Keywords: Vitamin D, Natural Testosterone Production, Androgen Synthesis, Vitamins, Sunlight and Testosterone There have been several clinical reports that an increase in Vitamin D consumption can increase production of testosterone in men. In fact, some men include Vitamin D supplementation while on testosterone replacement therapy to enhance natural testosterone production. Vitamin D is necessary for proper sperm and gonadal (testicular) health. Given vitamin D receptors are expressed throughout the male reproductive tract, it is theorized that vitamin D receptor are important for steroid and more specially androgen synthesis. Vitamin D receptors are present in the Leydig cells of the testicles. Leydig cells are responsible for testosterone production in men. Low levels of vitamin D are associated with lower levels of testosterone and elevated levels of Estradiol (E2) in men. Given the association of hypogonadism with low levels of Vitamin D, it can be beneficial for men on testosterone replacement therapy to supplement Vitamin D with therapy. In a study by Pilz et al. published in 2011, Effect of Vitamin D Supplementation on Testosterone Levels in Men, 54 healthy men who were deficient in vitamin D were given 84 micrograms of Vitamin D daily for 1 year or a placebo. Men in the treatment group, compared to baseline values, had an increase in serum total testosterone, free testosterone and bioavailable testosterone levels. Studies such as Wehr et. al. Association of vitamin D status with serum androgen levels in men and Lee et. al. Association of hypogonadism with vitamin D status: the European Male Aging Study confirm such findings. Vitamin D is an essential nutrient that the body obtains from two sources, food and sunlight. If you are planning to use a vitamin D supplement , it is best to take it with a meal to enhance absorption and increase levels more efficiently. Foods that are rich in vitamin D include salmon, mushrooms, tuna, herring, sardines, egg yolks, oatmeal and cod oil to name a few.

The gold stand for measuring serum testosterone is through a blood sample utilizing a mass spectrometry base method. Yet, obtaining a blood sample can be invasive for some patients. Disadvantages of drawing blood include discomfort from venipuncture, price, necessity to travel to a lab and reliance on a phlebotomist. A noninvasive test that could measure total and free testosterone reliably and accurately would be of great value to a clinician and patient. Salivary testosterone measurement is an easy, at home, fast, noninvasive and non-painful means to measure testosterone. However, salivary testosterone testing is beset with inaccurate test results and is extremely sensitive to storage and collection methods. The inability of salivary testosterone testing to consistently and reliably produced accurate results makes it far from ideal to diagnose and manage hypogonadism in male patients. Salivary testosterone measurement makes for a good measurement and index of free testosterone, but not total testosterone. Saliva contains the free portion testosterone only. Total testosterone is measurement of both bound and unbound testosterone. It is the unbound fraction, also known as free testosterone, that exerts the biological effect on the androgen receptor. Bound testosterone is attached to proteins such as albumin and sex hormone binding globulin that inactivate testosterone’s ability to exert an effect until released. The additional advantages of measuring testosterone in saliva is there is no interference or variations in levels caused by the presence of albumin and sex hormone binding globulin which exists in blood. However, the reliability and accuracy of salivary testosterone testing has kept it from being the gold standard or mainstream testing method. The method in which salivary testosterone is collected aids and influences the inaccuracy of the test results. For instance, salivary testosterone levels greatly vary in response to chewing, increase salivary flow and presence of contaminates within the oral cavity. In addition, small microscopic gingival injuries can contaminate the specimen, by leaking blood into saliva altering the testosterone concentration and reliability of results. In regards to how well measured salivary testosterone mirrors serum total testosterone levels, studies by Shirtcliff et. al (2002), Gragner et. al (1999) and Landman et. al have demonstrated salivary testosterone may significantly underestimate and varies when compared to serum testosterone levels. This can lead to over or under diagnosis of Low-T in men. In a study by Lawrence et. al, Salivary testosterone measurement does not identify biochemical hypogonadism in aging me: a ROC analysis, demonstrated a poor relationship between serum testosterone levels (Free Testosterone, Total Testosterone, Bioavailable testosterone) and salivary testosterone levels. In conclusion, salivary testosterone does not accurately and reliably diagnose Low-T in men. Salivary testosterone is a good indicator of free testosterone. Free testosterone has been utilized as a diagnostic marker by the Endocrine Society Guidelines for the management and diagnosis of hypogonadism in men. Serum total testosterone is the gold standard measurement for the diagnosis and management of Low-T. While the clinical utility of serum testosterone needs improvement in reliability and accuracy in reporting results, salivary testosterone testing may be able to play an integral part in the management and monitoring of Low-T symptoms after a diagnosis has been made through a serum measurement of testosterone.

Many men may not respond to Viagra or Cialis. There are several important steps you can take before moving on to second line therapies for ED. Keywords: Cialis, Viagra, Stendra, Staxyn, Levtira, Erectile Dysfunction therapy, ED Meds, ED meds dont work, Nitric Oxide The first line treatment for erectile dysfunction therapy is the use of oral medications called phosphodiesterase inhibitors (PDE5i). PDE5i are more commonly known as Viagra, Cialis, Levitra, Stayxn and Stendra. Oral medications for ED are an easy option for men to improve their rigidity and stamina during activity. Yet often times men can find themselves not responding to the medication. Oral ED meds have an overall effectiveness of approximately 60-70%. Oral ED meds in clinical trials fail to achieve a response in 30-35% of men. In clinical practice the failure of rate of oral ED medication can be as much as 50%, given patients may have more severe vascular conditions that prevent the efficacy of the drug. What can a man do next if oral ED meds don’t work? What is the best next step? Approximately 1/3 of patients who find themselves not responding to ED meds may be salvaged with counseling and appropriate dosing. There are no guidelines or a standardize stepwise approach for men who fail oral ED meds other than to move on to second line therapies. When a physician is evaluating a patient, who has failed to respond to oral ED meds consider the following issues: Medication Issues Effectiveness Reliability Side Effects Cost Clinical Issues Inadequate instructions Inappropriate dosing Vascular Health Neurologic Health Androgen Health Lack of Follow up Patient/Partner Issues Unrealistic expectations Lack of persistence Reluctance to treat Unaddressed physiological issues Partner issues Couple Issues When counseling the patient, it’s important to find out if there was an actual physical response. Was there any engorgement or rigidity to the phallus during stimuli? Was it satisfactory for penetration or to weak? Was the patient able to achieve climax or was there premature ejaculation? When counseling a patient about oral ED meds, the majority of failures can be improved by proper counseling on how to best use the medication. Patients should be aware of the following: ED meds only work with sexual stimuli. Foreplay is advised and can improve response. Often times men say they can get an erection on their own but not with a partner. This can be more performance anxiety induced ED. This can be secondary to having a new partner and desiring to meet their expectation. Often a medication to reduce nervous tendencies can be instituted. Make sure the patient is not taking the medication with food. Most ED meds, especially Viagra has a reduced effectiveness when taken with food. Reduce and/or omit alcohol consumption when taking ED meds. This can lower blood pressure and may also make the medication less effective while reducing sexual stimuli response. · Ensure the patient is swallowing the medication. Some patients may be dissolving it in water (believe it or not) Other counseling aspects a physician should consider: Sexual stimulation and foreplay needed When should PDE5i taken? If patient has eaten, delay intercourse Avoid excessive alcohol Side effects PDE5i to expensive Trial of at least 7-8 doses Dosage titration Often times patients may ask to increase the dosage of medication. This has been studied in several clinical trials and is not effective as one may think. One study in particular of 54 men who did not initially respond to Sildenafil 100mg who had ED secondary to a vascular, post radical prostatectomy or psychogenic cause were treated with increasing dosages over a month of Sildenafil 100mg, 150mg and 200mg. Improvement in ED scores were 37%, 46%, 68% respectively. However more importantly 63% patients on 200mg experienced headache, flushing, nasal congestion, visual disturbances, and dizziness that were not tolerable. Increasing the dosage may shift the benefit to risk ratio in favor of adverse events and side effect. This approach is not advised. An alternative approach is to try a different oral ED medication. A meta-analysis of 1118 clinical trials suggest Tadalafil and Vardenafil may be more effective than Sildenafil based on changes in IIEF scores. IIEF is the International Index of Erectile Function, it is a question that can quantify erectile dysfunction severity. The questionnaire is set of 5 questions that pertain to the past 6 months of activity: How do you rate your confidence that you could achieve and keep and erection? When you had erections with sexual stimulation, how often were your erections hard enough for penetration? During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner? During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse? When you attempted sexual intercourse, how often was it satisfactory for you? An additional option a patient may try is switching from an on-demand dosing to a daily dosing of ED medication. In a prospective open label study: Tadalafil 5mg Daily vs Tadalafil daily + Sildenafil 50mg on demand was utilized. Patients on combination therapy who had a baseline of severe ED had greater improvement than men who had mild ED at baseline. Adverse events were not significantly different in either group Testosterone therapy can make non responder to oral ED medications into responders. Men with low testosterone levels may find it hard to get an erection with medication (no pun intended). Testosterone replacement (TRT) can improve response to ED medication significantly. Increased testosterone levels are associated with significantly improved sexual activity, sexual desire and erectile function. In trials of patients with testosterone deficiency, treatment with testosterone undecanoate or enanthate improves erectile response to vardenafil and tadalafil. Finally, noninvasive Low Intensity Shockwave Therapy for ED can turn non responders into responders to ED medications. Several clinical trials have documented this phenomenon. LISWT is a great noninvasive next best option in patients who fail to respond to ED meds. A protocol for LISWT is treatment once per week for 12 weeks. 3000 shocks applied at 6 sites along the phallus. 500 shocks per site at proximal and distal corpora. All patients to remain on once-daily dosing of Cialis during therapy. In Summary Next Best Option for Non-Responders to ED Medication Failure to respond, offer an alternative medication Assess medications, patient/partner issues, help define patient as a true PDE5i failure Limited data to support raising the dosage above the standard guidelines, only increases significant risk of SE. Consider Low Intensity Shockwave Therapy (LISWT)

What makes an expert testosterone clinic? How to evaluate your testosterone therapy treatment? How to evaluate your provider? How to review a testosterone clinic website? How to find the best testosterone clinic. Keywords: Mens T Clinic, Testosterone Clinic, TRT Center, TRT online, Testosterone online, Doctors who prescribe testosterone, Mens T clinic cost, Mens T Clinic Reviews, Testosterone Doctor Testosterone clinics are becoming more common place in countries around the world. Approximately 10-40% of men across the globe suffer from androgen deficiency and this may increase to 80% in men with several comorbidities. In 2011 over $1.8 billion dollars in testosterone prescriptions were administered, with the majority of prescriptions written for off-label indications. With an ever-increasing aging population more prescriptions for testosterone will undoubtably be written. The United States alone accounts for 80% of the global testosterone prescriptions. The increase in testosterone can be attributed to media presence, direct to consumer and social media advertisements. In must be understood that testosterone is not a benign medication, it has both risks and benefits that must be monitored and managed by a trained physician. Making the correct diagnosis of testosterone deficiency is just as important as the right treatment. Treating low-testosterone is about more than just measuring your testosterone levels alone. In fact, the majority of testosterone prescriptions today are written for off-label purposes and patients may not obtain the necessary monitoring every 3-6 months advocated by many professional medical societies. Having a low testosterone level does not make a man a necessary candidate for testosterone therapy. Vice versa, only having the symptoms of Low-T does not justify testosterone replacement therapy if hormone levels are normal. There any many other conditions that can mimic Low-T and understanding why a man has those symptoms is just as important as the right treatment. The treatment of low-testosterone demands a physician’s expertise to confirm a more serious health condition is not the underlying cause for the symptoms. When looking for a testosterone replacement physician or clinic, begin by asking the following set of principle question to help guide your health and treatment. 1. Reviewing Testosterone clinic websites When reviewing a testosterone clinic website, it’s important to first look at the providers. Are the physicians managing your care properly trained? Review the bio if present. Some websites may not even list the providers, and this has been of much concern in the medical community. Observe the professional associations your doctor is participating and have membership. Professional medical and surgical associations such as the American Urologic Association (AUA) provide continued medical education to physicians to stay on the cutting edge of new research, therapies and announcements pertaining to men’s health. Physicians who are not members of such associations may not be and learning new insights or new risks associated with men’s therapies. Next, observe if the physicians are board – certified. Board certification is an additional level of expert training and education a physician must procure to practice at the top of their profession. A Board-Certified Physician must continually undergo exams and continued learning to maintain this tittle. Most hospitals require that a physician be board certified to obtain privileges. If a provider is board certified this is an excellent attribute to their practice and level training and patient can trust. 2. Will I see a doctor every time during my visit? This is your body, and your health. Its common that testosterone clinics may not provide their patients with a physician visit every time or at all. It’s important to know if your care is being managed by an assistant or a physician. Finding the correct medication, monitoring, and optimizing your response to therapy should be done by a physician rather than a medical assistant or nurse. This is the best way to reach your goals and to be safe. 3. Does my provider have discretion to say that I am not a candidate for Testosterone replacement therapy? If a man has his testosterone levels checked, and are within the normal range but still has the symptoms of testosterone deficiency, a more in-depth evaluation of symptoms should be undertaken. Being advised to start testosterone therapy despite a normal testosterone level without a detailed explanation should concern a patient and question the discretion of the provider. A man may suffer from other metabolic and hormone derangements that testosterone replacement cannot improve and this is important to protect your health and safety. 4. Is it convenient for my lifestyle? Testosterone should be easy and convenient to apply and administer. The goal is improving quality of life among other performance and stamina factors. If a man has to make weekly visits to a clinic to get an injection this can be time consuming and tedious. Some clinics may charge for each individual injection, it’s important to ask. See if the clinic can teach you how to administer your own therapy , this is important and will save you time and expense. Also ask if a clinic provides alternative testosterone formulations such as a topical gel. This is important to note, that a clinic provides multiple types of therapy options. Testosterone therapy is not a one size fits all. A physician should be knowledge in all aspects of testosterone delivery and a patient should desire such expertise in their management. 5. Am I being thoroughly monitored? Testosterone therapy should be monitored every 3-6 months with a complete panel of labs. Follow up visits should be with a physician. It is also important to know that testosterone testing and measurement should be done through a process called LCMS (Liquid Chromatography Mass Spectrometry). This is a blood test to measure testosterone and is the gold standard and provides the most accurate testosterone serum level result. Most clinic may test your blood in the clinic and provide an instant read of your level. This is often a less accurate method to testing your levels and may compromise your results. 6. Am I confident in the experts around me? Is the place of business taking treatment seriously? Can the physicians answer all my questions about my health and am I content with the answers? Is the physician available to speak with me after hours? Do I feel I get personalized attention to my health? Is the clinic well maintained and clean? Asking some of these basic questions will help you know what feels right, and that you are in good hands. Physician availability is important and should be valued by every patient. 7. Am I being offered more than one testosterone delivery method? Testosterone should be tailored to man’s lifestyle and be easy to apply or administer for the patient. There are a variety of testosterone delivery methods from injections, topical gels, and pellets to name a few. An expert in the field of testosterone replacement therapy (TRT) is knowledgeable in all aspects of testosterone delivery methods that are available to the patient. 8. Am I being offered other medications to improve my testosterone if I want to preserve fertility? Most patients who desire to maintain reproductive potential or are actively trying to conceive should be offered alternatives to testosterone therapy. Testosterone is an infertility drug for men, and this should be explained in detail during a patient visit. Even when HCG is administered along with testosterone therapy, spermatogenesis can still be reduced. A patient should be explained about the reduced fertility potential that testosterone therapy can induce. 9. Did the physician providing me testosterone perform a full physical examination? I advise patients that one objective measure to ensure your health is made a priority at a testosterone clinic is by observing the following: Did the provider perform a testicular examination for size, breast examination for gynecomastia and if a man is above 40 years of age, a prostate examination must be performed. A physical examination is paramount to confirming no other causes are present to cause testosterone deficiency. Finding a prostatic nodule on physical examination can preclude the administration of testosterone and may need further workup. 10. If I have low-T what is the cause? There are a variety of causes for testosterone deficiency. These can be grouped into primary and secondary hypogonadism. A physician should partake in a full and comprehensive evaluation to understanding the etiology. A patient should be aware of the labs and steps a physician has undertaken to understand his causality for testosterone deficiency. There is no doubt that low-t centers are just about everywhere you turn. But your body and your health should be treated with care and taken seriously. Taking the steps to improve your health can have lasting impact. The key is doing it in the right way, at the right place, by the experts.

An Ask the Doc Blog Post from our patients. · What is HCG? · Should I be taking HCG with Testosterone? · What are SERMS? · Will Testosterone help my erections? · How can I boost my testosterone naturally? What is HCG and should I be taking it with Testosterone Therapy (TRT)? HCG stands for Human Chorionic Gonadotropin. It is composed of several amino acids and is identical to the pituitary hormone LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone) in both males and females. HCG is specifically produced in women by the placenta and secreted during the beginning of pregnancy to enrich and nourish the uterus for fetal growth. Because the alpha subunit of HCG is similar to LH and FSH, it can be used to mimic the normal function of LH and FSH in males. LH is secreted in males by the pituitary and acts upon the testes to maintain testicular size and produce testosterone. FSH in males is also secreted by the pituitary and maintains sperm production (spermatogenesis). Men who take HCG during testosterone replacement therapy (TRT) are doing so to maintain fertility and testicular size. Testosterone given without HCG acts upon the pituitary to shut down FSH and LH production. In effect, the body is telling itself there is too much testosterone, reduce natural production and reduce FSH and LH secretion. This process is termed a “negative feedback loop”. The effect of down-regulation of LH and FSH can be testicular atrophy and a decrease in spermatogenesis. Therefore, it is important to note that testosterone taken alone is an infertility drug for men. Every patient presenting for testosterone therapy should have a discussion about their fertility concerns and desire for children. Testosterone therapy alone will make a man infertile, however, stopping therapy the system will rebound, and spermatogenesis may improve over baseline. The necessity to take HCG for each individual on testosterone replacement is unique and depends on the patient’s desire to maintain fertility. Also, if a patient is experiencing any testicular atrophy while on testosterone therapy alone, HCG administration may alleviate testicular atrophy. HCG can also be used on its own without taking TRT. For men who want a more natural alternative to taking testosterone therapy, HCG administration will up regulate a body’s own natural secretion of testosterone. HCG mono therapy may achieve similar results to testosterone therapy while maintaining reproductive potential. What are selective estrogen receptor modulators and how can it improve my Testosterone level? Selective estrogen receptor blocker or modulators ( SERMs) act upon the hypothalamus to prevent the negative inhibitory effects of estrogen on the hypothalamus. By blocking the negative feedback of estrogen on the hypothalamus, SERMs up-regulate the pituitary secretion of LH and FSH. This, in turn, maintains spermatogenesis and increases testosterone production by the testicles. SERMs were first approved in the United States in 1967 to treat infertility in women. In men, SERM use is off-label, however, many men like to use the medication because testosterone levels increase 2-3x while maintaining fertility. Furthermore, SERMs are an oral medication and is taken every other day. The levels of testosterone that a man achieves may not be as high as administering exogenous testosterone. For many men, SERMs provide the performance, energy and strength building enhancements desired. Will Testosterone help with my erectile dysfunction? I advise many patients that testosterone replacement will help increase your desire for sexual activity, and can improve your erectile dysfunction (ED). The primary treatment for ED is not testosterone replacement, however, testosterone does play a pivotal role in maintaining penile tissue health and function. We know some men do see a significant improvement in their erectile function while on testosterone therapy. This may be due to several factors. First, we find many men with hypogonadism to have other associated conditions that can cause ED which includes diabetes, hypertension, elevated lipid profiles, and obesity. Testosterone replacement improves insulin sensitivity, reduces obesity, improves body composition, encourages a healthier lifestyle change and reverses metabolic derangements. This process may assist in improving erectile function. Second, testosterone does have an effect on erectile tissues (cavernosa). Within the cavernosa of the penis are androgen receptors. Testosterone replacement therapy enhances activation of androgen receptors, up regulating nitric oxide synthase (NOS) and promoting new DNA synthesis. NOS is the principal enzyme responsible for penile smooth muscle relaxation and achievement of tumescence (engorgement of blood within the penis to achieve an erection). Men who are hypogonadal and have erectile dysfunction (ED) may not respond to PDE5 inhibitors such as Viagra and Cialis. Testosterone replacement has been shown in clinical trials to improve the response to oral ED meds. A meta-analysis of the results of testosterone replacement therapy on sexual function as measured by the International Index of erectile function scores (IIEF) found an increase in IIEF scores with a mean difference of 2.31 in men with testosterone therapy replacement. Furthermore, other aspects of the IIEF score domains were also improved including libido, intercourse satisfaction, orgasm, and overall sexual satisfaction. Checking testosterone in men with ED is imperative to optimize and obtain the best results. The workup for E.D, in short, begins with a history and physical examination to define the cause of the condition and differentiating between a neurogenic, vasculogenic or psychogenic causes of ED. Defining the cause for ED will direct the proper treatment. More often oral medications, termed PDE5 inhibitors are first-line therapy, followed by injection therapy and possibly a penile implant to follow. This algorithm can differ depending on several variables, patient health, medication usage, obesity, and recent pelvic surgery or trauma and psychogenic causes. Men with low testosterone who have ED can benefit from testosterone replacement significantly. How can I boost my Testosterone Naturally? The best way to improve your testosterone naturally is with a healthy diet and regular exercise that consists of both resistance training and vigorous aerobic exercise. A study by the American Physiological Society applied a 12-week vigorous exercise program to overweight males. The study looked specifically at the effect of a regular exercise program on testosterone levels. None of the men in the study performed regular daily exercise. The men completed a 40-60-minute jogging or walking exercise one to three days per week. Findings confirmed that all parameters of testosterone levels were increased including total and bioavailable testosterone levels. The takeaway message I advocate to all our patients is a healthy lifestyle accompanied by a well-balanced diet and regular exercise routine will improve your testosterone naturally. Men who are also on TRT will have enhanced results to therapy if they abide by the regimen as well. Another way exercise can boost testosterone naturally is through a regiment called HIIT workouts. HIIT stands for high-intensity interval workouts. This includes a regiment using moderate and heavy weights during a high intensity burst of exercising. Then during the rest period you say active until again repeating the short burst of high intensity exercise with weights. This training is then repeated. Lightweight with high repetitions will increase endurance and burn fat and enhance metabolism. Workouts that are efficient to boost testosterone levels and increase metabolism are both aerobic in nature and include resistance.

Let’s discuss some commonly asked questions about Testosterone and Weight Loss. · Testosterone use for weight loss, does it work? · Can Testosterone help me lose weight? · Can TRT motivate me to lose weight? · Can TRT improve and treat obesity? · Is Low-T associated with obesity and being overweight? (TRT) Testosterone Replacement Therapy (Low-T) Low-Testosterone FACTS : · Long term testosterone therapy in men with testosterone deficiency improves body composition and quality of life · Long term testosterone therapy in obese men with testosterone deficiency improves all metabolic syndrome components. · Long term testosterone therapy in men with testosterone deficiency, with or without lifestyle modification may prove effective in the treatment of obesity. (1) Testosterone is very important metabolic and androgenic hormone. Testosterone regulates carbohydrates, lipids and protein metabolism, muscle mass, adipose tissue, inflammation, insulin sensitivity and body composition. Low testosterone (Low-T) levels, contributes to a decrease in muscle size, weight gain, increased fat mass, insulin resistance and metabolic syndrome. It is a well-known fact that obese and overweight men have lower testosterone levels compared to lean men. Men who utilize TRT can improve weight loss, waist circumference and muscle size. In some clinical studies testosterone replacement therapy (TRT) can increase lean muscle size and mass and decrease fast mass in as little as 3 months. A number of well published interventional studies have confirmed that when testosterone is given to obese men, testosterone can ameliorate metabolic syndrome components, reduce waist circumference, improve quality of life, and improve body composition. Some studies have suggested that testosterone therapy be considered an adjunct to the treatment of obese men. The potential mechanisms relating Low-T to weight gain include increased levels of sex hormone binding globulin (SHBG), low levels of luteinizing hormone (LH), adipocyte (fat cell) dysfunction, androgen resistance, and insulin resistance. Sex Hormone Binding Globulin (SHBG) Also known as testosterone-binding globulin, sex-steroid binding protein (SBP), testosterone-oestradiol- binding globulin (TeBG) The action of testosterone depends upon bioavailable testosterone in the body. Bioavailable testosterone is also known as free testosterone. A man’s total testosterone is combination of free testosterone and testosterone bound to proteins. One of these proteins that bind reversibility with high affinity and inactivates testosterone is SHBG. Approximately 60-80% of testosterone in the body is bound to SHGB, 20-40% bound to albumin and only 2-3% is free and active. SHBG levels are increased in conditions where estrogen levels increase such as liver disease (cirrhosis), hyperthyroidism, prolonged calorie restriction, and medications. Low-T promotes elevated levels of SHBG and contributes to low testosterone levels and weight gain. Luteinizing Hormone (LH) LH is a signaling hormone released by the pituitary gland. When LH is released into the body, it travels to the testicles and binds to a receptor on the Leydig Cells. The Leydig Cells are located in the testicles and synthesize testosterone. More specially Leydig Cells convert cholesterol to testosterone. Men who are overweight or obese have a low levels of LH secretion and therefore less testosterone synthesis. In prospective study Saad F et. al 423 men with Low-T were given injections of testosterone undecanoate in 12-week intervals for up to 10 years. Body weight decreased from 97.3 to 84.6 kg. Waist circumference decreased from 107 to 92cm and BMI decreased 31 to 27kg/m2.. Results supported that TRT increased lean body mass and decrease fast mass. Testosterone acts directly on adipose tissue, decreasing fat mass and reducing visceral (around the abdomen) fat. Fat acts differently to testosterone therapy depending on its location in the body. The effect of testosterone on fat distribution is becoming more well known. Adipocytes (fat cells) differ in their histological and biochemical characteristics depending on their location in the body. For instance, abdominal fat is made up mostly of large adipocytes that aromatize testosterone to estrogen more than other fat cells. Lipoprotein lipase an enzyme found in fat cells that breaks down triglycerides to energy for the body to utilize has higher activity in fat cells predominately located in femoral fat (thighs and legs). As a general rule, adipose tissue anywhere in the body, will in some degree metabolize testosterone. There is a direct correlation between body weight and the clearance rate of androgens. Clinical studies have found that men and women with higher body weight and obesity have higher metabolic clearance rates of testosterone than age-matched controls with normal body weight. Obesity increases the breakdown of testosterone and increases estrogen in the body that can lead to further insulin resistance and further weight gain. The mechanism by which testosterone reduces fat cell loss is hypothesized to be from inhibiting adipogenesis (the formation of new adipocytes/fat cells) and up regulating myogenesis (muscle building). Testosterone is believed to cause nitrogen retention which may signal protein synthesis, promoting muscle and lean mass growth. An Increase in lean muscle mass will increase metabolism propagating the fat cell loss cycle. For men with Low-T desiring to lose weight and reduced waist circumference testosterone supplementation is a viable alternative when combined with an exercise routine and a healthy diet. Testosterone therapy can be a great motivator as well to weight loss. TRT has been shown in clinical studies in men with Low-T to improve mood, reduce fatigue, enhance energy thereby motivating a man be more active. 1) Traish et. al, Testosterone and Weight Loss: The evidence. Curr Opin Endrocinol Diabets Obes. 2014 Oct; 21(5) 313-322, 2014 Aug 28.

How does Clomid work to increase testosterone levels in men? Who should consider Clomid? How It Works Clomid is the brand name for clomiphene citrate. Clomid is a selective estrogen receptor modulator (SERM). A SERM acts directly on the estrogen receptors in the hypothalamus and pituitary gland to increase the secretion of gonadotropin-releasing hormones (GnRH). Elevated GnRH increases Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) section from the pituitary gland. LH and FSH signal the testicle to increase sperm production and increase testosterone production. Clomid was approved by the FDA in 1967 for the use in women to increase ovulation. It’s use in men to enhance natural endogenous testosterone production was first investigated in 1968. The use of Clomid in men is considered off-label yet for many men Clomid is a great alternative to being on testosterone if fertility is desired to be preserved. Men who are on Clomid can experience the same benefit as testosterone replacement therapy with reported improvements in libido, energy, cognition and sports performance. Several studies have shown that men with low-T who utilize Clomid can improve their testosterone levels above 500 ng/dl. Given that Clomid is stimulating your natural production of testosterone, supra-physiological levels of testosterone are not normally achieved as in exogenous testosterone admirations where levels can surmount above 1104 ng/dl. In a study of 52 men who received testosterone replacement therapy (TRT) and 24 men who received Clomid for symptomatic relief of hypogonadism results revealed serum testosterone levels increased from pretreatment levels in all men regardless of therapy. Men treated with TRT showed significant increases in qADAM scores in libido, erectile dysfunction and sports performance measures. However, men who received Clomid, qADAM scores for libido were slightly lower following treatment. Unlike testosterone replacement therapy, Clomid may not improve libido as much as exogenous testosterone administration. The etiology of Clomid’s effect on libido has not been fully elucidated, but it is theorized that modulation of the estrogen receptor could have negative effects on libido. Estrogen is an important hormone to maintain male libido. Modulation of the estrogen receptor by Clomid can impair estrogen action and impair sex drive. TRT is more effective in raising serum testosterone levels and improving hypogonadal symptoms compared to Clomid. Yet, Clomid remains a viable treatment alternative to utilizing exogenous testosterone. Side effects of Clomid include dizziness, flushing, headache, abdominal discomfort and visual symptoms. The average dosing Clomid is 25-50mg every day or every other day. Dose titration is optimal. Clomid remains a great alternative to testosterone therapy, in cases where reproductive potential is desired to be maintained and preserved. Given Clomid’s ease of use, oral tablet, many men select this option of therapy.

What are the Symptoms of Low-T? What is the serum level of testosterone for Low-T? What are the benefits of Testosterone Replacement Therapy (TRT)? The most common reason men want testosterone therapy is to improve sex drive (libido) and improve overall wellbeing. This was documented in a clinical survey recently published in the Journal of Urology. Approximately 35% of men want testosterone therapy because they were tested for Low-T and desired treatment. Simply having Low-T was enough for a man to desire treatment despite not having symptoms. 30% of men desire testosterone for improved energy and sports performance. Most men on testosterone therapy claim to feel the greatest benefit after 3 months. After 3 months the most pronounced symptoms experienced by men are an improvement in daily and social energy, libido and muscle growth. Testosterone replacement therapy for men has increased significantly worldwide within the last two decades. In 2013 alone, over 2$ billion dollars were spent on testosterone prescriptions. Since 2016, the United States has accounted for 80% of testosterone prescriptions. The majority of men in the United States on testosterone replacement therapy for Low-T are actually receiving the medication off- label. The off-label use of testosterone such as late onset hypogonadism (LOH) or age related low-T and the treatment of androgen levels without a reported diagnosis are the most common reasons testosterone has been prescribed. Let’s define Low Testosterone: Low-T There is a difference between Low-T and Testosterone Deficiency. Low-T is simply a number. It is a value of your serum testosterone level measured in nanograms per deciliter (ng/dl). Testosterone deficiency is both a low serum testosterone level accompanied by clinical signs and symptoms. It is important to note that having Low-T but no signs or symptoms does mean you have testosterone deficiency. In other words, simply having Low-T does not necessitate treatment with testosterone unless a man also has symptoms. What are the Symptoms of Low-T? The signs and symptoms of Low-T can be divided in Physical, Cognitive, and Sexual categories: Physical Signs & Symptoms · Reduced energy and endurance · Diminished work performance · Diminished physical performance · Loss of body hair · Decreased strength · Reduced beard growth · Fatigue · Reduced lean muscle mass · Losing Muscle · Weight gain and/or obesity · Infertility · Gynecomastia (breast enlargement) Cognitive Signs & Symptoms · Depressive symptoms · Reduced motivation to complete tasks · Poor concentration · Forgetfulness · Irritability personality Sexual Signs & Symptoms · Reduced sex drive and desire · Erectile dysfunction (ED) · Lack of morning erection The symptoms of Low-T are very nonspecific. The specificity of the following symptoms representing Low-T is no greater than 25%. The above noted signs and symptoms of Low-T can also be secondary too metabolic syndrome (hypertension, high cholesterol, obesity), hypothyroid, liver dysfunction, multiple medications, liver dysfunction among others. Do I have Low-T? The American Urologic Association has defined the cut off for testosterone deficiency as a value less than or equal to 300 ng/dl. Other trials and studies have defined Low-T as having a testosterone level less than or equal to 250ng/dl. A man who has some of the above noted symptoms and testosterone level less than or equal to 300ng/dl, Low-T is diagnosed. The next step in working up the diagnosis of Low-T, is understanding why a man has Low-T. Aging is a possibility but there are other causes. Does have a man have Low-T because his pituitary gland is not sending the correcting signals to the testicles to make testosterone? Are the testicles receiving the correct signal, but just not producing enough testosterone? Is there something else physiologic going on in the brain? These are the questions every man should know and ask their provider before being prescribed testosterone replacement therapy for Low-T. Understanding why you have Low-T is just as important as the prescription. What are the benefits of testosterone replacement therapy? The primary treatment for Low-T is testosterone replacement therapy. Testosterone therapy can include the use of injections, gels, patches, or pellets, though injections and gels are most common. Testosterone therapy can improve the following symptoms of low-T: Correcting insulin resistance Increasing bone and muscle mass Decreasing subcutaneous fat Lowering low-density lipoprotein cholesterol, triglycerides, blood glucose, HbA1c, and blood pressure Increasing high-density lipoprotein cholesterol Improving erectile function and life parameters (such as increased energy and friendliness, decreased anger and anxiety, etc.) Improve energy & performance Reduce daytime fatigue If you believe you have Low-T and desire testosterone replacement therapy (TRT) call REGENX Health today. A REGENX Health urologist will provide a full and comprehensive workup to find out why you have Low-T and then tailor a medication regiment to best meet your performance desires.

Keywords: Blood Clot, Venous Thromboembolism, DVT, Testosterone, Heart Attack, Hemoglobin, Hematocrit, FDA Warning Label, Thrombophilia Blood clotting, also known as coagulation, is an important process that occurs to prevent excessive blood loss when the body is injured. Blood components called platelets and plasma work in a delicate balance to stop bleeding when a blood vessel is injured. Sometimes this clotting cascade can occur within a blood vessel and this leads to the development of a blood clot. There are many types of blood clots that are classified depending on their location in the body. A VTE (Venous Thromboembolism) is a blood clot that occurs in the venous system of the body. VTE’s can be characterized into both DVT (Deep Vein Thrombosis) and PE (Pulmonary Embolism). DVT’s more commonly occur in the veins of the legs, while a PE is blood clot that travels through the bloodstream and into the lungs. There are a variety of causes for developing DVT’s such as genetic predisposition, clotting disorders, lack of movement (stasis) among others. There has been concern that testosterone therapy may increase a man’s risk for developing a DVT. Much of the concern for the relationship between testosterone replacement therapy (TRT) and the risk of developing a DVT stems in part from the FDA labeling warnings. In 2005, the first FDA warning label for testosterone products under the “Adverse Reactions” section of the label was amended to note that one patient during an open label extension of the clinical trial had suffered a DVT. An update to the label in 2009 under New Medication Guideline listed “Blood Clots in the legs” among the serious side effects of testosterone therapy. In 2014 the FDA made their final label update and statement on the risk of DVT and testosterone therapy. On the testosterone label itself, the FDA statement is as follows: 5.4 Venous Thromboembolism There have been post marketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products such as Androgel 1%. Evaluate patients who report symptoms of pain edema, warmth, erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with Androgel 1% and initiate appropriate therapy and management. The FDA in 2014 released a statement requiring all manufactures of testosterone products to include a warning label about the risk of developing blood clots. The FDA warning label and required statement was impart a result of reports and surveillance of patients who developed a DVT while on TRT (1). Other pressures towards the FDA for the testosterone warning label were from public interest groups, such as Public Citizen (2) . The FDA at this time was concerned about the increasing use of testosterone therapy among males in the United States. Between 2001 to 2011 the use of TRT tripled among men in the United States above age 40. 75% of those men, who were on TRT, did not regularly have their blood testosterone or associated labs monitored. Rightfully so, the FDA is tasked with protecting the public and given that TRT use in men greater than 40 was becoming increasingly more common, the FDA wanted to ensure the public’s safety. One of the principle studies reported to be used by the FDA to craft the label warning relating testosterone to blood clot risk was a noted study published by Glueck CJ et. al. in 2011 entitled Thrombotic events after starting exogenous testosterone in men with previously undiagnosed familial thrombophilia. In this particular study it is important to note that those men who developed a DVT after starting TRT had an increased risk of developing a blood clot given an undiagnosed thrombophilia (blood clotting disorder). The researchers hypothesized that men with an undiagnosed familial thrombophilia are at increased risk of developing blood clots secondary to increased aromatization of testosterone to E2 (Estradiol). The effect of elevated E2 in patients with familial thrombophilia may exacerbate a preexisting clotting disorder. Some studies have recommended screening for thrombophilia in men before starting TRT (3) (4). Yet for men on testosterone therapy who do not have a predisposition to forming clots, there have been no satisfactory evidence showing any risk of DVT’s while on TRT. There have been four large observational studies since 2014 that have not revealed any increased risk of VTE in men undergoing testosterone replacement therapy. In addition, the American Urologic Association (AUA) has made the following guideline statement. Guideline Statement 19. Patient should be informed that there is no definitive evidence linking testosterone therapy to a higher incidence of VTE. To date there have been no randomized, placebo-controlled studies to evaluate the increased risk of DVT’s with testosterone therapy and the current evidence, although low, does not reveal any increased risk. A randomized controlled study in 2016 published in the Journal of Urology by Maggi et al. monitored 715 hypogonadal (Low-T) men for approximately 16 weeks. Men in the study were 18 years of age or older and with a total testosterone level less than 300ng/dl. Patients had to have one symptom of testosterone deficiency. Patients were randomized to either receive a topical testosterone solution or a topical placebo used daily. Results of the study revealed no major adverse cardiovascular events or VTE in the testosterone group. A case-controlled study published in the Mayo Clinic proceedings in August 2015 by Baillargeon et al. titled Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy did not show any increased risk of VTE in men on testosterone therapy. The study observed 30,572 men who were 40 years and older and who suffered a VTE. The study matched 3 controls on event/index month, age, geographic region, diagnosis of hypogonadism, and diagnosis of any underlying prothrombotic condition. Exposure to testosterone therapy, regardless of route of administration did not increase the risk of DVT, even if given 15 days prior to an associated VTE event. A retrospective cohort study by Sharm et al. titled Association Between Testosterone Replacement Therapy and the incidence of DVT and Pulmonary Embolism compared the incidence of DVT/PE between those who received TRT and subsequently had normal on-treatment testosterone levels, those who received TRT but continued to have low on-treatment testosterone levels, and those who did not receive TRT. Patients with prior history of DVT/PE, cancer, hypercoagulable state, and chronic anticoagulation were excluded. The study did find any significant association between testosterone therapy and risk of VTE. For men who have a familial or acquired thrombophilia’s such as Factor V Leiden heterozygosity, lupus anticoagulant and lipoprotein(a, ) TRT may increase the incidence of VTE. Men with such conditions should be cautioned about the use of testosterone therapy and the possible development of a VTE. A VTE event in men who are at higher risk, usually occur within three months of starting therapy. Yet, for men who have no risks factors, TRT does not impose a higher risk of VTE development, supported by our current scientific research and studies. 1) 1. Charles J. Glueck,* Naila Goldenberg, and Ping Wang, Testosterone Therapy, Thrombophilia, Venous Thromboembolism, and Thrombotic Events. J Clin Med. 2019 Jan; 8(1): 11. Published online 2018 Dec 21. 2) 2. Sarita O. Metzger, Arthur L. Burnett Impact of recent FDA ruling on testosterone 2. replacement therapy (TRT) Transl Androl Urol. 2016 Dec; 5(6): 921–926 3) 3. Glueck C.J., Prince M., Patel N., Patel J., Shah P., Mehta N., Wang P. Thrombophilia in 67 Patients With Thrombotic Events After Starting Testosterone Therapy. Clin. Appl. Thromb. Hemost. 2016;22:548–553. 4) 4. Glueck C.J., Goldenberg N., Wang P. Thromboembolism peaking 3 months after starting testosterone therapy: Testosterone-thrombophilia interactions. J. Investig. Med. 2018;66:733–738. 5) 5. Baillargeon J., Urban R.J., Morgentaler A., Glueck C.J., Baillargeon G., Sharma G., Kuo Y.F. Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy. Mayo Clin. Proc. 2015;90:1038–1045.

Keywords: Raise Testosterone with exercise, Raising Testosterone with Food, HCG, Arimidex, Weight Loss, Muscle Growth, Low-T, Obesity, Clomid, Clomiphene Citrate, Sleep, Sex Drive. Testosterone is a hormone that affects many physiological processes in the body that includes sex drive, erectile function, vascular and heart health, mental health, lipid parameters, bone density and body mass to name a few. Defined by the endocrine society low testosterone is a “clinical syndrome” that is representative of the testicles inability to produce physiological levels of testosterone and symptoms. Symptoms of low testosterone include: erectile dysfunction reduced sex drive loss of muscle mass, obesity reduced energy and endurance loss of body hair, reduced beard growth weight gain, bone fractures fatigue & reduced motivation depression & poor memory The criteria for the diagnosis of late-onset hypogonadism, also known as Low-T, is a patient must present with both symptoms of low testosterone and low testosterone blood levels. In the research literature hypogonadism is defined many ways, but all have commonalities of both symptoms and low testosterone levels. The European Male Aging Study (EMAS) proposed the criteria for hypogonadism of at least 3 sexual symptoms accompanied by low testosterone level less than 11nmol/L and free testosterone levels less than 220 pmol/L. Another study by Harman et al defined low testosterone as circulating testosterone less than 325ng/dL. Using these criteria for defining low testosterone approximately 3%-8% of men in the United States between the age of 20-45 have androgen deficiency. Testosterone decreases in men after age 30, 1% each year. Treatment of testosterone deficiency in men is accomplished by the administration of exogenous testosterone. Although testosterone replacement therapy has benefits of improved sexual function, cognition, muscle strength, lean body mass, bone strength and improves cardiovascular health there are associated side effects. Such side effects can include erythrocytosis, accelerated prostate growth, male infertility, testicular atrophy, and gynecomastia. Given the necessity of being on lifelong testosterone therapy to reverse the symptoms of low testosterone many patients do seek alternative methods. There are a variety of alternative medical and natural methods patients can undertake to improve the symptoms of low testosterone that are safe, preserve fertility and have a lower side effect profile than exogenous testosterone therapy. These alternatives to testosterone therapy include HCG, aromatase inhibitors, select estrogen receptor modulators, stress relief, sleep, diet, nutrition and weight loss. Human Chorionic Gonadotropin (HCG) Human Chorionic Gonadotropin (HCG) is hormone derived from the female placenta that mimics the actions of luteinizing hormone (LH). LH is normally produced by the pituitary gland to stimulate the testicular Leydig cells to produce testosterone. HCG has a similar effect on the testicular Leydig cells raising testosterone levels. There are a variety of studies that have demonstrated exogenous HCG administration can increase testosterone in males. In 2011 Kim et al demonstrated that administration of 1500 to 2000 IU of HCG 3 times per week significantly improved testosterone levels. Vicari et al in 2012 further demonstrated 1,500 IU 3 times per week of HCG could increase testosterone levels significantly over a 24-month duration. Another benefit of HCG found in the study is the improved semen parameters in patients undergoing therapy. HCG stimulates not only testosterone production from Leydig cells but also enhances spermatogenesis. Thus in men who desire to preserve fertility, maintain testicular size and raise testosterone levels, HCG can be a great option. In men who are taking testosterone, the addition of HCG 3 times per week, can maintain spermatogenesis, fertility and testicular size. Risks of HCG administration do include a headache and possible fatigue. Long-term data to support its efficacy and other side effects are lacking in publication. Selective Estrogen Receptor Modulators (SERMs) SERMs are oral medications that act to inhibit the estrogen receptor at the level of the pituitary and hypothalamus. Estrogen has an inhibitory effect on the pituitary to prevent the release of LH and FSH. LH and FSH stimulate the Leydig cells and Sertoli cells within the testicles to enhance spermatogenesis and produce testosterone. By preventing the inhibitory effect of estrogen on the pituitary with SERMs, gonadotropin release can be up-regulated. Several studies in men taking SERMs have been performed. In 2011 Katz et.al performed a prospective study that examined 86 men age 22-36 years of age with testosterone levels less than 300ng/dL. Patients received 25 to 50 mg of medication every other day for 19 months. Results revealed testosterone increase from 192 at baseline to 485. A study by Shabsigh et al. prospectively observed 36 Caucasian men who were administered 25mg of a SERM. Follow up visits at four and six weeks revealed a mean testosterone increase from 247ng/dL to 610ng/dL. SERMs have great oral bioavailability and are a great alternative for men who desire to boost testosterone levels and maintain fertility. It is a safe off-label alternative for men who are considering testosterone replacement therapy. Aromatase Inhibitors (AIs) AIs is an oral medication that inhibits the conversion of testosterone to estrogen. AIs act upon an enzyme called aromatase that is most prominent in the bodies peripheral tissues. The action of AIs reduces estradiol levels in men inhibiting the negative feedback of estradiol on the pituitary. This will, in turn, raise testosterone level production by the Leydig cells of the testicles. Treatment with AIs is considered off-label in men, yet several studies performed have detailed their beneficial effects as an alternative to testosterone therapy. A few side effects that have been reported with AIs include hot flashes, weight gain, insomnia, decreased bone mineral density. While taking AIs, estrogen and testosterone levels need to be monitored to tailor the medication dosage and duration for a patient to get the desired results. Lifestyle: Diet, Exercise & Weight Loss Men with late-onset hypogonadism will most commonly have 1 of 3 conditions that include: diabetes mellitus, metabolic syndrome, and obesity. Chronic medical conditions are a significant cause for hypogonadism. Improving comorbidities through healthy lifestyle changes can improve testosterone levels. Nondrug therapies are inexpensive yet very effective in boosting testosterone levels naturally and can be accomplished by healthy nutrition, exercise, obtaining adequate sleep and decreasing stress. A study by Kumagai et. al found that 44 obese men who performed a 12-week lifestyle modification program involving aerobic exercise three times per week and a diet limited to 1680 kcal/day increased their testosterone levels. Even in the absence of exercise, weight loss itself by way of eating healthy can induce a rise in testosterone levels. This was shown in 2013 in a study by Corona et al. They performed a meta-analysis review of 13 studies evaluating the effect of low-calorie diets. Their results found that weight loss achieved through diet or bariatric surgery was associated with increases in total testosterone. With to diets, the Mediterranean diet (low-fat dairy, eggs, poultry, fish, and vegetables) demonstrated improved total sperm counts. A study by Corona et al. in 2006 demonstrated a linear relationship between the severity of metabolic syndrome (hypertension, increased waist circumference, and high blood sugar) and testosterone levels. Men with low testosterone levels are more likely to have components of metabolic syndrome. Men with metabolic syndrome were also found to have higher anxiety and stress levels that are pivotal to proper sexual function and a healthy libido. Sleep Improvement in sleep quality and duration can improve testosterone levels in men. It has been shown that men with obstructive sleep apnea (OSA) not only have high rates of erectile dysfunction but also have lower testosterone levels. This was conveyed in a study by Santamaria et. al, in 1998 that prospectively observed 12 men with OSA who were treated with therapy (uvulopalatopharyngoplasty) and found at 3 months postoperatively to have increased testosterone levels. Duration of sleep is also just as important as the quality of sleep to improve testosterone levels. Sleep deprivation (less than 5 hours per night) can decrease testosterone levels by 10-15% in men. Stress Relief The bodies natural stress hormone is cortisol. Cortisol is secreted during times of stress and anxiety. Elevated cortisol levels can negatively impact the production of testosterone. One theory is that cortisol acts upon the Leydig cells of the testis to inhibit the natural steroidogenic pathway for testosterone production. Stress management has been studied as means to improve testosterone levels and improve health and mental clarity. Studies have found that majority of men where stress was a common factor in their lifestyle had the following attributes: held 1 or more jobs, worked 50-60 hours per week, long commutes to work and were held to deadline and work quotas. Reducing these lifestyle factors can improve testosterone levels in men. In conclusion, there are a variety of methods men can undertake to increase their testosterone levels from prescription medication to lifestyle changes. Each individual patient who desires to be on testosterone replacement therapy must first be evaluated by a physician to ascertain the cause of low testosterone. Without making the right diagnosis, the correct treatment cannot be administered successfully. Second, each patient is different. Each patient has a desired goal and expectation of therapy that must be discussed with the physician prior to starting therapy. Testosterone replacement is not for everyone and there are alternatives mentioned above. At REGENX Health we ensure all our patients meet with a physician and all options of therapy are discussed. We discuss every patient’s goals and expectation of therapy and their desire for fertility. To schedule a consultation with a REGENX Health Urologist please give us a call or visit us at www.REGENXHEALTH.com. You can also submit questions through our online physician request form for more information. Stay tuned for our next article to improve your health and wellbeing. References Eric M. Lo et al, Alternative to Testosterone Therapy: A Review: Sexual Medicine Reviews 2018 106-113 Katz et.al. Outcomes of SERM treatment in young Hypogonadal men. BJU Int 2012; 110: 573-578. Shabsigh et. Al, SERM’s effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med 2005; 2:716-721. Vicari et. al. Therapy with human chorionic gonadotropin alone induces spermatogenesis in men with isolated hypogonadotropic hypogonadism-long-term follow up Int J Androl 1992; 15:320-329 Kim et. al, Penile growth response to human chorionic gonadotropin (HCG) treatment in patients with idiopathic hypogonadotropic hypogonadism. Corona et. al, Physiobiologic correlates of the metabolic syndrome and associated sexual dysfunction. Eur Urol 2006;50:595-604. Santamaria et.al., Reversible reproductive dysfunction in men with obstructive sleep apnea. Clin Endocrinol 1988;28:461-470. Kumagai et. al. Lifestyle modification increases serum testosterone levels and decreases central blood pressure in overweight and obese men. Endocr J 2015; 62:423-430.

1) What is the difference between Cialis and Viagra ? 2) What medication should I take, Cialis or Viagra ? 3) Which ED medication is best for me ? 4) Can testosterone help my erectile dysfunction ? As a practicing urologist and specialist in testosterone replacement therapy for Low-T and erectile dysfunction (ED) treatments, I commonly get asked by men with ED the following questions during a visit: 1) What is the difference between Cialis and Viagra? 2) What medication should I take, Cialis or Viagra? 3) Which ED medication is best for me? 4) Can testosterone help my erectile dysfunction? I will address each question, but first let’s discuss a little about ED meds and the first line treatment for ED. The first line of treatment for men with ED is oral medication. Oral ED medications such as Viagra, Cialis, Levitra, Stendra & Stayxn are all phosphodiesterase type 5 inhibitors (PDE5i). They all act on the same physiological pathway in the human body. PDE5 is an enzyme in the penis (corpora cavernosa tissue) that prevents an erection from occurring. All oral ED medication work to inhibit this enzyme and are therefore called PDE5 inhibitors. The difference between all the ED medications is their specificity for the PDE5 enzyme. There are many PDE enzymes in the body. The level of specificity for the PDE5 enzyme is different for all ED meds. Other aspects of ED medications that are different include bioavailability (how long it last in the body for use), ability to be taken with or without food and side effect profile. Let’s address these topics as they relate to Viagra and Cialis. 1) “What is the difference between Cialis and Viagra?” There are very several important differences between Cialis and Viagra that patients should be aware, because choosing the right medication will ultimately lead to the best result. Viagra, also known as Sildenafil (the active ingredient), was the first ED medication to enter the market. It was a groundbreaking achievement in the field of medicine that men could improve their erectile function with just a tablet. Viagra was actually discovered on accident, as researches at Pfizer were originally investigating the drug for the treatment of angina (chest pain). They noticed that men were having improved erectile function during their follow up visits during the clinical trials. As thus, they changed the trial to investigate the drug for erectile dysfunction purposes and so began the birth of Viagra. On March 27,1998 Pfizer received FDA approval for Viagra for the treatment of ED at 50mg and 100mg dosages. Viagra has since been used by over 20 million men in over 110 countries and is one the best studied pharmacological substances available. Viagra is best used when taken 1 hour prior to sexual activity and will last in the body for 4-5 hours. Viagra reaches peak levels in the body approximately 30min – 2 hours after oral ingestion. Viagra must be taken on empty stomach, as food will impair its absorption. Side effects of Viagra include: blurry vision and dizziness among others. In comparison, Cialis (also known as Tadalafil) is a second-generation ED medication. Cialis is different than Viagra in the following ways. First, and most noteworthy, is Cialis can be taken with food. Food does not impair the absorption of Cialis. This is important to note because in clinical studies the majority of sexual activity occurs after dinner between the hours of 9pm-1am. Cialis makes it easier for men to be more spontaneous and not have to worry about food intake with medication usage. Second, Cialis has a duration of action of 36 hours, compared to Viagra of only 4-5 hours. Many men find this longer duration of action more appealing because the ability to get multiple erections becomes easier to sustain within than 36-hour window. This does not mean you will an erection lasting 36 hours, but rather the window period of 36 hours makes it much easier to obtain, achieve and sustain an erection much longer than Viagra. Third, Cialis has a lower side effect profile than Viagra. Main side effects of Cialis include congestion and slight back pain among others. Fourth, Cialis can be taken daily. The FDA approved Cialis for erectile dysfunctional and BPH (Benign Prostatic Hyperplasia). A low dose 5mg Cialis, can be taken daily to provide men more spontaneity with their sexual activity and not have to worry about taking medication before sex. This sense of freedom makes Cialis more attractive for men as an ED tablet compared to Viagra. The daily Cialis will also improve symptoms of an enlarged prostate such as waking up at night to urinate, straining to urinate, or frequency and urgency of urination. 2) “What medication should I take, Cialis or Viagra?” Now that we have discussed the main differences between Cialis and Viagra, which one should you choose? I tell many of my patients it really depends on lifestyle and the amount sexual activity you are having. For instance, for a man who has sex multiple times per week and does not plan sexual activity, then Cialis is a more attractive option. For a man who plans his sexual activity, such as a married couple who goes out to dinner and then plans to engage in sex, then Viagra can be a better option. Most men, including the partners of men, prefer Cialis over Viagra. 73% of patients prefer Cialis over Viagra, and 63% of men preferred the freedom and dosing instructions Cialis provides. Couples who are anticipating more frequent sexual activities and spontaneity prefer Cialis. With Cialis you don’t have to link sex with medication, because Cialis can be taken daily. This feature is preferred by most men and provides greater freedom and less planning. In studies of men using Cialis, men felt less time pressure, less sense of urgency, and less planning before and during sexual intercourse when taking Cialis compared to Viagra. Men who take Cialis state they have the “ability to get an erection long after having taken Cialis” and the “ability to get an erection every time.” Men who use Viagra score higher in sexual self-confidence domains. Men on Viagra feel the “ability to get an erection every time” and the erections are firmer. 3) “Which ED medication is best for me?” When it comes to choosing the right erectile dysfunction medication it’s important to take into account lifestyle and frequency of sexual activity. Some men respond better to Cialis than Viagra and vice versa. If you are having sex often, Cialis is enjoyed by most men. Viagra may better for more planned sexual activity. Also, Cialis (Tadalafil) and Viagra (Sildenafil) can be formulated to work faster, enhance stamina, sensitivity, rigidity and delay ejaculation. These are new and emerging formulations that REGNEX Health provides than enhanced Sildenafil and Tadalafil. Currently, Cialis and Viagra are made as a film coated tablet. The film acts as a barrier to absorption and must be broken done by the gut. The gut and liver also breaks down the medication and less active ingredients are available. With oral rapid dissolving tablets, the film coating is removed and the tablets dissolve fast under the tongue. Absorption is across the mucus membrane in the mouth, bypassing the gut, and going directly into circulation. More active ingredient is available and onset for an erection to occur is much faster. A study from 2003 evaluated the velocity by which sildenafil acted when the film coated tablets were crushed. Crushed tablets were taken under the tongue and allowed to dissolve. Researches noted faster onset of activity. The benefits of oral dissolving ED tablets include: 1) Higher Bioavailability (less breakdown of the drug by the stomach or gut) 2) Discrete intake since no water is needed 3) Elimination of any swallowing issues 4) Faster time to peak concentration (Tmax) 5) Shorter duration of time of onset (faster acting) (Tonset) A REGENX Health urologist can guide you on the best treatment and regiment for ED. Speak with a REGENX Health Urologist today and get the expert treatment and medication that is right for you. 4) “Can testosterone help my erectile dysfunction” Yes. Men with who have low testosterone (Low-T) should be informed that testosterone replacement therapy can improve erectile dysfunction. Several studies have confirmed that ED meds are more effective when combined with testosterone replacement therapy. There are 5 randomized controlled trials that observed men who took ED meds combined with testosterone replacement had better outcomes compared to men who only took ED meds without testosterone. Patients on testosterone therapy and ED meds had higher erectile function scores and more pronounced sex drive. It’s imperative that all men with ED have their testosterone and estradiol levels checked. Optimizing therapy may include hormone replacement. Testosterone therapy is not an effective mono-therapy for ED, but when combined with an ED med such as Viagra or Cialis, results can be enhanced. If you have any questions about the information above or desire to speak with a REGENX Health Urologist today, please give us a call at 1.888.6.REGENX.

The two largest laboratory testing agencies in the Unites States are LabCorp and Quest. If you are undergoing testosterone replacement therapy you will most likely be having your blood drawn and analyzed by either of these two laboratory agencies. Your clinician should be aware that there exist differences in the way each laboratory analyzes testosterone and how the normal references ranges of testosterone are reported. LabCorp In 2017 LabCorp changed their normal reference range of serum testosterone values from 348-1197ng/dL to the a much lower 264-916ng/dL. The reason for the change was to encompass more men who are obese in the population and are known to have a lower serum testosterone level. This change is direct reflection that more men in society are overweight leading to a new normal lower serum testosterone reference range. LabCorp offers high pressure liquid chromatography and tandem mass spectrometry (LC/MS) to measure serum testosterone. This is the gold standard as maintained and reported by the CDC Hormone Standardizations. LabCorp recommends total testosterone be measured between 800am and 12pm. Quest Similar to LabCorp, Quest laboratories also provide LC/MS as the gold standard measurement assay for serum testosterone. Yet despite both companies utilizing LC/MS the normal reference ranges of testosterone are different. According to the Quest website the normal testosterone reference range for men is 250-1110ng/dL. This is significantly different from LabCorp. The importance of this difference, relies upon the diagnosis of Low-T that some insurance companies may rely upon. For example, if any individual has a testosterone value measured to be 255ng/dL, according to the Quest laboratory reference range this individual has a normal testosterone value. When this level is applied to the LabCorp reference range, this individual would be outside the reference range and be considered to have hypogonadism. While the American Urologic Association (AUA) defines Low-T as less than 300ng/dL, obtaining coverage for medication from insurance companies can also rely upon the assay results as depicted above. For this reason, a clinician should seek to treat the patient, sign and symptoms of Low-T, rather than numerical value of testosterone if within the low normal reference range.