Premature Ovarian Insufficiency (POI) or Premature Menopause

When Periods Stop Prematurely

The menopause signifies the ending of fertility for a woman and it is a natural part of the lifecycle. It results from the loss of ovarian function so that eggs and hormones, primarily oestrogen but also testosterone are no longer produced. It is the loss of oestrogen and to some extent testosterone that results in the various symptoms of the menopause and also increases the risk of osteoporosis and heart disease.

Menopause usually occurs around the age of fifty but it can occur much earlier. In 1% of women it occurs before the age of forty and this is termed Premature Ovarian Insufficiency (POI) or Premature Menopause. In 0.1% of women it occurs before the age of thirty.

In some women Premature Menopause can occur before the age of thirty.

POI Health Risks and Loss of Fertility

Women with Premature Ovarian Insufficiency will experience the usual symptoms of menopause (See Table 1) and they will also have an even greater risk of osteoporosis and heart disease resulting an increase in overall mortality. It is however the loss of fertility that is often the most distressing consequence of POI.

Symptoms of Premature Menopause

Symptoms of the menopause tend to be more severe with POI, but they may not always be recognised by the woman or her doctor as being due to ovarian failure, especially if the periods are regular, which is often the case in the early phase of this condition. 

The psychological symptoms associated with premature menopause can include depression, mood swings, anxiety and loss of libido and are especially troublesome in this relatively young age group. Often these symptoms are made worse by the loss of fertility or the feeling of premature loss of femininity. Sadly, women are often treated with anti-depressants which is inappropriate and can actually make some symptoms such as tiredness and loss of libido worse.

Causes of POI

In the vast majority of cases the cause of POI is unknown but there may be a familial tendency and a woman is more likely to suffer POI if her mother or older sister have been diagnosed with this. Sometimes menopause can result from the treatment of cancer with chemotherapy or from surgery to remove the ovaries.

Other causes of POI can include the following:

  • Certain viral infections such as mumps may increase the risk of POI, and women with HIV are also more likely to develop an early menopause.
  • POI may also be part of a wider auto-immune disease process. There is an association with other auto-immune diseases such as Addison’s disease, thyroid disease and vitiligo
  • Chromosomal disorders such as Turners syndrome can also lead to POI but these cases are very rare.

Diagnosis of POI

The diagnosis of POI is usually made on the basis of the symptoms being experienced and confirmed by blood test. Two blood tests are usually required at least 4-6 weeks apart. These diagnostic hormone tests typically show a reduced oestradiol (E2) level along with an elevated Follicle Stimulating Hormone (FSH) level, but a normal blood test does not necessarily exclude this diagnosis. This is because ovarian function and therefore hormone levels can fluctuate widely. In the initial stages of this condition phases of near normal hormone levels may be experienced, along with normal cycles with only mild or no symptoms, and at other times marked symptoms with low blood levels of oestradiol are experienced.

However, while blood tests may not always be reliable in making the diagnosis of POI they are essential in excluding other problems with similar symptoms such as hypothyroidism and hyperprolactinaemia.

In practice the diagnosis is usually not difficult and decisions are based on a thorough consideration of all of the symptoms combined with the results from the blood tests. 

Impact of POI on fertility

In the UK the average age for a woman having their first child is around 30 years. Many women with POI will therefore not have had children, meaning that a diagnosis can be particularly distressing. However, even for women who have had children the loss of fertility is often troubling.

Following a diagnosis of POI, fertility is greatly reduced but it is still possible to get pregnant because the ovarian function fluctuates and ovulation can occur intermittently. The likelihood of pregnancy is reduced to around 5% in women with POI and sadly, there is no effective treatment to improve this statistic. Treatment with drugs such as clomiphene to induce ovulation is of no benefit. The longer a woman has had POI, the less likely it is that she will be able to conceive naturally. It is extremely unlikely that a woman with POI who has not had a natural period for two or more years will conceive.

The only real fertility treatment option available is IVF with donor eggs. This treatment is highly successful but there is a great shortage of egg donors in the UK.  

Who Should Freeze Eggs?

Women at risk of POI such as women about to undergo chemotherapy or young women with a strong family history may consider freezing eggs while their ovarian function is normal. However, this is not a useful option once the ovarian function has already diminished or ceased.

The longterm effects of POI

In addition to the symptoms described above that can impact on quality of life, POI also increases the risk of heart disease and osteoporosis - with an associated risk of bone fractures. The overall mortality is therefore increased. Recent studies have also shown an increased incidence of dementia in women with POI.

Treatment of POI

The most appropriate treatment for POI is hormone replacement therapy (HRT), which will help with the symptoms, as well as reduce the risk of osteoporosis and heart disease. 

HRT is best given trans-dermally as this method avoids the first pass effect through the liver and avoids any excess risk of thrombosis. We favour 17β-oestradiol which is identical to the hormone produced by the human ovary and is manufactured in the laboratory.

We favour 17β-oestradiol which is identical to the hormone produced by the human ovary

In addition to oestrogen, women will also benefit from testosterone. This is often assumed to be exclusively a male hormone, but testosterone is an important hormone in women too. Testosterone can improve moods, energy, libido and headaches as well as sleep.

Women receiving oestrogen also need to take cyclical progesterone for ten to fourteen days a month to ensure a regular withdrawal bleed and to protect against endometrial hyperplasia (thickening of the womb lining), which may be precancerous. While many HRT preparations contain synthetic progestogens, we tend to favour the natural progesterone as it has fewer side effects. Some women who are particularly sensitive to progesterone can develop PMS type symptoms when taking the natural progesterone. These side effects can be reduced if the progesterone is taken vaginally but it is sometimes necessary to reduce the dose and duration to seven or ten days in women who are particularly sensitive to progesterone. Women who have had a hysterectomy can take oestrogen without having to take progesterone.

Benefits of HRT

HRT will alleviate the various symptoms of the menopause including hot flushes, night sweats, anxiety, depression, tiredness and loss of libido. 

In the long-term hormonal therapy will prevent osteoporosis and reduce the risk of bone fractures. HRT will also reduce the risk of heart disease and dementia. 

Safety of HRT 

HRT is safe and the benefits far out-weigh any theoretical risk and this is especially so in women who suffer a premature menopause and are at increased risk of osteoporosis and heart disease as a result.

Women with POI should be encouraged to take HRT at least until the age of fifty and by doing so will not increase their risk of heart disease or breast cancer. 

Table 1 

Women with Premature Ovarian Insufficiency (POI) will experience the usual symptoms of menopause - as set out below.

Symptoms of the Menopause
Symptom

 Prevalence (%)

 

Vasomotor instability (Hot Flushes/night sweats)     36 - 87
Sleep disturbances     40 - 60
Mood Symptoms 15 - 78
Weight Gain 60 - 70
Muscle/joint pain   48 - 72
Palpitations       44 - 50
Headache 32 - 71
Poor memory   41 - 44
Urinary symptoms   25 - 30
 Sexual dysfunction         20 - 30

 

A rare disorder of the adrenal glands leading to deficiency of the hormones cortisol and aldosterone.

Full medical glossary
A fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. Full medical glossary
Abnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. Full medical glossary
Malignant, a tumour that may invade surrounding tissues or spread to distant parts of the body. Full medical glossary
The basic unit of all living organisms. Full medical glossary
The use of chemical substances to treat disease, particularly cancer. Full medical glossary
Decline in mental capacity, brain functioning and memory that affects day-to-day living. Full medical glossary
Feelings of sadness, hopelessness and a loss of interest in life, combined with a sense of reduced emotional well-being Full medical glossary
The process of determining which condition a patient may have. Full medical glossary
Relating to the endometrium. Full medical glossary
A viral infection affecting the respiratory system. Full medical glossary
An abbreviation for follicle-stimulating hormone, a hormone produced by the pituitary gland. Full medical glossary
The abbreviation for human immunodeficiency virus, which is the cause of AIDS. Full medical glossary
A substance produced by a gland in one part of the body and carried by the blood to the organs or tissues where it has an effect. Full medical glossary
The administration of female hormones in cases where they are not sufficiently produced by the body. Abbreviated to HRT. Full medical glossary
Abbreviation for hormone replacement therapy, the administration of female hormones in cases where they are not sufficiently produced by the body. Full medical glossary
A condition involving excess levels of the hormone prolactin in the blood. Full medical glossary
Prefix suggesting a deficiency, lack of, or small size. Full medical glossary
Underproduction of the thyroid hormones by the thyroid gland. Full medical glossary
The surgical removal of the uterus (womb). Full medical glossary
The number of new episodes of a condition arising in a certain group of people over a specified period of time. Full medical glossary
Invasion by organisms that may be harmful, for example bacteria or parasites. Full medical glossary
Stopping or ceasing for a time. Full medical glossary
In vitro fertilisation. Fertilisation of the female reproductive cell (ovum) outside the body, before implantation into the uterus (womb). Full medical glossary
Sexual drive. Full medical glossary
A large abdominal organ that has many important roles including the production of bile and clotting factors, detoxification, and the metabolism of proteins, carbohydrates and fats. Full medical glossary

The time of a woman’s life when her ovaries stop releasing an egg (ovum) on a monthly cycle, and her periods cease

Full medical glossary
Tiny, harmless, hard, white spots that usually occur in clusters around the nose and on the upper cheeks in newborn babies and also in young adults. Full medical glossary
Relating to the part of the nervous system that carries information from the brain and spinal cord to cause activity in a muscle or gland. Full medical glossary
multiple sclerosis Full medical glossary
A viral infection common in schoolchildren. It may cause fever, vomiting and swelling of the parotid glands, the largest salivary glands. Full medical glossary
The main female hormone. Full medical glossary
A hormone involved in female sexual development, produced by the ovaries. Full medical glossary
A condition resulting in brittle bones due to loss of bony tissue. Full medical glossary
relating to the ovaries Full medical glossary
Female reproductive organs situated one on either side of the uterus (womb). They produce egg cells (ova) and hormones in a monthly cycle. Full medical glossary
When one or more eggs are released from the ovary. Full medical glossary
A craving to eat non-food substances such as earth or coal. Full medical glossary
the period from conception to birth Full medical glossary
A hormone produced by the pituitary gland in the brain that stimulates breast growth and milk production. Both men and women produce some prolactin, but levels increase in women during pregnancy and breastfeeding Full medical glossary
Relating to injury or concern. Full medical glossary
The main male sex hormone. Full medical glossary
The formation of a blood clot. Full medical glossary
A gland in the neck that produces hormones with a role in controlling metabolism. Full medical glossary
The muscula passage, forming part of the femal reproductive system, between the cervix and the external genitalia. Full medical glossary
A common disorder of skin pigmentation, in which patches of skin, usually on the face, hands, armpits and groin, lose their colour. It is thought to be an autoimmune disease. Full medical glossary
The uterus. Full medical glossary