The most common endocrine pathology in women of childbearing age, polycystic ovary syndrome, or PCOS, however, is not always easy to diagnose. Its involvement in infertility is frequent but not systematic.

Polycystic ovary syndrome is an endocrine pathology. It is also called Stein-Leventhal syndrome after the name of the two doctors who first described it in 1935.

Its name refers to one aspect of this syndrome visible on ultrasound, namely the accumulation around the ovaries of multiple small cysts. These cysts are actually follicles that refuse to grow during the last stage of the follicular phase. This aspect is however only one facet of PCOS, a syndrome which can manifest itself differently according to the women in more or less complete forms, with multiple repercussions on the female health.

In its full form, PCOS causes an absence of ovulation and therefore an inability to get pregnant. 50% of women affected by PCOS have primary infertility, and 25% secondary infertility (1). PCOS is therefore responsible for more than 70% of infertility caused by anovulation (2). Infertility is therefore frequent, but not systematic.

We do not yet fully understand the pathophysiological mechanisms at the origin of PCOS and they can certainly not be explained by a single cause, but by a succession of causes that act in a vicious circle (3). Basically, there is hyperandrogenism, that is to say an excessive secretion of androgens, and resistance to insulin. Both are presumably of genetic origin.

PCOS is the most common endocrine pathology in women of childbearing age, with 5% to 10% of women affected (4).

PCOS affects the ovaries but since it is an endocrine disease, it has an impact on the entire hormonal balance and can cause various complications at the metabolic, cardiovascular, reproductive and also general levels. We also speak of systemic affection. Among the possible complications we note:

• subfertility;
• in pregnancy, an increased risk of miscarriage, premature labor, gestational diabetes and pre-eclampsia. This risk is all the more increased in the event of overweight;
• glucose intolerance and type 2 diabetes;
• lipid abnormalities (hypertriglyceridemia, hypercholesterolemia);
• high blood pressure;
• depression ;
• sleep apnea syndrome;
• cardiovascular diseases (macroangiopathy, thrombophilia);
• certain female cancers (endometrium, breast, ovary according to some studies, but other risk factors such as obesity must be taken into account).

PCOS can manifest itself through different clinical signs, with different tables and degrees depending on the woman:

Gynecological signs:

• irregular (spaniomenorrhea), infrequent (oligomenorrhea) or absent (amenorrhea) periods
• excessive bleeding during menstruation (menorrhagia);
• an increase in the size of the ovaries with the formation of many small cysts inside;
• difficulty conceiving.

Skin disorders, consequences of androgyny:

• hirsutism (hairiness on areas normally hairless in women: face, neck, etc.). This sign is found in 70% of women with PCOS (5)
• an acne;
• alopecia (hair loss)

Or signs of insulin resistance:

• un Nigerian acanthosis (browning and thickening of the skin in the area of ​​the neck, groin, armpits and skin folds)

Metabolic signs:

• weight gain or obesity;
• an increase in the level of sugar in the blood;

The hereditary factor is to date the only suspected risk factor.

The clinical heterogeneity of PCOS sometimes makes its diagnosis difficult.

In 2003, the first diagnostic criteria for PCOS were established. These are the Rotterdam criteria (6). In 2013, the American Society of Endocrinology established new guidelines for the diagnosis of PCOS (7), adopted in 2014 by the European Society of Endocrinology. Today, the diagnosis of PCOS is made in the presence of at least 2 of the Rotterdam criteria, namely:

• clinical (hirsutism, acne, androgenic alopecia) or biological hyperandrogenism;
• oligo-anovulation (irregular or absent ovulation). According to the Rotterdam criteria, cycles shorter than 21 days or longer than 35 days are considered anovulatory;
• on endovaginal ultrasound, the presence of at least one ovary with more than 12 follicles of 2 to 9 mm and diameter and / or an ovarian volume greater than 10 ml without the presence of cyst or dominant follicle.

To establish this diagnosis, in addition to questioning the medical and gynecological history, various examinations are carried out:

• cycle analysis;
• a clinical examination;
• an endovaginal ultrasound of the ovaries (2D or 3D);
• hormonal assays (testosterone, delta 4 androstenedione, LH, FSH, estradiol, 17 hydroxyprogesterone, glycemic balance and HCG).

Before making the diagnosis of PCOS, it is important to rule out other pathologies: congenital adrenal hyperplasia, hyperprolactinemia, a thyroid disorder.

There is no cure for PCOS. The management is therefore based on the treatment of the manifestations of the syndrome and the prevention of complications, in particular cardiovascular:

• against hyperandrogenism and the various manifestations that result from it (menstruation disorders, acne, hirsutism), estrogen-progestogen contraception is the first-line treatment (in case of unwanted pregnancy). Progesterone inhibits the secretion of LH (luteinizing hormone) and thereby the production of ovarian androgens, while estrogen will increase SHGB (sex hormone binding globulin), a sex hormone binding protein, with the effect of a decrease in the level of bioavailable androgens;
• in overweight or obese women, weight loss is recommended to limit metabolic complications. This weight loss may also be sufficient to restore ovulation in some patients;
• against infertility, clomiphene citrate is the first-line treatment for ovulation disorders induced by PCOS. This ovulation inducer is an anti-estrogen: it blocks estrogen receptors in the hypothalamus, which causes an increase in the level of GnRH then FSH and facilitates the maturation of the follicles. Induction of ovulation with clomiphene citrate leads to pregnancy in 35 to 40% of patients (8). Other treatments can be considered in case of failure of hormonal stimulation (after generally 6 test cycles):
  • other hormonal stimulation treatments: a combination of metformin and clomiphene citrate, gonadotropins, or aromatase inhibitors, such as Letrozole. The latter seems promising (9);
  • ovarian drilling: this surgical technique consists of performing laparoscopy a “multiperforation” of the ovary in order to restore its proper functioning;
  • in vitro fertilization sometimes preceded by in vitro maturation of oocytes (IVM) (oocytes are collected before ovulation, at a late stage of follicular maturation, and finish their maturation in vitro).
• against insulin resistance, different treatments are being studied. Treatment with metformin is recommended in patients with diabetes or pre-diabetes, after failure of lifestyle and dietary measures (10).

It is not possible to prevent PCOS, however lifestyle and dietary measures to combat overweight are essential to prevent complications.