Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in young women.  10% of premenopausal women have PCOS.  While some women with obvious signs of PCOS are diagnosed soon after adolescence, others are not diagnosed until learning they have fertility issues.  This can include difficulties with conception and miscarriages.  Women with PCOS have a 1st trimester miscarriage rate of 30-50%, so anyone who has a miscarriage should be evaluated for PCOS. While enlarged ovaries with cysts are seen with PCOS, the actual cause of PCOS is hyperinsulinemia (excess insulin) and associated insulin resistance.  In this article, we will review the symptoms of PCOS, the mechanism of those symptoms and a great way to treat those symptoms.

The 2 most commonly known signs of PCOS are hirsutism (hairiness) due to increased testosterone and obesity. 50% of women with PCOS are not overweight and many do not exhibit hirsutism.  Acne and skin discoloration are also common and when more severe, male pattern hair thinning may be seen.  Women with PCOS are at risk for cardiac disease.  This is because of lipid abnormalities and insulin resistance, which leads to excess inflammation.  Women with PCOS have higher levels of aldosterone, which is an inflammatory marker that is associated with increased cardiovascular disease.  There is associated glucose intolerance, which leads to diabetes.

Testosterone increases for 2 reasons, leading to the androgen symptoms of hirsutism, acne and thinning hair.  Hyperinsulinemia results in increased LH production.  This is a hormone that stimulates production of testosterone.  Also, testosterone is either bound or free.  When bound, it does not cause androgen symptoms.  However, with PCOS, increased insulin leads to decreased binding of testosterone because of decreased sex hormone binding globulin (SHBG).  The increased free testosterone further increases androgen symptoms.  It is important to understand that the main culprit of PCOS is insulin and when insulin is decreased and insulin resistance is improved, the androgen symptoms will improve.

Women with PCOS are often anovulatory, meaning they do not ovulate.  Without ovulation, there is inadequate progesterone, leading to a condition of estrogen dominance.  Some symptoms might include breast swelling and tenderness or bloating.  More concerning is that the estrogen dominance leads to hyperstimulation of the uterus and breast tissue, increasing risk for uterine and breast cancer. 

The key to successful treatment is reducing insulin resistance.  The first-line drug to decrease insulin resistance is metformin.  It is important to start slowly and gradually increase the dose to help minimize the side effect of abdominal discomfort.  When the insulin resistance is reduced, there will be less LH produced, leading to decrease in testosterone production.  Furthermore, decreased insulin resistance leads to increased SHBG so that the testosterone will be bound, not free.  Thus, there will be less free testosterone, decreasing androgen symptoms.  Metformin has the added benefit of reducing the miscarriage rate for women with PCOS.

Improving diet can also improve insulin resistance.  Carbohydrates stimulate insulin production so it is important to reduce carbohydrate intake.  Exercise will also decrease insulin resistance.  Thus, improving lifestyle with a low carbohydrate diet and an exercise regimen will complement and enhance the treatment of PCOS.

Spironolactone plays a key role in treating the androgen symptoms.  This lowers the sensitivity of the body hair follicle receptors to testosterone.  Hair grows in a follicle over 3-6 months so there may be a lag of 6-12 months before the effects of decreased hair.  Aldosterone, as noted above, increases risk for cardiovascular disease.  By reducing aldosterone, spironolactone has positive cardiac benefits for women with PCOS. 

Another key aspect of treatment is to optimize thyroid function.  This is because thyroid plays a vital role in regulating metabolism.  One of the effects of insulin resistance is increased visceral fat.  Thyroid has been shown to reduce visceral fat and central adipose tissue.  This helps with weight loss, which is a challenge for many women with PCOS.  Furthermore, optimal thyroid function is essential for regulating the menstrual cycle, which is often abnormal in PCOS. 

The estrogen dominance and resulting endometrial proliferation is treated with a low-estrogen oral contraceptive or progesterone.  Oral contraceptives will reduce ovarian estrogen production, reducing the estrogen-dominant symptoms.  Oral contraceptives have the additional benefit of blocking ovarian production of testosterone, which reduces the androgen symptoms. 

Progesterone protects uterine and breast tissue by reducing estrogen’s proliferative effects.  This is especially essential due to the increased risk of uterine and breast cancer with PCOS.  Also, progesterone is essential for fertility by preparing the uterus for implantation of a fertilized egg.  To maintain pregnancy, progesterone levels need to be maintained during the first trimester. 

To summarize, PCOS is a condition of increased insulin and associated insulin resistance, leading to menstrual abnormalities and androgen symptoms.  The keystone of treatment is to reduce the insulin resistance with metformin, diet and exercise.  The excess androgen symptoms are treated with spironolactone and consideration of oral contraceptives. The estrogen dominance is improved with either oral contraceptives or progesterone.  Optimizing thyroid function plays a key role in reducing visceral fat, which helps with insulin resistance and weight loss.  A successful pregnancy can be achieved with metformin, progesterone and optimal thyroid function.  The negative consequences of PCOS include androgen symptoms, cardiovascular disease, uterine cancer, breast cancer and infertility.  The good news is that with appropriate treatment, these consequences can be prevented.

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