Primary Ovarian Insufficiency
Ani Amelia Zainuddin, Fong Ai Hsing, Rahana, Abd Rahman, Ng Beng Kwang|
Department of Obstetrics & Gynaecology, UKM Medical Centre)

The majority of women will undergo menopause between the ages of 45 and 55 years, with the average age of occurring at 51 years. This is because around this age, the ovaries do not function as normal anymore and have stopped producing oestrogen. With this, women will start experiencing menopausal symptoms like hot flushes, sleep disturbances, mood liability and decreased energy. They will also experience urinary problems and vaginal dryness causing discomfort and pain during sexual intercourse. If a woman is having premature menopause, this means that she is undergoing menopause prior to the age of 40 years. This condition can occur spontaneously or as the result of medical interventions such as surgical removal of the ovaries or due to chemotherapy or radiation treatment, which damages the ovaries.

Primary ovarian insufficiency (POI) is a new term for premature ovarian insufficiency that has been increasingly used to encompass conditions where the ovaries are failing to function, eventually leading to premature menopause. It occurs in 1 out of 1,000 women at the age of 30 years and one out of 100 women at the age of 40 years. It can be due to various causes. Unfortunately, in most cases of POI, the cause will not be found. Women with POI will usually start having irregular menses then not have any menses at all for 6 months. If this condition happens before they reach pubertal age, they will then not attain menarche at all and may eventually experience the menopausal symptoms as mentioned above.

What are the causes of POI?

The causes of POI include:

What are the symptoms experienced in women with POI?

Sometimes, when a woman complains of irregular menstruation, the doctor may put it down to stress however irregular menses is the commonest symptom in women with POI. Amenorrhea (no menstrual period at all) or oligomenorrhea (menstrual periods occurring at intervals longer than 35 days) are the main symptoms. Eventually, after some time, women with POI will also experience menopausal symptoms.

When should I go to a doctor?

If a woman is younger than 40 years old and begins having abnormal bleeding patterns for 4 months or longer, you might need to pay the doctor a visit.

First of all, the doctor will interview you to get information regarding your problem and the background information of your health, then he / she will perform a pregnancy test to rule out an unexpected pregnancy as the reason for missed periods. Next, the doctor will examine you physically to look for signs of other disorders that cause irregular menses.

After the physical examination, for those who are suspected of having POI, the doctor will then take a sample of your blood to measure the level of the hormone Follicle- Stimulating Hormone (FSH) in order to confirm the diagnosis. If the basal FSH levels are elevated into the menopausal range (>40IU/ml), the doctor will repeat this test in at least a months’ time. If both FSH levels are greater than 40 IU/ml then a diagnosis of primary ovarian insufficiency can be confirmed. Other investigations include Anti-mullerian hormone (AMH) to assess the ovarian reserve and serum oestradiol level usually less than 50pmol/L. The doctor will also take your blood samples to test for other conditions that cause POI such as chromosomal, genetic and endocrine causes such as karyotyping, serum thyroid stimulating hormone (TSH) and Fragile X carrier screening. The doctor will also perform a pelvic ultrasound to assess your uterus and ovaries. There is also a possibility that further investigations on your bone such as DEXA scan.

What are the implications of POI?

The consequences of POI can be divided into short and long-term. Short-term consequences include vasomotor symptoms and long-term consequences include:

• Reduced life expectancy
  Untreated POI might reduce patient’s life expectancy up to 2 years because of cardiovascular disease. The risk of mortality from ischaemic heart disease increased 80% in women with POI as compared to women who menopause over 55 years.
• Bone Mineral Density reduction
  Patients with POI are at high risk of having osteoporosis (brittle bones) due to oestrogen deficiency as oestrogen helps to inhibit bone resorption as it aids in the intestinal absorption of calcium, which is necessary to maintain bone strength. Thus the patients with POI need to take 1,200 to 1,500mg of calcium each day with adequate intake of vitamin D, which helps absorption of calcium. They should also have dairy food in their diet like milk and cheese as it can help in increasing bone density.
• Cardiovascular disease
  Also, due to oestrogen deficiency, patients with POI have higher rates (up to 1.7x) of illness and death from heart disease because studies showed that exposure to estrogen help protects against heart disease.
• Cognitive problem
  These patients will have memory loss and lose their ability to focus.
• Infertility
  Patients with POI will have problems in conceiving because of the impaired function of the ovary, as the ovaries are not producing the oocytes (eggs) that can be fertilized by the sperms. However, 5-10% of women having POI may able to conceive because of spontaneous recovery or with medical treatment.
• Autoimmune disease
  It is estimated that up to 30% cases of POI are immune in origin. Thus, the incidence of autoimmune hypothyroidism, type I diabetes mellitus, adrenal insufficiency and hypoparathyroidism is increased.

What are the treatments for Primary Ovarian Insufficiency?

Currently, there is no proven treatment to restore normal function to a woman’s ovaries.  Research is still needed to define optimal treatments that balance benefits and risks. But there are some treatments for some of the symptoms of POI as well as treatments to reduce health risks.

• Hormonal replacement therapy (HRT)
  For women having POI, HRT can provide the body with oestrogen and progesterone (another hormone that is provided by the ovaries and which are also not produced in women with POI). The doctors will give oestrogen to women having POI and they will need to take it everyday as well as progestogen (replacement for progesterone) for 10-14 days every month for those women with intact uterus. This will enable the women to have withdrawal bleeds (similar to regular menstrual periods) and prevent them from getting cardiovascular disease and osteoporosis. These women with POI are advised to take HRT until approximately age of 51 years (as this is the average age of menopause for most women).  They are required to have a follow up every 6 months with their doctor. Thyroid function test, calcium and cortisol need to be done yearly. A bone mineral density (BMD) scan should be done every two years, this is a test to measure the bone mineral density to make sure they are not having osteoporosis.

If they are having endocrine (hormonal) problems, they will be referred to the endocrine specialist. If they wish to conceive, they will be referred to the infertility specialist. Women with POI definitely need psychological support from doctors, family and friends.

Conclusion
Women experiencing menstrual problems and / or menopausal symptoms are recommended to visit the doctor as soon as possible for an assessment to confirm the diagnosis of POI. These women also need psychological support from doctors and family members in order to have a good quality of life.   

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