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Ovarian failure: causes, symptoms, treatments

1 to 2% of women under 40 are affected by premature ovarian failure (PDI). Sometimes called, erroneously, “early menopause”, this IOP actually covers multiple situations.

Definition of ovarian failure

Ovarian failure is an inevitable physiological process in women. This is called menopause, which occurs on average at age 51. This menopause is called early when it occurs before age 40. There is also talk of early ovarian failure (IOP).

Early ovarian failure is clinically defined as amenorrhea (absence of menses) more than four months before the age of 40, associated with high FSH levels in at least two samples taken within a few weeks of each other.

Early ovarian failure leads to infertility because without ovulation, there is no fertilization possible. However, some women with PDI may intermittently have eostrogen production and ovulate, and in 5 to 10% of cases, have a baby.

The causes of Ovarian failure

As a reminder, in the girl, the stock of ovarian follicles is constituted in utero. Thus at birth, each ovary contains a “pool” of 1 to 2 million ovarian follicles. From puberty to menopause, at each cycle, a small portion of this stock matures during the follicular phase. A dominant follicle matures and ovulates, while other follicles die. At the same time, there is a normal phenomenon of apoptosis, or “programmed death,” of a certain part of the follicle pool. This phenomenon accelerates after 37 years and menopause occurs when the number of follicles is less than 1000.

During this physiological process, three different mechanisms may cause early ovarian failure:

  • an abnormality of follicular stock formation in utero;
  • a block of follicular maturation (there is a stock of follicles but they are not maturing);
  • abnormally fast depletion of the follicular stock.

Different causes can be at the origin of these mechanisms:

  • iatrogenic causes. Treatment with radiotherapy and / or chemotherapy can accelerate the process of apoptosis and lead to early depletion of the ovarian reserve;
  • a genetic anomaly, the most common being Turner’s syndrome which is characterized by the absence of one of the X chromosomes. But many other abnormalities located on the autosomes (ie all the genes other than the sex chromosomes) or on the X chromosome can lead to an IOP. To date, various genetic mutations have been identified and research is continuing;
  • autoimmune causes, that is, an abnormal response of the immune system that turns against the body. IOP is also often associated with other autoimmune endocrine pathologies such as Graves’ disease, type 1 diabetes or APS (Autoimmune Polyendocrinopathy Syndrome);
  • viral causes. Here again, research must continue on this possible viral track.

But in more than 80% of cases, the IOP remains idiopathic: its cause remains unknown .

Prevalence

The prevalence of the IOP is estimated at:

  • 1/10 000 for women under 20;
  • 1/1000 for women under 30;
  • 1% among women under 40.

Evolution and possible complications

The main complications of ovarian failure are twofold:

  • complications related to hypoestrogenesis: increased risk of cardiovascular disease, osteoporosis, etc .;
  • infertility.

It is also known that young women with PDI have an increased risk of developing autoimmune adrenal insufficiency.

Symptoms of early ovarian failure

Depending on its cause (and especially the fact that it is present or not at birth), ovarian failure can manifest itself by various symptoms:

  • an absence of puberty and primary amenorrhea (the girl never had her period). This is generally the case for IOPs linked to a genetic anomaly;
  • A secondary amenorrhea: the woman had her period normally, but these stop, sometimes abruptly. This amenorrhea may also occur after stopping an oral contraceptive or after pregnancy;
  • sometimes the rules are still present, but irregular, especially in cases of early ovarian failure. There is also talk of occult ovarian failure;
  • various symptoms, related to the estrogen deficiency, can accompany the stopping of the rules: flushing, insomnia, fatigue, disorders of the mood.

Difficulties to conceive can also be a motive for consaltation.

Risk factors for early ovarian failure

The family history of IOP is the main risk factor. About 10% of the cases of IOP are indeed family. The family history of certain genetic abnormalities (premutations of the FMR1 gene in particular) is also risk factors.

Diagnostic of Ovarian failure

The diagnosis of IOP is made in the presence of these two elements:

  • amenorrhea of ​​at least four months;
  • two doses of FSH at one month intervals with results greater than 20 IU / L.

Ultrasound is not a determining factor in the diagnosis of IOP. Ovarian biopsy is useless.

Once the diagnosis is made, we will try to find the cause of the IOP with different elements: interrogation on the personal and family medical history, clinical examination, karyotype, etc.

Treatment of Ovarian failure

The processing of the IOP is based on two axes:

  • treat symptoms and limit the risk of cardiovascular and bone complications due to estrogen deficiency, with hormone replacement therapy;
  • manage infertility if the patient wants to have a baby. Currently, there is no treatment to restore ovulation in women with PDI. IVF with oocyte donation is therefore the only possible AMP treatment.

Prevention

With the exception of sampling and egg freezing prior to anti-cancer treatment in young women, no prevention exists against IOP. It is also impossible to predict the occurrence of an IOP because there is no predictive marker of its occurrence. However, it is important to consult when previously irregular cycles become irregular, in order to detect early ovarian failure as early as possible.

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