Premature ovarian failure (POF) or primary ovarian insufficiency is a suspected condition when menstrual cycle irregularities are very frequent, prolonged or simply disappear long before the age of 40.
The frequency of premature ovarian failure is very low (1% of women suffer from it), and it is even less frequent when it occurs before the age of 30 (one in a thousand women). Only in 10% of cases can the exact cause of this condition be found, but it is worth carrying out the necessary studies in order to be able to prescribe a specific treatment.
It is common for a woman’s menstrual cycles to become more irregular at a certain age, around 40, and may even disappear from one month to the next, until they finally cease completely and a new stage called menopause begins. In the case of premature ovarian failure, this irregular ovulation may begin several years earlier.
Causes of premature ovarian failure (POF)
The cause of early ovarian failure is related to problems in the follicles, which are small sacs where your eggs grow and mature. When the follicles stop functioning earlier than normal or for some external reason do not function properly, you may have developed this condition.
In most cases (90%), the cause of the follicle problem is not known (this is called an idiopathic cause), meaning simply that the number of ovarian follicles a woman has at birth is insufficient. But when it can be identified, the most frequent causes are:
- Turner syndrome (45X or mosaic 45X/46X or 45X/47XXX)
- Fragile X syndrome (caused by a premutation in the FMR1 gene)
These disorders are usually evident by the age of 35 and increase the risk of germ cell ovarian cancer.
In this case, the follicles are observed to be dysfunctional, due to the existence of antibodies that act against the ovarian cells. The most frequently associated autoimmune diseases are:
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Diseases of the adrenal glands with a high risk of potentially life-threatening primary adrenal insufficiency (Addison’s disease).
Surgical, radio and chemotherapy treatments
It can occur in women who for some reason suffer damage to their ovaries, either during aggressive surgery for endometriosis or ovarian cysts.
But chemotherapy or radiotherapy can also cause accelerated follicular atresia (resorption of the ovarian follicles before they reach maturity).
External toxic agents
Finally, perhaps not as common, one of the possible causes associated with premature ovarian failure is related to toxic or environmental agents such as tobacco, pesticides, solvents, etc.
What is the difference between premature ovarian failure and early menopause?
The signs and symptoms of premature ovarian failure are very similar to those that occur at the onset of menopause, which is why they are often confused. The main difference is that premature ovarian failure is a pathology, and is not due to the early onset of a natural physiological process.
Symptoms and diagnosis of premature ovarian failure
One of the main and most striking symptoms of premature ovarian failure is the absence of menstruation (amenorrhea) in women under the age of 40, although we can also find cycles that are significantly shortened.
In addition, the presence of hot flushes, vaginal dryness, or sleep disorders, which are symptoms that can appear due to a lack of oestrogen, are evaluated.
In order to establish whether there is a cause, diagnostic studies and the following tests will be carried out:
- Serum FSH and oestradiol levels. Serum FSH and oestradiol levels are assessed weekly for 2-4 weeks. If FSH levels are high (> 20 mIU/mL, but usually > 30 mIU/mL) and oestradiol levels are low (usually < 20 pg/mL), ovarian failure is confirmed.
- Anti-Müllerian hormone. Blood levels of this hormone have been used to try to diagnose diminished ovarian reserve. Normal levels range from 1.5 to 4.0 ng/mL. A very low level suggests diminished ovarian reserve.
Testing for FMR1 premutation is recommended when there is a family history of primary ovarian insufficiency or when there is intellectual disability, tremor or ataxia.
Tests for autoimmune diseases
If the genetic tests have been negative or if an autoimmune cause is suspected, tests for serum adrenal gland and 21- hydroxylase antibodies (adrenal autoantibodies) are conducted to determine whether primary adrenal insufficiency (Addison’s disease) is present.
A morning cortisol level measurement or an adrenocorticotropic hormone (ACTH) stimulation test is likely to be added to the previous test to confirm the diagnosis.
Testing for autoimmune hypothyroidism is also recommended, including measuring thyroid-stimulating hormone (TSH), thyroxine (T4), and anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies.
Other tests can be done to establish whether autoimmune dysfunction is present, including a complete blood count with differential, erythrocyte sedimentation rate, and measurement of antinuclear antibodies and a rheumatoid factor test.
Can you get pregnant with premature ovarian failure?
A woman with premature ovarian failure does not always fail to menstruate and her ovaries do not always stop functioning completely.
Therefore, a diagnosis of primary ovarian insufficiency or premature ovarian failure does not mean that pregnancy is impossible, nor does it imply that a woman is ageing prematurely; it only means that her ovaries, at a young age, for some reason, are not functioning normally.
About 5-10% of women with primary ovarian insufficiency eventually become pregnant spontaneously, without fertility treatments. In all other cases, we recommend that you consult a specialist in assisted reproduction.
Treatments for premature ovarian failure
Young women who have primary ovarian insufficiency and do not want to get pregnant can be treated with oral contraceptives (cyclic or extended cycle). Another option is cyclic combined hormone therapy, but this is recommended until around the age of 51 (the average age of menopause). In any case, before recommending hormones, the doctor will assess whether or not there are contraindications.
This therapy relieves the symptoms of oestrogen deficiency, helps maintain bone density and may help prevent coronary heart disease, Parkinson’s disease, mood swings (including depression), atrophic vaginitis and dementia.
Once women reach the average age of menopause, whether to continue hormone therapy depends on a woman’s individual circumstances.
In vitro fertilisation
For women who wish to become pregnant, one option is In Vitro Fertilisation (IVF) using donor oocytes, with the recipient’s endometrium prepared by using exogenous oestrogens and progestogens, a treatment known as egg donation, which allows the endometrium to support the transferred embryo.
Thanks to technical advances, there are other options such as: cryopreservation of ovarian tissue, oocytes or embryos and embryo donation. These techniques can be used before or during ovarian failure, especially in cancer patients who know they will receive aggressive treatment that could affect their fertility.
If you think you need a consultation or have any doubts, you can make an appointment at Eugin so that we can help you. The first medical consultation with a specialist in assisted reproduction is free of charge, and we carry out a medical diagnosis and provide personalised advice, as well as an assessment of the medical tests provided and a vaginal ultrasound (if necessary).