In the normal state, the hypothalamus secretes gonadotropin-releasing hormone (GnRH) in a pulsatile manner. The pituitary gland responds to GnRH by releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a similar cycle. In the follicular phase of the menstrual cycle, LH acts primarily on the theca cells of the ovary to increase the production of androgenic precursors. Concurrently, FSH acts on the granulosa cells to promote conversion of the androgens into estrogens, particularly estradiol, which assists in follicular development. During the follicular phase, increasing levels of estradiol lead to an LH surge. In a complex interaction, the LH surge, the elevated levels of estradiol and an increase in the circulating progesterone level trigger the midcycle surge of FSH.
In polycystic ovaries syndrome, the cycle is disturbed. Any of several possible precipitating factors may contribute to the imbalance. Evaluation of blood serum levels typically reveals elevated LH levels and normal or low FSH levels. Patients also have increased levels of free estrogen, primarily estrone and estradiol. Estrogens exert a complex feedback effect on the pituitary gland that results in the suppression of FSH secretion and the increased release of LH. Thus, the production and release of androgen precursors by ovarian theca cells is increased. The peripheral conversion of androgens to estrogens, primarily estrone, strengthens the feedback effect on the pituitary gland.
The same androgens also inhibit the production of sex hormone-binding globulin in the liver, indirectly increasing levels of free estrogen in the bloodstream as well. Locally, elevated androgen levels in the ovary exert a direct inhibitory effect on follicular maturation. In conjunction with the diminished but steady presence of FSH, the follicles continue to develop without ever maturing. Thus, numerous follicles are present in the polycystic ovary and show varying phases of development and atresia.
The proposed causes of polycystic ovaries syndrome are numerous and may, in fact, be multiple. They vary from increased androgen production by the adrenal glands at puberty or times of stress to disturbances in the cyclic pattern of GnRH release by the hypothalamus. Several studies have revealed an inherited form of the disease that appears to exhibit autosomal dominant transmission with incomplete penetrance.
Insulin resistance is also a key feature in PCOS, as insulin helps regulate ovarian function. In insulin resistance person, cells throughout the body do not readily respond insulin circulating in blood. For this reason, the amount of insulin remains high in the blood [Hyper insulinemia]. High levels of insulin can contribute to lack of ovulation, high androgen levels, infertility and early pregnancy loss.