The Pituitary gland and its effect on male hormones

Your pituitary gland is about the size of a pea (6 x 9 mm) and is situated in a bony hollow in the base of the skull immediately below the brain and just behind the bridge of your nose. The pituitary is an important gland and is often referred to as the 'master gland' because it controls several other organs that produce hormones. Hormones are chemicals that the body uses to convey messages to other organs. Where an organ's main function is to produce hormones it is called a gland. The pituitary gland is controlled by a region of the brain called the Hypothalamus. The hypothalamus produces a number of hormones by which it regulates hormone release from the pituitary gland. One of the hormones released by the hypothalamus is called gonadotrophin-releasing hormone (GnRH). GnRH controls the release of two hormones from the pituitary gland known as the Gonadotrophins. These are Luteinising hormone (LH) and Follicle-stimulating hormone (FSH).

The functions of the testes are controlled by the gonadotrophins which travel via the bloodstream to the testes (see diagram). LH acts on specialised cells within the testes and stimulates release of the male sex hormone, Testosterone. FSH acts on a separate population of cells within the testes to stimulate the production of sperm. During puberty testosterone is essential for growth, increasing muscle bulk, development of the penis and for male pattern hair growth. In adult life it is important in maintaining the strength of your muscles and bones, improves general well-being and energy levels and is intricately involved in both your normal sex drive (libido) and erections. Lack of the male sex hormone, testosterone, is termed Hypogonadism.

The action of GnRH from the hypothalamus on the pituitary,
and the subsequent action of LH and FSH from the pituitary
on the testes to stimulate testosterone and sperm production.

What are the effects of lack of male hormones?

Infertility

Anything that affects the normal functioning of the testes can cause hypogonadism and subfertility. In this booklet, we are concerned with problems caused by the lack of stimulation of the testes by the pituitary hormones LH and FSH. If the pituitary gland does not produce enough, or any, gonadotrophin hormones this can affect fertility in men because:

• reduced production of FSH will affect the numbers of sperm produced;
• reduced production of LH will affect the production of testosterone.

What does this mean?

Subfertility

In order for fertilisation to occur, a man's semen must contain sufficient sperm. A normal sperm concentration is considered to be more than 20 million per ml. Fertilisation becomes less likely as the sperm concentration falls progressively below this level.

Sexual function

Testosterone is an essential male hormone and it must be present both for interest in sexual activity (libido) and for the ability to have an erection.

Other effects

Hypogonadism affects more than sexual function and reproduction, important as these are. As shown in Table 1, other effects can include lack of energy, depression, loss of body and facial hair, muscular weakness and, in the long-term, Osteoporosis (the thinning of the bones). In some men a lack of testosterone can also cause Gynaecomastia (increased breast tissue). When hypogonadism occurs during childhood or adolescence, puberty will not progress. As Kallmann's syndrome is present before birth it may also be associated with micropenis and undescended testes.

On a day-to-day basis, many men will find these effects of hypogonadism at least as important as the effects on fertility and sexual function. As one Pituitary Foundation member explained, "testosterone is much more to do with one's emotional response to life's setbacks than with one's libido." Another member commented, "Gynaecomastia is acutely embarrassing for a man and does affect his self esteem".

How are hypogonadism and infertility diagnosed? What tests are carried out?

The tests that are used to diagnose sub-fertility and hypogonadism are relatively straightforward. The most informative test in relation to your fertility is your sperm count. A semen sample is obtained by masturbation and is then examined under a microscope so that the number of sperm present and their activity can be determined. Blood tests will be performed to measure the relative amounts of hormones (testosterone, LH and FSH) in your blood. The levels of these hormones vary from man to man, and doctors have tested many healthy men to determine the range of levels that are considered 'normal'. The results of these blood tests usually need to be confirmed by taking a second sample. This is so that your doctor can be sure that the results are correct before you start treatment. The initial tests may be carried out by your GP, preferably in the morning, but you may have to attend a specialist clinic for further tests.

These further tests may include a scan to see whether there is any sign of enlargement of the pituitary gland. This is usually an MRI (magnetic resonance imaging) scan which involves lying on a moveable table and passing inside the cylindrical measuring equipment. You may find this a bit noisy or claustrophobic but most people have no trouble. If you are unable to have an MRI scan, a CT (computed tomography) scan is an alternative. Sometimes a special scan of your hips and spine may be recommended to check whether there is any sign of thinning of the bones (osteoporosis).

How are hypogonadism and infertility treated?

The good news is that missing hormones can be easily replaced - this is called hormone replacement therapy. The type of treatment(s) that you receive will depend on whether you imminently want a family. The general aim of treatment is to restore normal hormonal levels, and thus restore normal sexual function and well-being.

Restoring sexual function and general wellbeing using testosterone replacement therapy

Testosterone replacement therapy will restore normal libido, male sexual characteristics, general well-being and help maintain muscle and bone strength. There are now many ways to take testosterone replacement therapy. You will need to discuss these with your doctor - the method that is best for you will depend on a number of different factors. It may also be helpful to contact other men who have tried this treatment via your local Pituitary Foundation Support Group or by talking to a fellow member by phone. Remember that this is not a once and for always decision - if you have problems with one type of treatment, or simply wish to try a different preparation, you can.

Restoring fertility using gonadotrophin replacement therapy

If you want to start a family, therapy needs to be aimed not only at restoring testosterone levels, but also at inducing sperm production. This is achieved by taking injections to replace the pituitary gonadotrophin hormones, LH and FSH. Preparations called human chorionic gonadotrophin (hCG) and human menopausal gonadotrophin (hMG) are used to treat both men and women for infertility. Don't be alarmed - they will not turn you into a female. In men, these preparations act on the testicles and encourage the production of both testosterone and sperm. They are given by injection two or three times a week, and may be required for up to two years to induce adequate sperm production. It is important to remember that, although this treatment seems complicated, you will only need to take gonadotrophins until you have fathered a child. At this stage sperm can be stored so that it is available for future use. After this, testosterone replacement therapy will be enough to maintain your sexual activity and avoid other problems that can result from lack of testosterone.

Methods of taking testosterone replacement therapy

Whichever type of testosterone replacement therapy you use, you will need to have your blood levels of testosterone measured to check that you are getting the right amount of hormone. This will involve giving a blood sample within a few weeks of starting therapy. Your doctor will also want to see you regularly to monitor how you are getting on and it may be necessary to repeat the blood test at intervals. In patients over the age of 40 the prostate should be checked each year by blood test. Checks should be made too of haemoglobin levels because, with testosterone, the blood can sometimes become too thick. Sustanol may have these effects more often than gels.

Common questions

Q Is the treatment safe?

A Hormone replacement therapy can have some side effects, like most medical therapies. Side effects are not common, because the treatments are designed to return your body to 'normal' by replacing natural hormones that you are missing. Your doctor will discuss any possible side effects with you and monitor your progress regularly.

Q What are the benefits?

A It is hoped that testosterone replacement therapy will improve your sexual function, libido and emotional stability. Your energy and physical stamina will increase and your physical appearance will change - you will see increased hair growth and a more 'masculine' body shape. Longer-term benefits include changes in skin texture and a decreased risk of osteoporosis and depression.

Replacing the gonadotrophins with hCG/hMG will increase your sperm production and thus improve your fertility. It will also increase your production of testosterone, which will have the same benefits as taking testosterone replacement itself.

Q What are the possible side effects?

A The most common side effects with hormone replacement therapy are local reactions. If you are receiving replacement hormones by intramuscular injections, these may be skin redness, swelling and bruising. The most common side effects with testosterone patches are itching, discomfort and transient local irritation, although the patch causes significantly less irritation. Implants may work their way out of the insertion site or cause local infections. Other side effects due to hormone replacement therapy seem to be very rare. Remember, the aim is to restore your body's normal levels of hormones, not to turn you into Superman! Testosterone replacement very rarely leads to aggressive behaviour in men and this is more common if the individual has never before had normal hormone levels.

Q How long will I need to take the treatment?

A If your pituitary gland is missing or irreversibly damaged, you will need to replace testosterone for the rest of your life. As you get older, the amount of testosterone that you are given may decrease - testosterone levels normally fall in men as they get older.

Gonadotrophin replacement is only needed if you wish to have a child - once this has been achieved you should discuss your treatment options with your doctor. Gonadotrophin injections are given until sufficient sperm is present in the ejaculate which may take up to two years. Sperm can also be frozen for future use.

Q How often do I have to take this treatment?

A Testosterone patches are replaced every day and should be worn for 22 to 24 hours every day. The gels are applied on a daily basis and the buccal preparation needs to be replaced every 12 hours. Implants are replaced every three to six months. Testosterone injections have generally been given every two to three weeks, however the new long-acting formulation may require injections only every three months - your doctor will work out exactly how often you need them. Gonadotrophin replacement injections are given two or three times every week - it may be necessary to combine two different types of preparation to achieve adequate sperm production.

Q Will other people notice the therapy?

A Some people have found that the normal skin testosterone patches, which can be worn on your upper arms, abdomen, thigh or back, are obtrusive because they are quite large and may rustle. Remember that the patches can be removed for up to two hours a day, for example if you wish to bath, swim or have sex. The testosterone implants themselves should not be obvious once the small incision heals, although implant scars may be visible when clothing is removed, particularly after a long course of testosterone replacement therapy through implants. Other preparations are not visible to other people.

Q What kind of tests will I need once I am taking the hormones?

A Whichever type of testosterone replacement therapy you take, you will need to have your levels of testosterone measured a few weeks after you begin, in order to check that you are getting the right amount of hormone. This will involve giving a blood sample. It may be necessary to repeat this blood test at intervals. Improvements in symptoms such as your sex drive, impotence and growth of body hair will also show that the testosterone treatment is working.

In order to monitor how you are responding to gonadotrophin replacement, your doctor will check semen samples to see if your sperm count has risen.

Q Am I at greater risk of developing prostate cancer if I am taking the hormones?

A Doctors will want to check older men (over 40 years of age) for prostate cancer - this disease is more common in men as they get older and testosterone replacement may promote growth of pre-existing cancer. The development of prostate cancer is no more frequent in men on testosterone replacement than in men who's testosterone is derived from normally functioning testes.

Q Is the treatment painful?

A Intramuscular injections may be painful, especially after you have been injecting for some time. The testosterone implants are given using a local anaesthetic - there may be some pain for a few days until the incision heals. Patches, gels and buccal tablets are a relatively pain free option - though you may experience some local itching or irritation.

Q Can I use this therapy myself or do I need to see the doctor each time?

A Some men find that they can give themselves intramuscular injections or their partner may be happy to give them. Otherwise you will need to visit your GP's surgery for these injections. Implants are inserted at the hospital outpatient department. Patches, gels and buccal testosterone are the simplest methods of taking testosterone because you can apply them yourself.

Q What do I do if a testosterone patch falls off?

A You can reapply the patch immediately if it falls off. The patch can also be removed for up to two hours during the normal wearing period - for example while you have a bath or a shower, or go swimming. If the patch is removed for more than two hours, you should use a new one.

Q How do I store my medicines?

A The hormones for injection and the testosterone patches can all be stored at normal room temperature (up to 25°C).

Q Will this treatment affect my children?

A Gonadotrophin therapy (injections to replace the pituitary gonadotrophin hormones, LH and FSH - see previous section "Restoring fertility using gonadotrophin replacement therapy") is designed to allow your body to produce normal sperm and to enable you to have normal sexual activity. It should not affect the quality of your sperm. Once your partner has conceived, the pregnancy should proceed like any other pregnancy and there is no reason why it should not result in a normal healthy baby. Testosterone therapy alone will not induce sperm production, and therefore will not improve your chance of conceiving a child.

Q Is a pituitary tumour hereditary?

Aftercare

It is likely that your condition will require long-term monitoring and this will be shared by your Endocrinologist and GP. Because pituitary conditions are relatively rare, you might find that you will be the only patient with hypogonadism your GP is treating and (s)he might find it helpful to have a copy of our Pituitary Disease Factfile for General Practitioners.

Other Factors to Consider

Prescriptions

If you will have to take Hydrocortisone, Thyroxine or Desmopressin permanently you will get free prescriptions for all medicines. Ask at your GP's surgery, hospital or pharmacist for form FP92 (EC92A in Scotland). The form (which will need to be signed by your doctor) tells you what to do. You will then receive an exemption certificate. These certificates only last for a finite period after which they must be renewed. Your health authority may automatically send out an application for renewal.

Information about free prescriptions and the full list of medical conditions which qualify for exemption from prescription charges can be found in leaflet HC11, available from pharmacies and main Post Offices or on www.dh.gov.uk. If you are not sure whether you are entitled to free prescriptions, you must pay for your prescription and ask for a NHS receipt (form FP57 in England, EC57 in Scotland) when you pay; you can't get one at a later date. This form tells you how to get your money back. You must claim within three months.

If you don't qualify for free prescriptions and need more than five prescription items in four months, or more than 14 in a year, ask your pharmacist about pre-payment certificates. This will be more economical way of paying for a large number of prescription items.

Driving

You have a legal obligation to advise the Driver and Vehicle Licensing Agency (DVLA) if there is any reason why you should not drive. Many patients with pituitary conditions will find there are no restrictions on their driving, but you should check with your GP. The only condition likely to affect you is problems with your eyesight. Transsphenoidal surgery does not in itself limit your entitlement to drive. Your doctor or specialist will give you full advice. You may also seek extra advice from the DVLA by contacting the Medical Adviser, The Drivers' Medical Branch, 2 Sandringham Park, Swansea Vale, Llansamlet, Swansea SA6 8QD. 0870 0600 0301. There is a 24 hours answering machine.

Alcohol and Replacement Hormones

There is no interaction between alcohol and these drugs, and you are allowed to drink in moderation. You should restrict yourself to one to two units of alcohol a day.

Insurance and Pensions

Each case will need to be assessed individually. As a guide, if a pituitary tumour has been completely removed, you will probably be accepted at normal rates. Of course, each insurance company will have its own practices. You need to persevere and be specific about your condition, as the people you speak to initially may not have any medical knowledge themselves. It is not unheard of, for instance, for Diabetes Insipidus to be confused with diabetes mellitus (sugar diabetes). If you would like more information, please email us on helpline@pituitary.org.uk or telephone 0845 450 0375.

Employment Problems

If your pituitary condition is causing you difficulties in retaining, seeking, or returning to employment, contact the helpline or your local citizens advice bureau for the most up to date information about employment rights and where to get advice about benefits.

Personal and Medical Identification

If you are taking hormone replacement medication, it is a good idea to wear a medical information bracelet or equivalent, as the information will help the doctors if you have an accident and are unconscious. There are various medical identification products available, please click here for further information.

Members have tried:

• MedicAlert® The MedicAlert Foundation, 1 Bridgewharf, 156 Caledonian Road, London N1 9UU. Tel: 0800 581420. Website: www.medicalert.org.uk
• MediTag, 37 Northampton Street, Hockley, Birmingham B18 6DU. Tel: 0121 200 1616. Website: www.medi-tag.co.uk .
• Doctag, 31-33 West Pilton Drive, Edinburgh, EH4 4HS. Email: info@doctag.net. Website: www.doctag.net.

What hypogonadism has meant to us

The following are three stories that show how different treatments suit different people. You should feel free to discuss the various treatment options with your consultant.

Andrew's Story

So it was a cyst that was causing these headaches and loss of vision. When they first told me about it, I couldn't even pronounce it, let alone spell 'Craniopharyngioma'. At least it wasn't cancerous.

However, it was 'tangled up with the clockwork' - as the neurosurgeon put it - and, when it came out, my pituitary gland came out too. So since then I have had hypopituitarism and have been on replacement hormones.

They didn't put me on testosterone for the first three months or so. I don't think that it was just the operation that left me feeling tired, listless and pathetic. I was 46 and for the whole of my adult life I had been coping with challenges and setbacks by facing up to them and pushing myself to overcome them. All of a sudden, I found I couldn't do that anymore. I would miss a bus and burst into tears. I didn't know who I was or what was wrong.

When you think about it, this was quite understandable. Testosterone is what makes boys into men. For thirty years I had been responding to life in a masculine way and now I couldn't. One of the important ingredients that had shaped me as a person was missing.

When my wife asked the first Registrar that we saw about testosterone, he looked at her as if she was a nymphomaniac. "You've already had your family", he said. But he was forgetting about the importance of Sex hormones to reduce the risk of osteoporosis and was unaware of how much the lack of it could affect my daily life as a whole, not just my sex life.

Soon after, I was put onto testosterone at another hospital and was offered three choices: pills, injections or implants - patches, gels and buccal preparations were not around at that time. Pills were not thought to be terribly reliable, so I started with injections and they made an enormous difference. By that time I had accepted that I would not be quite the same person I was before, but the injections were a big step in getting me back to something like normal.

The trouble was that they wore off. I was having them every three weeks and, by the time I was due for the next one, the emotional problems of lack of drive and confidence were coming back. With the new injection I would be fine for a while until it too started to wear off.

So I ended up with an implant. I have five 200 mg pellets inserted under the skin of my abdomen every six months. This also tends to wear off a bit but, because it does so over a longer period, I avoid the rollercoaster effect of injections. The implant takes a little while to put in and is not without problems - the implant is a foreign body and so it is no surprise that your body tries to reject it. Then about five months after each implant, I have a blood test to monitor how well the level is holding up. I have not tried patches - I have sensitive skin, which puts me off the idea ' but I do know others who have had success with them and they can give an even steadier level.

Through all of this I have found that life can get back to normal. Perhaps not the same normal that was there before but something close and definitely worth living for (whilst your testosterone levels stay up).

Mark's Story

I'm a 43-year-old hypopituitary patient, previously on testosterone replacement by injection for over ten years. This gave quite marked emotional swings - a tendency to feel aggressive and feisty, immediately after the injection followed by a slow fall of in confidence and general mood to the point of feeling very 'flat' just before next dose, although this was moderated by increasing frequency from four to three weekly!

Before starting to use a gel I had to stop having the injection and wait until my testosterone blood level had fallen below a certain figure (about ten days after next injection would have been), and I do remember feeling particularly low during this time, I then began applying 50mg gel sachet in the morning after showering - at first it seemed a very messy ordeal, and I wondered if I could do this every day but that was eleven months ago. I'm fine with the daily ritual and my mood is now down to how I feel and not the testosterone roller coaster ride it used to be. I feel as if I had been slightly out of control of my emotions, but now I have a level base from which to work. This is supported by my family who had also noticed my moods change in unison with my injection appointments - in fact they were more aware of it than I!

David's Story

Up until my late twenties, I had always been healthy in every way. Then quite suddenly, I developed all of the symptoms of hypopituitarism, and my body seemed to be falling apart. I lost two stone, my chest hair fell out, I barely needed to shave, and I became weak and tired and could not concentrate. After a few weeks of this illness, the condition was diagnosed and I was put on full hormone replacement, which included a testosterone injection every three weeks. This regime had an immediate and positive effect and I quickly began to feel better. Although my testosterone levels tended to peak after the injection and trough over the following weeks before the next one, I was more or less able to resume normal life. I say 'more or less' because it was difficult at first to mentally get away from the knowledge that I needed injections to be well. In particular, I felt that my experience of sex changed in the aftermath of the diagnosis in subtle ways. Physically, I think that nothing much had changed - it may have had something to do with the knowledge that fertility would require medical intervention, and this is always tough to bring up with a partner.

After some time had passed, I met my wife-to-be, and we were married. I was totally honest from the time we met about the condition, and I think that this was essential to being able to handle it all. After we were married, we requested fertility treatment. This created the usual bureaucratic fuss within the NHS as to whose budget was going to pay for it and this took at least a year to resolve. This was a very trying process to go through, as bureaucracy can be very frustrating to deal with. The fertility injections were tough to do. You have to do them daily, without fail. It was OK at first, but after time, you can occasionally develop bruising, which is uncomfortable, but passes. Mentally, it can be a strain too, as you are trying to have a child when for years you thought that you might not be able to. However, we were very fortunate, as my wife became pregnant within about ten months and a beautiful, healthy baby arrived in due course.

After the pregnancy was established, I stopped the treatment and resumed testosterone replacement. I discussed all the options available with my consultant and she explained the advantages and disadvantages of each one. The hospital did not support all the options I had heard about, but had a good range of choices. I opted to try a gel this time as it gives a smoother level of testosterone. It is a minor nuisance to apply in the mornings, but it is much easier overall than the injection regime. It has the major advantage of avoiding peaks and troughs of testosterone levels and I do not miss the injections!

I am aware of several new treatment options becoming available and I try to keep up to date with whatever is coming on-stream. I plan to try some of them over time. It is important to me that I stay up to date on developments surrounding hypopituitarism and the treatments that are available. It really helps me in maintaining a sense of control over my life!

Other Support Organisations

There are a number of excellent specialist help groups that provide support for people with infertility problems. They include:

Additional information about infertility problems can be found at the following website: http://www.ferti.net.

General information on lifestyle issues and useful addresses are also available on this web site.

This leaflet has been prepared for patients with hypogonadism or infertility issues.  The aim of this page is to provide general information about these issues and how they are treated.  It is written in general terms, therefore, not all of it will apply to you. Hopefully you will find it helps you to understand your condition better and gives you a basis for discussion with your GP or endocrinologist.

We would like to emphasise that all patients are different and you should always seek advice from your specialist or GP.

©2008  The Pituitary Foundation.  This material may not be stored or reproduced in any form or by any means without the permission of the authors and The Pituitary Foundation.

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