Polycystic Ovary Syndrome

What is PCOS?

Polycystic Ovary Syndrome, or PCOS, is a health condition that affects about 10% of women. Despite the name, ovarian cysts are just a symptom of this condition, and only about half the women with PCOS develop cysts. PCOS is an endocrine disorder affecting multiple body systems including the pancreas, adrenals, and sometimes the ovaries. In PCOS, the body isn’t as responsive to insulin as it should be and is producing a higher amount of androgens (male hormones) than normal. Excess androgens are responsible for many PCOS symptoms including acne, unwanted hair, thinning hair, irregular periods, and infertility.

The key players in PCOS are:

Androgens (male hormones, mainly testosterone). All females make androgens, mostly by the ovaries, and some by the adrenal glands.

Insulin. This hormone allows the body to absorb glucose (blood sugar) into the cells for energy. 

SHBG. (Sex Hormone Binding Globulin). A protein circulating in the bloodstream that attaches to testosterone and estrogen preventing them from being used by the body.

Insulin Resistance

Insulin is a hormone produced by cells in the pancreas, and plays an important role in many bodily functions. The pancreas releases insulin into the bloodstream where it travels around telling the body's cells that they should pick up sugar from the blood, which decreases blood sugar levels. However, due to various reasons, sometimes the cells stop responding to the insulin. In other words, they become "resistant" to the insulin. When this happens, blood sugar remains high and the pancreas produces even more insulin to bring the levels down. This leads to high insulin levels in the blood, termed hyperinsulinemia.

Androgens and SHBG:

The two primary sex hormones are testosterone and estrogen. Both men and women produce both hormones. When discussing sex hormones two important terms are used, total and free. “Total” is very straight forward, it is the total amount of hormone produced. “Free” refers to how much of the Total” is available for use (bioavailability).  The protein SHGB (Sex Hormone Binding Globulin) which circulates in the bloodstream attaches to the sex hormone preventing it from being used by the body. Only a very small fraction of sex hormone, about 1 to 2% is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. The higher the level of SHBG the lower the level of available hormone. The reverse is also true, the lower the SHBG the higher the hormone. Although SHBG likes both sex hormones it likes testosterone 20x more than it likes estrogen. 

Insulin and SHBG

Insulin and SHBG have a direct and invers relationship. The higher level of one equals the lower level of the other.

What this all Means:

PCOS and its symptoms are an insulin resistance issue. As you improve insulin resistance (lowering blood insulin levels), you increase blood SHBG levels which decreases the level of free testosterone.  Free testosterone responsible for many PCOS symptoms including acne, unwanted hair, thinning hair, irregular periods, and infertility.

Types of Fat

There are two types of fat, subcutaneous (which is just under the skin) and visceral (which is inside the abdominal cavity). A Harvard University study showed that around 10% of our total fat is likely to be stored as visceral fat, so if you are 20 pounds overweight you have at least 2 pounds of visceral fat.

Why Visceral Fat is Bad

Visceral fat is sometimes referred to as 'active fat' because research has shown that this type of fat plays a distinctive and potentially dangerous role affecting how our hormones function. It is stored within the abdominal cavity and is therefore stored around a number of important internal organs such as the liver, pancreas and intestines. Multiple studies show that visceral fat either causes insulin resistance or is a very early effect of it, and imply that reducing visceral fat should reduce insulin resistance. Visceral fat also makes aromatase.

Aromatase

Aromatase is an enzyme that, essentially, breaks down testosterone into estrogen. At first this might seem like a good thing but it leads to a vicious chain of events. Here is how it works:

Visceral fat either causes insulin resistance or develops very early during the insulin resistance process. When cells stop responding to the insulin "become resistant" blood sugar remains high and the pancreas produces even more insulin to bring the levels down. This high insulin level “hyperinsulinemia” increases ovarian production of testosterone, while deacreasing SHBG, leading to even higher testosterone levels. Visceral fat then releases aromatase to break down the testosterone into estrogen. Although testosterone levels have been lowered by this process they are still well above normal. Additionally, estrogen levels are now higher than normal as well. This sustained elevation of both estrogen and testosterone disrupts, or stops, the menstrual cycle.

Progesterone (P4)     

Progesterone is the counter balance to estrogen and plays a very important role in both the menstrual cycle and in maintaining the early stages of pregnancy. In PCOS progesterone production is suppressed by the constantly elevated estrogen level. This is the primary reason why many women with PCOS do not have normal menstrual cycles, and development of ovarian cyst.

Why Low Progesterone Matters 

There are several reasons why progesterone is crucial to the overall health and wellbeing of women. First of all, research shows that sustained low progesterone levels increases the risk of endometrial and uterine cancers by 60% and breast cancer risk by 40%. It is also the hormone that supports and maintains the early stages of pregnancy. Women with PCOS have a 30-50% chance of miscarriage during the first trimester mainly due to low progesterone. Around week 10 the placenta starts secreting progesterone and the miscarriage risk decreases.   

During pregnancy, progesterone plays an important role in the development of the fetus; stimulates the growth of maternal breast tissue; and strengthens the pelvic wall muscles in preparation for labor. 

Clomid and Progesterone

Clomid is a wonderful medication that is very helpful to women trying to get pregnant. But, Clomid does nothing to treat PCOS or increase progesterone production. For any woman with PCOS that is attempting to have a child, it is essential to take a micronized progesterone (P4) supplement. Preferably, the micronized progesterone would be started several weeks or months before conception and continued at least into the second trimester.  Clomid will help you get pregnant, progesterone will help you have a child.

I recommend continuing progesterone throughout the pregnancy and postpartum period. (It helps dramatically  in reducing the occurrence and/or symptoms of postpartem depresion.)  When a woman with PCOS is placed on Metformin and micronized progesterone before conception, or shortly after, the chance of miscarriage during the first trimester drops to below 10%. 

In fact, I strongly recommend all women with PCOS (regardless of age) take a micronized progesterone (P4) daily to decrease their chance of developing endometrial, uterine, and breast cancers, as well as protecting against cardiovascular disease.

PROGESTIN (MPA) IS NOT PERGESTERONE (P4).

I can not stress enough that progestins (Medroxyprogesterone Acetate "MPA") such as Provera are NOT the same thing as a micronized progesterone (P4).  Some people, and even some medical providers, confuse these two different medications and mistakenly think that they are interchangeable and carry the same benefits and risks. Please avoid any progestin (MPA).

The key to successful overall management of PCOS is restoring hormonal balance by correcting insulin resistance. Achieving this is a process that takes time, so it is also important to treat symptoms of PCOS to improve the quality of life, while providing protection against cardiovascular disease, breast and endometrial cancer throughout the process. The first step is in this process is weight reduction by:

1. Low-carb anti-inflammatory diet
2. Exercise
3. Medications (Discuses in the next section)

A large number of research studies have shown it only takes a modest amount of weight loss, 5-10% of initial body weight to:

1. Reduce insulin resistance by about 50%
2. Restore regular menstrual cycles
3. Improve fertility
4. Improve emotional health (self-esteem, anxiety, depression)
5. Reduce risk factors for diabetes and heart disease
6. Decrease acne and unwanted hair growth

Some of the fortunate few are able to effectively manage their PCOS with diet and exercise alone. But, the majority of women suffering from this disease require medications to see significant improvement of symptoms.     

These are the most common medications used to treat PCOS:

Inositol- Improves insulin resistance, helps restore normal menstruation. Two types Myo-inositol and D-Chiro inositol.  Both improve symptoms, but a combination supplement of the two is the most beneficial. 

Metformin- Improves insulin resistance and decreases the chance of first trimester miscarriage. Is safe to use throughout pregnancy and breast feeding

NP Thyroid- Increases metabolism and decreases visceral fat and improving insulin resistance. Is safe to use throughout pregnancy and breast feeding.

Progesterone (P4)-  Lowers the risk of first trimester miscarriage. Decrease chance of developing endometrial, uterine, and breast cancers, as well as protecting against cardiovascular disease. Is safe to use throughout pregnancy and breast feeding.

Spironolactone- Improves acne and reduces unwanted hair growth on face while improving hair growth on scalp. NOT SAFE DURING PREGNANCY OR BREAST FEEDING.