· How to manage estrogen levels in men on TRT · Estrogen response in men on TRT · Use of selective estrogen receptor modulators (SERMS): Tamoxifen and Clomid · How estrogen is affected on testosterone replacement therapy · Importance of estrogen in sexual function Keywords: High estrogen, Estrogen in men, symptoms of high estrogen in men, what causes high estrogen levels in men, estrogen imbalance, gynecomastia, Tamoxifen, Clomid, SERM, Arimidex, Anastrozole, Estrogen Estrogen is a hormone that is not only prevalent in females, but also plays an important role in male physiology. The role of estrogen in men has received much attention since the evolving popularity of testosterone replacement therapy (TRT). It is well known that men on TRT will have a corresponding rise in their estrogen level. Monitoring and managing estrogen levels is paramount to optimizing testosterone therapy results. Estrogen has long been known as an important hormone for bone and vascular health in both males and females, but its role in sexual function, erectile function, sex drive, weight loss, and performance are becoming more well known. In men on Testosterone therapy who look to optimize performance, sex drive, muscle growth and weight loss, estrogen management must also be a component of therapy. Estrogen circulates in the body in three forms: E1, E2, E3. The most prominent form of estrogen in males is E2 (Estradiol). Estradiol is most important form of estrogen to manage during TRT. Estrogen Production in Men The majority of estrogen in the male body is a breakdown product of testosterone. Other sources and production of estrogen in men include the Leydig Cells in the testicles, adrenal glands and peripheral tissues (adipocytes: fat cells). Men with Low-T who use exogenous testosterone are subject rises in estrogen levels. Testosterone acts a substrate for estrogen production, the more testosterone administered into the body the me that can be converted into estrogen. This is especially true in obese males who have significant amount of fat cells that house aromatase. Men who are obese tend to have higher estradiol levels than men of normal weight. Elevated estrogen levels can stimulate male breast enlargement (gynecomastia). As men age testosterone production declines and the ratio of estrogen to testosterone rises in favor of estrogen. It is often the ratio and balance of estrogen to testosterone that effects male physiology. The use of an aromatase inhibitors, (Arimidex or Anastrozole) can stop this conversion and breakdown of testosterone. Arimidex has been used in coordination with TRT in many men’s health testosterone clinics to reduce the breakdown of testosterone, reduce estrogen production and as a treatment for gynecomastia. Estrogen in Overweight Men Overweight men commonly suffer from metabolic syndrome; a combination of obesity, high blood pressure, elevated blood sugar and high cholesterol. This collection of conditions increases the risk for cardiovascular disease and diabetes. Obese men with metabolic syndrome have a low testosterone level and elevated estrogen levels. Obese men with metabolic syndrome tend to have lower Sex Hormone Binding Globin (SHBG) levels. While one would think this would provide more bioavailable testosterone, it does not. Obese men tend to aromatize estrogen more than the normal weight individuals. Given the higher density of adipose (fat cells) in obese men, which is the primary source for aromatase, more testosterone is broken down into estrogen. Elevated estrogen, via negative feedback on the pituitary gland prevents testosterone production. Furthermore, elevated Leptin levels in obese men prevents LH release from the pituitary gland further reducing testosterone levels. Men with reduced testosterone levels are subject to increasing weight gain, depression, loss of muscle mass and erectile dysfunction among others. Aromatase Activity and Adipose Tissue (Fat Cells) Aromatase is predominately found in adipose tissues, principally in the central fat deposits of the abdomen. Obesity is one of most common conditions associated with low testosterone (Low-T). Large amount of fat cells convert testosterone into estradiol. The more fat cells a man has centrally located, the more aromatase enzyme that is present. Furthermore, fat cells release pro-inflammatory markers that promote cholesterol build up in arteries (plaque) and reduce pituitary signals that normally raise testosterone levels. Fat cells also release Leptin, a molecule that inhibits the release of GnRH (Gonadotropin Releasing Hormone). Lower levels of GnRH reduces LH and FSH secretion from the pituitary gland thereby reducing testosterone production and release from the testicles. The Role of Estrogen in Testosterone Production Estrogen is a breakdown product of testosterone. Estrogen plays a pivotal role in controlling the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus and the release of Luteinizing Hormone (LH) from the pituitary gland. Both of these signalizing hormones, GnRH and LH, are necessary for testosterone production. Estrogen can act to block the release of these signaling hormones and halt testosterone production. This is the principle reason why monitoring and managing Estrogen levels during TRT is important. When estrogen levels are too high in men the result can be a decrease in testosterone production. When men undergo testosterone replacement therapy, aromatase will act to breakdown newly injected testosterone into estrogen. Blocking the aromatizing enzyme can improve and maintain injected testosterone. In fact, aromatase inhibitors such as Arimidex (Anastrozole) can be used in men with elevated estrogen levels for the primary treatment of hypogonadism and increase testosterone levels without impairing fertility. Estrogen Response during Testosterone Replacement Therapy (TRT) Men who are administered testosterone in any formulation (injection, topical gel, topical cream, pellet, or patch) will have a corresponding rise in estradiol levels. In particular, testosterone injections, such as testosterone cypionate or testosterone enanthate, will have a higher rise in estradiol levels than other testosterone formulations. A study by Amory et. al also found that men on combined Testosterone enanthate and Finasteride had a greater increase in estradiol levels than man on Testosterone enanthate by itself. This may be a result of finasteride blocking the conversion of Testosterone to DHT and providing more substrate for aromatase to act upon. There is a greater increase in estradiol levels in older men and more obese men on testosterone. As thus, this particular population of men and men on finasteride who are on TRT should have their estradiol monitored and advised. The Role of Estrogen and Erectile Function Estrogen may play a role in male orgasm, penile detumescent and penile erection. Estrogen receptors and the aromatase enzyme do reside in penile tissue. Studies have confirmed that penile development is also an estrogen dependent process in addition to testosterone. While the exact mechanism and pathway estrogen plays during an erection is still be understood, through clinical observation men with very low or even very high estrogen levels can have erectile dysfunction and decreased sexual desire. The goal of estrogen monitoring and treatment is to keep estrogen levels stable and within a specific and tailored range. Sexual desire is an androgen dependent process, principally a result of testosterone. Much less is known about the role of estrogen in male sexual desire. It is believed that the ratio of testosterone to estrogen is the important factor in male sexual behavior rather than the presence of one individual hormone alone. In an interesting observational study in men who do not have the aromatase enzyme (aromatase-deficient men), estrogen supplementation increased sexual behavior. It is important for any man who is undergoing to undergo testosterone replacement therapy (TRT) or estrogen management, to understand that estrogen (principally estradiol) plays a pivotal role during treatment. The goal of therapy should not be to lower estradiol levels to undetectable levels as this could affect male sexual behavior, desire and erectile function. The balance should be focused on the ratio of testosterone to estradiol levels in addition to keeping estradiol within a specific therapeutic range. Arimidex The most widely used medication to manage estrogen levels during TRT is Arimidex. Arimidex is an aromatase inhibitor (AI). Aromatase acts upon testosterone and breaks it down by a process called aromatization into estradiol (a form of estrogen). The aromatase enzyme has found to be present in the testicles, brain, fat tissue, muscle, hair, and vascular tissues. In men Arimidex is used off -label. AI’s are classified into two categories, either steroidal and non-steroidal and by generation (first, second and third generations). Steroidal aromatase inhibitors are commonly not utilized in men on TRT. Steroidal aromatase inhibitors bind to aromatase strongly (irreversibly). Non-steroidal aromatase inhibitors, such as Anastrozole (Arimidex) reversibly bind to aromatase. Arimidex is a third generation AI. Third generation AI’s do not completely inhibit the aromatase enzyme completely. This partial inhibition of aromatase may impart some benefit when used in men because it allows some degree of estrogen production. Complete absence or very low levels of estrogen in men can be detrimental affecting sexual function vascular health, and weight gain. While Arimidex is known to reduce estrogen in men by inhibiting aromatase, the medication can also increase testosterone production. Arimidex prevents estrogen from blocking pituitary signals that stimulate testosterone production, mainly LH and FSH. In several clinical studies Arimidex given 1mg daily has been shown to increase, often double, bioavailable testosterone. Unlike TRT, patients who use Arimidex as mono therapy do not experience a rise in hematocrit and hemoglobin levels or an elevation in prostate- specific antigen (PSA). A study in 2004 by Leder et al. reveled that anastrozole was able to in raise testosterone levels in men with Low-T. Also, a randomized placebo-controlled study by Massachusetts General Hospital and Harvard Medical School to assess the effects of anastrozole on testosterone levels found testosterone values peaked at 3 months compared to the placebo group and estradiol levels decreased significantly in men on anastrozole mono therapy. During the study clinicians found no change in PSA, worsening of lower urinary tract symptoms (LUTS) , hemoglobin and hematocrit levels. Of primary importance, despite a rise in testosterone levels the body composition and strength improvements normally accompanied by TRT was not witnessed in men on anastrozole mono therapy. To Learn more about Arimidex click here. According to the American Urologic Association guideline Arimidex, for off label use in men, Arimidex is dosed at 0.05 to 1mg every three days. Side effects of the medication include hot flashes, dyspnea, peripheral edema, and bone pain. Selective Estrogen Receptor Modulators (SERMS) Pharmaceutical medications such as Clomid (Clomiphene Citrate) and Tamoxifen are selective estrogen receptor modulators (SERM’S). SERMs act to block the estrogen receptor in target tissues and glands. This is different that Anastrozole which inhibits the enzymes that converts testosterone in to estrogen. By blocking the estrogen receptor in the pituitary or hypothalamus, estrogen is unable to impact signaling hormones that stimulate testosterone production. Furthermore, SERM’s act to decrease tissue responses to estrogen. For instance in men on TRT, the increase in estrogen can stimulate breast tissue enlargement (Gynecomastia). The use of SERM’s can prevent male breast tissue from enlarging or shrink breast tissue that has enlarged. Tamoxifen Tamoxifen is an off-label medication used in men to prevent and treat gynecomastia. Tamoxifen exerts an effect by binding to estradiol (E2) receptors in estrogen sensitive tissues (such as the male breast) and prevents estrogen from exerting an effect. Tamoxifen has and can be used in men on TRT who experience gynecomastia. Gynecomastia is enlargement of male breast tissue and is a result of an imbalance between testosterone and estradiol levels. The use of Tamoxifen (20mg daily) can reduce breast tissue enlargement in men on TRT. Arimidex can also be used in combination with Tamoxifen to combat male breast tissue enlargement. According to the American Urologic Association guideline Tamoxifen, for off label use in men, is dosed at 20mg orally daily. Side effects of the medication include liver enzyme changes, ocular (eye) changes and increased risked of thromboembolic events. Clomid Clomiphene Citrate (Brand name Clomid) is a selective estrogen receptor modulator. Initially developed in the 1960’s to treat female infertility, Clomid is commonly used off-label in men to treat male infertility and low testosterone. In men with Low-T, Clomid is an excellent and effective oral medication to raise serum testosterone levels and improve the testosterone to estradiol ratio. Clomid can improve and raise testosterone. In some men Clomid can raise testosterone above 1000 ng/dL. Clomid works by blocking the estrogen receptor leading to an increase in both FSH and LH. These two signaling hormones released by the pituitary stimulate the testis to raise testosterone levels and enhance spermatogenesis (sperm production). For more information on Clomid click here. When to Measure Estrogen in Patients on Testosterone Replacement Therapy According to the American Urologic Association guidelines for testosterone replacement therapy, there are specific instances and situations estrogen levels should be measured. In men with low testosterone who present with breast symptoms or gynecomastia., a clinician should check an estradiol level at baseline. Optional to measure Estradiol levels in all patients with testosterone deficiency at baseline to assess pre-testosterone therapy level. Optional to measure Estradiol in all patients who are using SERMs. Treating Elevated Estrogen (Estradiol/ E2) in Men on TRT. In men who use testosterone there is evidence that a corresponding rise in estradiol levels will result. A clear indication for the treatment of estradiol levels in men on TRT is the development of breast tenderness or enlargement of breast tissue while on therapy. In some clinical practices, men who are on Testosterone therapy also provided Arimidex form the start. This practice may be performed secondary to prior research that men on combination Testosterone therapy and Arimidex compared to Testosterone alone had greater sexual drive and interests. Other clinical practices have preferred to observe the rise in estradiol while on testosterone therapy before treating. Sources Nieschlag et al. Testosterone Action, Deficiency, Substitution. Fourth Edition, Published 2004. Tan et. al. Clinical use of Aromatase Inhibitors in Adult Males. Journal of Sexual Medicine. April 2014. Vol. 2. Iss. 2. Pages 79-90. Wheeler et. al. Clomiphene Citrate for the Treatment of Hypogonadism. Journal of Sexual Medicine. April 2019 Vol. 7, Iss 2, Pages 272-276. Kacker et. al. Estrogens in Men: Clinical Implications for Sexual Function and the Treatment of Testosterone Deficiency. June 2012 Volume 9. Issue 6 Pages 1681-1696.

Testosterone Replacement Therapy (TRT) and the Prostate Low-T is a Risk Factor for Prostate Cancer Testosterone and Prostate Health Prostate: Testosterone Saturation Model FDA Label Warning AUA Guidelines Keywords: Prostate health, BPH, LUTs, Urinary symptoms, TRT, Testosterone and Prostate Health, Prostate Cancer and TRT, Rising PSA, Prostate Specific Antigen, PSA rise on Testosterone Therapy, Saturation Model of Testosterone Therapy, High- Dose Testosterone Therapy for Prostate Cancer Treatment. BPH BPH stands for Benign Prostatic Hyperplasia. The prostate is a gland present only in men and serves only to provide fertility. The prostate is located just below the bladder and envelopes the urethra. As a man matures his prostate can grow causing compression of the urethra and abutting the bladder. This can lead to lower urinary tract symptoms, often termed LUTs. Symptoms of an enlarged prostate include straining to urinate, frequency and urgency to void, waking up a night to void and a weak urinary stream. Prostate growth is an androgen dependent process. Testosterone and its derivative DHT (dihydrotestosterone) play an integral role in prostate development and growth. Testosterone & BPH It is the concern of clinicians and men that testosterone can increase prostate growth and therefore exacerbate the symptoms of BPH such as frequency of urination, urinary urgency, staining to urinate, waking up at night to urinate or weak urinary stream. In fact, there is evidence to support just the opposite, that testosterone can improve lower urinary tract symptoms (LUTS). As shown in clinic studies men with Low -T who receive testosterone supplementation experience no significant change in urinary symptoms scores or worsening of LUTS. Some clinical studies have shown that testosterone can and may improve symptoms of an enlarged prostate, improve bladder emptying, voided volumes, and improve IPSS (International Prostate Symptom Score) and AUASS (American Urologic Association Symptom Score). IPSS and AUASS are questionnaires developed by physicians to understand the severity of urinary symptoms in men. Testosterone can improve Nitric Oxide (NO) and Nitric Oxide Synthase (NOS) in the bladder and prostate, causing smooth muscle relaxation and easing the passage of urine during voiding. Men with low testosterone may have lower levels of NO and NOS in the tissue of the prostate and bladder, lending to worsening LUTS. Testosterone Replacement Therapy (TRT) and Prostate Cancer For years clinicians have been concerned that providing testosterone replacement therapy (TRT) could cause and increase the risk of developing prostate cancer. This idea was born from the current treatment of prostate cancer algorithm. Men with metastatic prostatic cancer are treated by medical castration (medication used to stop testosterone production by the testicles and or by blocking the androgen receptor). That is per say, the treatment for prostate cancer is to lower testosterone levels. So, the opposite has been believed to be true, receiving exogenous testosterone can cause prostate cancer. In addition, it is believed that the use of testosterone in patients with prostate cancer may exacerbate the disease and spread prostate cancer. This theory that exogenous testosterone usage could spread prostate cancer was initially postulated decades ago by Fowler and Whitmore, and by Charles Huggins and Hodges who found that prostate cancer was an androgen provoked condition. We know today, after years of research and clinical trials there is no evidence that links any increased risk of developing prostate cancer in men undergoing TRT. There is no evidence that normal levels of testosterone have any relationship to prostate cancer. In fact, we know today that men who have low testosterone actually have a higher risk of developing prostate cancer. Having low testosterone level is a significant risk factor for developing prostate cancer. In fact, under clinical investigation at John Hopkins Kimmel Cancer center is the use of high dose testosterone therapy to treat metastatic prostate cancer. There has also been a myriad of studies that have documented treating patients who have or had prostate cancer with TRT and there has not been any association or increased risk of prostate cancer development, prostate cancer spread or continued rise in prostate specific antigen (PSA). We know today that frequency of prostate cancer development in men on TRT is the same as men not being treated with testosterone. There has been no association between the level of testosterone, free testosterone or DHT levels and risk of developing prostate cancer. A meta-analysis of over 19 clinical studies by Calof et. al in men with Low-T found no increased risk of prostate cancer in men being treated with testosterone compared to a group of men receiving placebo medication. Furthermore, several studies to date have investigated giving testosterone to men with a history of treated prostate cancer and observe any increased risk of recurrence as a result of testosterone supplementation. Several studies have found no increased risk of PSA recurrence in men treated with radiation therapy, brachytherapy or surgical radical prostatectomy. Prostate: Testosterone Saturation Model The Prostate: Testosterone saturation model provides a reasonable scientific explanation why exogenous testosterone supplementation does not result in a rising PSA or prostate enlargement. If we consider that the body has a finite amount of androgen receptors in the body, then we can also conclude that there is testosterone level in which all these androgen receptors are saturated. Any rise in testosterone above this level in which all androgen receptor are saturated would not exert any further effect on prostate growth or rise in PSA. The prostate: testosterone saturation model theory predicts that PSA and prostate tissue are stimulated and sensitive to exogenous testosterone at low testosterone levels. Several studies have revealed that testosterone is maximally bound to all receptors at testosterone concentrations of 60-90ng/dL. This means that men with low testosterone levels who receive testosterone supplementation may experience a slight rise in their PSA or prostate growth until this threshold is met. Any testosterone level above this level does not stimulate the prostate any further. This theory has been supported by several studies, but of note some prostate cancers that may not adhere to such principles. Low Testosterone is an Independent risk factor for Prostate Cancer. It is a common practice in urology when screening a man for prostate cancer with a digital rectal examination and PSA level to also include a testosterone level. There is a significant association between a low testosterone level and an increased detection of prostate cancer and unfavorable pathology on prostate biopsy. As thus men who present for TRT and are above the age of 40, a PSA level should be coordinated with the testosterone level to ascertain any increased risk of prostate cancer. A study by Pichon et. al. revealed that a low serum testosterone level was an independent risk factor for upgrading prostate cancer stage after radical prostatectomy. From the San Francisco et. al. study, men on active surveillance (active monitoring of diagnosed low grade prostate cancer) with low serum testosterone levels at a higher risk (x4) of being upstaged. Testosterone Replacement Therapy (TRT) is safe even with a History of Prostate As reported the American Urologic Association 2018 annual meeting, men with a history of prostate cancer who undergo testosterone supplementation do not have an increased risk of prostate cancer recurrence. Several studies have looked at men with a history of prostate cancer treated by radical prostatectomy, and found no significant rise in PSA or recurrence of prostate cancer when these men underwent testosterone replacement therapy post operatively. This also holds true for men who underwent radiation or brachytherapy for prostate cancer, no increased risk of recurrence or significant rise in PSA when undergoing testosterone injections. Urologist have long been giving patients testosterone therapy even after being diagnosed and treated for prostate cancer. To date, there are approximately a total of 9 published studies on TRT in men after treatment for prostate cancer. Only 10 men or 2.8% of men, were noted to have biochemical recurrence. Furthermore, a study by Moregentaler et. al published in the 2011 Journal of Urology looked at men with untreated prostate cancer who were given testosterone therapy found - No significant changes in PSA - No change in prostate volume - No prostate cancer progression - No cancer identified in 54% of follow up biopsies. There is now basic science data that testosterone may even be protective against prostate cancer. FDA Label Worsening of Benign Prostate Hyperplasia (BPH) and Potential Risk of Prostate Caner o Patients with BPH treated with androgens are an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. o Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens. o Androgen 1% is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate. Of note: There is not a single study that shows that men on T therapy have a worsening of their BPH symptoms. On the contrary there are studies that show improvement in urinary flow and symptoms of BPH of men on androgen therapy. AUA Guidelines Clinicians should inform patients of the absence of evidence linking testosterone therapy to development of prostate cancer. Patients with testosterone deficiency and a history of prostate cancer should be informed that there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy. According to the American Urologic Association guidelines, “while the FDA retains a warning regarding the potential risk of prostate cancer in patients who are prescribed testosterone products, there is accumulating evidence against the link between testosterone therapy and prostate cancer development.” Sources Ronny et. al. Testosterone and the Prostate. Journal of Sexual Medicine. Vol. 2, Issues 3-4, P112-120. Pub. October 2014 Khera et al. Testosterone Replacement in Men Treated and Untreated Prostate Cancer. Journal of Sexual Medicine. Vol. 1. Pages 143-149. Pub. 2013 Traish AM, Williams DF, Hoffman ND, Wotiz HH. Valida- tion of the exchange assay for the measurement of androgen receptors in human and dog prostates. Prog Clin Biol Res 1988;262:145–60. Yasmin AA et al. World J Urology. 2008; 26(4): 359-364 Huggins C. Effect of orchiectomy and irradiation on cancer of the prostate. Ann Surg 1942; 115: 1192–200 Yano M, Imamoto T, Suzuki H et al. The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening. Eur Urol 2007; 51: 375–80 Pichon A, Neuzillet Y, Botto H, Raynaud JP, Radulescu C, Molinie V, Herve JM and Lebret T. Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading. Prostate Cancer Prostatic Dis. 2015; 18:382-387.

A patient guide to Penile injection therapy, formulations, dosages, and unique injection techniques. Keywords: Impotence, Atropine Sulfate, Penile injection, Trimix, Bimix, Edex, Alprostadil, Priapism, Alprostadil, Papaverine, Quad Mix, Caverject, Muse, Intracavernosal Injection, ICI, Introduction Penile injections have long been used for the diagnosis and treatment of erectile dysfunction (ED). Before the dawn of Viagra, the primary treatment methods for ED were microvascular surgeries, penile prosthesis implantation, psychosocial interventions and penile injection therapies. For patients who fail oral ED medication such as Viagra or Cialis the next line therapy can be 1) change the type of oral ED medication or 2) proceed to penile injections. While penile shockwave therapy is gaining much attraction as a therapy that can fit nicely between patients who fail to respond to ED meds penile injection therapy remains the next step in therapy and has high satisfaction rates. Penile injection therapies remain a mainstay of therapy in the field Urology and have several benefits: Benefits of Penile Injection Therapy for Men. 1) Provides a rapid and natural erection to occur within 5-10 minutes of injection 2) Dosage can be titrated to promote erection duration and hardness of erection. 3) No sexual stimulation or erotic thoughts are required for an erection to occur. 4) Maintains full penile sensation and orgasmic function. Side effects of Penile Injection Therapy for Men 1) Risk of priapism 2) Reduces ability of spontaneity 3) Requires a small, painless injection into the penis 4) Medication does require refrigeration Benefits of TRIMIX compared to Viagra and Cialis In some men, Viagra, Cialis and other ED meds are contraindicated. In men who have a history of heart attack or who use nitrates for chest pain may not be able to used oral ED medication. Some men cannot tolerate the systemic side effects that can occur with oral ED meds such as stuffy nose, headaches, muscle pain, back pain, or blurry vision. In these particular situations, penile injections can be an option. Unique to penile injection therapy is the mechanism of action and localization of the medication. Penile injections do not exert an effect on the entire body unlike oral ED meds. Penile injections are localized within the penile cavernosal tissue. Furthermore, the mechanism of action of penile injection is significantly different than the normal pathway utilized by ED meds to assist in achieving an erection. This can owe to the lower side effect profile of penile injections and can be a safer, better and more efficacious treatment option for men with contraindication to oral ED medication usage. Much of the barrier to penile injection therapy is the anxiety surrounding an injection into the penis. It is known that men who consistently used penile injections, also known as intracavernosal injections or ICI, have high satisfaction rates. Many patients can attest that the injections can be made virtually painless. How to Properly Administer Penile Injections According to the American Urologic Association (AUA) guidelines an in-office test injection should be performed to ascertain the following by the urologist: 1) the length of duration of penile erection 2) injection response 3) penile rigidity after injection 4) penile injection technique (how to give injection/location on penis) 5) observe for priapism 6) observe for pain on erection 7) evaluate penile anatomy 8) provide men the confidence to perform their own injection 9) educating the patients partner about the injection technique and site for injection. TRIMIX Penile Injection Components Trimix is a non-FDA approved product for the treatment of erectile dysfunction. The only FDA approved penile injection therapy for the treatment of ED is Alprostadil, also known as Caverject, Edex or Muse. Trimix, on the other hand, is a combination of three vasoactive ingredients. The components of Trimix include Papaverine, Phentolamine, and Alprostadil. The three components together are commonly called combination therapy. Together Trimix utilizes several different mechanisms to achieve an erection, such as: 1) Increasing corporal smooth muscle relaxation 2) Decreasing smooth muscle and blood vessel contraction 3) Increasing blood vessel dilation Papaverine A vasodilating agent that promotes the widening of the blood vessels and influx of blood volume into the penis. Mechanism of action is by relaxing the smooth muscle contained within the walls of blood vessels. Phentolamine An alpha blocker that prevents the excitatory signals to blood vessels that normally keeps blood vessel constricted, thereby leading to muscle relaxation. Alprostadil Alprostadil is the only FDA approved mono therapy penile injection for the treatment for ED. Alprostadil was introduced in the early 1980’s and approved by the FDA in 1994. Alprostadil acts by stimulating the production of cAMP (Cyclic adenosine monophosphate) in both penile smooth muscle and blood vessels. A cascade of events leads to muscle relaxation, penile hardness and a rigid erection. Alprostadil is unique compared to oral ED medication , it does not rely on the Nitric Oxide pathway utilized by oral ED meds to encourage an erection. Most men who fail to respond to oral ED meds have an underlying neurogenic injury or history of radical prostatectomy (removal of the prostate for prostate cancer). For men with neurogenic ED who use Alprostadil mono-therapy a lower dose should be utilized. Bimix Penile Injection Bimix is composed of two components, Papaverine and Phentolamine Mesylate. Men who are candidates for Bimix injection, compared to Trimix, are those men who are very sensitive to low doses of Trimix. Often times, men who have a neurologic injury require a very low dose of penile injection medication. The dosage of Trimix can be so low, on the magnitude of 0.1 or 0.05 micrograms, that the patient will have difficulty drawing this dosage into a syringe. In this particular clinical scenario, Bimix is great candidate medication to utilize. Quad Mix for Penile Injection Quad Mix has the same components as Trimix with the addition of atropine sulfate. Atropine sulfate inhibits nervous system receptors responsible for smooth muscle control. In effect, atropine sulfate provides further smooth muscle relaxation in combination with the other three components of trimix. Quad Mix is a great option for men who fail Trimix and have achieved the maximum dosage. Combining Trimix and Oral ED Meds There are several studies that report a high satisfaction rate in men who utilized a combination of both ED meds with penile injection therapy. In effort to improve penile function and penile rehabilitation, men post radical prostatectomy, have performed the following: Intracavernosal injection of alprostadil 2-3x times per week in addition to use of the Viagra ™ during sexual activity. It is important to note that Alprostadil was injected 2-3x per week on a scheduled basis and not during sexual activity. Satisfaction scores my men who use this therapy were high, especially in men who had failed oral ED meds and did not want to perform penile injection just before activity. Another study treated 35 men post non nerve sparing radical prostatectomy with Quad Mix (papaverine hydrochloride, prostaglandin E1, phentolamine mesylate, and atropine) three times weekly combined with Cialis ( Tadalafil) 20mg given 2 hours prior to sexual activity ( on days penile injection was not used). This unique protocol conveyed an acceptable level of patient satisfaction with limited adverse events. How to improve Spontaneity with Penile Injection Therapy Trimix has to be refrigerated at all times and this makes it difficult to be spontaneous with a partner. Also, trimix has to be injected, reducing spontaneity. One easy way patients have improved their spontaneity is by pre-fill the syringes with the prescribed dosage of trimix. Keep the pre-filled syringes in the refrigerator as opposed to the trimix bottle. This will provide the individual a quick and easy opportunity to excuse himself, inject with a pre-filled syringed and enjoy the moment. Having to draw up TRIMIX every time during an intimate time can be difficult and time consuming. Sources Mydlo JH, Volpe MA, Macchia RJ. Initial results utilizing combination therapy for patients with a suboptimal response to either alprostadil or sildenafil monotherapy. Eur Urol. 2000;38:30-34. 2 Raina R, Nandipati KC, Agarwal A, et al. Combination therapy: medicated urethral system for erection enhances sexual satisfaction in sildenafil citrate failure following nerve-sparing radical prostatectomy. J Androl. 2005;26:757-760. Nehra A, Blute ML, Barrett DM, Moreland RB. Rationale for combination therapy of intraurethral prostaglandin E(1) and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy. Int J Impot Res. 2002;14 (1 suppl):S38-S42. McMahon CG, Samali R, Johnson H. Treatment of intracorporeal injection nonresponse with sildenafil alone or in combination with triple agent intracorporeal injection therapy. J Urol. 1999;162:1992-1997 E. Ventimiglia et.al. 679 Proposal of new rehabilitation protocol based on the use of intracavernous injections and Tadalafil. Preliminary results from a pilot study. The Journal of Sexual Medicine, Vol. 15, Issue 7, S390. Published in issue: July 2018

A greater than 10% decrease in weight, significantly improves testosterone levels by 85ng/dL. 15% of weight loss can increase testosterone by 180ng/dL Keywords: Diet, Testosterone Levels, Free Testosterone Levels, Fat Restrictive Diet Ketogenic Diet, Androgen, Cholesterol, Statins, Testosterone, Diabetes, Weight Loss, Introduction While many men who have low testosterone look to androgen replacement as solitary treatment option, a multifaceted approach is best. To enhance and expedite testosterone replacement therapy results and rise serum testosterone levels more efficiently patients should be advised to incorporate a healthy diet, exercise and weight loss routine while on therapy. As mentioned in prior posts a man can improve their serum testosterone levels exponentially by weight loss alone. Weight loss is associated with a 72% decrease in fat free mass and loss of fat free mass increases testosterone levels. Testosterone can increase resting basal energy expenditure promoting the weight loss cycle. With the addition of a testosterone enhancing diet and exercise routing, the cycle of weight loss and rise in serum testosterone is amplified. Fat Restrictive Diet Prior studies examining diet and serum testosterone levels revealed that low fat diets (less than 25% caloric consumption) had no effect on Testosterone levels. Even a diet restricting caloric consumption of less than 10% had no effect on increasing serum testosterone levels. With this information one may consider that a nonrestrictive diet or a diet that does not restrict calories may be best for enhancing serum testosterone. We know from many studies that weight loss in the obese population from a fat restrictive diet can an increase serum testosterone levels of 182 to 240ng/dL. In normal weight males who adhere to a fat restrictive diet, we do not see this same increase in serum testosterone level. One theory to explain this phenomenon may be that fat is a precursor to steroid and testosterone production. Significant caloric and fat restriction may prevent the necessary precursors to make testosterone. Ketogenic Diet The Ketogenic diet consists of ingesting high fat and low carbohydrates. The ketogenic diet aids in weight loss by the mechanism that utilizes ketones and glucose restriction. This replicates the effects of fasting on the body. The Ketogenic diet has been used for centuries, primarily to aid in seizure control in patients with epilepsy. Today, the ketogenic diet is used by many individuals for weight loss and hunger control. As it relates to an increase in serum testosterone, a study by Wilson et. al examined a Ketogenic Diet in resistance training athletes may increase serum testosterone levels from 570ng/dL to 690ng/dL after a 12-week regiment. While robust evidence and well controlled studies may be lacking, considering that steroidogenesis relies upon a healthy intake of fat, the ketogenic may increase testosterone in this manner. Cholesterol Medication Usage (Statins) Cholesterol lowering medication such as Statins appear to reduce the production of testosterone in men. While the degree of such testosterone reduction may be negligible, it is worth mentioning in the following context of this article. A meta-analysis of 11 placebo-controlled randomized trials of statins effect on testosterone levels by School et. al, in 2013, revealed that statins may decrease testosterone production. Statins inhibit cholesterol synthesis and cholesterol is the key component of testosterone. While the impact of statins on the broader health of the individuals may be more relevant, it’s worth understanding how statins can and may lower testosterone for any man desiring to raise their serum testosterone levels. Also, one must consider that any individual on statin medication may already have other underlying comorbidities such as obesity, diabetes and hypertension that can lead to reduced testosterone production as a result of metabolic syndrome. The use of statin medication most certainly would outweigh (no pun intended) the negligible decrease in testosterone production. The Ideal Testosterone Enhancing Diet For any man who desires to enhance serum testosterone naturally without any medication, a multi modal approach consisting of diet, exercise and adequate sleep (greater than 8 hours) should be undertaken. While there is not specific diet, supported through research, that has shown a significant improvement in serum testosterone levels, one may consider a diet with moderate amount of fat (not restrictive) and includes high protein intake. Men who restrict protein intake may impair the hypothalamic pituitary- gonadal axis (HPG), necessary for proper signaling for the production of testosterone in men. In addition, a case-controlled study examining a vegetarian diet on testosterone levels revealed no significant increase in serum testosterone levels. Sources Fantus et.al., The Association between Popular Diets and Serum Testosterone among Men in the United States. Journal of Urology. Vol 203, 398-404, February 2020. Schooling, C.M., Au Yeung, S.L., Freeman, G. et al. The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. BMC Med 11, 57 (2013). https://doi.org/10.1186/1741-7015-11-57

Keywords: Penile Implant, Penile Extension. Penile length and girth Improvement, Cosmetic Penile Implant, Silicone Penile Implant. What is the Penuma ® penile cosmetic implant? The Penuma ® is a new FDA approved silicone cosmetic penile implant used to enhance penile length and girth. What materials is the Penuma ® penile cosmetic implant made of? The Penuma ® cosmetic penile implant to enhance penile length and girth is made of medical grade silicon. The silicon cosmetic implant also contains an inlayed mesh to facilitate the implant’s stability and fixation to the penile tissues to prevent erosion and implant sliding. Are there different sizes of the Penuma ® penile implant for length and girth expansion? The Penuma ® cosmetic penile implant is provided in L, XL, and XXL which corresponds to 14,16, 18cm lengths and 42, 50, and 60gm weights respectively. The thickness of the silicon varies from 1.5-2.5cm and varies depending on the proximal or distal aspect of the implant for more a natural penile contour and reveal. What is the difference between a Cosmetic Penile Implant and a Three-Piece Penile Prosthesis for ED? For men who have erectile dysfunction the three-piece inflatable penile will restore a man’s ability to get an erection on demand without sexual stimulation. Penile sensation and pleasure are maintained. The silicone cosmetic penile implant is for a man who has good erectile function and desires added length and girth to his penile size and appearance. The silicon penile implant does not improve erectile function. How long does it take to insert a cosmetic penile implant for length and girth expansion? While most 3-piece penile implant procedures take approximately 30 minutes to 1 Hour to perform, according to reports the Penuma® cosmetic implant for length and girth expansion takes approximately 45 minutes to insert. How long after the implant before I return to sexual activity? Approximately 6 weeks. What are the risks of the cosmetic penile implant procedure? Like any procedure, the risk of infection, pain and bleeding are always a risk. Relating to the silicon cosmetic penile implant the following risks are appreciated: 1) Implant erosion 2) Implant infection 3) Seroma 4) Hematoma 5) Pain 6) Penile nerve injury 7) Urethral Injury 8) Implant breakage 9) Temporary loss of skin sensation 10) Penile skin ulcer 11) Scar formation Who is the ideal candidate for a cosmetic penile implant to enhance penile length and girth? 1) Circumcised penis (the patient must have been circumcised at least 2 months before the procedure). 2) No prior subcutaneous/sub-dermal penile insertion procedures 3) No active infection in the body. 4) No clinically persistent or recurrent cancer. 5) No exhibition of psychological instability that may affect outcome, which can be screened using validated dysmorphia surveys 6) Sufficient tissue to adequately cover the implant. 7) No systemic disorders that could lead to poor wound healing or soft tissue deterioration over the implant. 8) Willingness by the patient to comply with all postoperative instructions. 9) Non-smoker within 30 days of the elective procedure. 10) Not currently on anticoagulants Is the cosmetic penile implant covered by insurance? At this current time, no insurance carrier is providing coverage for the Penuma ® penile implant. On the other hand, the three-piece inflatable penile implant is covered by several insurance carriers. Who performs the cosmetic penile implant procedure? A Board – Certified Prosthetic Urologist is an expert in penile implant surgery.

If I have been prescribed testosterone replacement therapy should I stop? If I have Low-T, is it safe for me take testosterone replacement therapy (TRT)? What you need to know about Low-T and Cardiovascular Events It is a common question by all men who are considering testosterone replacement therapy: Will testosterone replacement cause me to have a heart attack? Am I at an increased risk of having a heart attack if I get testosterone therapy? To best answer this question lets first consider the history of testosterone therapy and its clinical use in managing patients with cardiovascular conditions. In the early 1930’s testosterone therapy was once considered a treatment for angina pectoris (chest pain) and peripheral vascular diseases. Physicians during this time injected testosterone to improve vascular flow to lower limbs in patients with intermittent claudication and peripheral vascular disease. In the 1940’s a variety of published studies observed testosterone’s ability to vasodilate (expand) small arteries and improve blood flow to areas of the body with diminished blood inflow. In men who presented with chest pain secondary to small vessel blockage or vessel wall spasm, testosterone was given during an acute chest pain attack (heart attack) as a treatment. Studies revealed “marked improvement” in patients’ symptoms and the use of testosterone was able to reduce not only the severity of attacks of chest pain but also the occurrences. It was not until the early 1980’s, that testosterone deficiency (also known as Low-T) was being heralded as a new diagnosis in aging males. Testosterone therapy was becoming more popular as its effects to promote lean muscle mass, improving weight loss, cognition, sex drive, erectile function and improve the quality of life of men were becoming more apparent. The boom of the testosterone marketplace was announced as pharmacological companies began producing a variety testosterone formulations (patches, gels, pellets) to capitalize on this new and expanding marketplace. Given the media’s attention towards testosterone’s abilities and its new expansion in the medical area, so did much of the scrutiny surrounding testosterone replacement, especially that testosterone therapy can cause heart attacks. This culminated in the following FDA label change of testosterone in 2015. FDA Testosterone Package Insert Warning 2015 Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiological studies and randomized controlled studies have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, cardiovascular death with use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patient should be informed of this possible risk when deciding whether to use or to continue to use Androgel 1%. What do the Testosterone studies show? The risk factors for testosterone deficiency (Low-T) and risk factors for heart attacks are the same: obesity, hypertension, dyslipidemia, hyperglycemia, insulin resistance and metabolic syndrome. Many men who are on testosterone also have and share risk factors for cardiovascular disease (CVD) and may already have underlying CVD prior to starting testosterone therapy. There are a number of clinical studies and evidence that supports that low testosterone levels are a risk factor for cardiovascular disease and replacing testosterone can improve cardiac health. The following are statements with the number of supporting testosterone clinical studies: · Low T increases incidence of coronary artery disease (6) · Low T increases mortality (8) · Low T correlates with increased severity of Coronary Artery Disease (4) · TRT decreases obesity (6) · TRT improves cholesterol levels (3) · TRT improves glycemic control 6) · TRT decreases markers of inflammation (8) In the largest testosterone study to date, The Testosterone Trials (T-Trials), the risk of cardiovascular events ( such as a heart attack) is no different between men treated with testosterone or men not treated with testosterone. What do the American Urologic Association Guidelines say about Testosterone Therapy risk and Heart Attack? The American Urologic Association (AUA) identifies and has confirmed the following: 1) Low Testosterone is a risk factor for cardiovascular events. This includes heart attack, strokes and premature death. 2) There is no robust evidence to demonstrate that testosterone replacement therapy increases or decreases cardiovascular events while on testosterone therapy. 3) It is recommended that testosterone replacement therapy (TRT) not be prescribed to a man within 3-6 months of the occurrence of a cardiovascular event. 4) Intramuscular testosterone injection therapy can cause polycythemia. Current evidence does not link testosterone replacement therapy to an increased risk of venothromboembolic events (VTE). 5) Since the FDA testosterone label changes, 4 large observations studies have been published that show no increased risk of VTE with patients on testosterone therapy. AUA 2018 Guidelines · Clinicians should inform testosterone deficient patients that low testosterone is a risk factor for cardiovascular disease · Prior to initiating treatment clinicians should counsel patients that, at this time, it cannot be stated definitively whether testosterone therapy increases or decreases the risk of cardiovascular events. · Testosterone therapy should not be commenced for a period of three to six weeks in patients with a history of cardiovascular events. Endocrine 2018 Guidelines · We recommend against testosterone therapy in men with … heart failure, Myocardial infarction or stroke within at least 6 months (low quality of evidence) · …there is no conclusive evidence that Testosterone supplementation is associated with increased cardiovascular risk in hypogonal men. · Thus, there are insufficient data to establish a causal link between Testosterone therapy and cardiovascular events. As It stands with our current literature and research, there can be no definitive statement if testosterone therapy increases or decreases the risk of a heart attack. However, there is robust data from several clinical trials to state the following: 1) Low Testosterone is a risk factor for cardiovascular events such as a heart attack. 2) Testosterone therapy can improve the risk factors associated with heart attacks and cardiovascular events such as improving glycemic control, obesity and weight loss, cholesterol, reducing metabolic syndrome. 3) No current studies prove that testosterone replacement therapy will cause a heart attack or stroke. If I have been prescribed testosterone replacement therapy should I stop? If you are currently being prescribed testosterone replacement therapy and are under the care of a Urologist, there is no clear indication for you to stop therapy as a result of the current information. If you have an increased risk of heart disease such as a family history of heart disease or have medical conditions such as high blood pressure, high cholesterol or diabetes, discussing with your doctor the benefits of testosterone replacement therapy can be useful to optimize your health and safety. Is testosterone replacement therapy safe? All medical therapies have a risk. When a physician considers starting a patient on any therapy, a physician must ensure the benefits out way the risks. Pertaining to testosterone replacement therapy, testosterone administration is a safe medication if given under the guidance and monitoring of a trained urologic physician. Testosterone replacement risks include a rise in hemoglobin and hematocrit levels, rise in prostate specific antigen, gynecomastia, lower extremity swelling, acne, reduction in sperm production and possible reduction in testicular size. While the following risks are all reversible with cessation of testosterone administration, understanding these risks before undergoing therapy will help optimize therapy outcomes and mitigate risks. Will I get prostate cancer if I take testosterone replacement therapy? No. Testosterone replacement therapy does not increase the risk or cause the development of prostate cancer. While it was thought years ago that that prostate cancer could be caused by giving someone testosterone replacement, several clinical studies have proven this hypothesis to be false. There is no level one evidence that supports shows testosterone replacement causes or increases the risk of prostate cancer. On the contrary, there is supporting evidence that men who have low testosterone and an elevated PSA are at an increased risk of having a higher grade or more aggressive form of prostate cancer. If a man currently has prostate or received prostate cancer and is now cancer free but also has a low testosterone level with associated symptoms, meeting with a urologist discuss the risk and benefits of testosterone replacement therapy would be advised.

Keywords: Stock Market, Testosterone Levels, Financial Gain, Androgens, Testosterone and Financial Decision Making, Money Market and Testosterone, High Testosterone and Financial Risk Taking. Testosterone an androgenic hormone that is well known to affect a man’s ability to concentrate, make decisions and can affect risk taking. There have been several studies that have investigated testosterone levels in stock traders and how testosterone levels affect trading behavior, financial risk taking and financial profits. A study by Coates and Herbet from 2008, investigated testosterone levels in stock traders and how such levels related to financial risk taking, and financial return (profitability). Results of this study revealed male stock traders with higher testosterone levels made greater financial returns (profit) when their testosterone levels were highest compared to when their testosterone levels were lower. They also found that men who had higher testosterone levels were more likely to make riskier stock trades in the financial market. The study recruited 17 male stock traders in the City of London. The hypothesis investigated was whether testosterone levels change significantly throughout the day as traders made or loss money. Measuring the levels of testosterone during those moments when stock traders had financial gains or losses and correlating these moments to hormone levels was of interest to the investigators. The investigators followed 17 male stock traders for 8 consecutive business days and took salivary testosterone tests twice per day at 11 am and 4pm and also during times of trading (especially when traders were making bulk trades). At each time of the trade, male traders would record their profit or loss. While other parameters were held constant the results were able to bare some insight that testosterone levels when highest gleaned riskier trading but also higher profits. One hypothesis to explain such results is that high testosterone levels during times of stress or concentration promotes fearlessness, persistence, performance enhancement and a thirst for risk. Elevated testosterone levels increase dopamine release in the brain, an “androgenic priming” for stimulating risk taking. These findings were expanded upon in studies by Apicella et. al Testosterone and Financial Risk Preferences. In another study by Nadler et. al. The Bull of Wall Street: Experimental Analysis of Testosterone and Asset Trading, investment traders were given testosterone injections and observed how investment trading strategy, performance and mood were affected. Results from the study revealed stock traders who received testosterone replacement therapy were more likely to perceive prices as lower on average, and often felt they were buying stocks too low. Stock traders treated with testosterone were more likely to invest more capital in the market and increase their bid prices. Financial assets in this particular experimental setting were increased in stock traders who received testosterone compared to the control group. It is believed by investigators that testosterone increases risk taking and enhances attempts to capitalize on financial gains, this may be to enhance social status. Testosterone is well known to affect cognition, mental clarity, the decision-making processes and may provoke risk taking that may have positive attributes as revealed in this study.

Keywords: Male Pattern Baldness, Androgenic Alopecia, TRT, Testosterone, Androgens and Hair Loss, Finasteride, Proscar, Dutasteride, Avodart, Propecia, Hair Transplant. Will Testosterone replacement cause male pattern hair loss? The most common regulator of human hair growth in men are androgens, principally testosterone. Androgenic alopecia, also known as male pattern baldness, affects approximately 80% of men. Male pattern baldness is characterized by a recession, thinning and loss of hair primarily from the temporal zones and vertex of the scalp. Men who have androgenic alopecia or male pattern baldness are genetically predisposed to hair loss, principally from the actions of Dihydrotestosterone (DHT). DHT is similar to testosteron, but it is much more potent androgen. DHT acts upon the bulb of the hair follicle to induce hair thinning and eventual hair loss. Unlike hair on the vertex and temporal zones of the scalp, hair located on the side the scalp are resistant to androgens. DHT is an androgen that is derived from the breakdown of testosterone. Testosterone is broken down into DHT by an enzyme called 5-α (alpha)-reductase. For men who are genetically predisposed to have male pattern baldness the use of testosterone replacement therapy may accelerate the hair loss cycle by increasing the amount of circulating DHT. Testosterone replacement therapy may not cause hair loss in men who are not genetically susceptible to androgenic alopecia. Some hairs are resistant to the presence of DHT or testosterone and this explains why some men present with baldness and others do not. From clinical studies men on testosterone replacement therapy (TRT) who are at risk of experiencing androgenic alopecia will present with hair loss most often after the first year of being on TRT. Developing hair loss during the first year of TRT was found to be low, even in males who had preexisting male pattern baldness. Furthermore, studies have shown that the duration of testosterone supplementation may correlate with hair loss, with longer exposures to exogenous testosterone increasing the risk of male pattern baldness. There been no difference in the type testosterone used (gel, injection, pellet) and loss of hair. While men on testosterone replacement therapy may accelerate androgenic alopecia, testosterone use has been shown to increase facial and body hair growth. In men who are on TRT and are showing signs of hair loss, the use of finasteride (Propecia) can slow and mitigate male pattern baldness. How does Finasteride (Propecia, Proscar) prevent hair loss? Finasteride is a 5-Alpha-reductase inhibitor. Finasteride is the generic form of Proscar and Propecia. Finasteride works to prevent hair loss in men who are predisposed to androgenic alopecia by reducing the amount of circulating DHT. Less DHT prevents less hair recession, regression and loss. What is the difference between Finasteride (Proscar, Propecia) and Dutasteride (Avodart)? There are several noticeable and important difference between Finasteride and Dutasteride. Foremost; Finasteride is a competitive inhibitor of the Type -2, 5-Alpha-reductase isoform that is principally found in the prostate and scalp. Dutasteride is a competitive inhibitor of both Type-2, and Type -1, 5-Alpha-reductase (more common in liver and skin) owing to a more complete reduction in DHT levels by approximately 20-24 weeks. The half life of Dutasteride is 35 days compared to the half life of Finasteride of 0.3 days. Dutasteride stays around longer in circulation. Dutasteride reduces prostate size and decrease urinary symptoms more so than Finasteride. The sexual side effect profile of both Dutasteride and Finasteride are the same. Are there sexual side effects of Dutasteride (Avodart) or Finasteride (Proscar, Propecia)? Dutasteride and Finasteride can both have sexual side effects that can impair ejaculatory function and erections. The rate of ED in men who use Finasteride is approximately 5% to 9%. According to the Proscar Long Term Efficacy and Safety (PLESS) study, sexual side effects from Finasteride were reported in 15% of subjects only after 1 year of treatment. In the PLESS Study 5mg Finasteride was used for the treatment of an enlarged prostate (BPH). For men with male pattern baldness or androgenic alopecia the recommended dosage is only 1mg of Finasteride. The sexual side effects for men who take Finasteride for hair loss may be substantially lower than the 5mg dosing of Finasteride man take for an enlarged prostate. In a study called, The Finasteride Male Pattern Hair Loss Study, 1553 men between the ages of 18 and 41 years of age and with male pattern hair loss received either Finasteride 1mg daily or a placebo. The study observed both groups for hair growth (hair counts), hair loss rate, appearance of hair and sexual side effects. Sexual side effects were found to be only 3.8% vs 2.1% in the finasteride treated group compared to the placebo group. Sexual side effects included loss of sex drive, decrease in ejaculatory volume and erectile dysfunction. According the medication package insert for Propecia, men who take finasteride 1mg daily for 48 weeks may experience a decrease in ejaculatory volume of 0.3mL. What is the difference between Proscar and Propecia? Propecia and Proscar are both medications with the active ingredient Finasteride. Propecia and Proscar provide difference dosages of the active ingredient, Finasteride. Propecia is 1mg of Finasteride with an FDA approved use for male pattern baldness. Proscar is 5mg of Finasteride and indicated for use in men with an enlarged prostate and associated lower urinary tract symptoms. Is Dutasteride or Finasteride better to prevent hair loss? In a randomized controlled open label study, Dutasteride was shown to have more efficacy compared to Finasteride towards improving 1) new hair growth 2) decrease thin hair count in men with androgenic alopecia (male pattern baldness). What is the dosage of Finasteride for male pattern baldness? 1mg per day of Finasteride, also known as Propecia, is used to treat male pattern baldness. Can I take Finasteride (Propecia) with or without food? Finasteride (Propecia) for male pattern baldness can be taken with or without food. Food does not affect the absorption of the medication. Most men take Propecia in the AM as part of the morning routine.

Keywords: Subcutaneous injection of Testosterone, Intramuscular Injection of Testosterone, Xyosted ®, Testosterone Enanthate, Painless Testosterone Injection. Since the 1950’s testosterone has been primarily administered by intramuscular injection for men with testosterone deficiency (< 300ng/dL) and symptoms of Low-T. Testosterone replacement formulations have evolved since the 1950's and many androgen formulations are available to choose from to replace testosterone : transdermal patches, topical gels, nasal testosterone, sub-dermal testosterone pellets, oral testosterone. Yet, there has been increasing evidence and support that testosterone can be given by subcutaneous injection, rather than by intramuscular injection. Benefits of subcutaneously injecting testosterone include less discomfort and pain, smaller needle size, and possibly lesser dosages of testosterone needed to sustain steady state levels of serum testosterone. In a pilot study by Al-Futaisi MD et. al., Subcutaneous Administration of Testosterone, 22 male patients with primary and secondary hypogonadism were recruited from a Canadian endocrine clinic and asked to inject 25-50mg of testosterone enanthate using a 0.5 ml insulin syringe. Patients reportedly warmed the testosterone ester by placing the bottle underneath the axilla (arm pit) for 5 min prior, reducing the compounds viscosity and easing the injection application. Patients’ serum testosterone levels were then measured and monitored over a 1-year period from January 2002 to December 2002. Results of the study revealed that serum testosterone peaks and troughs were 100% within the normal range of testosterone. Furthermore, subcutaneous injection of testosterone weekly was able to maintain testosterone levels within the normal reference range. An additional study from Spratt et. al, Subcutaneous Injection of Testosterone Is an Effective and Preferred Alternative to Intramuscular Injection…, published in the Journal of Clinical Endocrinology and Metabolism, 63 patients were provided subcutaneous testosterone injection at an initial dose of 50mg weekly. Results, in short, revealed that the subcutaneous route of injecting testosterone was able to normalize testosterone levels, reduce injection site pain and is well tolerated and preferred by some patients. A new subcutaneous auto injector pre-filled with Testosterone Enanthate (with dosages of 50mg, 75mg and 100mg) called Xyosted ® was recently approved by the FDA in 2018 for testosterone deficiency. This medication type is new step in the direction of subcutaneous testosterone injections becoming more mainstream and as alternative to the commonly advocated intra muscular route. According to studies, subcutaneous use of testosterone enanthate (Xysoted ®) resulted in a steady level of testosterone after 6 weeks of use, with very narrow testosterone fluctuations. According to the manufacturer’s website, patients are started on 75mg of Testosterone Enanthate weekly, and 50% patients of do not need dose adjustments. The most common side effect of Xyosted® includes an elevation in blood pressure most commonly experienced by users during the first 12 weeks of treatment.

Keywords: BodyBuilding Testosterone Dosage, TRT, Low-T, Free Testosterone, Testosterone levels. Anabolic Steroids, Physique Athlete, LabCorp, Quest According the American Urologic Association (AUA) Guidelines, a testosterone value of less than 300ng/dL is recommended as a reasonable cutoff to support the diagnosis and confirmation of low testosterone (Low-T). The AUA guidelines are the most often utilized guidelines for diagnosing and managing Low-T. Other medical guidelines report a recommendation of 250ng/dL or 350nd/dL as a serum testosterone value for the laboratory diagnosis of Low-T. The 300ng/dL value for the diagnosis of Low-T was established by the FDA and used by many insurance companies in order to establish a diagnosis of Low-T and cover testosterone medication. However, some men experience signs and symptoms of Low-T despite their serum testosterone level being within the normal reference range. The normal reference range of testosterone can be between 300ng/dL – 800ng/dL depending on which laboratory and assay utilized. For example the two most popular and largest laboratory testing sites are LabCorp and Quest. The LabCorp testosterone assay has a normal testosterone reference range of 264-916 ng/dL. In comparison the Quest Lab testosterone assay has a normal testosterone reference range of 250-1100ng/dL. While both laboratories are roughly within a similar range, there exists variability. Given the wide range of normal testosterone level values, men can still exhibit signs and symptoms of Low-T despite their testosterone being in the reference rage. If all other causes for symptoms of Low-T have been excluded and a man’s serum testosterone level is within the low normal reference range, a clinical argument can be made for a trial period of testosterone. If symptoms are improved with testosterone replacement therapy, a patient can continue on testosterone replacement therapy (TRT). Cut off values should not be utilized as a hard-fast rule, but rather interpreted in coordination with the patient’s signs and symptoms. Do I have need to have a testosterone value below 300ng/dL in order to get Testosterone replacement therapy (TRT)? No. Not all men respond to testosterone the same. For example, a man who has testosterone level of 500ng/dL may not exhibit signs and symptoms of Low-T, while another man with the same testosterone value of 500ng/dL may have significant signs and symptoms of Low-T. A clinical judgement can be made that a man can still be on testosterone replacement therapy even if their serum testosterone value falls within the normal reference range. How should I use free testosterone during my testosterone therapy management? The AUA guidelines do not provide a recommendation on the utilization of free testosterone in the work up and management of Low-T. Several clinicians and studies have argued and demonstrated, respectively, that free testosterone is a more clinically relevant maker of low testosterone symptoms in a man. While total testosterone is excellent indicator and marker of a man’s androgen status, total testosterone is invariably affected by other parameters such as sex hormone binding globulin concentrations. If man has a total testosterone level that is within the normal reference range, but free testosterone is low ( < 100pg/mL or <1.5ng/dL) , testosterone therapy can still and should be warranted. For more about the utilization of free testosterone in the management of Low-T Visit our following the article: Click Here. What is a common body building regimen and dosage of testosterone replacement therapy? It is estimated approximately 1-3 million men in the United States use testosterone recreationally. In and among bodybuilding athletes the majority of high doses of testosterone and steroid use is guided on anecdotal evidence, word of mouth rather than clinical trials and guidelines. As thus, most regiments among elite athletes is difficult to uncover, yet several investigations and sources have concluded some of the following information. Testosterone is often combined with other anabolic agents and used in cyclic fashion often between 4-12 weeks in duration. After this time most athletes report a plateau effect and increasing unwanted side effects. As thus, intervals of steroid rest, often termed cycling, exists before resuming the anabolic steroid regimen. More experienced bodybuilding athletes often have rest cycles of steroid use between 4-6 weeks before resuming the cycle. More regular and recreational users of have several months of steroid free intervals before resuming anabolic steroids. Resting provides medication to clear from the body, reducing overt side effects and reduce the plateau effect. Testosterone regimens for bodybuilders can range from 500mg to 1000mg IM weekly. Other athletes, use may use a weight-based regiment of 1mg/kg. Combining testosterone with other anabolic steroid agents has been practiced by 88% of men desiring a bodybuilding physique. Stacking is a term often used to describe the addition of multiple medications together to enhance their synergistic properties. Other non-steroidal agents that bodybuilding and other physique athletes may use include Ephedrine, L-Thyroxine, Growth Hormone, Furosemide, Tamoxifen, Anastrozole. What is the goal testosterone level a clinician should try to achieve when administering testosterone replacement therapy to a male patient? According to the AUA guidelines the treatment goal of testosterone replacement therapy is to achieve a serum testosterone level of 450-650ng/dL. If the goal of of therapy is to alleviate symptoms of Low-T, some men may require a higher goal to be reached such as 750-1000ng/dL to achieve the benefits of testosterone replacement therapy. Goals of therapy should be individualized and tailored to the patient’s symptoms rather than to an exact number. While serum testosterone levels greater than 1000ng/dL can raise the risk to benefit ratio, therapy should be guided by symptom relief, reduce unwarranted side effects and safe and monitoring of acceptable laboratory values of Hemoglobin, Hematocrit, Liver Function Tests , and Prostate Specific Antigen among others.

Will Testosterone cause me to get acne? What are some acne treatments I can use while on Testosterone Replacement? Do all men experience acne on Testosterone Replacement ? It is a common question asked by most men are considering testosterone replacement therapy (TRT), “Will testosterone replacement therapy cause acne?”. To answer this question let’s understand how testosterone affects the skin. Testosterone is a sex hormone that has both anabolic and androgenic properties. Anabolic properties of testosterone include improved muscle size, strength and weight loss. Androgenic properties of testosterone include facial hair production, deepening of the voice, and among others an increase in oil production from sebaceous glands in the skin. Within the skin are glands that secrete and oily substance called sebum. Skin glands produce sebum to remove dead skin cells that have accumulated over time for their removal from the surface. When these glands become blocked by an accumulation of both dead skin cells and sebum, acne can result. Androgen receptors are present in skin glands. Testosterone stimulates the androgen receptors in skin glands to produce more sebum. This is often witnessed more prominently in young men going through puberty who have more oily skin they produce more testosterone in their early teen years. The most common sites for acne formation for men on testosterone replacement therapy, are similar to men who go through puberty, on the face and back predominately. It is important to note, that not all men will experience the same skin changes, such as acne formation, when undergoing testosterone replacement therapy. There exists in every man androgen receptor variability, small structural changes in the androgen receptor the predisposes some men to respond to testosterone different. This is called androgen receptor polymorphisms. Some men may experience a more robust response when on TRT compared to others, relating to skin manifestations. This is also a very exciting concept in testosterone replacement and an evolving concept in male hormone replacement. Our understanding how testosterone binds to the androgen receptor differently in various parts of the body can lead to new and more effective testosterone preparations and formulations to enhance outcomes most desired desired my men and reduce unwanted side effects. It is worth mentioning, then men on testosterone replacement often see an enlargement in very specific muscle groups compared to others secondary to the differences in the androgen receptor density in different muscles. For men who are on TRT and who are experiencing an increase oily skin or an increase in acne there are several treatment options available. (please consult with your physician prior to use). 1) Skin Hygiene For men who are on testosterone replacement therapy and are experiencing an increase in skin oil production or acne formation, utilizing a daily facial and body wash to remove excess oil can help. Often recommend are body and facial washes that contain Salicylic Acid and/or Benzyl Peroxide. 2) Salicylic Acid Salicylic Acid is a topical agent that has been used extensively for the treatment of acne and as an exfoliating to gently cleanse the skin. Salicylic acid acts as a “keratolytic" agent by breaking down and softening the bonds between keratin cells in the top most layers of the skin for easy removal. In addition, Salicylic Acid also penetrates deep into the pores to remove dead skin cells that may block skin pores. For men who experience acne while on testosterone secondary to increase sebum production a Salicylic Acid facial and body wash are sold over the counter and can be a great first option to combat acne formation. When choosing a facial wash consider using only 2% Salicylic Acid solution. 3% Salicylic Acid is best for the body and not the face. 3) Benzyl Peroxide Unlike Salicylic Acid, Benzyl Peroxide works by killing bacteria that live underneath skin cells and removes dead skin cells known to cause acne. Benzyl Peroxide has been used since the early 1950’s to treat and manage acne and can be found in concentrations ranging from 2.5% to 10%. Benzyl Peroxide can be found in over the counter body and facial washes. Be careful, as Benzyl Peroxide can cause skin irritation if over used and may also stain clothing. 4) Topical Retinoids Topical retinoids work by slowing the buildup of dead skin cells on the outer layer of dermis. Retinoids are available in a variety of gels, creams and liquids and can also function well for spot treatments for severe acne. Men who use retinoids should be aware that use of a topical retinoid and overt sun exposure can harm and irritate the skin. Skin exposure to sun while using retinoid compound is not advised. Most men often use it before bed to avoid sun exposure.

Testing your Testosterone Levels. What you need to know about Low Free Testosterone levels and Total Testosterone Levels. When should free testosterone be measured? What conditions affect free testosterone levels? Which value is better free or total testosterone? How to increase free testosterone levels. Keywords: #freetestosterone , free testosterone calculator, increasing free testosterone, free T, low free testosterone levels, Free testosterone free testosterone normal levels, low free testosterone treatment When evaluating the symptoms of Low-T, the gold standard is to measure serum total testosterone. This has been supported by several clinical trials and guideline statements of various professional medical associations. Free testosterone, a component of total testosterone, is often not tested but does have clinical utility that will be described in today’s article. Testosterone circulates in the body in both bound and unbound forms. The majority of testosterone in the body is bound to proteins such as albumin and sex hormone binding globulin (SHBG). Unbound forms of testosterone are known as free testosterone. Bioavailable testosterone is the fraction of testosterone that is free and loosely bound to albumin (ready to dissociate and be active/free). It is the free testosterone that is biologically active and available to exert an effect on the androgen receptor. Only 2% of circulating testosterone is free. Total testosterone is calculated as the sum of Free testosterone plus SHBG bound testosterone plus Albumin bound testosterone. See the equation below: Total Testosterone = Free T + SHBG Bound T + Albumin Bound T Free T = T unbound Bioavailable T= FT + Albumin Bound T Normal Testosterone Ranges in the Body Free Testosterone 1-2% Weekly Bound Testosterone to Albumin 50-65% SHBG Tightly Bound Testosterone 30-45% When free testosterone is ordered from a lab, it can be measured through an assay or indirectly calculated. The gold standard for measuring free testosterone is by tedious process called equilibrium dialysis. The limitations of this test are expense, dependence on total testosterone accuracy, temperature control, sample dilution among other factors. This type of lab testing is often only found in research laboratories and often not performed routinely. The best cost-effective assessment of free testosterone levels is a mathematical calculation using both total testosterone level and SHBG. The equation used for calculating free testosterone is the Vermeulen Equation. Free testosterone calculator: Visit http://www.issam.ch/freetesto.htm and place your information within the fields to calculate your free testosterone levels. An easy way to calculate your free testosterone is multiply your total testosterone by .1-.3%. This can give a good estimate of your free T level. What can I do to boost my free testosterone levels? Free testosterone is affected by, Total testosterone, albumin and SHBG concentrations as seen in the above formulas. Boosting your total testosterone levels will improve your free testosterone levels. Conditions that can alter SHBG and albumin levels and ultimately affect free testosterone levels are the following: Conditions that increase SHBG Aging Thyrotoxicosis Acromegaly Smoking Cirrhosis of the Liver Anticonvulsants HIV Rosiglitazone Conditions that decreased SHBG Insulin resistance Obesity (may also be increased because of low-T and increase estrogen) Metabolic Syndrome Type 2 Diabetes Atorvastatin Hypothyroidism Glucocorticoids Anabolic Steroids Low albumin states (Nephrotic Syndrome) The clinical utility of ordering a free testosterone level can be during conditions where testosterone levels are normal yet patients are symptomatic. When SHBG are abnormal, accurate identification of free testosterone levels are required. Two large studies looked at free testosterone levels in men with low testosterone levels. The Veterans Administration analyzed data from 3700 men with hypogonadism. Researchers found that men with symptoms of hypogonadism 15% of men had low free testosterone levels of less than 24pg/mL. The EMAS Study (European Male Aging Study) was a multi-center study of more than 3,000 men who were given questionnaires related to the diagnoses of androgen deficiency. The authors concluded that men with findings of erectile dysfunction, decreased sexual thoughts and weak morning erections with total testosterone levels less than 230-317ng/dl and free testosterone level < 7ng/ml ( 20pmol/L) correlated best with syndromic late onset hypogonadism. Free Testosterone Levels Associated with the following symptoms. Free T 46 : Decreased frequency of morning erections Free T 81 : Decreased frequency of sexual thoughts Free T 81 : Erectile dysfunction Free testosterone levels can be used to utilized to understand a man’s symptoms if testosterone levels are normal and the above noted medical conditions are present. In these cases, symptoms may better correlate with free testosterone and not total testosterone. If free testosterone is low, some practitioners may consider total testosterone irrelevant, given it’s the free testosterone that enters the cell to exert an effect. In the absence of symptoms of androgen deficiency, conditions that merit measurement of total testosterone and free testosterone levels are the following: Anemia Bone density loss Diabetes Exposure to chemotherapy Exposure to testicular radiation HIV/AIDS Chronic narcotic use Male infertility Pituitary Dysfunction Chronic corticosteroid Use