PCOS – The Misunderstood Disease

Polycystic Ovarian Syndrome (PCOS) is one of the most misunderstood and, consequently, mistreated disease states in medicine.

PCOS is actually a subgroup disorder in the much larger disorder of androgen excesses (overproduction). Androgens are male hormones that every woman produces, though generally in levels much lower than those produced by a man. Women produce androgens in the adrenal glands and in the ovaries. If one or both of these glands becomes overactive in androgen production, then a woman will demonstrate typical physical signs of testosterone’s effects. These signs include oily skin, acne, hirsutism (excess hair growth), irregular and occasionally heavy menses, and often sub-fertility or infertility secondary to excess androgens interfering with ovulations.

In PCOS, the source of the overproduction of androgens is the ovaries. While there are several mechanisms that can cause the ovaries to overproduce androgens, including an enzyme defect or a tumor, PCOS is one of the more common causes.

In the ovary there are several different types of cells. Some of the cells (theca cells and interstitial cells) produce testosterone when stimulated by LH or insulin. Other ovarian cells (granulosa cells) absorb the testosterone and convert it to the estrogen, estradiol, under the influence of the enzyme aromatase. This is a normal, physiologic activity in the ovary and is how the ovary produces estrogens.

High levels of testosterone in the ovary shut down the activity of the aromatase enzyme that converts the testosterone to estradiol. These high testosterone levels can be caused by a number of sources. These sources include overproduction by the adrenal glands, with the elevated levels of testosterone being released into the bloodstream in high enough levels that the aromatase enzyme activity in the ovary is shut down. This then permits the testosterone being produced at a normal rate by the theca and interstitial cells of the ovary to build up and then directly shut down aromatase enzyme activity in the ovary. The excess testosterone produced in the ovary then spills out of the ovary and into the bloodstream and general circulation. In addition to creating the physical signs of a testosterone excess noted above, the elevated levels of circulating testosterone are then converted to estrogen by other tissues of the body including fat, liver, skin, and brain tissue. This results in higher than normal levels of estrogen for these individuals in the brain which, in turn, stimulates the pituitary gland to release higher concentrations of the ovarian stimulating hormone LH (leutinizing hormone). These elevated levels of LH then directly stimulate the theca and stromal cells of the ovary to produce even higher levels of testosterone, continuing the shutdown of the aromatase enzyme. A self-perpetuating, vicious circle is then established.

The high local levels of testosterone also lock follicle and egg development in the preantral phase at 10 to 12 mm in diameter. These small 10–12 mm cysts do not resolve each month but continue to increase in number each month causing the ovaries to enlarge and develop their “polycystic” appearance. Ovulation does not occur, which leads to both irregular menses, prolonged and heavy menses when menstrual bleeding does occur, and infertility.

For this reason, a woman with true PCOS will have an LH/FSH ratio greater than 3/1 with the LH greater than 20 IU’s/liter. The mere presence of the LH being 3 times higher than the FSH (follicle-stimulating hormone) is not adequate to create PCOS. Instead, one must have this ratio but also have the LH elevated to 20 IU’s or higher to get adequate stimulation to the theca and the interstitial cells to produce enough testosterone locally to start this cascading action of shutting down the aromatase enzyme activity.

Insulin resistance, with elevated levels of insulin needed to maintain normal blood sugar levels, can also cause the ovaries to overproduce testosterone. This occurs because insulin, along with LH, has the ability to directly stimulate the theca and interstitial cells to produce testosterone. With increased production of testosterone by the cells in the ovaries under the influence of insulin the effect on the aromatase enzyme is the same. The aromatase enzyme shuts down and stops converting the testosterone in the ovary to estrogen. Therefore, while the clinical pictures of these 2 conditions can look similar, the actual disease mechanism is significantly different. The best treatment results are achieved when the etiology of the ovarian androgen overproduction is determined and treated directly.