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What is meant by Hormone Imbalance? Is it the same thing as PCOS? When people use the term "Hormone Imbalance," they are typically describing a girl - or teen, or adult woman - who they suspect have higher than typical levels of testosterone, or other "male" hormones. Often, a child is referred to me for a hormone imbalance when they have early pubic hair, irregular/absent periods, acne, or hair growth on their body or face (or hair loss on their head). Levels of androgens in the blood - also termed "male" hormones - are often measured at above typical levels. In some parts of the country, "hormone imbalance" is a common term, and in others, the medical term "PCOS" is used as a shorthand for elevated androgen levels, even though the medical term for that is "hyperandrogenism."
Polycystic Ovarian Syndrome (PCOS) has been defined as a teen or woman having elevated levels - or signs of elevated levels - of androgens (male hormones), absent or few (fewer than eight) periods per year, and/or enlarged ovaries containing 12 or more follicles ("cysts"). Up to 12 % of teens and women of childbearing age - including teens - can be considered to have this diagnosis. It is a common reason for difficulty in conceiving - something some teens and women worry about - even if many who have had a diagnosis of PCOS go on to have children without significant intervention. The difference between a "hormone imbalance/hyperandrogenism" and PCOS is the presence of irregular periods - on average, fewer than one menstrual period every 42 days.
What causes PCOS? The most common cause of PCOS is a condition termed insulin resistance (IR). There are other causes of PCOS - particularly for women with familial, or genetic, elevated androgens, or for women who have been exposed to supplements or topical or implants containing androgens. All of these cause elevated androgens that often lead to absent or irregular menses. So, although there are some with PCOS without clear insulin resistance, most of those with PCOS have insulin resistance.
What is insulin? Insulin is what lets sugar enter cells. All cells use sugar as their basic fuel. Sugar is absorbed from food we eat directly, or is broken down from more complex carbohydrates. Sugar is also created in our liver between meals and overnight in a process called gluconeogenesis. This glucose circulates in our blood to be delivered to our body's cells. In every cell in our bodies, glucose is used as fuel for proteins to be made, for upkeep and repair, and for cell division and growth. Insulin receptors in cells respond to insulin like a key that unlocks a door to the cell, allowing sugar to enter. As a result, sugar enters most cells only when insulin levels are sufficient to "open the door" to the cell.
And what is insulin resistance? When someone has insulin resistance, a typical, low level of insulin doesn't open the door. The amount of insulin needed for the body to process sugar and use it for energy is significantly elevated. As a result, sugar can't enter cells easily; there is a lag from the time sugar is available until enough insulin is released to allow its passage into the cells. We can picture the usual cell's "keyhole" for insulin to be sticky, or not quite fitting the key, so that a high insulin level is needed to smooth or expand that keyhole. During this lag, blood sugar continues to rise, cells are still awaiting energy, and chemical stress hormones are released. As a result of insulin resistance and the delay in cells receiving energy, the liver creates and releases extra sugar, and more food - especially carbohydrates - are craved and consumed.
Is insulin resistance the same thing as having diabetes? Thankfully, no. IR is far more common than diabetes, and a diagnosis of IR is not a diagnosis of diabetes. But, with IR, the liver creates and releases extra sugar, and more food - especially carbohydrates - are craved and consumed. When the insulin resistance is high enough that insulin levels can't rise to meet the demand, then blood sugars rise to above normal ranges. This is called diabetes. Diabetes is a condition of chronically elevated blood sugar, diagnosed by measuring elevated blood glucose levels on multiple occasions. If a fasting blood sugar level rises to 125 mg/dl or above, or if blood sugar reaches 200 mg/dl or above at any time, then a person is diagnosed with diabetes. The majority of people with insulin resistance have normal blood sugar levels. This is because as long as someone can make enough insulin to match their resistance, they can have severe insulin resistance without developing diabetes. Other people have much more limited ability to make insulin, so even a little resistance results in high blood sugar. As long as a person's ability to make insulin matches their insulin resistance, then diabetes does not develop.
Surprisingly, insulin resistance can lead to subsequent low blood sugars. This happens when, following a rise in blood sugar, the insulin level reaches the threshold for passage of the glucose from the bloodstream into the body's cells. Sometimes insulin resistance is mild, and insulin levels are only double the typical level, but sometimes they are 100x the level. The higher the insulin levels climb, the more rapidly blood glucose levels subsequently fall, as the body's hungry cells quickly use up their delivered fuel.
How does insulin resistance lead to weight gain? The role of insulin to feed cells is described above. High levels of insulin over time lead to weight gain. This is because insulin drives sugar from the bloodstream into cells, the cells accumulate extra energy, which then needs to be stored. Excess energy in the body is stored as fat, so insulin resistance leads to weight gain. And since weight gain leads to greater insulin resistance, it can be a vicious cycle and a snowballing effect.
How does insulin resistance lead to PCOS? Insulin serves as a growth factor for individual cells to grow. In the ovary, some cell types are quite sensitive to insulin's push to grow. Sensitive cells supporting and surrounding ovarian follicles produce more testosterone when insulin levels are high, and also multiply to thicken the tissue surrounding the maturing follicle, trapping it, not permitting ovulation and fertilization of the mature ovum. These two activities cause testosterone and other androgens levels to further rise, be released into the bloodstream, where the brain's fertility hormones in the pituitary and hypothalamus respond by raising LH and decreasing FSH levels. These cause an ongoing snowball effect of higher male hormone levels, and fewer fertile cycles. These rising testosterone levels, with or without effects on ovulation, often also cause considerable acne and extra body hair.
Why does having insulin resistance matter? Unfortunately, elevated insulin levels have other impacts in the body, leading to health concerns. Insulin resistance is associated with diabetes and impaired fertility, but also with heart disease and many cancers. As a result, trying to halt and reverse insulin resistance - at any age - is a worthwhile goal.
Why does insulin resistance happen? IR is strongly inherited, along with a family history of PCOS, gestational diabetes and Type 2 Diabetes, but the risk for high insulin levels also markedly increases with weight gain, low physical activity, and diet high in saturated fat (animal fats and processed vegetable oils) and/or simple carbohydrates (foods that break down quickly into sugar). Other contributing factors to IR are health conditions associated with chronic inflammation, steroid use, working and eating overnight rather than during the day, sleep apnea, and chronic stress and/or depression.
How is insulin resistance measured? In general, endocrinologists don't need to measure insulin levels in someone with clear signs of IR. That said, some lab tests make more clear that it is present, which can spur people to start making changes. For many, triglyceride levels rise with insulin resistance. For some, IR can be significant enough that there is "impaired fasting glucose," where fasting blood sugar level is at least 100, or cause impaired glucose tolerance, where blood sugar rises to at least 140 two hours after a meal. With a lag in insulin response, the average blood sugar may rise, leading to an elevated "Hemoglobin-A-1-C" (aka HgbA1C > 5.6%). On physical examination, several aspects speak to insulin resistance: persistent or rapid weight gain, elevated BMI associated with higher waist circumference, and the presence of acanthosis nigricans - dark, velvety patches around the neck, in underarms, and between the legs.
At what age can insulin resistance start? There can be hints of it at a very young age. There is a strong correlation between early and rapid weight gain and insulin resistance. And rapid gain can be the result of family history, diet, steroid use, sleep apnea, and chronic stress. These can occur even in early childhood.
At what age can PCOS be diagnosed? Because PCOS is defined as fewer than 8 menstrual periods/year, along with elevated androgens (male hormones), PCOS can only be diagnosed at an age when regular menstruation would be expected. This is typically not for at least one year after the first period (menarche) would be expected, or not prior to three years following the start of pubertal development. As a result, the youngest age for a diagnosis of PCOS is not typically before 12 years in girls with early maturation, or as late as 16 years in a girl with somewhat delayed maturation. If there has been clear maturation for four years, with breast and pubic hair development, the teen is at least 14 years old, and there are signs of elevated androgens - acne, extra body hair growth, and irregular periods - then PCOS can and should be considered.
How is PCOS treated? The underlying cause for PCOS is insulin resistance, but is also intertwined with elevated androgens - in itself a factor in developing insulin resistance. Over the years, PCOS has been treated with surgery, hormonal therapies, and insulin sensitizing medications, as well as with lifestyle changes - exercise, dietary changes, and weight loss.
Decades ago, it was recognized that many women who also had elevated androgen levels had "cystic ovaries" - composed of trapped follicles that look like cysts, although not at all infections, and not dangerous. Surgical removal of sections of those enlarged, cystic ovaries, allowed rapid normalization of the androgen levels and normalized menstrual patterns and fertility. Women who were treated with these "wedge resections" typically had restored fertility by eliminating the hormone-producing follicles. These are no longer performed unless there is additional concern for an abnormal cyst or tumor requiring investigation.
Birth control pills treat PCOS by raising estrogen, thereby causing suppression of the pituitary hormones LH and FSH. Without their ovarian stimulation, there is reduced testosterone production, halting the snowball effect of rising ovarian testosterone levels and disrupted ovulation. Once the androgen levels decline, there is often at least a few months of restored ovulatory menstrual cycles even if testosterone levels later rise. For teens not interested in current fertility, birth control pills often suppress androgen levels very well, and address the cosmetic challenges of PCOS. Birth control pills containing at least a medium level of estrogen are used to better suppress testosterone levels. These pills also contain a progesterone to protect the uterus and cause periodic bleeding. Some pills contain a progesterone that has an androgenic effect, but others oppose those effects, helping treat body hair and acne. While some have been marketed as particularly effective for PCOS, a combination of birth control pill plus spironolactone - a weak androgen that displaces more powerful androgens - is often used by me and many of my colleagues with excellent effect on acne and body hair, and greater ability to personalize treatment. For my colleagues treating adults and focusing on stimulating ovulation, Clomiphene is effectively used in many women.
Starting in the 1980's, but much more prominently in the 1990's after several small studies were published, insulin sensitizing medications have been a mainstay of PCOS treatment. Metformin reduces insulin resistance, leading to reduced androgens by 3-6 months. While it reduces androgens more slowly than birth control pills, it is hoped that by reducing insulin resistance, insulin sensitizers have a more holistically beneficial effect on health than by focusing solely on shorter-term ovulation and fertility goals. Other medication used to reduce insulin resistance and treat diabetes (PPAR-gamma medications) are commonly used to treat adults, but due to their higher risk of side effects, are not recommended for children. A set of supplements - myo-inositol and D-chiro-inositol - that appear to aid insulin's effects within cells - especially ovarian cells involved in testosterone production - show promise alone and in combination with Metformin.
Lifestyle changes include multiple modalities for reversing insulin resistance. Exercise - both aerobic and strength training - has been associated with decreasing insulin resistance in all ages. For those with familial insulin resistance, there is often extra fat cells within muscles, called "intramyocellular lipid deposition" that improves with greater use of those muscles, as in weight training, high intensity interval training and Pilates.
Dietary changes that are successful typically reduce processed foods and simple sugars, and expand produce and lean proteins within meals. Some have found success with very low carbohydrate diets, intermittent fasting and ketogenic diets, but a plan that is focused on whole grains, legumes, lean proteins, and expanding produce - also termed a "Mediterranean diet" - is more likely sustainable and socially acceptable for teens and young adults.
Weight stored in the midsection, highly correlated with insulin resistance, is termed "visceral fat" and is treated with weight loss, rather than any specific activity. Indeed, a 5-10 pound weight loss in women who carry weight in their abdomen can cause marked changes in insulin resistance. With this decade's emergence of more effective weight-loss medications (phentermine/phentermine and topiramate/GLP-1 agonists and receptor blocking medications), many adults have found weight loss to be more rapid and consistent with medication, thereby sharply reducing insulin resistance quickly and effectively treating PCOS. Some of these medications are approved for teens, but with use needed indefinitely for ongoing weight management, it is considered by many pediatric endocrinologist an important but not uncomplicated modality for treatment.
For most children with insulin resistance, and teens with PCOS, it is likely multiple factors - heredity, as well as nutritional, medical, and functional challenges - that are additive and contributing to a child's insulin resistance. Each of these must be addressed for comprehensive evaluation and deciding on an optimal treatment plan. Addressing the unique set of underlying causes for a particular child can avoid treatment that may superficially promote a desired effect in the short term that fails to optimize health for a child's lifetime.
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