Management of Menorrhagia Associated With Chemotherapy-Induced Thrombocytopenia in Women With Hematologic Malignancy

Jill S. Bates, Pharm.D., M.S.; Larry W. Buie, Pharm.D.; C. Brock Woodis, Pharm.D.

Disclosures

Pharmacotherapy. 2011;31(11):1092-1110. 

In This Article

Danazol for Menorrhagia Refractory to Traditional Pharmacotherapy

Danazol has been shown to be significantly more effective at reducing menstrual blood loss in patients with menorrhagia than placebo, mefenamic acid, or norethindrone.[65–67] Until the introduction of vaginal danazol, the use of danazol remained questionable due to adverse effects including hot flashes, weight gain, increased serum glutamic-oxaloacetic transaminase levels, and myalgias. When used intravaginally, these adverse effects are reduced. Intravaginal danazol reaches low serum concentrations and does not inhibit the ovarian-pituitary axis, and no inhibition of ovulation occurs.[68] Lower serum concentrations resulting from intravaginal delivery would also be less thrombogenic and may be a preferable option in a hypercoagulable state.[69,70]

In a small, prospective, observational study performed in Italy of 55 women, all participants received danazol 200 mg/day intravaginally for 6 months.[71] Exclusion criteria were extensive, including patients with von Willebrand's disease, coagulopathies, hormone-dependent malignancies, or thromboembolic disorders. Women were instructed to keep a diary to record the presence of adverse effects and to complete a pain assessment.

All women in the study reported a decrease in the duration of bleeding. Mean duration decreased from 6 to 3 days, with decreases in utilization of tampons or pads decreasing from 6 to 2 each day. In 30% of women, the severity of the blood loss was reduced after 1 month, with 90% of women having less severe bleeding by 3 months. Hemoglobin level, hematocrit, and erythrocyte count were significantly increased at the end of the 6-month study period (p<0.05). Dysmenorrhea, dyspareunia, and pelvic pain were decreased at 3 months (p<0.01) and remained decreased at the end of the study period (p<0.01).

In the cancer population with thrombocytopenia, often myelosuppression induces a neutropenic immune state in which the patient is highly susceptible to infection (defined as absolute neutrophil count < 500 cells/mm 3). In patients with neutropenia, intravaginal insertion of a drug is contraindicated secondary to increased risk of infection due to microbial translocation. For patients who are experiencing thrombocytopenia- associated menorrhagia without neutropenia, danazol may be a treatment option; however, in this patient population, these numbers should be relatively small.

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