When Testosterone Replacement Doesn’t Lead to Better Erections

Excerpt from the book: Testosterone: A Man's Guide

Most men find that their sexual desire increases after they start testosterone replacement. Sexual dreams and nighttime/morning erections may be more easily achievable, but in some cases testosterone alone does not make erections strong or lasting enough for successful intercourse.  So, some men need some extra help to make sure that their improved sex drive matches an improved and hard erection.

Before we start covering other options for improving erections, let’s talk about steps you should take before you start combination therapy of testosterone plus other options. If erectile dysfunction or sex drive is not improved while on testosterone, ask your doctor about adjusting your dose of testosterone. Ensure that your total testosterone level is between 500 and 1000 ng/dL. Also, have your doctor check your blood levels of estradiol and prolactin. High estradiol blood levels caused by conversion of testosterone into this female hormone by the aromatase enzyme may cause sexual dysfunction (this can be treated with low dose anastrazole). So is high prolactin's effect on erectile function. Low levels of thyroid hormone, infections, lack of sleep, alcohol, smoking, medications and depression also can cause erectile dysfunction in the presence of normal testosterone levels. Blood pressure medications are known to be one of the main causes of erectile dysfunction, so discuss the different type of medications to keep your blood pressure in normal ranges (high blood pressure is also a risk factor for erectile dysfunction). Last but not least, lack of attraction for our sexual partner can get in the way of achieving a strong erection. 

If high estradiol of over 30 pg/dl is found (by ultrasensitive testing), then anastrozole at 1mg three times a week may be enough to bring it down to healthy levels. Remember that estradiol is important for men to keep healthy skin, hair, and brain function.  High prolactin can be treated with cabergoline.

HCG- As mentioned before, human chorionic gonadotropin (HCG) mimics LH and stimulates the Leydig cells of the testicles to produce testosterone. HCG has been successfully used alone or in combination with testosterone replacement to normalize testicular size after long term anabolic steroid or testosterone use.  It has also anecdotally helped men whose sexual drive does not improve on testosterone replacement alone.

No published studies have been done on this benefit, however.  Doses of 250-500 IU twice a week while on testosterone replacement are being prescribed by several physicians who report that their patients perceive improvements in sexual desire and erectile function on this regimen. We do not know if this effect lasts after long term HCG use or if it is better to cycle it on and off.

PD-5 Inhibitors- For many older men the use of prescription phosphodiesterase type 5 inhibitor (PD-5) medications like Viagra, Cialis, and Levitra—may be needed in combination with testosterone replacement. However, some men do not respond well to these oral agents or have side effects such as headaches, nasal congestion, flushing, gut problems, and, in the case of Cialis, back pain. Cialis may last longer than the others (36 hours compared to 4 hours for Viagra or Levitra), but so may its side effects. Some men take Claritin and ibuprofen with these drugs to pre-treat nasal congestion and headaches, respectively.

Sildenafil (Viagra) was the first PDE5 inhibitor to enter on the market in 1998. The usual dose of sildenafil is 50 mg (25 to 100 mg) taken one hour before sex. The effects of sildenafil last for approximately four hours, and patients should be instructed to use no more than one dose within 24 hours. Fatty meals reduce the absorption of sildenafil; therefore, the drug should be taken on an empty stomach. This may be an inconvenient factor that needs careful planning of which some patients are not aware.

Vardenafil (Levitra), the first second-generation PDE5 inhibitor to be developed, is given at a usual dose of 10 mg (2.5 to 20 mg) one hour before sex. Older men and those with moderate liver dysfunction should receive a lower initial dose of 5 mg. Vardenafil begins working within 30 to 45 minutes after administration and lasts for about four hours. As with sildenafil, patients taking vardenafil should not use more than one dose within a 24-hour period. Patients should not take vardenafil within three hours of fatty meals, due to a reduction in absorption.

The newest PDE5 inhibitor is tadalafil (Cialis), which has a longer duration of action--approximately 36 hours--than sildenafil or vardenafil. In addition, the usual dose of 10 mg (5 to 20 mg) should be taken about 30 minutes before sexual activity. This shorter onset time can possibly allow patients more opportunity for spontaneity. Food intake does not appear to affect the absorption of tadalafil; this makes it very practical for men who do not plan ahead when they have sex. Cialis is approved for low dose daily use, but most insurance companies will not pay for it. If you want to try a 5 or 10 mg dose daily, you can get a free 30 day supply after getting a doctor’s prescription and taking the following voucher to your pharmacy after downloading it and printing it (you have to answer some questions online first). You are better off asking your doctor for a prescription for 10 mg per day and cut the pills in half for the first week to see if 5 mg per day works well enough for you. If not, you can go up in dose. Here is the web site address to download the voucher:

Free One Month Supply Voucher

Though considered generally safe for most patients, including those taking multiple antihypertensives, PDE5 inhibitors are not a viable treatment option for every man with ED.   They need to be used with careful monitoring in patients with a cardiovascular history that includes heart attacks or stroke (within the past two weeks) and hypotension (blood pressure <90/50 mmHg),

Because PDE5 is inhibited in penile tissue as well as extra genital tissue, patients treated with PDE5 inhibitors may experience headache, facial flushing, nasal congestion, dyspepsia, and dizziness. Sildenafil also inhibits PDE type 6 in the retina. Therefore, patients treated with sildenafil may experience sensitivity to light, blurred vision, and loss of blue-green color discrimination, all of which are generally considered reversible. Tadalafil also inhibits PDE type 11 in skeletal tissue, possibly leading to back and muscle pain.

ED drugs are available by prescription but I have heard that some men are ordering them without a prescription from overseas websites to save money (overseas sources can be ten times cheaper than products in the United States). This book does not endorse the use of these drugs without a prescription, but it is my duty to mention facts about what is happening out in the real world. For a review of online sites that sell erectile dysfunction drugs, visit:

Review Online Pharmacies

The following table shows how long each commercially available PD-5 drug starts working and how long they stay in your body. This numbers vary depending on the amount of food or alcohol you ingest before taking them, your body weight, and your liver metabolism.

 If you are older than age 65, or have serious liver or kidney problems, your doctor may start you at the lowest dose (25 mg) of Viagra or any of the other two drugs.

Tell your doctor about all the medicines you take. ED drugs and other medicines may affect each other.  Especially tell your doctor if you take any of these:

•    Medicines  called  alpha-blockers.  These  include  Hytrin® (terazosin HCl), Flomax® (tamsulosin HCl), Cardura® (doxazosin mesylate), Minipress® (prazosin HCl), Uroxatral® (alfuzosin HCl), or Rapaflo® (silodosin). Alpha-blockers are sometimes prescribed for prostate problems or high blood pressure. In some patients the use of PDE5 inhibitor drugs with alpha-blockers can lower blood pressure significantly, leading to fainting. You should contact the prescribing physician if alpha-blockers or other drugs that lower blood pressure are prescribed by another healthcare provider

•    HIV  protease  inhibitors  including  Ritonavir  (Norvir®)  or indinavir sulfate (Crixivan®), saquinavir    (Fortavase® or Invirase®) or atazanavir (Reyataz®)

•    Antifungals  like ketoconazole  or   itraconazole  (such   as Nizoral® or Sporanox®)

•    Antibiotics like erythromycin or clarithromycin

•    Tell your doctor if you take medicines that treat abnormal heartbeat. These include quinidine, procainamide, amiodarone, and sotalol. Patients taking these drugs should not use ED drugs.

If you are taking HIV protease inhibitors your doctor may recommend the lowest dose of each ED drug to start with and work your way up if the starting dose does not provide the desire benefits. Norvir, part of HIV protease inhibitor regimens, can boost blood levels of Ed drugs by slowing down the liver’s clearance of those drugs, so lower doses are needed to achieve the desired effect with the fewest side effects.

In rare instances, men taking PDE5 inhibitors have reported a sudden decrease or loss of vision. It is not possible to determine whether these events are related directly to these medicines or to other factors. If you experience sudden decrease or loss of vision, stop taking PDE5 inhibitors and call a doctor right away.

Sudden decrease or loss of hearing has been rarely reported in people taking PDE5 inhibitors. It is not possible to determine whether these events are related directly to the PDE5 inhibitors or to other factors. If you experience sudden decrease or loss of hearing, stop taking the oral ED drug and contact a doctor right away.

If you have prostate problems or high blood pressure for which you take medicines called alpha blockers, your doctor may start you on a lower dose of ED drugs.

People who use recreational drugs called “poppers” like amyl nitrite and butyl nitrite should be careful while using ED drugs since a sudden decrease in blood pressure can occur.

Other options for men who need an extra erectile boost while using testosterone replacement:

Yohimbine—Available over-the-counter or by prescription (Yocon); increases sex organ sensitivity. It can raise blood pressure and cause insomnia and anxiety, so talk to your doctor. A small study showed that men who used yohimbine with the amino acid arginine had better erections (read section on supplements in this book)

Muse (alprostadil)—this is a prescription pellet that inserts into the urethra to produce an erection. Not very popular since some men do not respond well or are afraid to hurt themselves if they do not stick the pellet applicator carefully through the external urethral orifice of the penis head. You can ask your urologist for a sample with a training video that comes with it to see if this option is for you.

Trimix or Quadmix—Available by prescription from compounding pharmacies. These are mixtures of prostaglandins and papaverine that increase blood flow and retention into the penis. Prostaglandins are mediators and have a variety of strong physiological effects, such as regulating the contraction and relaxation of smooth muscle tissue. Prostaglandins are not hormones and they are not produced at one discrete site, but rather in many places throughout the human body. 

Trimix is a mixture of two prostaglandins (phentolamine and alprostadil) plus papaverine (a vasodilator medication) that increase blood flow to the penis and cause strong and lasting erections, with or without sexual stimulation. These compounds appear to act together to increase arterial inflow, dilate smooth muscles, and restrict venous outflow promoting erectile rigidity with greater success and in smaller doses than if these compounds were used as single therapies.

An example of a dosage combination for tri-mix is 10 micrograms of alprostadil, 500 micrograms of phentolamine and 15 mg of papaverine. Dosing of tri-mix preparations has not been standardized.

Trimix is injected directly into the side of the penis through a fine- gauge “insulin-style” needle in very small amounts (0.1-0.5 cc) that increase blood flow to the penis. It results in strong and lasting erections. The main potential side effect are hematomas (bruising), fibrosis if used too frequently and on the same injection site, pain, and    dangerously long-lasting erections (priaprism). Priaprism may sound great but this can literally kill your penis by causing gangrene of the tissue after stagnant blood coagulates inside it.  I know men who had to go to an emergency room 8 hours after having used too much Trimix and have the blood drained from their penis.  To ensure perfect injection technique and dosing, it is imperative to be trained on how to dose this with the help of an urologist.

Compounding pharmacies sell two types of Trimix formulations: Freeze dried (powder to be mixed later with water) or pre-mixed vials. Some men find the freeze dried form not to be as effective.

It is extremely important to remember never to use Viagra, Cialis, or Levitra before or at the same time as you use Trimix. This is a dangerous combination that can increase the risk of priaprism. Be particularly careful with Cialis since it can stay in your blood stream for a longer time. I know someone who had priaprism since he had forgotten he had taken Cialis two days before using Trimix.

Most men who use Trimix love it, even if they have had to learn the hard way about priaprism during one instance. Most of these men did not respond well nor had too many side effects to oral agents like Viagra or Cialis.

For instructions on how to inject Trimix, read:

            Instructions and general information about Trimix

For instructions for physicians on how to treat priaprism in the unfortunate case that it happens:

              Priapism in Emergency Care

A 10 cc bottle of Trimix can cost from $70 to $100 in compounding pharmacies. If a dose of 0.15 cc is needed per erection, this bottle can be good for 67 erections. In comparison with Cialis and Viagra ($16 a pill), this option seems economical. APSMeds.com has good prices, quality control and customer service, and can ship to your home.  

You will need a prescription written as : TRIMIX  (10 micrograms of alprostadil, 500 micrograms of phentolamine and 15 mg of papaverine)  , 5 mls, as directed. Make sure you ask for insulin syringes (30 gauge, 1 inch needles), and alcohol swabs with your order. 

Caverject— This is an injectable form of alprostadil. Injections of alprostadil have been reported to cause pain, bleeding, hematomas and scar tissue leading to Peyronie’s Disease (excessive curvature of the penis) in some patients.  Caverjet is available by prescription and it is not a compounded product, so some doctors who are not comfortable prescribing compounded products feel more at ease prescribing it. However, it is not as effective as Trimix, it requires a large injection volume, and it comes preloaded in syringes with thick needles.  It is also

10 times more expensive than Trimix but several insurance companies pay for it (Trimix is rarely covered by insurance). This injection into the penis that produces an erection that can last 1 to 2 hours.  Follow instructions from your urologist since overdosing can also cause priaprism.

For the best treatment algorithm for physicians who want to learn more about how to prescribe, dose and manage injectable ED drugs like Trimix, Caverjet and other formulations, this article is probably the most comprehensive. It was written by Jeffrey A. Albaugh, who is an Advanced Practice Urology Clinical Nurse Specialist at Northwestern Memorial Wellness Institute in Chicago (source:Urol Nurs. 2006;26(6):449-453. © 2006 Society of Urologic Nurses and Associates ) :

Penile restriction rings—these rubber or leather restricting bands (commonly known as “cock rings”) can be very effective at maintaining erections after the penis fills up with blood. Be careful not to use it too tight. Neoprene and leather rings are the most common.  They can be found online.

Other options are penile vacuum devices and penile implants. Due to the scope of this book, these two options will not be reviewed. Plenty of information can be found by Googling those terms.

For information on penile implants, visit: http://www.urologicalcare.com/advanced-ed-treatments/types-penile-implants/

It is estimated that some degree of ED affects half of all men over the age of 40 and that 150 million men worldwide suffer from ED. Up to 35% of men with ED are non-responsive to standard therapies with phosphodiesterase-5 inhibitors, representing an estimated market of $500 to $600 million per year. So, there is a huge interest from pharmaceutical companies to keep researching new drugs in this field.

Out of many that are being tested, there are about 4 new erectile dysfunction medications that have made it through several clinical trials and many of them are in the final stages of being approved.   The ED market is an extremely competitive field. Viagra will lose its patent in the near future and generic versions will become widely available. Whether this will mean that Viagra will be cheaper in the United States then is yet to be seen.  Many drugs have become generic and yet their prices do not drop when that happens.

Medications that could cause decreased sex drive or erectile dysfunction:

One reason that testosterone may not lead to better erections and sex drive is the use of medications that may interfere with those two benefits.

 A great review of all studies of drugs that affect sexual function in men was provided by Dr. Walter K.H. Krause in his book “Drugs Compromising Male Sexual Health”. He was able to identify evidence from different studies (many uncontrolled and small) about the common classes of prescription medications that can cause erectile dysfunction. It is not known if testosterone replacement can counteract the effects of these medication classes. Among the medications are:

•    Antidepressants: Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, monoamine oxidase inhibitors 

•    Blood     pressure     medications     (antihypertensives):    Alpha andregenergic antagonists, beta-blockers, diuretics, guanethidine, methyldopa

•    Narcotics and opiates

•    Barbiturates and benzodiazepines

•    Hormone related products: Anabolic steroids, antiandrogens used in prostate cancer, estrogens, medroxyprogesterone, 5-alpha- reductase inhibitors (Proscar, Propecia)

•    Anti-acids: Histamine 2 receptor antagonists (Tagamet), proton pump inhibitors (Prilosec)

•    Cholesterol –lowering agents: Bile acid sequestrants, fenofibrates

(Tricor, etc), statins (Lipitor, etc)

For more information, read Testosterone: A Man's Guide