BMA Concise Guide to Medicine & Drugs

HORMONES AND ENDOCRINE SYSTEM

The endocrine system is a collection of glands located throughout the body that produce hormones and release them into the bloodstream. Each endocrine gland produces one or more hormones, each of which governs a particular body function, including growth and repair of tissues, sexual development and reproductive function, and the body’s response to stress.

The pituitary gland produces hormones that regulate growth, and sexual and reproductive development, and also stimulate other endocrine glands.

The thyroid gland regulates metabolism. Hyperthyroidism or hypothyroidism may occur if the thyroid does not function well.

The adrenal glands produce hormones that regulate the body’s mineral and water content and reduce inflammation (see Corticosteroids).

The pancreas produces insulin to regulate blood glucose levels, and glucagon, which helps the liver and muscles to store glucose.

The kidneys produce a hormone, erythropoietin, needed for red blood cell production. Patients with kidney failure lack this hormone and become anaemic; they may be given epoetin, a version of the hormone.

The ovaries (in women) secrete oestrogen and progesterone, responsible for female sexual and physical development.

The testes (in men) produce testosterone, which controls the development of male sexual and physical characteristics.

Most hormones are released continuously from birth, but the amount produced fluctuates with the body’s needs. Others are produced mainly at certain times – for example, growth hormone is released mainly during childhood and adolescence. Sex hormones are produced by the testes and ovaries from puberty onwards.

Many endocrine glands release their hormones in response to triggering hormones produced by the pituitary gland. This gland releases a variety of pituitary hormones, each of which, in turn, stimulates the appropriate endocrine gland to produce its hormone.

A feedback system usually regulates blood hormone levels: if the blood level rises too high, the pituitary responds by reducing the amount of stimulating hormone produced, thereby allowing the blood hormone level to return to normal.

WHAT CAN GO WRONG

Endocrine disorders, usually resulting in too much or too little of a particular hormone, have a variety of causes. Some are congenital in origin; others may be caused by autoimmune disease (including some forms of diabetes mellitus), malignant or benign tumours, injury, or certain drugs.

WHY DRUGS ARE USED

Natural hormone preparations or their synthetic versions are often prescribed to treat deficiency. Sometimes drugs are given to stimulate increased hormone production in the endocrine gland, such as oral antidiabetic drugs, which act on the insulin-producing cells of the pancreas. When too much hormone is produced, drug treatment may reduce the activity of the gland.

Hormones or related drugs are also used to treat certain other conditions. Corticosteroids related to adrenal hormones are prescribed to relieve inflammation and to suppress immune system activity. Several types of cancer are treated with sex hormones. Female sex hormones are used as contraceptives and to treat menstrual disorders.

MAJOR DRUG GROUPS

· Corticosteroids

· Drugs used in diabetes

· Drugs for thyroid disorders

· Drugs for pituitary disorders

· Male sex hormones

· Female sex hormones

Corticosteroids

Corticosteroid drugs – often simply referred to as steroids – are derived from, or are synthetic variants of, the natural corticosteroid hormones formed in the outer part (cortex) of the adrenal glands, situated on top of each kidney. Release of these hormones is governed by the pituitary gland.

Corticosteroids may mainly have either glucocorticoid or mineralocorticoid effects. Glucocorticoid effects include the maintenance of normal levels of sugar in the blood and the promotion of recovery from injury and stress. The main mineralocorticoid effects are regulation of the balance of mineral salts and the water content of the body. When present in large amounts, corticosteroids act to reduce inflammation and suppress allergic reactions and immune system activity. They are distinct from another group of steroid hormones, the anabolic steroids.

Although corticosteroids have broadly similar actions, they vary in their relative strength and duration of action. Their mineralocorticoid effects also vary in strength.

WHY THEY ARE USED

Corticosteroids are used primarily for their effect in controlling inflammation, whatever its cause. Topical preparations containing corticosteroids are often used for the treatment of many inflammatory skin disorders. These drugs may also be injected directly into a joint or around a tendon to relieve inflammation caused by injury or disease. However, when local administration of the drug is either not possible or not effective, corticosteroids may be given systemically, either by mouth or by intravenous injection.

Corticosteroids are commonly part of the treatment of many disorders in which inflammation is thought to be due to excessive or inappropriate activity of the immune system. These disorders include inflammatory bowel disease, rheumatoid arthritis, glomerulonephritis (a kidney disease), and some rare connective tissue disorders, such as systemic lupus erythematosus. In these conditions corticosteroids relieve symptoms and may also temporarily halt the disease.

Corticosteroids may be given regularly by mouth or inhaler to treat asthma, although their effect on relieving acute asthma attacks is delayed by a few hours (see Bronchodilators and Drugs for asthma).

An important use of oral corticosteroids is to replace the natural hormones that are deficient when adrenal gland function is reduced, as in Addison’s disease. In these cases, the drugs most closely resembling the actions of the natural hormones are selected and a combination of these may be used.

Some cancers of the lymphatic system (lymphomas) and blood (leukaemias) may also respond to corticosteroid treatment. These drugs are also widely used to prevent or treat rejection of organ transplants, usually in conjunction with other drugs, such as azathioprine (see Immunosuppressants).

HOW THEY WORK

Given in high doses, corticosteroid drugs reduce inflammation by blocking the action of chemicals such as prostaglandins that are responsible for triggering the inflammatory response. These drugs also temporarily depress the immune system by reducing the activity of certain types of white blood cell.

HOW THEY AFFECT YOU

Corticosteroid drugs often produce a dramatic improvement in symptoms. Given systemically, corticosteroids may also act on the brain to produce a heightened sense of well-being and, in some people, a sense of euphoria. Troublesome day-to-day side effects are rare. Long-term corticosteroid treatment, however, carries a number of serious risks for the patient.

RISKS AND SPECIAL PRECAUTIONS

In the treatment of Addison’s disease, corticosteroids can be considered as “hormone replacement therapy”, with drugs replacing the natural hormone hydrocortisone. Because replacement doses are given, the adverse effects of high-dose corticosteroids do not occur.

Drugs with strong mineralocorticoid effects, such as fludrocortisone, may cause water retention, swelling (especially of the ankles), and an increase in blood pressure. Because corticosteroids reduce the effect of insulin, they may create problems in people with diabetes and may even give rise to diabetes in susceptible people. They can also cause peptic ulcers.

Because corticosteroids suppress the immune system, they increase susceptibility to infection. They also suppress symptoms of infectious disease. People taking cortico-steroids should avoid exposure to chickenpox or shingles; if they catch either disease, drugs such as aciclovir tablets may be prescribed.

With long-term use, corticosteroids may cause a variety of adverse effects, such as mood changes, acne, a moon-shaped face, increased blood pressure and fluid retention, peptic ulcers, a fat pad on the top of the back, thin skin, and easy bruising. Doctors try to avoid the long-term use of corticosteroid drugs in children because prolonged use may retard growth.

Long-term use of corticosteroids suppresses the production of the body’s own corticosteroid hormones. For this reason, treatment that lasts for more than a few weeks should be withdrawn gradually to give the body time to adjust. If the drug is stopped abruptly, the lack of corticosteroid hormones may lead to sudden collapse.

People taking corticosteroids by mouth for longer than one month are advised to carry a warning card. If someone who is taking steroids long-term has an accident or serious illness, his or her defences against shock may need to be quickly strengthened with extra hydrocortisone, administered intravenously.

COMMON DRUGS

Alclometastone, Beclometasone, Betamethasone, Budesonide, Clobetasol, Clobetasone, Deflazacort, Dexamethasone, Diflucortolone, Fludrocortisone, Fludroxycortide, Flumetasone, Flunisolide, Fluocinolone, Fluocinonide, Fluocortolone, Fluticasone, Hydrocortisone, Methylprednisolone, Mometasone, Prednisolone, Triamcinolone

Drugs used in diabetes

The body obtains most of its energy from glucose, a simple form of sugar made in the intestine from the breakdown of starch and other sugars. Insulin, one of the hormones produced in the pancreas, enables body tissues to take up glucose from the blood, either to use it for energy or to store it. In diabetes mellitus (or sugar diabetes), there is either a complete lack of insulin or too little is produced. This results in reduced uptake of glucose by the tissues and therefore the glucose level in the blood rises abnormally. A high blood glucose level is known medically as hyperglycaemia.

There are two main types of diabetes mellitus. Type 1 (insulin-dependent) diabetes usually appears in young people, with 50 per cent of cases occurring around the time of puberty. The insulin-secreting cells in the pancreas are gradually destroyed. An autoimmune condition (where the body recognizes its pancreas as “foreign” and tries to eliminate it) or a childhood viral infection is the most likely cause. Although the decline in insulin production is slow, the condition often appears suddenly, brought on by periods of stress (for example, infection or puberty) when the body’s insulin requirements are high. Symptoms of Type 1 diabetes include extreme thirst, increased urination, lethargy, and weight loss. This type of diabetes is fatal if it is left untreated.

In Type 1 diabetes, insulin treatment is the only treatment option. It has to be continued for the rest of the patient’s life. Several types of insulin are available, which are broadly classified by their duration of action (short-, medium-, and long-acting).

Type 2 diabetes, formerly known as non-insulin-dependent diabetes mellitus (NIDDM), or maturity-onset diabetes, tends to appear at an older age (usually over 40, although it has become increasingly common in younger age groups) and to come on much more gradually – there may be a delay in its diagnosis for several years because of the gradual onset of symptoms. In this type of diabetes, the levels of insulin in the blood are usually high. However, the cells of the body are resistant to the effects of insulin and have a reduced glucose uptake despite the high insulin levels. This results in hyperglycaemia. Obesity is the most common cause of Type 2 diabetes.

In both types of diabetes, an alteration in diet is vital. A healthy diet consisting of a low-fat, high-fibre, low simple sugar (cakes, sweets) and high complex sugar (pasta, rice, potatoes) intake is advised. In Type 2 diabetes, a reduction in weight alone may be sufficient to lower the body’s energy requirements and restore blood glucose to normal levels. If an alteration in diet fails, oral antidiabetic drugs, such as metformin, acarbose, or sulphonylureas, are prescribed. Insulin may need to be given to people with Type 2 diabetes if the above treatments fail, or in pregnancy, during severe illness, and before the patient undergoes any surgery requiring a general anaesthetic.

IMPORTANCE OF TREATING DIABETES

If diabetes is left untreated, the continuous high blood glucose levels damage various parts of the body. The major problems are caused by atherosclerosis, in which a build-up of fatty deposits in the arteries narrows them, reducing the flow of blood. This can result in heart attacks, blindness, kidney failure, reduced circulation in the legs, and even gangrene. The risk of these conditions is greatly reduced with treatment. Careful control of diabetes in young people, during puberty and afterwards, is of great importance in reducing possible long-term complications. Good diabetic control before conception reduces the chance of miscarriage or abnormalities in the baby.

HOW ANTIDIABETIC DRUGS WORK

Insulin treatment directly replaces the natural hormone that is deficient in diabetes mellitus. Human and pork insulins are the most widely available. When transferring between animal and human insulin, alteration of the dose may be required.

Insulin cannot be taken by mouth because it is broken down in the digestive tract before it reaches the bloodstream; regular injections are therefore necessary (see Administration of insulin).

Sulphonylurea oral antidiabetics encourage the pancreas to produce insulin. They are therefore effective only when some insulin-secreting cells remain active; this is why they are ineffective in the treatment of Type 1 diabetes. Metformin alters the way in which the body metabolizes sugar. Acarbose slows digestion of starch and sugar. Both slow the increase in blood sugar that occurs after a meal. Nateglinide and repaglinide stimulate insulin release. Pioglitazone reduces the body’s resistance to insulin. Exenatide and sitagliptin stimulate insulin release and block the release of glucagon (a substance that raises blood glucose), thereby helping to prevent the rise in blood sugar after a meal.

ADMINISTRATION OF INSULIN

The body normally produces a background level of insulin, with additional insulin being produced as required in response to meals. The insulin delivery systems currently available cannot mimic this process precisely. In people with Type 1 diabetes, short-acting insulin is usually given before meals, and medium-acting either before the evening meal or at bedtime. Insulin pen injectors are useful for daytime administration because they are discreet and easy to carry and use. In patients with Type 2 diabetes who require insulin, a mixture of short- and medium-acting insulin may be given twice a day. Special pumps that deliver continuous subcutaneous insulin seem to have no advantage over multiple subcutaneous injections. Some new insulins called insulin analogues (e.g. Insulin lispro) act very rapidly and may be better at mimicking the insulin-producing behaviour of the normal pancreas.

INSULIN TREATMENT AND YOU

The insulin requirements in diabetes vary greatly between individuals and also depend on physical activity and calorie intake. Hence, insulin regimens are tailored to particular needs, and the person is encouraged to take an active role in his or her own management.

A regular record of home blood glucose monitoring should be kept. This is the basis on which insulin doses are adjusted, preferably by the person with diabetes.

A person with diabetes should learn to recognize the warning signs of hypoglycaemia. A hypoglycaemic event may be induced by giving insulin under medical supervision. The symptoms of sweating, faintness, or palpitations are produced, but they disappear when glucose is administered. Therefore, anyone with diabetes should always carry glucose tablets or sweets with them. Recurrent “hypos” at specific times of the day or night may require a reduction of insulin dose. Rarely, undetected low glucose levels may lead to coma. The injection of glucagon rapidly reverses this. A relative may be instructed how to perform this procedure.

Repeated injection at the same site may disturb the fat layer beneath the skin, producing either swelling or dimpling. This alters the rate of insulin absorption and can be avoided by regularly rotating injection sites.

Insulin requirements are increased during illness and pregnancy. During an illness, the urine should be checked for ketones, which are produced when there is insufficient insulin to permit the normal uptake of glucose by the tissues. If high ketone levels occur in the urine during an illness, urgent medical advice should be sought. The combination of high blood glucose, high urinary ketones, and vomiting is a diabetic emergency and the person should be taken to an Accident and Emergency department without delay.

Exercise increases the body’s need for glucose. Therefore extra calories may be needed before and during exertion. The effects of vigorous exercise on blood glucose levels may last up to 18 hours, and the subsequent (post-exercise) doses of insulin may need to be reduced by 10–25 per cent to avoid hypoglycaemia.

It is advisable for anyone with diabetes to carry a card or bracelet detailing their condition and treatment. This may be useful in a medical emergency.

ANTIDIABETIC DRUGS AND YOU

The sulphonylureas may lower the blood glucose too much: a condition called hypoglycaemia. This can be avoided by starting treatment with low doses and ensuring a regular food intake. Rarely, these drugs cause a decrease in the blood cell count, a rash, or intestinal or liver disturbances. Interactions may occur with other drugs, so your doctor should be informed of your treatment before prescribing any medicines for you.

Unlike the sulphonylureas, metformin does not cause hypoglycaemia. Its most common side effects are nausea, weight loss, abdominal distension, and diarrhoea. It should not be used in people with liver, kidney, or heart problems. Acarbose does not cause hypoglycaemia if used on its own. The tablets must either be chewed with the first mouthful of food at meal times or swallowed whole with a little liquid immediately before food. Sitagliptin is taken orally once a day, either with or without food. Exetanide, used mainly in obese patients, is given by injection twice a day before meals.

COMMON DRUGS

Sulphonylurea drugs Glibenclamide, Gliclazide, Glimepiride, Glipizide, Tolbutamide

Other drugs Acarbose, Diazoxide, Exenatide, Glucagon, Insulin, Insulin aspart, Insulin glargine, Insulin glulisine, Insulin lispro, Metformin, Nateglinide, Pioglitazone, Repaglinide, Sitagliptin

Drugs for thyroid disorders

The thyroid gland produces the hormone thyroxine, which regulates the body’s metabolism. Thyroxine is essential during childhood for normal physical and mental development. Calcitonin, also produced by the thyroid, regulates calcium metabolism and is used as a drug for certain bone disorders.

HYPERTHYROIDISM

In this condition (often called thyrotoxicosis), the thyroid is overactive and produces too much thyroxine. Women are more commonly affected than men. Symptoms include anxiety, palpitations, weight loss, increased appetite, heat intolerance, diarrhoea, and menstrual disturbances. Graves’ disease is the most common form of hyperthyroidism. It is an autoimmune disease in which the body produces antibodies that stimulate the thyroid to produce excess thyroxine. Patients with Graves’ disease may develop abnormally protuberant eyes (exophthalmos) or a swelling involving the skin over the shins (pretibial myxoedema). Hyperthyroidism can be caused by a benign single tumour of the thyroid (an adenoma) or a pre-existing multinodular goitre. Rarely, an overactive thyroid may follow a viral infection, a condition called thyroiditis. Inflammation of the gland leads to the release of stored thyroxine.

Goitre is a swelling of the thyroid gland. It may occur only temporarily, during puberty or pregnancy, or may be due to abnormal growth of thyroid tissue that requires surgical removal. Goitre may also, rarely, be brought about by iodine deficiency, which can be prevented or treated with iodine supplements.

MANAGEMENT OF HYPERTHYROIDISM

There are three possible treatments: antithyroid drugs, radioactive iodine (radio-iodine), and surgery. The most commonly used antithyroid drug is carbimazole, which inhibits the formation of thyroid hormones and reduces their levels to normal over about 4–8 weeks. In the early stage of treatment, a beta blocker may be prescribed to control symptoms. This should be stopped once thyroid function returns to normal. Long-term carbimazole is usually given for 12–18 months to prevent relapse. A “block and replace” regimen may also be used. In this treatment, the thyroid gland is blocked by high doses of carbimazole and thyroxine is added when the level of thyroid hormone in the blood falls below normal.

Carbimazole may produce minor side effects such as nausea, vomiting, skin rashes, or headaches. Rarely, the drug may reduce the white blood cell count. Propylthiouracil may be used as an alternative antithyroid drug.

Radio-iodine is frequently chosen as a first-line therapy, especially in the elderly, and is the second choice if hyperthyroidism recurs following use of carbimazole. It acts by destroying thyroid tissue. Hypothyroidism occurs in up to 80 per cent of people within 20 years after treatment. Long-term studies show radio-iodine to be safe, but its use should be avoided during pregnancy and breast-feeding, and in patients with thyroid eye disease.

Surgery is a third-line therapy. Its use may be favoured for patients with a large goitre, particularly if it causes difficulty in swallowing or breathing. Exophthalmos may require corticosteroids as it does not respond to other treatments.

HYPOTHYROIDISM

This is a condition resulting from too little thyroxine. Sometimes it may be caused by an autoimmune disorder, in which the body’s immune system attacks the thyroid gland. Other cases may follow treatment for hyperthyroidism. In newborn babies, hypothyroidism may be the result of an inborn enzyme disorder. In the past, it also arose from a deficiency of iodine in the diet.

The symptoms of adult hypothyroidism develop slowly and include weight gain, mental slowness, dry skin, hair loss, increased sensitivity to cold, and heavy menstrual periods. In babies, low levels of thyroxine cause permanent mental and physical retardation and, for this reason, babies are tested for hypothyroidism shortly after birth.

MANAGEMENT OF HYPOTHYROIDISM

Lifelong oral treatment with synthetic thyroid hormones (thyroxine (levothyroxine), or liothyronine) is the only option. Blood tests are performed regularly to monitor treatment and permit dosage adjustments. In the elderly and people with heart disease, gradual introduction of thyroxine is used to prevent heart strain.

In severely ill patients, thyroid hormone may be given by injection. This method of administration may also be used to treat newborn infants with low levels of thyroxine.

Symptoms of thyrotoxicosis may appear if excess thyroxine replacement is given. Otherwise, no adverse events occur since treatment is adjusted to replace the natural hormone that the body should produce itself.

COMMON DRUGS

Drugs for hypothyroidism Levothyroxine (thyroxine), Liothyronine

Drugs for hyperthyroidism Carbimazole, Iodine, Nadolol, Propranolol, Propylthiouracil, Radioactive iodine (radio-iodine)

Drugs for pituitary disorders

The pituitary gland, which lies at the base of the brain, produces a number of hormones that regulate physical growth, metabolism, sexual development, and reproductive function. Many of these hormones act indirectly by stimulating other glands, such as the thyroid, adrenal glands, ovaries, and testes, to release their own hormones.

Thyroid-stimulating hormone stimulates production and release of thyroid hormones.

Prolactin stimulates glands in the breast to produce milk in women and helps sperm production in men.

Corticotrophin (ACTH) controls production and release of adrenal corticosteroid hormones.

Gonadotrophins called follicle-stimulating hormone (FSH) and luteinizing hormone (LH) act on the sex glands to stimulate egg production and release in females, and sperm production in males. They also control the output of the sex hormones oestrogen, progesterone, and testosterone.

Growth hormone promotes normal growth and development.

Melanocyte-stimulating hormone controls skin pigmentation.

Antidiuretic hormone (ADH or vasopressin) regulates the output of water in the urine.

An excess or a lack of one of the pituitary hormones may produce serious effects, the nature of which depends on the hormone involved. Abnormal levels of a particular hormone may be caused by a pituitary tumour, which may be treated with surgery, radiotherapy, or drugs. In other cases, drugs may be used to correct the hormonal imbalance.

The more common pituitary disorders that can be treated with drugs are those involving growth hormone, antidiuretic hormone, prolactin, adrenal hormones, and the gonadotrophins. The first three are discussed here. For information on the use of drugs to treat infertility arising from inadequate levels of gonadotrophins. Lack of corticotrophin, leading to inadequate production of adrenal hormones, is usually treated with corticosteroids.

DRUGS FOR GROWTH HORMONE DISORDERS

Growth hormone (somatotropin) is the principal hormone required for normal growth in childhood and adolescence. Lack of growth hormone impairs normal physical growth. Doctors administer hormone treatment only after tests have proven that a lack of this hormone is the cause of the disorder. If treatment is started at an early age, regular injections of somatropin, a synthetic form of natural growth hormone, administered until the end of adolescence, usually allow normal growth and development to take place.

Growth hormone deficiency in adults is rare but may cause loss of strength and stamina, reduced bone mass, weight gain, and psychological symptoms such as poor memory and depression. In some cases, it may be treated with somatotropin.

Less often, the pituitary produces an excess of growth hormone. In children this can result in pituitary gigantism; in adults, it can produce a disorder known as acromegaly. This disorder, which is usually the result of a pituitary tumour, is characterized by thickening of the skull, face, hands, and feet, and enlargement of some internal organs.

The pituitary tumour may either be surgically removed or destroyed by radiotherapy. In the frail or elderly, drugs such as bromocriptine and octreotide are used to reduce growth hormone levels. Octreotide is also used as an adjunctive treatment before surgery and in those with increased growth hormone levels occurring after surgery. People who have undergone surgery and/or radiotherapy may require long-term replacement with other hormones (such as sex hormones, thyroid hormone, or corticosteroids).

DRUGS FOR DIABETES INSIPIDUS

Antidiuretic hormone (also known as ADH or vasopressin) acts on the kidneys, controlling the amount of water retained in the body and returned to the blood. A lack of ADH is usually caused by damage to the pituitary; this in turn causes diabetes insipidus. In this rare condition, the kidneys cannot retain water and large quantities pass into the urine. The chief symptoms are constant thirst and the production of large volumes of urine.

Diabetes insipidus is treated with ADH or a related synthetic drug, desmopressin. These replace naturally produced ADH. Alternatively, a thiazide diuretic may be prescribed for mild cases (see Diuretics). The usual effect of such drugs is to increase urine production, but in diabetes insipidus they have the opposite effect, reducing water loss from the body.

DRUGS USED TO REDUCE PROLACTIN LEVELS

Prolactin, also called lactogenic hormone, is produced in both men and women. In women, prolactin controls the secretion of breast milk following childbirth. The function of this hormone in men is not understood, although it appears to be necessary for normal sperm production.

The disorders associated with prolactin are all concerned with overproduction. High levels in women can cause galactorrhoea (lactation that is not associated with pregnancy and birth), amenorrhoea (lack of menstruation), and infertility. If excessive prolactin is produced in men, the result may be galactorrhoea, erectile dysfunction, or infertility.

Some drugs, notably methyldopa, oestrogen, and the phenothiazine antipsychotics, can raise the prolactin level in the blood. More often, however, the increased prolactin results from a pituitary tumour and is usually treated with bromocriptine or cabergoline, which inhibit prolactin production.

COMMON DRUGS

Drugs for growth hormone disorders Bromocriptine, Lanreotide, Octreotide, Somatropin

Drugs for diabetes insipidus Carbamazepine, Chlortalidone, Desmopressin, Vasopressin (ADH)

Drugs to reduce prolactin levels Bromocriptine, Cabergoline, Quinagolide

Male sex hormones

Male sex hormones, or androgens, are responsible for the development of male sexual characteristics. The principal androgen is testosterone, which in men is produced by the testes from puberty onwards. Women produce testosterone in small amounts in the adrenal glands, but its exact function in the female body is not known.

Testosterone has two major effects: an androgenic effect and an anabolic effect. Its androgenic effect is to stimulate the appearance of the secondary sexual characteristics at puberty, such as the growth of body hair, deepening of the voice, and an increase in genital size. Its anabolic effects are to increase muscle bulk and accelerate growth rate.

There are a number of synthetically produced derivatives of testosterone that produce varying degrees of the androgenic and anabolic effects mentioned here. Derivatives with a mainly anabolic effect are called anabolic steroids.

Testosterone and its derivatives have been used under medical supervision in both men and women to treat a number of conditions.

WHY THEY ARE USED

Male sex hormones are mainly given to men to promote the development of male sexual characteristics when hormone production is deficient. This may be the result of an abnormality of the testes or of inadequate production of the pituitary hormones that stimulate the testes to release testosterone.

They are also sometimes given to adolescent boys if the onset of puberty is delayed by pituitary problems. The treatment may also help to stimulate development of secondary male sexual characteristics and to increase sex drive (libido) in adult men with inadequate testosterone levels. This has been found to reduce sperm production, however. (For information on the drug treatment of male infertility.) An anti-androgen (a substance that inhibits the effects of androgens) may be used in the treatment of benign prostatic hyperplasia, or BPH (an enlarged prostate gland).

Androgens may also be prescribed for women to treat certain types of cancer of the breast and uterus (see Anticancer drugs). Testosterone can be given by injection, gel, patches, or surgically inserted pellets.

HOW THEY WORK

Taken in low doses as part of replacement therapy when natural production is low, male sex hormones act in the same way as the natural hormones. In adolescents suffering from delayed puberty, hormone treatment produces both androgenic and anabolic effects, initiating the development of secondary sexual characteristics over a few months; full sexual development usually takes place over three to four years. When sex hormones are given to adult men, the effects on physical appearance and libido may begin to be felt within a few weeks.

RISKS AND SPECIAL PRECAUTIONS

The main risks with these drugs occur when they are given to boys with delayed puberty and to women with breast cancer. Given to initiate the onset of puberty, they may stunt growth by prematurely sealing the growing ends of the long bones. Doctors normally try to avoid prescribing hormones in these circumstances until growth is complete. High doses given to women have various masculinizing effects, including increased facial and body hair, and a deeper voice. The drugs may also produce enlargement of the clitoris, changes in libido, and acne.

ANABOLIC STEROIDS

Anabolic steroids are synthetically produced variants that mimic the anabolic effects of the natural hormones. They increase muscle bulk and body growth.

Doctors occasionally prescribe anabolic steroids and a high-protein diet to promote recovery after serious illness or major surgery. The steroids may also help to increase the production of blood cells in some forms of anaemia and to reduce itching in chronic obstructive jaundice.

Anabolic steroids have been widely abused by athletes because these drugs speed up the recovery of muscles after a session of intense exercise. This enables the athlete to go through a more demanding daily exercise programme, which results in a significant improvement in muscle power. The use of anabolic steroids by athletes to improve their performance is condemned by doctors and athletic organizations because of the risks to health, particularly for women. The side effects range from acne and baldness to psychological changes, fluid retention, reduced fertility in men and women, hardening of the arteries, a long-term risk of liver disease, and certain forms of cancer.

COMMON DRUGS

Primarily androgenic Mesterolone, Testosterone

Primarily anabolic Nandrolone

Anti-androgens Cyproterone, Dutasteride, Finasteride

Female sex hormones

There are two types of female sex hormones: oestrogen and progesterone. In women, these hormones are secreted by the ovaries from puberty until the menopause. Each month, the levels of oestrogen and progesterone fluctuate, producing the menstrual cycle. During pregnancy, oestrogen and progesterone are produced by the placenta. Production of oestrogen and progesterone is regulated by the two gonadotrophin hormones (FSH and LH) produced by the pituitary gland.

Oestrogen is responsible for the development of female sexual characteristics, including breast development and widening of the pelvis. Progesterone prepares the lining of the uterus for implantation of a fertilized egg; it is also important for the maintenance of pregnancy.

Synthetic forms of these hormones, known as oestrogens and progestogens, are used medically to treat a number of conditions.

WHY THEY ARE USED

The best-known use of oestrogens and progestogens is in oral contraceptives. Other uses of oestrogens and progestogens include the treatment of menstrual disorders and certain hormone-sensitive cancers. This article discusses the drug treatments that are used for natural hormone deficiency.

HORMONE DEFICIENCY

Deficiency of female sex hormones may occur as a result of deficiency of gonadotrophins caused by a pituitary disorder or by abnormal development of the ovaries (ovarian failure). This may lead to the absence of menstruation and lack of sexual development. If tests show a deficiency of gonadotrophins, preparations of these hormones may be prescribed. These trigger the release of oestrogen and progesterone from the ovaries. If pituitary function is normal and ovarian failure is diagnosed as the cause of hormone deficiency, oestrogens and progestogens may be given as supplements. In this situation, these supplements ensure development of normal female sexual characteristics but cannot stimulate ovulation.

MENOPAUSE

A decline in the levels of oestrogen and progesterone occurs naturally following the menopause, when the menstrual cycle ceases. The sudden reduction in levels of oestrogen often causes distressing symptoms, and many doctors suggest that hormone supplements be used around the time of the menopause (see Effects of hormone replacement therapy (HRT)). Such hormone replacement therapy may also be prescribed for women who have undergone early or premature menopause, for example, as a result of surgical removal of the ovaries or radiotherapy for ovarian cancer.

HRT helps to reduce the symptoms of the menopause, including hot flushes and vaginal dryness. It is not normally recommended for long-term use or for the treatment of osteoporosis, however, because of the increased risk of disorders such as breast cancer, stroke, and thromboembolism occurring. Oestrogen is used together with a progestogen unless the woman has had a hysterectomy, in which case oestrogen alone is used. If dryness of the vagina is a particular problem, a cream containing an oestrogen drug may be prescribed for short-term use.

HOW THEY AFFECT YOU

Hormones that are given to treat ovarian failure or delayed puberty take three to six months to produce a noticeable effect on sexual development. Taken for menopausal symptoms, they can dramatically reduce the number of hot flushes within a week.

Both oestrogens and progestogens can cause fluid retention, and oestrogens may cause nausea, vomiting, breast tenderness, headache, dizziness, and depression. Progestogens may cause breakthrough bleeding between menstrual periods. In the comparatively low doses used to treat these disorders, side effects are unlikely.

RISKS AND SPECIAL PRECAUTIONS

Because oestrogens increase the risk of hypertension (raised blood pressure), thrombosis (abnormal blood clotting), and breast cancer, there are risks associated with long-term HRT. Treatment is prescribed with caution for women who have heart or circulatory disorders, and in those who are overweight or who smoke. Oestrogens may also trigger the onset of diabetes mellitus or aggravate blood glucose control in women with diabetes. Tibolone has both oestrogenic and progestogenic properties and can be used on its own.

The use of oestrogens and progestogens as replacement therapy in ovarian failure carries few risks for young women who are otherwise healthy.

EFFECTS OF HORMONE REPLACEMENT THERAPY (HRT)

HRT is primarily used to alleviate symptoms of the menopause, such as hot flushes and vaginal dryness. It may also be used to prevent or treat osteoporosis in some women. However, the benefits of HRT must be weighed against the various increased health risks associated with its use, such as breast cancer, stroke, and thromboembolism.

Breasts There is a slightly increased risk of breast cancer with long-term use of HRT. The increase in risk is related to the length of time for which HRT is used. If HRT is stopped, however, the risk reduces to its pre-treatment level within about five years.

Heart and circulation HRT increases the risk of thromboembolism and does not prevent coronary artery disease.

Bones For women who go through premature menopause, HRT reduces the thinning of bone that occurs in osteoporosis and thus protects against fractures.

Brain HRT increases the risk of stroke.

Reproductive organs Thinning of the vaginal tissues leading to painful intercourse can be prevented by HRT.

COMMON DRUGS

Oestrogens Conjugated oestrogens, Estradiol, Estriol, Estrone, Estropipate, Ethinylestradiol, Tibolone

Progestogens Desogestrel, Dydrogesterone, Levonorgestrel, Medroxyprogesterone, Norethisterone, Norgestrel, Progesterone

Other drugs Raloxifene