Amenorrhoea

Amenorrhoea is defined as the absence of menses, when a woman does not see her menstrual period. This can be normal in the case of pre-pubertal girls, pregnancy or following menopause.

However, in other women it is a sign of a gynaecological problem, although the menstrual cycle can also be affected by other diseases.

It is divided into two groups:

1. Primary amenorrhoea – this is when a female has never had menses. This is considered abnormal if menses has not started by age 16 or if there has been no development of breasts or pubic hair by age 14. It is a problem affecting about 3 percent of younger women.

2. Secondary amenorrhoea – this is when a woman who had menses previously, then experiences no menses for six months or more. This can affect women of any age. These women have normal breast and pubic hair development.

The two types have different causes and treatments and these will be discussed in the next section. There are many potential causes but the commonest are highlighted in bold.

The commonest reasons are weight related. If the cause is low weight or excessive exercise then lifestyle advice and a healthy weight will prevent further problems and the menses should return. The most common causes of amenorrhoea are weight-related. If the woman is affected by polycystic ovarian syndrome this is commonly exacerbated with weight gain. Again, lifestyle and diet to reduce weight to normal in these women is likely to result in more regular cycles.

Secondary amenorrhoea

Secondary amenorrhoea is commoner so it will be discussed first and in more detail.

There are two areas of the brain which influence the menstrual cycle – the hypothalamus and the pituitary. The hypothalamus produces gonadotrophin releasing hormone (GnRH) which stimulates the anterior pituitary to produce luteinising hormone (LH) and follicle stimulating hormone (FSH). The anterior pituitary hormones then affect the ovaries causing release of oestradiol, progesterone and inhibin. These hormones have a intricate link and the timings and amounts affect the menstrual cycle.

The diagram below illustrates the influence of the brain and ovaries on the production of hormones.

Hypothalamic causes

• The commonest reason for problems at this level is low weight or a low body mass index. If a woman’s weight is below 10-15 percent of her expected normal range it may be that the levels of GnRH are reduced and this can cause amenorrhoea.
• Excessive exercise may result in a low body mass index/weight, but there may be other factors.
• General health problems such as tuberculosis or sarcoidosis, which are rare, but can also affect menses at this level.
• Severe head injury or previous radiotherapy to the brain can cause decreased GnRH leading to amenorrhoea.
• Although rare, brain tumours, both benign and malignant, can cause amenorrhoea.

Pituitary causes

• Sometimes a tumour, usually benign, of the pituitary can cause high levels of prolactin which decrease GnRH production from the hypothalamus causing amenorrhoea.
• If a woman has experienced major haemorrhage, requiring intensive treatment and blood transfusions, usually at childbirth when the pituitary is larger and more sensitive, this can result in damage to the pituitary reducing the release of FSH and LH and causing amenorrhoea.

Ovarian causes

• Polycystic ovarian syndrome (PCOS) is one of the most common causes of amenorrhoea and is found in about 8 percent of the female population.
• Premature ovarian failure is defined as the stopping of menses prior to age 40, with high levels of FSH and LH. The cause in most women is not found but it can be a result of treatment with medication such as chemotherapy; radiotherapy; infection; autoimmune disease; or very rarely a chromosomal problem.
• Rarely, benign cysts of the ovaries, dermoid cysts can cause amenorrhoea.

Other causes

• Cervical stenosis, a blockage that occurs in the cervical canal, when the menses cannot flow out of the uterine cavity, may result in amenorrhoea. This can be caused by surgery.
• Ashermann’s syndrome which is caused by surgery or infection that results in scar tissue within the uterine cavity. This causes the endometrium, lining of the uterus, to not develop normally causing amenorrhoea.
• Drugs may influence the menses and these may be taken as part of the treatment for heavy menses e.g. progesterones or hormone replacement therapy or the combined pill if taken continuously. Other drugs such a medications for nausea can have side effects of stopping the normal menstrual cycle, but this is rare.
• Any chronic health problems may influence the menstrual cycle and cause amenorrhoea, e.g. diabetes, renal failure, thyroid disease, liver disease.
• Very rarely, tumours of the adrenal glands, a gland near the kidney can cause amenorrhoea.

Primary amenorrhoea

Again, the causes can be split into the various levels.

Commonly it can be constitutional, often following a family pattern, which is the commonest cause. However, it can also be due to the effect of other chronic illnesses such as diabetes.

Anorexia nervosa or excessive exercise can be a cause in teenagers. Problems with the development of the pituitary or tumours of the pituitary or hydrocephalus are much rarer causes.

Problems with the normal functioning of the ovaries or the absence of ovaries can also result in no menses. This can be due to abnormal development, premature ovarian failure, genetic problems, autoimmune disease, infections or following chemotherapy/ radiotherapy.

Genetic problems can be a rare cause of amenorrhoea e.g. Turner syndrome which is when the child only has one copy of the X chromosome.

Anatomical causes are more common in primary amenorrhoea:

• Imperforate hymen, which is a hymen with no opening which also usually presents with pain.
• Developmental abnormalities of the vagina, cervix and uterus such as a vaginal septum, or even absent uterus.

History and examination

Your doctor should take a detailed history from you and examine you. This should include a breast examination and a check for other signs of normal sexual development e.g. axillary and pubic hair growth, especially in women who are younger and never had a menses.

The examination may include a check of your visual fields by the doctor. It is usual to examine both the external genitalia and a vaginal examination both with a speculum and a bimanual examination.

Your height and weight should be taken and your body mass index calculated.

Investigations

A pregnancy test should be offered as this is the commonest cause of secondary amenorrhoea. A range of hormone tests may be ordered depending on the symptoms and signs: • Follicle Stimulating Hormone (FSH) • Luteinising Hormone (LH) • Oestradiol • Prolactin • Testosterone • Sex hormone binding globulin • Thyroid function It is usual to have an ultrasound of the pelvis to assess the uterus and ovaries. In women who have been sexually active or have used tampons during menses, this can be carried out using a small vaginal probe, which should not be painful. Other investigations which rarely may be required are: • CT or MRI to exclude rare tumours of the hypothalamus, pituitary, or adrenal glands. • Blood tests for chromosomes. • A hysteroscopy, an investigation when a small camera is passed into the uterus through the vagina and cervix.

The treatment is dependent on the cause.

For women who are underweight resulting in amenorrhoea, lifestyle and dietary advice is the mainstay. However, if their oestrogen levels are very low they may benefit from hormone therapy to prevent osteoporosis.

For women with polycystic ovarian syndrome there is no cure as the exact cause for it is still not completely known. However, weight loss in women with high BMI can help the return of more regular menses.

Women not wishing to conceive who are not seeing their menses are usually advised to start hormonal treatment. This is especially important if the menses come less frequently than three-monthly, as this in the longer-term increases the chance of endometrial abnormalities and over the years can increase the risk of endometrial cancer. Therefore, the combined pill or progesterones every three months can be used to provoke a bleed to shed the endometrium. Metformin is a non-hormonal daily treatment which can sometimes be considered. It is important to stress that there are many treatments to help if you are trying to conceive.

Problems with excess facial or body hair are experienced by many women with PCOS. Creams which can be used to slow the growth of the hair, along with laser treatment can help with this. A specific type of the combined pill can also be helpful for symptoms of excess hair growth or acne.

High levels of prolactin normally just requires treatment with medication, rarely is surgery required. A referral to a Specialist in this area, an Endocrinologist, is usual.

Premature ovarian failure is not normally reversible, and this can cause women to consider oocyte donation with fertility treatment if pregnancy is desired. This can be a very difficult diagnosis and extra psychological support may be needed.

Hormone replacement therapy is normally advised either in the form of the combined oral contraceptive pill or hormone replacement therapy to prevent osteoporosis in the long term, which has significant morbidity and mortality compared to the risks of treatment.

Surgery may be required for tumours in the hypothalamus, ovary or adrenal gland, as well as for intrauterine adhesions or problems with cervical stenosis.

If the cause of the amenorrhoea is due to other disease then optimising the control of these medical problems is the key to treatment.