Ovulation is a period of a woman’s monthly cycle when a mature egg is released into the fallopian tubes. Her encounter with a sperm in the next 24 hours, in which she is fit for fertilization, is absolutely necessary for pregnancy to occur. In some cases, the monthly cycle can be anovulatory – ie. no ovulation. Every woman in her reproductive period has had at least one anovulatory cycle. The reasons can be many and most often they are due to a dyscoordination along the axis hypothalamus-pituitary-ovaries. Usually, the first few monthly cycles after the onset of the first menstruation (menarche) are anovulatory, due to immaturity of the sexual axis and failure to achieve adequate regulation of the processes. Perimenopausally, anovulatory cycles are also more common, due to fluctuations in estrogen levels. However, a number of conditions can lead to chronic anovulation and in this article we will focus on the causes of this. There is no precise definition of when chronic anovulation is present, but it should be considered in women with irregular menstrual cycles and/or amenorrhea. The most important consequence of anovulation is infertility. How does a normal ovulatory cycle work? Normally, the normal monthly cycle is a succession of follicular phase, ovulation and luteal phase. Monthly menstrual bleeding is the result of shedding of the uterine lining that has been prepared to receive the fertilized egg. Physiologically, the processes are well coordinated by the hormones of the hypothalamus, pituitary gland and ovaries, and for the occurrence of ovulation it is very important to follow the physiological fluctuations in their levels. The hypothalamus releases gonadotropin-releasing hormone (GnRH), which stimulates the synthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. The two hormones have different effects on the ovaries. FSH stimulates the growth and maturation of follicles, the formation of the dominant follicle from them and the synthesis of estrogens. LH modulates androgen synthesis by ovarian theca cells. The two extremely important factors for ovulation to occur are: the drastic rise in estrogen levels until reaching the so-called “estrogen peak” which, through positive feedback, also leads to a peak in LH levels. However, the initiating factor to drive the cascade of processes is gonadotopic-releasing hormone. Causes Hyperprolactinemia is a common endocrine problem that presents clinically with oligomenorrhea (prolonged menstrual cycle) and/or amenorrhea (absence of menstruation). High levels of prolactin suppress the secretion of GnRH from the hypothalamus, leading to deficiency of the luteal phase of the cycle or amenorrhea and, accordingly, chronic anovulation. NEWS_MORE_BOX Other common causes of dysregulation are stress, chronic anxiety disorders, and the eating disorders anorexia and bulimia. They belong to the group of functional causes. They have impaired pulsatile secretion of the gonadotropin-releasing hormone,for which the main culprit is the so-called stress hormones. In times of stress, our body readjusts to mobilize and deal with the situation, while reproductive processes remain in the background. Polycystic ovary syndrome also leads to chronic anovulation, and the mechanisms by which this occurs are not fully understood. There are two possible theories for this – the first is the persistence of high levels of LH and the second is the retention of the follicles in the early follicular phase and their inability to form a dominant follicle. The most likely causes of the syndrome are metabolic factors – insulin resistance and hyperinsulinemia. Therefore, just as underweight girls are at risk of anovulatory cycles, so are overweight and obese women at high risk. Women with hyper- or hypothyroidism may also have problems ovulating. Dysfunctions of the thyroid gland can disrupt the balance of sex hormones in the body.