LOS ANGELES – It's reasonable to consider the anticonvulsant valproate as a last option for women with bipolar disorder, given the drug's associations with the risk of developing isolated features of polycystic ovary syndrome, according to Dr. Harold Carlson.
“I don't have any problem with that,” he said, when an audience member suggested it and also noted the drug's teratogenicity.
Women under age 25, and particularly adolescents in their midteens, are most at risk for valproate-induced PCOS, usually within the first year of treatment, said Dr. Carlson, professor of endocrinology at Stony Brook (N.Y.) University.
In one study, 9 of 86 women with bipolar disorder (10.5%) treated with valproate developed PCOS; 2 of 144 women with bipolar disorder (1.4%) developed PCOS when treated with other mood stabilizers (Biol. Psychiatry 2006;59:1078-86).
Valproate seems to pose a particular risk for the condition driven by something more than the weight gain caused by the drug.
After all, “the folks [who] gain all that weight on olanzapine don't get PCOS,” Dr. Carlson noted.
Valproate appears to act directly on the ovaries, altering their hormone production. Cultured ovarian cells produce more testosterone in its presence. The excess testosterone shuts off menstruation, and causes acne and hirsutism. Obesity, insulin resistance, and dyslipidemia are problems in PCOS, as well.
When valproate cannot be switched out for a mood stabilizer, prescribing birth control pills at the start of therapy might be a smart move, Dr. Carlson said at the meeting, sponsored by the American Academy of Child and Adolescent Psychiatry. That appeared to help prevent PCOS in valproate-treated women in one study (Seizure 2003;12:323-9).
Baseline pelvic ultrasounds might seem like a good idea, too, but they're “not worth doing,” he said. The reason is that 10%–15% of healthy women have cysts on their ovaries without having PCOS, and ovarian cysts aren't always present in PCOS.
When women are started on the drug, ask them “every time you see them about their menstrual function. Look at them and see if they are getting acne and hirsutism. Ask them about it. Provide some counseling on diet and exercise to avoid the excessive weight gain, which only makes it worse,” Dr. Carlson said.
Should PCOS develop, Metformin is the first-line symptom treatment. Clomiphene can induce ovulation if pregnancy is the goal. Endocrinology, urology, or gynecology referrals also are in order to help with symptoms, he said.
Dr. Carlson said he is a consultant to Eli Lilly & Co., and has received research funding from GlaxoSmithKline.
Ask patients on valproate about their menstrual function. Look to see if they are getting acne and hirsutism.
Source DR. CARLSON