In view of the low power of this test, we will also consider the I² statistic, which quantifies inconsistency across trials, to assess the impact of heterogeneity on the meta‐analysis (Higgins 2002; Higgins 2003). We will investigate the impact of imputation on meta‐analyses by performing sensitivity analyses, and we will report for every outcome which trials had imputed SDs. Where included trials do not report means and SDs for outcomes and we are unable to obtain the necessary information from trial authors, we will impute these values by estimating the mean and variance from the median, range, and the size of the sample (Hozo 2005). In trials where the standard deviation (SD) of the outcome is not available at follow‐up or we cannot recreate it, we will standardise by the mean of the pooled baseline SD from those trials that reported this information. We will investigate attrition rates (e.g. dropouts, losses to follow‐up, withdrawals) and will critically appraise issues concerning missing data and use of imputation methods (e.g. last observation carried forward). This definitive study by Corona et al. also suggests that TTh may be a useful monotherapy in men with mild ED. The mean change in IIEF-EF, however, was greater when data were stratified by baseline testosterone level. In early 2017, Corona et al. performed meta-analysis of 14 RCTs that studied the effect of TTh on erectile function in men with late onset hypogonadism, and compared pre- and post-IIEF scores . TE for weekly subcutaneous injection has been recently approved in the United States for treating adults with hypogonadism. For this reason, the few available studies in adolescent males applied patches for a shorter time (usually for 12 hours daily) instead of the 24-hour recommended adult application 76, 77. Finally, treatment with T gel resulted in appropriate and adequate increases in serum T concentrations in 104 boys with Klinefelter syndrome, although specific doses and regimens were not described . In this study, proper dosing became an issue, given the variable responses in individual adolescents . For T gel, the pediatric experience is limited to a single prospective study, a few retrospective analyses, and a case series. For many men, the symptoms of low testosterone are enough to make them jump headfirst into any viable treatment option. When your testosterone levels are out of whack, your quality of life can take a serious nosedive. Low testosterone symptoms span a wide range of unpleasant side effects and can impact how you look, feel, and even think. Currently available testosterone supplementation therapy options include intramuscular injections, transdermal, subcutaneous pellets, oral, and buccal formulations (Giagulli 2011; Shoskes 2016). Recent US data showed that 2.2 million men were prescribed testosterone in 2013 compared to 1.2 million in 2010 (Nguyen 2015). Testosterone has been available for more than 70 years, and the number of new testosterone preparations has increased dramatically over the last two decades (Nieschlag 2014). In the case of a total testosterone level above 12 nmol/L, testosterone supplementation therapy should not be recommend . However, they are all based on expert opinion or consensus rather than evidence provided by carefully designed studies 10, 22, 37, 62. In a prospective, randomized, crossover study, overnight application of a 5-mg patch in 8 boys simulated physiologic T secretion and increased short-term growth . In a retrospective study in adolescent males with CDGP, 10 mg daily of 2% testosterone gel for 3 months had a similar effect on height velocity as TE 50 mg monthly for 3 months . Administration at starting doses of 0.5 g daily for 6 months or less increased serum T concentrations to normal, age-matched levels . Rogol et al retrospectively evaluated the clinical response to T gel 1% in a subgroup from a prospective, open-label, observational study of 86 adolescent boys (age years) with primary hypogonadism due to Klinefelter syndrome or anorchia. How to Get Testosterone Replacement Therapy In addition, the evidence presented in this study provides reassuring data regarding TTh safety, addressing in particular the two most common concerns, namely the risks of prostate cancer and CV disease. If testosterone concentrations are found to be low, TTh has to be considered not only for its beneficial effects on sexual function but also for its metabolic effects that are profound and widespread. Although for decades it was believed that TTh increased the risk of developing prostate cancer, we have now entered an era where TTh is being used in clinical trials for potential therapeutic and protective effects. In this study, we provide summaries of selected key areas of testosterone research to provide a scientific basis for the argument that TD is an important health risk and TTh offers valuable health care benefits with a reassuring safety profile. Benefits of TTh versus placebo were demonstrated in multiple areas, including not just the expected sexual symptoms such as libido and erections, but also physical activity, self-reported sense of increased energy, mood, bone density and bone strength, and resolution of unexplained anemia. Due to a lack of research on long-term safety, testosterone therapy isn't right for women with heart, blood vessel or liver disease. Randomized and non-randomized comparative studies assessing the benefits and harms of TTh in hypogonadal, borderline eugonadal and eugonadal men suffering from sexual dysfunction were included. Another study looking at the effect of red clover on the quality of life, and sexual function in men found that this supplement did not change sexual or erectile function, and resulted in a significant increase in liver transaminases . Additionally, testosterone plays a vital role in vascular health by improving endothelial function, which is crucial for maintaining cardiovascular health in men. The purpose of this study was to evaluate the composition of “T boosting” supplements, their advertised claims, and compare them with both the published literature and FDA recommendations. It is important that these men have access to information that is evidence-based and will give them a realistic picture of what they can hope to see after using these supplements. However, despite this clear FDA statement, there continue to be products that either directly claim or imply to have certain effects on medical conditions. Approximately 50% of American adults consume dietary supplements to promote overall health and fill dietary gaps 4,5. Estimated mean changes from baseline Once you start testosterone therapy, can you stop? The biggest difference is that the doses of testosterone used in TRT are small, designed to achieve natural levels of the hormone in the blood. Congestive heart failure.Men with severe congestive heart failure should generally not take testosterone replacement, as it can worsen the condition. Studies demonstrate that this route of administration provides a safety profile and effective therapy without the fluctuations in blood levels commonly seen with transdermal administration or intramuscular injection . Implants were first described as an alternative treatment for menopausal symptoms in the 1950s . Despite this, some women see symptomatic improvement 4–6 weeks after the start of treatment . In addition, hyperlipidemia and hepatic dysfunction are contraindications for T therapy. However, additional long-term dosing studies should be conducted to evaluate T deficiency in women 1,14. The quality of evidence for these outcomes ranged from low to moderate, due to high heterogeneity and low-to-moderate risk of bias. One-fifth of the studies reported treatment adherence assessment, and only 25% analyzed participants as randomized (intention-to-treat analysis). Whenever appropriate (more than 10–20 studies and low between-study heterogeneity), we assessed publication bias using the Egger regression asymmetry test and visual inspection of funnel plots (26, 27). It is important to note that men enrolled in this study on average had moderate ED, and so this improvement in erectile function was not considered clinically significant. Erections are initiated when nitric oxide and other neuroendocrine factors induce relaxation of the smooth muscles of the cavernous arteries and tissues resulting in increased penile blood inflow. The IIEF-EF is often used in studies to trend changes in erectile function, with a change of 2 IIEF-EF points being clinically significant for men with mild ED. Multiple longitudinal studies have observed that as men age, they experience a decline in total serum testosterone beginning in the third decade of life 1, 2. The most widely used assay to measure total T in women is the radioimmunoassay (RIA) . Therefore, the calculation of bioavailable T is one of the best parameters for evaluating the androgenic profile in women as it disregards T values linked to SHBG . There is no standard analysis for women since much of the total circulating T is biologically unavailable due to its binding to sex hormone-binding globulin (SHBG). An average blood level of T and what laboratory parameters should be used to guide clinicians in treatment still need to be improved. Therefore, because of these events, we observe that the use of T for treating HSDD in women remains controversial. Appendix 2. 'Risk of bias' assessment Eventually, that drop could lead to hypogonadism, or low testosterone. The number of men who take testosterone has dropped dramatically in the past few years, in part because of growing awareness of the risks that may accompany it. We will present the overall certainty of the evidence for each outcome specified below according to the GRADE approach, which takes into account issues related not only to internal validity (risk of bias, inconsistency, imprecision, publication bias) but also to external validity, such as directness of results. A prediction interval needs at least three trials to be calculated and specifies a predicted range for the true treatment effect in an individual trial (Riley 2011). Similar effects on growth and pubertal maturation were observed in a larger, retrospective study of 96 Danish boys treated with TU daily (40-mg daily doses escalated up to 80 mg twice daily) for an average of 0.8 years and 63 untreated controls . Earlier forms of oral testosterone (methyltestosterone and 17α derivatives) led to hepatic dysfunction and are no longer marketed . T propionate results in wide T fluctuations, requires frequent injections, and was therefore deemed unsuitable for treatment of male hypogonadism . In general, trials that used larger doses of testosterone and achieved greater gains in lean body mass, and measured maximal voluntary strength with isoinertial exercise devices have tended to show significant improvements in lower extremity strength (3, 14). These regional differences in the response of different muscle groups to androgens have been reported in other studies (32). Men in the testosterone-treated group significantly increased both lower and upper extremity power more than men receiving placebo. Eligible studies prior to July 2008 were identified from previous Endocrine Society guidelines (20), from a previously published systematic review addressing the same question by the Cochrane collaboration (21), and from a review about T without HRT (7).The changes in leg-press strength did not differ between the intervention groups even though upper extremity strength improved significantly more in the testosterone-treated men.Subjective erectile function can be assessed using validated questionnaire metrics including the international index of erectile function (IIEF) with the erectile function domain (IIEF-EF) being the most specific for assessing ED.At the same time, its impact on mental health, particularly in alleviating depressive symptoms, underscores its multifaceted nature.Furthermore, a study in the August 2015 Mayo Clinic Proceedings showed no link between TRT and blood clots in veins among 30,000 men.The number of men who take testosterone has dropped dramatically in the past few years, in part because of growing awareness of the risks that may accompany it.However, approximately 50% to 70% of testosterone in the blood is tightly bound to sex hormone‐binding globulin (SHBG); 20% to 30% is loosely bound to albumin; 4% is bound to other proteins; and 1% to 3% is the free, non‐bound form in men (Diver 2009).A smaller randomized controlled trial (RCT) of premenopausal women showed no adverse effects of a transdermal T spray versus placebo .This systematic review has provided a comprehensive examination of testosterone's physiological roles, emphasizing the need for further research to address existing gaps in knowledge. The specific needs of adolescent males with chronic illnesses and functional hypogonadism should also be addressed. The first involves the absence of data on the impact of TRT, as it is currently implemented, on various health parameters, including quality of life and adult health outcomes. Research confirms the multiple anabolic effects of T, including those on bone 1, 3, 4, 22, 120. The goals of monitoring during therapy are to ensure appropriate growth and virilization and screen for potential adverse effects. We will search the following sources from the inception of each database to the date of search and will place no restrictions on language of publication or publication status. We will consider clinically important difference for the review outcomes to rate the certainty of the evidence for imprecision in the 'Summary of findings' table (Johnston 2010). Testosterone supplementation therapy has been performed in younger androgen deficient men for many years. Testosterone plays a critical role in the development of the male reproductive organs such as the testes and prostate, as well as promoting secondary sexual characteristics during puberty (Gannon 2016; Ohlander 2016). Follicle‐stimulating hormone is responsible for sperm production, and LH is responsible for testosterone secretion in the testis. To assess the quality of the included study, we used Cochrane Collaboration's Risk of Bias assessment tool (23).However, despite this clear FDA statement, there continue to be products that either directly claim or imply to have certain effects on medical conditions.Testosterone also increases bone density, muscle mass, and insulin sensitivity in some men.A recent randomized controlled trial conducted in Malaysia investigated the efficacy and safety of TU in the treatment of aging men with TD Tan et al. 2013.There are data to support the use of testosterone in patients suffering from sexual dysfunction and, more specifically, from what is termed hypoactive sexual desire disorder (HSDD).A double-blind study in the Feb. 18, 2016 issue of The New England Journal of Medicine reviewed the effects of TRT on 790 men ages 65 and older. Older men with limited mobility who experienced cardiovascular events had greater increases in serum free T levels compared with control subjects Basaria et al. 2013. In addition, subject selection was based solely upon T values, rather than in combination with defined clinical symptoms of TD. The predominant criticism of this study was that there was a high prevalence of hypertension, diabetes, hyperlipidemia, obesity, and metabolic syndrome among the participants, with a substantially advanced age. The primary outcome was to evaluate the change from baseline of maximal voluntary muscle strength in leg-press exercise with secondary outcomes measuring chest press, 50 m walking speed, and stair climbing. The Testosterone in Older Men (TOM) trial, a double-blind randomized-controlled trial of 209 men of mean age 74 years, was performed to assess the effects of TRT in men with low serum T and limited mobility Basaria et al. 2010. Testosterone levels naturally decline with age, which can lead to sarcopenia (age-related muscle loss) and decreased muscle strength. This anabolic effect enhances muscle growth and repair, making testosterone essential for maintaining muscle mass 15,16-17. There is a huge association between testosterone level and bone density, which is related to a decrease in the testosterone hormone level, which will cause a reduction in bone density . Testosterone is critically involved in regulating libido in both men and women; it affects various brain regions involved in sexual desire, including the hypothalamus, which is responsible for sexual motivation and arousal . In general, in a healthy population, the normal level of testosterone hormone in men is an average of 264 to 916 ng/dL . The major criticism is the absence of diagnostic criteria and therapeutic doses established in pre and postmenopausal women. The second retrospective study, with a 9-year follow-up, demonstrated a reduction of 35.5% in breast cancer incidence in both T and T and E2 hormone implant users compared to age-specific SEER incidence rates (223/100,000) . The long-term impact of biosimilar T therapy showed no increase in breast cancer incidence. The men with a total testosterone level higher than 900 ng/dL (31.2 nmol/L) had their testosterone dose reduced to 5 g. Participants were randomly assigned to receive either 7.5 g of 1% testosterone gel (75 mg of testosterone) or placebo gel daily for 3 years. The participants were stratified by age group and site, and randomly assigned to receive either 1% testosterone transdermal gel or placebo gel. Before participation in the study, all subjects provided written informed consent. Serum T in the OSA group was significantly lower compared with controls, and a statistically significant inverse correlation was found between serum T level and depressive symptoms Bercea et al. 2013. The remaining three trials did not adequately assess the relationship between TRT and OSA but offered some interesting results. The same authors, using the same cohort, also sought to evaluate body compositional and cardiometabolic effects of TRT with TU in men with obesity and severe OSA Hoyos et al. 2012b. Our literature search retrieved five studies that evaluated this association Barrett-Connor et al. 2008; Bercea et al. 2013; Hoyos et al. 2012a, 2012b; Killick et al. 2013. Although IPSS scores were shown to significantly improve with TRT over the first 5 years of therapy, one might postulate that if prostate volume continues to increase with continued use of TRT, then LUTS may subsequently worsen after a period of improvement. Sensitivity analysis These lines of evidence argue strongly for the need for greater awareness in the medical community of the impact of TD on health, and of the health benefits of TTh. Continued exploration of testosterone's role may lead to improved therapeutic strategies that enhance the quality of life and health outcomes across diverse populations. At the same time, its impact on mental health, particularly in alleviating depressive symptoms, underscores its multifaceted nature. This occurs as testosterone stimulates androgen receptors in hair follicles, promoting increased hair growth. We will provide information including trial identifier for potentially relevant ongoing trials in the 'Characteristics of ongoing studies' table and in a joint appendix 'Matrix of trial endpoint (publications and trial documents)'. We will attempt to identify other potentially eligible trials or ancillary publications by searching the reference lists of included trials, systematic reviews, meta‐analyses, and health technology assessment reports. Finally, testosterone is thought to exert a variety of beneficial effects on blood vessels and the heart though improvement of lipid profiles, insulin sensitivity, and exercise tolerance (Kloner 2016). In addition, testosterone modulates male sexual desire, spontaneous sexual thoughts, motivation, attentiveness to erotic stimuli, and sexual activity (Gannon 2016). Two review authors (JHJ, HWK, BR, JSL, or HSY) will independently extract key participant and intervention characteristics for the included trials.Exogenous oral and transdermal T studies at physiologic levels do not lead to insulin resistance or changes in fasting glucose 57,58,59,60.The long-term impact of biosimilar T therapy showed no increase in breast cancer incidence.Don't have any symptoms at all,Those who received TRT for one year, versus those on placebo, saw improvements in sexual function, including activity, desire, and erectile function.Most randomized controlled trials involving TTh have been of short duration."If the issue that caused your testosterone levels to drop in the first place resolves, you should have a trial off treatment and be re-evaluated by your doctor," says Dr. Hayes Bhasin researched the data for the article. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a result, their dosing is not very flexible and does not permit easy titration, which is essential for therapy in adolescents. Lack of TRT guidelines for adolescent males reflects the lack of appropriate data to guide recommendations. Clearly, more studies with better designs are required to determine the rate and reasons for dissatisfaction with current TRT options in adolescents. First, it is reasonable to assume pharmaceutical industry funded studies may be more robustly funded overall and should in theory report adverse events more diligently. It should be noted that trials that were not supported directly by the pharmaceutical industry Basaria et al. 2010 commonly used T doses of 100–150 mg in older and frail men. The potential that TD may be involved in the pathogenesis of CVD would create a notion that TRT would result in improved cardiovascular outcomes, yet no current evidence exists to support this claim. The highlighted studies addressed in this paper can be used to guide the clinician in how to best monitor patients on TRT, especially those with the comorbid conditions detailed below. However, many physicians continue to promote narratives that we should continue to hold back on treating these patients because of the unknown effects of testosterone, and that if they are treated, they should only be treated with FDA-approved preparations used in men. Mature osteoblasts have been shown to increase bone formation and increase BMD in both women and men. The major cause of osteoporosis in women has erroneously been thought to be estrogen deficiency due to menopause, while in men, age-related testosterone deficiency . Studies have shown that in women, both testosterone and estradiol can counter many of these and thus reduce beta amyloid deposition, improve the brain’s ability to metabolize glucose, and improve blood flow 15,16,17. It is important to know that, as well as several medications having side effects, testosterone hormone is not the exception because it can cause hirsutism, the excessive growth of coarse, dark hair in male-pattern areas such as the face, chest, and abdomen. Moreover, testosterone enhances endothelial function by promoting nitric oxide production, supporting the growth and repair of endothelial cells, and reducing inflammation. Additionally, testosterone is essential for muscle mass regulation, as it promotes protein synthesis and muscle hypertrophy by binding to androgen receptors in muscle cells . Transdermal preparations of T (patches or gel) are appealing options for TRT because they combine ease of administration with physiological and constant T levels. To overcome the erratic absorption of oral TU, a new oral formulation that is less affected by the lipid content of meals was approved by the FDA for hypogonadism in men . In addition, oral TU (40 mg daily for 8 weeks) had an effect on growth similar to an IM T ester mixture (Sustanon 50; Aspen Pharma Trading Limited, Dublin, Ireland) in a randomized crossover comparison study in boys with CDGP . The increase in sex steroid production during puberty speeds up bone mineral accumulation and causes sex-specific variations in bone growth; after mid-puberty, the male population experiences a greater increase in periosteal bone growth than the female population, who shows more pronounced endocortical bone formation . The hypothalamic-pituitary-gonadal (HPG) axis, a crucial part of the endocrine system, controls the production of testosterone. The synthesis and regulation of testosterone, a vital steroid hormone, are highly complicated procedures that involve intricate interactions among multiple endocrine glands, including the hypothalamus, pituitary gland, and gonads, as well as feedback mechanisms that maintain homeostasis within the body. Dysregulation of this feedback mechanism can lead to a variety of pathophysiological conditions, particularly testosterone deficiency; such disruptions may occur due to aging, disease processes, or lifestyle factors, underscoring the importance of accurate diagnosis and appropriate therapeutic interventions . Study selection Unfortunately, there have been no randomized head-to-head trials comparing transdermal delivery with sub-cutaneous pellets. The subcutaneous administration of testosterone has been used worldwide for decades. I have had many years of experience with sub-cutaneous administration of testosterone and estrogen with the use of pellets, and there are peer-reviewed publications to support this type of administration . There are many ways to prescribe testosterone, including transdermal, oral, intramuscular, and subcutaneous pellet implant application. HSDD is a sexual disorder characterized by distress related to a loss of or decline in sexual interest. Two prospective studies demonstrated a lower risk of cardiovascular disease (CVD) in women with endogenous T levels at the higher reference quintiles 61,62. Successful results have been observed with STT in reducing symptoms with minimal side effects by maintaining serum T levels between 150 and 250 ng/dL in women. This includes decreased memory, sense of well-being and libido, reduced muscle mass and bone mass, increased irritability, anxiety, fatigue, and symptoms of depression 1,3,4. 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. These advantages include better vascular function, mood, muscle strength, bone density, and sexual health in healthy men. Testosterone supplements can have a good impact on a number of important aspects of men's health, such as vascular endothelial function, mood (particularly in lowering depression), muscle strength, bone health, and sexual function. Descriptive, observational, and experimental studies including healthy men-more especially, those assessing the effects of testosterone therapy-were required for inclusion. For instance, the No. 1 contributor to falling levels is weight gain. "If you can identify the source for declining levels, often you can address that problem and increase low levels naturally," says Dr. Hayes. Several tests are required, as levels can fluctuate daily and be influenced by medication and diet. For a selected subgroup of men, the therapy can be a viable option. TRT's relationship with other health issues is also mixed. Androgens are essential for women in both female reproductive function and hormonal balance and as vital precursors in synthesizing female hormones such as E2 . Despite these data, there is still much controversy about the existence of androgen deficiency, its diagnosis, and clinical treatment. The rational use of androgens in women’s health and well-being is of great interest. In this perspective, we summarize whether it is prudent to develop an approach for managing postmenopausal women through STT, evaluating its possible CV benefits and risks. T therapy alone, at physiological doses, has been reported to be more effective than estradiol (E2)-T therapy or E2 alone for relieving postmenopausal symptoms with the same cardiovascular (CV) safety . Unfortunately, the study could not localize which cell types underwent apoptosis but others have confirmed that castration induces smooth muscle cell apoptosis 41, 42. The finding that T enhances both PDE5 and NOS activity seems to undermine its potential positive effect on erectile function, but one hypothesis is that this mechanism leads to a recycling of factors that are necessary to respond to the next sexual stimuli . A study using light microscopy to examine dorsal nerve sections from control and castrated rats showed that castration increased the axonal cross-sectional area (i.e. swelling) of the dorsal nerve neurons and decreased the density of the dorsal nerve fibers . T deprivation significantly increased serum SIP levels, SIP-2, and SIP-3 receptor mRNA transcription; led to a two-fold increase in CCSM contractility; and diminished erection response scores. Its etiology is multi-factorial in most men with risk factors that include psychiatric disorders, endocrine dysfunction, vascular disease, penile structural anomalies, substance abuse, and medication use 12,13,14,15,16,17. Taking magnesium as a supplement has been shown to increase free and total testosterone values.Sharper focus mentally, with improved levels of concentration and memory make completing tasks both at work and at home easier.Late‐onset hypogonadism is a relatively common medical condition affecting the aging male, but is difficult to diagnose since there are no clear‐cut differences in relation to the physiological aging process.Limitations of our study are that we used only Google as our search engine, and there may be regional and geographic differences in search engine results.In these cases, a hormonal factor is often not the primary cause of dysfunction, and thus while TTh should be considered, other treatments are likely to be more effective.Then, over the next 3 years, the number of men taking it dropped by half as studies revealed potential risks, particularly to heart health.“It’s very important to have an open discussion about the benefits and the risks of HRT.”There are numerous benefits of testosterone for men and women that will be discussed here. Levels of testosterone gradually decline because of increasing age or they reduce abruptly following oophorectomy. Women actually produce three times as much testosterone as oestrogen before the menopause. Testosterone is one of the sex hormones that women produce, yet it is often overlooked. STT dosages should be individualized, respecting the woman’s weight and symptomatology more than laboratory levels. Common drug-related adverse events include increase in hematocrit, acne, breast tenderness, gynecomastia, and exogenous testosterone can lead to a state of transitory infertility. Testosterone plays an essential role in several aspects of men’s health. However, healthy habits that boost testosterone, like getting good sleep and exercising, certainly won't hurt. There aren't studies to back up using it for other symptoms. Increased cortisol levels can also cause you to overeat, which can contribute to weight gain and lowered testosterone. Sleep is essential for your good health, and it affects your testosterone. Notably, both groups experienced a decline in their erectile function gains and serum T levels 6 weeks after stopping combination therapy, suggesting that this therapy may require long-term use for sustained effect. Of note, the inverse relationship between the efficacy of TRT and a eugonadal state may explain why a contemporary study did not find a benefit of T supplementation on erectile function, as nearly half of the study population had normal baseline levels of T . An increase in the IIEF erectile function domain (EFD) score of 4 points after treatment with oral pharmacotherapy has been shown to indicate a meaningful clinical improvement . T deficiency or hypogonadism can be accompanied by symptoms across multiple systems, including fatigue, mood disturbance, diminished libido, and erectile dysfunction (ED) 4,5,6. Consensus is still lacking in several areas, such as the threshold of low T severity for which replacement therapy is most beneficial; the timing for initiating combination therapy; and the duration of treatment. Number of subjects with baseline and at least 1 postrandomization physical function test or body composition record.Men with low testosterone levels may experience problems with erections and may suffer from brittle bones (osteoporosis), weakness, feeling down (low mood) and tiredness.After mid-puberty, boys exhibit a greater increase in periosteal bone growth than girls, who, in turn, experience more significant endocortical bone formation .Similarly, it is difficult to estimate the number of adolescent boys with functional hypogonadism, who would also benefit from TRT.Recent US data showed that 2.2 million men were prescribed testosterone in 2013 compared to 1.2 million in 2010 (Nguyen 2015).Was responsible for conducting the search, compiling the eligible studies, interpreting the studies, writing the manuscript, creating the tables, and organizing the reference lists. What can you expect from testosterone treatment? One downside is that these pills are expensive and may not be covered by insurance, unless you've tried other methods of treatment and had no success or bad side effects. A nurse or technician may give you testosterone as a shot directly into a muscle. Beyond these physical advantages, testosterone plays a crucial role in male reproductive health by affecting spermatogenesis (the generation of sperm), libido, and erectile function. In addition, there has been a surge in Men's Health clinics and online direct-to-consumer Web sites, making testosterone replacement therapy much more readily accessible. We believe the evidence presented in this study support the position that the importance of TD in health care and the benefits of TTh in these men is under-recognized and underappreciated. They will also do a physical exam and ask whether you have the symptoms of low T before prescribing anything. You need a prescription from your doctor to access testosterone. Also, the steroids are often combined ("stacked") with other substances like stimulants, pain relievers, and growth hormones to boost the overall muscle-building effect. These steroids usually contain testosterone or chemicals that act like testosterone. If your levels are low because of aging, you don't need TRT. A patient with basic insurance using a medical center paid around $500 for the evaluation, plus about $200 for follow-up and 3 months of treatment. During the time you're on TRT, your body stops making testosterone, so you'll want to give it time to start making its own male hormone again. If you do want to discontinue taking testosterone, don't stop cold turkey. The researchers found that for 92 patients (61%), the effects of TRT did not continue, but they did for the other 59 patients (39%). In the study “Low complication rates of testosterone and estradiol implants for androgen and estrogen replacement therapy in over 1 million procedures” , a proprietary dosing algorithm was used to achieve testosterone levels between 150 and 250 ng/dL. The injectable and transdermal male preparations, however, have been shown to cause elevated spikes in serum testosterone levels and an increased risk of side effects and secondary reactions . Numerous studies have shown that adding testosterone to hormonal therapy can improve sexual function and general wellbeing among women during their menopause. The parameters with the most consistent evidence for improvement after testosterone replacement therapy (TRT) are anemia, bone mineral density, lean body mass, depressive symptoms, and ED 7,8,9,10. However, these studies are rarely cited in clinical guidelines, with many neglecting even to mention TTh as a possible option. Many of these studies have been published in high-impact medical journals by highly regarded investigators. Yet this open-minded approach to new and evolving information seems to not apply to studies involving TTh. There were no adverse events related to subcutaneous T therapy; besides increased facial hair and mild acne, these doses had minimal side effects. Although models of supraphysiologic T levels, such as polycystic ovarian disease (PCOS), have shown an increased risk of presenting CAD. Consistently, previous studies have shown an association between a low T level and an increased risk of CV diseases 38,41,42 and a lower T level in men with CAD compared to those without 43,44. A key component of human physiology is hormonal regulation, which intricately regulates a wide range of biological processes and maintains homeostasis across multiple systems; from the many hormones that regulate bodily functions, testosterone stands out for its significant and complex effects on male health . 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. We think our findings offer some reassurance to doctors and patients that testosterone replacement therapy does not increase the risk of heart problems. 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. For example, the outcome of bone health was only reported in three RCTs that were not designed to study bone health. Other androgenic side effects were also reported in some trials (weight gain, alopecia, and voice deepening); however, data were insufficient for meta-analysis. The quality of evidence is moderate for both due to moderate risk of bias of the included studies. The quality of evidence was moderate for LDL and low for HDL, rated down due to moderate risk of bias in the included studies and significant heterogeneity for studies that assessed HDL. The quality of evidence for both of these outcomes is low to moderate, downgraded due to high inconsistency and moderate risk of bias in the included studies. It can sometimes take several weeks or even months for a woman to notice the beneficial effects of testosterone. The normal range of testosterone is difficult to define as most of the available tests do not provide the accuracy or precision required when testing the low serum concentrations in women. Commonly used testosterone replacement in menopause5 The group found that TRT offered slight improvements to sexual and erectile function; they found no other benefits. Another concern is whether TRT actually improves symptoms linked to low testosterone. From 2001 to 2013, prescriptions rose by 300% following marketing efforts that proclaimed it could restore energy, alertness, mental focus, and sexual function. However, it has been recognised that diagnosis of late‐onset hypogonadism should be made only in men with consistent symptoms and signs and unequivocally low serum testosterone levels (Khera 2016; Lunenfeld 2013; Wang 2009). To assess the effects of testosterone compared to placebo or other medical treatments in men with sexual dysfunction. Beyond the well-described concerns of untreated hypogonadism on sexual development, bone, and cardiometabolic health, questions regarding the impact of sex steroids on neurocognition and executive function in these adolescents remain . T replacement therapy (TRT) has recently expanded in adults because of its increased use among men with functional hypogonadism . In men with low testosterone, “normalizing” testosterone levels has multiple benefits, most notably improved libido and improved erectile function when used as monotherapy in men with mild ED. Our primary objective was to systematically review all data published in the last two decades on testosterone boosters and determine their efficacy. Our knowledgeable team is equipped with the expertise and cutting-edge treatments to empower you to reclaim your life once and for all. And since your Focal Point experience puts you in the driver’s seat, you have the flexibility to choose your path to a happier, healthier you. In addition to personalized treatments, Focal Point Vitality also offers a wide range of age management therapies to complement TRT. The best testosterone therapies are the ones that have been tailored by an experienced professional, just for you. Testosterone does decline in women as they age, especially after menopause, but most of the time, TRT is not needed. Most of the testosterone is produced in the ovaries. Women and people assigned female at birth do produce testosterone as well as estrogen, though the amounts of testosterone are much smaller than those produced by men. For example, the study that examined castration-induced upregulation of sphingosine-1-phosphate and consequent contraction of rat CCSM showed that administering an S1P receptor antagonist reinstated CCSM relaxation . The literature presented herein illustrates that T mediates erectile function, but it is imperative to note that T is not necessary for satisfactory erections. This may indicate that in men with ED and serum T at the lower limits of normal, PDE5i alone could be offered upfront and after the failure of monotherapy, TRT could be used adjunctively. Areas of heterogeneity include criteria for hypogonadism (total serum T ≤ 330 to 400 ng/dL); baseline ED criteria (IIEF-EFD score 2). The most recent meta-analysis on the efficacy of combination therapy included eight RCTs with 913 hypogonadal men with ED. However, the study lacked a true control arm during the open-label portion of the trial, limiting the ability to make this conclusion. This finding suggests that benefits of TTh on libido plateau after 3 months of therapy. Recently, the Sexual Function sub-trial of the Testosterone Trials examined sexual desire. ” Like the IIEF-EF domain, the IIEF-SD questions can be used to diagnose mild, mild to moderate, moderate, and severe dysfunction . Libido, or sexual drive, is affected by a multitude of factors, including physiologic ones, such as a defect in the hypothalamic-pituitary access or depression, or environmental ones, such as marital discourse or anxiety 3, 35, 36. These are supplements that contain things like vitamins, minerals, and herbs that are meant to increase your body's natural production of testosterone. Your ideal level of testosterone is difficult to calculate. You may be interested in natural testosterone boosters instead. Testosterone levels naturally decline as you age. Yet TRT remains controversial because of its uncertain benefits and potential health risks. Testosterone replacement therapy (TRT) has surged in popularity over the past decade. Gene-editing therapy lowers harmful blood fats in early study Risks and benefits of testosterone therapy in older men. All data analyzed during this study are included in this published article or in the data listed in “References.” Since the early 1940s it was believed that TTh increased the risk of prostate cancer. There is no scientific basis for the belief that a man with a known cause of TD merits treatment but a man without a known cause does not, since in both cases the problem is a deficiency of the same molecule, that is, testosterone. In medicine, Nobel Prize winner Charles Huggins wrote in 1941 that testosterone “activates” prostate cancer, and this belief persists to the present day despite overwhelming evidence to the contrary,11 as reviewed hereunder. Also called androgen replacement therapy, this is a medical treatment your doctor may prescribe if blood tests show unusually low levels of testosterone. The outcomes included sexual function, psychological symptoms, bone health, body measurements, lipid profile, and incidence of hirsutism and acne. Conclusively, testosterone is an essential hormone that is involved in many physiological processes throughout men's lives; in addition to controlling libido, testosterone is closely linked to bone density, muscle growth, and repair; its influence on mental health, especially in reducing symptoms of depression, emphasizes its complex nature. In men with hypogonadism, including elderly individuals, testosterone replacement therapy may offer antidepressant effects, providing therapeutic benefits for those with testosterone deficiency . Regarding the results of our PubMed review, there were no studies looking at the effect of the individual supplements on T levels for 67 of the supplements (61.5%). However, one study found that 87.8% men with low T were not receiving treatment, despite adequate access to care . The symptoms of low T are relatively non-specific and can be seen with several other medical conditions, and an accurate diagnosis is vital to direct treatment. Men take testosterone (T) boosting supplements to naturally improve T levels. By identifying limitations in existing studies and suggesting directions for future investigations, we hope to encourage the research community to pursue more robust and methodologically sound studies that will further strengthen the evidence base. Since the WHI studies almost twenty years ago, much confusion has occurred regarding estrogen supplementation, and this has led to many negative and inaccurate perceptions around the use of testosterone in women. This has resulted in millions of women suffering in silence with very common symptoms of perimenopause and menopause that could easily be addressed with the use of testosterone. There is an urgent need to ensure gender equality in effectively managing women with sexual dysfunction related to hypoandrogenic states. There are little long-term safety data on the use of testosterone in menopausal women beyond 2 years. The Most Misunderstood Molecule in Medicine An additional small number of uncontrolled or retrospective studies confirmed a positive effect of TE on growth and pubertal maturation in boys with CDGP 14, 17, 21, 84. Testicular size and serum T concentrations were greater in boys treated with TE vs their respective controls 1 year after initiation of therapy . Both reported increases in height velocity compared to controls, with no adverse bone age advancement. Two prospective controlled trials, published in 1995 or earlier, evaluated 2 regimens for pubertal induction in adolescents with CDGP 11, 83. As most menopausal women can be managed in primary care, the new BMS guidance will aid GPs to feel confident to initiate testosterone, if appropriate, or to continue prescriptions that have been started in specialist clinics. Having a licensed testosterone preparation available for women would certainly be a step in the right direction. Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess, with a serum total testosterone level every 6 months to screen for overuse. An international task force of experts from leading medical societies, brought together by the International Menopause Society, has recently produced a Global Position Statement to provide clear guidance regarding the prescribing and measurement of testosterone for female testosterone therapy, as well as advice on testosterone prescribing practices that have the potential to be ineffectual or cause harm. Current BMS guidance suggests that, when monitoring women who are using testosterone, the level of FAI should be maintained at Box 2).5 These benefits include improvements in sexual function, bone health, muscle strength, mood, and vascular endothelial function in healthy individuals. Since TRT returns your testosterone levels to a healthier range, you get back your “groove” and enjoy intimacy again. But as men get older and their testosterone levels dip, so does bone density. Testosterone (T) therapy is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. We searched PubMed for articles (in English) on testosterone therapy, androgens, adolescence, and puberty in humans. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs. All data analyzed during this study are included in this published article or in the data listed in “References.”Of these, 17 trials (3431 participants) provided individual participant data.The reduction in estrogen replacement therapy that occurred after WHI led to tens of thousands of deaths in women according to one study .Another critical point was the lack of safety studies of long-term androgen administration in women and the certainty of the correlation between sexual symptoms and plasma T levels.Reassuring evidence is emerging on the use of transdermal T to induce and maintain puberty.In addition, previous studies have not confirmed side effects such as deepening of the voice and worsening of cholesterol .This study then evaluated the effect of TRT on mortality in men in the low T group that was divided into men who did and did not receive TRT.Current TRT regimens are based on consensus and expert opinion, but evidence-based guidelines are lacking.The role of Testosterone Therapy (TTh) in the management of male sexual dysfunction remains unclear. We will present information on abstracts or conference proceedings in the 'Characteristics of studies awaiting classification' table. In addition, we will contact authors of included trials to identify any additional information on the retrieved trials or any further trials we may have missed. Should we identify new trials for inclusion, we will evaluate these and incorporate the findings into our review draft (Beller 2013). After we submit the final review draft for editorial approval, the CMED group will perform a complete search update on all databases available at the editorial office and will send the results to the review authors. We will continuously apply a MEDLINE (via Ovid SP) email alert service established by the Cochrane Metabolic and Endocrine Disorders (CMED) group to identify newly published trials using the same search strategy as described for MEDLINE (Appendix 1). In another randomized trial, oral TU at the dose of 40 mg daily was equally effective as oxandrolone 2.5 mg daily in terms of growth, pubertal maturation, and bone age advancement in boys with CDGP . Two double-blind, randomized, placebo-controlled trials tested 2 different doses of TU (20 mg daily for 6 months in one vs 40 mg daily for 3 months in another) in small numbers of boys with CDGP 59, 60. They both have suboptimal pharmacokinetic profiles and reach supraphysiological T concentrations a few days after injection that gradually decrease to subphysiologic levels within the following 2 to 3 weeks 58, 85. Your body slowly absorbs the testosterone into the bloodstream. They do this by making a small cut in your skin and using a special tool to implant 10 pellets of testosterone. A health care provider inserts these pellets under your skin (usually in the buttocks area) every 3 to 6 months. The patch continuously releases testosterone into the blood through the oral tissues. Be careful about letting children or female loved ones touch the treated area or touch unwashed clothes that were in contact with the gel, as testosterone may get transferred to them. In diabetic men TTh improves insulin resistance, and a large 2-year controlled study in men with abnormal glucose tolerance showed a substantially reduced rate of diabetes among men treated with TTh compared with untreated controls. Several studies have demonstrated that TTh in men with TD reduced all-cause and cardiovascular mortality. In a roundtable symposium, investigators summarized the contemporary evidence in several key clinical areas. This article does not contain any study with human participants or animals performed by any of the authors. We conducted a systematic review and meta-analysis of randomized trials to summarize the best available evidence regarding the benefits and harms of systemic T in postmenopausal women with normal adrenal function. Testosterone replacement therapy (TRT) is a well-established option for those with symptomatic hypogonadism related to low T levels. Additionally, there is a significant correlation between bone density and testosterone levels; a decrease in testosterone can result in decreased bone density . Choose doctors who understand how Low T affects the body and the treatment that is required to correct it. Years of research and knowledge are available to provide the finest care in both diagnosis of Low T and its ensuing treatment. Sharper focus mentally, with improved levels of concentration and memory make completing tasks both at work and at home easier. Early studies have shown that TTh can improve the response to PDE5 inhibitors in non-responders. In a 2012 RCT, Spitzer et al. studied 140 men on sildenafil and then randomly assigned them to either receive testosterone or placebo gel. The severity of ED is then classified as mild, mild to moderate, moderate, and severe dysfunction. Subjective erectile function can be assessed using validated questionnaire metrics including the international index of erectile function (IIEF) with the erectile function domain (IIEF-EF) being the most specific for assessing ED. The National Institute of Health (NIH) defines ED as the “inability to achieve or maintain an erection that is satisfactory for sexual performance” . Low endogenous T levels correlate with an increased risk of adverse CVD events, and endothelial dysfunction and increased atherosclerosis are means by which male hypogonadism may contribute to an increased risk of death Jackson et al. 2010. TRT has been shown to increase serum T to physiologic levels, improve libido, improve erectile dysfunction, improve overall sexual function, increase energy, improve mood, increase bone mineral density, decrease body fat mass, and increase lean body muscle mass Bhasin et al. 2010; Corona et al. 2013. If you have low testosterone levels but no symptoms, low testosterone treatment isn't recommended. In the event of duplicate publications, companion documents, or multiple reports of a primary trial, we will maximise the information yield by collating all available data and will use the most complete data set aggregated across all known publications. We will email authors of all included trials to ask if they would be willing to answer questions regarding their trials. We will attempt to locate the protocol for each included trial and will report primary, secondary, and other outcomes in comparison with data in publications in a joint appendix.