In short, the cause of PCOS is unknown. However, the story is starting to unravel and several important lines of evidence have emerged that offer clues about a central mechanism. The central question remains whether PCOS is a single entity. Is there only one, or are there many causes of PCOS? PCOS is a “final common pathway” of a variety of disorders and the diagnosis PCOS itself remains one of exclusion. Still, an important principle of medicine is that we always first attempt to link all physical complaints and clinical findings into a single disorder. Although thus far, we have not been able to do this with PCOS, it does not mean that we can not do so in the future.

Let’s first look at several characteristics those individuals with PCOS universally tend to share–what binds not separates. We know that PCOS is inherited. For the present, it also means that a cure is unlikely, so we must stick with trying to control, or correct, the abnormalities of PCOS. Elevated levels of male hormones (hyperandrogenism) also characterize PCOS. Hormones are natural chemicals that are released by the body into the bloodstream and in very small quantities and have dramatic effects on distant sites throughout the body. As such, and the case of PCOS, the entire body is affected by relatively small hormonal abnormalities. There is also the important observation that surgical removal of a portion of the ovary, known as a wedge resection, restores menses and fertility in many PCOS patients. For this reason, it has been suggested that the ovary is the origin of the abnormality.

All estrogens, the female sex hormone, are made from androgens. It is only when androgens are present in abnormally large quantities, or the balance of estrogens to androgens is disrupted, do the unwanted effects of hyperandrogenism appear. A large percentage of the androgens circulating in the bloodstream are produced in fat cells. A larger number of fat cells create a greater potential for androgen production. The remainder of androgen production normally is divided about equally between the adrenal gland and ovary. There may be adrenal and ovarian forms of PCOS depending from where the greater portion of androgens arise. In the ovary, androgens are produced in the smaller size follicles that characterize PCOS. That the ovary is filled with increased numbers of smaller follicles, 4-10 mm, has led some to postulate that some factor blocking follicle development is the key to PCOS. The cells surrounding these follicles (theca cells) are sensitive to the higher amounts of LH, also a characteristic of PCOS. LH stimulates androgen production. The smaller follicle has not developed the enzymatic machinery capable of converting these androgens to estrogens.

Whether this is a specific block in the ovary, or a consequence of other factors outside the ovary is not known. A genetically acquired abnormality in steroid steroidogenesis, insulin resistance and/or hypothalamic-pituitary- ovarian axis abnormality probably act in concert as in the etiology of PCOS. The degree of participation of each of these etiologies varies between patients. Regardless, the ovaries are arrested in a relatively static situation, a grid-lock, log-jam that prevents the eventful maturation of the follicles.