Normally, the treatment of hypogonadism requires small initial doses, usually in the form of injections, which are gradually increased to adult levels over a period of several years until, as in normal puberty, the secondary sexual characteristics (see answer to Question 6) have appeared. However, it is worth remembering that the fundamental cause of Kallmann's syndrome is the failure of a defective hypothalamus to secrete GnRH, and even after the successful induction of puberty, the hypothalamus will remain defective. Therefore, in order to maintain those changes to the body experienced during "puberty", some form of hormone replacement therapy must be continued for life.

During normal puberty, the body experiences changes to both its endocrine and reproductive systems. When puberty is artificially induced, it is usual to first encourage the development of the secondary sexual characteristics and to deal with the patient's infertility at a later stage if he or she wishes wishes to become a parent. The next few paragraphs relate to the initial phase of treatment, the treatments on offer for infertility being discussed in the answer to Question 24.

One of the cheapest and most widely available methods of hormone replacement therapy on offer to men is testosterone injections. There are several brand names of testosterone available on prescription, all of which are man-made, synthetic preparations but which have the same effect as natural testosterone. For maximum effect, testosterone is given every few weeks, normally injected into the buttock or thigh. Unless your doctor is confident that you are able to administer the injections yourself, these injections should be given by your GP or a practising nurse.

Your first few injections of testosterone will be in small doses, about the same level as those you would have experienced during the early stages of normal puberty. Gradually, over a period of three or four years, the dosage is increased to adult levels. During this time, you will have acquired the secondary sexual characteristics which would otherwise have been absent.

Testosterone, like other sex hormones, is known as a steroid and like any other drug, it is perfectly safe as long as its administration is monitored by your doctor. There can be side-effects to controlled testosterone injection therapy, but these are minor and are generally harmless. One side-effect can be mild skin irritation around the injection site, but this is more to do with the needle than the testosterone itself. Synthetic testosterone is a thick liquid and there can be some minor discomfort and swelling around the site of the injection, but this usually disappears after a few days.

Natural testosterone is produced by the testes and released in pulses about every 90 minutes in response to the pulses of LH from the pituitary gland (Question 6). These pulses follow a regular daily "cycle" with testosterone levels at their highest overnight, falling significantly during the day. On the other hand, testosterone injections are given every few weeks and consequently, these daily peaks and troughs cannot be simulated. Very often, there is a large peak of testosterone in the blood which lasts for several days after the injection, but then this gradually decreases over the following weeks until another injection is given. The result is that you may be alert and full of energy just after you have the injection, but after a couple of weeks you may feel increasingly tired as testosterone levels in your blood decrease.

If you do not like needles or injections, you may be interested to know that there are other forms of testosterone therapy. These tend to simulate the daily testosterone cycle more closely than injections, making some patients feel less tired and more energetic. Oral therapy by means of testosterone tablets has been available for many years, but tablets must be taken several times a day and even then, their effectiveness varies from patient to patient.

A much less common treatment of male hypogonadism is by implanting testosterone "pellets" under the skin into the abdominal wall. This has to be done by a doctor under local anaesthetic and have to be replaced every four to eight months.

Testosterone "patches" may soon become more widely available, perhaps even replacing testosterone injections. Patches have been on offer to patients for a number years, but in order for the testosterone to be absorbed into the bloodstream, these have had to be placed on the scrotum where the skin is sufficiently thin. Unfortunately, the patch needed to be replaced almost daily and the scrotum shaved of pubic hair every time for maximum adhesion. However, recent advances in medical research have resulted in a more effective patch which may be stuck on almost any part of the body, such as the arm or shoulder. Although the new patch will also have to be replaced regularly, it will soon be a convenient form of hormone replacement therapy on offer to hypogonadal men. Typically, two fresh testosterone patches would need to be applied daily for the best results.

Remember, testosterone on its own will not make you fertile. Testosterone replacement therapy will not "repair" the hypothalamus and make it release GnRH. Instead, the injected or absorbed testosterone circulates in the blood and affects many organs and systems of the body which are responsive to it. These organs do not include the pituitary gland and the testes, because the release of the main fertility-promoting hormone, the gonadotrophin FSH, depends on hypothalamic GnRH and not on testosterone alone. Consequently, if as a sufferer of Kallmann's syndrome you want to become fertile, you will require an alternative form of hormone treatment and this is discussed in the answer to Question 24.

Other forms of hormone replacement therapy on offer to male sufferers of hypogonadotrophic hypogonadism are hCG ("human chorionic gonadotrophin") therapy and GnRH pulsatile therapy. hCG is a human-derived hormone similar in composition to LH, one of the gonadotrophins released by the pituitary gland. LH encourages the development of those areas of the testes (the Leydig or interstitial cells) in which testosterone is produced and hCG has an identical function. While treatment may be switched subsequently to testosterone, starting with hCG has the advantage of enlarging the testes as the interstitial cells develop. hCG is normally given in the form of one or two injections a week and is sometimes used to trigger puberty if this is delayed in otherwise normal and healthy children. As an alternative to surgery, it has been shown that some boys with undescended testes (cryptorchidism) respond successfully to hCG treatment, their testes being made to descend into their scrotum. Some patients prefer hCG to testosterone therapy because regular injections of hCG help to maintain a more even distribution of testosterone over time and therefore, the extremes of feeling full of energy and feeling tired are less pronounced between injections. GnRH pulsatile therapy is discussed in more detail later, but it basically replaces the missing GnRH at the hypothalamic level and the pituitary gland and gonads respond by releasing hormones of their own. In the answer to Question 24, you will read about how both of these forms of HRT can be used to treat infertility.

As a woman, you can also be treated successfully for your absent puberty. As in the case of men with Kallmann's syndrome, the artificial induction of puberty for women must be completed in stages. This is most simply and conveniently done by taking tablets containing a powerful derivation of a naturally occurring oestradiol (ethinyloestradiol), one of the female sex hormones normally produced by the ovaries. Treatment with is essential to promote the physical changes of female sexual maturity, such as the enlargement of your breasts, the widening of your hips and the growth of your pubic and armpit hair. Typically, you would have to take these tablets daily, starting off with very low doses. Gradually, these doses are increased over a period of up to two and a half years or until such time as your doctor thinks you are ready for the second phase of treatment

As you know, healthy women have a regular monthly cycle (the menstrual cycle) which involves a certain amount of bleeding (menstruation) usually lasting no more than a week. After taking the ethinyloestradiol tablets for a while, the first signs of menstrual bleeding should appear. Once this has occurred, the next stage is to simulate a "proper" period as closely possible. Usually, you will be asked to continue taking the ethinyloestradiol tablets every day, but for the first 14 days of each month, your doctor will prescribe additional medication in the form of tablets of semi-synthetic progesterone (medroxyprogesterone acetate).

Normally, progesterone helps build to maintain the inner lining of the womb, preparing it for pregnancy. If fertilisation of the egg does not occur, the levels of progesterone in the blood fall rapidly and the lining of the womb and many of its tiny blood vessels begin to degenerate. This is the cause of the bleeding observed during the period. In your case, the progesterone tablets also increase the thickness of the womb, but since you are still infertile, your ovaries can't produce any eggs. Consequently, the only way you will have a regular period is by stopping to take the progesterone tablets for, say, the last 14 days of each calendar month.

As an alternative to taking both ethinyloestradiol and medroxyprogesterone acetate tablets at the first signs of menstrual bleeding, your doctor may prescribe the "pill" instead. The most common use of the contraceptive pill is, of course, for the purpose of birth control. However, the pill is also a rich source of both oestrogen and progesterone. High levels of these hormones "tell" the pituitary gland to stop releasing LH and FSH and this in turn prevents ovulation, the release of an egg from the ovary. A healthy woman is therefore highly unlikely to become pregnant for as long as she takes the pill. In your case however, the oestrogen and progesterone contained in the pill may be used to simulate the menstrual cycle, but your egg cells are still unable to develop, meaning that you remain infertile.

Eventually, healthy women reach the age of the menopause between the ages of 45 and 55. During the menopause, levels of the sex hormones in the blood gradually decrease. When women with Kallmann's syndrome reach the "menopause", standard hormone replacement therapy (HRT) is sometimes offered. HRT alleviates some of the symptoms commonly associated with the menopause, such as "hot flushes" and an increased risk of osteoporosis or brittle bone disease. HRT for post-menopausal women with Kallmann's syndrome has similar benefits.

Two other forms of treatment are available and these do not only treat absent puberty, but they can also be used to treat infertility in men as well as women. The first is combined hCG / hMG therapy and the second is the already briefly discussed GnRH pulsatile therapy. Remember that treatment with oestrogen and progesterone alone will not make you fertile. You will need specialised fertility treatment such as combined hCG / hMG therapy or GnRH pulsatile therapy (see answer to Question 24).