What Is Primary Ovarian Insufficiency?

Primary ovarian insufficiency (POI) is a condition that affects the reproductive health of females, characterised by the premature depletion of ovarian follicles that results in low levels of oestrogen. POI can result in infertility, early menopause, and other health complications. It is important to gain awareness and knowledge about this condition to understand its impact on the reproductive health of those assigned female at birth. 

This article will delve into understanding primary ovarian insufficiency, its causes, symptoms, diagnosis, and treatment options.

Overview

POI, or premature ovarian failure, affects approximately 1-37% of females under 40.¹ It is a condition in which the normal functionality of the ovaries reduces or stops, leading to irregular or absent menstrual cycles. Females with ovarian insufficiency may have difficulty conceiving without medical assistance, as their ovaries may not release eggs.^1,2

Ovariesare made up of functional units called follicles, which consist of an oocyte surrounded by granulosa cells. Primordial follicles, which include diplotene oocytes and flattened granulosa cells, determine a female's reproductive life based on the size of the follicle pool and rate of activation. Primordial follicles activation involves the growth of the oocyte and changes in the granulosa cells, but it is irreversible. Follicles that are not selected for ovulation will undergo atresia (or breakdown) continuously.^3,4,5

POI accounts for 10-28% of cases of primary amenorrhea in females and 4-18% of cases of secondary amenorrhea.⁶ Unlike menopause, POI is characterised by the continued activity of ovarian function and primordial follicles. Menopause, on the other hand, occurs when there are no more primordial follicles, leading to the absence of menstruation, known as amenorrhea. Secondary amenorrhea can also be caused by various factors, including but not limited to hypothyroidism, pregnancy, genetic abnormalities, and the onset of menstruation in adolescents and teenagers.

Causes of POI

In some females, there is a possibility of developing spontaneous primary ovarian insufficiency without a known cause. Some known factors include;¹

• Genetic disorders 
• Autoimmune disorders
• Chemotherapy or radiation treatment
• Ovarian surgery
• Infections such as pelvic inflammatory disease

Signs and symptoms of POI

Irregular periods or absence of periods are the most common signs of POI, but other symptoms may include;

• Hot flashes
• Night sweats
• Vaginal dryness
• Mood changes
• Difficulty sleeping

Having one or more of these symptoms mentioned above does not automatically mean a person has primary ovarian insufficiency, hence, the need for a proper diagnosis. Other conditions and factors that may cause the symptoms above include the following:⁷

• Pregnancy
• Hypothalamic amenorrhea
• Polycystic ovarian syndrome
• Pituitary diseases, such as prolactinoma
• Hypothyroidism and hyperthyroidism
• Chronic medical conditions such as poorly controlled diabetes or celiac disease
• Abnormalities of the uterus, ranging from chromosomal abnormalities like Turner syndrome to Mullerian anomalies, which include Mullerian agenesis and imperforate hymen
• Lifestyle habits, including poor caloric intake and excessive exercise

Management and treatment for POI

POI has no cure, but certain treatments can help manage the condition and alleviate symptoms. These treatments come in three forms: hormone replacement therapy (HRT), fertility treatment, and psychological support.

HRT, which involves replacing the estrogen and progesterone typically produced by the ovaries, can effectively alleviate menopausal symptoms and provide protection against certain medical conditions. However, it's important to note that HRT may not be suitable for females with a history of breast cancer or certain cardiovascular diseases.⁸

The Endocrine Society recommends HRT to be tailored to the patient's specific needs, taking into account other factors such as age, overall health, and risk of cardiovascular disease. Females with POI may benefit from lifestyle changes such as consuming enough vitamin D, hyaluronic acid, exercising, and eating a healthy diet to help support healthy ovarian function and reduce the risk of oestrogen deficiency and related conditions.^9,10

Fertility treatment, such as donor eggs or in vitro fertilisation (IVF), may also be offered to those who want to conceive; however, the chances of success can vary depending on the individual's ovarian reserve, which can be measured by a blood test to determine levels of follicle-stimulating hormone.⁷

In managing and treating primary ovarian insufficiency, females with POI may experience drastic psychological changes that will require psychological support. It is imperative to monitor POI patients closely and assign them to a behavioural therapist who will helpcope with emotional stressors that arise from primary ovarian insufficiency. A significant other and families may also be affected psychologically and may need support.²

Diagnosis of POI

Diagnosis for POI begins with a medical history and physical exam, followed by blood tests to evaluate hormone levels and ovarian function. Other tests like an ultrasound may be used to evaluate the ovarian reserve and rule out other causes of menstrual irregularities.^1,7

Some tests that your gynaecologist may carry out include:

• Pregnancy test
• Thyroid hormones, prolactin, early morning cortisol, and androgen levels
• Vitamin B 12 and folic acid
• Karyotype
• FMR genotype, especially if there is a family history of POI or the woman is less than 30
• Anti-adrenal antibodies
• Autoantibody screen, including thyroid and tissue antibodies

Risk factors

Genetic conditions such as Turner syndrome, Fragile X syndrome, and autoimmune conditions such as Addison's disease or adrenal insufficiency, Graves' disease, and hypothyroidism are risk factors for developing primary ovarian insufficiency. Chemotherapy and radiation therapy can both increase the likelihood of developing POI. Females who have had ovarian surgery or who have a low ovarian reserve may be at a higher risk as well.^1,2

Complications

Females with primary ovarian insufficiency may be at an increased risk of certain health conditions such as cardiovascular disease, osteoporosis, and breast cancer. In addition, the emotional and social impact of POI on a woman's life can be significant, necessitating assistance from family, friends, and healthcare providers.^9,10

FAQs

Can POI be prevented

Primary ovarian insufficiency cannot be prevented, but maintaining a healthy lifestyle can lower the risk of developing it.

How common is POI

Primary ovarian insufficiency is a rare condition estimated to occur in less than 1% of females under 40. However, it may be underdiagnosed or misdiagnosed, meaning the prevalence may be higher.

When should I see a doctor

Females with primary ovarian insufficiency are at a higher risk of developing breast cancer so regular screenings may be recommended. If menstruation has stopped for four (4) consecutive months before age 40, or if you are experiencing symptoms like hot flashes or mood changes, it is recommended to see a doctor who can provide testing and treatment options.

It is important to note that spontaneous primary ovarian insufficiency does not always result in early menopause, and some females may still have periods or ovulations on a regular basis. Furthermore, in some females with POI, approximately 4-10% may still have viable ovarian tissue for fertility treatment. A group of 358 patients with POI with an unknown cause were monitored for nearly six (6) years after diagnosis. At 48 months, the cumulative pregnancy course after spontaneous conception was 4.3%. In this cohort, 21 spontaneous pregnancies, 16 live births, one twin birth, four miscarriages, and one elective abortion were recorded. Two pregnancies were complicated by gestational diabetes mellitus, one by hypothyroidism, and one of the singleton pregnancies ended in premature birth.⁹

Summary

Primary ovarian insufficiency (POI), also referred to as premature ovarian failure or premature ovarian insufficiency, is a condition that affects many females. It is commonly diagnosed through a blood test and can have long-term complications that may require ongoing management. 

It is important for females to be aware of the signs and symptoms of POI and to seek medical advice if they are experiencing any of them. Early diagnosis and treatment will ensure that appropriate care is given to help manage the physical and emotional effects of POI and improve quality of life. Those concerned about their menstrual cycle, fertility, or menopausal symptoms should consult their doctor or a reproductive medicine specialist for guidance and care.

POI can be a challenging condition to live with, but with proper management and treatment, females with POI can lead healthy and fulfilling lives. Fertility treatment and hormone replacement therapy are common treatment options, and working with a healthcare professional to determine the next steps is essential.