What is POI (Premature Ovarian Insufficiency)?

Definition:

POI is a clinical condition where ovarian function ceases before the age of 40 years, characterized by menstrual irregularities (such as amenorrhoea or oligomenorrhoea) alongside biochemical confirmation of ovarian insufficiency (elevated FSH and low estrogen levels).

Terminology:

Other terms historically used include primary ovarian insufficiency, premature ovarian failure, premature menopause, and hypergonadotropic hypogonadism, but POI is now the recommended and preferred term.

Prevalence:

POI affects approximately 4% of women under the age of 40.

What is “Early Menopause”?

When ovarian insufficiency occurs in women aged 40–44 years, this is referred to as early menopause, reflecting its proximity to—but distinction from—POI.

Causes of POI:

1. Idiopathic

In many cases (potentially up to around two-thirds), the root cause remains unknown.

2. Genetic/Chromosomal

POI can be caused when there's a change (a "mutation") in a person's DNA.

Examples include Turner syndrome, Fragile X pre-mutation, and rare gene mutations (e.g., FOXL2, NOBOX).

For instance, women with an FMR1 premutation have about a 20% risk of developing Fragile X associated POI (FXPOI).

3. Autoimmune Processes

Autoimmune diseases are health conditions that happen when your immune system attacks your body instead of defending it.

Autoantibodies (commonly thyroid, sometimes adrenal) may be present in some women with POI, suggesting an autoimmunity-mediated mechanism in some women.

4. Iatrogenic

Medical treatments like chemotherapy, radiotherapy, or ovarian surgery—for cancer or benign conditions—can damage the ovaries and lead to POI.

5. Environmental, Infectious, Metabolic

Exposures to toxins (e.g., phthalates, bisphenols), metabolic disorders, or infections (e.g., mumps, HIV) have also been linked.

Symptoms of POI:

• Menstrual changes: Irregular or absent periods.

• Hormonal profile: Elevated FSH (in the postmenopausal range) and low estrogen (hypoestrogenism).

Menopausal-like symptoms:

o Hot flashes, night sweats, vaginal dryness, dry skin

o Decreased libido, mood disturbances (anxiety, depression), brain fog, irritability.

Psychological and emotional impact:

o Feelings of shock, devastation, confusion, grief over fertility loss, lowered self-esteem, and stigmas associated with infertility.

Long-term health consequences:

o Increased risk of osteoporosis and reduced bone density

o Cardio metabolic risks

o Autoimmune vulnerability

o Neurological and psychological effects.

Diagnostic Criteria (ESHRE-based)

1) Still menstruating irregularly or amenorrhoeic before age 40

2) At least two concurrent measurements (typically ≥4 weeks apart) showing:

o Elevated FSH

o Low estrogen levelsThis confirms ovarian insufficiency.

Summary:

• POI is a clinically and biologically distinct condition from natural menopause, defined by menstrual irregularity plus elevated FSH and low estrogen before age 40.

• If the pattern emerges between 40–44 years, it's termed early menopause.

• Etiologies are broad: genetic, autoimmune, iatrogenic—but often unknown despite evaluation.

• Symptoms reflect hormonal deficiency and carry profound emotional and long-term health implications, highlighting the need for holistic management and support.