Leah Morton, MD, Santa Fe, NM.

JACKSON HOLE—Think about insulin resistance in women who have polycystic ovary disease, said Leah Morton, MD, at a course entitled, “Food as Medicine,” sponsored by the Center for Mind-Body Medicine.

“Polycystic ovarian syndrome (PCOS), is a prototype of women’s health issues related to nutrition,” said Dr. Morton, a gynecologist in Santa Fe, NM. “It is a derangement of the essential female organs—the ovaries. And I believe, as some others do, that it is acquired. PCOS is the “Syndrome X” of the ovaries.”

Dr. Morton said that for years, she tried to treat PCOS patients by “trying to dicker around with their hormones, to support the luteal phase with natural progesterones and try to get regular periods.” After repeated failures, she began to look into nutrition and dietary interventions. She now finds that by reducing sugar and carbohydrates and bringing the patients back to euglycemia, PCOS often resolves.

The Lens of Hyperglycemia

“Look at this through the lens of hyperglycemia. Think of PCOS as being caused by insulin resistance. Insulin resistance is so disruptive to ovarian function.”

In PCOS, the follicles are partially stimulated, but do not mature fully, leaving many partially matured follicles around the periphery of the ovary. Incidence of polycystic ovaries on random ultrasound examination is about 20%.

The “classic” clinical manifestations of PCOS are hirsutism, acne, obesity, infertility, amenorrhea, oligomenorrhea (N Engl J Med. 1995; 333(13): 853–860). Some women also show male-pattern hair loss. But not all have these “stigmata”. By best estimate, 5–7% of reproductive age women will have clinical diagnoses of PCOS based on hyperandrogenism and anovulation. But there are many women who look quite normal despite polycystic ovaries on ultrasound.

Metabolically and hormonally, PCOS patients have marked increases in luteinizing hormone (LH), and consequently increased LH/FSH ratios. They have high androgen levels, increased IGF-1 binding protein, increased insulin, and increased insulin/glucose ratios. These latter changes, said Dr. Morton, are the key to understanding the disorder.

When resected ovarian tissue is bathed in insulin, it responds by producing androgens and LH. Physiologically, when LH is present before the natural point for the LH surge, you get suppression of estrogen, resulting in a high LH/FSH ratio, with no estrogen being released. This creates a vicious cycle because low estrogen levels tend to increase insulin resistance. And insulin resistance means more free insulin to promote LH and androgen production in the ovary.

When insulin hits the ovary and pituitary, the result is a steady LH level, and even though FSH is also stimulated, the LH overwhelms it, resulting in a down-regulation of estrogen. The normal periodicity of the woman’s hormone cycle is disrupted.

There is substantial evidence supporting the link between insulin resistance, glucose intolerance, and PCOS (For good review articles on the subject, see Norman RJ. Curr Opin Obstet Gynecol. 2001; 13(3): 323–327. Zacur HA. Obstet Gynecol Clin North Am. 2001; 28(1): 21–33). The connection is particularly strong among those PCOS patients with abdominal obesity.

Reversing Insulin Resistance

If PCOS is acquired and related to insulin resistance, then is it reversible? Dr. Morton believes it is. Metformin, an agent that increases insulin sensitivity, has been shown to reverse PCOS (Nestler et al. N Engl J Med. 1998; 338(26): 1876–1880). Velasquez et al. have shown that metformin can actually be used to treat PCOS and induce normal menstrual cycling (Metabolism 1994; 43(5): 647–654. Obstetrics & Gynecology 1997; 90(3): 392–395). More than once, metformin has resulted in unexpected pregnancy in women with PCOS who were previously infertile.

“Metformin is one of the 70% of drugs out there whose mechanism is unknown. But we know that it does block glucose absorption in the gut, and if gut absorption decreases, insulin resistance would decrease as well.”

But metformin is not without side effects, including nausea, vomiting, and lactic acidosis. The latter, while estimated to occur in only 3 of every 100,000 patients on this drug, can be very serious or even fatal. Metformin is hardly the ideal way of managing PCOS.

Dr. Morton believes drug therapies are no substitute for dietary interventions, which can make a tremendous difference for women with PCOS. But patients should be steered away from the popular low-fat, high-carbohydrate diets. High carbohydrate intake will only fuel the insulin resistance and dysglycemia.

“Insulin is secreted in proportion to the glucose level in the portal vein, and it promotes glucose uptake by hepatic cells.” The glucose is transformed into glycogen, triglycerides and cholesterol in the liver, and the natural conversion of sugars into fats is actually a physiologic protection mechanism in that lipids are much less oxidizable and less toxic to the tissues.

“In terms of oxidative stress, sugar is far worse than lipid,” said Dr. Morton. “Everything is set up to protect the body under stress, and this is fine in young healthy women who exercise.”

The problems arise when the supply of glucose greatly exceeds the demand. Fat storage continues, and this typically results in central obesity, which drives further insulinemia. A high carbohydrate diet, in the context of increased insulin secretion raises triglycerides.

Ultimately, if allowed to persist, insulin resistance in its final stages induces hepatic changes, making glucose uptake from the portal vein difficult. This results in frank hyperglycemia and diabetes mellitus.

Accentuate the Positive

PCOS patients need to reduce carbohydrate intake, but Dr. Morton said. But don’t begin by telling your patients to eat less carbohydrate. “It is better to tell them what is good for them to eat: avocados, macadamia nuts, salmon, olives, and olive oil. I want my patients to enjoy their nutrition, not have it be a restrictive, negative experience,” Dr. Morton said.

Avoid following the standard “food pyramid,” which is heavy on the high-glycemic foods like cereals and grains. “I try to put low glycemic fruits and vegetables at the base of the pyramid, fats in the middle, and be rather sparing with cereals and proteins, which tend to be highly glycemic.”

PCOS patients, and many others with insulin resistance, will benefit from increased fiber intake, particularly soluble fibers. “They wrap around the sugar molecules and slow the absorption, making it a more steady absorption rather than a surge.”