Polycystic ovary syndrome (PCOS) is an infertility leading cause. In fact, it is the most common hormonal disease in women of childbearing age. It can cause fertility and hair disorders (hirsutism), as well as metabolic complications (diabetes). Up to date, there is no specific treatment. But ongoing research could be a game-changer by improving the current imperfect understanding of the mechanisms behind this disease.
What is polycystic ovary syndrome?
As a matter of fact, polycystic ovary syndrome is due to a hormonal imbalance of ovarian and/or central origin (in the brain). It causes excessive production of androgens, especially testosterone, usually produced in small quantities in the female body. This results in an increase in testosterone levels in the blood of the women concerned.
The name of this disease comes from its description made in the 1930s. That is, it's based on the observation of what were thought to be cysts in the ovaries of patients. In reality, it was multitudes of undeveloped follicles.
Polycystic ovary syndrome causes:
The causes of these disorders are most likely multifactorial:
- Genetic: About twenty genes predisposing to the syndrome are responsible, but they would explain less than 10% of PCOS cases.
- Epigenetic: Family history nevertheless exposes you to a higher risk of about 30% of developing the disease.
- Environmental: Environmental factors such as endocrine disruptors are also suspected to play a role in causing the disease, with no established evidence to date.
Polycystic ovarian syndrome (PCOS) vs Polycystic ovary (PCO):
Women often has a major misconception of the two terms, PCOS and PCO. Actually, PCO describes an ultrasound image of ovaries with polycystic appearance. In other words, the ovaries tend to have a great number of partially mature ovaries. On the other hand, PCOS is a metabolic disorder that had no genetic link to the presence or absence of polycystic ovaries.
Symptoms of polycystic ovary syndrome:
Indeed, irregular cycles, hyperpilosity and metabolic disorders are the major symptoms. PCOS affects about 10% of women, but its symptoms vary greatly from one patient to another. In other words, the disease can manifest itself very mildly, as well as being very disabling.
The symptoms are as follows:
Ovulation disorder: the scarcity or absence of ovulation (dysovulation or anovulation) results in irregular cycles, longer than 35 to 40 days, or even in the total absence of periods (amenorrhea). These disorders cause infertility in about half of women with polycystic ovary syndrome.
Hyperandrogenism: excessive testosterone production results in hyperpilosity in 70% of women with PCOS, acne and hair loss (alopecia).
Metabolic syndrome: excessive adiposity due to hyperandrogenism adds up the risk to insulin resistance and diabetes. Patients also have a higher risk of high blood pressure and cardiovascular disease.
Notably, the clinical picture worsens in the event of weight gain. Besides, there is a correlation between the body mass index and the infertility resulting from this disease.
The presentation of at least two of these three symptoms, in the absence of another disease-causing androgen secretion (such as genetic adrenal disease or ovarian or adrenal tumors), leads to a diagnosis of PCOS.
How to diagnose polycystic ovary syndrome?
At the beginning of the menstrual cycle, each ovary normally contains 5 to 10 small follicles of about 5 mm. Only one of them will become a fertilizable oocyte. In PCOS, there's a blockage of follicular maturation by excess androgens and immature follicles accumulate, with no dominant follicle.
A pelvic ultrasound therefore shows many small follicles (at least 20 follicles with a diameter of less than 9 mm) and/or a large ovarian volume (greater than 10 ml). In addition, there's neither a cyst nor a dominant follicle.
Nevertheless, this observation is not sufficient for the diagnosis of PCOS because women of childbearing age are concerned without presenting the other symptoms of the pathology.
A biological assessment is therefore also carried out, between the 2nd and 5th day of the cycle. In patients who do not menstruate, these are induced by progesterone therapy given for 10 days.
This assessment includes the dosage of FSH and LH, two hormones produced by the pituitary gland. The pituitary gland is located at the base of the brain, its hormones control ovarian hormonal production and the ovarian cycle.
Several other molecules are also measured: prolactin, testosterone, delta 4 androstenedione, SDHA, 17 beta-estradiol, 17 hydroxy progesterone, TSH, and sometimes blood sugar and insulin.
In case of PCOS, the results show:
- An inversion of the FSH/LH ratio
- An increase in androgens
- A tendency to diabetes and hyperinsulinemia
Treatment of polycystic ovary syndrome:
The treatment of PCOS is only symptomatic and lasts until menopause.
It is based on an improvement in lifestyle, drug treatment in the event of hirsutism and/or infertility, and psychological support when necessary.
In case of overweight, a loss of about 10% of the initial weight reduces hyperandrogenism and shows a beneficial effect on amenorrhea, with a potential benefit on fertility. In the longer term, this weight loss will have a positive impact on the risk of metabolic complications which results from PCOS. On the other hand, for women whose weight is normal, losing weight does not bring any benefit.
In case of hirsutism, an estrogen-progestogen pill is necessary as first-line treatment. Its progestogen component inhibits the secretion of LH and reduces the production of ovarian androgens. The estrogenic component decreases the level of circulating androgens. If the estrogen-progestogen pill fails, anti-androgen (cyproterone acetate) combined with a natural estrogen is an alternative. Cyproterone acetate is effective in three months on acne and in six months on hirsutism.
As for metabolic abnormalities, they are treated by first-line dietary and lifestyle measures, then by oral antidiabetic drugs if necessary.
When PCOS is the only factor responsible for infertility, treatment is based on stimulation of ovulation by clomiphene citrate, or by injectable exogenous gonadotropins as a second intention. Aromatase inhibitors, used for the treatment of certain breast cancers, are currently being evaluated as ovulation inducers and may be more effective than clomiphene. If these treatments lead to ovarian hyperstimulation that is difficult to control or in the absence of pregnancy, consider medically assisted procreation.
Complications:
When hyperandrogenism is there, it often manifests itself from puberty by severe acne, hyperpilosity, and irregular menstruation too often blamed on adolescence.
If the hyperandrogenism is moderate, the diagnosis is often later, around 25–30 years old, when the patient consults for infertility.
The hypersecretion of androgens by the ovary promotes the development of:
- Adiposity which leads to insulin resistance
- Metabolic syndrome (overweight, dyslipidemia, arterial hypertension, blood sugar disorder)
- Diabetes
- Cardiovascular disease (myocardial infarction, stroke, etc.)
- Endometritis
- Endometrial cancer.
References:
-Legro RS. Evaluation and Treatment of Polycystic Ovary Syndrome. [Updated 2017 Jan 11]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. available from: https://www.ncbi.nlm.nih.gov/books/NBK278959/#_NBK278959_pubdet_
-Rasquin Leon LI, Anastasopoulou C, Mayrin JV. Polycystic Ovarian Disease. [Updated 2021 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. available from: https://www.ncbi.nlm.nih.gov/books/NBK459251/#_NBK459251_pubdet_
-Wang S, Zhao H, Li F, Xu Y, Bao H, Zhao D. Higher Chronic Endometritis Incidences within Infertile Polycystic Ovary Syndrome Clinical Cases. J Healthc Eng. 2022;2022:9748041. Published 2022 Apr 11. doi:10.1155/2022/9748041
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