Dr F C W Wu
Manchester Royal Infirmary

Patients suffering from Hypogonadism are treated by either replacing the Gonadotrophins or replacing sex steroids (Testosterone in men and Oestrogen in women) in order to stimulate gonadal function. The most straightforward method to induce or maintain virilisation in a male patient who is unable to produce gonadotrophins or testosterone is to use testosterone replacement. This stimulates development of the secondary sexual features and also maintains secondary sexual function. However, this does not restore fertility because testosterone does not stimulate the testes to produce sperm. The same principle applies for females with respect to oestrogen replacement.

In a patient who is deficient in gonadotrophins as a result of pituitary disease, fertility is stimulated by the use of human chorionic gonadotrophin (hCG) and also human menopausal gonadotrophin (hMG). hCG is a slightly longer acting version of Luteinising hormone (LH) and hMG has a biological activity similar to follicle stimulating hormone (FSH). These hormones stimulate spermatogenesis in men and follicular development and ovulation in the female.

Puberty occurs when the sex hormone levels in the body rise in response to changes in the Hypothalamus. There are almost no gonadotrophins in a child until this happens. As a result of this, gonadotrophin deficiency cannot be diagnosed until the start of puberty. Once a diagnosis of hypogonadism is established the start of testosterone treatment should not be delayed. The ideal is to keep the child in line with their peers and the usual time to start testosterone replacement is around 13 or 14 years of age. Giving testosterone too early may stop growth prematurely, but this observation was made at a time when testosterone was given to teenagers in full adult replacement doses. When a hypogonadotrophic teenager is started on testosterone replacement the dosage is usually built up gradually with the aim of maximising their growth potential. Approaches to gonadotrophin replacement can differ between doctors.

There is no need to use gonadotrophins to stimulate gonadal development from an early age. Patients presenting in their late teens or early twenties are usually mainly interested in the virilisation function of testosterone and this hormone is most conveniently replaced by injection or transdermal patches. Giving gonadotrophins tends to be more complex, more expensive and possibly more demanding on a daily basis. Treatment for fertility can then be deferred until there is an actual requirement for fertility. At this time, the sex steroids will be stopped and then the gonadotrophins started. There is no loss in the potential for treatment even when a person has been on replacement sex steroids for a number of years. The principle for treatment therefore is to induce and maintain secondary sexual features with sex steroids and then introduce gonadotrophins instead of the sex steroids when there is a requirement for fertility.

A study performed in Germany investigated the use of hMG and hMG to induce spermatogenesis and fertility in a number of male patients with both congenital and acquired gonadotrophin deficiency. With combined injections of hMG and hMG over a period of treatment of between 3-6 months and up to 2 years duration in the vast majority of patients there was a dramatic increase in the appearance and concentration of sperm. At the end of the treatment course 18 out of 20 patients produced sperm in the ejaculate and out of these pregnancy occurred in 6 out of 10. In the case of patients with acquired gonadotrophin deficiency (including hypopituitary patients) the response was very much better and 80% achieved fertility.

An alternative treatment for infertility is IVF. For females, many IVF clinics decline infertility treatment after the age of 37 although this is not a hard and fast rule. In general, patients do not want an age limit but for high financial aspects of infertility treatments many patients are advised against it.

The male Sex hormones, which include testosterone and androstenedione, are known as Androgens. Androgens are necessary for the normal sexual function response, but are not sufficient on their own as not all of the components of male sexual function are due to the androgens. Major elements of human male sexual function are sexual appetite/desire, sexual arousal, erectile potency, sexual activity and orgasm. Blood pressure and sweating are also increased.

Nocturnal Penile Tumescence (NPT) are erections that occur during sleep. An absence of NPT can be linked to low testosterone levels, but with testosterone replacement NPT are restored. Spontaneous erections also occur with replacement of androgens to normal levels.

In premenopausal women, the ovaries provide approximately half the circulating testosterone. An article in the New England Journal of Medicine, published in September 2000, reported that after a hysterectomy many women experience impaired sexual functioning despite oestrogen replacement. The report evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause. Despite an appreciable placebo response, the higher testosterone dose resulted in further increases in scores for frequency of sexual activity and orgasm. Positive well-being also increased.

Oestrogen and testosterone also have other effects. They both increase bone density, but testosterone also causes acne and hirsutism in women. Other potential long-term side-effects for women need to be investigated.