Olanzapine Use in Women With Antipsychotic-Induced Hyperprolactinemia

To the Editor: Typical antipsychotics, as well as risperidone, elevate serum prolactin levels through the blockade of dopamine 2 (D₂) receptors in the tuberoinfundibular region of the brain (1). Antipsychotic-induced hyperprolactinemia in women with schizophrenia frequently results in menstrual dysfunction and galactorrhea. In men, the novel antipsychotic olanzapine does not appear to elevate serum prolactin significantly (2), despite its potential to block D₂ receptors. Little, however, is known about the effect of olanzapine on prolactin levels in women. We report on two women with antipsychotic-induced hyperprolactinemia, menstrual dysfunction, and galactorrhea, who experienced improvement in these side effects during treatment with olanzapine.

Case 1. Ms. A, a 45-year-old woman with schizophrenia, experienced amenorrhea and galactorrhea shortly after beginning as well as during treatment with perphenazine, 32 mg/day. Previously, she had been treated with various typical neuroleptics; she recalled one other occasion (excluding pregnancy) when her menses had ceased for several months. Before treatment with perphenazine, however, Ms. A had been having regular monthly menstrual periods. Medical evaluation revealed an elevated serum prolactin level (greater than 200 ng/ml; normal=1.39–26.70 ng/ml), a negative pregnancy test, normal thyroid function tests, and premenopausal levels of follicle-stimulating hormone and luteinizing hormone. Magnetic resonance imaging (MRI) showed no evidence of pituitary adenoma. Alternative treatment with olanzapine was initiated and titrated to 10 mg/day.

After 1 month of olanzapine treatment, Ms. A’s monthly menses resumed and the galactorrhea ceased. Serum prolactin levels, although still elevated, trended downward to 116 ng/ml, 105 ng/ml, and 72 ng/ml, after 2, 4, and 6 months of olanzapine treatment, respectively. Her psychiatric condition remained stable.

Case 2. Ms. B, a 26-year-old woman with schizophrenia, developed menstrual dysfunction and galactorrhea soon after beginning a regimen of risperidone, 6 mg/day. She reported having monthly menses before treatment. After 1 month of treatment, there was a reduction in menstrual flow; by the second month, menses were absent and galactorrhea began. Ms. B was not pregnant. Her prolactin level was 127.80 ng/ml, and an MRI showed no evidence of pituitary adenoma. Her worsening psychiatric status necessitated an increase of risperidone to 8 mg/day. At this dose, she continued to experience amenorrhea and galactorrhea and developed moderate extrapyramidal symptoms. Consequently, the risperidone was tapered, and olanzapine was initiated and titrated to 15 mg/day.

After 1 month of olanzapine treatment, monthly menses resumed and galactorrhea resolved. The serum prolactin fell to a normal level (25.10 ng/ml). Ms. B’s psychiatric condition improved, and the extrapyramidal side effects resolved.

In both cases, olanzapine treatment resulted in reduction of serum prolactin levels, improved menstrual function, and resolution of galactorrhea. The fact that Ms. A continued to have a moderate elevation in prolactin 1) supports the idea that women may have greater sensitivity than men to dopamine blockade in the tuberoinfundibulum (3) and 2) raises the possibility that even olanzapine may produce some prolactin elevation in certain women. Nonetheless, since iatrogenic hyperprolactinemia often causes menstrual dysfunction and galactorrhea and may increase the risk of osteoporosis (4), olanzapine’s reduced potential to elevate prolactin may provide a treatment advantage for women with schizophrenia. Moreover, since menstrual cycles may normalize during treatment with olanzapine, women treated with this drug may have improved fertility when compared with women receiving typical antipsychotics and risperidone; women taking olanzapine should, therefore, be informed of the need for contraception. Further studies will be required to assess the comparative effects of olanzapine and other antipsychotics on prolactin levels, related side effects, and fertility.