BACKGROUND Semen quality is taken as a surrogate measure of male fecundity in clinical andrology, male fertility, reproductive toxicology, epidemiology and pregnancy risk assessments. Reference intervals for values of semen parameters from a fertile population could provide data from which prognosis of fertility or diagnosis of infertility can be extrapolated. METHODS Semen samples from over 4500 men in 14 countries on four continents were obtained from retrospective and prospective analyses on fertile men, men of unknown fertility status and men selected as normozoospermic. Men whose partners had a time-to-pregnancy (TTP) of < or =12 months were chosen as individuals to provide reference distributions for semen parameters. Distributions were also generated for a population assumed to represent the general population. RESULTS The following one-sided lower reference limits, the fifth centiles (with 95th percent confidence intervals), were generated from men whose partners had TTP < or = 12 months: semen volume, 1.5 ml (1.4-1.7); total sperm number, 39 million per ejaculate (33-46); sperm concentration, 15 million per ml (12-16); vitality, 58% live (55-63); progressive motility, 32% (31-34); total (progressive + non-progressive) motility, 40% (38-42); morphologically normal forms, 4.0% (3.0-4.0). Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men. CONCLUSIONS The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.

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World Health Organization reference values for human semen characteristics

The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in primates. In general, other neurotransmitters appear unaffected. In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users.

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

Despite significant advances in contraceptive options for women over the last 50 yr, 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 half of all pregnancies are still unwanted or unplanned. Clearly, there is a need for expanded, reversible, contraceptive options. Multicultural surveys demonstrate the willingness of men 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 one 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 methods and perceived regulatory obstacles, which stymie introduction to the marketplace. However, advances in oral and injectable androgen delivery are cause for optimism that these hurdles may be overcome. Nonhormonal 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 nonhormonal 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.

Advances in male contraception.

Objective: The objective of the study was to evaluate the current state of clinical assays for total and free testosterone. Participants: The five participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion. Evidence: Data were gleaned from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), the College of American Pathologists, and the clinical and laboratory experiences of the participants. Consensus Process: The statement was an effort of the committee and was reviewed in detail by each member. The Council of The Endocrine Society reviewed a late draft and made specific recommendations. Conclusions: Laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method. When such standardization is in place, normative values for total and ...

Position statement: Utility, limitations, and pitfalls in measuring testosterone: An endocrine society position statement

The Merck Index of Chemicals and Drugs An Encyclopedia for the Chemist, Pharmacist, Physician and Allied Professions Sixth edition Pp xiv + 1167 (Rahway, NJ: Merck and Company, Inc, 1952) 750 dollars; thumb-indexed, 8 dollars

The Merck Index

Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic–androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.

/pdf/pharmacology-of-anabolic-steroids-2yhwm6fl8o.pdf

Pharmacology of anabolic steroids

/pdf/recent-advances-in-doping-analysis-y9bphgb7zg.pdf

Recent Advances in Doping Analysis

Widespread public perception is that illicit drugs contain substances that are a serious risk to health, even though adulterants are often not considered in clinical or forensic toxicology. This review attempts to present an evidence-based overview of adulterants in illicit drugs, and their associated toxicity. Adulterants are deliberately added to increase bulk, enhance or mimic a pharmacological effect, or to facilitate drug delivery. Those present unintentionally are as a result of poor manufacturing techniques. From the reports gathered, adulterants are predominantly substances which are readily available, commonly being caffeine, procaine, paracetamol, and sugars. These are likely to have minimal impact on users' health at low dosages. Other adulterants, particularly in injectable drugs, have the potential to cause serious health issues, but the quantities reported, such as strychnine in heroin, are not life-threatening. The most commonly identified bacterial contaminants identified are Bacillus and Clostridium species. When death or serious illness due to adulteration occurs, circulation of information is particularly vital, such as in the USA regarding heroin and cocaine adulterated with fentanyl, and in Scotland recently regarding anthrax contaminated heroin. The complex interactions of supply, demand, and control of illicit drugs have a tangible impact on their adulteration. Continuing vigilance and the circulation of information is, therefore, desirable as a public health issue. As part of that strategy, analyses performed for adulterants needs to be encouraged, which are considerably limited in number and scope at the moment.

Adulterants in illicit drugs: a review of empirical evidence

Background: Immunoassay is unsatisfactory for measuring the testosterone concentrations typically found in women. Bench-top tandem mass spectrometers are a viable alternative technology for measurements in the clinical laboratory.

Methods: We used stable-isotope dilution liquid chromatography–tandem mass spectrometry (ID/LC-MS/MS) to measure testosterone in plasma and serum. The sample volume was 50 μL in duplicate; preparation and analysis were carried out in a single tube, and a batch of 192 tubes was analyzed in 17.5 h.

Results: Intra- and interassay imprecision was 8 nmol/L. Various steroids added to double charcoal-stripped serum showed no interference at the retention time of the testosterone peak.

Conclusions: The ID/LC-MS/MS method has improved accuracy compared with immunoassay. The low sample volume and simplicity, rapidity, and robustness of the method make it suitable for use as a high-throughput assay in routine clinical biochemistry laboratories.

Testosterone measurement by isotope-dilution liquid chromatography-tandem mass spectrometry: Validation of a method for routine clinical practice

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)78744-4.pdf

Andrew T. Kicman

Papers

Pharmacology of anabolic steroids

Recent Advances in Doping Analysis

Adulterants in illicit drugs: a review of empirical evidence

Testosterone measurement by isotope-dilution liquid chromatography-tandem mass spectrometry: Validation of a method for routine clinical practice

Low-dose MDMA (“ecstasy”) induces vasopressin secretion