Hyperinsulinemia, Not Ovaries, at Core of PCOS

Hyperinsulinemia, Not Ovaries, at Core of PCOS.
Family Pratice News, Jan 15, 2001, by Bruce Jancin

DALLAS — Polycystic ovary syndrome is in sore need of a new name, Dr. Barbara S. Apgar said at the annual meeting of the American Academy of Family Physicians.

Put aside the traditional notion that the primary defect in polycystic ovary syndrome (PCOS) involves the ovaries. Focus instead on hyperinsulinemia, which lies at the core of this common endocrinopathy, advised Dr. Apgar, a family physician at the University of Michigan, Ann Arbor.

Indeed, the finding of enlarged ovaries on palpation or polycystic ovaries on ultrasound in merely a sign of PCOS. Insulin abnormalities precede the elevated androgen levels that characterize PCOS. And switching off the ovaries via a GnRH agonist doesn’t affect the hyperinsulinemia and insulin resistance, she noted.

PCOS is probably the most common endocrine disorder in women. It’s estimated that up to 10% of premenopausal women are affected.

In PCOS, hyperinsulinemia leads to hyperandrogenism, resulting in chronically elevated LH levels. The hair follicles are genetically sensitive to androgen stimulation, so acne and hirsutism are commonly part of the PCOS picture. Glucose intolerance, type 2 diabetes, and lipid abnormalities also are common. And 40%-60% of patients with PCOS are obese.

“Treatment is not directed at the ovary. It’s directed at the hair follicle level and also at the pancreatic level, where we see the insulin resistance,” she explained.

The disorder requires a multimodal approach. Treatment may include clomiphene citrate (Clomid) to stimulate ovulation, OCs or a progestin to prevent endometrial hyperplasia, and statins or other lipid-lowering agents for cardiovascular protection. Spironolactone is probably the best option for treating hirsutism. Use finasteride with great caution and only after obtaining informed consent in women of reproductive age; it is a teratogen.

The most exciting development in PCOS therapy involves pharmacologic reversal of the primary defect: hyperinsulinemia. Metformin is the best-studied drug. Studies to date are small but generally show metformin cuts fasting insulin, LH, and free testosterone levels by half. The drug also restores menstrual cyclicity and fertility, reverses hirsutism, and reduces body mass index.

“This is a really interesting drug. I think down the road it might become much more widely used because reducing all of those things is certainly getting at the etiology,” Dr. Apgar observed.

COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group

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