Primary Ovarian Insufficiency
Five to ten percent of women with POI can successfully conceive without medical help.

Primary ovarian insufficiency (POI) (also known as premature ovarian insufficiency, premature ovarian failure, or premature ovarian insufficiency syndrome) refers to when the ovaries cease to function normally before the age of 40 years.

In contrast to the average menopausal age from 45 to 52 years, women with POI experience menopause before the age of 40 years. According to the American Pregnancy Association, 1 in 1,000 women between the ages of 15 and 29 years and 1 in 100 women between the ages of 30 and 39 years have POI.

POI is thought to affect 1 in 100 women younger than 40 years, 1 in 1,000 women younger than 30 years, and 1 in 10,000 women younger than 20 years. Despite its prevalence, POI is a condition that is not well discussed.

Geographic and ethnic differences are evident in POI, such as:

  • 0.1 percent prevalence in Japanese
  • 1 percent of Caucasians
  • 1.4 percent of African Americans and Hispanics

Since many medical professionals are still unaware of the condition, POI is frequently underdiagnosed and poorly managed. Because the diagnosis is frequently delayed, some studies report that the incidence may even be higher. People may see more than one specialist before they receive a diagnosis of POI.

POI is the loss of eggs in the ovaries or abnormal ovarian function, causing periods and the entire menstrual cycle to stop for long periods or permanently before the age of 40 years. POI is more common in women in their 30s than in their 20s or adolescent years.

What is the difference between primary ovarian insufficiency and premature menopause?

In primary ovarian insufficiency (POI), there is seldom a chance of spontaneous ovulation and pregnancy even without medical intervention. The ovaries are not technically a "failure" but rather "insufficient," which distinguishes POI from premature menopause and menopause where the chance of ovulation is nil. 

Premature menopause and menopause both indicate the end of fertility and ovarian function, whereas POI still gives a rare hope of ovulation and pregnancy. Hence, POI is a chronic condition and is different from premature menopause and menopause.

What are the common signs and symptoms of primary ovarian insufficiency?

Most of the symptoms of menopause and perimenopause overlap with those of primary ovarian insufficiency (POI). The most typical symptom for the majority of women is a gradual cessation of menstruation.

In about 1 in 10 women with POI, the menstrual cycle may not even begin, and they first show symptoms at a very young age, typically before the age of 20 years. Others may see a change in their period cycle or duration.

One in four affected women does not experience any POI symptoms. 

Common symptoms of POI

  • Hot flushes
    • The most common menopausal symptom affects three out of every four women. They usually strike suddenly and spread throughout your body, including the chest, neck, and face. They range in duration from a few minutes to several hours. 
    • Can cause symptoms such as sweating, dizziness, light-headedness, and even heart palpitations. They usually occur on their own, but they can occur after eating certain foods or drinking alcohol, particularly wine.
  • Night sweats
    • Extremely prevalent and problematic. Many women report having multiple nighttime awakenings, becoming "drenched" in perspiration, and needing to change out of their clothes and sheets.
  • Mood swings
    • Although not all women experience mood swings, for some of them, they can seriously disrupt their lives.
  • Tiredness and poor sleep
    • Can be connected to sleep disturbances brought on by night sweats, but many women find that during the perimenopausal stage, their sleep cycle may get disrupted. 
    • Even if sleep is unaffected, women might find themselves getting more exhausted during the day.
  • Lack of libido
    • When your hormone levels drop, you may experience decreased or absent libido (sex drive). This could also be due to abnormal sex hormone levels in your body.
  • Poor concentration
    • Unable to focus as effectively as they previously did. Many women find it difficult to multitask, which can be incredibly irritating.
  • Pain in the joints
    • Estrogen is essential for joint lubrication and can help minimize joint inflammation. Low estrogen levels due to POI can cause several joints to feel tight and achy.
  • Hair and skin changes
    • Estrogen is necessary for the formation of collagen—the protein that sustains the structure of your skin. 
    • Lower estrogen levels can cause skin changes such as dry skin, fine wrinkles, and skin becoming thinner and itchy.
    • Because estrogen is essential for hair development, you may find that your hair grows thin and become less lustrous.
  • Depression, anxiety, panic attacks, and irritability
    • Some women discover that their symptoms of depression, anxiety, panic attacks, anger, and irritation worsen to the point where they seriously impair their quality of life. 
    • Emotional health may be affected by these symptoms, which also significantly increase stress levels.
  • Poor memory
    • It is possible to frequently forget words, appointments, birthdays, and even personal things.
    • It can seriously impair the ability to work and function when women notice that their brains do not feel as engaged as they once did.
  • Vaginal dryness and urinary symptoms
    • Atrophic vaginitis refers to changes in the vagina that occur when blood estrogen levels drop noticeably. 
    • Estrogen is crucial for maintaining moisture in the vagina by acting as a natural lubricant. The tissues surrounding the vagina typically become thinner, dryer, and inflamed when estrogen levels are low. 
    • Each woman experiences these changes differently, and they can take months or even years to materialize. 
    • Sexual contact may become more painful or uncomfortable due to dryness in the vagina, and women may experience itchiness down there. Thrush episodes occur more frequently.
    • Low estrogen levels can make the bladder less elastic and thin, leading to frequent urination or recurrent urinary infections such as cystitis.

Menstrual cycles become irregular, and for most women, they cease completely. In terms of fertility and conception, 5 to 10 percent of women may achieve a spontaneous pregnancy because it’s possible to sporadically ovulate with POI. Menopausal symptoms can frequently have a very negative effect on personal and professional lives. 

Symptoms frequently come and go; you may feel completely normal for some months and have unpleasant symptoms for other months that hurt your quality of life. Some women report feeling extremely depressed and even guilty because POI can affect fertility.

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What are the possible causes of primary ovarian insufficiency?

The majority of instances of primary ovarian insufficiency (POI) are idiopathic, which means there is no known reason. Genetic and autoimmune factors are the most common causes. 

However, POI can also result from medical interventions such as chemotherapy, radiation therapy for cancer, or surgical ovarian removal.

Women who have a family history of POI are more vulnerable. In addition to certain lifestyle choices, rare metabolic conditions can result in POI.

Potential causes of and risk factors for POI

  • Autoimmune disease
    • Occurs when the body's immune system attacks its tissues. POI can arise when the ovaries are damaged. It is hypothesized that autoimmune illness causes POI in about five percent of women.
    • POI has been linked to various autoimmune conditions such as hypothyroidism, type I diabetes, and Addison’s disease.
  • Genetic causes
    • POI can be caused by genetic changes in the female sex chromosome (the X chromosome) or other genes that control sex hormones. Turner syndrome is the most frequent of these, in which one of the two X chromosomes is missing. 
    • POI has been linked to other uncommon illnesses that run in families, such as Fragile X syndrome and galactosemia.
    • Ten to twenty percent of girls with POI have an affected family member, such as a mother, sister, aunt, or grandmother.
    • Genetic reasons are more likely in women with a family history of POI, diagnosed with POI at a young age (teens or early twenties), and whose periods never begin.
  • Infection
    • There have been cases of POI appearing after diseases such as mumps, tuberculosis, and malaria; however, these are rare instances.
  • Surgery
    • An additional form of POI is surgical ovarian removal before the age of 40 years. Frequently, the abrupt onset of menopausal symptoms is caused by this sudden removal of ovarian hormones. 
    • For several conditions, such as ovarian cancer, ovarian cysts, endometriosis, or severe premenstrual syndrome, the ovaries must be removed (with or without a hysterectomy). 
    • To help reduce menopausal symptoms, it is hoped that this type of surgery will be planned, giving chance to talk with specialists about the possibility of beginning hormone replacement therapy either right before or very soon after surgery.
  • Cancer treatment
    • In addition to surgery, cancer treatments such as chemotherapy or radiotherapy can harm the ovaries permanently or temporarily, leading to POI. 
    • The likelihood of this depends on the chemotherapy medications used, radiotherapy treatment site, and age at the time of treatment.
  • Toxins
    • Viruses, chemicals, pesticides, and cigarette smoke can hasten ovarian failure.
  • Age
    • Risk increases with age (35 to 40 years). POI can occur in younger women, even in teens, despite being uncommon before the age of 30 years.

Approximately 76 percent of people with POI have normal, regular periods during puberty and adulthood, but this is followed by menstrual disruptions. Sadly, ovarian function varies widely in people with POI.

How to diagnose primary ovarian insufficiency

A thorough history and physical examination are necessary for the evaluation of primary ovarian insufficiency (POI). The doctor may ask for symptoms and comorbidities that could indicate a potential cause. A thorough personal and family history may reveal circumstances connected to POI.

Other causes may be ruled out in women who present with irregular menstrual cycles after ruling out pregnancy as a possibility. Some tests are recommended to confirm the diagnosis, whereas others may be requested to rule out any potential causes.

Hormonal assessment

  • Follicle-stimulating hormone (FSH): Levels higher than 25 mIU/mL measured in two different samples at least four weeks apart in women younger than 40 years confirm POI diagnosis.
  • Prolactin: To rule out other possible causes.
  • Thyroid-stimulating hormone: Assessment of an association with autoimmune thyroid disease.
  • Antimullerian hormone: Serum marker of follicular reserve; highly restricted indication.

Genetic investigation

  • Karyotype: Requested for all women with noniatrogenic POI, especially younger than 30 years.
  • FMR1 gene premutation workup (fragile X syndrome): Indicated for an etiological diagnosis and family genetic counseling.
  • Routine investigation of genetic autosomal abnormalities: Recommended on suspicion of a specific mutation.

Necessary tests

  • Thyroid antibodies: Recommended for women with POI of unknown cause or upon suspicion of autoimmune disease.
  • Adrenal antibodies: Recommended for women with POI of unknown cause or upon suspicion of autoimmune disease.
  • General medical health testing: Testing for diabetes, cholesterol, and other conditions.

Imaging tests

  • Bone densitometry: POI is a significant cause of bone loss and osteoporosis. Initial assessment of bone mass by bone densitometry is recommended. Subsequent tests should be performed depending on these initial results.
  • Pelvic ultrasound: Indicated to rule out other causes.

The most common test is a blood test that measures the amount of a hormone called FSH. This blood test is repeated four to six weeks later to confirm POI. Other blood tests, such as genetic testing, may also be recommended. You may be advised to get a bone density test to check the strength of your bones.

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How to treat primary ovarian insufficiency

There is currently no proven treatment to restore normal ovarian function; however, several treatment options can reduce symptoms and other risk factors linked with primary ovarian insufficiency (POI). 

Five to ten percent of women with POI can successfully conceive without medical help. This is because certain cases with POI maintain some of the ovary's capabilities, which is known as "spontaneous remission." This implies that the ovaries return to normal functioning, and if fertility is restored, women can get pregnant

Premature ovarian insufficiency management

  • Psychological support
    • Immediate concerns for women with POI include psychological discomfort of the diagnosis, especially if the diagnosis was delayed and the woman is nulliparous. 
    • A face-to-face consultation is essential to educate a woman about the diagnosis, and numerous meetings may be necessary to convey information regarding POI. Women should be given educational materials and emotional support. 
    • When faced with the diagnosis of POI and its implications for future generations, parents of younger people may experience significant sadness and loss; hence, counseling and advice for the entire family are essential. 
    • In an optimal situation, there should be access to multidisciplinary care.
  • Hormone replacement therapy (HRT)
    • In the absence of contraindications, women with POI may choose HRT. An increasing number of observational studies reported possible favorable benefits of HRT in women in the prevention of bone loss, as well as a potential reduction in cardiovascular disease and dementia
    • The current strategy is to treat women using HRT that mimics normal physiology until the typical age of natural menopause (50 to 51 years). 
    • HRT is a mix of natural estrogen and synthetic progestin, intrauterine progestin, or natural progesterone. HRT offers physiological estrogen replacement and is not a contraceptive.
    • The combination oral contraceptive pill includes synthetic estrogen and is thus a contraceptive, which may be beneficial for certain women because it is less expensive. Younger women may find being on a medicine indistinguishable from their peers more acceptable. 
  • Androgen replacement
    • Only used to treat sexual dysfunction. Recent guidelines advise against the systematic use of dehydroepiandrosterone for sexual function (or other purposes) in menopausal women due to its low effectiveness and lack of long-term safety data. 

Nonhormonal options

Recommended for women in whom HRT is contraindicated.

  • Selective serotonin reuptake inhibitors
  • Serotonin-norepinephrine reuptake inhibitors
  • Antiepileptics and centrally acting medications

Supplements

Physical activity

  • Physical activity, such as adopting a solid exercise plan to maintain optimal body weight, can help lower the complications of POI.

In vitro fertilization

  • Popular therapy for infertility can assist you in becoming pregnant rather than relying on your menstrual cycle to track dates.

Women must seek complete hormone treatment for POI and receive individualized holistic care, yearly checkups, and assistance for acute concerns, as well as long-term health monitoring. More research and randomized controlled trials will be conducted in the future to define precise HRT regimens (including delivery methods and dosages) and investigate the long-term repercussions for women's health.

What is the life expectancy of people with primary ovarian insufficiency?

Women with primary ovarian insufficiency (POI) have a two-year lower life expectancy than those without POI. The illness can have a negative influence on sex life, mental and cognitive health, fertility, bone health, and cardiovascular health. 

The doctor should discuss with women the consequences of POI, including infertility, decreased bone mineral density, increased fracture risk later in life, poor effect on psychological well-being and quality of life, and potentially harmful effects on cognition. 

If untreated, POI is associated with a lower life expectancy, mostly owing to cardiovascular disease; hence, smoking cessation; regular measurement of blood pressure, diabetic parameters, and lipids, and encouragement of a “cardiac-friendly” lifestyle should be pursued.

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Medically Reviewed on 10/5/2022
References
Image Source: iStock image

Primary Ovarian Insufficiency in Adolescents and Young Women: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/07/primary-ovarian-insufficiency-in-adolescents-and-young-women

What Is Premature Ovarian Failure? https://www.webmd.com/menopause/premature-ovarian-failure

Premature Ovarian Insufficiency - an update on recent advances in understanding and management: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710309/

What is Premature Ovarian Insufficiency (Also Called Premature Ovarian Failure)? https://www.reproductivefacts.org/news-and-publications/patient-fact-sheets-and-booklets/documents/fact-sheets-and-info-booklets/what-is-premature-ovarian-insufficiency-also-called-premature-ovarian-failure/

Primary Ovarian Insufficiency: https://www.endocrine.org/patient-engagement/endocrine-library/primary-ovarian-insuffiency