A time-resolved fluorescence immunoassay for the measurement of testosterone in saliva: Monitoring of testosterone replacement therapy with testosterone buciclate

Monitoring of testosterone replacement therapy requires a reliable method for testosterone measurement. Determination of salivary testosterone, which reflects the hormone's biologically active plasma fraction, is a superior technique for this purpose. The aim of the present study was to establish a new sensitive time-resolved fluorescence immunoassay for the accurate measurement of testosterone levels in saliva and to validate it by monitoring testosterone replacement therapy in eight hypogonadal men. A clinical phase I- study with the new ester testosterone buciclate was performed to search for new testosterone preparations to produce constant serum levels in the therapy of male hypogonadism. After two control examinations eight male patients with primary hypogonadism were randomly assigned to two treatment groups (n = 2x4) and given single doses of either 200 mg (group I) or 600 mg (group II) testosterone buciclate intramuscularly. Saliva and blood samples were obtained 1, 2, 3, 5 and 7 days post injection and then weekly for three months. The time-resolved fluorescence immunoassay for salivary testosterone shows a detection limit of 16 pmol/l, an intra-assay CV of 8.9% (at a testosterone concentration of 302 pmol/l), an inter-assay CV of 8.7% (at a testosterone concentration of 305 pmol/l) and a good correlation with an established radioimmunsassay of r = 0.89. The sample volume required by this method is only 180 mu l for extraction and duplicate determination. The assay procedure requires no more than three hours. In group I (200 mg) testosterone did not increase to normal levels either in saliva or in serum. However, in group II, androgen levels increased significantly and were maintained in the normal range for up to 12 weeks with maximal salivary testosterone levels of 303 +/- 18 pmol/l (mean+/-SE) and maximal testosterone levels of 13.1 +/- 0.9 nmol/l (mean+/-SE) in serum in study week 6 and 7. The time-resolved fluorescence immunoassay for salivary testosterone provides a useful tool for monitoring androgen status in men and women and is well suited for the follow-up of testosterone replacement therapy on an outpatient basis. The long-acting ester testosterone buciclate is a promising agent for substitution therapy of male hypogonadism and in combination with testosterone monitoring in saliva offers an interesting new perspective for male contraception

The effects and safety of testosterone replacement therapy for men with hypogonadism: the TestES evidence synthesis and economic evaluation

Background: Low levels of testosterone cause male hypogonadism, which is associated with sexual dysfunction, tiredness and reduced muscle strength and quality of life. Testosterone replacement therapy is commonly used for ameliorating symptoms of male hypogonadism, but there is uncertainty about the magnitude of its effects and its cardiovascular and cerebrovascular safety. Aims of the research: The primary aim was to evaluate the safety of testosterone replacement therapy. We also assessed the clinical and cost-effectiveness of testosterone replacement therapy for men with male hypogonadism, and the existing qualitative evidence on men\u27s experience and acceptability of testosterone replacement therapy. Design: Evidence synthesis and individual participant data meta-analysis of effectiveness and safety, qualitative evidence synthesis and model-based cost-utility analysis. Data sources: Major electronic databases were searched from 1992 to February 2021 and were restricted to English-language publications. Methods: We conducted a systematic review with meta-analysis of individual participant data according to current methodological standards. Evidence was considered from placebo-controlled randomised controlled trials assessing the effects of any formulation of testosterone replacement therapy in men with male hypogonadism. Primary outcomes were mortality and cardiovascular and cerebrovascular events. Data were extracted by one reviewer and cross-checked by a second reviewer. The risk of bias was assessed using the Cochrane Risk of Bias tool. We performed one-stage meta-analyses using the acquired individual participant data and two-stage meta-analyses to integrate the individual participant data with data extracted from eligible studies that did not provide individual participant data. A decision-analytic Markov model was developed to evaluate the cost per quality-adjusted life-years of the use of testosterone replacement therapy in cohorts of patients of different starting ages. Results: We identified 35 trials (5601 randomised participants). Of these, 17 trials (3431 participants) provided individual participant data. There were too few deaths to assess mortality. There was no difference between the testosterone replacement therapy group (120/1601, 7.5%) and placebo group (110/1519, 7.2%) in the incidence of cardiovascular and/or cerebrovascular events (13 studies, odds ratio 1.07, 95% confidence interval 0.81 to 1.42; p = 0.62). Testosterone replacement therapy improved quality of life and sexual function in almost all patient subgroups. In the testosterone replacement therapy group, serum testosterone was higher while serum cholesterol, triglycerides, haemoglobin and haematocrit were all lower. We identified several themes from five qualitative studies showing how symptoms of low testosterone affect men\u27s lives and their experience of treatment. The cost-effectiveness of testosterone replacement therapy was dependent on whether uncertain effects on all-cause mortality were included in the model, and on the approach used to estimate the health state utility increment associated with testosterone replacement therapy, which might have been driven by improvements in symptoms such as sexual dysfunction and low mood. Limitations: A meaningful evaluation of mortality was hampered by the limited number of defined events. Definition and reporting of cardiovascular and cerebrovascular events and methods for testosterone measurement varied across trials. Conclusions: Our findings do not support a relationship between testosterone replacement therapy and cardiovascular/cerebrovascular events in the short-to-medium term. Testosterone replacement therapy improves sexual function and quality of life without adverse effects on blood pressure, serum lipids or glycaemic markers. Future work: Rigorous long-term evidence assessing the safety of testosterone replacement therapy and subgroups most benefiting from treatment is needed. Study registration: The study is registered as PROSPERO CRD42018111005. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/68/01) and is published in full in Health Technology Assessment; Vol. 28, No. 43. See the NIHR Funding and Awards website for further award information.Testosterone is a hormone which is vital for sexual activity, bone growth and muscle development in men. Men with low testosterone levels may experience problems with erections and may suffer from brittle bones (osteoporosis), weakness, feeling down (low mood) and tiredness. The manifestations of low testosterone can be treated with testosterone replacement therapy. However, there is current uncertainty about the positive effects of testosterone replacement therapy and its safety. We brought together results from all available medical studies that looked at the use of testosterone replacement therapy in men with low testosterone and contacted the doctors who led these studies to gather further information on their participants. We found 35 studies (5601 participants) conducted in different countries, 17 of which provided additional information on their participants. We did not find any evidence to show that testosterone replacement therapy increases the risk of heart problems, or any evidence to show that some men who take testosterone replacement therapy benefit more than others. Men with low testosterone reported having low mood, poor concentration and lack of energy; however, medical studies often failed to prove that these manifestations improved with testosterone replacement therapy. Most medical studies were conducted among white men in North America using questionnaires designed specifically for them; therefore, the results may not reflect the experiences of men in other countries and from more diverse ethnic backgrounds. There is too much uncertainty about the benefits of testosterone replacement therapy to accurately estimate its value for money for the NHS. We think our findings offer some reassurance to doctors and patients that testosterone replacement therapy does not increase the risk of heart problems. New studies are needed to find out whether some groups of men (such as older or younger men) are more likely to benefit from testosterone replacement therapy more than others. It is also important to develop tools which better reflect the experience of men from a diverse range of social and ethnic backgrounds. To inform men with low testosterone about our findings, we are creating a website with dedicated YouTube video clips

Testosterone replacement therapy

Physicians and scientists have suspected that the testes secrete a substance into the body that causes male secondary sexual characteristics for hundreds of years. However, testosterone was not synthesized until 1935 and it was not until the 1940's when scientists could accurately measure the amount of this hormone in the blood. Since then, scientists have been able to make correlations between the levels of testosterone in the body and men's health Scientists have long observed higher levels of testosterone to be associated with an increase in levels of Hematocrit (Hct). As a result, Testosterone Replacement Therapy (TRT) has been used to treat anemia associated with chronic diseases. In recent years, prescription sales for testosterone have sky rocketed due to new clinical uses such as androgen deficiency in older men. In fact, the rate of prescription for testosterone products has increased by over 170% in the previous five years. Long-term data shows that the level of testosterone in the male body begins to decrease at about the age of 30. As the life expectancy of the general population continues to increase, TRT may be a viable option for older men with low testosterone to increase the quality and duration of life. However, an increase in Hct continues to be a major side effect of TRT. New research is beginning to make clear the mechanism by which testosterone affects erythropoeisis. New research suggests TRT suppresses hepcidin and leads to an increase in the rate of iron (Fe) retention in red blood cells (RBCs). Inter-individual differences in the pharmacogenetic effects of TRT have been observed. In the future TRT could be genetically tailored based on the individuals DNA. In this case, the optimal dose of testosterone can be given to maximize benefits and reduce side effects. Here, the risks and benefits associated with TRT and a review of the updated Clinical Guidelines for its use will be presented. The effects of TRT on erythropoeisis will be investigated via a review of the literature. The main objective of this review is to provide a general understanding of TRT and a major side effect of its use, excessive erythropoeisis

Testosterone Therapy and Risk of Recurrence After Treatment for Prostate Cancer

Evidence-Based Answer: Men with symptomatic androgen deprivation who have had clinically curative treatment for organ-confined prostate cancer may have symptomatic improvement with testosterone replacement therapy. (Strength of Recommendation [SOR]: C, based on two small case series.) There are no studies evaluating the risk of cancer recurrence in patients receiving testosterone replacement therapy. However, testosterone replacement therapy may be associated with increased prostate-specific antigen (PSA) levels. (SOR: C, based on one case report.) Some men discontinue therapy because their symptoms do not improve. (SOR: C, based on a small case series.

Testosterone deficiency in the adult males

Testosterone deficiency leads to multiple problems but can be difficult to diagnose. However, replacement therapy can be rewarding and a life changer for the patient.peer-reviewe

Testosterone replacement therapy

Physicians and scientists have suspected that the testes secrete a substance into the body that causes male secondary sexual characteristics for hundreds of years. However, testosterone was not synthesized until 1935 and it was not until the 1940's when scientists could accurately measure the amount of this hormone in the blood. Since then, scientists have been able to make correlations between the levels of testosterone in the body and men's health Scientists have long observed higher levels of testosterone to be associated with an increase in levels of Hematocrit (Hct). As a result, Testosterone Replacement Therapy (TRT) has been used to treat anemia associated with chronic diseases. In recent years, prescription sales for testosterone have sky rocketed due to new clinical uses such as androgen deficiency in older men. In fact, the rate of prescription for testosterone products has increased by over 170% in the previous five years. Long-term data shows that the level of testosterone in the male body begins to decrease at about the age of 30. As the life expectancy of the general population continues to increase, TRT may be a viable option for older men with low testosterone to increase the quality and duration of life. However, an increase in Hct continues to be a major side effect of TRT. New research is beginning to make clear the mechanism by which testosterone affects erythropoeisis. New research suggests TRT suppresses hepcidin and leads to an increase in the rate of iron (Fe) retention in red blood cells (RBCs). Inter-individual differences in the pharmacogenetic effects of TRT have been observed. In the future TRT could be genetically tailored based on the individuals DNA. In this case, the optimal dose of testosterone can be given to maximize benefits and reduce side effects. Here, the risks and benefits associated with TRT and a review of the updated Clinical Guidelines for its use will be presented. The effects of TRT on erythropoeisis will be investigated via a review of the literature. The main objective of this review is to provide a general understanding of TRT and a major side effect of its use, excessive erythropoeisis

Testosterone Replacement Therapy in Aging Males

The U.S. Food and Drug Administration (FDA) cautions health care providers and patients regarding the use of testosterone replacement therapy products for the aging process, including a decrease in muscle strength, muscle mass, and lack of energy or sexual desire, due to an increased risk of heart attacks and strokes. Testosterone replacement therapy products are indicated for genetic defects, chemotherapy damage, or damage to the hypothalamus or pituitary gland, where testosterone is produced. A patient and his team of health care professionals must seriously consider the risks and benefits when using these products for other indications. Use of testosterone replacement therapy products for low testosterone due to natural aging has been on the rise due to disease state awareness, pharmaceutical marketing and media attention. Pharmacists can make a difference in patients\u27 lives by conducting patient education and counseling for these products

Investigating the basis of sexual dysfunction during late-onset hypogonadism

Late-onset hypogonadism (LOH) is the term used to describe the decline in serum testosterone levels associated with increasing age in men above 40 years. A number of symptoms are attributed to LOH, but the most common association is that of sexual dysfunction. LOH has recently come under greater scrutiny with the widespread use of testosterone therapy, and concerns regarding the efficacy and safety of testosterone replacement therapy have been raised. In particular, the cardiovascular safety and the beneficial effects of testosterone replacement therapy on general health have been questioned. This review will give an overview of the current evidence for the relationship of LOH and male sexual dysfunction

ROLE OF TESTOSTERONE IN THE TREATMENT OF ED

Hypogonadism may play a significant role in the pathophysiology of erectile dysfunction (ED). A threshold level of testosterone may be necessary for normal erectile function. Testosterone replacement therapy is indicated in hypogonadal patients and is beneficial in patients with ED and hypogonadism. Monotherapy with testosterone for ED is of limited effectiveness and may be most promising in young patients with hypogonadism and without vascular risk factors for ED. A number of laboratory and human studies have shown the combination of testosterone and other ED treatments, such as phosphodiesterase type 5 (PDE5) inhibitors, to be beneficial in patients with ED and hypogonadism, who fail PDE5 inhibitor therapy alone. There is increasing evidence that combination therapy is effective in treating the symptoms of ED in patients for whom treatment failed with testosterone or PDE5 inhibitors alone. Testosterone replacement therapy has potentially evolved from a monotherapy for ED in cases of low testosterone, to a combination therapy with PDE5 inhibitors. Screening for hypogonadism may be useful in men with ED who fail prior PDE5 inhibitors, especially in populations at risk for hypogonadism such as type 2 diabetes and the metabolic syndrome