what is considered to be a low testosterone level?
Proc (Bayl Univ Med Cent). 2014 Oct; 27(iv): 321–324.
Diagnosing and managing low serum testosterone
Abstruse
Measuring testosterone levels became easier in the 1970s, and it wasn't long before levels were being checked in men across all historic period groups. At that time, several authors reported an historic period-associated decline of serum testosterone levels kickoff in the 4th or fifth decades of life. Other studies plant that the decline in testosterone with historic period might be more related to comorbidities that develop in many aging men. Aggressive marketing campaigns past pharmaceutical companies accept led to increased awareness of this topic, and primary intendance physicians are seeing more than patients who are concerned almost "low T." Unfortunately, testosterone replacement therapy has not been straightforward. Many men with low testosterone levels take no symptoms, and many men with symptoms who receive treatment and reach goal testosterone levels have no improvement in their symptoms. The bodily prevalence of hypogonadism has been estimated to be 39% in men anile 45 years or older presenting to primary intendance offices in the The states. Equally the Usa population ages, this number is probable to increase. This commodity, targeted to primary intendance physicians, reviews the concept of belatedly-onset hypogonadism, describes how to determine the patients who might benefit from therapy, and offers recommendations regarding the workup and initiation of treatment.
A 56-year-old overweight man with symptoms of low free energy, daytime sleepiness, and decreased libido happens to be watching a golf tournament on Television from his favorite recliner and of a sudden a commercial appears. This patient is in your office the post-obit Monday and asks y'all, "Is it low T?"
Aggressive marketing campaigns by pharmaceutical companies take led to increased awareness of hypogonadism amid men, who may and then present to the clinic requesting testing or treatment (ane). As a consequence, primary care physicians are seeing more patients like the one described above. The physiological age-related decrease in testosterone production should be differentiated from late-onset hypogonadism (LOH), defined equally the presence of three sexual symptoms and low testosterone (low T) in aging men (2). This definition was proposed to help clinicians identify aging men with low testosterone who could potentially benefit from hormonal replacement therapy. The purpose of this article is to review the data on LOH, also known as low T, and present the most recent evidence and recommendations regarding the approach to the patient from our case scenario.
PHYSIOLOGY AND DEFINITIONS
Male reproductive endocrine physiology involves the hypothalamic-pituitary-target organ and feedback model. Disruptions at different levels of this pathway can lead to disturbed androgenic furnishings: primary disorders of the testes (primary hypogonadism), disorders of the pituitary or hypothalamus (secondary hypogonadism), and disorders of androgen action on target tissue or androgen resistance. Other less common entities that manifest as androgen deficiency include chronic stress (by suppressing gonadotropin-releasing hormone secretion) and exogenous glucocorticoids, which can theoretically block the effects of testosterone on its target tissues (three).
In men, testosterone levels increase from puberty to adulthood and then progressively turn down starting by the quaternary or fifth decade of life (iv). Multiple studies accept raised the question of whether or not the declining T level seen in aging men is a natural historic period-related procedure or is caused by the aggregating of multiple chronic medical illnesses that virtually all aging men feel. One pocket-sized study investigated this question by looking at groups of men across different historic period groups who were in "very good or excellent health" (5). The authors found no statistically significant deviation in serum total testosterone levels across the cohorts grouped by decades of age. Their information back up the idea that "the decline in serum T with male person ageing is a not-specific effect of the common co-morbidities that accrue during ageing" (5). Despite this novel study'due south results, the fact remains that well-nigh aging men seen in primary care offices are very likely to take at least ii chronic medical illnesses (6) and are dissimilar from the study population. It would be helpful if wellness intendance professionals could identify men with low serum testosterone levels who are likely experiencing symptoms purely from androgen deficiency and would therefore do good from treatment.
LATE-ONSET HYPOGONADISM
Symptoms of hypogonadism are highly nonspecific and include decreased libido, erectile dysfunction, decreased volume of ejaculate, loss of body and facial hair, decreased os density, decreased lean torso mass, increased torso fat, fatigue, weakness, increased anxiety, profuse sweating, and anemia (7). It is challenging to differentiate these symptoms from those that outcome from crumbling per se, and this was one of the reasons why the concept of LOH was introduced.
LOH is defined as a full testosterone level <300 ng/dL combined with the presence of iii sexual symptoms:
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Decreased frequency of morning erection
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Erectile dysfunction
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Decreased frequency of sexual thoughts
Sexual symptoms have been constitute to be more strongly associated with androgen deficiency and are therefore specified in the definition of LOH (eight). This syndromic approach involving clinical and biochemical criteria allows physicians to identify patients who are symptomatic from androgen deficiency and separate them from those with isolated biochemical hypogonadism and nonspecific symptoms from aging. Further research by the European Male Aging Study has found an association between LOH and stop-organ deficits compatible with androgen deficiency, specifically low hemoglobin, reduced bone mineral density, and reduced muscle mass (ii).
Data on the prevalence of low T are highly variable due to the different cutoffs used to define low testosterone and the clinical syndrome of LOH (three, 9, ten). The Massachusetts Male Aging Study (10), an observational cohort written report conducted on salubrious men aged 40 to 70 years from the Boston surface area, estimated that the prevalence of androgen deficiency (total testosterone <400 ng/dL) in men in this age group was 25.iii% to 39.3%, but when considering the presence of at least three signs or symptoms of depression T (the definition of LOH), the prevalence dropped to half dozen% to 12%.
DIAGNOSIS
Guidelines, including the most recent guidelines published past the Endocrine Society in 2010, recommend against screening asymptomatic patients and against case finding with tools such as the ADAM (Androgen Deficiency in the Aging Male) questionnaire. Guidelines do recommend considering case detection, which involves testing specific groups of patients that may be at higher hazard of androgen deficiency due to certain comorbid diseases (blazon 2 diabetes mellitus, moderate to astringent chronic obstructive pulmonary disease, obesity, etc.) (11).
Symptoms are by and large nonspecific. Even the sexual symptoms tin be due to many other weather condition, including vascular disease, chronic alcohol use, and depressive disorders. Thus, many men are seeking solutions for these bothersome symptoms, which may involve indiscriminant testing and possible overtreatment.
The physical test also is mostly nonspecific. Typical examination or diagnostic findings include obesity, loss of torso pilus, gynecomastia, balmy anemia, and osteoporosis. Testicular volume may exist decreased (normal volume 15 to thirty mL, equivalent to the size of a quarter dollar money). In improver to size determination, the testes should be palpated to rule out the presence of a mass, which may represent a benign or malignant tumor. A pituitary mass may cause visual field deficits, and prolactinomas specifically tin crusade galactorrhea (11, 12).
The diagnostic approach to hypogonadism is illustrated in Effigy 1 . Normal values for testosterone levels vary among different sources (2, 11, 12). The most common cutoff transitioning from normal to low ranges from 280 ng/dL to 320 ng/dL; the guidelines recommend using 300 ng/dL as the cutoff (11). Serum testosterone levels exhibit ultradian and cyclic variation, providing physiologic sources of biologic variability. Ultradian fluctuations (rhythmic fluctuations of less than a 24-hour menstruum but more than than one hour) are more pronounced in older men, while circadian variation in testosterone is blunted, simply notwithstanding present, in older men (12). Therefore, except in older men, a morning (7 to 11 AM) serum total testosterone should be checked initially, if testing is necessary. At that place is some evidence that a glucose load tin significantly decrease testosterone levels for a short time, so conducting this exam in the fasting country may result in improved accuracy (thirteen). If initial test results are depression, repeat measurements are recommended in two to 3 weeks, since repeat levels may be within the normal range in up to 30% of cases. Additionally, at this indicate it is prudent to consider exterior influences on sex hormone production and accost these problems showtime if advisable. Such issues include use of corticosteroids or opiates, malnutrition, acute disease, alcoholism, and cirrhosis (5, eleven, 12). If the testosterone levels are equivocal, consider checking a free or bioavailable testosterone level. Information technology is important to note that there is an age-associated increment of sex hormone binding globulin levels by about i.2% per twelvemonth, so the decrease of complimentary testosterone is larger than that of total serum testosterone in older patients.
Diagnostic approach for patients suspected of having hypogonadism.
If testosterone is confirmed to be low, information technology is recommended to categorize the hypogonadism as primary or secondary by checking levels of luteinizing hormone and follicle-stimulating hormone. Elevated levels of these hormones would indicate main testicular failure. Causes include LOH, Klinefelter syndrome, and infectious diseases such as chlamydia- and gonorrhea-associated epididymo-orchitis and mumps. If luteinizing hormone and follicle-stimulating hormone levels are depression (or inappropriately normal), secondary hypogonadism is diagnosed and hypothalamic/pituitary pathologies should be considered (xi, 12) depending on the patient'south presentation.
TREATMENT
One time the diagnosis of LOH is confirmed, testosterone replacement therapy (TRT) should be considered with the goals of improving secondary sexual characteristics, sexual function, sense of well-being, and bone mineral density. During the initial workup, if a clear treatable condition that explains androgen deficiency is diagnosed, it should exist addressed first (11, fourteen).
In obese individuals, several studies accept demonstrated that intense lifestyle intervention and weight loss are associated with a rising in testosterone levels. Androgen ascent has been plant to exist greater in those patients who lose more weight (xiv, 15). Information technology is therefore important to recommend weight loss either prior to or concomitant with TRT in obese patients. Obese patients should likewise be assessed for obstructive slumber apnea, which is also an important cause of low T (16).
TRT in older men with depression testosterone concentrations has been associated with improved libido, sexual part, mood, and mayhap musculus force (12, 17). Comeback in bone mineral density has been reported, simply no studies exist that determine whether the risk of fractures in these patients decreases when receiving TRT (11, 12, eighteen).
Controversy exists about the long-term safe of TRT. Although several studies have reported a significant reduction of carotid intima media thickness; decreases in fatty mass, blood pressure level, fasting glucose, and insulin resistance; and increases in high-density lipoprotein cholesterol (12, 19), the effect of TRT on cardiovascular risk is still uncertain. One written report in men older than 65 years of age with limitations in mobility and a high prevalence of chronic disease concluded that the application of a testosterone gel was associated with an increased take chances of cardiovascular agin events (20). Many argue that the investigators used higher dosages of testosterone than recommended by the guidelines or that the results might have been associated with increased hematocrit in the treatment group. In dissimilarity, other studies have constitute increased cardiovascular bloodshed in patients with testosterone deficiency (19). Further studies are needed to decide the exact role of testosterone and TRT in cardiovascular risk. This is an issue patients should be aware of when considering TRT. Debate also surrounds to what extent metastatic prostate cancer and breast cancer may be stimulated during testosterone treatment. For this reason, all men should be assessed for hazard of breast and prostate cancer prior to treatment. Other potential side effects of TRT include fluid retentiveness, acne, slumber apnea, gynecomastia, and infertility (11). The 2010 guidelines list the following contraindications to TRT: breast cancer, astringent lower urinary tract symptoms, and poorly controlled heart failure.
The different testosterone preparations bachelor include intramuscular formulations, topical gels, solutions, and skin patches. Tablets and implanted subcutaneous pellet formulations are less commonly used options. Each preparation has advantages and disadvantages and should be presented every bit an option to the patient (Tabular array 1). Intramuscular injections are administered every 2 to three weeks and merchandise the inconvenience of bimonthly injection visits with the abstention of possible medication contact with other household members. A disadvantage of the injections is the fluctuation in serum testosterone concentration that can cause fluctuating libido, free energy level, and mood. Transdermal forms offer more stable concentrations (13), but they can cause rash in the applied area.
Tabular array 1.
Therapeutic options for testosterone replacement therapy
| Preparation | Route | Advantage | Disadvantage |
|---|---|---|---|
| Testosterone cypionate, Testosterone enanthate | Intramuscular | Constructive, avoids daily assistants | Requires intramuscular injection of oily solution |
| Patch | Transdermal | Relatively convenient, stable serum concentrations | Daily application, rash in up to xxx%, unavailable in some countries |
| Gels | Transdermal | Consequent serum levels | Daily application, theoretical transfer to others upon skin contact |
| Injection (pellets) | Subcutaneous fat implants | Only needed every 3–6 months | Requires surgical implantation |
| Fluoxymesterone, Methyltestosterone | Oral | Convenience | Up to iv daily doses may be needed, potentially significant hepatic furnishings and first-laissez passer metabolism leading to ineffective therapy |
| Testosterone undecanoate | Oral | Convenience | Aforementioned every bit other orals but mayhap fewer hepatic effects; available in Canada and Europe, not USA |
| Buccal testosterone | Oral (patch that adheres to buccal mucosa) | Convenience | Some dropout in trials due to discomfort due to patch |
MONITORING AND FOLLOW-UP
The general target level for testosterone ranges from 350 to 750 ng/dL, which is roughly the range for good for you, androgen-sufficient adult men. Testosterone levels should exist monitored 3 to 6 months after initiation of handling. Patients receiving the intramuscular testosterone enanthate or cypionate should have levels checked midway between injections, and levels should be checked 3 to 12 hours afterward application in the instance of transdermal patches (11, 13).
The recommended duration of testosterone assistants is uncertain. A hematocrit examination is recommended prior to therapy initiation to found a baseline for future monitoring. Hematocrit and prostate-specific antigen (PSA) levels should be measured 3 to 6 months afterwards handling initiation then annually. TRT should be reconsidered in patients with a hematocrit >50%. An increase in PSA of more than than ane.iv ng/mL within a 12-month period of testosterone treatment or an International Prostate Symptom Score higher up nineteen should prompt urological evaluation. On the other hand, what should a clinician practise with a PSA value that increases to a bottom caste per year but is steadily increasing every fourth dimension information technology is checked? This tin can be managed using the concept of PSA velocity. Any PSA velocity >0.4 ng/mL per year should also prompt urological evaluation (at to the lowest degree 2 years of measurements are needed, based on PSA values measured at to the lowest degree half dozen months after initiating therapy). For case, PSA levels of 1.5 ng/mL, 2.three ng/mL, and iii.3 ng/mL over 3 years do not see the first indication for urology referral (more than 1.four ng/mL over a twelvemonth'southward fourth dimension) but show an average PSA velocity of 0.9 ng/mL and require referral based on that criterion (xi).
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255853/
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