Andropause & The Mid-Life Crisis (3)

Testosterone Replacement Therapy

On this page - the mechanism of testosterone, how your penis becomes erect, why you may lose your erections, and how your penis can be restored to full sexual health.

Many men with andropausal symptoms, especially impotence, could be helped by testosterone supplementation. Unfortunately, many doctors think testosterone doesn't restore sexual function because they don't understand the role of SHBG and estradiol in male physiology. So if you want to try testosterone supplementation, you may have a hard time persuading your doctor to prescribe it.

I know of men who have felt terrible, tired and depressed, and whose libido has disappeared, who've managed to persuade their doctors to test for testosterone, and had their concerns dismissed when the tests showed low levels that are "in the normal range".

Apart from the tragedy of this, and the despair that men in this position are liable to feel, what strikes me is the arrogance of so many doctors who do not hear what their patients are saying to them. Faced with the evidence of a patient complaining that the whole basis of his existence and sense of maleness has changed on the one hand, and on the other the results of tests to which they apply "normal" reference levels of testosterone, the doctors ignore the patient and go with the scientific evidence.

At least, they do if they are untrained in, and insensitive to, male issues. The key is to find someone who knows what he is doing. You can make a start on this by reading the books recommended below, and then searching the web on key words such as "andropause", "testosterone", "male menopause", "hormone replacement", and "impotence".

The other factor to keep in mind is that the range of testosterone that makes a man function effectively can be very different between individuals. A normal reference range might be considered to be

Testosterone: 13 - 40 nmol/l     or     370 - 1100 ng/dl

Estradiol:        55 -165 pmol/l      or    10 - 30 ng/dl

These numbers represent such a wide range of "normality" that assessing a man's hormonal state on his absolute blood hormone levels is not an approach which will necessarily lead to the correct solutions for his problems. In other words, the doctor must exercise judgment about what is right for each patient. 

And not all impotence does stem from low hormone levels, a fact about which there is more information below.

The issue of replacement therapy for men with low levels of testosterone is very complicated. You need the help of an expert. There are many ways of providing testosterone: injections, creams, pellet implants, oral preparations, and, most recently developed, gel and patches to put on the skin.

The prescribing of oral testosterone has been controversial in the past, and has perhaps even done this field of medicine some harm. However, modern oral preparations of testosterone esters are quite safe and have no effect on the liver. 

There are two main oral compounds: the first is testosterone undecanoate, the second is a milder androgen called mesterolone. These are marketed under various brand names - Restandol and Andriol (for the undecanoate), and Proviron (for the mesterolone). 

As a mild treatment, these may be the first prescriptions that a testosterone deficient male receives. How effective are they? The general consensus seems to be "variable". The reason lies in the rapid processing of the hormones by the liver. Testosterone undecanoate relies on absorption into the body via the fatty products of digestion passing into the lymphatic system.

If you take it, you can certainly feel it kick in, with sexy thoughts and often an erection, but you can also feel its effects disappear after a few hours. It is metabolized out of the system quite quickly. This means that repeated doses through the day may be necessary, which is potentially inconvenient, besides being expensive and in some cases upsetting to the stomach because of the oil in which the testosterone is dispersed.

The next step in treatment might be the classic route of injections of  long-acting (i.e. one, two or three weeks) testosterone esters in an oil-based carrier  into the muscles of the buttock. There are various preparations available, which last for different lengths of time.

They all work on the same principle - they are metabolized to testosterone at the site of injection. The problem commonly reported with these preparations is that each injection gives a supra-normal level of testosterone, which has an immediately positive effect on the patient's energy, drive, mood, and libido, but as time elapses, the levels of hormone in the man's system may drop below the "normal" range, thereby giving him a few days of irritability, mood swings, and low libido before the next injection. This can be a major problem for men on this regime.

However, the treatment does have some advantages as well: it is cheap, easy to administer (in fact it can be administered by the patient) and it is effective. One man on a regime using an injectable preparation made of a mixture of different  testosterone esters told me that he was very happy with his situation - he was sexier and fitter at 56 than he had been at 18, and boasted of being able to have sex as many times a week as he wanted.

Other men have reported that they have been able to overcome the mood and libido swings by self-injecting smaller doses on a more regular basis, that is to say, splitting the prescription into smaller units and injecting, say, weekly, instead of every two weeks.

The evidence seems to suggest that with some experimentation, and a helpful doctor, treatment can work quite well.

I think testosterone replacement is rarely a perfect remedy for the problems it seeks to cure, for the complexity of the human hormonal system is profound. For one thing, testosterone delivered at a constant level through a hormone replacement regime will switch off the production of testicle stimulating hormones like LH and FSH (which come from the pituitary). 

The consequence of this is that you may stop producing sperm (although this is a fully reversible effect!) and your testes may shrink somewhat.

One man said that of all the changes that the failure of his hormonal system and the therapy he was now on had produced, the hardest for him to deal with was the shrinkage of his testicles.

There are some new preparations under development - testosterone cyclodextrin and testosterone buciclate being two of them. These are longer acting esters of testosterone.

There was also an investigation into injectable microspheres of pure testosterone, although this work did not progress very far. The objective of any treatment is to produce hormone replacement that approximates as nearly as possible to a steady-state regime with no resultant mood swings and changes in libido.

These new compounds also hold out the prospect of longer intervals between injections, which will certainly increase the acceptability of these treatment methods for the patient. 

Subdermal implants of pure crystallized testosterone have used by some doctors.

Update - these pellets are no longer available. (December 2018)

The benefits are: convenience, long intervals between treatments (up to six months), effective replacement with consistent levels of hormone, and restoration of normal mood, libido, levels of energy and motivation. Of course, the question arises as to why this method has not found greater favor if it is so good. 

The pellets come in two sizes, 100mg and 200mg sizes. Between four and ten of them are implanted, under local anesthetic in the doctor's office, through a small incision in one of various sites such as the subdermal fatty tissue just above the buttocks. The wound heals quickly and is accompanied only by minor temporary discomfort.

The testosterone leaches from the pellets into the intercellular fluid. The pellets are designed in such a way that the rate of hormonal release, after an initial surge which lasts only for a day or so, is constant throughout the life of the pellets. A 200mg pellet releases about 1.3 mg of testosterone per day, compared to the average production in a healthy young man's testes of 6 - 7 mg per day, which implies that about 6 pellets would produce a physiological dose, although individual variability could mean more were required.

The pellets have few side-effects and are generally well-tolerated. Sometimes one or more of the pellets will track back along the insertion line, and pop out, but this is quite rare. This is a convenient method for those who find regular injections inconvenient.

However, there are problems. First, there is the limited availability of this approach. And it isn't especially cheap, although the exact cost depends on local health care systems. If you are paying for it yourself, it is cheaper than oral medication, and about the same as injectable testosterone.

Second, I actually had this testosterone treatment myself for a while, and the biggest problem I had with it was the rather brutal nature of the operation needed to implant the pellets. It is quite traumatic to the tissues, and you might prefer testosterone injections. These work quite well if you can establish how long between injections suits you.

One of the more recent developments in the field of replacement therapy for men has been the development of the patch. The book Testosterone (see below) offers some suggestions as to whether or not they are helpful. The patches come in two sizes, and deliver either 2.5 or 5 mg of testosterone per 24 hours.

 In the book, the authors reviewing this treatment method state that the patches are effective in raising testosterone levels to a normal range, on a fairly consistent basis (60 % in the first 12 hours, 40% in the second 12 hours). They do observe that according to when the patches are freshly applied, it is possible to mimic the normal daily rhythm of testosterone production in the male body, which is at its highest in the morning. 

The patches were clearly superior in keeping estradiol levels within the normal range when compared to injectable preparations (pg 401), which for men who have a sensitivity to estradiol, or a high rate of conversion, could be an important factor in the effectiveness  of their treatment.

The authors observe that transdermal patches are as effective as injected testosterone (and pellets) in restoring erectile function, and observe that "these studies are in agreement with other studies showing that androgen therapy improves erectile function." (p 405). However, when I tried these conventions patches, they left sore and inflamed places on my skin.

There is, as Dr Carruthers has pointed out, now a new preparation, which is applied to the skin of the scrotum, skin which is much more permeable to testosterone than other skin, and this has been a great success!

Finally, there is a slightly different route to testosterone replacement, which is for a man to take human gonadotropin - the hormone that stimulates the testicles to produce testosterone and sperm. By taking this, a man can achieve higher production of his own testosterone and a much more normal routine of sexual arousal and penile erections.

Whatever the way it is delivered, androgen therapy restores sexual function and libido and eliminates hot flushes, impotence and depression. The final choice of treatment may actually be based on what is available in your area as well as the doctor's view.

Viagra, impotence, and hormone replacement therapy

Viagra can be very useful for men with penile problems like erectile difficulties. It doesn't increase your sex drive - you have to have a pre-existing libido - but it can certainly help many men to maintain a firm erection. A combination of Viagra and testosterone therapy is often used by the doctors who specialize in male sexual dysfunction.

The prostate and hormone replacement therapy

As men age, the prostate tends to enlarge, causing a variety of "gentlemen's problems", chief among which is difficulty in urinating or the need to urinate frequently. Whether the prostate is growing benignly or malignantly, a test for prostate specific antigen in the blood - the PSA test - can reveal much about the health of this organ. A digital examination through the anus by a doctor can be helpful too, of course, although it's less likely to be attractive to the patient. (Fortunately there is now an ultrasonic scan which doesn't need the anal probe.) Some doctors have suggested that high testosterone is a factor in the development of prostate cancer.

In his book, Eugene Shippen refers to several studies which demonstrated absolutely no link between testosterone levels and the development of prostates cancer or raised PSA levels. More interestingly, he points out that there was a striking correlation between the levels of estrogen in a man's blood and the chances of  him developing prostate disease. In an interesting reversal of the normal perspective, Shippen puts a convincing case forward that testosterone therapy actually inhibits prostate disease. And apart from the case that he argues in his book, he also points out that the experience of doctors administering hormone replacement therapy is highly suggestive - prostate disease is rare among patients who are on hormone replacement therapy. It's a powerful argument, and although not proven, it seems clear to me that testosterone does not encourage the development of prostate disease - if anything, it inhibits it. 

Impotence, one reason why it can happen, and how hormones may help    

As many as 3% of men at age forty may be impotent. This is a shocking figure and it does not get any better as men get older. By age seventy, 40+ % of men are impotent. Why is this? To understand one possible cause, we need to look at the mechanism of erection.

Dr Eugene Shippen describes this in great detail. To sum up what he says: two muscles extend forward from the bones on which we sit, to support and anchor the base of the penis.

The fibers of one of these muscles, called the ischio cavernosa, surround the main chambers of the penis, the corpora cavernosa, at their base, and are mainly responsible for allowing arterial dilation and promoting venous constriction during an erection so that blood cannot escape.

There is in fact up to eight times more blood in an erect penis than a flaccid one. Another muscle of the penis is called the bulbo cavernosa;  it causes the expansion in the chamber at the head of the penis.

It also allows a man to "twitch" his penis upwards, and is responsible for the force of ejaculation and the pleasurable sensations that go with it. All of the muscles - and even the nerve fibers - in the genital region have many more testosterone receptors than those in other parts of the body. This is no coincidence. 

As Shippen emphasizes, it is testosterone that maintains the conditioning of the vital muscles of the genital region. Without hormonal input, the muscles gradually wither and sustained fullness of erection becomes impossible. Even more catastrophically, a decrease in the tension of the ischio cavernosa prevents blood from being maintained in the chambers of the penis, with results as "deflating to the ego as a flat tire in the Indianapolis 500".

Shippen says hormonal solutions to erectile dysfunction will work in a majority of cases, although he does admit that not every man gets erectile function back after hormone administration.

He points out that many things can damage the circulatory system of the penis: drinking, smoking, fatty deposits in the arteries, and the actions of certain drugs can all destroy the workings of the arteries and veins of the penis. Indeed, one of the tests of correct functioning is a blood pressure test.

If the pressure in the man's penis is not the same as in his arm, there may have been some permanent degeneration of the vascular system in the penis that means he can't be restored to sexual function.

And Shippen also points out that estrogen, or more correctly estradiol, can be as much of an enemy on the testosterone receptors of the genital region as it is elsewhere on a man's body. He also emphasizes that restoration of sexual function may take a while as the muscles and nerves regenerate to a fully effective state. Indeed, he says that it may take as long as a year, but he maintains that the majority of his patients are restored to sexual function. 

You may have heard of the Kegel exercises that women are encouraged to undergo when they experience weakness of the muscles of the sphincters of the bladder or anus. Men have these muscles too - known as the levator ani muscles - and with regular Kegel exercises, men can achieve an improvement in sexual function. The object of Kegels is to strengthen all of the elements of the sexual system, not just the penis, so they work at full effectiveness and provide maximum sexual pleasure and sensation.

If you are interested in hormone replacement therapy, begin by reading up on the subject (see the books below). You might then want to look at the Gold Cross Medical Services site, to judge for yourself whether you are a likely candidate.


The books - highly recommended

Male Menopause, Jed Diamond, pub by Sourcebooks, Inc, Naperville, 1997. Essential  reading for anyone facing andropausal challenges.

Maximizing Manhood, Dr Malcolm Carruthers, published by Harper Collins, London (1997) Malcolm Carruthers' book is the definitive statement about the andropause based on his experience of treating thousands of men experiencing these problems. It is a must-read if you are over 40. Clear and concise, but not written in technical language, it will help you understand what is happening to you and what you CAN do about it. You'll breath a sigh of relief when you read his accounts of other men's andropause experience ("I'm not alone in this!" - and you're not, of course).

The Testosterone Syndrome, Eugene Shippen, published by M Evans & Co, New York (1998) Another great book on the subject: clear, concise, very well-written, accessible to all men. Dr Eugene Shippen is an expert, like Dr Carruthers, and he has the answers to so many men's questions about failing sexual performance and  ageing. His burning passion to save men from the sense that they are demasculinized by their failing sexual ability is very clear too.

Buy either of the next two books if you're a medical expert, scientist, doctor or informed layman. They are the definitive textbooks on the pharmacology of the male hormonal system and andrology. More information than you ever dreamed of.


E. Nieschlag (Editor), H. Behre (Editor)

Testosterone: Action, Deficiency, Substitution, edited by E Nieschlag  H M Behre, published by Springer, 1998 

Other pages on the andropause

Andropause 1
Andropause 2 / midlife crisis
Andropause 3 / testosterone
Andropause 4 / testosterone
Testosterone therapy
Self help for the andropause

Other pages on this site - home page
Masturbation and the penis
Male arousal and desire
Andropause: low testosterone
Orgasm and ejaculation
Male initiation: rites of passage
All about semen
The testicles and scrotum
Mature masculinity
How to have better sex
Condoms & contraception
Penile and genital piercing