Male Screening for Hypogonadism

1a. Quality Improvement Initiative

Hypogonadism or testosterone deficiency (TD) is a disease characterized by the low levels of serum or testosterone that is accompanied by the pituitary and testicular disorders. Low serum testosterone is characterized by various cardiovascular risk factors such as dyslipidemia and adverse levels in the profile of clotting (American Association of Clinical Endocrinologist, 2002). The quality improvement initiative for patients with hypogonadism is testosterone replacement therapy, which would lead to improvement in mood associated with the potentiality of reduced total levels of cholesterol and serum tumor necrosis factor α ( Rastrelli et al., 2015) . The improvement in the signs and symptoms of hypogonadism occur at different times depending on the organ systems. For instance, the reduction in the fat mass and increase in the lean body mass occurs within 12-16 weeks. On the other hand, improvements in libido are experienced within 3-6 weeks of commencement of TRT. 

1b. Background of Hypogonadism

There has been an increasing prevalence in the hypogonadism in older male population, where its effects increase with the age ( Araujo et al., 2004) . Hypogonadism resulting from defected gonads was traditionally referred to as the primary hypogonadism, where the best examples include Klinefelter and Turner syndrome, while that resulting from defects in the hypothalamus or the pituitary gland was conventionally known as secondary or central hypogonadism ( Lawrence et al., 2017) . The disease is highly associated with other comorbidities like obesity, type II diabetes, and hypertension. Hypogonadism in the male is secondary to renal failure, where it is recognized in patients having the end-stage renal disease ( Rastrelli et al., 2015) . It has always been thought to contribute to the high levels of dysfunction in sex as the affected population experiences osteoporosis. The major setback in the characterization of hypogonadism has been the creation of its association with the lesser degrees of renal dysfunction. 

1c. Goal Consideration for Screening in Primary Care Setting

Several screening tests have been recommended for hypogonadism in the primary care settings, where the main goal has been to diagnose the patients with underproduction of the sex hormones ( Huhtaniemi, 2014) . The type and number of screening tests are highly dependent on the symptoms of the patient and the overall health (American Association of Clinical Endocrinologist, 2002). Screening is carried out to distinguish the different forms of congenital hypogonadism that may require long-term substitution and to differentiate between the congenital and the acquired hypogonadism ( Lunenfeld et al., 2015) . The other screening objective is to detect a tumor or specific issues with the pituitary gland, which is carried out by imaging tests. 

Pathophysiology and Targets

2a. Primary versus Secondary Hypogonadism

Primary Hypogonadism results from the testicular failure, where it is associated with the low levels of serum testosterone and high concentrations of follicle-stimulating and luteinizing hormone. In this case, the primary type of hypogonadism is also referred to as the hypogonadotropic hypogonadism ( Rastrelli et al., 2015) . The primary form of hypogonadism can result from all forms of injury to the testis or development of a tumor to the testicles. It may also result from genetic defects that affect the testicular development such as the Klinefelter syndrome. In some special cases, primary hypogonadism may be caused by exposure to chemotherapy, radiation treatment or abuse of alcohol. 

Secondary hypogonadism is also known as the hypogonadotropic hypogonadism, which is characterized by the defects in hypothalamic and pituitary defects that result in the lowered levels of testosterone ( Araujo et al., 2004) . The testosterone levels are normally lowered because of the stimulations in the Leydig cells. The disease is highly associated with low levels of the follicle-stimulating and luteinizing hormones ( Fui et al., 2014) . The patients having this type of hypogonadism can have their fertility restored using the application of a suitable stimulating hormone, while infertility caused by the primary type of hypogonadism cannot be reversed ( Rastrelli et al., 2015) . There are various causes of secondary hypogonadism, where the primary cause is the disorders in the hypothalamus and the pituitary glands as well as the Kallmann syndrome (American Association of Clinical Endocrinologist, 2002). The other cause is the infection resulting from medical procedures and infections from certain illnesses that affect the hypothalamic-pituitary system. The lowered levels of testosterone can be caused by the primary and secondary types of hypogonadism, a condition known as the mixed hypogonadism. The combined form of hypogonadism is highly susceptible in men with sickle cell anemia and among the aged patients. 

2b. Screening Targets

Age Demographics: In countries like Baltimore, 19% of the men aged 60 years and above are found to have low levels of testosterone. On the other hand, the Hypogonadism in Males (HIM) study reveals that the prevalence of the disease is 39% in men who are between the ages of 18-45 years ( Rastrelli et al., 2015) . The study shows that the fraction of hypogonadal men who are undergoing treatment is 5-35%. Screening for hypogonadism is essential in the determination of the testosterone levels among specific populations. Screening does not only look at the testosterone levels, but also the measurement of the clinically significant symptoms. 

Comorbidities: The higher prevalence rates of hypogonadism compared t the general population is highly associated with infections from certain diseases and specific conditions ( Araujo et al., 2004) . The HIM study depicts the odds ratios for these conditions, while the consequence of lowered testosterone levels is not clear. In as much as study findings show that the low levels of testosterone are highly connected to the etiology of the disease, other findings show that this is one of the causes of the hypogonadism. 

Complaints: The negative view of the impact of testosterone on cardiovascular high-density lipoprotein (HDL) levels of cholesterol decrease among people undergoing oral testosterone therapy ( Rastrelli et al., 2015) . It also decreases when taken in supraphysiological doses especially among physically active people. Most of the patients complain about the increase in the BMI levels, and testosterone deficiency syndrome. 

Signs: The most recommended clinical test for hypogonadism is determining the testosterone levels. The tests will be positive for hypogonadism if the testosterone levels are lower than 8 nmol/L. The other common sign is the changes in the circadian rhythms as they affect the levels of testosterone ( Mah & Wittert, 2010) . Low testosterone levels with elevated follicle-stimulating hormone are warning signs of primary hypogonadism. On the other hand, low testosterone levels with low normal luteinizing hormone levels are warning signs of secondary hypogonadism. 

Symptoms: Hypogonadism is characterized by high levels of hematocrit or polycythemia. Prostate cancer infection may also be a symptom of the disease. The patients may also experience untreated obstructive sleep apnea with severe or poorly controlled heart failure. Infertility in men is also a contraindication to the infection from hypogonadism. 

Importance of Screening

Diagnosis of Cause

In the course of screening for secondary hypogonadism, it is vital to further evaluate and carry out tests to identify the possible causes of hypothalamic or pituitary dysfunction. Screening is vital to determine the possible causes, which may include the medication use, infection from the destructive or infiltrative disease, deficiency in nutrition, hyperprolactinemia and lesions in the pituitary glands ( Rastrelli et al., 2015) . It is recommended that the serum levels of the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to determine if the cause of primary or secondary origin ( Pitteloud et al., 2005) . The etiology for primary hypogonadism is low levels of testosterone with high LH/FSH and uncorrected cryptorchidism, while low levels of testosterone with low or normal levels of LH/FSH is a suggestion of the secondary etiology of hypogonadism. 

Timing

In patients presenting with symptoms of hypogonadism, it is highly recommended that a thorough physical and biochemical workup should be carried out ( Araujo et al., 2004) . The primary laboratory tests that are used to confirm the presence of the disease are the determination of the serum total and the free testosterone (American Association of Clinical Endocrinologist, 2002). It is evident that the transient decrease in the serum testosterone levels might be due to the acute effects of the illness, where this should be excluded by careful clinical examination and repeated hormone measurement ( Fui et al., 2014) . Guidelines show that the lowest recommended testosterone level is 12.1 nmol/L, while the individual differences in the sensitivity of testosterone may lead people to exhibit symptoms of hypogonadism with the concentration of testosterone being higher. The timing for obtaining the serum sample for TT tests is crucial as it influences the results of the screening process ( Pasquali et al., 1997) . The recommended timing is between 07.00 and 11.00 h for level 2a, Grade A, although there are diurnal differences that are substantially blunted for men who are older. 

Treatment Options

Different treatment options have been found to be valuable in responding to hypogonadism. The preparations of aromatizable T is used for TRT. In the current healthcare settings, there are intramuscular, subdermal and oral testosterone preparations that are safe and effective for treating hypogonadism ( Araujo et al., 2004) . The healthcare provider should be well versed in the knowledge of the pharmacokinetics and the advantages and drawbacks of each of the preparation for testosterone ( Rastrelli et al., 2015) . On the other hand, the short-acting TRT preparations have been shown to be less harmful as compared to the long-acting depot preparations as the latter may include the elevated hematocrit or PCa. In such adverse effects, it required that the TRT is discontinued. TRT use is also associated with high levels of dose-dependent increase in the hematocrit and hemoglobin levels. If the hematocrit levels are >54%, then it is advisable to start the testosterone therapy. 

Benefits to Resolve Comorbidities

Higher rates of hypogonadism compared to those of the general population are highly associated with different disease conditions. Resolution to comorbidities is essential as it reduces the levels of predisposing factors for infection from hypogonadism ( Rastrelli et al., 2015) . Various comorbidities have been found to pose significant complications in the treatment of hypogonadism. For instance, corticosteroid treatment is highly associated with the risk of hypogonadism as the medication impacts the HPG axis by inhibiting the release of LH. This implies that resolving the comorbidities is essential as it reduces the risks of exposure to the factors contributing to infection from hypogonadism. 

Screening Process

Patient Assessment

The patient assessment looks at the signs and symptoms that are related to the testosterone concentrations, where they indicate the diagnosis of hypogonadism ( Araujo et al., 2004) . The clinical physicians should assess the testosterone levels for men with symptoms related to hypogonadism. Screening tools have been valuable in the identification of the patients having the highest probability of lowered testosterone levels. The assessment is carried out by filling in the androgen deficiency in aging males (ADAM) questionnaire. This questionnaire is vital in starting the conversation on the symptoms of the disease ( Rastrelli et al., 2015) . The questionnaire should never be used in isolation, where it should be used alongside other clinical tests to determine the exact cause of the disease. The physician should gain knowledge on the symptoms such as reduced libido, lack of the effects of the PDE5 inhibitors for erectile dysfunction and reduction in the mass and strength of the muscles ( Fui et al., 2014) . The physical should also assess the mood of depression in the patient and the possible decrease in the energy or vitality. 

Laboratory

Total Blood Serum Testosterone levels and unbound levels: The normal serum levels of testosterone in serum should be above 12.1nmol.L. Values of testosterone below this value is considered as abnormal and can lead to the dysfunction of the body organs, which is also characterized by the infections from hypogonadism. Patients with the low levels of blood testosterone as low as 8nmol/L should be considered as having lower levels of the hormone, which affects their sexual functionality (American Association of Clinical Endocrinologist, 2002). In as much as there lacks an agreement among the reviewed guidelines on the serum TT level that is diagnostic for male hypogonadism, the current researchers have shown that the TT levels of less than 8 nmol/L would warrant treatment, while the levels of over 12 nmol/L are not considered as appropriate for TRT. There are variations between the timing of performance of the lab tests for testosterone levels, where a morning lab draw is a clear indication that the blood serum levels of the hormone can be used in the prediction of the levels of hypogonadism ( Rastrelli et al., 2015) . There are also evident variations in the guidelines regarding the FSH, LH and prolactin levels, which are used as an indication of the difference between the primary and secondary hypogonadism. Further research is eminent in terms of the determination of the additional research behind the lower levels of the adherence to guidelines in the determination of the serum concentration in terms of the testosterone levels. 

Serum Sex Hormone Binding Globulin (SHBG) Levels : A portion of testosterone test is bounded to the SHBH in as much as it considered being biologically active. The increase in the levels of SHBG leads to the decrease in the levels of the bioavailable testosterone levels. Once the TT levels are within the low and normal range, there are altered SHBH levels that are normally characterized by the infections from diseases such as thyroid disease, diabetes and diseases resulting from old age (American Association of Clinical Endocrinologist, 2002). There are guidelines that have been set for the management of the disease, where it is evident that once the testosterone levels are lower than 8 nmol/L and it is less than 12nmol/L, while the patient depicts elevated levels of SHBG, then the patient would require further evaluation. 

Serum Luteinizing Hormone (LH) Levels: The Luteinizing hormone is synthesized in the pituitary glands, where it is responsible for luteinizing the mature follicle inside the ovaries in the course of ovulation. The levels of the hormone may vary during the menstrual cycle and the peak prior to ovulation. The LH values are between 3 and 10 mlU/ml, where they can be raised by the inducing drugs such as clomiphene citrate. If a patient is suffering from hypogonadism, the LH levels are lowered, where they are less thal 2mlU/ml. 

Serum Follicle-stimulating Hormone: The FSH is a glycoprotein polypeptide hormone, which is synthesized and secreted through the gonadotrophic cells, where it is the responsibility of regulating the reproductive system in the body (American Association of Clinical Endocrinologist, 2002). The hormone stimulates spermatocytes as they undergo the process of meiosis in the course of formation of the secondary spermatocytes. The hormone enhances the production of androgen-binding protein as a function of the Sertoli cells of the testes through binding of the hormone receptors on their basolateral membranes. The hormone is typically measured during the early phases of the follicular menstrual cycle, counted from the initiation of the process of spermatogenesis. 

Serum Thyroid Stimulating Hormone: Screening for the TSH level in the blood is helpful as it reveals the amount of T4 in the pituitary gland in relation to the amounts that the thyroid gland should make ( Rastrelli et al., 2015) . High levels of the THS may mean that the patient has an underactive thyroid or a situation that may lead to hypothyroidism. The normal levels of the TSH in serum should be 0.4 mil units per liter expressed as 4.0 mU/L. Patients with high levels of TSH present with signs of hypogonadism.

Serum Prolactin Levels: Screening for prolactin is essential in the determination of deviations. The normal range of the prolactin in the blood among males should be 2-18 nanograms per milliliter of blood. Male highly require the tests of the prolactin if they display symptoms of prolactinoma ( Fui et al., 2014) . These symptoms include reduced sex drive, which is a viable indicator of infections resulting in hypogonadism. Such patients would experience problems such as erectile dysfunction among other signs. 

Sleep Study

Research depicts that the plasma testosterone levels depict circadian variations, where they peak during sleep and reach a nadir in the late afternoons. Patients having these signs signal the presence of hypogonadism, where such patients may be superimposed ultradian rhythm with the pulses every one and a half hours (American Association of Clinical Endocrinologist, 2002). The reduction in testosterone levels leads to the reduction in sleep, where the sleep patterns are highly correlated with the hypogonadism disorder. The disease leads to changes in the circadian rhythm, which is dependent on the brain activity and the consequential duration of sleep. 

Treatment

Testosterone Replacement Therapy

Intramuscular Injections: Intramuscular injections have traditionally been used to increase the strength of the muscles ( Araujo et al., 2004) . The intramuscular deliver the medication into the muscle tissue, which allows the medication to be absorbed into the bloodstream. The intramuscular shots are delivered at an angle of 90 degrees at a gauge of 22-23 with a length of 1-1.5 inches with an adjusted thickness for the site ( Rastrelli et al., 2015) . 

Transdermal Patches: the transdermal patch is a medical adhesive patch that is normally placed in the skin for the delivery of specific dose medications through the skin, where the medication goes straight into the bloodstream. This medication promotes healing to the harmed area of the body ( Rastrelli et al., 2015) . The blood vessels, in this case, are considered to be the vital part in the course of transmission of medication from the patch to the bloodstream. The layers of the skin absorb medication via the transdermal patches, which allows the medication to be absorbed through the vessels of the blood to the bloodstream. 

Transdermal Gels

Transdermal gel products are medications that are specially prepared in the special base, which are specifically designed for the absorption of the testosterone through the skin ( Rastrelli et al., 2015) . The products are applicable if the patient cannot get the medication through the oral procedures since the testosterone is absorbed well through the skin. The testosterone gel is rubbed onto the upper arms and shoulders (American Association of Clinical Endocrinologist, 2002). The patients are subjected to the gel through the stomach area such as the abdomen, penis, scrotum and the armpits. 

Buccal Tablets

Testosterone buccal systems are designed in such a way that they can treat the symptoms of low testosterone in adult males who are diagnosed with hypogonadism ( Fui et al., 2014) . Testosterone is applied to men who have low testosterone levels caused by the adverse medical conditions. Buccal testosterone comes as a tablet-shaped patch, which applies to the upper gum ( Rastrelli et al., 2015) . Under normal circumstances, it should be applied twice in a day. The testosterone buccal systems are applied to areas of the upper gum and above the areas above the left and right incisors. 

Subcutaneous Pellets

The testosterone hormone is implanted under the skin in the form of pellets, especially near the hip joint. The pellets act as the long-acting form of the testosterone therapy. The pellets deliver a stable and steady dosage of testosterone that typically provides the needed level of the hormone for more than five months. 

Oral Testosterone Tablet/Capsule

The oral tablet is taken by the mouth within a period of four times in a day. The dosage is highly dependent on the medical condition of the patient, his testosterone body vessels and the response that the patient portrays to treatment. The capsule is made of methyltestosterone and is viable for patients who have been used in high dosages. 

Secondary Treatments

CPAP: The continuous positive airway pressure (CPAP) therapy has become one of the current secondary treatments that act as an alternative to the testosterone therapy (American Association of Clinical Endocrinologist, 2002). The therapy is based on the principle that the improvement in sleep patterns can result in high levels of libido marked by the improvement in the levels of production of testosterone ( Fui et al., 2014) . Research on sleep apnea has shown that there are high levels of correlation between the sleeping patterns and stimulation of a man’s libido. 

Lifestyle: Hypogonadism is a condition that can be cured through changes in lifestyle such as drug cessation and consistent exercise ( Rastrelli et al., 2015) . Fluid intake is also considered as one of the lifestyle changes that can reduce the vulnerability of infection from hypogonadism ( Araujo et al., 2004) . Fluids are known to reduce the cardiovascular events with the consequent reduction in hematocrit levels since the T receptor has a vasodilator that reduces the anti-atherosclerotic effects. 

Contraindications

Testosterone replacement therapy has some contraindications based on the risks that the medication poses. The risks of the therapy are highly dependent on age, the life circumstances and the history of medication of the patient. Non-pharmacological treatments have been found out to be the remedy in responding to the risks posed by testosterone replacement therapy. Such forms of treatment include the adherence to lifestyle modifications such as weight loss and discontinuation of drugs like opioids. 

Survey

A. Recipients

The recipients of this healthcare plan are the middle and older-aged male populations. This population forms the audience of the findings in the sense that there are high prevalence rates of hypogonadism at this age ( Rastrelli et al., 2015) . A feature that is consistent with this study is that the levels of vulnerability to hypogonadism infection increases with age. The findings are relevant in the sense that the increase in life expectancy in most of the developed nations will lead to the increase in the number of the elderly. This implies that the prevalence rates of the disease will also increase. 

B. Questions and Delivery

The assessment is carried out by filling in the androgen deficiency in aging males (ADAM) questionnaire. These questions are meant to gather information on the primary symptoms that the patient experiences ( Araujo et al., 2004) . These questions are open-ended in nature, where they are meant to test the perceptions of the patient as a way of gathering enough clinical evidence that can aid in the right decisions regarding hypogonadism infection. The questions are delivered using online platforms of communication. 

C. Response Rate

The response rate among the recipients is high, where the old-aged males are found to have high levels of prevalence of hypogonadism compared to the young age. It is imperative to note that the rate of incidence of hypogonadism characterized by the low testosterone levels increases with the increase in the number of years of a person ( Rastrelli et al., 2015) . Most of the recipients aged 65 and above and found out to be vulnerable to symptoms such as low libido and lack of the PDE5 inhibitors. Most of the recipients are also in contention with the fact that testosterone replacement therapy is highly correlated with the improved health outcomes. 

Results

Qualitative Comparison

It is evident that guidelines for screening of patients with hypogonadism have not endorsed a universal screening for adult males with the symptoms of the disease. In as much as some of the guidelines endorse screening for men presenting with hypogonadism symptoms, other guidelines suggest the screening for other comorbidities such as type II diabetes mellitus and metabolic syndrome ( Rastrelli et al., 2015) . Consequently, there are guidelines that suggest the screening for opioid and glucocorticoid use as a model of determining the influence of lifestyle in the prevalence of hypogonadism. 

The primary type of hypogonadism is characterized by low serum testosterone and high LH and FSH concentrations, while the second type of the disease is characterized by low levels of testosterone and low LH and FHS concentrations ( Araujo et al., 2004) . Patients with secondary hypogonadism can be treated and their fertility restored, while the primary type of condition is irreversible. Primary hypogonadism is caused by injury or infections that affected the development of the tentacles, while secondary hypogonadism is caused by the pituitary disorders and the Kallmann Syndrome. 

It is imperative that different guidelines for screening in the course of diagnosis of hypogonadism. As a disease marked by low levels of testosterone in the serum of males, hypogonadism is caused by different comorbidities, which gives the requirement of development of different guidelines in the course of diagnosis. Screening for the primary type of hypogonadism involves checking for the effect of the PDE5 inhibitors. In this case, lack of the PDE5 inhibitors is an indication of the primary hypogonadism. On the other hand, screening for the secondary hypogonadism involves checking for signs such as sleep patterns and gynecomastia. Testosterone replacement therapy has been found out to be one of the responsive models in responding to the effects of hypogonadism. However, the therapy offers high levels of risks including elevated hematocrit or PCa, a condition associated with the high serum T-receptor concentrations. In such adverse conditions, it is advisable that the TRT should be discontinued. 

References

American Association of Clinical Endocrinologist. (2002, November). American Association of Clinical Endocrinologist Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hypogonadism in Adult Male Patients. Endocrine Practice, 8 (6), 439-453.

Araujo, A. B., O’donnell, A. B., Brambilla, D. J., Simpson, W. B., Longcope, C., Matsumoto, A. M., & McKinlay, J. B. (2004). Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study.  The Journal of Clinical Endocrinology & Metabolism ,  89 (12), 5920-5926.

Fui, M. N. T., Dupuis, P., & Grossmann, M. (2014). Lowered testosterone in male obesity: mechanisms, morbidity, and management. Asian Journal of Andrology ,  16 (2), 223.

Huhtaniemi, I. (2014). Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis, and treatment. Asian Journal of Andrology ,  16 (2), 192.Dandona, P., & Rosenberg, M. T. (2010). A practical guide to male hypogonadism in the primary care setting.  International journal of clinical practice ,  64 (6), 682-696.

Lawrence, K. L., Stewart, F., & Larson, B. M. (2017). Approaches to male hypogonadism in primary care.  The Nurse Practitioner ,  42 (2), 32.

Lunenfeld, B., Mskhalaya, G., Zitzmann, M., Arver, S., Kalinchenko, S., Tishova, Y., & Morgentaler, A. (2015). Recommendations on the diagnosis, treatment, and monitoring of hypogonadism in men. The Aging Male ,  18 (1), 5-15.

Mah, P. M., & Wittert, G. A. (2010). Obesity and testicular function.  Molecular and cellular endocrinology ,  316 (2), 180-186.

Pasquali, R., Macor, C., Vicennati, V., De Iasio, F. R., Mesini, P., Boschi, S., ... & Vettor, R. (1997). Effects of acute hyperinsulinemia on testosterone serum concentrations in adult obese and normal-weight men.  Metabolism ,  46 (5), 526-529.

Pitteloud, N., Hardin, M., Dwyer, A. A., Valassi, E., Yialamas, M., Elahi, D., & Hayes, F. J. (2005). Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men.  The Journal of Clinical Endocrinology & Metabolism ,  90 (5), 2636-2641.

Rastrelli, G., Carter, E. L., Ahern, T., Finn, J. D., Antonio, L., O'Neill, T. W., ... & Maggi, M. (2015). Development of and recovery from secondary hypogonadism in aging men: prospective results from the EMAS. The Journal of Clinical Endocrinology & Metabolism ,  100 (8), 3172-3182.