By causing ovulation to stop before the age of 40, early menopause, or premature ovarian failure (PID), can affect female fertility. How to explain the appearance of this sydrome? What are the possible treatment options? Some elements of explanation.

The term menopause describes the cessation of ovarian function. If it occurs on average at age 51, menopause is said to be early if it appears before age 45. In some women (1,9%), stopping ovulation can occur before age 40, sometimes much earlier. This is called premature ovarian failure (POI).

The first sign of premature ovarian failure is disruption of menstrual cycles, which can be variable according to the women.

• For some, the diagnosis is made after the onset of secondary amenorrhea (an absence of periods for more than 3 months in a woman who has already had her period). In the absence of resumption of ovulation, this amenorrhea may become permanent. However, resumption of ovarian activity remains possible in about one in two women, with a return of menstruation sometimes several years after diagnosis. In fact, estrogen production, natural ovulation and pregnancy are likely in 5 to 10% of them.
• For others, periods vary in frequency and intensity (oligomenorrhea).

Other symptoms, due to estrogen deficiency and similar to those experienced by women whose menopause is later, may appear. The manifestations of this climacteric syndrome:

• vasomotor disorders (hot flashes, excessive sweating, palpitations, etc.)
• insomnia,
• mood disorders (irritability, etc.)
• vaginal dryness,
• urinary disorders: urination burns, urgency (urgent desire for which we can not help ourselves),
• a decrease in desire and sexual disorders,
• a weight change,
• more rarely, depression, even disturbances in attention and memory.

In the vast majority of cases, the origins of premature ovarian failure are not found. However, certain family history, pathologies and iatrogenic causes (linked to medical treatment) are systematically sought by the practitioner, namely:

• an autoimmune disease (hypothyroidism, hypoparathyroidism, celiac disease, type 1 diabetes, rheumatoid arthritis, Graves’ or Addison’s disease),
• a history of chemotherapy, radiotherapy or ovarian surgery,
• a family history of PID,
• a family history suggesting premutations of the FMR1 gene (FRAXA region of the X chromosome associated with Fragile X Syndrome in particular.

The most significant effect of early menopause in women of childbearing age is usually infertility. However, in the longer term, IOP has other repercussions on health. Thus, it can promote bone fragility and fractures due to osteoporosis, as well as cardiovascular disease. In addition, about 3% of women with POI are likely to develop autoimmune adrenal insufficiency, which, if not detected, can be serious.

How is the diagnosis of early menopause made?

 Faced with a suspicion of PID, several examinations are carried out as a first-line treatment, namely:

• a pregnancy test,
• serologies to assess the level of prolactin, FSH and estradiol.

 Once the premature ovarian failure has been confirmed, the practitioner can recommend the following:

• a karyotype to identify possible abnormalities in the number or structure of the X chromosome (Turner syndrome, triple X, X deletion, ring X chromosome, etc.),
• a search for premutations of the FMR1 gene to detect ovarian failure linked to a premutation of the FRAXA region.

In the event of premature menopause, several treatments can be considered, in particular in the event of desire for a child.

Treatment of infertility

Even if spontaneous pregnancies are possible, they are very rare as the ovulation capacity of women with OIP is reduced. Moreover, this is the main problem with which infertility specialists are confronted: there is no treatment whose effectiveness has been proven to restore ovulation in the event of early menopause. However, two avenues of therapy can be explored depending on the patient profile:

• a protocol based on gonadotropins combined with estrogen, which appears to significantly improve ovulation rate.
• IVF with egg donation.

Treatment of hormonal deficiency 

Beyond infertility, it is essential in the face of early menopause to prevent the effects of estrogen deficiency. A hormonal treatment mimicking ovulation with estradiol (oral or cutaneous) and progesterone is then recommended during the first 12 days of the month.