About Primary Ovarian Insufficiency

PRIMARY Ovarian Insufficiency (POI) — also known as premature ovarian failure, premature menopause or gonadal dysgenesis — is often an emotional diagnosis for a woman, her spouse and her family.

This is because diagnosis for POI comes when depletion of follicles and oestrogen occurs before the age of 40.

“Oestrogen is one of the main hormones which is secreted from follicles within the ovaries, and contributes to a woman’s overall well-being and sexual function. Women are born with around one million follicles, which are lost at a rate of 1,000 follicles per month. At around 51, these follicles have completely depleted and there is a subsequent decrease in oestrogen levels. When depletion of follicles and oestrogen has occurred prior to the age of 40, this is called primary ovarian insufficiency,” explained obstetrician-gynaecologist Dr Daryl Daley.

The ObGyn said that POI affects one in 100 women below the age of 40, and there is no identifiable cause in the majority of cases. This makes the diagnosis extremely frustrating, but underlying health issues are often common causes of the condition.

“Chemotherapy and radiotherapy for treatment of childhood cancers can result in irreparable damage to the ovaries, and this is a common cause of POI. In autoimmune conditions, the immune system produces antibodies that attack and destroy organs – including the ovaries, thus causing POI,” he continued.

Dr Daley further explained: “Women normally have two X chromosomes, which are derived from either parent. In Turner’s Syndrome (Gonadal Dysgenesis), there is only one functioning X chromosome, which leads to improper development of the ovaries and predisposes the patient to POI. Fragile X syndrome is an abnormal expression of a gene on the X chromosome that leads to mental retardation in boys. This genetic defect can also be present in women and can cause POI. Lastly, as a cause of POI, there may be defects in the production or activity of ovarian hormones even in the presence of normal ovaries.”

Dr Daley added that women in their mid-40s may have irregularities in their menstrual cycles as they approach natural menopause, but in POI, patients may present similarly with frequent skipped periods or may have complete absence of periods; however, there are other details which should not be ignored.

“There will also be difficulty in conceiving and associated infertility. Due to the lack of oestrogen, patients will also present with the classic menopausal signs and symptoms, which include hot flashes, night sweats, irritability, poor concentration, decreased sex drive, vaginal dryness and painful sexual intercourse,” he explained.

He added that oestrogen encourages bone strength and integrity, so a lack of same can predispose patients with POI to osteoporosis. He also mentioned that with low oestrogen, there are abnormal lipid and cholesterol levels, which can lead to cardiovascular dysfunction in the form of heart attacks and strokes in the long term.

To confirm the condition, Dr Daley said the patient’s history and complaints, examination, laboratory investigations and imaging are used. He said that in the menopausal period, hormones secreted from the brain that aid in regulating the ovaries are increased up to fivefold and can be detected within the blood.

“This, in combination with low or absent oestrogen levels, will confirm POI. Circulating antibodies, which can destroy the ovaries, can also be detected. Genetic testing can confirm abnormal chromosomes such as those associated with Turner’s Syndrome and Fragile X Syndrome. On an ultrasound the ovaries may appear small and very few follicles will be seen, suggesting POI,” he said.

Though the thought of early menopause and its sequel can be quite traumatic to the patient, her spouse and her family, Dr Daley said it is very important to incorporate adequate counselling, sometimes with a mental health aide, as these patients are prone to depression.

Dr Daley said there are two main areas of focus for treatment — treating the low oestrogen levels and treating infertility.

“The aim of oestrogen replacement is to decrease the menopausal symptoms due to the lack of oestrogen and its long-term complications,” he said. “Oestrogen can be administered orally, via patches or via devices which are placed both under the skin and topically.”

He added: “The oestrogen is continued until the time of normal menopause (around age 51). Some women may not be able to have oestrogen, such as women with a history of previous blood clots. In these women, alternative non-hormonal medication such as anti-depressive medication can be used, and have been proven beneficial. All women with this condition should be encouraged to have a balanced diet and to exercise regularly.”

Of note, Dr Daley said 10 per cent of women with POI will be able to conceive naturally. However, for women who cannot conceive naturally, assisted reproduction in the form of in-vitro fertilisation could be considered.