Early menopause or premature ovarian insufficiency: symptoms, diagnosis and treatment

People often talk about early menopause when they mean premature ovarian insufficiency, but current guidelines prefer the latter term because ovarian function can be intermittent in some cases. It does not always describe a complete and permanent end to ovarian activity: occasional ovulation and even spontaneous pregnancy are possible, although fertility is greatly reduced.

What premature ovarian insufficiency actually is

Premature ovarian insufficiency, also known as POI, is a loss of ovarian function before the age of 40. It usually shows up as irregular or absent menstrual cycles and is confirmed by blood tests showing ovarian insufficiency. International guidelines have been moving away from the term premature ovarian failure because it can suggest a completely irreversible situation, and that is not always the case.

Biologically, it is linked to follicle depletion or to dysfunction of the ovarian follicles, which is associated with lower oestradiol and raised FSH. If you want to place this problem within the wider picture of hormonal change, it may help to read what perimenopause is and how long it lasts, although POI is a distinct condition because of the age at which it appears and the way it is managed.

Is it common?

For years a prevalence of around 1% was the accepted figure, but more recent studies suggest it may be more common than was thought. A global meta-analysis of 31 studies estimated a prevalence of 3.7%, with a 95% confidence interval of 3.1% to 4.3%.

Symptoms that may raise suspicion

The symptoms supported by the guidelines include amenorrhoea or oligomenorrhoea, hot flushes and night sweats, vaginal dryness and other genitourinary symptoms, as well as difficulty conceiving. Not every woman experiences it in the same way: some seek help because their periods have stopped or become irregular, and others because of symptoms closer to those of a typical menopause.

Beyond the immediate symptoms, POI has an impact on bone, cardiovascular, sexual and psychological health and on quality of life. The 2024 international guideline stresses that the diagnosis can have a significant psychological impact and recommends assessing mental health too, not just blood results.

When vaginal dryness or painful sex are the main issues, it is worth understanding that this is neither a minor detail nor unusual: vaginal dryness and painful sex in menopause have a hormonal basis and affect quality of life.

Why it happens

The 2024 international guideline distinguishes between non-iatrogenic and iatrogenic causes, and stresses that in many cases no exact cause is identified. Recognised associations include genetic or chromosomal abnormalities, including the FMR1 premutation.

Iatrogenic causes include chemotherapy, radiotherapy, ovarian surgery or bilateral salpingo-oophorectomy before the age of 40. If the cause is unknown, the guidelines recommend investigating the cause, including screening for adrenal autoimmunity, and considering genetic testing with appropriate genetic counselling. In POI of unexplained cause, testing for 21-hydroxylase antibodies is also recommended.

How it is properly diagnosed

The NICE guideline bases the diagnosis on compatible symptoms, above all absent or infrequent periods, and on raised FSH in 2 blood tests taken 4–6 weeks apart, and asks that POI not be diagnosed on the basis of a single blood test. The 2024 international guideline simplified that criterion: with compatible symptoms, a single raised FSH above 25 IU/l is enough, and repeating the FSH or measuring AMH is reserved for cases where the diagnosis is in doubt.

Pregnancy must also be ruled out if periods have stopped. And there is an important practical point: hormonal contraceptives or other hormonal therapies can mask amenorrhoea or alter FSH, so they sometimes have to be stopped in order to confirm the diagnosis.

AMH should not be used as the main routine diagnostic test. It can form part of the clinical picture, but a low AMH on its own is not enough to make the diagnosis.

Treatment: what the guidelines recommend

Hormone therapy or combined hormonal contraception should be offered to women with POI unless there is a contraindication. The 2024 international guideline recommends hormone therapy until the usual age of menopause to reduce illness and mortality, even when there are no clear vasomotor symptoms. It also notes that hormone therapy improves the symptoms of oestrogen deficiency.

The guidelines link not using hormone therapy with a higher risk of cardiovascular events and mortality, and also recommend this treatment to reduce the possible risk of cognitive decline or dementia. NICE also notes that both hormone therapy and combined contraceptives protect the bones.

If the womb is still present, a progestogen must be added to the oestrogen to prevent endometrial hyperplasia or cancer. For genitourinary symptoms, the guideline recommends vaginal oestrogen; lubricants and moisturisers can also be used. If you need a broader view of the treatment framework, you can read what menopausal hormone therapy is, who it is for and what its real risks are and what modern hormone therapy with oestradiol and micronised progesterone looks like.

That said, the evidence comparing specific regimens with one another in POI is limited. The 2022 Cochrane review, which focused on the development of the womb and endometrium, found only 3 studies involving 52 women and concluded that, with very low-certainty evidence, no clear conclusions can be drawn about which hormone regimen is best.

Which options are available in Spain

In Spain, AEMPS/CIMA lists oestradiol formulations such as Estradot, Estraderm Matrix, Oestraclin, Divigel, Meriestra and Progynova. It also lists oral micronised progesterone such as Progeffik and Lugesteron, and vaginal progesterone such as Utrogestan. Mirena is authorised in Spain.

If there is migraine with aura, the guideline advises preferring transdermal oestrogen. In women with a history of breast cancer, hormone therapy is generally not recommended. At the same time, in young women with POI, the available evidence does not show that hormone therapy increases the risk of breast cancer compared with women of the same age without POI.

Another important point is that hormone replacement therapy is not a contraceptive. And in women with intermittent ovarian function who want to conceive naturally, the recommendations on hormone therapy do not change, and it does not appear to affect the chances of natural conception.

Fertility: what is known and what is not

POI greatly reduces the likelihood of natural conception, but it does not mean permanent infertility. Intermittent follicular activity may persist, with occasional ovulation and the possibility of spontaneous pregnancy.

At the same time, the guidelines are clear on another point: no interventions have been reliably shown to increase ovarian activity or natural conception. This is especially relevant given the messages that promise to reactivate the ovary without a solid basis.

Testosterone and “bioidentical” preparations: two common questions

In CIMA, the testosterone products on record are indicated for male hypogonadism and are contraindicated in women or should not be used by them. The 2024 guideline only considers testosterone for hypoactive sexual desire disorder in selected cases and notes the lack of long-term safety data.

Compounded bioidentical preparations are not recommended because of the lack of data on efficacy and safety. If you want to separate evidence from marketing in this area, you may find it useful to read which menopause pills really exist and which require a prescription.

What to take away

The key idea is this: premature ovarian insufficiency is not confirmed with a single blood test and does not always mean a total, permanent loss of ovarian function, but it does deserve a rigorous diagnosis and medical care because it affects far more than your periods. In Spain today there are medical treatment options with a prior assessment, a prescription where appropriate from a registered doctor and ongoing follow-up. If you would like to find out whether menopause treatment suits your case, you can check in a few minutes whether you are eligible.