 24 months. Hormonal male contraceptive regimens show full reversibility within a predictable time course. Various covariables affect the rate but not the extent of recovery, although their effect sizes are minor. These data are crucial for the further safe and practical development of such regimens. (author's) Language: English Keywords: RESEARCH REPORT | CLINICAL RESEARCH | MULTIVARIATE ANALYSIS | MEN | CONTRACEPTIVE AGENTS, MALE | SPERMATOGENESIS | SPERMATOGENESIS BLOCKING AGENTS | ANDROGENS | CONTRACEPTIVE AGENTS, PROGESTIN | TIME FACTORS | CONTRACEPTIVE EFFECTIVENESS | LUTEINIZING HORMONE | STERILIZATION REVERSAL | Research Methodology | Data Analysis | Demographic Factors | Population | Contraceptive Agents | Contraception | Family Planning | Reproduction | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Female | Population Dynamics | Gonadotropins, Pituitary | Gonadotropins | Reversible Sterilization | Sterilization, Sexual Document Number: 299578 |
| 17. Title: Cytogenetic analysis of azoospermic patients: karyotype comparison of peripheral blood lymphocytes and testicular tissue. Author: Stipoljev F; Vujisic S; Parazajder J; Hafner D; Jezek D Source: European Journal of Obstetrics, Gynecology and Reproductive Biology. 2006 Feb 1;124(2):197-203. Abstract: The objective was to compare the results of a complete chromosomal, genetic and histological investigation in 13 azoospermic men with the results of the intracytoplasmic sperm injection (ICSI) procedure. Peripheral blood samples were used for the measurement of follicle-stimulating hormone (FSH) levels, chromosomal analysis, microdeletions in the azoospermia factor (AZF) region of the Y chromosome and cystic fibrosis transmembrane conductance regulator (CFTR) mutation analysis. Testicular tissue was used for histological scoring and cytogenetic evaluation. Peripheral blood cytogenetic analysis revealed a normal male karyotype in all cases. Chromosomal analysis from testicular tissue revealed a mosaicism for the terminal deletion of chromosome 22 with a breakpoint site at 22q13 in one patient with congenital bilateral absence of the vas deferens (CBAVD). Deletions in the AZFa, ATFb, and AZFc regions were not detected. The CFTR mutational analysis showed normal results in all patients. Cytogenetic evaluation of testicular tissue should be performed in non-obstructive and obstructive azoospermic patients as well as in patients with multiple failed IVF and recurrent spontaneous abortion. (author's) Language: English Keywords: CROATIA | RESEARCH REPORT | CLINICAL RESEARCH | MEN | INFERTILITY | CHROMOSOME ABNORMALITIES | SPERMATOGENESIS | TESTIS | EXAMINATIONS AND DIAGNOSES | CYTOLOGY | Developing Countries | Europe, Southeastern | Europe | Research Methodology | Demographic Factors | Population | Reproduction | Neonatal Diseases and Abnormalities | Diseases | Genitalia, Male | Genitalia | Urogenital System | Physiology | Biology | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health Document Number: 296807 |
| 18. Title: Hormonal approaches to male contraception: approaching reality. Author: Wu FC Source: Molecular and Cellular Endocrinology. 2006 May 16;250(1-2):2-7. Abstract: The 'pre-testicular' suppression of gonadotrophins is the most likely approach for reversible therapeutic male fertility control to reach imminent clinical application. Maintenance of spermatogenesis depends on adequate gonadotrophin and intratesticular testosterone concentrations. Hormonal contraception for men interrupts this physiological axis by various means of gonadotrophin suppression; this interferes with spermatogonial differentiation and meiosis entry resulting in reversible azoospermia or severe oligozoospermia in virtually all men. Clinical trials have confirmed that high contraceptive efficacy, similar to female hormonal contraceptives, can be reliably attained with few side effects. However, the simultaneous suppression of Leydig cell steroidogenesis mandates the requirement for testosterone replacement in hormonal male contraception. Combination regimens of new synthetic progestins and androgens at various stages of development are being investigated with the lead products poised to go into phase III trials. Heterogeneity in response to spermatogenesis suppression has been observed within and between population; the mechanisms are unclear. This new method of reversible and effective contraception has registered high acceptability in surveys of both men and women. The recent entry of pharmaceutical companies into this area of research and development has considerably enhanced the prospects of translating years of academic efforts into new products which provide added family planning choice for many couples. (author's) Language: English Keywords: UNITED KINGDOM | RESEARCH REPORT | CLINICAL TRIALS | CONTRACEPTION | ANDROGENS | TESTOSTERONE | LOW-DOSE PROGESTINS | SPERMATOGENESIS | Europe, Western | Europe | Developed Countries | Clinical Research | Research Methodology | Family Planning | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Reproduction Document Number: 306370 |
| 19. Title: The common variant N372H in BRCA2 gene may be associated with idiopathic male infertility with azoospermia or severe oligozoospermia. Author: Zhoucun A; Zhang S; Yang Y; Ma Y; Zhang W Source: European Journal of Obstetrics, Gynecology and Reproductive Biology. 2006;124:61-64. Abstract: The objective was to explore the possible association between the common single nucleotide polymorphism N372H in human breast cancer susceptibility gene 2 (BRCA2) and the idiopathic male infertility with azoospermia or severe oligozoospermia. The study included 240 infertile patients with idiopathic azoospermia or severe oligozoospermia and 250 fathered controls. The allele and genotype frequencies of the polymorphism N372H in BRCA2 gene were investigated in both patients and controls using denaturing high performance liquid chromatography analysis (DHPLC). The frequency of allele H of the polymorphism N372H in patients was significantly higher than that of the controls (23.5% versus 17.6%, OR = 1.49, 95% CI 1.06-1.97, P = 0.02) and the subjects bearing rare allele H (NH + HH) significantly increased in patients compared with controls (41.7% versus 32.4%, 95% CI 1.03-2.15, P = 0.03). The results of this study suggested that the polymorphism N372H in BRCA2 gene may be associated with idiopathic male infertility with azoospermia or severe oligozoospermia. (author's) Language: English Keywords: CHINA | RESEARCH REPORT | MEN | INFERTILITY | GENETICS | CHROMOSOME ABNORMALITIES | RISK FACTORS | SPERMATOGENESIS | SPERMATOZOA | Developing Countries | Asia, Eastern | Asia | Demographic Factors | Population | Reproduction | Biology | Neonatal Diseases and Abnormalities | Diseases | Germ Cells | Genitalia | Urogenital System | Physiology Document Number: 293392 |
| 20. Title: Intramuscular testosterone enanthate plus very low dosage oral levonorgestrel suppresses spermatogenesis without causing weight gain in normal young men: a randomized clinical trial. Author: Anawalt BD; Amory JK; Herbst KL; Coviello AD; Page ST Source: Journal of Andrology. 2005 May-Jun;26(3):405-413. Abstract: The development of a safe, well-tolerated, effective, and reversible male hormonal contraceptive would be a major clinical advance for couples planning their family size and for control of population growth. High-dosage parenteral testosterone (T) esters alone or in combination with a progestogen (eg, depot medroxyprogesterone) have been shown to confer effective and reversible male contraception in clinical trials, but these regimens are associated with weight gain and suppression of serum high-density lipoprotein cholesterol (HDL) levels. We have previously demonstrated that intramuscular T enanthate 100 mg weekly plus oral levonorgestrel (LNG) 125, 250, or 500 µg daily suppresses spermatogenesis to levels associated with effective contraception, but there is a LNG–dosage-dependent effect of weight gain and HDL suppression. We hypothesized that intramuscular T enanthate 100 mg weekly plus a very low dosage of oral LNG would effectively suppress spermatogenesis in normal men without inducing weight gain or HDL suppression. We conducted a randomized trial comparing 6 months of intramuscular T enanthate (100 mg weekly) plus 31.25 µg of oral LNG daily (T+LNG 31; n = 20) or 62.5 µg of oral LNG daily (T+LNG 62; n = 21). The 2 regimens were equally effective in suppressing spermatogenesis to azoospermia, fewer than 1 million sperm/mL and fewer than 3 million sperm/mL (T+LNG 31 [60%, 85%, and 90%] vs T+LNG 62 [62%, 91%, and 95%] for azoospermia, fewer than 1 million and fewer than 3 million, respectively; P = NS). The T+LNG 31 group did not gain weight (0.25 ± 1.08 kg; P = NS compared with baseline), but the T+LNG 62 group gained 2.5 ± 0.77 kg (P < .05 compared with baseline). Serum HDL cholesterol levels declined significantly in both groups (percentage decline month 6 of treatment vs baseline: 12.0% ± 2.6% and 15.1% ± 3.0%; P < .05 for T+LNG 31 and 62 respectively). Serum low-density lipoprotein cholesterol levels also declined in both groups (percentage decline month 6 of treatment vs baseline: 6.9 ± 3.9 and 6.0% ± 4.1%; P < .05 for T+LNG 31 and P = NS for T+LNG 62). There were no clinically significant adverse events or significant changes in hematology or chemistry profiles in either group during the study. We conclude that 1) intramuscular T plus oral LNG has a very potent synergistic effect in suppressing spermatogenesis at LNG dosages equal to or lower than dosages used in common female oral contraceptive regimens and 2) large, long- term contraceptive efficacy trials should be conducted with a variety of androgenprogestogen combinations including long-acting T formulations such as depot T pellets or intramuscular T undecanoate plus depot LNG or very low dosage oral LNG. (author's) Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | CLINICAL TRIALS | MALE CONTRACEPTION | GONADOTROPINS | TESTOSTERONE | SPERMATOGENESIS | North America | Americas | Developed Countries | Clinical Research | Research Methodology | Contraception | Family Planning | Hormones | Endocrine System | Physiology | Biology | Androgens | Reproduction Document Number: 292601 |
| 21. Peer Reviewed Title: Time course of changes in sperm morphometry and semen variables during testosterone-induced suppression of human spermatogenesis. Author: Garrett C; Liu DY; McLachlan RI; Baker HW Source: Human Reproduction. 2005 Nov;20(11):3091-3100. Abstract: Quantification of changes in semen may give insight into the testosterone (T)-induced disruption of spermatogenesis in man. A model analogous to flushing of sperm from the genital tract after vasectomy was used to quantify the time course of semen changes in subjects participating in male contraceptive trials using 800 mg T-implant (n = 25) or 200 mg weekly intramuscular injection (IM-T; n = 33). A modified exponential decay model allowed for delayed onset and incomplete disruption to spermatogenesis. Semen variables measured weekly during a 91-day period after initial treatment were fitted to the model. Sperm concentration, total count, motility and morphometry exhibited similar average decay rates (5 day half-life). The mean delay to onset of decline in concentration was 15 (IM-T) and 18 (T-implant) days. The significantly longer (P < 0.005) delays deduced for the commencement of fall in normal morphology (41 days), normal morphometry (40 days) and sperm viability (43 and 55 days), and the change of morphometry to smaller more compact sperm heads are consistent with sperm being progressively cleared from the genital tract rather than continued shedding of immature or abnormal sperm by the seminiferous epithelium. A significant negative relationship was found between lag time and baseline sperm concentration, consistent with longer sperm-epididymal transit times associated with lower daily production rates. (author's) Language: English Keywords: AUSTRALIA | RESEARCH REPORT | CLINICAL RESEARCH | MEN | SPERMATOGENESIS | TESTOSTERONE | TIME FACTORS | SEMEN | SPERM IMMOBILIZING AGENTS | SPERM COUNT | CONTRACEPTIVE AGENTS, MALE | Developed Countries | Oceania | Research Methodology | Demographic Factors | Population | Reproduction | Androgens | Hormones | Endocrine System | Physiology | Biology | Population Dynamics | Seminal Vesicles | Genitalia, Male | Genitalia | Urogenital System | Spermicidal Contraceptive Agents | Contraceptive Agents | Contraception | Family Planning | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses Document Number: 292345 |
| 22. Peer Reviewed Title: Treatment of male infertility. Author: Isidori A; Latini M; Romanelli F Source: Contraception. 2005;72:314-318. Abstract: Male factor infertility is a general term that describes a situation in which the inability to conceive is associated with an alteration identified in the male partner. This dysfunction may be associated with low sperm concentration (oligozoospermia), poor sperm motility (asthenozoospermia) or abnormal sperm morphology (teratozoospermia); however, generally, a disturbance of all these variables, oligoasthenoteratozoospermia, is mostly frequent in male subfertility. For many andrological disorders, it is not possible to find a reasonable cause and various uncontrolled treatments have been applied to infertile men, often just on an empirical basis. More recently, after the explosive development of modern assisted reproduction techniques (ARTs), feasible with a single spermatozoon [intracytoplasmic sperm injection (ICSI)], the treatment of male infertility has received new meaning and andrologists are no longer expected to achieve a quantitative increase in sperm number but are instead asked to improve the fertility potential of the single sperm cell in order to achieve better results in both in vitro fertilization and ICSI. Additional prospective studies are needed to better understand the possible role of therapy in ART candidate patients. (author's) Language: English Keywords: ITALY | LITERATURE REVIEW | PROSPECTIVE STUDIES | CLINICAL RESEARCH | MEN | INFERTILITY | SPERM TRANSPORT | SPERMATOGENESIS | REPRODUCTIVE TECHNOLOGIES | FERTILITY AGENTS | IN VITRO | TREATMENT | Europe, Southern | Europe | Developed Countries | Studies | Research Methodology | Demographic Factors | Population | Reproduction | Reproductive Control Agents | Family Planning Document Number: 290816 |
| 23. Title: Control of spermatogenesis in primate and prospect of male contraception. Author: Liu YX Source: Archives of Andrology. 2005 Mar-Apr;51(2):77-92. Abstract: The present review is a summary of mechanisms of spermatogenesis in primates with emphasis on anti-spermatogenesis of testosterone (T), gossypol, and “testicular heat stress” for development of male contraception. Both FSH and testosterone stimulate all phases of spermatogenesis. FSH is capable of amplifying the population of the differentiated spermatogonia (B1, B2, B3 and B4) and controls the spermatogonia production rate, and, in synergy with testosterone, regulating spermatogenesis in adult monkeys. Pituitary FSH beta gene expression is governed by a feedback of Beta inhibin, which is a major component of the testicular negative feedback signals. Beta inhibin secreted by Sertoli cells is in turn inhibited by testosterone from Leydig cells under the control of LH. Disturbance of the normal interaction of pituitary FSH with Sertoli cell Beta inhibin is responsible for azoospermia or oligozoospermia induced by exogenous T. Three possible regimens of T, gossypol and “heat stress” have been suggested for male contraception. They act on different sites and stages of spermatogenesis in testis or sperm activity in epididymis. Apoptosis induced by testosterone occurs mainly at stages VII-VIII of spermatogenesis while that by testicular “heat stress” mostly occurs at stages I-IV and X-XII. Low dose of gossypol mainly influences the sperm activity in the epididymis although it also acts on testicular spermatids. (author's) Language: English Keywords: CHINA | LITERATURE REVIEW | RESEARCH REPORT | RESEARCH ACTIVITIES | ANIMALS | MEN | TESTOSTERONE | CONTRACEPTION RESEARCH | MALE CONTRACEPTION | SPERMATOGENESIS | FOLLICLE STIMULATING HORMONE | LUTEINIZING HORMONE | Developing Countries | Asia, Eastern | Asia | Research Methodology | Natural Resources | Environment | Demographic Factors | Population | Androgens | Hormones | Endocrine System | Physiology | Biology | Contraception | Family Planning | Reproduction | Gonadotropins, Pituitary | Gonadotropins Document Number: 291645 |
| 24. Title: Contraceptive vaccines. Author: Naz RK Source: Drugs. 2005;65(5):593-603. Abstract: The world’s population is growing at a tremendous rate, affecting growth and development. Apart from this population growth, unintended pregnancies resulting in elective abortions continue to be a major public health issue. In over half of these unintended pregnancies, the women have used some type of contraception. Thus, there is an urgent need for a better method of contraception that is acceptable, effective and available. The contraceptive choices available to women at this time include steroid contraceptives, intrauterine devices, barrier methods, spermicides, natural family planning, male and female sterilisation, and recently available emergency contraceptives. Contraceptive vaccines (CVs) may provide viable and valuable alternatives that can fulfill most, if not all, properties of an ideal contraceptive. Since both the developed and most of the developing nations have an infrastructure for mass immunisation, the development of vaccines for contraception is an exciting proposition. The molecules that are being explored for CV development either target gamete production (gonadotropin releasing hormone, follicle-stimulating hormone and luteinising hormone), gamete function (zona pellucida [ZP] proteins and sperm antigens) or gamete outcome (human chorionic gonadotropin [hCG]). Disadvantages of CVs targeting gamete production are that they affect sex steroids and/or show only a partial effect in reducing fertility. CVs targeting gamete function are better choices. Vaccines based on ZP proteins are quite efficacious in producing contraceptive effects. However, they invariably induce oophoritis affecting sex steroids. Sperm antigens constitute the most promising and exciting targets for CVs. Several sperm-specific antigens have been delineated in several laboratories and are being actively explored for CV development. Antisperm antibody-mediated immunoinfertility provides a naturally occurring model to indicate how an antisperm vaccine will work in humans. Vaccines targeting gamete outcome primarily focus on the hCG molecule. The hCG vaccine is the first vaccine to undergo phase I and II clinical trials in humans. Both the efficacy and the lack of immunotoxicity have been reasonably well demonstrated for this vaccine. The present studies focus on increasing the immunogenicity and efficacy of this birth control vaccine. (author's) Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | CONTRACEPTION RESEARCH | ADULTS | CONTRACEPTIVE VACCINES | PREGNANCY | FERTILITY | SPERMATOGENESIS | CONTRACEPTIVE METHODS | North America | Americas | Developed Countries | Contraception | Family Planning | Age Factors | Population Characteristics | Demographic Factors | Population | Contraception, Immunological | Reproduction | Population Dynamics Document Number: 291984 |
| 25. Title: Development of newer approaches to male contraception: prospects of availability for mass application in the near future. Author: Rao AJ Source: Journal of Reproduction and Contraception. 2005;16(4):243-254. Abstract: Progress in development of a simple, effective reversible male contraceptive has been difficult due to the indispensable role of testosterone in spermatogenesis and maintenance of secondary sexual characters. Efforts are in progress to develop methods, which do not interfere with testosterone production. These include blockade of FSH action by immunization against FSH or FSHR, and interfere with sperm maturation by interfering with estrogen action or by immunization against epididymal or sperm specific proteins. An evaluation of these various approaches for practical application is also presented. (author's) Language: English Keywords: GLOBAL | LITERATURE REVIEW | LABORATORY ANIMALS | MALE CONTRACEPTION | RESEARCH AND DEVELOPMENT | CONTRACEPTIVE VACCINES | TESTOSTERONE | FOLLICLE STIMULATING HORMONE | LUTEINIZING HORMONE | ESTROGENS | SPERM MATURATION | SPERMATOGENESIS | Clinical Research | Research Methodology | Contraception | Family Planning | Technology | Economic Factors | Contraception, Immunological | Androgens | Hormones | Endocrine System | Physiology | Biology | Gonadotropins, Pituitary | Gonadotropins | Reproduction Document Number: 293685 |
| 26. Title: Hormonal contraception in men. Author: Walton M; Anderson RA Source: Current Drug Targets: Immune, Endocrine and Metabolic Disorders. 2005 Sep;5(3):249-257. Abstract: All major advances in the development of hormonal methods of contraception over the past 40 years have been exclusively female orientated with male hormonal contraception forever “just around the corner”. Despite this, the last few years have seen a significant increase in the pace of research and increased involvement from the pharmaceutical industry. This is essential if the progress derived from the public sector is to be translated into a real product for widespread use. Current male methods of contraception, condoms and vasectomy, are relied on by 30% of couples throughout the world but there have been no new male contraceptive methods introduced in the last century. There is currently an increasing emphasis on male involvement in family planning, and evidence both that some men would be keen to shoulder this responsibility and that their partners would trust them to do so. There are several potential novel approaches to male contraception, but the hormonal one is the only one at the stage of clinical research. This method is based on the normal regulation of spermatogenesis by the pituitary gonadotrophins: suppression of gonadotrophin secretion results in a reduction in the rate of spermatogenesis, and azoospermia, the absence of sperm from the ejaculate, can be achieved. Current approaches are now getting close to the ideal of inducing azoospermia in all men. This approach also results in suppression of testicular testosterone production, thus androgen ‘add-back’ is an essential component of a contraceptive regime. Many different steroids and delivery methods –oral, buccal, transdermal, subcutaneous implants- are under exploration at present, each with their own advantages and drawbacks. The use of synthetic androgens is also starting to be explored: these have the potential advantage of offering tissue-specific actions. (author's) Language: English Keywords: UNITED KINGDOM | RESEARCH REPORT | CLINICAL TRIALS | MEN | MALE CONTRACEPTION | CONTRACEPTIVE METHOD ACCEPTABILITY | SPERMATOGENESIS | TESTOSTERONE | PROGESTERONE | Developed Countries | Europe, Western | Europe | Clinical Research | Research Methodology | Demographic Factors | Population | Contraception | Family Planning | Contraceptive Usage | Reproduction | Androgens | Hormones | Endocrine System | Physiology | Biology | Progestational Hormones Document Number: 291812 |
| 27. Title: Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen. Author: Coviello AD; Bremner WJ; Matsumoto AM; Herbst KL; Amory JK Source: Journal of Andrology. 2004 Nov-Dec;25(6):931-938. Abstract: Intratesticular testosterone (ITT) is thought to play a key role in the control of spermatogenesis in man but is rarely measured. The purposes of this study were 1) to examine the relationship between intratesticular fluid and serum testosterone (T) at baseline and during treatment with a contraceptive regimen known to suppress spermatogenesis and 2) to measure intratesticular fluid androgenic bioactivity. Seven men received 6 months of T enanthate (TE) 100 mg weekly intramuscularly plus levonorgestrel (LNG) 62.5 or 31.25 µg orally daily. Testicular fluid was obtained by percutaneous aspiration at baseline and during month 6. Mean luteinizing hormone (LH) was suppressed 98% from 3.79 ± 0.80 IU/L at baseline to 0.08 ± 0.03 IU/L. Mean follicle stimulating hormone (FSH) was suppressed 97%, from 3.29 ± 0.67 IU/L to 0.10 ± 0.03 IU/L. Mean serum T levels were similar before (22.8 ± 1.9 nmol/L) and during treatment (28.7 ± 2.0 nmol/L) (P = .12). ITT (822 ± 136 nmol/L) was ~40x higher than serum T (P < .001) at baseline. ITT was suppressed 98% during treatment to 13.1 ± 4.5 nmol/L, a level similar to baseline serum T (P = .08) but significantly lower than on- treatment serum T (P = .01). At baseline, intratesticular fluid androgenic bioactivity (583 ± 145 nmol/L) was 70% of the ITT concentration measured by radioimmunoassay. Intratesticular androgenic bioactivity was suppressed 93% to 40 ± 22 nmol/L (P < .01) during treatment, but was 3x higher than ITT (13.1 ± 4.5 nmol/L). Sperm counts declined from 65 ± 15 million/mL to 1.3 ± 1.3 million/mL. In summary, TE plus LNG dramatically suppressed ITT (98%) and intratesticular androgenic bioactivity (93%) to levels approximating those in serum. ITT levels comparable with serum T were insufficient to support normal spermatogenesis. Intratesticular androgenic bioactivity was higher than ITT during treatment, suggesting that other androgens may be prevalent in the low- ITT environment. (author's) Language: English Keywords: UNITED STATES OF AMERICA | MARYLAND | RESEARCH REPORT | MALE CONTRACEPTION | SPERMATOGENESIS | GONADOTROPINS, PITUITARY | ANDROGENS | CONTRACEPTIVE AGENTS, PROGESTIN | North America | Americas | Developed Countries | Contraception | Family Planning | Reproduction | Gonadotropins | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Female | Contraceptive Agents Document Number: 284869 |
| 28. Title: Male hormonal contraception: suppression of spermatogenesis by injectable testosterone undecanoate alone or with levonorgestrel implants in Chinese men. Author: Gui YL; He CH; Amory JK; Bremner WJ; Zheng EX Source: Journal of Andrology. 2004 Sep-Oct;25(5):720-727. Abstract: Monthly injections of testosterone undecanoate (TU) act as a male contraceptive by reversibly suppressing spermatogenesis to azoospermia or severe oligoazoospermia in 95% of Chinese men. In 5% of Chinese men, however, monthly TU administered alone fails to suppress spermatogenesis into contraceptive ranges, or sperm “rebound,” leading to occurrences of pregnancy during treatment. Since combinations of progestins and androgens are associated with greater degrees of sperm suppression in white men, we hypothesized that the combination of TU and the progestin levonorgestrel (LNG) would result in improved spermatogenic suppression in Chinese men. Sixty-two healthy Chinese men were randomly assigned to one of the following 3 regimens: group I (n = 21) received 4 LNG rods (75 mg each), which were followed 4 weeks later by 500 mg of TU by intra-muscular (IM) injection every 8 weeks for 24 weeks; group II (n = 20) received 4 LNG implants, which were followed 4 weeks later by 1000 mg of TU by IM injection every 8 weeks for 24 weeks; and group III (n = 21) received TU 1000 mg by IM injection every 8 weeks for 24 weeks. Sperm counts, serum testosterone (T), luteinizing hormone, follicle-stimulating hormone, and LNG were measured every 2 weeks before, during, and after treatment. During treatment, group II demonstrated a trend toward a greater attainment of azoospermia than groups I and III (90% vs 62% [group I] vs 67% [group III]; P = .09). Attainments of either azoospermia or oligozoospermia (sperm density, <3 x 10(6)/mL) were 95%, 100%, and 86% for groups I, II, and III, respectively (P > .05 for comparisons between groups). Spermatogenesis in all subjects returned to the normal range after the implants were removed. No serious adverse events and no significant changes in serum chemistry occurred during the study. These results demonstrate that the combination of IM injections of high-dose TU every 2 months and LNG implants is associated with marked suppression of spermatogenesis in Chinese men. The combination of high-dose TU every 2 months and LNG implants is a promising candidate for future large-scale efficacy studies of hormonal male contraception in Chinese men. (author's) Language: English Keywords: CHINA | RESEARCH REPORT | MEN | IMPLANTATION | LEVONORGESTREL | TESTOSTERONE | MALE CONTRACEPTION | SPERMATOGENESIS | CONTRACEPTION RESEARCH | Developing Countries | Asia, Eastern | Asia | Demographic Factors | Population | Pregnancy, First Trimester | Pregnancy | Reproduction | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Androgens | Hormones | Endocrine System | Physiology | Biology Document Number: 284867 |
| 29. Title: Progress towards hormonal male contraception. Author: Kamischke A; Nieschlag E Source: Trends in Pharmacological Sciences. 2004 Jan;25(1):49-57. Abstract: The use of androgens is an essential part of all experimental approaches to hormonal male contraception and involves the suppression of gonadotrophins, leading to inhibition of spermatogenesis. Although clinical trials have proven the concept of hormonal male contraception, their modalities have been unacceptable for practical use for several reasons. Because the efficacy of all self-administered androgen preparations has been disappointing, recent studies have focused on either androgen implants or injectable, long-acting testosterone esters such as testosterone undecanoate. However, in contrast to East Asian men, only two-thirds of Caucasian men respond to such androgen-based regimens with the desired azoospermia (no sperm produced), and thus additional agents are required. Over the past decades various combinations of androgen preparations with different progestins or gonadotrophin-releasinghormone antagonists have been tested in clinical trials. Of these, testosterone administered in combination with either depot medroxyprogesterone acetate, norethisterone enanthate, desogestrel or etonogestrel have shown promising efficacy. (author's) Language: English Keywords: GERMANY | CLINICAL TRIALS | SUMMARY REPORT | MEN | MALE CONTRACEPTION | CONTRACEPTION RESEARCH | SPERMATOGENESIS | ASIANS | Europe, Central | Europe | Developed Countries | Clinical Research | Research Methodology | Demographic Factors | Population | Contraception | Family Planning | Reproduction | Ethnic Groups | Cultural Background | Population Characteristics Document Number: 277519 |
| 30. Title: Cell-cell interactions at the ectoplasmic specialization in the testis. Author: Mruk DD; Cheng CY Source: Trends in Endocrinology and Metabolism. 2004 Nov;15(9):439-447. Abstract: During spermatogenesis, the movement of developing germ cells across the seminiferous epithelium involves the restructuring of adherens junctions that form between Sertoli cells and between Sertoli and germ cells such as the ectoplasmic specialization (ES). At the ultrastructural level, the ES has been thoroughly studied for the past three decades. Until recently, however, relatively little has been known about the molecular architecture, not to mention the mechanism, that regulates the ES. Recent findings in the field have highlighted several areas of research that deserve attention in future studies. For example, proteins that constitute the ES can be targeted to compromise cell adhesion. This approach will not only provide a better understanding of ES dynamics, but also will yield innovative approaches for the development of male contraceptives. (author's) Language: English Keywords: UNITED STATES OF AMERICA | SUMMARY REPORT | TESTIS | SPERMATOGENESIS | GERM CELLS | MALE CONTRACEPTION | CONTRACEPTION RESEARCH | North America | Americas | Developed Countries | Genitalia, Male | Genitalia | Urogenital System | Physiology | Biology | Reproduction | Contraception | Family Planning Document Number: 284795 |
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